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Willis HJ, Asche SE, McKenzie AL, Adams RN, Roberts CGP, Volk BM, Krizka S, Athinarayanan SJ, Zoller AR, Bergenstal RM. Impact of Continuous Glucose Monitoring Versus Blood Glucose Monitoring to Support a Carbohydrate-Restricted Nutrition Intervention in People with Type 2 Diabetes. Diabetes Technol Ther 2025; 27:341-356. [PMID: 39527030 DOI: 10.1089/dia.2024.0406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Introduction: Low- and very-low-carbohydrate eating patterns, including ketogenic eating, can reduce glycated hemoglobin (HbA1c) in people with type 2 diabetes (T2D). Continuous glucose monitoring (CGM) has also been shown to improve glycemic outcomes, such as time in range (TIR; % time with glucose 70-180 mg/dL), more than blood glucose monitoring (BGM). CGM-guided nutrition interventions are sparse. The primary objective of this study was to compare differences in change in TIR when people with T2D used either CGM or BGM to guide dietary intake and medication management during a medically supervised ketogenic diet program (MSKDP) delivered via continuous remote care. Methods: IGNITE (Impact of Glucose moNitoring and nutrItion on Time in rangE) study participants were randomized to use CGM (n = 81) or BGM (n = 82) as part of a MSKDP. Participants and their care team used CGM and BGM data to support dietary choices and medication management. Glycemia, medication use, ketones, dietary intake, and weight were assessed at baseline (Base), month 1 (M1), and month 3 (M3); differences between arms and timepoints were evaluated. Results: Adults (n = 163) with a mean (standard deviation) T2D duration of 9.7 (7.7) years and HbA1c of 8.1% (1.2%) participated. TIR improved from Base to M3, 61-89% for CGM and 63%-85% for BGM (P < 0.001), with no difference in change between arms (P = 0.26). Additional CGM metrics also improved by M1, and improvements were sustained through M3. HbA1c decreased by ≥1.5% from Base to M3 for both CGM and BGM arms (P < 0.001). Diabetes medications were de-intensified based on change in medication effect scores from Base to M3 (P < 0.001). Total energy and carbohydrate intake decreased (P < 0.001), and participants in both arms lost clinically significant weight (P < 0.001). Conclusion: Both the CGM and BGM arms saw similar and significant improvements in glycemia and other diabetes-related outcomes during this MSKDP. Additional CGM-guided nutrition intervention research is needed.
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Affiliation(s)
- Holly J Willis
- International Diabetes Center, HealthPartners Institute, Minneapolis, Minnesota, USA
| | | | | | | | | | | | - Shannon Krizka
- International Diabetes Center, HealthPartners Institute, Minneapolis, Minnesota, USA
| | | | | | - Richard M Bergenstal
- International Diabetes Center, HealthPartners Institute, Minneapolis, Minnesota, USA
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Assmann M, Albrecht I, Frenser M, Marquardt T, Fischer T. Database Analysis of Application Areas and Global Trends in Ketogenic Diets from 2019 to 2024. Nutrients 2025; 17:1478. [PMID: 40362787 PMCID: PMC12073691 DOI: 10.3390/nu17091478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2025] [Revised: 04/24/2025] [Accepted: 04/25/2025] [Indexed: 05/15/2025] Open
Abstract
Background: After being developed in the 1920s, the ketogenic diet fell into disuse, only to make a comeback at the end of the 20th century. In addition to its original use in the treatment of epilepsy, research on the ketogenic diet is now focusing on many other indications. Methods: Based on a systematic literature analysis according to the PRISMA guidelines, an overview of the current research on specific topics in the last five years (2019 to August 2024) was compiled. Results: A total of 290 trials were included. In total, 32 topics were analyzed, most of which were related to overweight and obesity, as well as exercise and epilepsy. The articles included 1981 authors from 47 countries, who published their results from intervention and observational studies in 153 journals. In total, 227 studies lasted less than six months, while 61 studies lasted more than six months. Conclusions: The results and the increasing amount of research underline the growing scientific attention and potential of the ketogenic diet to offer new therapeutic and individual preventive approaches. These trends indicate that the ketogenic diet remains an important international research topic.
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Affiliation(s)
- Marc Assmann
- Center for Nutrition and Therapy (NuT), University of Applied Sciences Muenster, Corrensstraße 25, 48149 Muenster, Germany
| | - Isabel Albrecht
- Center for Nutrition and Therapy (NuT), University of Applied Sciences Muenster, Corrensstraße 25, 48149 Muenster, Germany
| | - Marius Frenser
- Center for Nutrition and Therapy (NuT), University of Applied Sciences Muenster, Corrensstraße 25, 48149 Muenster, Germany
| | - Thorsten Marquardt
- Department of Pediatrics, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany
| | - Tobias Fischer
- Center for Nutrition and Therapy (NuT), University of Applied Sciences Muenster, Corrensstraße 25, 48149 Muenster, Germany
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Lu X, Jin F. Analysis of Factors Influencing Clinical Inertia in the Treatment of Type 2 Diabetes Mellitus Patients With Metformin. Br J Hosp Med (Lond) 2025; 86:1-13. [PMID: 40265556 DOI: 10.12968/hmed.2024.0645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/24/2025]
Abstract
Aims/Background Medication therapy is a crucial measure for type 2 diabetes mellitus (T2DM). However, approximately 50% of diabetes patients in China fail to achieve their blood glucose control targets despite receiving hypoglycemic treatment. Studies have indicated that clinical inertia is often a key factor contributing to poor long-term blood glucose control in most patients. This study aims to investigate the factors influencing clinical inertia in the treatment process of patients using metformin. Methods A retrospective study method was adopted, and 86 T2DM patients treated with metformin who have clinical inertia between June 2021 and June 2023 at Zhejiang Hospital were treated as the inertia group. Additionally, 87 patients who received the same medication treatment and follow-up evaluation without clinical inertia during the same period were selected as the control group. By comparing general data, family and economic situations, lifestyle, and diabetes conditions between the two groups, a logistic multivariate analysis model was used to analyze the factors influencing clinical inertia in the treatment process of T2DM patients using metformin. Results The proportion of male patients and those with an elementary education or below was significantly higher in the inertia group compared to the control group (p < 0.05). Additionally, the proportion of patients without commercial insurance was significantly higher in the inertia group (p < 0.05). The proportion of patients practicing dietary control was lower in the inertia group compared to the control group (p < 0.05). Furthermore, the inertia group had a lower proportion of patients with initial glycated hemoglobin levels ≥8.0%, those conducting home blood glucose monitoring, patients with diabetes-related complications, and those receiving diabetes health education compared to the control group (p < 0.05). Male gender (odds ratio (OR) = 3.487, p = 0.001), elementary education or below (OR = 2.362, p = 0.027), lack of commercial insurance (OR = 3.783, p = 0.005), absence of home blood glucose monitoring (OR = 3.127, p = 0.007), absence of diabetes-related complications (OR = 2.995, p = 0.006), and lack of chronic disease health education (OR = 2.753, p = 0.017) were identified as risk factors for clinical inertia in the treatment of T2DM patients using metformin (p < 0.05). Conclusion The risk of clinical inertia during metformin treatment in T2DM patients is relatively high and is associated with various factors. Targeted intervention measures should be implemented for high-risk populations to reduce the risk of clinical inertia.
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Affiliation(s)
- Xuan Lu
- Department of Endocrinology, Zhejiang Hospital, Hangzhou, Zhejiang, China
| | - Fubi Jin
- Department of Endocrinology, Zhejiang Hospital, Hangzhou, Zhejiang, China
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Ramonda R, Ometto F, Striani G, Cozzi G, Basso D, Evangelista F, Lorenzin M, Scagnellato L, Aita A, Favero M, Brocadello F, Doria A. Ketogenic diet improves disease activity and cardiovascular risk in psoriatic arthritis: A proof of concept study. PLoS One 2025; 20:e0321140. [PMID: 40261944 PMCID: PMC12013891 DOI: 10.1371/journal.pone.0321140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 03/01/2025] [Indexed: 04/24/2025] Open
Abstract
OBJECTIVES Very low-calorie ketogenic diet (VLCKD) is a low-carbohydrate, low-calorie regimen that leads to rapid weight loss and may reduce inflammation. This study assessed the impact of VLCKD on anthropometric measurements, inflammatory biomarkers, metabolic health, and cardiovascular risk in psoriatic arthritis (PsA) patients moderately overweight or in class I obesity. METHODS A proof-of-concept single-arm monocentric study involved PsA patients undergoing a 9-week VLCKD treatment. Patients with Body Mass Index (BMI) ≥27 and <35, in stable (≥6 months) remission or low disease activity, as defined by Disease Activity in PSoriatic Arthritis (DAPSA) score, were included and underwent nutritional evaluations every 3 weeks. The study analyzed changes after the VLCKD intervention and the association between changes of anthropometric parameters and clinical and laboratory variables. RESULTS Twenty patients were enrolled since April 2022 and completed the study in May 2023. Median baseline BMI was 30.9 (interquartile range 29.1-33) kg/m². All participants exhibited low baseline disease activity, which correlated with BMI (Spearman's correlation coefficient (rs)=0.59,p=0.007). Following VLCKD, significant improvements were observed in all anthropometric measures (BMI -3.5[-4;-2.6]), PsA activity (DAPSA -6.1[-16.8;3.7]), cardiovascular parameters (SCORE2 index -0.2[-0.7;0.1]), insulin resistance (Homeostatic Model Assessment-Insuline Resistance -2.1[-1.1;-3.0]), and lipid profile. Most inflammatory biomarkers remained within normal limits. BMI reduction correlated with changes in DAPSA scores (rs=0.52,p=0.020). Patients with higher baseline weight or clinical activity experienced more pronounced improvements. CONCLUSIONS VLCKD significantly improved PsA activity and metabolic health. Patients with a higher BMI and less controlled disease are particularly motivated and could benefit more from VLCKD compared to those with lower BMI or better disease control.
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Affiliation(s)
- Roberta Ramonda
- Rheumatology Unit, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
| | - Francesca Ometto
- Rheumatology Outpatient Clinic, Local Health Unit 6 Euganea (Azienda ULSS 6 Euganea), Padova, Italy
| | - Giovanni Striani
- Rheumatology Unit, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
| | - Giacomo Cozzi
- Rheumatology Unit, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
| | - Daniela Basso
- Laboratory Medicine, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
| | - Filippo Evangelista
- Rheumatology Unit, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
| | - Mariagrazia Lorenzin
- Rheumatology Unit, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
| | - Laura Scagnellato
- Rheumatology Unit, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
| | - Ada Aita
- Laboratory Medicine, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
| | - Marta Favero
- Rheumatology Unit, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
- Internal Medicine 1, Department of Medicine (DIMED), AULSS2 Marca Trevigiana, Ca’ Foncello Hospital, Piazzale dell’Ospedale, Treviso, Italy
| | | | - Andrea Doria
- Rheumatology Unit, Department of Medicine (DIMED), Padova University Hospital, Padova, Italy
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Ibrahim RT, Moustafa YM, Alwaili MA, Alrebdi AN, Alharthi A, Noufal NR, Khodeer DM. Chromium and formoterol therapy for obesity-induced asthma in rats. Front Pharmacol 2025; 16:1537022. [PMID: 40242447 PMCID: PMC12000533 DOI: 10.3389/fphar.2025.1537022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 02/06/2025] [Indexed: 04/18/2025] Open
Abstract
The development of asthma is impacted by fat. Asthma is more common in obese persons. The purpose of the experimental study is to determine how chromium, formoterol, and their combination can improve the quality of life for obese people with lung anomalies. Thirty-six male Wistar rats were divided into six groups: control (C), obesity (CO), obese-asthma (COA), and obese-asthma groups treated with formoterol (OAF), chromium (OACR), or both (OACRF). Except for group C, all groups received a high-fat diet for 4 weeks. Subsequently, ovalbumin (OVA) was administered subcutaneously (s.c.) to all groups except C and CO to induce sensitization. Asthma was triggered via 1% OVA aerosol challenges on days 26-28. Over 5 days, OAF and OACRF received daily formoterol inhalations (50 μg/kg), while OACR and OACRF were given chromium (400 μg/kg). Treatments were timed to align with asthma induction protocols. Lipid profile and inflammatory indicators were examined at the end of the trial-Immunohistochemical analysis of lung tissue, Histopathological and lung tissue stained with Hematoxylin and Eosin. The combination therapy (OACRF) significantly reduced body weight (p < 0.05), lowered LDL and triglycerides, increased HDL, and normalized lung tissue architecture compared to controls. Immunohistochemistry revealed reduced IL-1β and IL-17α expression. The (OACRF) group demonstrated superior asthma control by reducing body weight, improving inflammatory indicators, and restoring lung tissue to its normal state by administering chromium and formoterol therapy. The most effective strategy for treating both obesity and asthma is to address their two connected conditions. These findings demonstrate that combined chromium and formoterol therapy effectively addresses metabolic and inflammatory components of obesity-induced asthma, offering a promising dual-target therapeutic strategy.
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Affiliation(s)
- Rania T. Ibrahim
- Department of Scientific Research, Egypt Healthcare Authority, Ismailia, Egypt
| | - Yasser M. Moustafa
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, Egypt, Egypt
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
| | - Maha Abdullah Alwaili
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Amjad N. Alrebdi
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Afaf Alharthi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia
| | - Noha R. Noufal
- Basic Medical Science Department, College of Medicine, Dar Al Uloom University, Riyadh, Saudi Arabia
- Pathology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Dina M. Khodeer
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
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Mazzilli R, Zamponi V, Mancini C, Giorgini B, Golisano B, Mikovic N, Pecora G, Russo F, Martiradonna M, Paravani P, Prosperi D, Faggiano A. Neuroendocrine tumors and diabetes mellitus: which treatment and which effect. Endocrine 2025; 88:36-50. [PMID: 39752043 DOI: 10.1007/s12020-024-04149-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 12/23/2024] [Indexed: 01/04/2025]
Abstract
Diabetes mellitus (DM) and neuroendocrine tumors (NET) can exert unfavorable effects on each other prognosis. In this narrative review, we evaluated the effects of NET therapies on glycemic control and DM management and the effects of anti-diabetic therapies on NET outcome and management. For this purpose, we searched the PubMed, Science Direct, and Google Scholar databases for studies reporting the effects of NET therapy on DM as well as the effect of DM therapy on NET. The majority of NET treatments appear to impair glycaemic control, both inducing hypoglycemic or, more commonly, hyperglycemia and even new-onset DM. However, glucose metabolism imbalance can be effectively managed by modulating anti-diabetic therapy and adopting an appropriate nutritional approach. On the other hand, the effects of anti-diabetic treatment, like insulin, sulfonylureas, thiazolidinediones, ipeptidyl-peptidase-4 inhibitors, Glucagon-like peptide-1 receptor agonists, and Sodium-glucose cotransporter-2 inhibitors on NET are unclear. Recently, metformin has been investigated in patients with gastroenteropancreatic NET resulting in improved progression free survival suggesting a potential antineoplastic role. Finally, the management of DM in patients with NET is of great clinical relevance to correctly perform radiological procedures and even more functional imaging procedures, as well as to optimize the therapy and avoid treatment withdrawal or discontinuation. In conclusion, understanding the mechanisms underlying therapy-induced DM and implementing appropriate monitoring and management strategies of DM are essential for optimizing NET patient outcome and quality of life.
