|
1
|
Dlamini M, Khathi A. Investigating the Effects of Diet-Induced Prediabetes on Skeletal Muscle Strength in Male Sprague Dawley Rats. Int J Mol Sci 2024; 25:4076. [PMID: 38612885 PMCID: PMC11012655 DOI: 10.3390/ijms25074076] [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: 03/06/2024] [Revised: 04/01/2024] [Accepted: 04/02/2024] [Indexed: 04/14/2024] Open
Abstract
Type 2 diabetes mellitus, a condition preceded by prediabetes, is documented to compromise skeletal muscle health, consequently affecting skeletal muscle structure, strength, and glucose homeostasis. A disturbance in skeletal muscle functional capacity has been demonstrated to induce insulin resistance and hyperglycemia. However, the modifications in skeletal muscle function in the prediabetic state are not well elucidated. Hence, this study investigated the effects of diet-induced prediabetes on skeletal muscle strength in a prediabetic model. Male Sprague Dawley rats were randomly assigned to one of the two groups (n = 6 per group; six prediabetic (PD) and six non-pre-diabetic (NPD)). The PD group (n = 6) was induced with prediabetes for 20 weeks. The diet that was used to induce prediabetes consisted of fats (30% Kcal/g), proteins (15% Kcal/g), and carbohydrates (55% Kcal/g). In addition to the diet, the experimental animals (n = 6) were supplied with drinking water that was supplemented with 15% fructose. The control group (n = 6) was allowed access to normal rat chow, consisting of 35% carbohydrates, 30% protein, 15% fats, and 20% other components, as well as ordinary tap water. At the end of week 20, the experimental animals were diagnosed with prediabetes using the American Diabetes Association (ADA) prediabetes impaired fasting blood glucose criteria (5.6-6.9 mmol/L). Upon prediabetes diagnosis, the animals were subjected to a four-limb grip strength test to assess skeletal muscle strength at week 20. After the grip strength test was conducted, the animals were euthanized for blood and tissue collection to analyze glycated hemoglobin (HbA1c), plasma insulin, and insulin resistance using the homeostatic model of insulin resistance (HOMA-IR) index and malondialdehyde (MDA) concentration. Correlation analysis was performed to examine the associations of skeletal muscle strength with HOMA-IR, plasma glucose, HbA1c, and MDA concentration. The results demonstrated increased HbA1c, FBG, insulin, HOMA-IR, and MDA concentrations in the PD group compared to the NPD group. Grip strength was reduced in the PD group compared to the NPD group. Grip strength was negatively correlated with HbA1c, plasma glucose, HOMA-IR, and MDA concentration in the PD group. These observations suggest that diet-induced prediabetes compromises muscle function, which may contribute to increased levels of sedentary behavior during prediabetes progression, and this may contribute to the development of hyperglycemia in T2DM.
Collapse
Affiliation(s)
| | - Andile Khathi
- Department of Human Physiology, School of Laboratory Medicine, Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban X54001, South Africa;
| |
Collapse
|
|
2
|
Khathi A, Dagogo-Jack S. Editorial: Prediabetes and endocrine function. Front Endocrinol (Lausanne) 2023; 14:1268552. [PMID: 37664837 PMCID: PMC10471125 DOI: 10.3389/fendo.2023.1268552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 08/03/2023] [Indexed: 09/05/2023] Open
Affiliation(s)
- Andile Khathi
- School of Laboratory Medicine and Medical Sciences, Discipline of Human Physiology, University of KwaZulu-Natal, Durban, South Africa
| | - Sam Dagogo-Jack
- Division of Endocrinology, Diabetes & Metabolism, The University of Tennessee Health Science Center, Memphis, TN, United States
| |
Collapse
|
|
3
|
Lenz B, Andrew BA, Ritter M, Karunakaran I, Gandjui NVT, Nchang LC, Surendar J, Ebob AOB, Ehrens A, Klarmann-Schulz U, Ricchiuto A, Kuehlwein JM, Fombad FF, Ngwa AM, Katcho TD, Hoerauf A, Wanji S, Hübner MP. The design and development of a study protocol to investigate Onchocerca volvulus, Loa loa and Mansonella perstans-mediated modulation of the metabolic and immunological profile in lean and obese individuals in Cameroon. PLoS One 2023; 18:e0285689. [PMID: 37267236 DOI: 10.1371/journal.pone.0285689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 04/10/2023] [Indexed: 06/04/2023] Open
Abstract
BACKGROUND Life-style metabolic diseases are steadily rising, not only in developed countries, but also in low- and middle-income countries, presenting a global health problem. Metabolic disorders like type 2 diabetes and cardiovascular diseases are among the ten leading causes of death defined by the WHO in 2019. Results from animal and observational human studies suggest a connection between the decline in human helminth infections and rise of life-style-associated metabolic diseases in developing regions. This trial was designed to investigate filarial infections and their impact on metabolic diseases in Cameroon. We hypothesize that the induction of regulatory immune responses during filarial infection reduces obesity-induced low-grade inflammatory immune responses and thereby improves metabolic parameters, whereas anthelmintic treatment abolishes this protective effect. METHODS/DESIGN Participants infected with Mansonella perstans, Onchocerca volvulus and/or Loa loa being lean (BMI <25), overweight (BMI >25 and <30) or clinically obese (BMI ≥30) from Littoral regions of Cameroon will be evaluated for their parasitological, immunological, metabolic and biochemical profile before and after treatment of their parasitic infections. Anthropomorphic measurements and a detailed questionnaire will complement our analysis. The investigation will assess blood immune cell populations, serum adipokines and cytokines that could be influenced by the parasite infection and/or metabolic diseases. Further, parameters like blood glucose, homeostatic model assessment of insulin resistance (HOMA-IR), circulating lipids and circulating makers of liver function will be monitored. Parameters will be assessed before treatment, 12 and 18 months after treatment. CONCLUSION The focus of this study is to obtain a comprehensive metabolic profile of the participants in rural areas of Cameroon and to investigate the relationship between filarial immunomodulation and metabolic diseases. This study will elucidate the effect of anti-filarial treatment on the metabolic and immunological parameters that partake in the development of insulin resistance, narrowing in on a potential protective effect of filarial infections on metabolic diseases. TRIAL REGISTRATION doi.org/10.1186/ISRCTN43845142, ISRCTN43845142 February 2020 Trial title Effects of filarial parasite infection on type 2 diabetes Issue date: 27.10.22, V.1.
Collapse
Affiliation(s)
- Benjamin Lenz
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
| | - Beng Amuam Andrew
- Parasite and Vector Biology Research Unit, Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon
- Research Foundation in Tropical Diseases and the Environment, Buea, Cameroon
| | - Manuel Ritter
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
| | - Indulekha Karunakaran
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
| | - Narcisse Victor Tchamatchoua Gandjui
- Parasite and Vector Biology Research Unit, Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon
- Research Foundation in Tropical Diseases and the Environment, Buea, Cameroon
| | - Lucy Cho Nchang
- Parasite and Vector Biology Research Unit, Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon
- Research Foundation in Tropical Diseases and the Environment, Buea, Cameroon
| | - Jayagopi Surendar
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
| | - Anita Obi Bate Ebob
- Parasite and Vector Biology Research Unit, Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon
- Research Foundation in Tropical Diseases and the Environment, Buea, Cameroon
| | - Alexandra Ehrens
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
- German Center for Infection Research (DZIF), Bonn, Germany
| | - Ute Klarmann-Schulz
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
- German Center for Infection Research (DZIF), Bonn, Germany
| | - Arcangelo Ricchiuto
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
| | - Janina M Kuehlwein
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
- German Center for Infection Research (DZIF), Bonn, Germany
| | - Fanny Fri Fombad
- Parasite and Vector Biology Research Unit, Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon
- Research Foundation in Tropical Diseases and the Environment, Buea, Cameroon
| | - Ambe Marius Ngwa
- Parasite and Vector Biology Research Unit, Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon
- Research Foundation in Tropical Diseases and the Environment, Buea, Cameroon
| | - Tatiana Djikeussi Katcho
- Parasite and Vector Biology Research Unit, Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon
- Research Foundation in Tropical Diseases and the Environment, Buea, Cameroon
| | - Achim Hoerauf
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
- German Center for Infection Research (DZIF), Bonn, Germany
- German-West African Centre for Global Health and Pandemic Prevention (G-WAC), Bonn, Germany
| | - Samuel Wanji
- Parasite and Vector Biology Research Unit, Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon
- Research Foundation in Tropical Diseases and the Environment, Buea, Cameroon
| | - Marc P Hübner
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
- German Center for Infection Research (DZIF), Bonn, Germany
| |
Collapse
|
|
4
|
Wei Y, Liu C, Liu Y, Zhang Z, Feng Z, Yang X, Liu J, Lei H, Zhou H, Shen Q, Lu B, Gu P, Shao J. The association between time in the glucose target range and abnormal ankle-brachial index: a cross-sectional analysis. Cardiovasc Diabetol 2022; 21:281. [PMID: 36514151 PMCID: PMC9746002 DOI: 10.1186/s12933-022-01718-y] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 12/04/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Time in range (TIR), a novel proxy measure of glucose control, is found closely related to diabetic microangiopathy and some other chronic complications, but the correlation between TIR and lower limb angiopathy has not been studied yet. Our purpose is to explore the relationship between TIR and abnormal ankle-brachial index(ABI) in type 2 diabetes. METHODS We retrospectively collected patients' information from the database and performed cross-sectional analysis. A total of 405 type 2 diabetes patients were enrolled in this study. ABI was measured and patients were stratified into low, normal, and high groups according to ≤ 0.9, > 0.9 and < 1.3, ≥ 1.3 ABI values. All patients underwent continuous glucose monitoring(CGM), and TIR was defined as the percentage of time in which glucose was in the range of 3.9-10 mmol/L during a 24-h period. Correlations between TIR and abnormal ABI were analyzed using Spearman analysis. And logistic regression was used to explore whether TIR is an independent risk factor for abnormal ABI. RESULTS The overall prevalence of abnormal ABI was 20.2% (low 4.9% and high 15.3%). TIR was lower in patients with abnormal ABI values (P = 0.009). The prevalence of abnormal ABI decreased with increasing quartiles of TIR (P = 0.026). Abnormal ABI was negatively correlated with TIR and positively correlated with hypertension, age, diabetes duration, UREA, Scr, ACR, TAR, MBG, and M values (P < 0.05). The logistic regression revealed a significant association between TIR and abnormal ABI, while HbA1C and blood glucose variability measures had no explicit correlation with abnormal ABI. Additionally, there was a significant difference in LDL between the low and high ABI groups (P = 0.009), and in Scr between normal and low groups (P = 0.007). And there were significant differences in TIR (P = 0.003), age (P = 0.023), UREA (P = 0.006), ACR (P = 0.004), TAR (P = 0.015), and MBG (P = 0.014) between normal and high ABI groups, and in diabetes duration between both normal and low (P = 0.023) and normal and high (P = 0.006) groups. CONCLUSIONS In type 2 diabetes patients, abnormal ABI is associated with lower TIR, and the correlation is stronger than that with HbA1C. Therefore, the role of TIR should be emphasized in the evaluation of lower limb vascular diseases.
Collapse
Affiliation(s)
- Yinghua Wei
- Department of Endocrinology, Affiliated Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Chunyan Liu
- Department of Endocrinology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China
| | - Yanyu Liu
- Department of Endocrinology, Affiliated Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Zhen Zhang
- Department of Endocrinology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China
| | - Zhouqin Feng
- Department of Endocrinology, Affiliated Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Xinyi Yang
- Department of Endocrinology, Affiliated Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Juan Liu
- Department of Endocrinology, The affiliated Jinling Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Haiyan Lei
- Department of Endocrinology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China
| | - Hui Zhou
- Department of Endocrinology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China
| | - Qiuyue Shen
- Department of Endocrinology, Affiliated Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Bin Lu
- Department of Endocrinology, Affiliated Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Ping Gu
- Department of Endocrinology, Affiliated Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
| | - Jiaqing Shao
- Department of Endocrinology, Affiliated Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
| |
Collapse
|
|
5
|
Gumede N, Ngubane P, Khathi A. Assessing the risk factors for myocardial infarction in diet-induced prediabetes: myocardial tissue changes. BMC Cardiovasc Disord 2022; 22:350. [PMID: 35918636 PMCID: PMC9347129 DOI: 10.1186/s12872-022-02758-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 04/19/2022] [Indexed: 11/24/2022] Open
Abstract
Background Hyperglycaemia is known to result in oxidative stress tissue injury and dysfunction. Interestingly, studies have reported hepatic and renal oxidative stress injury during prediabetes; however, any injury to the myocardium during prediabetes has not been investigated. Hence this study aims to assess changes in the myocardial tissue in an HFHC diet-induced model of prediabetes. Methods Male Sprague Dawley rats were randomly grouped into non-prediabetes and prediabetes (n = 6 in each group) and consumed a standard rat chow or fed a high-fat-high-carbohydrate diet respectively for a 20-week prediabetes induction period. Post induction, prediabetes was confirmed using the ADA criteria. Aldose reductase, NADH oxidase 1, superoxide dismutase, glutathione peroxide, cardiac troponins were analysed in cardiac tissue homogenate using specific ELISA kits. Lipid peroxidation was estimated by determining the concentration of malondialdehyde in the heart tissue homogenate according to the previously described protocol. Myocardial tissue sections were stained with H&E stain and analysed using Leica microsystem. All data were expressed as means ± SEM. Statistical comparisons were performed with Graph Pad instat Software using the Student's two-sided t-test. Pearson correlation coefficient was calculated to assess the association. Value of p < 0.05 was considered statistically significant. Results The prediabetes group showed a markedly high oxidative stress as indicated by significantly increased NADH oxidase 1 and malondialdehyde while superoxide dismutase and glutathione peroxide were decreased compared to non-prediabetes group. There was no statistical difference between cardiac troponin I and T in the non-prediabetes and prediabetes groups. Cardiac troponins had a weak positive association with glycated haemoglobin. Conclusion The findings of this study demonstrate that prediabetes is associated with myocardial injury through oxidative stress. Future studies are to investigate cardiac contractile function and include more cardiac biomarkers. Supplementary Information The online version contains supplementary material available at 10.1186/s12872-022-02758-8.
Collapse
Affiliation(s)
- Nompumelelo Gumede
- Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, X54001, South Africa. .,Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Room E2 401, Westville, South Africa.
| | - Phikelelani Ngubane
- Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, X54001, South Africa
| | - Andile Khathi
- Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, X54001, South Africa
| |
Collapse
|
|
6
|
Pesticide Exposure in Relation to the Incidence of Abnormal Glucose Regulation: A Retrospective Cohort Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19127550. [PMID: 35742799 PMCID: PMC9223857 DOI: 10.3390/ijerph19127550] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 06/16/2022] [Accepted: 06/18/2022] [Indexed: 12/04/2022]
Abstract
Diabetes and prediabetes (called abnormal glucose regulation (AGR)) are adverse health effects associated with exposure to pesticides. However, there are few epidemiological studies on the relationship between pesticide use and the incidence of AGR. We examined the causal relationship between pesticide use and AGR incidence in a rural population using data from a Korean Farmers’ Cohort study of 1076 participants. Poisson regression with robust error variance was used to calculate the relative risks (RR) and 95% confidence intervals (CI) to estimate the relationship between pesticide exposure and AGR. The incidence of AGR in the pesticide-exposed group was 29.1%. Pesticide use increased the RR of AGR (RR 1.32, 95% CI 1.03–1.69). We observed a low-dose effect related to exposure of pesticides to AGR and a U-shaped dose–response relationship in men. Pesticide exposure is related to the incidence of AGR, and the causal relationship differs between men and women.