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Affiliation(s)
- Rossella Mazzilli
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy.
| | - Virginia Zamponi
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Camilla Mancini
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Beatrice Giorgini
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Bianca Golisano
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Nevena Mikovic
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Giulia Pecora
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Flaminia Russo
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Maurizio Martiradonna
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Piero Paravani
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Daniela Prosperi
- Unit of Nuclear Medicine, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
| | - Antongiulio Faggiano
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
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Hu H, Ding G, Liang W. Dietary therapy to halt the progression of diabetes to diabetic kidney disease. Food Funct 2025; 16:2622-2636. [PMID: 40047381 DOI: 10.1039/d4fo06011c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/01/2025]
Abstract
Diabetic Kidney Disease (DKD) is a common and serious complication of diabetes, particularly Type 2 Diabetes Mellitus (T2DM), which significantly contributes to patient morbidity and mortality. The limitations of traditional treatments like ACE inhibitors and ARBs in managing DKD progression highlight the need for innovative therapeutic strategies. This review examines the impact of various dietary patterns, such as the Mediterranean diet, ketogenic diet, intermittent fasting, DASH diet, and vegetarian diet, on the management of DKD. Evidence suggests these diets can halt the progression of DKD, although further research is needed to confirm their long-term effectiveness and safety. Personalized dietary approaches tailored to individual needs may enhance outcomes for DKD patients.
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Affiliation(s)
- Hongtu Hu
- Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.
- Nephrology and Urology Research Institute of Wuhan University, Wuhan, China
| | - Guohua Ding
- Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.
- Nephrology and Urology Research Institute of Wuhan University, Wuhan, China
| | - Wei Liang
- Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.
- Nephrology and Urology Research Institute of Wuhan University, Wuhan, China
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8
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Dyńka D, Rodzeń Ł, Rodzeń M, Pacholak-Klimas A, Ede G, Sethi S, Łojko D, Bartoń K, Berry K, Deptuła A, Grzywacz Ż, Martin P, Unwin J, Unwin D. Ketogenic Diets for Body Weight Loss: A Comparison with Other Diets. Nutrients 2025; 17:965. [PMID: 40289934 PMCID: PMC11945412 DOI: 10.3390/nu17060965] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/04/2025] [Accepted: 03/07/2025] [Indexed: 04/30/2025] Open
Abstract
With the prevalence of obesity and overweight increasing at an alarming rate, more and more researchers are focused on identifying effective weight loss strategies. The ketogenic diet (KD), used as a treatment in epilepsy management for over 100 years, is additionally gaining popularity as a weight loss method. Although its efficacy in weight loss is well documented, the areas where it may be beneficial to other dietary approaches need to be carefully examined. The objective of this paper is to identify the potential benefits of the KD over alternative dietary weight loss strategies based on a comprehensive literature review. It has been shown that the KD may be more bioenergetically efficient than other dietary strategies, inter alia owing to its effect on curtailing hunger, improving satiety and decreasing appetite (influence on hunger and satiety hormones and the sensation of hunger), inducing faster initial weight loss (associated with lower glycogen levels and reduced water retention), and controlling glycaemia and insulinemia (directly attributable to the low-carbohydrate nature of KD and indirectly to the other areas described). These effects are accompanied by improved insulin sensitivity, reduced inflammation (through ketone bodies and avoidance of pro-inflammatory sugars), reduced need for pharmacological obesity control (the diet's mechanisms are similar to those of medication but without the side effects), and positive impacts on psychological factors and food addiction. Based on the authors' review of the latest research, it is reasonable to conclude that, due to these many additional health benefits, the KD may be advantageous to other diet-based weight loss strategies. This important hypothesis deserves further exploration, which could be achieved by including outcome measures other than weight loss in future clinical trials, especially when comparing different diets of equal caloric value.
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Affiliation(s)
- Damian Dyńka
- Institute of Health Sciences, Faculty of Medical and Health Sciences, University of Siedlce, 08-110 Siedlce, Poland
| | | | | | | | - Georgia Ede
- Independent Researcher, 197 Lions Mouth Road, Amesbury, MA 01913, USA
| | - Shebani Sethi
- Metabolic Psychiatry, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94305, USA
| | - Dorota Łojko
- Department of Psychiatry, Poznan University of Medical Science, 60-572 Poznan, Poland
| | | | - Ken Berry
- Independent Researcher, Holladay, TN 38341, USA
| | - Adam Deptuła
- Faculty of Production Engineering and Logistics, Opole University of Technology, 76 Prószkowska St., 45-758 Opole, Poland
| | - Żaneta Grzywacz
- Faculty of Production Engineering and Logistics, Opole University of Technology, 76 Prószkowska St., 45-758 Opole, Poland
| | - Peter Martin
- Funmed Clinics, Vastra Hamngatan 13A, 41117 Gothenburg, Sweden
| | - Jen Unwin
- The Collaborative Health Community Foundation, Oxford OX2 9HZ, UK
| | - David Unwin
- Faculty of Health Social Care and Medicine, Edge Hill University, Ormskirk L39 4QP, UK
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9
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Bachar A, Birk R. Ketogenic Diet Intervention for Obesity Weight-Loss- A Narrative Review, Challenges, and Open Questions. Curr Nutr Rep 2025; 14:43. [PMID: 40056334 PMCID: PMC11890254 DOI: 10.1007/s13668-025-00634-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/25/2025] [Indexed: 03/10/2025]
Abstract
PURPOSE OF REVIEW The ketogenic diet (KD) has gained clinical attention for its potential benefits in weight loss and metabolic syndrome. By mimicking fasting through carbohydrate (CHO) restriction, KD shifts energy utilization to ketone bodies (KB) instead of glucose. Despite promising results, the effects on different weight loss indicators remain controversial, with challenges in monitoring adherence standards, optimal macronutrient composition, potential risks, and long-term sustainability. This article aims to review the different weight-loss outcomes of KD interventions for obesity, monitored by KB (adherence indication). RECENT FINDINGS Current literature on KD interventions for obesity weight loss monitored by KB show reduction in different outcomes, including body weight, body mass index, waist circumference, visceral adipose tissue, fat mass, and body fat percentage. Minor decreases in lean body mass and skeletal muscle mass were noted without resistance training. Variability existed in adherence (KB markers), CHO intake (7-27% of daily energy), diet duration (28 days to 12 months), and follow-up frequency (weekly to biannual). KD, particularly accompanied by exercise, positively influenced appetite regulation. KD interventions improves weight-related outcomes in participants with obesity but presents challenges in lean body mass reduction without resistance training and adherence variability. Standardizing methodologies, refining interventions and suitability to sub-populations, setting KB markers, and defining clinical relevance are essential for optimizing KD effectiveness.
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Affiliation(s)
- Adina Bachar
- Nutrition Department, Health Sciences Faculty, Ariel University, Ariel, Israel
| | - Ruth Birk
- Nutrition Department, Health Sciences Faculty, Ariel University, Ariel, Israel.
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Li J, He W, Wu Q, Qin Y, Luo C, Dai Z, Long Y, Yan P, Huang W, Cao L. Ketogenic diets and β-hydroxybutyrate in the prevention and treatment of diabetic kidney disease: current progress and future perspectives. BMC Nephrol 2025; 26:127. [PMID: 40055596 PMCID: PMC11887203 DOI: 10.1186/s12882-025-04019-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 02/12/2025] [Indexed: 05/13/2025] Open
Abstract
Diabetic kidney disease (DKD) is the main cause of end-stage renal disease. Ketogenic diets (KD) is a high-fat, low-carbohydrate diet. KD produces ketone bodies to supplement energy in the case of insufficient glucose in the body. β-Hydroxybutyrate (BHB) is the main component of ketone bodies. BHB serves as "ancillary fuel" substituting (but also inducing) anti-oxidative, anti-inflammatory, and cardio-protective features by binding to several target proteins, including histone acylation modification, or G protein-coupled receptors (GPCRs). KD have been used to treat epilepsy, obesity, type-2 diabetes mellitus, polycystic ovary syndrome, cancers, and other diseases. According to recent research, KD and the induced BHB delay DKD progression by improving the metabolism of glucose and lipids, regulating autophagy, as well as alleviating inflammation, oxidative stress and fibrosis. However, due to some side-effects, the role and mechanism of action of KD and BHB in the prevention and treatment of DKD are controversial. This review focuses on recent progress in the research of KD and BHB in clinical and preclinical studies of DKD, and provides new perspectives for DKD treatment.
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Affiliation(s)
- Junle Li
- Department of Nephrology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan, 646000, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, 646000, China
| | - Wanhong He
- Department of Nephrology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan, 646000, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, 646000, China
| | - Qianshi Wu
- Department of Nephrology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan, 646000, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, 646000, China
| | - Yuanyuan Qin
- Department of Nephrology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan, 646000, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, 646000, China
- Luzhou People's Hospital, Luzhou, China
| | - Changfang Luo
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan, 646000, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, 646000, China
| | - Zhuojun Dai
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan, 646000, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, 646000, China
| | - Yang Long
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan, 646000, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, 646000, China
| | - Pijun Yan
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan, 646000, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, 646000, China
| | - Wei Huang
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
- Sichuan Clinical Research Center for Diabetes and Metabolic Diseases, Luzhou, Sichuan, 646000, China.
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, 646000, China.
| | - Ling Cao
- Department of Nephrology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, 646000, China.
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Baskin RG, Karp KA. Navigating the Spectrum of 4 Evidence-Based Nutrition Options for Type 2 Diabetes Management. J Clin Endocrinol Metab 2025; 110:S112-S117. [PMID: 39998924 DOI: 10.1210/clinem/dgae646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Indexed: 02/27/2025]
Abstract
CONTEXT Type 2 diabetes mellitus is a complex, pervasive disease that creates a health and financial burden. The goal is to head off progression to insulin requirement, and dietary changes have been recognized as a first-line intervention in the treatment protocol. Four evidence-based nutritional options are reviewed and their benefits for metabolic consequences. EVIDENCE ACQUISITION We conducted a comprehensive search of relevant literature using the PubMed database for recent systematic reviews, meta-analyses, and original research articles. EVIDENCE SYNTHESIS The Mediterranean and plant-based diets have demonstrated benefits for the prevention and treatment of diabetes, weight reduction, lipid improvements, and overall cardiovascular risk reduction. A low carbohydrate diet is another viable option for hemoglobin A1c (HbA1c) reduction, though it is not as uniformly defined and is difficult to maintain long term. The ketogenic diet is similarly very restrictive and produces significant HbA1c reductions. CONCLUSION Type 2 diabetes prevention and treatment is crucial in this widespread disease. The first-line treatment is lifestyle modifications with dietary interventions being at the forefront. With a unique clinical model and a variety of dietary options, our program strives for individualized evidence-based care. Nutritional modifications are the best initial approaches to overcoming insulin resistance and hyperinsulinemia. All dietary modifications, like any medical intervention, require education on benefits vs risks.
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Affiliation(s)
- Revital Gorodeski Baskin
- University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
| | - Kimberly A Karp
- Endocrinology, University Hospitals of Cleveland, Cleveland, OH 44106, USA
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12
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Tian W, Cao S, Guan Y, Zhang Z, Liu Q, Ju J, Xi R, Bai R. The effects of low-carbohydrate diet on glucose and lipid metabolism in overweight or obese patients with T2DM: a meta-analysis of randomized controlled trials. Front Nutr 2025; 11:1516086. [PMID: 39834467 PMCID: PMC11743357 DOI: 10.3389/fnut.2024.1516086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 12/13/2024] [Indexed: 01/22/2025] Open
Abstract
Background The dual burden of Type 2 Diabetes Mellitus (T2DM) and obesity is a critical public health issue. Low-carbohydrate diets have emerged as a potential intervention, yet clinical evidence remains inconclusive. Purpose This meta-analysis assesses the impact of low-carbohydrate diets on metabolic profiles in overweight or obese T2DM patients, aiming to guide clinical practice. Methods A systematic review identified randomized clinical trials (RCTs) comparing low-carbohydrate diets to control diets in T2DM patients from PubMed, Embase, and the Cochrane Library databases up to April 2023. Results Seventeen RCTs, encompassing 1,197 participants, demonstrated that low-carbohydrate diets significantly improved HbA1c levels and fasting plasma glucose (mean difference [MD] = -0.36, 95% CI -0.44 to -0.29, p < 0.00001; MD = -10.71, 95% CI -14.39 to -7.03, p < 0.00001). They also reduced triglycerides and increased HDL cholesterol (MD = -19.91, 95% CI -28.83 to -10.99, p < 0.00001; MD = 2.49, 95% CI 1.07-3.91, p = 0.0006), without affecting LDL and total cholesterol. Weight loss, reduced BMI, lower diastolic blood pressure, and decreased waist circumference were additional benefits. Conclusion Low-carbohydrate diets may enhance glycemic control and lipid profiles in overweight or obese T2DM patients, warranting consideration in T2DM management. However, the variability in diet definitions and methodologies underscores the necessity for further research to standardize dietary guidelines and evaluate long-term effects.
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Affiliation(s)
- Wende Tian
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Shuyu Cao
- Changping Traditional Chinese Medicine Hospital, Beijing, China
| | - Yongxin Guan
- Liaoning University of Chinese Medicine, Shenyang, China
| | - Zihao Zhang
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qiyu Liu
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jianqing Ju
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ruixi Xi
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ruina Bai
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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13
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Li M, Zhang L, Li X, Zhao Y. Impact of short-term ketogenic diet on sex hormones and glucose-lipid metabolism in overweight or obese patients with polycystic ovary syndrome. J Obstet Gynaecol Res 2025; 51:e16178. [PMID: 39662521 DOI: 10.1111/jog.16178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 11/22/2024] [Indexed: 12/13/2024]
Abstract
AIM This study evaluates the clinical effects of a ketogenic diet (KD) versus a traditional comprehensive intervention, including lifestyle changes and oral contraceptives, in overweight or obese polycystic ovary syndrome (PCOS) patients. METHODS A retrospective analysis of 70 overweight/obese PCOS patients (body mass index [BMI] ≥24 kg/m2) treated between December 2022 and December 2023 was conducted. The patients were categorized into two groups based on their past treatment modality: Group 1 received a KD treatment (N = 35), and Group 2 underwent comprehensive intervention (N = 35), with both treatments lasting 3 months. Changes in body weight, BMI, sex hormone levels, glucose-lipid metabolism indicators, and liver and kidney function were compared. RESULTS Both groups experienced significant reductions in body weight and BMI after treatment (p < 0.05), with the KD group showing a greater reduction (p < 0.05). luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), and total testosterone (TT) levels decreased significantly in both groups (p < 0.05). The KD treatment led to significant reductions in fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) (p < 0.05), while the comprehensive intervention resulted in decreased FBG and ALT, and increased high-density lipoprotein-cholesterol (HDL-c) (p < 0.05). Additionally, the KD group had a greater reduction in FBG, and showed decreases in TG and AST, which remained unchanged in the comprehensive intervention group (p < 0.05). CONCLUSION The short-term KD treatment provides significant weight loss and effectively improves hormone regulation and glucose-lipid metabolism in overweight or obese PCOS patients, offering a valuable therapeutic option for managing the condition.
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Affiliation(s)
- Meng Li
- Department of Gynecology, Fuxing Hospital, Capital Medical University, Beijing, China
| | - Lisong Zhang
- Department of Gynecology, Fuxing Hospital, Capital Medical University, Beijing, China
| | - Xiaoyu Li
- Department of Gynecology, Fuxing Hospital, Capital Medical University, Beijing, China
| | - Yanzhong Zhao
- Department of Gynecology, Fuxing Hospital, Capital Medical University, Beijing, China
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14
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Misra A, Vikram NK, Ghosh A, Ranjan P, Gulati S. Revised definition of obesity in Asian Indians living in India. Diabetes Metab Syndr 2025; 19:102989. [PMID: 39814628 DOI: 10.1016/j.dsx.2024.102989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 03/04/2024] [Accepted: 03/12/2024] [Indexed: 01/18/2025]
Abstract
AIM The prevailing guidelines for obesity in Asian Indians, published in 2009, relied solely on body mass index (BMI) criteria. Recognizing the limitations of BMI in accurately diagnosing obesity and the emergence of new research revealing the association between generalized and abdominal adiposity in Asian Indians and early-onset co-morbid diseases, a comprehensive redefinition was needed. METHOD In a Delphi process focused on obesity in India, experts were invited via email to participate in five rounds. The survey questions were administered through Google Form to gather insights from the selected experts. RESULTS In Stage 1 Obesity, individuals exhibit increased adiposity (BMI>23 kg/m2) without discernible effects on organ functions or daily activities. Stage 2 Obesity denotes a more advanced state characterized by heightened adiposity (generalized and abdominal), impacting both physical and organ functions, resulting in functional limitations during day-to-day activities, and contributing to co-morbid diseases. The criteria for Stage 2 Obesity include a mandatory BMI exceeding 23 kg/m2 and at least one of the following: excess waist circumference or waist-to-height ratio. Additionally, the presence of one or more symptoms indicative of limitations in daily activities or one or more obesity-related comorbid conditions/diseases are needed to support the stage 2 obesity. CONCLUSION This refined framework seeks to enhance precision in identifying obesity and its associated health risks among Asian Indians living in India, and facilitation of rational management, and aligns with worldwide initiative of new definition of obesity.
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Affiliation(s)
- Anoop Misra
- Fortis CDOC Center of Excellence for Diabetes, Metabolic Diseases and Endocrinology, New Delhi, India; National Diabetes Obesity and Cholesterol Foundation (N-DOC), New Delhi, India; Diabetes Foundation India, New Delhi, India.
| | - Naval K Vikram
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Amerta Ghosh
- Fortis CDOC Center of Excellence for Diabetes, Metabolic Diseases and Endocrinology, New Delhi, India; National Diabetes Obesity and Cholesterol Foundation (N-DOC), New Delhi, India
| | - Piyush Ranjan
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Seema Gulati
- National Diabetes Obesity and Cholesterol Foundation (N-DOC), New Delhi, India; Diabetes Foundation India, New Delhi, India
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Güzey Akansel M, Baş M, Gençalp C, Kahrıman M, Şahin E, Öztürk H, Gür G, Gür C. Effects of the Ketogenic Diet on Microbiota Composition and Short-Chain Fatty Acids in Women with Overweight/Obesity. Nutrients 2024; 16:4374. [PMID: 39770995 PMCID: PMC11679786 DOI: 10.3390/nu16244374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 12/11/2024] [Accepted: 12/13/2024] [Indexed: 01/11/2025] Open
Abstract
Background/Objectives: The ketogenic diet (KD) is a dietary model that can impact metabolic health and microbiota and has been widely discussed in recent years. This study aimed to evaluate the effects of a 6-week KD on biochemical parameters, gut microbiota, and fecal short-chain fatty acids (SCFAs) in women with overweight/obesity. Methods: Overall, 15 women aged 26-46 years were included in this study. Blood samples, fecal samples, and anthropometric measurements were evaluated at the beginning and end of this study. Results: After KD, the mean body mass index decreased from 29.81 ± 4.74 to 27.12 ± 4.23 kg/m2, and all decreases in anthropometric measurements were significant (p < 0.05). Fasting glucose, insulin, homeostasis model assessment of insulin resistance, hemoglobin A1C, urea, and creatinine levels decreased, whereas uric acid levels increased (p < 0.05). Furthermore, increased serum zonulin levels were noted (p = 0.001), whereas fecal butyrate, propionate, acetate, and total SCFA levels decreased (p < 0.05). When the changes in microbiota composition were examined, a decrease in beta diversity (p = 0.001) was observed. After the intervention, a statistically significant increase was noted in the Firmicutes/Bacteroidetes ratio (p = 0.001). Although Oscilibacter, Blautia, and Akkermensia relative abundances increased, Prevotella relative abundance and Bifidobacter abundance, which were the dominant genera before the KD, decreased. Moreover, the abundance of some pathogenic genera, including Escherichia, Klebsilella, and Listeria, increased. Conclusions: In healthy individuals, KD may cause significant changes in microbial composition, leading to dysbiosis and long-term adverse outcomes with changes in serum zonulin and fecal SCFA levels.
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Affiliation(s)
- Müge Güzey Akansel
- Department of Nutrition and Dietetics, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey;
| | - Murat Baş
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey; (M.B.); (M.K.)
| | - Cansu Gençalp
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey; (M.B.); (M.K.)
| | - Meryem Kahrıman
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey; (M.B.); (M.K.)
| | - Eray Şahin
- Biostatistics and Bioinformatics PhD Program, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34572, Turkey;
| | - Hakan Öztürk
- Department of Physiology, Faculty of Veterinary Medicine, Ankara University, Ankara 06110, Turkey;
| | - Gürsel Gür
- Agriculture and Rural Development Support Institution, Ankara 06490, Turkey;
| | - Ceren Gür
- Bağcılar Training and Research Hospital, University of Health Sciences, Istanbul 34200, Turkey;
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16
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Lim SL, Tay M, Ang SM, Wai SN, Ong KW, Neo WJ, Yap QV, Chan YH, Khoo CM. Development and Pragmatic Randomized Controlled Trial of Healthy Ketogenic Diet Versus Energy-Restricted Diet on Weight Loss in Adults with Obesity. Nutrients 2024; 16:4380. [PMID: 39771001 PMCID: PMC11677078 DOI: 10.3390/nu16244380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 12/13/2024] [Accepted: 12/15/2024] [Indexed: 01/11/2025] Open
Abstract
Introduction: The ketogenic diet (KD) is widely used for weight management by reducing appetite, enhancing fat oxidation, and facilitating weight loss. However, the high content of total and saturated fats in a conventional KD may elevate low-density lipoprotein (LDL)-cholesterol levels, a known risk factor for cardiovascular diseases, highlighting the need for healthier alternatives. This study aimed to investigate the effect of a newly developed Healthy Ketogenic Diet (HKD) versus an Energy-Restricted Diet (ERD) on weight loss and metabolic outcomes among adults with obesity. Methods: Multi-ethnic Asian adults (n = 80) with body mass index ≥ 27.5 kg/m2 were randomized either to HKD (n = 41) or ERD (n = 39) for 6 months. Both groups followed an energy-restricted healthy diet, emphasizing on reducing saturated and trans fats. The HKD group additionally limited net carbohydrate intake to no more than 50 g per day. Dietary adherence was supported via the Nutritionist Buddy app with dietitian coaching. The primary outcome was weight change from baseline at 6 months. Secondary outcomes included weight change at 3 months and 1 year, along with changes in metabolic profiles. Data were analyzed using linear regression with an intention-to-treat approach. Results: The HKD group achieved significantly greater mean weight loss at 6 months than the ERD group (-7.8 ± 5.2 kg vs. -4.2 ± 5.6 kg, p = 0.01). The mean weight loss percentage at 6 months was 9.3 ± 5.9% and 4.9 ± 5.8% for the HKD and ERD groups, respectively (p = 0.004). Improvements in metabolic profiles were also significantly better in the HKD group [glycated hemoglobin (-0.3 ± 0.3% vs. -0.1 ± 0.2%, p = 0.008), systolic blood pressure (-7.7 ± 8.9 mmHg vs. -2.6 ± 12.2 mmHg, p = 0.005), and aspartate transaminase (-7.6 ± 15.5 IU/L vs. 0.6 ± 11.5 IU/L, p = 0.01)], with no increase in LDL-cholesterol (-0.12 ± 0.60 mmol/L vs. -0.04 ± 0.56 mmol/L, p = 0.97) observed in either group. Conclusions: The HKD was more effective than the ERD in promoting weight loss and improving cardiometabolic outcomes without elevation in LDL-cholesterol. It can be recommended for therapeutic intervention in patients with obesity.
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Affiliation(s)
- Su Lin Lim
- Office of Allied Health & Pharmacy, National University Hospital, Singapore 119228, Singapore
| | - Melissa Tay
- Department of Dietetics, National University Hospital, Singapore 119074, Singapore; (M.T.); (S.M.A.); (S.N.W.); (K.W.O.); (W.J.N.)
| | - Siew Min Ang
- Department of Dietetics, National University Hospital, Singapore 119074, Singapore; (M.T.); (S.M.A.); (S.N.W.); (K.W.O.); (W.J.N.)
| | - Shu Ning Wai
- Department of Dietetics, National University Hospital, Singapore 119074, Singapore; (M.T.); (S.M.A.); (S.N.W.); (K.W.O.); (W.J.N.)
| | - Kai Wen Ong
- Department of Dietetics, National University Hospital, Singapore 119074, Singapore; (M.T.); (S.M.A.); (S.N.W.); (K.W.O.); (W.J.N.)
| | - Wen Joo Neo
- Department of Dietetics, National University Hospital, Singapore 119074, Singapore; (M.T.); (S.M.A.); (S.N.W.); (K.W.O.); (W.J.N.)
| | - Qai Ven Yap
- Biostatistics Unit, Yong Loo Lin School of Medicine, National University Singapore, Singapore 117597, Singapore; (Q.V.Y.); (Y.H.C.)
| | - Yiong Huak Chan
- Biostatistics Unit, Yong Loo Lin School of Medicine, National University Singapore, Singapore 117597, Singapore; (Q.V.Y.); (Y.H.C.)
| | - Chin Meng Khoo
- Department of Medicine, National University Hospital, Singapore 119074, Singapore;
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Pescari D, Mihuta MS, Bena A, Stoian D. Quantitative analysis of the caloric restriction versus isocaloric diets models based on macronutrients composition: impacts on body weight regulation, anthropometric, and bioimpedance parameters in women with obesity. Front Nutr 2024; 11:1493954. [PMID: 39726871 PMCID: PMC11670075 DOI: 10.3389/fnut.2024.1493954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 12/02/2024] [Indexed: 12/28/2024] Open
Abstract
Introduction Obesity is a growing public health issue, especially among young adults, with long-term management strategies still under debate. This prospective study compares the effects of caloric restriction and isocaloric diets with different macronutrient distributions on body composition and anthropometric parameters in obese women during a 12-week weight loss program, aiming to identify the most effective dietary strategies for managing obesity-related health outcomes. Methods A certified clinical nutritionist assigned specific diets over a 12-week period to 150 participants, distributed as follows: hypocaloric diets-low-energy diet (LED, 31 subjects) and very low-energy diet (VLED, 13 subjects); isocaloric diets with macronutrient distribution-low-carbohydrate diet (LCD, 48 subjects), ketogenic diet (KD, 23 subjects), and high-protein diet (HPD, 24 subjects); and isocaloric diet without macronutrient distribution-time-restricted eating (TRE, 11 subjects). Participants were dynamically monitored using anthropometric parameters: body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and bioelectrical impedance analysis (BIA) using the TANITA Body Composition Analyzer BC-418 MA III (T5896, Tokyo, Japan) at three key intervals-baseline, 6 weeks, and 12 weeks. The following parameters were evaluated: body weight, basal metabolic rate (BMR), percentage of total body fat, trunk fat, muscle mass, fat-free mass, and hydration status. Results All diets led to weight loss, but differences emerged over time. The TRE model resulted in significantly less weight loss compared to LED at the final follow-up (6.30 kg, p < 0.001), similar to the VLED (4.69 kg, p < 0.001). Isocaloric diets with varied macronutrient distributions showed significant weight loss compared to LED (p < 0.001). The KD reduced waist circumference at both 6 and 12 weeks (-4.08 cm, p < 0.001), while significant differences in waist-to-hip ratio reduction were observed across diet groups at 12 weeks (p = 0.01). Post-hoc analysis revealed significant fat mass differences at 12 weeks, with HPD outperforming IF (p = 0.01) and VLED (p = 0.003). LCD reduced trunk fat at 6 weeks (-2.36%, p = 0.001) and 12 weeks (-3.79%, p < 0.001). HPD increased muscle mass at 12 weeks (2.95%, p = 0.001), while VLED decreased it (-2.02%, p = 0.031). TRE showed a smaller BMR reduction at 12 weeks compared to LED. Conclusion This study highlights the superior long-term benefits of isocaloric diets with macronutrients distribution over calorie-restrictive diets in optimizing weight, BMI, body composition, and central adiposity.
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Affiliation(s)
- Denisa Pescari
- Department of Doctoral Studies, Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania
- Center for Molecular Research in Nephrology and Vascular Disease, Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania
| | - Monica Simina Mihuta
- Center for Molecular Research in Nephrology and Vascular Disease, Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania
| | - Andreea Bena
- Center for Molecular Research in Nephrology and Vascular Disease, Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania
- Discipline of Endocrinology, Second Department of Internal Medicine, Victor Babeș University of Medicine and Pharmacy Timisoara, Timisoara, Romania
| | - Dana Stoian
- Center for Molecular Research in Nephrology and Vascular Disease, Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania
- Discipline of Endocrinology, Second Department of Internal Medicine, Victor Babeș University of Medicine and Pharmacy Timisoara, Timisoara, Romania
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Hironaka J, Hamaguchi M, Ichikawa T, Nakajima H, Okamura T, Majima S, Senmaru T, Okada H, Ushigome E, Nakanishi N, Joo E, Shide K, Fukui M. Low-carbohydrate diets in East Asians with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. J Diabetes Investig 2024; 15:1753-1762. [PMID: 39360850 PMCID: PMC11615700 DOI: 10.1111/jdi.14326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 09/12/2024] [Accepted: 09/17/2024] [Indexed: 10/05/2024] Open
Abstract
AIMS Despite the reported success of low-carbohydrate diets in improving glycemic control in the Western countries, no studies have investigated the effects of such diets in Asians. We aimed to conduct a systematic review and meta-analysis of randomized controlled trials to examine the effects of low-carbohydrate diets on glycemic control in East Asian adults. MATERIALS AND METHODS We systematically searched the PubMed, Cochrane Library, and Embase databases from inception to June 28, 2023, to identify randomized controlled trials examining the efficacy of low-carbohydrate diets in patients with type 2 diabetes (PROSPERO number CRD 42023453007). The primary outcome was the difference in glycated hemoglobin levels between the low-carbohydrate diet and control groups. The secondary outcome was the difference in body mass index, fasting blood glucose level, blood pressure, and lipid profile. RESULTS Six randomized controlled trials met the eligibility criteria. The study duration ranged from 3 to 18 months, with five studies conducted within 6 months. The results showed that low-carbohydrate diets were more beneficial in lowering glycated hemoglobin levels and body mass index than control diets. The risk of bias for the six studies was minimal for two and moderate for four. The heterogeneity among the studies was low. CONCLUSIONS Low-carbohydrate diets improved glycated hemoglobin levels and body mass index in East Asians compared with control diets. Therefore, carbohydrate restriction may be effective for glycemic management in East Asians with type 2 diabetes for at least 6 months.