Collapse
|
|
7
|
Increased Platelet Reactivity and Proinflammatory Profile Are Associated with Intima-Media Thickness and Arterial Stiffness in Prediabetes. J Clin Med 2022; 11:jcm11102870. [PMID: 35628995 PMCID: PMC9142942 DOI: 10.3390/jcm11102870] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/16/2022] [Accepted: 05/17/2022] [Indexed: 01/25/2023] Open
Abstract
Alterations of glucose homeostasis are associated with subclinical vascular damage; however, the role of platelet reactivity in this process has not been fully investigated. In this cross-sectional study, we evaluated the correlation between markers of platelet reactivity and inflammation and markers of vascular disease in subjects with prediabetes. Markers of platelet reactivity such as 11-dehydro-thromboxane B2 urinary levels (11-dh-TXB2) and mean platelet volume (MPV) and inflammatory indexes such as platelet-to-lymphocyte ratio (PLR) were evaluated in subjects with prediabetes (n = 48), new-onset type 2 diabetes (NODM, n = 60) and controls (n = 62). Furthermore, we assessed the cardiovascular risk profile of the study population with arterial stiffness and quality intima–media thickness (qIMT). Subjects with prediabetes and NODM exhibited higher 11-dh-TXB2 urinary levels and MPV and a proinflammatory profile with an increased PLR, high-sensitivity C-reactive protein, ferritin and fibrinogen. Furthermore, after multiple regression analyses, we found that urinary 11-dh-TXB2 was one of the major determinants of IMT and arterial stiffness parameters. In conclusion, subjects with prediabetes exhibit increased platelet reactivity as well as a proinflammatory profile. Furthermore, this condition is associated with early markers of cardiovascular disease.
Collapse
|
|
8
|
Cheng X, Li Z, Yang M, Liu Y, Wang S, Huang M, Gao S, Yang R, Li L, Yu C. Association of HbA1c with carotid artery plaques in patients with coronary heart disease: a retrospective clinical study. Acta Cardiol 2022; 78:442-450. [PMID: 35356852 DOI: 10.1080/00015385.2022.2040822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
BACKGROUND AND AIMS Haemoglobin A1c (HbA1c) levels have been shown to be related to carotid artery plaques. However, studies on the relationship between HbA1c levels and carotid artery plaques in patients with coronary heart disease (CHD) are limited and inconsistent. Our objective was to examine the correlation between HbA1c levels and carotid artery plaques in patients with CHD. METHODS The study comprised 9275 Chinese adults with CHD from January 1, 2014, to September 30, 2020. HbA1c levels were assessed, and colour Doppler ultrasound was used to evaluate the carotid artery, including plaque presence, intima-media thickness, and plaque echo properties, to investigate the association between HbA1c and carotid plaque. A logistic regression model was used to assess the association between carotid artery plaques, carotid plaque echogenicity, and HbA1c. RESULTS The HbA1c level of the plaque-present group was higher than that of the plaque-absent group [6.1 (5.6-7.2) vs. 5.8 (5.5-6.5), p < 0.001]. In multiple linear regression analysis, intima-media thickness was associated with HbA1c (p < 0.001). Logistic regression showed that a higher HbA1c level was associated with plaque incidence as well as hyperechoic and heterogeneous plaques (p < 0.001). These associations persist after adjusting for age, sex, blood pressure, lipid profiles, alcohol consumption, and tobacco exposure. CONCLUSION HbA1c levels are notably associated with carotid artery plaque incidence, intima-media thickness, and plaque echogenicity in patients with CHD. These findings show that different levels of HbA1c may be an indicator for carotid artery plaques and thus, should be observed in patients with CHD.
Collapse
Affiliation(s)
- Xufeng Cheng
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Zhu Li
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Mingjie Yang
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yijia Liu
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shuo Wang
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Mengnan Huang
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shan Gao
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Rongrong Yang
- School of Health Science and Engineering, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Lin Li
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Chunquan Yu
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| |
Collapse
|
|
9
|
Di Pino A, Scicali R, Marchisello S, Zanoli L, Ferrara V, Urbano F, Filippello A, Di Mauro S, Scamporrino A, Piro S, Castellino P, Purrello F, Rabuazzo AM. High glomerular filtration rate is associated with impaired arterial stiffness and subendocardial viability ratio in prediabetic subjects. Nutr Metab Cardiovasc Dis 2021; 31:3393-3400. [PMID: 34625357 DOI: 10.1016/j.numecd.2021.08.030] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 07/08/2021] [Accepted: 08/04/2021] [Indexed: 11/27/2022]
Abstract
BACKGROUND AND AIMS High glomerular filtration rate (HGFR) is associated with cardiovascular damage in the setting of various conditions such as obesity and diabetes. Prediabetes was also associated with increased GFR, however, the association between prediabetes, HGFR and cardiovascular damage has not been investigated. In this study, we investigated the association between HGFR and early markers of cardiovascular disease in subjects with prediabetes. METHODS AND RESULTS Augmentation pressure (Aug), augmentation index (AIx), subendocardial viability ratio (SEVR), pulse wave velocity (PWV), intima-media thickness (IMT) and estimated GFR (eGFR) were evaluated in 230 subjects with prediabetes. The eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration formula. HGFR was defined as an eGFR above the 75th percentile. Prediabetic subjects were divided into two groups according to presence/absence of HGFR: 61 subjects with HGFR and 169 subjects without HGFR. Subjects with HGFR showed higher Aug, AIx and lower SEVR compared with prediabetic subjects with lower eGFR (14.1 ± 7.2 vs 10.8 ± 6.2, 32.9 ± 12.7 vs 27.6 ± 11.7, 153.5 ± 27.8 vs 162 ± 30.2, p < 0.05). No differences were found in PWV and IMT values between the two groups. Then, we performed multiple regression analysis to test the relationship between Aug, SEVR and several cardiovascular risk factors. In multiple regression analysis Aug was associated with age, systolic blood pressure (BP), HOMA-IR and eGFR; the major determinants of SEVR were systolic BP, HOMA-IR and eGFR. CONCLUSION Subjects with prediabetes and HGFR exhibited an increased Aug, AIx and a reduced SEVR. These alterations are associated with eGFR, insulin resistance and systolic BP.
Collapse
Affiliation(s)
- Antonino Di Pino
- Department of Clinical and Experimental Medicine, University of Catania, Torre Biologica F. Latteri, S. Sofia Street 89, 9512, Catania, Italy
| | - Roberto Scicali
- Department of Clinical and Experimental Medicine, University of Catania, Torre Biologica F. Latteri, S. Sofia Street 89, 9512, Catania, Italy
| | - Simona Marchisello
- Department of Clinical and Experimental Medicine, University of Catania, Torre Biologica F. Latteri, S. Sofia Street 89, 9512, Catania, Italy
| | - Luca Zanoli
- Department of Clinical and Experimental Medicine, University of Catania, Torre Biologica F. Latteri, S. Sofia Street 89, 9512, Catania, Italy
| | - Viviana Ferrara
- Department of Clinical and Experimental Medicine, University of Catania, Torre Biologica F. Latteri, S. Sofia Street 89, 9512, Catania, Italy
| | - Francesca Urbano
- Department of Clinical and Experimental Medicine, University of Catania, Torre Biologica F. Latteri, S. Sofia Street 89, 9512, Catania, Italy
| | - Agnese Filippello
- Department of Clinical and Experimental Medicine, University of Catania, Torre Biologica F. Latteri, S. Sofia Street 89, 9512, Catania, Italy
| | - Stefania Di Mauro
- Department of Clinical and Experimental Medicine, University of Catania, Torre Biologica F. Latteri, S. Sofia Street 89, 9512, Catania, Italy
| | - Alessandra Scamporrino
- Department of Clinical and Experimental Medicine, University of Catania, Torre Biologica F. Latteri, S. Sofia Street 89, 9512, Catania, Italy
| | - Salvatore Piro
- Department of Clinical and Experimental Medicine, University of Catania, Torre Biologica F. Latteri, S. Sofia Street 89, 9512, Catania, Italy
| | - Pietro Castellino
- Department of Clinical and Experimental Medicine, University of Catania, Torre Biologica F. Latteri, S. Sofia Street 89, 9512, Catania, Italy
| | - Francesco Purrello
- Department of Clinical and Experimental Medicine, University of Catania, Torre Biologica F. Latteri, S. Sofia Street 89, 9512, Catania, Italy.
| | - Agata M Rabuazzo
- Department of Clinical and Experimental Medicine, University of Catania, Torre Biologica F. Latteri, S. Sofia Street 89, 9512, Catania, Italy
| |
Collapse
|
|
10
|
Antoniou S, Naka KK, Papadakis M, Bechlioulis A, Tsatsoulis A, Michalis LK, Tigas S. Effect of glycemic control on markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus: A review. World J Diabetes 2021; 12:1856-1874. [PMID: 34888012 PMCID: PMC8613661 DOI: 10.4239/wjd.v12.i11.1856] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 07/29/2021] [Accepted: 10/09/2021] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular disease is the predominant cause of death in type 2 diabetes mellitus (T2DM). Evidence suggests a strong association between duration and degree of hyperglycemia and vascular disease. However, large trials failed to show cardiovascular benefit after intensive glycemic control, especially in patients with longer diabetes duration. Atherosclerosis is a chronic and progressive disease, with a long asymptomatic phase. Subclinical atherosclerosis, which is impaired in T2DM, includes impaired vasodilation, increased coronary artery calcification (CAC), carotid intima media thickness, arterial stiffness, and reduced arterial elasticity. Each of these alterations is represented by a marker of subclinical atherosclerosis, offering a cost-effective alternative compared to classic cardiac imaging. Their additional use on top of traditional risk assessment strengthens the predictive risk for developing coronary artery disease (CAD). We, herein, review the existing literature on the effect of glycemic control on each of these markers separately. Effective glycemic control, especially in earlier stages of the disease, attenuates progression of structural markers like intima-media thickness and CAC. Functional markers are improved after use of newer anti-diabetic agents, such as incretin-based treatments or sodium-glucose co-transporter-2 inhibitors, especially in T2DM patients with shorter disease duration. Larger prospective trials are needed to enhance causal inferences of glycemic control on clinical endpoints of CAD.
Collapse
Affiliation(s)
- Sofia Antoniou
- Department of Endocrinology, University of Ioannina, Ioannina 45110, Greece
| | - Katerina K Naka
- 2nd Department of Cardiology and Michaelidion Cardiac Center, University of Ioannina, Ioannina 45110, Greece
| | - Marios Papadakis
- Department of Surgery II, University of Witten-Herdecke, Wuppertal 42283, Germany
| | - Aris Bechlioulis
- 2nd Department of Cardiology and Michaelidion Cardiac Center, University of Ioannina, Ioannina 45110, Greece
| | | | - Lampros K Michalis
- 2nd Department of Cardiology and Michaelidion Cardiac Center, University of Ioannina, Ioannina 45110, Greece
| | - Stelios Tigas
- Department of Endocrinology, University of Ioannina, Ioannina 45110, Greece
| |
Collapse
|
|
11
|
Cai M, Bowe B, Xie Y, Al-Aly Z. Temporal trends of COVID-19 mortality and hospitalisation rates: an observational cohort study from the US Department of Veterans Affairs. BMJ Open 2021; 11:e047369. [PMID: 34400452 PMCID: PMC8370839 DOI: 10.1136/bmjopen-2020-047369] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
OBJECTIVES To investigate the temporal trends of 30-day mortality and hospitalisation in US Veterans with COVID-19 and 30-day mortality in hospitalised veterans with COVID-19 and to decompose the contribution of changes in the underlying characteristics of affected populations to these temporal changes. DESIGN Observational cohort study. SETTING US Department of Veterans Affairs. PARTICIPANTS 49 238 US veterans with a positive COVID-19 test between 20 March 2020 and 19 September 2020; and 9428 US veterans hospitalised with a positive COVID-19 test during the same period. OUTCOME MEASURES 30-day mortality rate and hospitalisation rate. RESULTS Between 20 March 2020 and 19 September 2020 and in COVID-19 positive individuals, 30-day mortality rate dropped by 9.2% from 13.6% to 4.4%; hospitalisation rate dropped by 16.8% from 33.8% to 17.0%. In hospitalised COVID-19 individuals, 30-day mortality rate dropped by 12.7% from 23.5% to 10.8%. Among COVID-19 positive individuals, decomposition analyses suggested that changes in demographic, health and contextual characteristics, COVID-19 testing capacity, and hospital occupancy rates accounted for 40.2% and 33.3% of the decline in 30-day mortality and hospitalisation, respectively. Changes in the underlying characteristics of hospitalised COVID-19 individuals accounted for 29.9% of the decline in 30-day mortality. CONCLUSION Between March and September 2020, changes in demographic and health characteristics of people infected with COVID-19 contributed measurably to the substantial decline in 30-day mortality and hospitalisation.
Collapse
Affiliation(s)
- Miao Cai
- Clinical Epidemiology Center, VA Saint Louis Health Care System, Saint Louis, Missouri, USA
- Veterans Research and Education Foundation of Saint Louis, Saint Louis, Missouri, USA
| | - Benjamin Bowe
- Clinical Epidemiology Center, VA Saint Louis Health Care System, Saint Louis, Missouri, USA
- Veterans Research and Education Foundation of Saint Louis, Saint Louis, Missouri, USA
- Department of Epidemiology and Biostatistics, College for Public Health and Social Justice, Saint Louis University, Saint Louis, Missouri, USA
| | - Yan Xie
- Clinical Epidemiology Center, VA Saint Louis Health Care System, Saint Louis, Missouri, USA
- Veterans Research and Education Foundation of Saint Louis, Saint Louis, Missouri, USA
- Department of Epidemiology and Biostatistics, College for Public Health and Social Justice, Saint Louis University, Saint Louis, Missouri, USA
| | - Ziyad Al-Aly
- Clinical Epidemiology Center, VA Saint Louis Health Care System, Saint Louis, Missouri, USA
- Veterans Research and Education Foundation of Saint Louis, Saint Louis, Missouri, USA
- Institute for Public Health, Washington University in Saint Louis, Saint Louis, Missouri, USA
- Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
- Nephrology Section, Medicine Service, VA Saint Louis Health Care System, Saint Louis, Missouri, USA
| |
Collapse
|
|
12
|
Giglio RV, Stoian AP, Haluzik M, Pafili K, Patti AM, Rizvi AA, Ciaccio M, Papanas N, Rizzo M. Novel molecular markers of cardiovascular disease risk in type 2 diabetes mellitus. Biochim Biophys Acta Mol Basis Dis 2021; 1867:166148. [PMID: 33892081 DOI: 10.1016/j.bbadis.2021.166148] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 03/15/2021] [Accepted: 04/13/2021] [Indexed: 02/07/2023]
Abstract
Diabetes represents the leading risk factor for the development of cardiovascular disease (CVD). Chronic hyperglycemia and/or acute post-prandial changes in blood glucose determine an increase in reactive oxygen species (ROS), which play a fundamental role in endothelial dysfunction and in the nuclear transport of pro-atherogenic transcription factors that activate the "inflammasome". In addition, the glycemic alteration favors the formation and stabilization of atherosclerotic plaque through the mechanism of non-enzymatic glycation of different molecules, with the establishment of the so-called "advanced glycosylation end products" (AGE). Laboratory information provided by the level of biomarkers could make a quantitative and qualitative contribution to the clinical process of screening, prediction, prevention, diagnosis, prognosis and monitoring of cardiovascular (CV) risk linked to diabetes. This review describes the importance of specific biomarkers, with particular focus on novel ones, for stratifying and management of diabetes CV risk.