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Affiliation(s)
- Junya Hironaka
- Department of Endocrinology and Metabolism, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Takahiro Ichikawa
- Department of Endocrinology and Metabolism, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Hanako Nakajima
- Department of Endocrinology and Metabolism, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Takuro Okamura
- Department of Endocrinology and Metabolism, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Saori Majima
- Department of Endocrinology and Metabolism, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Takafumi Senmaru
- Department of Endocrinology and Metabolism, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Hiroshi Okada
- Department of Endocrinology and Metabolism, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Emi Ushigome
- Department of Endocrinology and Metabolism, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Naoko Nakanishi
- Department of Endocrinology and Metabolism, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Erina Joo
- Department of Metabolism and Clinical NutritionKyoto University HospitalKyotoJapan
| | - Kenichiro Shide
- Department of Metabolism and Clinical NutritionKyoto University HospitalKyotoJapan
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
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19
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Zweers HEE, Kroesen SH, Beerlink G, Buit E, Gerrits K, Dorhout A, van Wegberg AMJ, Janssen MCH, Wortmann SB, Timmers S, Saris CGJ. Ketogenic diet in adult patients with mitochondrial myopathy. Mol Genet Metab 2024; 143:108610. [PMID: 39602868 DOI: 10.1016/j.ymgme.2024.108610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 11/01/2024] [Accepted: 11/01/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND This study aimed to explore the feasibility, safety and efficacy of a Modified Atkins Diet (MAD) in patients with mitochondrial myopathy (MM). METHODS Patients with genetically proven mitochondrial disorder and exercise intolerance or muscle weakness followed a twelve week MAD. Feasibility was measured by diet duration and ketone levels. Safety was assessed by monitoring adverse events (AE). Efficacy was assessed by a maximal incremental test and a muscle performance test. RESULTS Eight out of twenty patients completed the twelve week intervention. Reasons to discontinue were the occurrence of AE: rhabdomyolysis (n = 3), vomiting (n = 1), fatigue (n = 6), constipation (n = 1), in combination with a lack of improvement and adherence difficulties. On an individual level, various positive effects were reported including improvements in VO2peak (n = 6), anaerobic threshold (n = 9), muscle fatigue resistance (n = 5), muscle strength (n = 7), fatigue (n = 6), glucose tolerance (n = 7), migraine (n = 3), sleep (n = 3), and gastrointestinal complaints (n = 2). Lipid profile improved and thirteen patients lost weight. All patients with mitochondrial DNA (mtDNA) deletions, experienced muscle related AE. The five patients with the m.3243A>G mutation achieved the longest diet duration. DISCUSSION/CONCLUSION MAD feasibility, safety and efficacy is variable in MD patients. MAD appears to be unsuitable for MD patients with mtDNA deletions. All patients should be monitored closely for adverse events when initiating the diet. Further research should focus on predictive factors to consider the diet, effectiveness of less stringent carbohydrate restricted diets.
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Affiliation(s)
- Heidi E E Zweers
- Department of Gastroenterology and HepatologyDietetics, Radboudumc, Nijmegen, the Netherlands; Radboud Centre for Mitochondrial Medicine (RCMM), Nijmegen, the Netherlands.
| | - Sophie H Kroesen
- Department of Medical BioSciences, Radboudumc, Nijmegen, the Netherlands
| | - Gijsje Beerlink
- Department of Gastroenterology and HepatologyDietetics, Radboudumc, Nijmegen, the Netherlands; Radboud Centre for Mitochondrial Medicine (RCMM), Nijmegen, the Netherlands
| | - Elke Buit
- Radboud Centre for Mitochondrial Medicine (RCMM), Nijmegen, the Netherlands; Department of internal Medicine, Radboudumc, Nijmegen, The Netherlands
| | - Karlijn Gerrits
- Department of Gastroenterology and HepatologyDietetics, Radboudumc, Nijmegen, the Netherlands; Radboud Centre for Mitochondrial Medicine (RCMM), Nijmegen, the Netherlands
| | - Astrid Dorhout
- Department of Gastroenterology and HepatologyDietetics, Radboudumc, Nijmegen, the Netherlands; Radboud Centre for Mitochondrial Medicine (RCMM), Nijmegen, the Netherlands
| | - Annemiek M J van Wegberg
- Department of Gastroenterology and HepatologyDietetics, Radboudumc, Nijmegen, the Netherlands; Radboud Centre for Mitochondrial Medicine (RCMM), Nijmegen, the Netherlands
| | - Mirian C H Janssen
- Radboud Centre for Mitochondrial Medicine (RCMM), Nijmegen, the Netherlands; Department of internal Medicine, Radboudumc, Nijmegen, The Netherlands
| | - Saskia B Wortmann
- Radboud Centre for Mitochondrial Medicine (RCMM), Nijmegen, the Netherlands; University Children's Hospital, Paracelsus Medical University, Salzburg, Austria
| | - Silvie Timmers
- Human and Animal Physiology, Wageningen University, The Netherlands
| | - Christiaan G J Saris
- Radboud Centre for Mitochondrial Medicine (RCMM), Nijmegen, the Netherlands; Department of Neurology, Cognition and Behaviour, Donders Institute for Brain, Radboudumc, Nijmegen, the Netherlands
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20
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Losada-Díaz F, Lizarazo-Bocanegra S, Perdomo-Lugo JJ, Gutiérrez-Romero SA, Correa-Osio I, Mendivil CO. Differential Efficacy of Weight Loss Interventions in Patients with Versus Without Diabetes. Diabetes Ther 2024; 15:2279-2291. [PMID: 39276293 PMCID: PMC11467141 DOI: 10.1007/s13300-024-01646-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 08/27/2024] [Indexed: 09/16/2024] Open
Abstract
Obesity is both a major risk factor for diabetes and a serious comorbidity of the condition. The twin epidemics of obesity and diabetes have spread globally over the past few decades. Treatment of obesity in patients with diabetes provides a host of clinical benefits that encompass virtually all body systems. Despite this, multiple lines of evidence suggest that the efficacy of most therapies for weight loss is significantly reduced among patients with diabetes. With this background, we summarize the evidence of a differential effect of lifestyle, pharmacological, and surgical treatments for obesity in patients with existing diabetes, and explore the potential mechanisms involved in this phenomenon. This information is then used to formulate strategies to improve weight loss outcomes for patients with diabetes.
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Affiliation(s)
| | | | | | | | | | - Carlos O Mendivil
- School of Medicine, Universidad de los Andes, Bogotá, Colombia.
- Section of Endocrinology, Department of Internal Medicine, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
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21
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Malinowska D, Żendzian-Piotrowska M. Ketogenic Diet: A Review of Composition Diversity, Mechanism of Action and Clinical Application. J Nutr Metab 2024; 2024:6666171. [PMID: 39463845 PMCID: PMC11511599 DOI: 10.1155/2024/6666171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 05/16/2024] [Accepted: 09/30/2024] [Indexed: 10/29/2024] Open
Abstract
The ketogenic diet (KD) is a special high-fat, very low-carbohydrate diet with the amount of protein adjusted to one's requirements. By lowering the supply of carbohydrates, this diet induces a considerable change in metabolism (of protein and fat) and increases the production of ketone bodies. The purpose of this article is to review the diversity of composition, mechanism of action, clinical application and risk associated with the KD. In the last decade, more and more results of the diet's effects on obesity, diabetes and neurological disorders, among other examples have appeared. The beneficial effects of the KD on neurological diseases are related to the reconstruction of myelin sheaths of neurons, reduction of neuron inflammation, decreased production of reactive oxygen species, support of dopamine production, repair of damaged mitochondria and formation of new ones. Minimizing the intake of carbohydrates results in the reduced absorption of simple sugars, thereby decreasing blood glucose levels and fluctuations of glycaemia in diabetes. Studies on obesity indicate an advantage of the KD over other diets in terms of weight loss. This may be due to the upregulation of the biological activity of appetite-controlling hormones, or to decreased lipogenesis, intensified lipolysis and increased metabolic costs of gluconeogenesis. However, it is important to be aware of the side effects of the KD. These include disorders of the digestive system as well as headaches, irritability, fatigue, the occurrence of vitamin and mineral deficiencies and worsened lipid profile. Further studies aimed to determine long-term effects of the KD are required.
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Affiliation(s)
- Dominika Malinowska
- Medical University of Bialystok, Department of Hygiene, Epidemiology and Ergonomy, ul. Jana Kilińskiego 1, Białystok 15-089, Poland
| | - Małgorzata Żendzian-Piotrowska
- Medical University of Bialystok, Department of Hygiene, Epidemiology and Ergonomy, ul. Jana Kilińskiego 1, Białystok 15-089, Poland
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22
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Qu X, Huang L, Rong J. The ketogenic diet has the potential to decrease all-cause mortality without a concomitant increase in cardiovascular-related mortality. Sci Rep 2024; 14:22805. [PMID: 39353986 PMCID: PMC11445255 DOI: 10.1038/s41598-024-73384-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Accepted: 09/17/2024] [Indexed: 10/03/2024] Open
Abstract
The impact of the ketogenic diet (KD) on overall mortality and cardiovascular disease (CVD) mortality remains inconclusive.This study enrolled a total of 43,776 adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2018 to investigate the potential association between dietary ketogenic ratio (DKR) and both all-cause mortality as well as cardiovascular disease(CVD) mortality.Three models were established, and Cox proportional hazards regression analysis was employed to examine the correlation. Furthermore, a restricted cubic spline function was utilized to assess the non-linear relationship. In addition, subgroup analysis and sensitivity analysis were performed.In the adjusted Cox proportional hazards regression model, a significant inverse association was observed between DKR and all-cause mortality (HR = 0.76, 95% CI = 0.63-0.9, P = 0.003). However, no significant association with cardiovascular mortality was found (HR = 1.13; CI = 0.79-1.6; P = 0.504). Additionally, a restricted cubic spline(RCS) analysis demonstrated a linear relationship between DKR and all-cause mortality risk. In the adult population of the United States, adherence to a KD exhibits potential in reducing all-cause mortality risk while not posing an increased threat of CVD-related fatalities.
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Affiliation(s)
- Xiaolong Qu
- Department of Cardiovascular Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, 160 Pujian Road, Pudong New Area, Shanghai, 200120, China
| | - Lei Huang
- Department of Cardiology, Renji Hospital Ningbo Branch, Shanghai Jiao Tong University School of Medicine, 1155 Binhai 2nd Road, Hangzhou Bay New District, Ningbo, 315336, China
| | - Jiacheng Rong
- Department of Cardiology, Renji Hospital Ningbo Branch, Shanghai Jiao Tong University School of Medicine, 1155 Binhai 2nd Road, Hangzhou Bay New District, Ningbo, 315336, China.
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23
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Maleki MH, Khakshournia S, Heydarnia E, Omidi F, Taghizadeh M, Zeynolabedinzadeh M, Akbari M, Vakili O, Shafiee SM. Attenuation of brown adipocyte whitening in high-fat diet-induced obese rats: Effects of melatonin and β-hydroxybutyrate on Cidea, Fsp27 and MT1 expression. Diabetes Obes Metab 2024; 26:4551-4561. [PMID: 39118207 DOI: 10.1111/dom.15810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 06/25/2024] [Accepted: 07/04/2024] [Indexed: 08/10/2024]
Abstract
AIM To investigate the effects of β-hydroxybutyrate (BHB) and melatonin on brown adipose tissue (BAT) plasticity in rats fed a high-fat diet (HFD). METHODS We employed a 7-week experimental design for a study on 30 male Sprague-Dawley rats divided into five groups: (1) a control-diet fed group; (2) a high-fat diet (HFD)-fed group; (3) a group that received an HFD and a BHB solution in their drinking water; (4) a group that received an HFD with 10 mg/kg/day melatonin in their drinking water; and (5) a group that received an HFD and were also treated with the combination of BHB and melatonin. Following the treatment period, biochemical indices, gene expression levels of key thermogenic markers (including uncoupling protein 1 [UCP1], PR domain containing 16 [PRDM16], Cidea, fat-specific protein 27 [Fsp27], and metallothionein 1 [MT1]), and stereological assessments of BAT were evaluated. RESULTS Treatment with BHB and melatonin significantly boosted blood ketone levels, improved lipid profiles, and reduced weight gain from an HFD. It also downregulated genes linked to WAT, namely, Cidea and Fsp27, and upregulated key BAT markers, including UCP1, PRDM16 and peroxisome proliferator-activated receptor-gamma coactivator-1-alpha. Additionally, the co-treatment increased MT1 receptor expression and enhanced the structural density of BAT. CONCLUSION The combined oral administration of BHB and melatonin successfully prevented the whitening of BAT in obese rats fed an HFD, indicating its potential as a therapeutic strategy for obesity-related BAT dysfunction. The synergistic effects of this treatment underscore the potential of a combined approach to address BAT dysfunction in obesity.
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MESH Headings
- Animals
- Male
- Rats
- 3-Hydroxybutyric Acid/pharmacology
- Adipocytes, Brown/drug effects
- Adipocytes, Brown/metabolism
- Adipose Tissue, Brown/metabolism
- Adipose Tissue, Brown/drug effects
- Diet, High-Fat/adverse effects
- Melatonin/pharmacology
- Obesity/metabolism
- Obesity/drug therapy
- Rats, Sprague-Dawley
- Receptor, Melatonin, MT1/metabolism
- Receptor, Melatonin, MT1/genetics
- Thermogenesis/drug effects
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Affiliation(s)
- Mohammad Hasan Maleki
- Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sara Khakshournia
- Autophagy Research Center, Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Emad Heydarnia
- Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Fateme Omidi
- Students Research Committee, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Motahareh Taghizadeh
- Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahroo Zeynolabedinzadeh
- Nutrition and Food Sciences Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | | | - Omid Vakili
- Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sayed Mohammad Shafiee
- Autophagy Research Center, Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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24
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Amato ACM, Amato JLS, Benitti DA. The Efficacy of Ketogenic Diets (Low Carbohydrate; High Fat) as a Potential Nutritional Intervention for Lipedema: A Systematic Review and Meta-Analysis. Nutrients 2024; 16:3276. [PMID: 39408242 PMCID: PMC11478561 DOI: 10.3390/nu16193276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 09/20/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND Lipedema is a frequently misdiagnosed condition in women, often mistaken for obesity, which significantly deteriorates both quality of life and physical health. Recognizing the necessity for holistic treatment strategies, research has increasingly supported the integration of specific dietary approaches, particularly ketogenic diets focusing on low-carbohydrate and high-fat intake. OBJECTIVES to evaluate the impact of ketogenic diets on women with lipedema through a systematic review and meta-analysis. METHODS A systematic review and meta-analysis were conducted by reviewing published, peer-reviewed studies addressing the implications of a low-carbohydrate, high-fat (LCHF) ketogenic diet in managing lipedema following comprehensive scrutiny of digital medical databases, such as PubMed, PubMed Central, Science Direct, and the Web of Science. This research was governed by specified parameters, including an established search string composed of search terms and an eligibility criterion (PICO) as denoted by the principal authors. Statistical analysis was carried out using RevMan 5.4.1 software with the Newcastle-Ottawa Scale utilized for quality appraisal of the included studies. RESULTS Seven studies reporting statistical outcomes were included in the systematic review and meta-analysis following a rigorous quality appraisal and data identification process. Three hundred and twenty-nine female participants were diagnosed with lipedema and treated using a low-carbohydrate, high-fat diet. Data analysis identified the high-fat diet with a mean study duration of 15.85 weeks. Mean Differences (MDs) on changes pre- and post-intervention showed significant reductions in BMI and total body weight [4.23 (95% CI 2.49, 5.97) p < 0.00001 and 7.94 (95% CI 5.45, 10.43) p < 0.00001 for BMI and body weight, respectively]. Other anthropometric measurements, such as changes in waist/hip circumferences and waist/hip ratios, showed a significant reduction in these parameters, with an MD of 8.05 (95% CI 4.66, 11.44) p < 0.00001 and an MD of 6.67 (95% CI 3.35, 9.99) p < 0.0001 for changes in waist and hip circumferences from baseline, respectively. Lastly, changes in pain sensitivity were statistically significant post-intervention [MD 1.12 (95% CI, 0.44, 1.79) p = 0.001]. All studies scored fair on the Newcastle-Ottawa Scale. CONCLUSIONS despite the limited studies and low number of study participants, the review observed a significant reduction in anthropometric and body composition metrics, indicating a potentially beneficial association between LCHF ketogenic diets and lipedema management.
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Affiliation(s)
| | | | - Daniel Augusto Benitti
- Department of Vascular and Endovascular Surgery, Medical Valens Center, São Paulo 01533-010, Brazil;
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25
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Beretta MV, Flores CAO, Colameo GF, Echabe LW, Busnello FM. Low-Carbohydrate Dietary Interventions for Metabolic Control in Individuals With Type 2 Diabetes Mellitus: An Overview of Systematic Reviews. Nutr Rev 2024:nuae123. [PMID: 39298713 DOI: 10.1093/nutrit/nuae123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/22/2024] Open
Abstract
CONTEXT Dietary interventions providing different amounts of carbohydrates have been proposed as a means of achieving glycemic control and weight loss in type 2 diabetes mellitus (T2DM); however, the supporting evidence is heterogeneous, making this recommendation difficult to apply in nutritional clinical practice. OBJECTIVE The aim was to assess the quality of evidence from meta-analyses on low-carbohydrate (LC) dietary interventions for glycemic control, weight loss, and lipid profile in individuals with T2DM. DATA SOURCES The MEDLINE, Web of Science, and Scopus databases were searched until September 2023. DATA EXTRACTION A systematic review was conducted. Systematic reviews with meta-analysis of randomized clinical trials designed to assess glycated hemoglobin (HbA1c) reductions in individuals with T2DM were eligible. The AMSTAR-2 critical appraisal tool was used to evaluate the methodological aspects of all included studies. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to assess the certainty of the evidence. DATA ANALYSIS The LC interventions were associated with a reduction in HbA1c (%) of -0.42 (-1.45 to -0.09; high certainty of evidence) without considering follow-up time; at up to 3 months of follow-up of -0.28 (-0.13 to -0.43); at up to 6 months of follow-up of -0.40 (-0.61 to -0.09); at 6 to 12 months of follow-up of -0.32 (-0.49 to 0.11); and at >12 months of follow-up time of -0.31 (-0.14 to -0.65) compared with control diets. CONCLUSION LC diets can help reduce HbA1c in individuals with T2DM in the short term (up to 3 months). However, dietary recommendations must always be individualized, as the studies reviewed herein analyzed different populations and used different definitions of what constitutes an LC diet. SYSTEMATIC REVIEW REGISTRATION PROSPERO no. CRD42023404197.
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Affiliation(s)
- Mileni Vanti Beretta
- Graduate Program in Nutrition Sciences, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, RS 90050-170, Brazil
| | - Cíntia Aparecida Oliveira Flores
- Graduate Program in Nutrition Sciences, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, RS 90050-170, Brazil
| | - Gabriella Fontes Colameo
- Graduate Program in Nutrition Sciences, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, RS 90050-170, Brazil
| | - Luana Weissheimer Echabe
- Undergraduate Course in Nutrition, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, RS 90050-170, Brazil
| | - Fernanda Michielin Busnello
- Department of Nutrition and Graduate Program in Nutrition Sciences, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, RS 90050-170, Brazil
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26
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Hilary S, Östlundh L, Platat C, Al-Rifai RH, Almehairbi O, Alshamsi F, Ali HI, Al Dhaheri AS, Cheikh Ismail L, Stojanovska L. Effect of ketogenic diets on lipid metabolism in adults: protocol for a systematic review. BMJ Open 2024; 14:e076938. [PMID: 39260854 PMCID: PMC11409393 DOI: 10.1136/bmjopen-2023-076938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 02/27/2024] [Indexed: 09/13/2024] Open
Abstract
INTRODUCTION The ketogenic diet is a very low carbohydrate diet known for its ability to reduce weight and counteract hyperglycaemia. However, ketogenic diets recommend an increased intake of fats, raising concerns about cardiometabolic risk in adults. Due to the higher intake of fats in the ketogenic diet, there is significant variability in outcomes of lipid metabolism in the population. Interventions have reported improvements in lipid profile while other studies did not find changes, and there are reports of increased low density lipoprotein (LDL) and triglyceride values. Hence, this is a protocol for a systematic review of the published literature and a summary of the effect of ketogenic diets on lipid metabolism in adults. METHODS AND ANALYSIS Five databases (PubMed, Embase, Scopus, Cochrane Library and Web of Science) will be searched for studies on ketogenic diets in adult populations. Studies will be included if they report results from ketogenic diet interventions among adults. Exclusion is populations with diagnosed neurological disorders. Two reviewers will independently screen retrieved citations, extract data and appraise the risk of bias. Quantitative estimates (eg, standardised mean difference) measuring the change in the total cholesterol, LDL and triglyceride concentration will be pooled using random effects meta-analysis to produce one summarised weighted estimate. Sources of heterogeneity will be explored using subgroup analysis. This protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis for Protocols (PRISMA), and the final review will be reported following the PRISMA 2020 guidelines. ETHICS AND DISSEMINATION The present protocol and the systematic review to be carried out do not require ethics clearance. The data source will be published studies. This review will provide estimates to inform the public about the effect of ketogenic diets on lipid metabolism and the possible peril of increasing cardiometabolic risk. The results will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER CRD42022309665.
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Affiliation(s)
- Serene Hilary
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
| | - Linda Östlundh
- Örebro University Library, Örebro University, Örebro, Sweden
| | - Carine Platat
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
| | - Rami H Al-Rifai
- Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
| | - Osha Almehairbi
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
| | - Fayeza Alshamsi
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
| | - Habiba I Ali
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
| | - Ayesha S Al Dhaheri
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
| | - Leila Cheikh Ismail
- Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, Sharjah, UAE
- Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK
| | - Lily Stojanovska
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
- Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
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27
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Dyńka D, Rodzeń Ł, Rodzeń M, Łojko D, Kraszewski S, Ibrahim A, Hussey M, Deptuła A, Grzywacz Ż, Ternianov A, Unwin D. Beneficial Effects of the Ketogenic Diet on Nonalcoholic Fatty Liver Disease (NAFLD/MAFLD). J Clin Med 2024; 13:4857. [PMID: 39200999 PMCID: PMC11355934 DOI: 10.3390/jcm13164857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/11/2024] [Accepted: 08/12/2024] [Indexed: 09/02/2024] Open
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) is likely to be approaching 38% of the world's population. It is predicted to become worse and is the main cause of morbidity and mortality due to hepatic pathologies. It is particularly worrying that NAFLD is increasingly diagnosed in children and is closely related, among other conditions, to insulin resistance and metabolic syndrome. Against this background is the concern that the awareness of patients with NAFLD is low; in one study, almost 96% of adult patients with NAFLD in the USA were not aware of their disease. Thus, studies on the therapeutic tools used to treat NAFLD are extremely important. One promising treatment is a well-formulated ketogenic diet (KD). The aim of this paper is to present a review of the available publications and the current state of knowledge of the effect of the KD on NAFLD. This paper includes characteristics of the key factors (from the point of view of NAFLD regression), on which ketogenic diet exerts its effects, i.e., reduction in insulin resistance and body weight, elimination of fructose and monosaccharides, limitation of the total carbohydrate intake, anti-inflammatory ketosis state, or modulation of gut microbiome and metabolome. In the context of the evidence for the effectiveness of the KD in the regression of NAFLD, this paper also suggests the important role of taking responsibility for one's own health through increasing self-monitoring and self-education.
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Affiliation(s)
- Damian Dyńka
- Rodzen Brothers Foundation, 64-234 Wieleń, Poland
| | | | | | - Dorota Łojko
- Department of Psychiatry, Poznan University of Medical Science, 60-572 Poznan, Poland
| | - Sebastian Kraszewski
- Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology, 50-370 Wroclaw, Poland
| | - Ali Ibrahim
- Schoen Inpatient Children’s Eating Disorders Service, 147 Chester Rd, Streetly, Sutton Coldfield B74 3NE, UK
| | - Maria Hussey
- Private General Medical Practice Maria Hussey, Ojcowa Wola 5, 14-420 Mlynary, Poland
| | - Adam Deptuła
- Faculty of Production Engineering and Logistics, Opole University of Technology, 76 Prószkowska St., 45-758 Opole, Poland
| | - Żaneta Grzywacz
- Faculty of Production Engineering and Logistics, Opole University of Technology, 76 Prószkowska St., 45-758 Opole, Poland
| | - Alexandre Ternianov
- Primary Care Centre Vila Olimpica, Parc Sanitary Pere Virgili, c. Joan Miró 17, 08005 Barcelona, Spain
| | - David Unwin
- Faculty of Health Social Care and Medicine, Edge Hill University, Ormskirk L39 4QP, UK
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28
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Alluwyam AH, Estrella ED. Ketogenic Diet and Its Potential Role in Preventing Type 2 Diabetes Mellitus and Its Complications: A Narrative Review of Randomized Controlled Trials. Cureus 2024; 16:e66419. [PMID: 39246956 PMCID: PMC11380086 DOI: 10.7759/cureus.66419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/07/2024] [Indexed: 09/10/2024] Open
Abstract
Diabetes mellitus is a global health crisis affecting millions. Nutrition plays a vital role in its management and prevention. While carbohydrate reduction is beneficial for glycemic control, various dietary approaches exist. The ketogenic diet, characterized by very low carbohydrate intake, has shown promise in weight management and blood sugar control. However, its potential for preventing type 2 diabetes mellitus (T2DM) remains largely unexplored. To evaluate the ketogenic diet's potential in preventing T2DM, this review searched the PubMed database for studies published between 2013 and 2023. Findings suggest that the diet can effectively aid weight loss and improve blood glucose levels. Some evidence indicates reduced reliance on diabetes medications. However, effects on cholesterol levels are inconsistent, and long-term adherence challenges exist. Additionally, potential micronutrient deficiencies and safety concerns require careful consideration. While the ketogenic diet offers potential benefits, further research is needed to establish its efficacy and safety as a long-term prevention strategy for T2DM. However, the results of the present study indicate the need for further research in this area, utilizing rigorous methodology.
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Affiliation(s)
- Ali H Alluwyam
- Department of Preventive Medicine, Saudi Board of Preventive Medicine, Al-Ahsa, SAU
| | - Edric D Estrella
- Department of Public Health, College of Applied Medical Sciences, King Faisal University, Al-Ahsa, SAU
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Balestra F, Negro R, De Luca M, Depalo N, Rizzi F, Panzetta G, Arrè V, Mastrogiacomo R, Coletta S, Stabile D, Pesole PL, Cerabino N, Di Chito M, Shahini E, Giannelli G, De Pergola G, Scavo MP. Extracellular Vesicles Modulate Liver Cells Viability and Reactive Oxygen Species in Patients Following a Very Low-Calorie Ketogenic Diet. Nutrients 2024; 16:2386. [PMID: 39125267 PMCID: PMC11314450 DOI: 10.3390/nu16152386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 07/15/2024] [Accepted: 07/19/2024] [Indexed: 08/12/2024] Open
Abstract
The VLCKD is a diet recognized to promote rapid fat mobilization and reduce inflammation, hepatic steatosis, and liver fibrosis. Extracellular vesicles (EVs) mediate cell-to-cell communication. The aim of the study is to investigate the role of circulating EVs in cell proliferation, ketone bodies, and ROS production in patients on an 8-week VLCKD regimen. Participants were classified as responders (R) or non-responders (NR) to VLCKD treatment based on their fibroscan results. In vitro experiments with the hepatic cell lines HEPA-RG (normal hepatocytes) and LX-2 (stellate cells) were conducted to investigate the effects of circulating EVs on cell viability, ROS production, and ketone body presence. The findings reveal a notable reduction in cell viability in both cell lines when treated with exosomes (EXOs). In contrast, treatment with microvesicles (MVs) did not appear to affect cell viability, which remained unchanged. Additionally, the levels of ketone bodies measured in urine were not consistently correlated with the reduction of fibrosis in responders (R). Similarly, an increase in ketone bodies was observed in non-responders (NR), which was also not aligned with the expected reduction in fibrosis. This inconsistency stands in stark contrast to the levels of Reactive Oxygen Species (ROS), which exhibited a clear and consistent pattern in accordance with the dietary intervention. Finally, in this preliminary study, ROS has been identified as a potential diet adherence marker for VLCKD patients; the ROS levels reliably follow the progression of the fibrosis response, providing a more accurate reflection of the therapeutic effects.
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Affiliation(s)
- Francesco Balestra
- Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS “S. de Bellis”, Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy; (F.B.); (M.D.L.); (G.P.)
| | - Roberto Negro
- Laboratory of Personalized Medicine, National Institute of Gastroenterology IRCCS “S. de Bellis”, Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy; (R.N.); (V.A.)
| | - Maria De Luca
- Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS “S. de Bellis”, Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy; (F.B.); (M.D.L.); (G.P.)
| | - Nicoletta Depalo
- Institute for Chemical-Physical Processes, Italian National Research Council (IPCF)-CNR SS Bari, Via Orabona 4, 70125 Bari, Italy; (N.D.); (F.R.); (R.M.)
- National Interuniversity Consortium of Materials Science and Technology (INSTM), Bari Research Unit, Via Orabona 4, 70125 Bari, Italy
| | - Federica Rizzi
- Institute for Chemical-Physical Processes, Italian National Research Council (IPCF)-CNR SS Bari, Via Orabona 4, 70125 Bari, Italy; (N.D.); (F.R.); (R.M.)
- National Interuniversity Consortium of Materials Science and Technology (INSTM), Bari Research Unit, Via Orabona 4, 70125 Bari, Italy
| | - Giorgia Panzetta
- Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS “S. de Bellis”, Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy; (F.B.); (M.D.L.); (G.P.)
| | - Valentina Arrè
- Laboratory of Personalized Medicine, National Institute of Gastroenterology IRCCS “S. de Bellis”, Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy; (R.N.); (V.A.)
| | - Rita Mastrogiacomo
- Institute for Chemical-Physical Processes, Italian National Research Council (IPCF)-CNR SS Bari, Via Orabona 4, 70125 Bari, Italy; (N.D.); (F.R.); (R.M.)
- National Interuniversity Consortium of Materials Science and Technology (INSTM), Bari Research Unit, Via Orabona 4, 70125 Bari, Italy
- Department of Chemistry, University of Bari Aldo Moro, Via Orabona 4, 70125 Bari, Italy
| | - Sergio Coletta
- Department of Pathology, National Institute of Gastroenterology IRCCS “S. de Bellis”, Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy; (S.C.); (D.S.); (P.L.P.)
| | - Dolores Stabile
- Department of Pathology, National Institute of Gastroenterology IRCCS “S. de Bellis”, Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy; (S.C.); (D.S.); (P.L.P.)
| | - Pasqua Letizia Pesole
- Department of Pathology, National Institute of Gastroenterology IRCCS “S. de Bellis”, Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy; (S.C.); (D.S.); (P.L.P.)
| | - Nicole Cerabino
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “S. de Bellis”, Via Turi 27, 70013 Castellana Grotte, Italy; (N.C.); (M.D.C.); (G.D.P.)
| | - Martina Di Chito
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “S. de Bellis”, Via Turi 27, 70013 Castellana Grotte, Italy; (N.C.); (M.D.C.); (G.D.P.)
| | - Endrit Shahini
- Gastroenterology Unit, National Institute of Gastroenterology IRCCS “S. de Bellis”, Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy;
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology IRCCS “S. de Bellis”, Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy;
| | - Giovanni De Pergola
- Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS “S. de Bellis”, Via Turi 27, 70013 Castellana Grotte, Italy; (N.C.); (M.D.C.); (G.D.P.)
| | - Maria Principia Scavo
- Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS “S. de Bellis”, Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy; (F.B.); (M.D.L.); (G.P.)