Collapse
Affiliation(s)
- Rosaria Vincenza Giglio
- Department of Biomedicine, Neuroscience, and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Laboratory Medicine, University of Palermo, Palermo, Italy
| | - Anca Pantea Stoian
- Faculty of General Medicine, Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University, Bucharest, Romania
| | - Martin Haluzik
- Centre for Experimental Medicine and Department of Diabetes, Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
| | - Kalliopi Pafili
- Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece
| | - Angelo Maria Patti
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.
| | - Ali Abbas Rizvi
- Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University, Atlanta, Georgia, USA; Division of Endocrinology, Diabetes and Metabolism, University of South Carolina School of Medicine Columbia, South Carolina, USA
| | - Marcello Ciaccio
- Department of Biomedicine, Neuroscience, and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Laboratory Medicine, University of Palermo, Palermo, Italy; Department of Laboratory Medicine, University-Hospital, Palermo, Italy
| | - Nikolaos Papanas
- Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece
| | - Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy; Division of Endocrinology, Diabetes and Metabolism, University of South Carolina School of Medicine Columbia, South Carolina, USA
| |
Collapse
|
|
13
|
Arterial Stiffness: Its Relation with Prediabetes and Metabolic Syndrome and Possible Pathogenesis. J Clin Med 2021; 10:jcm10153251. [PMID: 34362033 PMCID: PMC8348675 DOI: 10.3390/jcm10153251] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 07/01/2021] [Accepted: 07/21/2021] [Indexed: 11/26/2022] Open
Abstract
Aims: To evaluate arterial stiffness indicators in people with prediabetes (PreD) and its possible pathogenesis. Materials and methods: Pulse wave velocity (PWV) was measured in 208 people with FINDRISC ≥ 13 (57 ± 8 years old, 68.7% women) and thereafter divided into those having either normal glucose tolerance (NGT) or PreD. In each subgroup we also identified those with/out insulin resistance (IR) measured by the triglyceride/HDL-c ratio (normal cut off values previously established in our population). Clinical and metabolic data were collected for all participants. PWV was compared between subgroups using independent t test. Results: Women and men had comparable clinical and metabolic characteristics with obesity (BMI ≥ 30) and antihypertensive-statin treatment, almost half with either NGT or PreD. Whereas 48% of NGT people presented IR (abnormally high TG/HDL-c ratio), 52% had PreD. PWV was significantly higher only in those with a complete picture of metabolic syndrome (MS). Conclusions: Since PWV was significantly impaired in people with a complete picture of MS, clinicians must carefully search for early diagnosis of this condition and prescribe a healthy life-style to prevent development/progression of CVD. This proactive attitude would provide a cost-effective preventive strategy to avoid CVD’s negative impact on patients’ quality of life and on health systems due to their higher care costs.
Collapse
|
|
14
|
Oza MJ, Laddha AP, Gaikwad AB, Mulay SR, Kulkarni YA. Role of dietary modifications in the management of type 2 diabetic complications. Pharmacol Res 2021; 168:105602. [PMID: 33838293 DOI: 10.1016/j.phrs.2021.105602] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/31/2021] [Accepted: 04/02/2021] [Indexed: 12/15/2022]
Abstract
Diabetes is a chronic metabolic disorder with a high rate of morbidity and mortality. Insufficient insulin secretion and insulin action are two major causes for the development of diabetes, which is characterized by a persistent increase in blood glucose level. Diet and sedentary life style play pivotal role in development of vascular complications in type 2 diabetes. Dietary modification is associated with a reprogramming of nutrient intake, which are proven to be effective for the management of diabetes and associated complications. Dietary modifications modulate various molecular key players linked with the functions of nutrient signalling, regulation of autophagy, and energy metabolism. It activates silent mating type information regulation 2 homolog1 (SIRT1) and AMP-activated protein kinase (AMPK). AMPK mainly acts as an energy sensor and inhibits autophagy repressor Mammalian target of rapamycin (mTOR) under nutritional deprivation. Under calorie restriction (CR), SIRT1 gets activated directly or indirectly and plays a central role in autophagy via the regulation of protein acetylation. Dietary modification is also effective in controlling inflammation and apoptosis by decreasing the level of pro-inflammatory cytokines like nuclear factor kappa- beta (NF-kβ), tissue growth factor-beta (TGF-β), tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). It also improves glucose homeostasis and insulin secretion through beta cell regeneration. This indicates calorie intake plays a crucial role in the pathogenesis of type 2 diabetes-associated complications. The present review, emphasizes the role of dietary modifications in diabetes and associated complications.
Collapse
Affiliation(s)
- Manisha J Oza
- SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai 400056, India
| | - Ankit P Laddha
- Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai 400056, India
| | - Anil Bhanudas Gaikwad
- Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India
| | - Shrikant R Mulay
- Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow 226031, India
| | - Yogesh A Kulkarni
- Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai 400056, India.
| |
Collapse
|
|
15
|
Scicali R, Di Pino A, Urbano F, Ferrara V, Marchisello S, Di Mauro S, Scamporrino A, Filippello A, Rabuazzo AM, Purrello F, Piro S. Analysis of steatosis biomarkers and inflammatory profile after adding on PCSK9 inhibitor treatment in familial hypercholesterolemia subjects with nonalcoholic fatty liver disease: A single lipid center real-world experience. Nutr Metab Cardiovasc Dis 2021; 31:869-879. [PMID: 33549441 DOI: 10.1016/j.numecd.2020.11.009] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 10/24/2020] [Accepted: 11/05/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD) may be crucial in subjects with familial hypercholesterolemia (FH). We aimed to evaluate the effect of the inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9-i) on steatosis biomarkers such as triglyceride-glucose index (TyG) and hepatic steatosis index (HSI) and analyse the role of TG/HDL in this population before and after adding-on PCSK9-i. METHODS AND RESULTS In this observational study, we evaluated 26 genetically confirmed FH patients with NAFLD and an LDL-C off-target despite high-intensity statins plus ezetimibe. All patients added PCSK9-i treatment and obtained biochemical analysis and TyG and HSI evaluation at baseline and after six months of PCSK9-i. No difference of steatosis biomarkers was found after adding-on PCSK9-i therapy. In a secondary analysis, we divided the study population in two groups according to TG/HDL median value: high TG/HDL group (H-TG/HDL) and low TG/HDL group (L-TG/HDL). TyG and HSI were significantly lower in the L-TG/HDL than H-TG/HDL group (for TyG 9.05 ± 0.34 vs 9.51 ± 0.32; for HSI 38.43 ± 1.35 vs 41.35 ± 1.83, p value for both < 0.05). After six months of PCSK9-i therapy, TyG and HSI were significantly reduced in the L-TG/HDL group after PCSK9-i therapy (-7.5% and -8.4% respectively, p value for both < 0.05) and these biomarkers were lower compared to H-TG/HDL group (for TyG 8.37 ± 0.14 vs 9.19 ± 0.12; for HSI 35.19 ± 1.32 vs 39.48 ± 1.33, p value for both < 0.05). CONCLUSION In conclusion, PCSK9-i therapy significantly ameliorate steatosis biomarkers in FH patients with low TG/HDL; our results appear to be consistent with a beneficial role of PCSK9-i on steatosis biomarkers in FH subjects with NAFLD.
Collapse
Affiliation(s)
- Roberto Scicali
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - Antonino Di Pino
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - Francesca Urbano
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - Viviana Ferrara
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - Simona Marchisello
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - Stefania Di Mauro
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | | | - Agnese Filippello
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - Agata M Rabuazzo
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - Francesco Purrello
- Department of Clinical and Experimental Medicine, University of Catania, Italy.
| | - Salvatore Piro
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| |
Collapse
|
|
16
|
Iida M, Ishiguro Y. Association of prediabetes with impaired left atrial contractility in patients with never-treated hypertension. J Diabetes Complications 2021; 35:107827. [PMID: 33422384 DOI: 10.1016/j.jdiacomp.2020.107827] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Revised: 09/27/2020] [Accepted: 12/05/2020] [Indexed: 01/11/2023]
Abstract
AIM Prediabetes defined by HbA1c 5.7-6.4 has been shown to be associated with left ventricular (LV) hypertrophy and diastolic dysfunction in hypertensive patients. We hypothesized HbA1c prediabetes may be related to the alterations of LA contractility or volume in nondiabetic hypertension. METHODS Nondiabetic individuals on sinus rhythm were enrolled; 107 patients with never-treated hypertension, 134 patients with treated hypertension, and 71 normotensive subjects. Participants were classified as normal glucose tolerance (NGT, HbA1c<5.7), prediabetes (HbA1c 5.7-6.4) according to the ADA criteria. They underwent echocardiography to measure left atrial (LA) phasic volumes and functions, as well as mitral E/e' and mitral e'. RESULTS In nondiabetic patients with never-treated hypertension, prediabetes saw lower LA total emptying fraction (53.7 ± 8.2 vs. 48.3 ± 9.9*) and mitral e' (7.38 ± 2.18 vs. 6.17 ± 1.50*) than NGT, implicating that the association of prediabetes with reduced LA contractility and LV stiffness. On the other hand, in nondiabetic patients with treated hypertension, prediabetes saw higher maximum LA volume/BSA (29.7 ± 7.1 vs. 32.9 ± 6.2* ml/mm2) and mitral E/e' (10.72 ± 3.08 vs. 12.37 ± 3.35*) than NGT, suggesting the relationship of prediabetes with increased LA preload. CONCLUSION Prediabetes may be involved in the progression of LA structural and functional alterations in nondiabetic hypertensive patients.
Collapse
Affiliation(s)
- Masato Iida
- Department of Cardiology, Aichi Sannomaru Clinic, Nagoya, Japan.
| | - Yuko Ishiguro
- Department of Cardiology, Aichi Sannomaru Clinic, Nagoya, Japan
| |
Collapse
|
|
17
|
Cai M, Xie Y, Bowe B, Gibson AK, Zayed MA, Li T, Al-Aly Z. Temporal Trends in Incidence Rates of Lower Extremity Amputation and Associated Risk Factors Among Patients Using Veterans Health Administration Services From 2008 to 2018. JAMA Netw Open 2021; 4:e2033953. [PMID: 33481033 PMCID: PMC7823225 DOI: 10.1001/jamanetworkopen.2020.33953] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
IMPORTANCE Lower extremity amputation (LEA) is associated with significant morbidity and mortality. However, national temporal trends of LEA incidence rates among US veterans and associated factors have not been well characterized. OBJECTIVE To describe the temporal trends of LEA, characterize associated risk factors, and decompose the associations of these risk factors with changes in temporal trends of LEA among US veterans using Department of Veteran Affairs (VA) services between 2008 and 2018. DESIGN, SETTING, AND PARTICIPANTS This cohort study used VA data from 2008 to 2018 to estimate incidence rates of LEA among veterans using VA services. Cox regression models were used to identify risk factors associated with LEA. Decomposition analyses estimated the associations of changes in prevalence of risk factors with changes in LEA rates. Data were analyzed from October 1, 2007, to September 30, 2018. MAIN OUTCOMES AND MEASURES Toe, transmetatarsal, below-knee, or above-knee LEA. RESULTS A total of 6 493 141 veterans were included (median [interquartile range] age, 64 [54-76] years; 6 060 390 [93.4%] men). Veterans were studied for a median (interquartile range) of 10.9 (5.6-11.0) years. Between 2008 and 2018, rates of LEA increased from 12.89 (95% CI, 12.53-13.25) LEA per 10 000 persons to 18.12 (95% CI, 17.70-18.54) LEA per 10 000 persons, representing a net increase of 5.23 (95% CI, 4.68-5.78) LEA per 10 000 persons. Between 2008 and 2018, toe amputation rates increased by 3.24 (2.89-3.59) amputations per 10 000 persons, accounting for 62.0% of the total increase in LEA rates. Transmetatarsal amputations increased by 1.54 (95% CI, 1.27-1.81) amputations per 10 000 persons; below-knee amputation rates increased by 0.81 (95% CI, 0.56-1.05) amputations per 10 000 persons; and above-knee amputation rates decreased by 0.37 (95% CI, 0.14-0.59) amputations per 10 000 persons. Compared with men, women had decreased risk of any LEA (hazard ratio [HR], 0.34 [95% CI, 0.31-0.37]). Factors associated with increased risk of any LEA included Black race (HR, 1.25 [95% CI, 1.21-1.28]) or another non-White race (ie, Asian, Latino, or other; HR, 2.36 [95% CI, 2.30-2.42]), obesity (HR, 1.59 [95% CI, 1.55-1.63]), diabetes (HR, 6.38 [95% CI, 6.22-6.54]), chronic kidney disease (CKD; eg, CKD stage 5: HR, 3.94 [95% CI, 3.22-4.83]), and smoking status (eg, current smoking: HR, 1.97 [95% CI, 1.92-2.03]). Decomposition analyses suggested that while changes in demographic composition, primarily driven by increased proportion of women veterans, associated with a decrease of 0.18 (95% CI, 0.14-0.22) LEA per 10 000 persons, and decreases in smoking rates, associated with a decrease of 0.88 (95% CI, 0.79-0.97) LEA per 10 000 persons. However, these were overwhelmed by increased rates of diabetes, associated with an increase of 1.86 (95% CI, 1.72-1.99) LEA per 10 000 persons; peripheral arterial disease, associated with an increase of 1.53 (95% CI, 1.41-1.65) LEA per 10 000 persons; CKD, associated with an increase of 1.45 (95% CI, 1.33-1.57) LEA per 10 000 persons; and other clinical factors, including body mass index, cancer, cardiovascular disease, cerebrovascular disease, chronic lung disease, dementia, and hypertension, associated with an increase of 1.45 (95% CI, 1.33-1.57) LEA per 10 000 persons. CONCLUSIONS AND RELEVANCE This cohort study found that incidence rates of LEA among veterans using VA services increased between 2008 and 2018. Efforts aimed at reducing burden of LEA should target the reduction of diabetes, peripheral arterial disease, and CKD at the individual and population levels.
Collapse
Affiliation(s)
- Miao Cai
- Clinical Epidemiology Center, Department of Veterans Affairs, St Louis Health Care Systems, St Louis, Missouri
- Veterans Research and Education Foundation of St Louis, St Louis, Missouri
| | - Yan Xie
- Clinical Epidemiology Center, Department of Veterans Affairs, St Louis Health Care Systems, St Louis, Missouri
- Veterans Research and Education Foundation of St Louis, St Louis, Missouri
- Department of Epidemiology and Biostatistics, College for Public Health and Social Justice, St Louis University, St Louis, Missouri
| | - Benjamin Bowe
- Clinical Epidemiology Center, Department of Veterans Affairs, St Louis Health Care Systems, St Louis, Missouri
- Veterans Research and Education Foundation of St Louis, St Louis, Missouri
- Department of Epidemiology and Biostatistics, College for Public Health and Social Justice, St Louis University, St Louis, Missouri
| | - Andrew K. Gibson
- Clinical Epidemiology Center, Department of Veterans Affairs, St Louis Health Care Systems, St Louis, Missouri
| | - Mohamed A. Zayed
- Section of Vascular Surgery, Department of Surgery, School of Medicine, Washington University in St Louis, St Louis, Missouri
- Department of Surgery, Veterans Affairs St Louis Health Care System, St Louis, Missouri
| | - Tingting Li
- Clinical Epidemiology Center, Department of Veterans Affairs, St Louis Health Care Systems, St Louis, Missouri
- Division of Nephrology, School of Medicine, Washington University in St Louis, St Louis, Missouri
| | - Ziyad Al-Aly
- Clinical Epidemiology Center, Department of Veterans Affairs, St Louis Health Care Systems, St Louis, Missouri
- Veterans Research and Education Foundation of St Louis, St Louis, Missouri
- Department of Medicine, School of Medicine, Washington University in St Louis, St Louis, Missouri
- Nephrology Section, Medicine Service, Department of Veteran Affairs St Louis Health Care System, St Louis, Missouri
- Institute for Public Health, Washington University in St Louis, St Louis, Missouri
| |
Collapse
|
|
18
|
Napoli R, Formoso G, Piro S, Targher G, Consoli A, Purrello F. Management of type 2 diabetes for prevention of cardiovascular disease. An expert opinion of the Italian Diabetes Society. Nutr Metab Cardiovasc Dis 2020; 30:1926-1936. [PMID: 32928628 DOI: 10.1016/j.numecd.2020.07.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 07/07/2020] [Accepted: 07/10/2020] [Indexed: 12/28/2022]
Abstract
AIMS Type 2 diabetes mellitus is characterized by an increased risk of developing long-term cardiovascular complications. Several underlying mechanisms have been proposed for the diabetes-related increase in cardiovascular risk, i.e. chronic hyperglycemia, duration of the disease, drug-induced hypoglycemia, coexistence of multiple cardiovascular risk factors, etc. In the last few years, new pharmacological approaches capable of treating chronic hyperglycemia without increasing the risk of hypoglycemia have emerged for the treatment of diabetes. DATA SYNTHESIS With data mainly obtained from randomized controlled trials recruiting patients with type 2 diabetes in secondary prevention of cardiovascular disease, some of these newer antihyperglycemic drugs have shown to significantly reduce the risk of cardiovascular disease. In addition, the combined control of traditional cardiovascular risk factors, e.g. dyslipidemia, hypertension, etc., has demonstrated to be effective in reducing the burden of cardiovascular diseases in patients with type 2 diabetes. CONCLUSIONS In this document written by some experts of the Italian diabetes society (SID), we will focus our attention on oral antihyperglycemic agents for people with type 2 diabetes in primary or secondary prevention of cardiovascular disease, excluding for brevity the injection therapies for diabetes, such as insulin and glucagon-like peptide-1 receptor agonists.