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Rojas R, Griñán-Ferré C, Castellanos A, Griego E, Martínez M, Navarro-López JDD, Jiménez-Díaz L, Rodríguez-Álvarez J, Del Cerro DS, Castillo PE, Pallàs M, Fadó R, Casals N. BETA-HYDROXYBUTYRATE COUNTERACTS THE DELETERIOUS EFFECTS OF A SATURATED HIGH-FAT DIET ON SYNAPTIC AMPA RECEPTORS AND COGNITIVE PERFORMANCE. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.01.23.576931. [PMID: 39091837 PMCID: PMC11291009 DOI: 10.1101/2024.01.23.576931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
The ketogenic diet, characterized by high fat and low carbohydrates, has gained popularity not only as a strategy for managing body weight but also for its efficacy in delaying cognitive decline associated with neurodegenerative diseases and the aging process. Since this dietary approach stimulates the liver's production of ketone bodies, primarily β-hydroxybutyrate (BHB), which serves as an alternative energy source for neurons, we investigated whether BHB could mitigate impaired AMPA receptor trafficking, synaptic dysfunction, and cognitive decline induced by metabolic challenges such as saturated fatty acids. Here, we observe that, in cultured primary cortical neurons, exposure to palmitic acid (200μM) decreased surface levels of glutamate GluA1-containing AMPA receptors, whereas unsaturated fatty acids, such as oleic acid and ω-3 docosahexaenoic acid (200μM), and BHB (5mM) increased them. Furthermore, BHB countered the adverse effects of palmitic acid on synaptic GluA1 levels in hippocampal neurons, as well as excitability and plasticity in hippocampal slices. Additionally, daily intragastric administration of BHB (100 mg/kg/day) for two months reversed cognitive impairment induced by a saturated high-fat diet (49% of calories from fat) in a mouse experimental model of obesity. In summary, our findings underscore the significant impact of fatty acids and ketone bodies on AMPA receptors abundance, synaptic function and neuroplasticity, shedding light on the potential use of BHB to delay cognitive impairments associated with metabolic diseases.
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31
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Giannakogeorgou A, Roden M. Role of lifestyle and glucagon-like peptide-1 receptor agonists for weight loss in obesity, type 2 diabetes and steatotic liver diseases. Aliment Pharmacol Ther 2024; 59 Suppl 1:S52-S75. [PMID: 38813830 DOI: 10.1111/apt.17848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 11/08/2023] [Accepted: 12/15/2023] [Indexed: 05/31/2024]
Abstract
BACKGROUND The current obesity pandemic has given rise to associated comorbidities and complications, including type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). During the last decade, certain glucagon-like peptide 1 receptor agonists (GLP-1RA), originally developed as antihyperglycemic drugs, also demonstrated efficacy for weight loss. AIMS To review shared pathophysiologic features of common metabolic diseases and compare therapeutic strategies to reduce body weight and related complications. METHODS We performed an extensive literature research to describe the effects of lifestyle modification, first-generation anti-obesity drugs, and GLP-1RA on weight loss in humans with obesity, type 2 diabetes and MASLD. RESULTS Until recently, treatment of obesity has been limited to lifestyle modification, which offer moderate degree and sustainability of weight loss. The few approved first-generation anti-obesity drugs are either limited to short term use or to certain forms of obesity. Some GLP-1RA significantly decrease caloric intake and body weight. Liraglutide and semaglutide have therefore been approved for treating people with obesity. They also lead to a reduction of hepatic fat content and inflammation in people with biopsy-confirmed MASLD. Possible limitations comprise adverse effects, treatment adherence and persistence. CONCLUSION Certain GLP-1RA are superior to lifestyle modification and first-generation anti-obesity drugs in inducing weight loss. They have therefore markedly changed the portfolio of obesity treatment with additional beneficial effects on steatotic liver disease.
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Affiliation(s)
- Anna Giannakogeorgou
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Neuherberg, Germany
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany
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Burgos MA, Ivaldi D, Oltra G, Escobar Liquitay CM, Garegnani L. Low-carbohydrate diet for people with type 2 diabetes mellitus. Cochrane Database Syst Rev 2024; 5:CD015954. [PMID: 39908069 PMCID: PMC11131143 DOI: 10.1002/14651858.cd015954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
OBJECTIVES This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of a low-carbohydrate diet in adults with type 2 diabetes mellitus.
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Affiliation(s)
- Mariana Andrea Burgos
- Research Department, Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Diego Ivaldi
- Research Department, Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Gisela Oltra
- Research Department, Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | | | - Luis Garegnani
- Research Department, Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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Conte C, Cipponeri E, Roden M. Diabetes Mellitus, Energy Metabolism, and COVID-19. Endocr Rev 2024; 45:281-308. [PMID: 37934800 PMCID: PMC10911957 DOI: 10.1210/endrev/bnad032] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 08/30/2023] [Accepted: 11/01/2023] [Indexed: 11/09/2023]
Abstract
Obesity, diabetes mellitus (mostly type 2), and COVID-19 show mutual interactions because they are not only risk factors for both acute and chronic COVID-19 manifestations, but also because COVID-19 alters energy metabolism. Such metabolic alterations can lead to dysglycemia and long-lasting effects. Thus, the COVID-19 pandemic has the potential for a further rise of the diabetes pandemic. This review outlines how preexisting metabolic alterations spanning from excess visceral adipose tissue to hyperglycemia and overt diabetes may exacerbate COVID-19 severity. We also summarize the different effects of SARS-CoV-2 infection on the key organs and tissues orchestrating energy metabolism, including adipose tissue, liver, skeletal muscle, and pancreas. Last, we provide an integrative view of the metabolic derangements that occur during COVID-19. Altogether, this review allows for better understanding of the metabolic derangements occurring when a fire starts from a small flame, and thereby help reducing the impact of the COVID-19 pandemic.
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Affiliation(s)
- Caterina Conte
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Rome 00166, Italy
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan 20099, Italy
| | - Elisa Cipponeri
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan 20099, Italy
| | - Michael Roden
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf 40225, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf 40225, Germany
- German Center for Diabetes Research, Partner Düsseldorf, Neuherberg 85764, Germany
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Popiolek-Kalisz J. Ketogenic diet and cardiovascular risk - state of the art review. Curr Probl Cardiol 2024; 49:102402. [PMID: 38232923 DOI: 10.1016/j.cpcardiol.2024.102402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 01/14/2024] [Indexed: 01/19/2024]
Abstract
The ketogenic diet is based on extreme carbohydrate intake reduction and replacing the remaining with fat and has become a popular dietary pattern used for weight loss. The relationship between the ketogenic diet and cardiovascular risk is a controversial topic. This publication aimed to present evidence on the ketogenic diet and cardiovascular risk factors and mortality. The ketogenic diet does not fulfill the criteria of a healthy diet. It presents the potential for rapid short-term reduction of body mass, triglycerides level, Hb1Ac, and blood pressure. Its efficacy for weight loss and the above-mentioned metabolic changes is not significant in long-term observations. In terms of cardiovascular mortality, the low-carb pattern is more beneficial than very low-carbohydrate (including the ketogenic diet). There is still scarce evidence comparing ketogenic to the Mediterranean diet. Other safety concerns in cardiovascular patients such as adverse events related to ketosis, fat-free mass loss, or potential pharmacological interactions should be also taken into consideration in future research.
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Affiliation(s)
- Joanna Popiolek-Kalisz
- Clinical Dietetics Unit, Department of Bioanalytics, Medical University of Lublin, ul. Chodzki 7, 20-059, Lublin, Poland; Department of Cardiology, Cardinal Wyszynski Hospital in Lublin, Poland.
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Volek JS, Yancy WS, Gower BA, Phinney SD, Slavin J, Koutnik AP, Hurn M, Spinner J, Cucuzzella M, Hecht FM. Expert consensus on nutrition and lower-carbohydrate diets: An evidence- and equity-based approach to dietary guidance. Front Nutr 2024; 11:1376098. [PMID: 38487629 PMCID: PMC10937533 DOI: 10.3389/fnut.2024.1376098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 02/14/2024] [Indexed: 03/17/2024] Open
Abstract
There is a substantial body of clinical evidence supporting the beneficial effects of lower-carbohydrate dietary patterns on multiple established risk factors associated with insulin resistance and cardiovascular diseases in adult populations. Nutrition and health researchers, clinical practitioners, and stakeholders gathered for, "The Scientific Forum on Nutrition, Wellness, and Lower-Carbohydrate Diets: An Evidence- and Equity-Based Approach to Dietary Guidance" to discuss the evidence base around lower-carbohydrate diets, health outcomes, and dietary guidance. Consensus statements were agreed upon to identify current areas of scientific agreement and spotlight gaps in research, education, and practice to help define and prioritize future pathways. Given the evidence base and considering that most American adults are living with at least one nutrition-related chronic disease, there was consensus that including a lower-carbohydrate dietary pattern as one part of the Dietary Guidelines for Americans could help promote health equity among the general population.
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Affiliation(s)
- Jeff S. Volek
- Department of Human Sciences, The Ohio State University, Columbus, OH, United States
| | - William S. Yancy
- Department of Medicine, Duke University, Durham, NC, United States
| | - Barbara A. Gower
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, United States
| | | | - Joanne Slavin
- Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN, United States
| | - Andrew P. Koutnik
- Sansum Diabetes Research Institute, Santa Barbara, CA, United States
| | - Michelle Hurn
- The Dietetian’s Dilemma, Portland, OR, United States
| | | | - Mark Cucuzzella
- Department of Family Medicine, West Virginia University, Martinsburg, WV, United States
| | - Frederick M. Hecht
- Osher Center for Integrative Health, University of California, San Francisco, San Francisco, CA, United States
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Szendi K, Murányi E, Hunter N, Németh B. Methodological Challenges and Confounders in Research on the Effects of Ketogenic Diets: A Literature Review of Meta-Analyses. Foods 2024; 13:248. [PMID: 38254549 PMCID: PMC10814162 DOI: 10.3390/foods13020248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 01/04/2024] [Accepted: 01/11/2024] [Indexed: 01/24/2024] Open
Abstract
Several meta-analyses have found a positive association between a popular type of "fad diet", ketogenic diets, and their effect on anthropometric and blood parameters. However, the non-specific inclusion criteria for meta-analyses may lead to incorrect conclusions. The aim of this literature review is to highlight the main confounders and methodological pitfalls of meta-analyses on ketogenic diets by inspecting the presence of key inclusion criteria. The PubMed, Embase, and Web of Science databases and the Cochrane Database of Systematic Reviews were searched for meta-analyses. Most meta-analyses did not define the essential parameters of a ketogenic diet (i.e., calories, macronutrient ratio, types of fatty acids, ketone bodies, etc.) as inclusion criteria. Of the 28 included meta-analyses, few addressed collecting real, re-measured nutritional data from the ketogenic diet and control groups in parallel with the pre-designed nutritional data. Most meta-analyses reported positive results in favor of ketogenic diets, which can result in erroneous conclusions considering the numerous methodological pitfalls and confounders. Well-designed clinical trials with comparable results and their meta-analyses are needed. Until then, medical professionals should not recommend ketogenic diets as a form of weight loss when other well-known dietary options have been shown to be healthy and effective.
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Affiliation(s)
- Katalin Szendi
- Department of Public Health Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
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Batsis JA, Batchek DJ, Petersen CL, Gross DC, Lynch DH, Spangler HB, Cook SB. Protein Supplementation May Dampen Positive Effects of Exercise on Glucose Homeostasis: A Pilot Weight Loss Intervention. Nutrients 2023; 15:4947. [PMID: 38068805 PMCID: PMC10707998 DOI: 10.3390/nu15234947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 11/23/2023] [Accepted: 11/24/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND The role of protein in glucose homeostasis has demonstrated conflicting results. However, little research exists on its impact following weight loss. This study examined the impact of protein supplementation on glucose homeostasis in older adults >65 years with obesity seeking to lose weight. METHODS A 12-week, nonrandomized, parallel group intervention of protein (PG) and nonprotein (NPG) arms for 28 older rural adults (body mass index (BMI) ≥ 30 kg/m2) was conducted at a community aging center. Both groups received twice weekly physical therapist-led group strength training classes. The PG consumed a whey protein supplement three times per week, post-strength training. Primary outcomes included pre/post-fasting glucose, insulin, inflammatory markers, and homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS Mean age and baseline BMI were 72.9 ± 4.4 years and 37.6 ± 6.9 kg/m2 in the PG and 73.0 ± 6.3 and 36.6 ± 5.5 kg/m2 in the NPG, respectively. Mean weight loss was -3.45 ± 2.86 kg in the PG and -5.79 ± 3.08 kg in the NPG (p < 0.001). There was a smaller decrease in pre- vs. post-fasting glucose levels (PG: -4 mg ± 13.9 vs. NPG: -12.2 ± 25.8 mg/dL; p = 0.10), insulin (-7.92 ± 28.08 vs. -46.7 ± 60.8 pmol/L; p = 0.01), and HOMA-IR (-0.18 ± 0.64 vs. -1.08 ± 1.50; p = 0.02) in the PG compared to the NPG. CONCLUSIONS Protein supplementation during weight loss demonstrated a smaller decrease in insulin resistance compared to the NPG, suggesting protein may potentially mitigate beneficial effects of exercise on glucose homeostasis.
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Affiliation(s)
- John A. Batsis
- Division of Geriatric Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; (D.H.L.); (H.B.S.)
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; (D.J.B.); (D.C.G.)
- The Dartmouth Institute for Health Policy, Dartmouth College, Hanover, NH 03755, USA;
- Center for Aging and Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Dakota J. Batchek
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; (D.J.B.); (D.C.G.)
| | - Curtis L. Petersen
- The Dartmouth Institute for Health Policy, Dartmouth College, Hanover, NH 03755, USA;
- Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH 03755, USA
| | - Danae C. Gross
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; (D.J.B.); (D.C.G.)
- Center for Aging and Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - David H. Lynch
- Division of Geriatric Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; (D.H.L.); (H.B.S.)
- Center for Aging and Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Hillary B. Spangler
- Division of Geriatric Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; (D.H.L.); (H.B.S.)
- Center for Aging and Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Summer B. Cook
- Department of Kinesiology, University of New Hampshire, Durham, NH 03824, USA;
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Jeziorek M, Chachaj A, Sowicz M, Adaszyńska A, Truszyński A, Putek J, Kujawa K, Szuba A. The Benefits of Low-Carbohydrate, High-Fat (LCHF) Diet on Body Composition, Leg Volume, and Pain in Women with Lipedema. J Obes 2023; 2023:5826630. [PMID: 38026822 PMCID: PMC10676278 DOI: 10.1155/2023/5826630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 11/06/2023] [Accepted: 11/09/2023] [Indexed: 12/01/2023] Open
Abstract
This study aimed to assess the potential benefits of a low-carbohydrate, high-fat (LCHF) diet on body composition, leg volume, and pain reduction in women with lipedema compared to overweight or women with obesity. The study included 113 female participants, 56 with lipedema and 57 with overweight/obesity (BMI >25 kg/m2) without lipedema. All subjects were prescribed a low-carbohydrate, high-fat (LCHF) diet with anti-inflammatory properties to adhere to for a duration of 7 months. Measurements of anthropometry, body weight, composition, and pain (VAS) were conducted at the study's commencement and conclusion. 52 participants completed the study. Both groups experienced a similar weight reduction, amounting to 12.9% compared to the baseline (-10.8 kg vs. -11.9 kg; p = 0.14, for lipedema and women with overweight/obesity, respectively). The most reduction was in body fat mass. Improvements in various parameters were observed, except for ankle circumferences, which decreased more in the lipedema group. Lipedema participants showed significantly reduced pain levels following the LCHF diet (4.6 ± 2.6 vs 3.0 ± 2.3; p < 0.001). The LCHF diet holds promise for weight loss, body fat reduction, leg volume management, and pain alleviation in women with lipedema. These findings provide valuable insights into potential therapeutic strategies for lipedema management.