Collapse
Affiliation(s)
- Raffaele Napoli
- Department of Translational Medical Sciences, Internal Medicine and Diabetes, Federico II University School of Medicine, Napoli, Italy.
| | - Gloria Formoso
- Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST, ex CeSI-Met), G. d'Annunzio University, Chieti-Pescara, Italy
| | - Salvatore Piro
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Agostino Consoli
- Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST, ex CeSI-Met), G. d'Annunzio University, Chieti-Pescara, Italy
| | - Francesco Purrello
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania, Italy
| |
Collapse
|
|
19
|
Tan X, Benedict C. Increased Risk of Myocardial Infarction Among Patients With Type 2 Diabetes Who Carry the Common rs10830963 Variant in the MTNR1B Gene. Diabetes Care 2020; 43:2289-2292. [PMID: 32616615 PMCID: PMC7440907 DOI: 10.2337/dc20-0507] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 05/12/2020] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The common MTNR1B single nucleotide polymorphism rs10830963 associates with risk of type 2 diabetes (T2D). Here, we examine the association between this gene variant and the risk of myocardial infarction (MCI) among patients with T2D. MCI is a main cause of death and disability among such individuals. RESEARCH DESIGN AND METHODS Data from the UK Biobank cohort were used in order to examine the association between rs10830963 and incidence of MCI (fatal and nonfatal) among 13,655 participants with probable T2D during a follow-up period of 6.8 years. RESULTS Assuming an additive genetic model, a positive association was found between the rs10830963 variant in the MTNR1B gene and the risk for incident MCI during the 6.8-year follow-up (adjusted hazard ratio per G allele 1.19 [95% CI 1.02, 1.40], P = 0.03). CONCLUSIONS The rs10830963 polymorphism may be a useful genetic marker for MCI in patients with T2D.
Collapse
Affiliation(s)
- Xiao Tan
- Department of Neuroscience, Uppsala University, Uppsala, Sweden
| | | |
Collapse
|
|
20
|
Mallu ACT, Vasudevan M, Allanki S, Nathan AA, Ravi MM, Ramanathan GS, Pradeepa R, Mohan V, Dixit M. Prediabetes uncovers differential gene expression at fasting and in response to oral glucose load in immune cells. Clin Nutr 2020; 40:1247-1259. [PMID: 32863060 DOI: 10.1016/j.clnu.2020.08.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 08/04/2020] [Accepted: 08/06/2020] [Indexed: 01/04/2023]
Abstract
BACKGROUND AND OBJECTIVE Metabolic disorders including diabetes are associated with immune cell dysfunction. However, the effect of normal glucose metabolism or impairment thereof on immune cell gene expression is not well known. Hence, in this cross-sectional pilot study, we sought to determine the differences in gene expression in the peripheral blood mono-nuclear cells (PBMCs) of normal glucose tolerant (NGT) and prediabetic (PD) Asian Indian men, at fasting and in response to 75 g oral glucose load. METHODS Illumina HT12 bead chip-based microarray was performed on PBMCs at fasting and 2-h post load conditions for NGT (N = 6) and PD (N = 9) subjects. Following normalization and due quality control of the raw data, differentially expressed genes (DEGs) under different conditions within and across the two groups were identified using GeneSpring GX V12.0 software. Paired and unpaired Student's t-tests were applied along with fold change cut-offs for appropriate comparisons. Validation of the microarray data was carried out through real-time qPCR analysis. Significantly regulated biological pathways were analyzed by employing DEGs and DAVID resource. Deconvolution of the DEGs between NGT and PD subjects at fasting was performed using CIBERSORT and genes involved in regulatory T-cell (Treg) function were further analyzed for biological significance. RESULTS Glucose load specifically altered the expression of 112 genes in NGT and 356 genes in PD subjects. Biological significance analysis revealed transient up-regulation of innate and adaptive immune response related genes following oral glucose load in NGT individuals, which was not observed in PD subjects. Instead, in the PD group, glucose load led to an increase in the expression of pro-atherogenic and anti-angiogenic genes. Comparison of gene expression at fasting state in PD versus NGT revealed 21,707 differentially expressed genes. Biological significance analysis of the immune function related genes between these two groups (at fasting) revealed higher gene expression of members of the TLR signaling, MHC class II molecules, and T-cell receptor, chemotaxis and adhesion pathways in PD subjects. Expression of interferon-γ (IFN-γ) and TNFα was higher and that of type-1 interferons and TGF-β was lower at fasting state in PD subjects compared to NGT. Additionally, expression of multiple proteasome subunits and protein arginine methyl transferase genes (PRMTs) were higher and that of Treg specific genes was significantly distinct at fasting in PD subjects compared to NGT. CONCLUSION Prediabetes uncovers constitutive TLR activation, enhanced IFN-γ signaling, and Treg dysfunction at fasting along with altered gene expression response to oral glucose load.
Collapse
Affiliation(s)
- Abhiram Charan Tej Mallu
- Laboratory of Vascular Biology, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, India
| | | | - Srinivas Allanki
- Laboratory of Vascular Biology, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, India
| | - Abel Arul Nathan
- Laboratory of Vascular Biology, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, India
| | - Mahalakshmi M Ravi
- Institute Hospital, Indian Institute of Technology Madras, Chennai, India
| | | | - Rajendra Pradeepa
- Department of Diabetology, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, Chennai, India
| | - Viswanathan Mohan
- Department of Diabetology, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, Chennai, India
| | - Madhulika Dixit
- Laboratory of Vascular Biology, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, India.
| |
Collapse
|
|
21
|
Prediabetes Is Independently Associated with Subclinical Carotid Atherosclerosis: An Observational Study in a Non-Urban Mediterranean Population. J Clin Med 2020; 9:jcm9072139. [PMID: 32645918 PMCID: PMC7408832 DOI: 10.3390/jcm9072139] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 06/29/2020] [Accepted: 07/06/2020] [Indexed: 12/14/2022] Open
Abstract
This was a prospective, observational study to compare the burden of subclinical atherosclerosis as measured by carotid ultrasonography in a cohort of subjects with prediabetes vs. subjects with normal glucose tolerance (NGT) from a non-urban Mediterranean population. Atherosclerosis was assessed through carotid intima-media thickness (c-IMT), the presence/absence of carotid plaques, and plaque number. Among 550 subjects included, 224 (40.7%) had prediabetes. The mean c-IMT and the prevalence of carotid plaque were significantly higher in the prediabetes group compared to the NGT group (0.72 vs. 0.67 mm, p < 0.001; and 37.9% vs. 19.6%; p < 0.001, respectively). Older age, male gender, and increased systolic blood pressure were positively correlated with c-IMT and were independent predictors of the presence of plaques. In contrast, prediabetes and low-density lipoprotein (LDL)-c were predictors of the presence of plaque (odds ratio [OR] = 1.64; 95% confidence interval [CI] = 1.05-2.57; p = 0.03 and OR = 1.01; 95% CI = 1.00-1.02; p = 0.006, respectively) together with tobacco exposure and the leukocyte count (OR = 1.77; 95% CI = 1.08-2.89; p = 0.023 and OR = 1.20; 95% CI = 1.05-1.38; p = 0.008, respectively). In a non-urban Mediterranean population, prediabetes was associated with established subclinical carotid atherosclerosis. These findings could have implications for the prevention and treatment of CV risk in these subjects before the first symptoms of cardiovascular disease appear.
Collapse
|
|
22
|
Kaur R, Singh J, Kapoor R, Kaur M. Putative functional non-coding polymorphisms in SELP significantly modulate sP-selectin levels, arterial stiffness and type 2 diabetes mellitus susceptibility. BMC Endocr Disord 2020; 20:70. [PMID: 32429899 PMCID: PMC7236446 DOI: 10.1186/s12902-020-00548-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 05/10/2020] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND P-selectin, encoded by SELP, has been implicated as an important molecule in the development of arterial stiffness, consequently leading to vascular complications in T2DM. SELP polymorphisms and increased levels of soluble P-selectin (sP-selectin) have been shown to be associated with several inflammatory diseases. The present work was designed to assess nine putative functional non-coding SELP variants in relation to sP-selectin levels and arterial stiffness in T2DM. METHODS The genetic distribution of rs3917655, rs3917657, rs3917739, rs2235302, rs3917843 was determined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Genotyping of rs3917779 was performed by tetra primer amplification-refractory mutation system (ARMS)- PCR. Three SNPs i.e. rs3917853, rs3917854, rs3917855 were genotyped by Sanger sequencing. Construction of haplotypes was performed using PHASE software. The data thus obtained was analyzed by appropriate statistical tools. RESULTS Two non-coding variants i.e. rs3917657 and rs3917854 of SELP were found to be associated with 2 and 1.7 -fold risk of disease development respectively. However, one non-coding variant rs2235302 was found to provide protection against disease development. Furthermore, variant allele of rs3917854 in T2DM patients was found to be associated with 2.07-fold very high vascular risk. Non-coding haplotype GCAGGCCGC was conferring 4.14-fold risk of disease development. Furthermore, overall sP-selectin levels were higher in T2DM patients when segregated according to genotypes as well as haplotypes. Significant genotype- phenotype correlation was observed for rs3917655 as well as rs3917739 variant in patients and for rs3917854 in controls. In vascular risk categories, a significant genotype- phenotype correlation was observed for rs3917655 and rs2235302. Furthermore, patients with CCGGGCCGC haplotype in high risk category were observed with higher levels of sP-selectin as compared to other haplotypes (p < 0.05). CONCLUSIONS Non-coding SELP variants may significantly modulate sP-selectin levels, vascular risk and T2DM susceptibility.
Collapse
Affiliation(s)
- Raminderjit Kaur
- School of Medicine, Wayne State University, Detroit, Michigan USA
- Department of Molecular Biology & Biochemistry, Guru Nanak Dev University, Amritsar, Punjab India
| | - Jatinder Singh
- School of Medicine, Wayne State University, Detroit, Michigan USA
| | - Rohit Kapoor
- Carewell Heart & Superspeciality Hospital, Amritsar, Punjab India
| | - Manpreet Kaur
- School of Medicine, Wayne State University, Detroit, Michigan USA
| |
Collapse
|
|
23
|
Joung KH, Kim JM, Choung S, Lee JH, Kim HJ, Ku BJ. Association between IL-1beta and cardiovascular disease risk in patients with newly diagnosed, drug-naïve type 2 diabetes mellitus: a cross-sectional study. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:225. [PMID: 32309372 PMCID: PMC7154468 DOI: 10.21037/atm.2020.01.17] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background To determine whether the pro-inflammatory cytokine interleukin (IL)-1beta, as a marker of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation, can be used to predict cardiovascular disease (CVD) risk in patients with newly diagnosed, drug-naïve type 2 diabetes mellitus (T2DM). Methods A total of 110 subjects with no history of diabetes were enrolled and divided into control subjects (non-DM group, n=52) and patients with newly diagnosed, drug-naïve T2DM (DM group, n=58). Results Serum IL-1beta levels were not different between the two groups. The Framingham CVD risk score (F-score) was positively correlated with the serum IL-1beta level in the DM group. Multivariate regression analyses showed that the F-score was independently associated with the serum IL-1beta level in the DM group. Patients with an intermediate to high CVD risk (F-score ≥10%) also had significantly higher serum IL-1beta levels than did those with a low CVD risk (F-score <5%). Smokers in the DM group had higher IL-1beta levels than did those in the non-DM group, regardless of the F-score. Conclusions These results suggest that serum IL-1beta levels might be useful as an independent risk factor predicting CVD risk in patients with newly diagnosed, drug naïve T2DM, particularly those who smoke.
Collapse
Affiliation(s)
- Kyong Hye Joung
- Department of International Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Ji Min Kim
- Department of International Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Sorim Choung
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Ju Hee Lee
- Department of International Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Hyun Jin Kim
- Department of International Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Bon Jeong Ku
- Department of International Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| |
Collapse
|
|
24
|
Welsh C, Welsh P, Celis-Morales CA, Mark PB, Mackay D, Ghouri N, Ho FK, Ferguson LD, Brown R, Lewsey J, Cleland JG, Gray SR, Lyall DM, Anderson JJ, Jhund PS, Pell JP, McGuire DK, Gill JMR, Sattar N. Glycated Hemoglobin, Prediabetes, and the Links to Cardiovascular Disease: Data From UK Biobank. Diabetes Care 2020; 43:440-445. [PMID: 31852727 DOI: 10.2337/dc19-1683] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 10/27/2019] [Indexed: 02/03/2023]
Abstract
OBJECTIVE HbA1c levels are increasingly measured in screening for diabetes; we investigated whether HbA1c may simultaneously improve cardiovascular disease (CVD) risk assessment, using QRISK3, American College of Cardiology/American Heart Association (ACC/AHA), and Systematic COronary Risk Evaluation (SCORE) scoring systems. RESEARCH DESIGN AND METHODS UK Biobank participants without baseline CVD or known diabetes (n = 357,833) were included. Associations of HbA1c with CVD was assessed using Cox models adjusting for classical risk factors. Predictive utility was determined by the C-index and net reclassification index (NRI). A separate analysis was conducted in 16,596 participants with known baseline diabetes. RESULTS Incident fatal or nonfatal CVD, as defined in the QRISK3 prediction model, occurred in 12,877 participants over 8.9 years. Of participants, 3.3% (n = 11,665) had prediabetes (42.0-47.9 mmol/mol [6.0-6.4%]) and 0.7% (n = 2,573) had undiagnosed diabetes (≥48.0 mmol/mol [≥6.5%]). In unadjusted models, compared with the reference group (<42.0 mmol/mol [<6.0%]), those with prediabetes and undiagnosed diabetes were at higher CVD risk: hazard ratio (HR) 1.83 (95% CI 1.69-1.97) and 2.26 (95% CI 1.96-2.60), respectively. After adjustment for classical risk factors, these attenuated to HR 1.11 (95% CI 1.03-1.20) and 1.20 (1.04-1.38), respectively. Adding HbA1c to the QRISK3 CVD risk prediction model (C-index 0.7392) yielded a small improvement in discrimination (C-index increase of 0.0004 [95% CI 0.0001-0.0007]). The NRI showed no improvement. Results were similar for models based on the ACC/AHA and SCORE risk models. CONCLUSIONS The near twofold higher unadjusted risk for CVD in people with prediabetes is driven mainly by abnormal levels of conventional CVD risk factors. While HbA1c adds minimally to cardiovascular risk prediction, those with prediabetes should have their conventional cardiovascular risk factors appropriately measured and managed.
Collapse
Affiliation(s)
- Claire Welsh
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, U.K
| | - Paul Welsh
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, U.K
| | | | - Patrick B Mark
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, U.K
| | - Daniel Mackay
- Institute of Health & Wellbeing, University of Glasgow, Glasgow, U.K
| | - Nazim Ghouri
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, U.K
| | - Fredrick K Ho
- Institute of Health & Wellbeing, University of Glasgow, Glasgow, U.K
| | - Lyn D Ferguson
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, U.K
| | - Rosemary Brown
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, U.K
| | - James Lewsey
- Institute of Health & Wellbeing, University of Glasgow, Glasgow, U.K
| | - John G Cleland
- Institute of Health & Wellbeing, University of Glasgow, Glasgow, U.K
| | - Stuart R Gray
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, U.K
| | - Donald M Lyall
- Institute of Health & Wellbeing, University of Glasgow, Glasgow, U.K
| | - Jana J Anderson
- Institute of Health & Wellbeing, University of Glasgow, Glasgow, U.K
| | - Pardeep S Jhund
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, U.K
| | - Jill P Pell
- Institute of Health & Wellbeing, University of Glasgow, Glasgow, U.K
| | | | - Jason M R Gill
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, U.K
| | - Naveed Sattar
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, U.K.
| |
Collapse
|
|
25
|
Analysis of HDL-microRNA panel in heterozygous familial hypercholesterolemia subjects with LDL receptor null or defective mutation. Sci Rep 2019; 9:20354. [PMID: 31889114 PMCID: PMC6937253 DOI: 10.1038/s41598-019-56857-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 12/06/2019] [Indexed: 12/18/2022] Open
Abstract
In the last years increasing attention has been given to the connection between genotype/phenotype and cardiovascular events in subjects with familial hypercholesterolemia (FH). MicroRNAs (miRs) bound to high-density lipoprotein (HDL) may contribute to better discriminate the cardiovascular risk of FH subjects. Our aim was to evaluate the HDL-miR panel in heterozygous FH (HeFH) patients with an LDLR null or defective mutation and its association with pulse wave velocity (PWV). We evaluated lipid panel, HDL-miR panel and PWV in 32 LDLR null mutation (LDLR-null group) and 35 LDLR defective variant (LDLR-defective group) HeFH patients. HDL-miR-486 and HDL-miR-92a levels were more expressed in the LDLR-null group than the LDLR-defective group. When we further stratified the study population into three groups according to both the LDLR genotype and history of ASCVD (LDLR-null/not-ASCVD, LDLR-defective/not-ASCVD and LDLR/ASCVD groups), both the LDLR/ASCVD and the LDLR-null/not-ASCVD groups had a higher expression of HDL-miR-486 and HDL-miR-92a than the LDLR-defective/not-ASCVD group. Finally, HDL-miR-486 and HDL-miR-92a were independently associated with PWV. In conclusion, the LDLR-null group exhibited HDL-miR-486 and HDL-miR-92a levels more expressed than the LDLR-defective group. Further studies are needed to evaluate these HDL-miRs as predictive biomarkers of cardiovascular events in FH.
Collapse
|
|
26
|
Liu H, Liu J, Zhao H, Wang H. Relationship between glycated hemoglobin and low Ankle-Brachial Index: a cross-sectional observational study from the Beijing Vascular Disease Evaluation Study (BEST Study). INT ANGIOL 2019; 38:502-507. [PMID: 31782279 DOI: 10.23736/s0392-9590.19.04210-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Studies have confirmed that the low Ankle Brachial Index (ABI) and high glycated hemoglobin (HbA1c) level were both risk factors of cardiovascular disease (CVD). However, the association has rarely been explored between ABI and HbA1c. This study was to evaluate the independent relationship between HbA1c and low ABI. METHODS A total of 3102 subjects (male 1539, female 1563, aged 67.72±10.69 years) were enrolled into the study from 2010 to 2018. The odds ratio (OR) and linear regression coefficient of low ABI group (defined as ABI≤0.9) and ABI value in associations with the HbA1c were modelled using multivariable logistic and linear regression analyses by adjusting for possible confounders. RESULTS Compared with participants with normal ABI, those presenting the low ABI showed a significantly older age, smoking rate, higher level of heart rate (HR), systolic blood pressure (SBP), pulse pressure (PP), fasting plasma glucose (FPG), triglyceride (TG), highly sensitive C-reactive protein (hs-CRP), HbA1c and carotid femoral pulse wave velocity (CF-PWV); and higher prevalence rate of hypertension, diabetes, coronary artery disease (CAD); and higher rate on medication of statins, diabetes drug and cardiovascular drug (all P<0.001). After multiple adjustment for age, sex, smoke, FPG, blood lipids, hs-CRP, SBP, diastolic blood pressure (DBP), PP, CF-PWV, hypertension, diabetes, CAD and medications, the OR of HbA1c for low ABI was of statistical significance (95% CI: 1.204-1.410, P<0.001). After further multivariate adjustment analysis by linear regression, with left and right ABI as dependent variables, the results showed that HbA1c was independently linearly correlated to left and right ABI (all P<0.001). CONCLUSIONS HbA1c was an independent associated factor of lower ABI and linearly correlated to ABI level independent of fasting plasma glucose and other cardiovascular factors. We should not only focus on the HbA1c in diabetes mellitus patients, but also people with lower ABI.
Collapse
Affiliation(s)
- Huan Liu
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China
| | - Jinbo Liu
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China
| | - Hongwei Zhao
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China
| | - Hongyu Wang
- Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, China -
| | | |
Collapse
|
|
27
|
Bulut A, Avci B. Carotid intima-media thickness values are significantly higher in patients with prediabetes compared to normal glucose metabolism. Medicine (Baltimore) 2019; 98:e17805. [PMID: 31689862 PMCID: PMC6946422 DOI: 10.1097/md.0000000000017805] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 09/13/2019] [Accepted: 10/07/2019] [Indexed: 12/22/2022] Open
Abstract
Carotid intima-media thickness (C-IMT) increases in patients with adult type-2 diabetes mellitus (DM) and is used for early detection of macrovascular complications. We aimed to investigate the change of C-IMT in prediabetes and type-2 DM patients compared to subjects with normal glucose metabolism (NGM).A total of 180 individuals (60 subjects with NGM, 60 patients with prediabetes and 60 patients with type-2 DM) were included in this study. Routine laboratory and micro-macrovascular involvement were investigated. Urine albumin-creatinine ratio (ACR) was measured for urinary albuminuria detection. In addition to routine laboratory examination, right-left common and internal C-IMT (CC-IMT and IC-IMT) were measured.Systolic and diastolic blood pressure values were found to be higher in prediabetes and type-2 DM groups than NGM group. The prevalence of nephropathy and presence of CAD were higher in type-2 DM groups than prediabetes. Glucose, glycated hemoglobin (HbA1c), total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, blood urea nitrogen, creatinine, high sensitive C reactive protein (hs-CRP) levels and urinary ACR were significantly higher in patients within prediabetes and type-2 DM groups than NGM group. Glucose, HbA1c and hs-CRP levels were found to be higher in type-2 DM groups than prediabetes. Estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol level was found to be lower in patients within prediabetes and type-2 DM groups than NGM group. Right-left-mean CC-IMT and IC-IMT values were found to be higher in prediabetes and type-2 DM groups than NGM group. Left IC-IMT, left CC-IMT, and mean IC-IMT values were found to be higher in type-2 DM patients compared to prediabetes. LDL and HDL cholesterols, HbA1c, and hs-CRP levels were independently associated with IC-IMT and CC-IMT.C-IMT values were significantly higher in impaired glucose metabolism compared to NGM. C-IMT measurement may be used as part of routine screening of macrovascular complication in patients with prediabetes and newly diagnosed type-2 DM.
Collapse
Affiliation(s)
| | - Begum Avci
- Department of Internal Medicine, University of Health Sciences - Adana Health Practice and Research Center, Adana, Turkey
| |
Collapse
|
|
28
|
Scicali R, Di Pino A, Urbano F, Ferrara V, Marchisello S, Di Mauro S, Scamporrino A, Filippello A, Piro S, Rabuazzo AM, Purrello F. Analysis of S100A12 plasma levels in hyperlipidemic subjects with or without familial hypercholesterolemia. Acta Diabetol 2019; 56:899-906. [PMID: 30963307 DOI: 10.1007/s00592-019-01338-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Accepted: 03/30/2019] [Indexed: 12/13/2022]
Abstract
AIMS Inflammation is a key regulatory process that links hypercholesterolemia and immune mechanisms promoting atherosclerosis. Inflammatory biomarkers may be helpful to better define the atherosclerotic burden in patients with high cholesterol levels such as familial hypercholesterolemia (FH). Our aim was to evaluate the concentration of S100A12 protein in FH patients and its association with pulse wave velocity (PWV). METHODS We measured glucose and lipid profile, S100A12, sRAGE, esRAGE and PWV in 39 patients with a genetically confirmed diagnosis of FH and 39 hypercholesterolemic subjects without a clinical diagnosis of FH (Dutch score ≤ 3). All subjects were on statin treatment at the time of the enrollment. RESULTS No difference of glucose and lipid profile was found in the two groups. FH patients had higher S100A12 plasma levels than non-FH subjects (12.87 ± 4.82 vs. 8.57 ± 4.87 ng/mL, p < 0.01). No difference of hs-CRP, sRAGE and esRAGE was found between the two groups. Also, PWV was higher in FH patients than non-FH subjects (8.63 ± 0.92 vs. 6.68 ± 0.73 m/s, p < 0.05). Finally, S100A12 was independently correlated with age (p < 0.01), genetic mutation (p < 0.01) and PWV (p < 0.001). CONCLUSIONS FH patients exhibited higher S100A12 levels than non-FH subjects. A novel vascular inflammation pathway, other than hs-CRP, might be useful to better characterize cardiovascular risk profile.
Collapse
Affiliation(s)
- Roberto Scicali
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo, 636 95122, Catania, Italy
| | - Antonino Di Pino
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo, 636 95122, Catania, Italy
| | - Francesca Urbano
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo, 636 95122, Catania, Italy
| | - Viviana Ferrara
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo, 636 95122, Catania, Italy
| | - Simona Marchisello
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo, 636 95122, Catania, Italy
| | - Stefania Di Mauro
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo, 636 95122, Catania, Italy
| | - Alessandra Scamporrino
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo, 636 95122, Catania, Italy
| | - Agnese Filippello
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo, 636 95122, Catania, Italy
| | - Salvatore Piro
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo, 636 95122, Catania, Italy
| | - Agata Maria Rabuazzo
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo, 636 95122, Catania, Italy
| | - Francesco Purrello
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo, 636 95122, Catania, Italy.
| |
Collapse
|
|
29
|
Li CH, Lu FH, Yang YC, Wu JS, Chang CJ. Increased Arterial Stiffness in Prediabetic Subjects Recognized by Hemoglobin A1c with Postprandial Glucose but Not Fasting Glucose Levels. J Clin Med 2019; 8:jcm8050603. [PMID: 31052480 PMCID: PMC6571836 DOI: 10.3390/jcm8050603] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Revised: 04/24/2019] [Accepted: 04/30/2019] [Indexed: 01/09/2023] Open
Abstract
Previous studies exploring the association between arterial stiffness and prediabetes remain controversial. This study aimed to investigate the association of the different domains of prediabetes categorized by glycated hemoglobin A1c (A1c) 5.7–6.4%, impaired fasting glucose (IFG), fasting plasma glucose of 5.6–6.9 mmol/L, and impaired glucose tolerance (IGT), two-hour post-load glucose of 7.8–11.0 mmol/L, on arterial stiffness. These were measured by brachial–ankle pulse-wave velocity (baPWV). We enrolled 4938 eligible subjects and divided them into the following nine groups: (1) normoglycemic; (2) isolated A1c 5.7–6.4%; (3) isolated IFG; (4) IFG with A1c 5.7–6.4%; (5) isolated IGT; (6) combined IGT and IFG with A1c <5.7%; (7) IGT with A1c 5.7–6.4%; (8) combined IGT and IFG with A1c 5.7–6.4%; and (9) newly diagnosed diabetes (NDD). The baPWV values were significantly high in subjects with NDD (β = 47.69, 95% confidence interval (CI) = 29.02–66.37, p < 0.001), those with IGT with A1c 5.7–6.4% (β = 36.02, 95% CI = 19.08–52.95, p < 0.001), and those with combined IGT and IFG with A1c 5.7–6.4% (β = 27.72, 95% CI = 0.68–54.76, p = 0.044), but not in the other subgroups. These findings suggest that increased arterial stiffness was found in prediabetes individuals having an A1c 5.7–6.4% with IGT, but not IFG. Isolated A1c 5.7–6.4% and isolated IGT were not associated with elevated arterial stiffness.
Collapse
Affiliation(s)
- Chung-Hao Li
- Department of Health Management Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
- Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
| | - Feng-Hwa Lu
- Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
- Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
| | - Yi-Ching Yang
- Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
- Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
| | - Jin-Shang Wu
- Department of Health Management Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
- Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
- Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
| | - Chih-Jen Chang
- Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
- Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
| |
Collapse
|
|
30
|
Fiorentino TV, Succurro E, Andreozzi F, Sciacqua A, Perticone F, Sesti G. One-hour post-load hyperglycemia combined with HbA1c identifies individuals with higher risk of cardiovascular diseases: Cross-sectional data from the CATAMERI study. Diabetes Metab Res Rev 2019; 35:e3096. [PMID: 30378248 DOI: 10.1002/dmrr.3096] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 10/09/2018] [Accepted: 10/25/2018] [Indexed: 12/30/2022]
Abstract
AIMS A value of 1-hour post-load plasma glucose (PG) ≥155 mg/dL combined with the recently established HbA1c diagnostic thresholds for prediabetes increases the ability to predict diabetes and to detect subclinical cardiovascular organ damage. Herein, we evaluated whether a value of 1-hour PG ≥155 mg/dL may recognize non-diabetic individuals with an increased risk of cardiovascular diseases (CVD) within HbA1c-defined glycemic categories. MATERIALS AND METHODS The prevalence of composite and individual CVD, including coronary artery disease (CAD) and cerebrovascular disease, was assessed in 1010 non-diabetic individuals. RESULTS Within the group with HbA1c <5.7%, a higher proportion of subjects with 1-hour PG ≥ 155 mg/dL had composite CVD and individual CAD in comparison to those having 1-hour PG˂155 mg/dL. Similarly, within the group with HbA1c-defined prediabetes (5.7%-6.4%), the prevalence of composite CVD and individual CAD in subjects with 1-hour PG ≥155 mg/dL was higher than in the group with individuals having 1-hour PG < 155 mg/dL. In a logistic regression analysis adjusted for several CVD risk factors individuals with HbA1c <5.7% and 1-hour PG ≥ 155 mg/dL and those with HbA1c 5.7% to 6.4% and 1-hour PG ≥ 155 mg/dL had a 4.5- (95%CI: 1.02-20.44) and 6.2- (95%CI: 1.29-29.74) fold increased risk of composite CVD and 6.2- (95%CI: 1.05-36.32) and 8.0- (95%CI: 1.25-51.70) fold increased risk of having CAD, respectively, in comparison to individuals with HbA1c <5.7% and 1-hour PG < 155 mg/dL. CONCLUSIONS 1-hour post-load hyperglycemia may identify a subset of individuals within HbA1c-defined glycemic categories at higher risk of having CVD.