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Affiliation(s)
- Małgorzata Jeziorek
- Department of Dietetics and Bromatology, Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland
| | - Angelika Chachaj
- Department of Angiology and Internal Medicine, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Monika Sowicz
- Department of Angiology and Internal Medicine, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Agnieszka Adaszyńska
- Department of Angiology and Internal Medicine, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Aleksander Truszyński
- Department of Angiology and Internal Medicine, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Justyna Putek
- Department of Angiology and Internal Medicine, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Krzysztof Kujawa
- Statistical Analysis Center, Wroclaw Medical University, Wroclaw, Poland
| | - Andrzej Szuba
- Department of Angiology and Internal Medicine, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland
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Veneti S, Grammatikopoulou MG, Kintiraki E, Mintziori G, Goulis DG. Ketone Bodies in Diabetes Mellitus: Friend or Foe? Nutrients 2023; 15:4383. [PMID: 37892458 PMCID: PMC10609881 DOI: 10.3390/nu15204383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 10/12/2023] [Accepted: 10/14/2023] [Indexed: 10/29/2023] Open
Abstract
In glucose-deprived conditions, ketone bodies are produced by the liver mitochondria, through the catabolism of fatty acids, and are used peripherally, as an alternative energy source. Ketones are produced in the body under normal conditions, including during pregnancy and the neonatal period, when following a ketogenic diet (KD), fasting, or exercising. Additionally, ketone synthesis is also augmented under pathological conditions, including cases of diabetic ketoacidosis (DKA), alcoholism, and several metabolic disorders. Nonetheless, diet is the main regulator of total body ketone concentrations. The KDs are mimicking the fasting state, altering the default metabolism towards the use of ketones as the primary fuel source. Recently, KD has gained recognition as a medical nutrition therapy for a plethora of metabolic conditions, including obesity and diabetes mellitus (DM). The present review aims to discuss the role of ketones, KDs, ketonemia, and ketonuria in DM, presenting all the available new evidence in a comprehensive manner.
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Affiliation(s)
- Stavroula Veneti
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
| | - Maria G. Grammatikopoulou
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
- Unit of Immunonutrition and Clinical Nutrition, Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, GR-41110 Larissa, Greece
| | - Evangelia Kintiraki
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
| | - Gesthimani Mintziori
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
| | - Dimitrios G. Goulis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
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Li YY, Tong LP, Wu XD, Lin D, Lin Y, Lin XY. Analysis of influencing factors and interaction of body weight and disease outcome in patients with prediabetes. World J Diabetes 2023; 14:1551-1561. [PMID: 37970128 PMCID: PMC10642418 DOI: 10.4239/wjd.v14.i10.1551] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 08/22/2023] [Accepted: 09/06/2023] [Indexed: 10/09/2023] Open
Abstract
BACKGROUND The trend of prediabetes progressing to type 2 diabetes mellitus (T2DM) is prominent, and effective intervention can lead to a return to prediabetes. Exploring the factors influencing the outcome of prediabetes is helpful to guide clinical intervention. The weight change in patients with prediabetes has not attracted much attention. AIM To explore the interaction between body weight and the factors affecting the progression of prediabetes to T2DM. METHODS We performed a retrospective analysis of 236 patients with prediabetes and 50 with normal glucose tolerance (NGT), and collected clinical data and follow-up results of all patients. Based on natural blood glucose outcomes, we classified 66 patients with progression to T2DM into the disease progression (DP) group, and 170 patients without progression to T2DM into the disease outcome (DO) group. We analyzed the factors that influenced prediabetes outcome and the influence of body weight on prediabetes blood glucose outcome by unconditional logistic regression. A general linear model (univariate) was used to analyze the inter-action between body weight and independent influencing factors. RESULTS There were 98 cases of impaired fasting glucose (IFG), 90 cases of impaired glucose tolerance (IGT), and 48 cases of coexistent IFG and IGT. The body weight, waist circumference, body mass index, fasting blood glucose, and 2 h plasma glucose of patients with IFG, IGT, and coexistent IFG and IGT were higher than those in patients with NGT (P < 0.05). Logistic regression analysis showed that body weight, glycosylated hemoglobin, uric acid, fasting insulin, and homeostatic model assessment for insulin resistance were independent factors affecting progression of prediabetes to T2DM (P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve predicted by the above indicators combined was 0.905 [95% confidence interval (CI): 0.863-0.948], which was greater than that predicted by each indicator alone. Logistic regression analysis with baseline body weight as an independent variable showed that compared with body weight 1, the odds ratio (95%CI) of body weight 3 was 1.399 (1.142-2.126) (P = 0.033). There was a multiplicative interaction between body weight and uric acid (β = 1.953, P = 0.005). CONCLUSION High body weight in patients with prediabetes is an independent risk factor for progression to T2DM, and the risk of progression is increased when coexisting with high uric acid level.
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Affiliation(s)
- Yan-Yan Li
- Department of General Practice, The First People’s Hospital of Wenling City, Wenling 317500, Zhejiang Province, China
| | - Lin-Ping Tong
- Department of General Practice, The First People’s Hospital of Wenling City, Wenling 317500, Zhejiang Province, China
| | - Xian-Dan Wu
- Department of General Practice, The First People’s Hospital of Wenling City, Wenling 317500, Zhejiang Province, China
| | - Dan Lin
- Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Yue Lin
- Department of General Practice, The First People’s Hospital of Wenling City, Wenling 317500, Zhejiang Province, China
| | - Xiao-Yang Lin
- Department of General Medicine, The First People’s Hospital of Wenling City, Wenling 317500, Zhejiang Province, China
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Chen S, Su X, Feng Y, Li R, Liao M, Fan L, Liu J, Chen S, Zhang S, Cai J, Zhu S, Niu J, Ye Y, Lo K, Zeng F. Ketogenic Diet and Multiple Health Outcomes: An Umbrella Review of Meta-Analysis. Nutrients 2023; 15:4161. [PMID: 37836444 PMCID: PMC10574428 DOI: 10.3390/nu15194161] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 09/22/2023] [Accepted: 09/22/2023] [Indexed: 10/15/2023] Open
Abstract
Numerous studies have examined the effects of ketogenic diets (KD) on health-related outcomes through meta-analyses. However, the presence of biases may compromise the reliability of conclusions. Therefore, we conducted an umbrella review to collate and appraise the strength of evidence on the efficacy of KD interventions. We conducted a comprehensive search on PubMed, EMBASE, and the Cochrane Database until April 2023 to identify meta-analyses that investigated the treatment effects of KD for multiple health conditions, which yielded 23 meta-analyses for quantitative analyses. The evidence suggests that KD could increase the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), the respiratory exchange rate (RER), and could decrease total testosterone and testosterone levels (all p-random effects: <0.05). The combination of KD and physical activity can significantly reduce body weight and increase the levels of LDL-C and cortisol. In addition, KD was associated with seizure reduction in children, which can be explained by the ketosis state as induced by the diet. Furthermore, KD demonstrated a better alleviation effect in refractory childhood epilepsy, in terms of median effective rates for seizure reduction of ≥50%, ≥90%, and seizure freedom. However, the strength of evidence supporting the aforementioned associations was generally weak, thereby challenging their credibility. Consequently, future studies should prioritize stringent research protocols to ascertain whether KD interventions with longer intervention periods hold promise as a viable treatment option for various diseases.
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Affiliation(s)
- Shiyun Chen
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No. 601 Huangpu Road West, Guangzhou 510632, China; (S.C.); (X.S.); (Y.F.); (R.L.); (J.L.); (S.C.); (S.Z.); (J.C.); (S.Z.)
| | - Xin Su
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No. 601 Huangpu Road West, Guangzhou 510632, China; (S.C.); (X.S.); (Y.F.); (R.L.); (J.L.); (S.C.); (S.Z.); (J.C.); (S.Z.)
| | - Yonghui Feng
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No. 601 Huangpu Road West, Guangzhou 510632, China; (S.C.); (X.S.); (Y.F.); (R.L.); (J.L.); (S.C.); (S.Z.); (J.C.); (S.Z.)
| | - Ruojie Li
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No. 601 Huangpu Road West, Guangzhou 510632, China; (S.C.); (X.S.); (Y.F.); (R.L.); (J.L.); (S.C.); (S.Z.); (J.C.); (S.Z.)
| | - Minqi Liao
- Institute of Epidemiology, Helmholtz Zentrum Munich-German Research Center for Environmental Health, Ingolstadt Landstr. 1, 85764 Neuherberg, Germany;
| | - Laina Fan
- Department of Clinical Medicine, International School, Jinan University, No. 601 Huangpu Road West, Guangzhou 510632, China;
| | - Jiazi Liu
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No. 601 Huangpu Road West, Guangzhou 510632, China; (S.C.); (X.S.); (Y.F.); (R.L.); (J.L.); (S.C.); (S.Z.); (J.C.); (S.Z.)
| | - Shasha Chen
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No. 601 Huangpu Road West, Guangzhou 510632, China; (S.C.); (X.S.); (Y.F.); (R.L.); (J.L.); (S.C.); (S.Z.); (J.C.); (S.Z.)
| | - Shiwen Zhang
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No. 601 Huangpu Road West, Guangzhou 510632, China; (S.C.); (X.S.); (Y.F.); (R.L.); (J.L.); (S.C.); (S.Z.); (J.C.); (S.Z.)
| | - Jun Cai
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No. 601 Huangpu Road West, Guangzhou 510632, China; (S.C.); (X.S.); (Y.F.); (R.L.); (J.L.); (S.C.); (S.Z.); (J.C.); (S.Z.)
| | - Sui Zhu
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No. 601 Huangpu Road West, Guangzhou 510632, China; (S.C.); (X.S.); (Y.F.); (R.L.); (J.L.); (S.C.); (S.Z.); (J.C.); (S.Z.)
| | - Jianxiang Niu
- General Surgery, The Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Road, Hohhot 010000, China;
| | - Yanbin Ye
- Department of Clinical Nutrition, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China;
| | - Kenneth Lo
- Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong 100872, China
- Research Institute for Future Food, The Hong Kong Polytechnic University, Kowloon, Hong Kong 100872, China
| | - Fangfang Zeng
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No. 601 Huangpu Road West, Guangzhou 510632, China; (S.C.); (X.S.); (Y.F.); (R.L.); (J.L.); (S.C.); (S.Z.); (J.C.); (S.Z.)
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Li S, Du Y, Meireles C, Sharma K, Qi L, Castillo A, Wang J. Adherence to ketogenic diet in lifestyle interventions in adults with overweight or obesity and type 2 diabetes: a scoping review. Nutr Diabetes 2023; 13:16. [PMID: 37709770 PMCID: PMC10502148 DOI: 10.1038/s41387-023-00246-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 08/20/2023] [Accepted: 08/29/2023] [Indexed: 09/16/2023] Open
Abstract
BACKGROUND/OBJECTIVES Despite the evidence supporting the efficacy of the ketogenic diet (KD) on weight and type 2 diabetes (T2D) management, adherence to the KD is challenging. Additionally, no studies have reported changes in PA among individuals with overweight/obesity and T2D who have followed KD. We mapped out the methods used to assess adherence to the KD and level of physical activity (PA) in lifestyle interventions for weight and T2D management in individuals with overweight/obesity and T2D and compared levels of KD adherence and PA in these interventions. METHODS Articles published between January 2005 and March 2022 were searched in MEDLINE, CINAHL, and Scopus. Studies that included KD in lifestyle interventions for adults with T2D and overweight/obesity and measured ketone levels were included. RESULTS The eleven included studies comprised eight randomized controlled trials. They mainly used self-reported measures to evaluate adherence to the KD and level of PA. We found studies reported higher carbohydrate intake and lower fat intake than the KD regimen. Great inconsistencies were found among studies on the measurement and reporting of ketone and PA levels. CONCLUSION Our results demonstrated the need to develop intervention strategies to improve adherence to the KD, as well as the necessity of developing standardized diet and PA assessment tools to establish a stronger evidence base for including KD in lifestyle interventions for weight and T2D management among adults with overweight/obesity and T2D.
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Affiliation(s)
- Shiyu Li
- School of Nursing, UT Health San Antonio, San Antonio, TX, USA
| | - Yan Du
- School of Nursing, UT Health San Antonio, San Antonio, TX, USA
| | | | - Kumar Sharma
- Center for Precision Medicine, Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA
| | - Lu Qi
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Cambridge, MA, USA
| | | | - Jing Wang
- College of Nursing, Florida State University, Tallahassee, FL, USA.
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Grigorescu ED, Lăcătușu CM, Floria M, Cazac GD, Onofriescu A, Sauciuc LA, Ceasovschih A, Crețu I, Mihai BM, Șorodoc L. Effects of Incretin-Based Treatment on the Diastolic (Dys)Function in Patients with Uncontrolled Type 2 Diabetes Mellitus: A Prospective Study with 1-Year Follow-Up. Diagnostics (Basel) 2023; 13:2817. [PMID: 37685355 PMCID: PMC10487011 DOI: 10.3390/diagnostics13172817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 08/19/2023] [Accepted: 08/29/2023] [Indexed: 09/10/2023] Open
Abstract
Left ventricular diastolic dysfunction (DD) is a subclinical cardiac abnormality in patients with type 2 diabetes mellitus (T2DM) that can progress to heart failure (HF) and increase cardiovascular risk. This prospective study evaluated the DD in T2DM patients without atherosclerotic cardiovascular disease after one year of incretin-based drugs added to standard treatment. Of the 138 enrolled patients (49.30% male, mean age 57.86 ± 8.82, mean T2DM history 5 years), 71 were started on dipeptidyl peptidase-4 inhibitor sitagliptin/saxagliptin, 21 on glucagon-like peptide-1 receptor agonist exenatide, and 46 formed the control group (metformin and sulphonylurea/acarbose). At baseline, 71 patients had grade 1 DD, another 12 had grade 2 and 3 DD, and 15 had indeterminate DD. After one year, DD was evidenced in 50 cases. Diastolic function improved in 9 cases, and 27 patients went from grade 1 to indeterminate DD. The active group benefited more, especially patients treated with exenatide; their metabolic and inflammation profiles also improved the most. An in-depth analysis of echocardiographic parameters and paraclinical results in the context of literature data justifies the conclusion that early assessment of diastolic function in T2DM patients is necessary and the benefits of affordable incretin-based treatment may extend to subclinical cardiovascular manifestations such as DD.
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Affiliation(s)
- Elena-Daniela Grigorescu
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (E.-D.G.); (A.O.); (B.-M.M.)
| | - Cristina-Mihaela Lăcătușu
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (E.-D.G.); (A.O.); (B.-M.M.)
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Mariana Floria
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (M.F.); (A.C.); (L.Ș.)
- Medical Clinic, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Georgiana-Diana Cazac
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (E.-D.G.); (A.O.); (B.-M.M.)
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Alina Onofriescu
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (E.-D.G.); (A.O.); (B.-M.M.)
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Livia-Amira Sauciuc
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania;
| | - Alexandr Ceasovschih
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (M.F.); (A.C.); (L.Ș.)
- Medical Clinic, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Ioana Crețu
- Crețu R. Ioana PFA, 1 Mărului, 707020 Aroneanu, Romania;
| | - Bogdan-Mircea Mihai
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (E.-D.G.); (A.O.); (B.-M.M.)
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Laurențiu Șorodoc
- Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (M.F.); (A.C.); (L.Ș.)