Collapse
Affiliation(s)
- Teresa Vanessa Fiorentino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Elena Succurro
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Francesco Andreozzi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Francesco Perticone
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Giorgio Sesti
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| |
Collapse
|
|
31
|
Nazish S, Zafar A, Shahid R, Albakr A, Alkhamis FA, Aljaafari D, Alabdali M, Alsulaiman A, Al-Mulla FA. Relationship Between Glycated Haemoglobin and Carotid Atherosclerotic Disease Among Patients with Acute Ischaemic Stroke. Sultan Qaboos Univ Med J 2019; 18:e311-e317. [PMID: 30607271 DOI: 10.18295/squmj.2018.18.03.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Revised: 12/03/2017] [Accepted: 03/25/2018] [Indexed: 11/16/2022] Open
Abstract
Objectives This study aimed to determine the relationship between glycaemic control and carotid atherosclerotic disease among patients with acute ischaemic stroke (AIS). Methods This retrospective cross-sectional study took place in the Neurology Department of King Fahad Hospital of University, Khobar, Saudi Arabia, from April to October 2017. Data were collected from the medical records of 244 patients with a diagnosis of AIS confirmed by computed tomography. Doppler ultrasounds of the carotid artery were performed to determine the presence of increased carotid intima media thickness (CIMT) and plaques. Results Significantly higher mean glycated haemoglobin (HbA1c) levels were noted in cases with high CIMT values (P = 0.002), but not in cases with carotid plaques (P = 0.360). In addition, there was a significant association between diabetes mellitus (DM) and high CIMT (P = 0.045), but not with carotid plaques (P = 0.075). Finally, while dyslipidaemia and age were independently correlated with high CIMT values (P = 0.034 and <0.001, respectively) and carotid plaques (P <0.001 each), no independent relationships were noted in terms of gender and other risk factors like DM, hypertension and smoking (P >0.050 each). Conclusion High HbA1c levels were associated with high CIMT values, but not with carotid plaques. Therefore, HbA1c levels may be useful as an indirect marker of the initial stages of carotid artery atherosclerosis.
Collapse
Affiliation(s)
- Saima Nazish
- Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Azra Zafar
- Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Rizwana Shahid
- Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Aishah Albakr
- Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Fahd A Alkhamis
- Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Danah Aljaafari
- Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Majed Alabdali
- Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Abdullah Alsulaiman
- Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Faisal A Al-Mulla
- Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| |
Collapse
|
|
32
|
Li G, Han L, Wang Y, Zhao Y, Li Y, Fu J, Li M, Gao S, Willi SM. Evaluation of ADA HbA1c criteria in the diagnosis of pre-diabetes and diabetes in a population of Chinese adolescents and young adults at high risk for diabetes: a cross-sectional study. BMJ Open 2018; 8:e020665. [PMID: 30093511 PMCID: PMC6089273 DOI: 10.1136/bmjopen-2017-020665] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE We aimed to assess haemoglobin A1c (HbA1c) for the diagnosis of pre-diabetes and diabetes in a population of Chinese youths at risk of metabolic syndrome. SETTING Beijing, China. PARTICIPANTS A total of 581 subjects aged 14-28 years underwent evaluation including an oral glucose tolerance test (OGTT). Insulin sensitivity, β-cell function and a number of cardiovascular disease risk factors were evaluated. Receiver operating characteristic (ROC) curves were used to assess the screening efficacy of HbA1c. RESULTS Using OGTT data as a standard, the majority (70.0%, 7/10) of subjects with diabetes would have been diagnosed with HbA1c ≥6.5%. In contrast, only 28.1% (16/57) of subjects with pre-diabetes possessed elevated HbA1cs, while the majority (68.4%) had normal HbA1cs. On the contrary, a total of 8.1% (39/479) of youths in the normal HbA1c category (<5.7%) and 21.3% in the pre-diabetes category had pre-diabetes. In the ROC analysis, the area under the curve (AUC) for HbA1c identifying pre-diabetes was 0.680(95% CI 0.640 to 0.719); the optimal threshold was 5.5%, with a sensitivity of 61.4% and specificity of 68.5%. For type 2 diabetes mellitus, the AUC for HbA1c was 0.970 (0.952 to 0.982), and the optimal threshold was 6.1%, with a sensitivity of 90.0% and a specificity of 98.7%. Applying these new cut-offs, pre-diabetic participants (HbA1c 5.5%-6.1%) had lower disposition index and higher risk of dyslipidaemia (OR=1.61,95% CI 1.10 to 2.37) and metabolic syndrome (OR=2.09, 1.27 to 3.45) than those with normal HbA1c (<5.5%). CONCLUSION The American Diabetes Association's established HbA1c criteria for pre-diabetes and diabetes (5.7% and 6.5%) may not be appropriately applied to adolescents and young adults in China. Our findings suggest that those with HbA1c of 5.5%-6.1% already exhibit impaired β-cell function and increased cardiometabolic risk factors which may warrant intervention. TRIAL REGISTRATION NUMBER NCT03421444.
Collapse
Affiliation(s)
- Ge Li
- Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, People’s Republic of China
| | - Lanwen Han
- Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Yonghui Wang
- Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Yanglu Zhao
- Epidemiology Department, Fielding School of Public Health, University of California Los Angeles, Los Angeles, California, USA
| | - Yu Li
- Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, People’s Republic of China
| | - Junling Fu
- Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, People’s Republic of China
| | - Ming Li
- Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, People’s Republic of China
| | - Shan Gao
- Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Steven M Willi
- Division of Endocrinology, The Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| |
Collapse
|
|
33
|
Cavero-Redondo I, Martínez-Vizcaíno V, Álvarez-Bueno C, Recio-Rodríguez JI, Gómez-Marcos MÁ, García-Ortiz L. Relationship between glycaemic levels and arterial stiffness in non-diabetic adults. Med Clin (Barc) 2018; 150:56-60. [PMID: 28923672 DOI: 10.1016/j.medcli.2017.06.072] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Revised: 06/18/2017] [Accepted: 06/22/2017] [Indexed: 01/22/2023]
Abstract
OBJECTIVE To examine, in a non-diabetic population, whether the association between arterial stiffness and glycaemic levels depends on the test used as a glycaemic indicator, fasting plasma glucose (FPG) or glycated haemoglobin A1c (HbA1c). PATIENT POPULATION AND METHODS A cross-sectional analysis of a 220 non-diabetic subsample from the EVIDENT II study in which FPG, HbA1c and arterial stiffness-related parameters (pulse wave velocity, radial and central augmentation index, and central pulse pressure) were determined. Mean differences in arterial stiffness-related parameters by HbA1c and FPG tertiles were tested using analysis of covariance. RESULTS All means of arterial stiffness-related parameters increased by HbA1c tertiles, although mean differences were only statistically significant in pulse wave velocity (p ≤.001), even after controlling for potential confounders (HbA1c <5.30% = 6.88 m/s; HbA1c 5.30%-5.59% = 7.06 m/s; and HbA1c ≥5.60% = 8.16 m/s, p =.004). Conversely, mean differences in pulse wave velocity by FPG tertiles did not reach statistically significant differences after controlling for potential confounders (FPG 4.44 mmol/l = 7.18 m/s; FPG 4.44 mmol/l-4.87 mmol/l = 7.26 m/s; and FPG ≥4.88 mmol/l = 7.93 m/s, p =.066). CONCLUSIONS Glucose levels in a non-diabetic population were associated with arterial stiffness but better when levels were determined using HbA1c.
Collapse
Affiliation(s)
- Iván Cavero-Redondo
- Centro de Investigación Sanitaria y Social, Universidad de Castilla-La Mancha, Cuenca, España
| | - Vicente Martínez-Vizcaíno
- Centro de Investigación Sanitaria y Social, Universidad de Castilla-La Mancha, Cuenca, España; Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, Chile.
| | - Celia Álvarez-Bueno
- Centro de Investigación Sanitaria y Social, Universidad de Castilla-La Mancha, Cuenca, España
| | - José Ignacio Recio-Rodríguez
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Unidad de Investigación de Atención Primaria, Centro de Salud La Alamedilla, Servicio de Salud de Castilla León, Salamanca, España; Departamento de Enfermería y Fisioterapia, Universidad de Salamanca, Salamanca, España
| | - Manuel Ángel Gómez-Marcos
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Unidad de Investigación de Atención Primaria, Centro de Salud La Alamedilla, Servicio de Salud de Castilla León, Salamanca, España; Departamento de Medicina, Universidad de Salamanca, Salamanca, España
| | - Luis García-Ortiz
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Unidad de Investigación de Atención Primaria, Centro de Salud La Alamedilla, Servicio de Salud de Castilla León, Salamanca, España; Departamento de Ciencias Biomédicas y Diagnósticas, Universidad de Salamanca, Salamanca, España
| |
Collapse
|
|
34
|
Scicali R, Di Pino A, Platania R, Purrazzo G, Ferrara V, Giannone A, Urbano F, Filippello A, Rapisarda V, Farruggia E, Piro S, Rabuazzo AM, Purrello F. Detecting familial hypercholesterolemia by serum lipid profile screening in a hospital setting: Clinical, genetic and atherosclerotic burden profile. Nutr Metab Cardiovasc Dis 2018; 28:35-43. [PMID: 28958694 DOI: 10.1016/j.numecd.2017.07.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Revised: 07/04/2017] [Accepted: 07/10/2017] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIMS Familial hypercholesterolemia (FH) is underdiagnosed and public cholesterol screening may be useful to find new subjects. In this study, we aim to investigate the prevalence of FH patients in a hospital screening program and evaluate their atherosclerotic burden using intima-media thickness (IMT). METHODS AND RESULTS We screened 1575 lipid profiles and included for genetic analysis adults with a low-density lipoprotein (LDL) cholesterol >190 mg/dL and triglycerides <200 mg/dL and first-degree child relatives with LDL cholesterol >160 mg/dL and triglycerides <200 mg/dL. The diagnosis of FH was presumed by Dutch Lipid Clinic Network (DLCN) criteria and confirmed by the presence of the genetic variant. Mean common carotid intima-media thickness (IMT) was assessed using consensus criteria. After confirming LDL cholesterol value and excluding secondary hypercholesterolemia, 56 subjects with a DLCN ≥4 performed genetic analysis. Of these, 26 had an FH genetic variant. The proportion of patients with a mutation having a DLCN score of 6-8 was 75%; in individuals with a DLCN score >8 it was 100%. Mean IMT was higher in FH patients compared to non FH (0.73 [0.61-0.83] vs 0.71 [0.60-0.75] mm, p < 0.01). Moreover, we detected two mutations not previously described. Finally, simple regression analysis showed a correlation of IMT with LDL cholesterol >190 mg/dL and corneal arcus (p < 0.01 and p < 0.001, respectively). CONCLUSIONS A hospital screening was useful to detect FH subjects with increased atherosclerosis. Also, next-generation sequencing was able to detect new FH mutations.
Collapse
Affiliation(s)
- R Scicali
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - A Di Pino
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - R Platania
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - G Purrazzo
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - V Ferrara
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - A Giannone
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - F Urbano
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - A Filippello
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - V Rapisarda
- Department of Clinical and Experimental Medicine, Section of Occupational Medicine, University of Catania, Italy
| | - E Farruggia
- Occupational Medicine Division, Garibaldi Hospital of Catania, Catania, Italy
| | - S Piro
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - A M Rabuazzo
- Department of Clinical and Experimental Medicine, University of Catania, Italy
| | - F Purrello
- Department of Clinical and Experimental Medicine, University of Catania, Italy.
| |
Collapse
|
|
35
|
Di Pino A, Currenti W, Urbano F, Scicali R, Piro S, Purrello F, Rabuazzo AM. High intake of dietary advanced glycation end-products is associated with increased arterial stiffness and inflammation in subjects with type 2 diabetes. Nutr Metab Cardiovasc Dis 2017; 27:978-984. [PMID: 28958695 DOI: 10.1016/j.numecd.2017.06.014] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Revised: 06/07/2017] [Accepted: 06/27/2017] [Indexed: 01/12/2023]
Abstract
BACKGROUND AND AIMS Modern diets are high in advanced glycation end-products (dAGEs), derived from processing methods, exerting a pivotal role in promoting atherosclerotic risk. In this cross-sectional study we investigate the relationship between dAGE intake, arterial stiffness, inflammatory profile and macronutrient composition, in subjects with type 2 diabetes without overt cardiovascular disease. METHODS AND RESULTS Arterial stiffness, carboxy-methyl-lysine, endogenous secretory receptor for AGEs (esRAGE), high sensitivity C reactive protein (hs-CRP), S100A12 and macronutrient intake were evaluated in 85 subjects with type 2 diabetes. The subjects were stratified into two groups according to dAGE consumption: high and low dAGE intake (≥ or <15.000 kU/day, respectively). Subjects with high dAGE intake (n = 45) showed a higher augmentation, augmentation index and pulse wave velocity (PWV) compared with those subjects with low dAGE intake (18 ± 5.4 vs 12.2 ± 6.3 mmHg, P < 0.05; 38.3 ± 5.4 vs 29.3 ± 10%; 9.2 ± 1.4 m/sec vs 7.9 ± 1.7, P < 0.05, respectively). hs-CRP were higher in subjects with high dAGE intake [0.42 (0.18-0.54) vs 0.21 (0.14-0.52) mg/dL, P < 0.05] whereas esRAGE plasma levels were lower [0.16 (0.23-0.81) vs 0.2 (0.14-0.54) ng/dL, P < 0.05]. Simple regression analysis showed a correlation between dAGEs and fat intake. Multivariate analysis showed an independent association between augmentation, systolic blood pressure (BP) and dAGE consumption; BMI and esRAGE were the major determinants of PWV. CONCLUSIONS Our data suggests that a chronic high dAGE diet could lead to a vascular dysfunction and inflammatory activation, contributing to the development of vascular complications in subjects with type 2 diabetes. Testing this hypothesis may represent a direction of future research.
Collapse
Affiliation(s)
- A Di Pino
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - W Currenti
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - F Urbano
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - R Scicali
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - S Piro
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - F Purrello
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
| | - A M Rabuazzo
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| |
Collapse
|
|
36
|
Di Pino A, Mangiafico S, Urbano F, Scicali R, Scandura S, D'Agate V, Piro S, Tamburino C, Purrello F, Rabuazzo AM. HbA1c Identifies Subjects With Prediabetes and Subclinical Left Ventricular Diastolic Dysfunction. J Clin Endocrinol Metab 2017; 102:3756-3764. [PMID: 28973588 DOI: 10.1210/jc.2017-00954] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 07/27/2017] [Indexed: 02/07/2023]
Abstract
CONTEXT Prediabetes is associated with subclinical cardiac changes associated with heart failure development. OBJECTIVE We investigated diastolic function and its association with markers of glycation and inflammation related to cardiovascular disease in patients with prediabetes. We focused on individuals with prediabetes identified only by glycated hemoglobin A1c [HbA1c; 5.7% to 6.4% and normal fasting glucose (NFG) and normal glucose tolerance (NGT) after an oral glucose tolerance test (OGTT)]. DESIGN Cross-sectional study. SETTING Departments of Clinical and Experimental Medicine and Cardiology, University of Catania, Catania, Italy. MAIN OUTCOME MEASURES HbA1c, OGTT, Doppler echocardiography, soluble receptor for advanced glycation end products (sRAGEs), and endogenous secretory RAGE (esRAGE) were evaluated. PATIENTS We recruited 167 subjects with NFG/NGT who were stratified according to HbA1c level: controls (HbA1c <5.7%) and HbA1c prediabetes (HbA1c 5.7% to 6.4%). RESULTS Patients with HbA1c prediabetes (n = 106) showed a lower peak mitral inflow in early diastole (E wave) to late diastolic atrial filling velocity (A wave) ratio (E/A ratio) than controls (n = 61) (1.10 ± 0.24 vs 1.18 ± 0.23; P < 0.05). They showed a higher left atrium volume (LAV) (28.4 ± 5 vs 22.1 ± 3; P < 0.05) and sphericity index (SI) (0.6 ± 0.06 vs 0.5 ± 0.05; P < 0.05). After multiple regression analyses, HbA1c, sRAGE, and esRAGE were the major determinants of E/A ratio, LAV, and SI. CONCLUSIONS Subjects with HbA1c prediabetes exhibited subclinical cardiac alterations associated with sRAGE, esRAGE, and HbA1c. These subjects would not have been classified as having prediabetes on the basis of fasting glycemia or post-OGTT values.
Collapse
Affiliation(s)
- Antonino Di Pino
- Department of Clinical and Experimental Medicine, Garibaldi Hospital, University of Catania, 95122 Catania, Italy
| | - Sarah Mangiafico
- Division of Cardiology, Ferrarotto Hospital, University of Catania, 95100 Catania, Italy
| | - Francesca Urbano
- Department of Clinical and Experimental Medicine, Garibaldi Hospital, University of Catania, 95122 Catania, Italy
| | - Roberto Scicali
- Department of Clinical and Experimental Medicine, Garibaldi Hospital, University of Catania, 95122 Catania, Italy
| | - Salvatore Scandura
- Division of Cardiology, Ferrarotto Hospital, University of Catania, 95100 Catania, Italy
| | - Veronica D'Agate
- Division of Cardiology, Ferrarotto Hospital, University of Catania, 95100 Catania, Italy
| | - Salvatore Piro
- Department of Clinical and Experimental Medicine, Garibaldi Hospital, University of Catania, 95122 Catania, Italy
| | - Corrado Tamburino
- Division of Cardiology, Ferrarotto Hospital, University of Catania, 95100 Catania, Italy
| | - Francesco Purrello
- Department of Clinical and Experimental Medicine, Garibaldi Hospital, University of Catania, 95122 Catania, Italy
| | - Agata Maria Rabuazzo
- Department of Clinical and Experimental Medicine, Garibaldi Hospital, University of Catania, 95122 Catania, Italy
| |
Collapse
|
|
37
|
Kiss LZ, Bagyura Z, Vadas R, Polgár L, Lux Á, Édes E, Szenczi O, Soós P, Szelid Z, Becker D, Jermendy G, Merkely B. Signs of subclinical atherosclerosis in asymptomatic patients at increased risk of type 2 diabetes mellitus. J Diabetes Complications 2017; 31:1293-1298. [PMID: 28576484 DOI: 10.1016/j.jdiacomp.2017.05.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Revised: 05/15/2017] [Accepted: 05/17/2017] [Indexed: 12/18/2022]
Abstract
AIMS We aimed to study carotid intima media thickness (CIMT) in asymptomatic patients with an increased risk of type 2 diabetes mellitus (T2DM) and in a pre-diabetic state. METHODS Diabetes risk assessment was performed in 2420 participants in a voluntary screening program between 2011 and 2013. The risk of T2DM was estimated by the Findrisc scoring system (FR). A FR≥12 was considered as increased risk. HbA1c% between 5.7 and 6.4% signified a pre-diabetic state. Carotid duplex scan was performed and CIMT above 0.9 mm was regarded as pathological. Patients with T2DM or a history of cardiovascular disease were excluded. RESULTS Overall 1475 subjects were included. Four groups were compared: "control" (normal HbA1c, FR<12), "HbA1c only" (HbA1c: 5.7-6.4%, FR<12), "Findrisc only" (normal HbA1c, FR≥12) and "combined" (HbA1c: 5.7-6.4%, FR≥12). Frequency of pathological maximal CIMT was 9.4%, 19.7%, 27.4% and 36.4% in the groups, respectively (p<0.001). Logistic regression analysis revealed that compared to control subjects, sex and risk factor-adjusted Odds Ratios for the presence of pathological maximal CIMT were 2.2 (p<0.001), 3.4 (p<0.001) and 5.1 (p<0.001) for the groups, respectively. CONCLUSIONS Evaluation of Findrisc score and HbA1c at population level may facilitate early recognition of subclinical vascular complications even in the pre-diabetic state.
Collapse
Affiliation(s)
- Loretta Zsuzsa Kiss
- Heart and Vascular Center, Semmelweis University, Varosmajor Street 68, Budapest H-1122, Hungary.
| | - Zsolt Bagyura
- MTA-SE Lendület Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Varosmajor Street 68, Budapest H-1122, Hungary.
| | - Réka Vadas
- Heart and Vascular Center, Semmelweis University, Varosmajor Street 68, Budapest H-1122, Hungary.
| | - Lívia Polgár
- Heart and Vascular Center, Semmelweis University, Varosmajor Street 68, Budapest H-1122, Hungary.
| | - Árpád Lux
- Heart and Vascular Center, Semmelweis University, Varosmajor Street 68, Budapest H-1122, Hungary.
| | - Eszter Édes
- Heart and Vascular Center, Semmelweis University, Varosmajor Street 68, Budapest H-1122, Hungary.
| | - Orsolya Szenczi
- Heart and Vascular Center, Semmelweis University, Varosmajor Street 68, Budapest H-1122, Hungary.
| | - Pál Soós
- Heart and Vascular Center, Semmelweis University, Varosmajor Street 68, Budapest H-1122, Hungary.
| | - Zsolt Szelid
- Heart and Vascular Center, Semmelweis University, Varosmajor Street 68, Budapest H-1122, Hungary.
| | - Dávid Becker
- Heart and Vascular Center, Semmelweis University, Varosmajor Street 68, Budapest H-1122, Hungary.
| | - György Jermendy
- Bajcsy-Zsilinszky Hospital, Maglódi Street 89-91, Budapest H-1106, Hungary.
| | - Béla Merkely
- Heart and Vascular Center, Semmelweis University, Varosmajor Street 68, Budapest H-1122, Hungary.
| |
Collapse
|
|
38
|
Marini MA, Fiorentino TV, Andreozzi F, Mannino GC, Succurro E, Sciacqua A, Perticone F, Sesti G. Hemorheological alterations in adults with prediabetes identified by hemoglobin A1c levels. Nutr Metab Cardiovasc Dis 2017; 27:601-608. [PMID: 28511905 DOI: 10.1016/j.numecd.2017.04.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 04/11/2017] [Accepted: 04/11/2017] [Indexed: 11/16/2022]
Abstract
BACKGROUND AND AIMS A link between increased blood viscosity and type 2 diabetes has been previously reported. Herein, we investigated the association of blood viscosity with prediabetes, identified by glycated hemoglobin A1c (HbA1c) according to the new American Diabetes Association criteria, and subclinical atherosclerosis. METHODS AND RESULTS The study cohort includes 1136 non-diabetic adults submitted to anthropometrical evaluation, an oral glucose tolerance test and ultrasound measurement of carotid intima-media thickness (IMT). Whole blood viscosity was estimated using a validated formula based on hematocrit and total plasma proteins. After adjusting for age, and gender, individuals with HbA1c-defined prediabetes (HbA1c 5.7-6.4% [39-47 mmol/mol]) exhibited significantly higher values of hematocrit, and predicted blood viscosity as compared with controls. Increased levels of IMT were observed in subjects with HbA1c-defined prediabetes in comparison to controls. Predicted blood viscosity was positively correlated with age, waist circumference, blood pressure, cholesterol, triglycerides, fibrinogen, white blood cell, HbA1c, fasting and 2-h post-load glucose levels, fasting insulin, IMT and inversely correlated with HDL and Matsuda index of insulin sensitivity. Of the three glycemic parameters, i.e. HbA1c, fasting and 2-h post-load glucose, only HbA1c showed a significant correlation with predicted blood viscosity (β = 0.054, P = 0.04) in a multivariate regression analysis model including multiple atherosclerosis risk factors. CONCLUSION The study shows that individuals with HbA1c-defined prediabetes have increased predicted blood viscosity and IMT. The HbA1c criterion may be helpful to capture individuals with an increased risk of diabetes and cardiovascular disease who may benefit from an intensive lifestyle intervention.
Collapse
Affiliation(s)
- M A Marini
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
| | - T V Fiorentino
- Department of Medical and Surgical Sciences, University Magna-Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
| | - F Andreozzi
- Department of Medical and Surgical Sciences, University Magna-Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
| | - G C Mannino
- Department of Medical and Surgical Sciences, University Magna-Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
| | - E Succurro
- Department of Medical and Surgical Sciences, University Magna-Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
| | - A Sciacqua
- Department of Medical and Surgical Sciences, University Magna-Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
| | - F Perticone
- Department of Medical and Surgical Sciences, University Magna-Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
| | - G Sesti
- Department of Medical and Surgical Sciences, University Magna-Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy.
| |
Collapse
|
|
39
|
Scicali R, Giral P, Gallo A, Di Pino A, Rabuazzo AM, Purrello F, Cluzel P, Redheuil A, Bruckert E, Rosenbaum D. HbA1c increase is associated with higher coronary and peripheral atherosclerotic burden in non diabetic patients. Atherosclerosis 2016; 255:102-108. [DOI: 10.1016/j.atherosclerosis.2016.11.003] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 09/22/2016] [Accepted: 11/02/2016] [Indexed: 12/27/2022]
|
|
40
|
Di Pino A, Urbano F, Piro S, Purrello F, Rabuazzo AM. Update on pre-diabetes: Focus on diagnostic criteria and cardiovascular risk. World J Diabetes 2016; 7:423-432. [PMID: 27795816 PMCID: PMC5065662 DOI: 10.4239/wjd.v7.i18.423] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Revised: 06/24/2016] [Accepted: 08/15/2016] [Indexed: 02/05/2023] Open
Abstract
Pre-diabetes, which is typically defined as blood glucose concentrations higher than normal but lower than the diabetes threshold, is a high-risk state for diabetes and cardiovascular disease development. As such, it represents three groups of individuals: Those with impaired fasting glucose (IFG), those with impaired glucose tolerance (IGT) and those with a glycated haemoglobin (HbA1c) between 39-46 mmol/mol. Several clinical trials have shown the important role of IFG, IGT and HbA1c-pre-diabetes as predictive tools for the risk of developing type 2 diabetes. Moreover, with regard to cardiovascular disease, pre-diabetes is associated with more advanced vascular damage compared with normoglycaemia, independently of confounding factors. In view of these observations, diagnosis of pre-diabetes is mandatory to prevent or delay the development of the disease and its complications; however, a number of previous studies reported that the concordance between pre-diabetes diagnoses made by IFG, IGT or HbA1c is scarce and there are conflicting data as to which of these methods best predicts cardiovascular disease. This review highlights recent studies and current controversies in the field. In consideration of the expected increased use of HbA1c as a screening tool to identify individuals with alteration of glycaemic homeostasis, we focused on the evidence regarding the ability of HbA1c as a diagnostic tool for pre-diabetes and as a useful marker in identifying patients who have an increased risk for cardiovascular disease. Finally, we reviewed the current evidence regarding non-traditional glycaemic biomarkers and their use as alternatives to or additions to traditional ones.
Collapse
|
|
41
|
Villegas-Rodríguez ME, Uribarri J, Solorio-Meza SE, Fajardo-Araujo ME, Cai W, Torres-Graciano S, Rangel-Salazar R, Wrobel K, Garay-Sevilla ME. The AGE-RAGE Axis and Its Relationship to Markers of Cardiovascular Disease in Newly Diagnosed Diabetic Patients. PLoS One 2016; 11:e0159175. [PMID: 27434539 PMCID: PMC4951143 DOI: 10.1371/journal.pone.0159175] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Accepted: 06/28/2016] [Indexed: 01/12/2023] Open
Abstract
AIM The purpose of the study was the simultaneous measurement of all the different components of the AGE-RAGE axis as well as several non-invasive markers of cardiovascular disease (CVD) in a cohort of newly diagnosed diabetic patients. MATERIALS AND METHODS In 80 newly diagnosed diabetic patients we measured serum carboxymethyllysine (CML), soluble RAGE (sRAGE) and peripheral mononuclear (PMNC) RAGE and AGER1 mRNA together with ICAM-1, VCAM-1, and malondialdehyde (MDA). We also assessed cardiovascular function by measurement of flow-mediated vasodilation (FMD), intima-media thickness (IMT) and arterial stiffness. Univariant correlation analysis was used to determine correlation between the variables in the study and multiple regression analysis was used to examine the association between the AGE-RAGE axis components and FMD, IMT and arterial stiffness. RESULTS Serum CML correlated positively with sRAGE, PMNC RAGE, HOMA-IR, ICAM-1, VCAM-1 and MDA, but inversely with PMNC AGER1. sRAGE and RAGE was positively correlated with AGER; IMT was positively correlated with HOMA-IR, ICAM-1, VCAM-1, MDA, and sRAGE and arterial stiffness had correlation with HOMA-IR, ICAM-1, VCAM-1, MDA, CML, sRAGE, AGER1 and RAGE. In multivariate analysis we found a significant relationship between CML with PMNC RAGE, HOMA-IR; sRAGE with VCAM-1 and MDA; PMNC RAGE with PMNC AGER1and CML; PMNC AGER1 with PMNC RAGE; FMD with sRAGE, CML and HbA1c; IMT with sRAGE, and arterial stiffness with sRAGE, sCML and AGER1. CONCLUSIONS We found significant and strong associations between the different components of the AGE-RAGE axis and also found significant association between AGE-RAGE axis markers, especially sRAGE with several noninvasive markers of cardiovascular disease risk. sRAGE, an easily measured parameter in blood, may potentially be used as a surrogate marker of AGEs-RAGE in patients with diabetes.
Collapse
Affiliation(s)
| | - Jaime Uribarri
- Department of Medicine. The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | | | - Martha E. Fajardo-Araujo
- Department of Medical Science. Division of Health Science. University of Guanajuato Campus. León, Guanajuato, México
| | - Weijing Cai
- Department of Medicine. The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Sofía Torres-Graciano
- Department of Medical Science. Division of Health Science. University of Guanajuato Campus. León, Guanajuato, México
| | - Rubén Rangel-Salazar
- Department of Medical Science. Division of Health Science. University of Guanajuato Campus. León, Guanajuato, México
| | - Kazimierz Wrobel
- Department of Chemistry, University of Guanajuato, Guanajuato, Guanajuato, México
| | - Ma. Eugenia Garay-Sevilla
- Department of Medical Science. Division of Health Science. University of Guanajuato Campus. León, Guanajuato, México
- * E-mail:
| |
Collapse
|
|
42
|
Di Pino A, Urbano F, Zagami RM, Filippello A, Di Mauro S, Piro S, Purrello F, Rabuazzo AM. Low Endogenous Secretory Receptor for Advanced Glycation End-Products Levels Are Associated With Inflammation and Carotid Atherosclerosis in Prediabetes. J Clin Endocrinol Metab 2016; 101:1701-9. [PMID: 26885882 DOI: 10.1210/jc.2015-4069] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
CONTEXT Prediabetes is associated with atherosclerotic vascular damage. OBJECTIVE We investigated the correlation of endogenous secretory receptor for advanced glycation end-products (esRAGE), total soluble RAGE (sRAGE) and markers of inflammation, with early cardiovascular disease in subjects with prediabetes. We particularly focused on individuals with prediabetes identified only by glycated hemoglobin A1c (HbA1c) (5.7–6.4%) who had normal fasting glucose and were normotolerant after oral glucose tolerance test. DESIGN This was a cross-sectional study. SETTING The study was conducted in the Department of Clinical and Molecular Medicine, University of Catania, Italy. MAIN OUTCOME MEASURE sRAGE, esRAGE, carboxymethyl-lysine, S100A12, HbA1c, fasting glycemia, oral glucose tolerance test, pulse wave velocity, and intima-media thickness were evaluated in subjects with prediabetes. PATIENTS Three hundred eighty subjects without previous history of diabetes were stratified into three groups: controls (n = 99), prediabetes (n = 220), and new-onset type 2 diabetes (n = 61). RESULTS Subjects with prediabetes exhibited the following: lower esRAGE (0.29 ± 0.18 vs 0.45 ± 0.26 ng/mL; P < .05) and higher S100A12 levels than controls. RT-PCR analysis in mononuclear cells revealed that the mRNA expression level of the esRAGE splice variant progressively decreased in patients with prediabetes and type 2 diabetes with respect to controls. No difference was observed in sRAGE and carboxymethyl-lysine plasma levels between the groups. After multiple regression analyses, only age, HbA1c, and hs-CRP were independently associated with esRAGE levels. Age, HbA1c, and esRAGE were the major determinants of intima-media thickness, whereas S100A12 and systolic blood pressure were the major determinants of pulse wave velocity. When we analyzed the subjects with HbA1c prediabetes (normal fasting glucose/normotolerant and HbA1c 5.7–6.4%), esRAGE and inflammatory markers plasma levels still remained significantly different in respect to controls. CONCLUSIONS Subjects with HbA1c prediabetes exhibited significantly reduced esRAGE levels and increased levels of markers of inflammation. These alterations are associated with early markers of cardiovascular disease.