- Medical Clinic, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
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Su J, Luo Y, Hu S, Tang L, Ouyang S. Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents. Int J Mol Sci 2023; 24:13381. [PMID: 37686185 PMCID: PMC10487533 DOI: 10.3390/ijms241713381] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 08/18/2023] [Accepted: 08/21/2023] [Indexed: 09/10/2023] Open
Abstract
Diabetes mellitus is a chronic multifaceted disease with multiple potential complications, the treatment of which can only delay and prolong the terminal stage of the disease, i.e., type 2 diabetes mellitus (T2DM). The World Health Organization predicts that diabetes will be the seventh leading cause of death by 2030. Although many antidiabetic medicines have been successfully developed in recent years, such as GLP-1 receptor agonists and SGLT-2 inhibitors, single-target drugs are gradually failing to meet the therapeutic requirements owing to the individual variability, diversity of pathogenesis, and organismal resistance. Therefore, there remains a need to investigate the pathogenesis of T2DM in more depth, identify multiple therapeutic targets, and provide improved glycemic control solutions. This review presents an overview of the mechanisms of action and the development of the latest therapeutic agents targeting T2DM in recent years. It also discusses emerging target-based therapies and new potential therapeutic targets that have emerged within the last three years. The aim of our review is to provide a theoretical basis for further advancement in targeted therapies for T2DM.
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Affiliation(s)
- Jingqian Su
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, Fujian Normal University, Fuzhou 350117, China; (J.S.); (Y.L.); (S.H.); (L.T.)
- Provincial University Key Laboratory of Microbial Pathogenesis and Interventions, Fujian Normal University, Fuzhou 350117, China
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Fujian Normal University, Fuzhou 350117, China
| | - Yingsheng Luo
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, Fujian Normal University, Fuzhou 350117, China; (J.S.); (Y.L.); (S.H.); (L.T.)
- Provincial University Key Laboratory of Microbial Pathogenesis and Interventions, Fujian Normal University, Fuzhou 350117, China
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Fujian Normal University, Fuzhou 350117, China
| | - Shan Hu
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, Fujian Normal University, Fuzhou 350117, China; (J.S.); (Y.L.); (S.H.); (L.T.)
- Provincial University Key Laboratory of Microbial Pathogenesis and Interventions, Fujian Normal University, Fuzhou 350117, China
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Fujian Normal University, Fuzhou 350117, China
| | - Lu Tang
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, Fujian Normal University, Fuzhou 350117, China; (J.S.); (Y.L.); (S.H.); (L.T.)
- Provincial University Key Laboratory of Microbial Pathogenesis and Interventions, Fujian Normal University, Fuzhou 350117, China
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Fujian Normal University, Fuzhou 350117, China
| | - Songying Ouyang
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, Fujian Normal University, Fuzhou 350117, China; (J.S.); (Y.L.); (S.H.); (L.T.)
- Provincial University Key Laboratory of Microbial Pathogenesis and Interventions, Fujian Normal University, Fuzhou 350117, China
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Fujian Normal University, Fuzhou 350117, China
- Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China
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Calcaterra V, Cena H, Sottotetti F, Hruby C, Madini N, Zelaschi N, Zuccotti G. Low-Calorie Ketogenic Diet: Potential Application in the Treatment of Polycystic Ovary Syndrome in Adolescents. Nutrients 2023; 15:3582. [PMID: 37630772 PMCID: PMC10459579 DOI: 10.3390/nu15163582] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 08/05/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Hyperandrogenism, hyperinsulinism and insulin resistance (IR) are the main drivers of clinical, metabolic and reproductive phenotypes of PCOS. In adolescence, the cornerstones of PCOS treatment are lifestyle and dietary interventions. In particular, the quality and quantity of carbohydrates introduced with the diet play a crucial role in the benefits of diet on PCOS. Recently, the ketogenic diet (KD) has attracted significant interest for the treatment of IR and for the control of carbohydrate metabolism, which has proven to be beneficial for several dysmetabolic conditions, including PCOS. The goal of the KD is to induce a fasting-like metabolism with production of chetonic bodies. Ketosis is a good regulator of calorie intake and mimics the starvation effect in the body, leading to body weight control and consequent metabolism. Additionally, during ketogenesis, insulin receptor sensitivity is also promoted. We proposed a broad overview of the available literature regarding KD indications and considered its metabolic benefits useful for improving PCOS management. The reported data support that a low-calorie ketogenic diet (LCKD) plays a positive role as a regulator of control weight, IR, glucose and lipid homeostasis and hormonal profile. Unfortunately, the evidence concerning the benefits of the very LCKD in adolescents with PCOS and excessive body weight is still numerically scarce. Further studies are necessary to understand whether these effects are due to weight loss or to the nutritional characteristics of this diet. Considering the long-term consequences of PCOS, it is crucial to detect the prospects of nutritional interventions to protect fertility, starting in adolescence.
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Affiliation(s)
- Valeria Calcaterra
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy;
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milano, Italy; (C.H.); (G.Z.)
| | - Hellas Cena
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (F.S.); (N.M.); (N.Z.)
- Clinical Nutrition and Dietetics Service, Unit of Internal Medicine and Endocrinology, ICS Maugeri IRCCS, 27100 Pavia, Italy
| | - Francesca Sottotetti
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (F.S.); (N.M.); (N.Z.)
| | - Chiara Hruby
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milano, Italy; (C.H.); (G.Z.)
| | - Nagaia Madini
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (F.S.); (N.M.); (N.Z.)
| | - Noemi Zelaschi
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (F.S.); (N.M.); (N.Z.)
| | - Gianvincenzo Zuccotti
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milano, Italy; (C.H.); (G.Z.)
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; (F.S.); (N.M.); (N.Z.)
- Department of Biomedical and Clinical Science, University of Milano, 20157 Milano, Italy
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Najafabadi MS, Moludi J, Salimi Y, Saber A. A comparison of the portfolio low-carbohydrate diet and the ketogenic diet in overweight and obese women with polycystic ovary syndrome: study protocol for a randomized controlled trial. Trials 2023; 24:509. [PMID: 37559131 PMCID: PMC10410796 DOI: 10.1186/s13063-023-07569-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Accepted: 08/04/2023] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is one of the most frequent endocrine disorders among women of fertile age. Women with PCOS manifest clinical symptoms like menstrual dysfunction, hirsutism, insulin resistance, and hyperinsulinemia. As excessive amounts of insulin levels directly increase ovarian production of androgens, hyperinsulinemia and insulin resistance are considered as the pathogenesis factors of PCOS. The portfolio low-carbohydrate diet (PLCD) is a plant-based diet with 40% carbohydrates combined with five cholesterol-lowering foods and nutrients. On the other hand, the ketogenic diet (KD) is a nutritional protocol with 10% carbohydrates. The purpose of this study is to determine whether PLCD or KD is more effective in alleviating PCOS symptoms. METHODS Forty-six overweight or obese women diagnosed with PCOS will be randomly stratified to receive either PLCD or KD for 8 weeks. Measures related to anthropometric and body composition, glucose, and insulin level, HOMA-IR, sex hormones, lipid profile, quality of life, dietary intake, physical activity, and Ferriman-Gallwey score of all participants will be accessed before and after the intervention. DISCUSSION Since the first line treatment of PCOS is lifestyle adjustment including diet control and exercise, there has not been determined the optimal diet for this population of women yet. Hence, the goal of conducting this study is to determine whether the PLCD or the KD could have more advantageous effects on attenuating PCOS manifestations. The result of this investigation will give us new insight into curing this disease and will provide evidence-based recommendations for prescribing an optimal diet for PCOS women. TRIAL REGISTRATION IRCT20200912048693N3, Trial registered 2022-12-14. https://www.irct.ir/trial/67548.
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Affiliation(s)
- Maryam Sharifi Najafabadi
- Student Research Committee, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Jalal Moludi
- Department of Nutritional Sciences, School of Nutritional Sciences and Food Technology, Across From Farabi Hospital, Kermanshah University of Medical Sciences, Isar Sq., P.O. Box 6719851552, Kermanshah, Iran
| | - Yahya Salimi
- Social Development & Health Promotion Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Amir Saber
- Department of Nutritional Sciences, School of Nutritional Sciences and Food Technology, Across From Farabi Hospital, Kermanshah University of Medical Sciences, Isar Sq., P.O. Box 6719851552, Kermanshah, Iran.
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47
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Dyńka D, Kowalcze K, Charuta A, Paziewska A. The Ketogenic Diet and Cardiovascular Diseases. Nutrients 2023; 15:3368. [PMID: 37571305 PMCID: PMC10421332 DOI: 10.3390/nu15153368] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 07/24/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
The most common and increasing causes of death worldwide are cardiovascular diseases (CVD). Taking into account the fact that diet is a key factor, it is worth exploring this aspect of CVD prevention and therapy. The aim of this article is to assess the potential of the ketogenic diet in the prevention and treatment of CVD. The article is a comprehensive, meticulous analysis of the literature in this area, taking into account the most recent studies currently available. The ketogenic diet has been shown to have a multifaceted effect on the prevention and treatment of CVD. Among other aspects, it has a beneficial effect on the blood lipid profile, even compared to other diets. It shows strong anti-inflammatory and cardioprotective potential, which is due, among other factors, to the anti-inflammatory properties of the state of ketosis, the elimination of simple sugars, the restriction of total carbohydrates and the supply of omega-3 fatty acids. In addition, ketone bodies provide "rescue fuel" for the diseased heart by affecting its metabolism. They also have a beneficial effect on the function of the vascular endothelium, including improving its function and inhibiting premature ageing. The ketogenic diet has a beneficial effect on blood pressure and other CVD risk factors through, among other aspects, weight loss. The evidence cited is often superior to that for standard diets, making it likely that the ketogenic diet shows advantages over other dietary models in the prevention and treatment of cardiovascular diseases. There is a legitimate need for further research in this area.
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Affiliation(s)
| | | | | | - Agnieszka Paziewska
- Institute of Health Sciences, Faculty of Medical and Health Sciences, Siedlce University of Natural Sciences and Humanities, 08-110 Siedlce, Poland; (D.D.); (K.K.); (A.C.)
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Jing T, Zhang S, Bai M, Chen Z, Gao S, Li S, Zhang J. Effect of Dietary Approaches on Glycemic Control in Patients with Type 2 Diabetes: A Systematic Review with Network Meta-Analysis of Randomized Trials. Nutrients 2023; 15:3156. [PMID: 37513574 PMCID: PMC10384204 DOI: 10.3390/nu15143156] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/07/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND Dietary patterns play a critical role in diabetes management, while the best dietary pattern for Type 2 diabetes (T2DM) patients is still unclear. The aim of this network meta-analysis was to compare the impacts of various dietary approaches on the glycemic control of T2DM patients. METHODS Relevant studies were retrieved from PubMed, Embase, Web of Knowledge, Cochrane Central Register of Controlled Trials (CENTRAL), and other additional records (1949 to 31 July 2022). Eligible RCTs were those comparing different dietary approaches against each other or a control diet in individuals with T2DM for at least 6 months. We assessed the risk of bias of included studies with the Cochrane risk of bias tool and confidence of estimates with the Grading of Recommendations Assessment, Development, and Evaluation approach for network meta-analyses. In order to determine the pooled effect of each dietary approach relative to each other, we performed a network meta-analysis (NMA) for interventions for both HbA1c and fasting glucose, which enabled us to estimate the relative intervention effects by combing both direct and indirect trial evidence. RESULTS Forty-two RCTs comprising 4809 patients with T2DM were included in the NMA, comparing 10 dietary approaches (low-carbohydrate, moderate-carbohydrate, ketogenic, low-fat, high-protein, Mediterranean, Vegetarian/Vegan, low glycemic index, recommended, and control diets). In total, 83.3% of the studies were at a lower risk of bias or had some concerns. Findings of the NMA revealed that the ketogenic, low-carbohydrate, and low-fat diets were significantly effective in reducing HbA1c (viz., -0.73 (-1.19, -0.28), -0.69 (-1.32, -0.06), and -1.82 (-2.93, -0.71)), while moderate-carbohydrate, low glycemic index, Mediterranean, high-protein, and low-fat diets were significantly effective in reducing fasting glucose (viz., -1.30 (-1.92, -0.67), -1.26 (-2.26, -0.27), -0.95 (-1.51, -0.38), -0.89 (-1.60, -0.18) and -0.75 (-1.24, -0.27)) compared to a control diet. The clustered ranking plot for combined outcomes indicated the ketogenic, Mediterranean, moderate-carbohydrate, and low glycemic index diets had promising effects for controlling HbA1c and fasting glucose. The univariate meta-regressions showed that the mean reductions of HbA1c and fasting glucose were only significantly related to the mean weight change of the subjects. CONCLUSIONS For glycemic control in T2DM patients, the ketogenic diet, Mediterranean diet, moderate-carbohydrate diet, and low glycemic index diet were effective options. Although this study found the ketogenic diet superior, further high-quality and long-term studies are needed to strengthen its credibility.
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Affiliation(s)
- Tiantian Jing
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; (T.J.)
| | - Shunxing Zhang
- Department of Global Public Health/Media, Culture, and Communication, Steinhardt School of Culture, Education, and Human Development, New York University, New York, NY 10016, USA
| | - Mayangzong Bai
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; (T.J.)
| | - Zhongwan Chen
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; (T.J.)
| | - Sihan Gao
- School of Public Health, University of Washington Seattle Campus, Seattle, WA 98105, USA
| | - Sisi Li
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; (T.J.)
| | - Jing Zhang
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; (T.J.)
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Paoli A, Bianco A, Moro T, Mota JF, Coelho-Ravagnani CF. The Effects of Ketogenic Diet on Insulin Sensitivity and Weight Loss, Which Came First: The Chicken or the Egg? Nutrients 2023; 15:3120. [PMID: 37513538 PMCID: PMC10385501 DOI: 10.3390/nu15143120] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 07/05/2023] [Accepted: 07/06/2023] [Indexed: 07/30/2023] Open
Abstract
The ketogenic diet (KD) is, nowadays, considered an interesting nutritional approach for weight loss and improvement in insulin resistance. Nevertheless, most of the studies available in the literature do not allow a clear distinction between its effects on insulin sensitivity per se, and the effects of weight loss induced by KDs on insulin sensitivity. In this review, we discuss the scientific evidence on the direct and weight loss mediated effects of KDs on glycemic status in humans, describing the KD's biochemical background and the underlying mechanisms.
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Affiliation(s)
- Antonio Paoli
- Department of Biomedical Sciences, University of Padua, 35127 Padua, Italy
- Research Center for High Performance Sport, UCAM, Catholic University of Murcia, 30107 Murcia, Spain
| | - Antonino Bianco
- Sport and Exercise Sciences Research Unit, University of Palermo, 90144 Palermo, Italy
| | - Tatiana Moro
- Department of Biomedical Sciences, University of Padua, 35127 Padua, Italy
| | - Joao Felipe Mota
- School of Nutrition, Federal University of Goiás, Goiânia 74605-080, Brazil
- APC Microbiome Ireland, Department of Medicine, School of Microbiology, University College Cork, T12 YT20 Cork, Ireland
| | - Christianne F Coelho-Ravagnani
- Research in Exercise and Nutrition in Health and Sports Performance-PENSARE, Post-Graduate Program in Movement Sciences, Institute of Health (INISA), Federal University of Mato Grosso do Sul, Campo Grande 79070-900, Brazil
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50
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Papadopoulou SK, Nikolaidis PT. Low-Carbohydrate Diet and Human Health. Nutrients 2023; 15:nu15082004. [PMID: 37111222 PMCID: PMC10143153 DOI: 10.3390/nu15082004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 04/02/2023] [Accepted: 04/17/2023] [Indexed: 04/29/2023] Open
Abstract
Low-carbohydrate diets were initially recommended as a therapeutic dietary scheme for epilepsy, while increasing evidence suggests their potential application in the management of several other pathologies, such as diabetes, neoplasms, gastrointestinal and lung diseases, diseases of the cardiovascular system, as well as obesity [...].
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Affiliation(s)
- Sousana K Papadopoulou
- Department of Nutritional Sciences and Dietetics, School of Health Sciences, International Hellenic University, 57001 Thessaloniki, Greece
| | - Pantelis T Nikolaidis
- School of Health and Caring Sciences, University of West Attica, 12243 Athens, Greece
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