Collapse
Affiliation(s)
- Antonino Di Pino
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Francesca Urbano
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Rose Maria Zagami
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Agnese Filippello
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Stefania Di Mauro
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Salvatore Piro
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Francesco Purrello
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| | - Agata Maria Rabuazzo
- Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy
| |
Collapse
|
|
43
|
Zagami RM, Di Pino A, Urbano F, Piro S, Purrello F, Rabuazzo AM. Low circulating vitamin D levels are associated with increased arterial stiffness in prediabetic subjects identified according to HbA1c. Atherosclerosis 2015; 243:395-401. [DOI: 10.1016/j.atherosclerosis.2015.09.038] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Revised: 09/25/2015] [Accepted: 09/29/2015] [Indexed: 02/07/2023]
|
|
44
|
Monneret D. Evaluation of HbA1c as a prognostic biomarker of cardiovascular events and mortality in nondiabetic patients: Methodological considerations. Atherosclerosis 2015; 242:19-21. [DOI: 10.1016/j.atherosclerosis.2015.06.047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2015] [Revised: 06/03/2015] [Accepted: 06/22/2015] [Indexed: 11/30/2022]
|
|
45
|
Mostaza JM, Lahoz C, Salinero-Fort MA, de Burgos-Lunar C, Laguna F, Estirado E, García-Iglesias F, González-Alegre T, Cornejo-Del-Río V, Sabín C, López S. Carotid atherosclerosis severity in relation to glycemic status: a cross-sectional population study. Atherosclerosis 2015; 242:377-82. [PMID: 26275375 DOI: 10.1016/j.atherosclerosis.2015.07.028] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Revised: 07/13/2015] [Accepted: 07/14/2015] [Indexed: 10/23/2022]
Abstract
OBJECTIVE Intima-media thickness (IMT) is increased in subjects with prediabetes or newly diagnosed diabetes. However, no previous studies have evaluated the relationship between the severity of carotid atherosclerosis, assessed by the presence of carotid plaques or stenosis, and the glycemic status, assessed either by fasting glucose, an oral glucose tolerance test (OGTT) or A1C levels. METHODS Cross-sectional analysis of 1475 subjects (mean age 62 years, 44% males), randomly selected from the population. A fasting blood sample was obtained to determine glucose, lipids, and A1C levels. An OGTT was performed in non-diabetic subjects. Carotid atherosclerosis was evaluated by echo-doppler. RESULTS A 10.5% of the population had a previous diagnosis of diabetes. Of the 1320 non-diabetic participants, 349 (26.4%) had normal fasting glucose, normal glucose tolerance and A1C < 5.7%, and were considered controls. Prediabetes was diagnosed in 850 subjects (64.4%), and diabetes was newly diagnosed in 121 (9.2%). The prevalence of patients with carotid plaques was 34.2% in controls, 45.1% in prediabetics, 64.2% in newly diagnosed diabetics, and 72.9% in established diabetic patients. These numbers were 0.3%, 1.1%, 5.0% and 7.7% for carotid stenosis, respectively. In multivariate analysis, glycemic status remained significantly associated with the prevalence of carotid plaques after adjusting for age, sex, statin treatment, and cardiovascular risk factors. CONCLUSIONS Glycemic status is associated with all grades of carotid atherosclerosis, from early signs, as demonstrated by the IMT, to intermediate degrees, as demonstrated by the presence of carotid plaques, to advance atherosclerosis, as established by the presence of carotid stenosis.
Collapse
Affiliation(s)
- Jose M Mostaza
- Atherosclerosis Unit, Internal Medicine Department, Hospital Carlos III, Madrid, Spain.
| | - Carlos Lahoz
- Atherosclerosis Unit, Internal Medicine Department, Hospital Carlos III, Madrid, Spain
| | - Miguel A Salinero-Fort
- Gerencia Adjunta de Planificación y Calidad, Atención Primaria, Servicio Madrileño de Salud, Madrid, Spain
| | | | - Fernando Laguna
- Atherosclerosis Unit, Internal Medicine Department, Hospital Carlos III, Madrid, Spain
| | - Eva Estirado
- Atherosclerosis Unit, Internal Medicine Department, Hospital Carlos III, Madrid, Spain
| | | | | | | | | | | | | |
Collapse
|
|
46
|
Ma X, Shen Y, Hu X, Hao Y, Luo Y, Tang J, Zhou J, Bao Y, Jia W. Associations of glycated haemoglobin A1c and glycated albumin with subclinical atherosclerosis in middle-aged and elderly Chinese population with impaired glucose regulation. Clin Exp Pharmacol Physiol 2015; 42:582-7. [DOI: 10.1111/1440-1681.12394] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Revised: 01/19/2015] [Accepted: 02/01/2015] [Indexed: 12/16/2022]
Affiliation(s)
- Xiaojing Ma
- Department of Endocrinology and Metabolism; Shanghai Key Laboratory of Diabetes Mellitus; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai China
| | - Yun Shen
- Department of Endocrinology and Metabolism; Shanghai Key Laboratory of Diabetes Mellitus; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai China
| | - Xiang Hu
- Department of Endocrinology and Metabolism; Shanghai Key Laboratory of Diabetes Mellitus; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai China
| | - Yaping Hao
- Department of Endocrinology and Metabolism; Shanghai Key Laboratory of Diabetes Mellitus; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai China
| | - Yuqi Luo
- Department of Endocrinology and Metabolism; Shanghai Key Laboratory of Diabetes Mellitus; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai China
| | - Junling Tang
- Department of Endocrinology and Metabolism; Shanghai Key Laboratory of Diabetes Mellitus; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai China
| | - Jian Zhou
- Department of Endocrinology and Metabolism; Shanghai Key Laboratory of Diabetes Mellitus; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai China
| | - Yuqian Bao
- Department of Endocrinology and Metabolism; Shanghai Key Laboratory of Diabetes Mellitus; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai China
| | - Weiping Jia
- Department of Endocrinology and Metabolism; Shanghai Key Laboratory of Diabetes Mellitus; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai China
| |
Collapse
|
|
47
|
Biswas SK. Soluble receptor for advanced glycation end products and insulin resistance during development of type 2 diabetes mellitus. J Diabetes Complications 2015; 29:611. [PMID: 25817173 DOI: 10.1016/j.jdiacomp.2015.03.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 03/12/2015] [Indexed: 11/26/2022]
Affiliation(s)
- Subrata Kumar Biswas
- Department of Biochemistry, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh.
| |
Collapse
|
|
48
|
Buysschaert M, Medina JL, Bergman M, Shah A, Lonier J. Prediabetes and associated disorders. Endocrine 2015; 48:371-93. [PMID: 25294012 DOI: 10.1007/s12020-014-0436-2] [Citation(s) in RCA: 100] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Accepted: 09/20/2014] [Indexed: 12/14/2022]
Abstract
Prediabetes represents an elevation of plasma glucose above the normal range but below that of clinical diabetes. Prediabetes includes individuals with IFG, IGT, IFG with IGT and elevated HbA1c levels. Insulin resistance and β-cell dysfunction are characteristic of this disorder. The diagnosis of prediabetesis is vital as both IFG and IGT are indeed well-known risk factors for type 2 diabetes with a greater risk in the presence of combined IFG and IGT. Furthermore, as will be illustrated in this review, prediabetes is associated with associated disorders typically only considered in with established diabetes. These include cardiovascular disease, periodontal disease, cognitive dysfunction, microvascular disease, blood pressure abnormalities, obstructive sleep apnea, low testosterone, metabolic syndrome, various biomarkers, fatty liver disease, and cancer. As the vast majority of individuals with prediabetes are unaware of their diagnosis, it is therefore vital that the associated conditions are identified, particularly in the presence of mild hyperglycemia, so they may benefit from early intervention.
Collapse
Affiliation(s)
- Martin Buysschaert
- Department of Endocrinology and Diabetology, University Clinic Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | | | | | | | | |
Collapse
|
|
49
|
Rebnord EW, Pedersen ER, Strand E, Svingen GFT, Meyer K, Schartum-Hansen H, Løland KH, Seifert R, Ueland PM, Nilsen DWT, Nordrehaug JE, Nygård O. Glycated hemoglobin and long-term prognosis in patients with suspected stable angina pectoris without diabetes mellitus: a prospective cohort study. Atherosclerosis 2015; 240:115-20. [PMID: 25770690 DOI: 10.1016/j.atherosclerosis.2015.02.053] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Revised: 01/23/2015] [Accepted: 02/23/2015] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Associations of glycated hemoglobin A1c (HbA1c) levels to incident coronary and cardiovascular events among non-diabetic patients with coronary artery disease are unclear. We investigated relations of HbA1c to long-term prognosis in such patients. METHODS A prospective cohort of 2519 patients undergoing elective coronary angiography for suspected stable angina pectoris (SAP) was divided into pre-defined categories according to HbA1c (%) levels (<5.0, 5.0-5.6 (reference), 5.7-6.4), and followed for median 4.9 years. The primary end-point was major coronary events (including non-fatal and fatal acute myocardial infarctions, and sudden cardiac death). Secondary end-points were death from cardiovascular disease (CVD) and all-cause mortality. Hazard ratios (HRs) (95% confidence intervals [CIs]) were obtained by Cox regression. RESULTS Median age at inclusion was 62 years, 73% were males, median HbA1c was 5.6% and random plasma-glucose 5.4 mmol/L. After multivariate adjustment, HbA1c levels within the pre-diabetic range were not associated with risk of major coronary events, HR (95% CI): 1.13 (0.79-1.62); P=0.49, death from CVD or all-cause mortality HR (95% CI): 0.95 (0.55-1.66) and 1.04 (0.70-1.53), respectively; P≥0.85. Similarly, there was no significant association between HbA1c values within the lowest category and risk of study outcomes, (P≥0.18). CONCLUSION In non-diabetic patients with suspected SAP, there was no overall association between HbA1c levels and prognosis, questioning an independent role of glycemia in the pathogenesis of atherosclerotic complications in these patients.
Collapse
Affiliation(s)
- Eirik Wilberg Rebnord
- Department of Heart Disease, Haukeland University Hospital, 5021 Bergen, Norway; Department of Clinical Science, University of Bergen, Mailbox 7804, 5021 Bergen, Norway.
| | - Eva Ringdal Pedersen
- Department of Clinical Science, University of Bergen, Mailbox 7804, 5021 Bergen, Norway.
| | - Elin Strand
- Department of Clinical Science, University of Bergen, Mailbox 7804, 5021 Bergen, Norway.
| | | | - Klaus Meyer
- BEVITAL, Laboratoriebygget, 9th Floor, Jonas Lies veg 87, 5021 Bergen, Norway.
| | - Hall Schartum-Hansen
- Department of Heart Disease, Haukeland University Hospital, 5021 Bergen, Norway.
| | | | - Reinhard Seifert
- Department of Clinical Science, University of Bergen, Mailbox 7804, 5021 Bergen, Norway.
| | - Per Magne Ueland
- Department of Clinical Science, University of Bergen, Mailbox 7804, 5021 Bergen, Norway; Laboratory of Clinical Biochemistry, Haukeland University Hospital, 5021 Bergen, Norway.
| | - Dennis W T Nilsen
- Department of Clinical Science, University of Bergen, Mailbox 7804, 5021 Bergen, Norway; Division of Cardiology, Stavanger University Hospital, 4011 Stavanger, Norway.
| | - Jan Erik Nordrehaug
- Department of Clinical Science, University of Bergen, Mailbox 7804, 5021 Bergen, Norway; Division of Cardiology, Stavanger University Hospital, 4011 Stavanger, Norway.
| | - Ottar Nygård
- Department of Heart Disease, Haukeland University Hospital, 5021 Bergen, Norway; Department of Clinical Science, University of Bergen, Mailbox 7804, 5021 Bergen, Norway; K. G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Mailbox 7804, 5021 Bergen, Norway.
| |
Collapse
|
|
50
|
Yang L, Shen X, Yan S, Xu F, Wu P. The effectiveness of age on HbA1c as a criterion for the diagnosis of diabetes in Chinese different age subjects. Clin Endocrinol (Oxf) 2015; 82:205-12. [PMID: 24821380 DOI: 10.1111/cen.12494] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Revised: 02/13/2014] [Accepted: 04/02/2014] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To analyse the effectiveness of age on HbA1c as a criterion for the diagnosis of diabetes in Chinese different age subjects. METHODS This retrospective study enrolled a total of 1147 outpatients with untreated newly diagnosed diabetes (aged 18-80 years, 42·55% women) from the Fujian Province, China, and 427 age and gender-matched (control) subjects without diabetes. Receiver operating characteristic curve (ROC) was plotted to determine the performance of HbA1c against results of oral glucose tolerance test (OGTT) performed at the same time according to specific age groups. The ORs and 95%CIs between diabetes and other metabolic disorders were analysed. RESULTS (i) HbA1c provided an age-specific diagnosis for diabetes: there was a high diagnostic titter of HbA1c in the 18- to 39-year age group; conversely, there was a low diagnostic titter of HbA1c in the ≥70-year-old age groups. (ii) After adjusted for age, individuals with diabetes by OGTT criteria but not by WHO HbA1c criteria had an increased chance of having abnormal weight, hypertriglyceridaemia, HDL hypocholesterolaemia and insulin resistance. (iii) The diagnostic cut-off points of HbA1c for diabetes in different age groups (18-39, 40-49, 50-59, 60-69 and ≥70 years) were 6·1, 6·3, 6·4, 6·5 and 6·4, respectively. The age-specific HbA1c criteria exhibited the higher positive rate, sensitivity and lower false-negative rate when compared with WHO HbA1c criteria. CONCLUSIONS This provided evidence indicating that there may be drawbacks in the use of HbA1c in the diagnosis of diabetes. Thus, we proposed that the impact of introducing HbA1c for diabetes diagnosis should be considered in terms of age. Cohort studies are needed to further confirm the suitability of age-specific HbA1c criteria for the diagnosis of diabetes.
Collapse
Affiliation(s)
- Liyong Yang
- Endocrinology Department, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | | | | | | | | |
Collapse
|