|
1
|
Dominguez LJ, Veronese N, Barbagallo M. Magnesium and the Hallmarks of Aging. Nutrients 2024; 16:496. [PMID: 38398820 PMCID: PMC10892939 DOI: 10.3390/nu16040496] [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: 12/31/2023] [Revised: 02/01/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Magnesium is an essential ion in the human body that regulates numerous physiological and pathological processes. Magnesium deficiency is very common in old age. Age-related chronic diseases and the aging process itself are frequently associated with low-grade chronic inflammation, called 'inflammaging'. Because chronic magnesium insufficiency has been linked to excessive generation of inflammatory markers and free radicals, inducing a chronic inflammatory state, we formerly hypothesized that magnesium inadequacy may be considered among the intermediaries helping us explain the link between inflammaging and aging-associated diseases. We show in this review evidence of the relationship of magnesium with all the hallmarks of aging (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, disabled autophagy, dysbiosis, and chronic inflammation), which may positively affect the human healthspan. It is feasible to hypothesize that maintaining an optimal balance of magnesium during one's life course may turn out to be a safe and economical strategy contributing to the promotion of healthy aging. Future well-designed studies are necessary to further explore this hypothesis.
Collapse
Affiliation(s)
- Ligia J. Dominguez
- School of Medicine, “Kore” University of Enna, 94100 Enna, Italy;
- Geriatric Unit, Department of Medicine, University of Palermo, 90127 Palermo, Italy;
| | - Nicola Veronese
- Geriatric Unit, Department of Medicine, University of Palermo, 90127 Palermo, Italy;
| | - Mario Barbagallo
- Geriatric Unit, Department of Medicine, University of Palermo, 90127 Palermo, Italy;
| |
Collapse
|
|
2
|
Oost LJ, Slieker RC, Blom MT, 't Hart LM, Hoenderop JGJ, Beulens JWJ, de Baaij JHF. Genome-wide association study of serum magnesium in type 2 diabetes. GENES & NUTRITION 2024; 19:2. [PMID: 38279093 PMCID: PMC10811844 DOI: 10.1186/s12263-024-00738-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 01/15/2024] [Indexed: 01/28/2024]
Abstract
People with type 2 diabetes have a tenfold higher prevalence of hypomagnesemia, which is suggested to be caused by low dietary magnesium intake, medication use, and genetics. This study aims to identify the genetic loci that influence serum magnesium concentration in 3466 people with type 2 diabetes. The GWAS models were adjusted for age, sex, eGFR, and HbA1c. Associated traits were identified using publicly available data from GTEx consortium, a human kidney eQTL atlas, and the Open GWAS database. The GWAS identified a genome-wide significant locus in TAF3 (p = 2.9 × 10-9) in people with type 2 diabetes. In skeletal muscle, loci located in TAF3 demonstrate an eQTL link to ATP5F1C, a gene that is involved in the formation of Mg2+-ATP. Serum Mg2+ levels were associated with MUC1/TRIM46 (p = 2.9 × 10-7), SHROOM3 (p = 4.0 × 10-7), and SLC22A7 (p = 1.0 × 10-6) at nominal significance, which is in combination with the eQTL data suggesting that they are possible candidates for renal failure. Several genetic loci were in agreement with previous genomic studies which identified MUC1/TRIM46 (Pmeta = 6.9 × 10-29, PQ = 0.81) and SHROOM3 (Pmeta = 2.9 × 10-27, PQ = 0.04) to be associated with serum Mg2+ in the general population. In conclusion, serum magnesium concentrations are associated with genetic variability around the regions of TAF3, MUC1/TRIM46, SHROOM3, and SLC22A7 in type 2 diabetes.
Collapse
Affiliation(s)
- Lynette J Oost
- Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Roderick C Slieker
- Department of Epidemiology and Data Science, Amsterdam UMC, Vrije Universiteit, Amsterdam, Amsterdam, the Netherlands
- Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands
- Amsterdam Public Health, Health Behaviors and Chronic Diseases, Amsterdam, the Netherlands
| | - Marieke T Blom
- Amsterdam Public Health, Health Behaviors and Chronic Diseases, Amsterdam, the Netherlands
- Amsterdam Cardiovascular Sciences, Diabetes & Metabolism, Amsterdam, the Netherlands
- Department of General Practice, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Leen M 't Hart
- Department of Epidemiology and Data Science, Amsterdam UMC, Vrije Universiteit, Amsterdam, Amsterdam, the Netherlands
- Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands
- Amsterdam Public Health, Health Behaviors and Chronic Diseases, Amsterdam, the Netherlands
- Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Joost G J Hoenderop
- Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Joline W J Beulens
- Department of Epidemiology and Data Science, Amsterdam UMC, Vrije Universiteit, Amsterdam, Amsterdam, the Netherlands
- Amsterdam Public Health, Health Behaviors and Chronic Diseases, Amsterdam, the Netherlands
- Amsterdam Cardiovascular Sciences, Diabetes & Metabolism, Amsterdam, the Netherlands
| | - Jeroen H F de Baaij
- Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands.
| |
Collapse
|
|
3
|
Basiri R, Seidu B, Cheskin LJ. Key Nutrients for Optimal Blood Glucose Control and Mental Health in Individuals with Diabetes: A Review of the Evidence. Nutrients 2023; 15:3929. [PMID: 37764713 PMCID: PMC10536295 DOI: 10.3390/nu15183929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 08/31/2023] [Accepted: 09/08/2023] [Indexed: 09/29/2023] Open
Abstract
Diabetes is associated with an increased risk of mental disorders, including depression, anxiety, and cognitive decline. Mental disorders can also contribute to the development of diabetes through various mechanisms including increased stress, poor self-care behaviors, and adverse effects on glucose metabolism. Consequently, individuals suffering from either of these conditions frequently experience comorbidity with the other. Nutrition plays an important role in both diabetes and mental health disorders including depression and anxiety. Deficiencies in specific nutrients such as omega-3 fatty acids, vitamin D, B vitamins, zinc, chromium, magnesium, and selenium have been implicated in the pathogenesis of both diabetes and mental disorders. While the impact of nutrition on the progression and control of diabetes and mental disorders is broadly acknowledged, there is a notable knowledge gap concerning the implications of distinct nutrients in preventing and mitigating symptoms of both conditions when they coexist. The aim of this study was to examine the role of nutrition in improving glucose homeostasis and promoting mental well-being among individuals with diabetes. Further, we evaluated the preventive or delaying effects of key nutrients on the simultaneous manifestation of these conditions when one of them is present. Our findings indicated that the use of personalized dietary interventions and targeted nutrient supplementation can improve metabolic and mental health outcomes in patients with type 2 diabetes.
Collapse
Affiliation(s)
- Raedeh Basiri
- Department of Nutrition and Food Studies, George Mason University, Fairfax, VA 22030, USA
- Institute for Biohealth Innovation, George Mason University, Fairfax, VA 22030, USA
| | - Blessing Seidu
- Department of Nutrition and Food Studies, George Mason University, Fairfax, VA 22030, USA
| | - Lawrence J. Cheskin
- Department of Nutrition and Food Studies, George Mason University, Fairfax, VA 22030, USA
- Institute for Biohealth Innovation, George Mason University, Fairfax, VA 22030, USA
- Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
| |
Collapse
|
|
4
|
Nartea R, Mitoiu BI, Ghiorghiu I. The Link between Magnesium Supplements and Statin Medication in Dyslipidemic Patients. Curr Issues Mol Biol 2023; 45:3146-3167. [PMID: 37185729 PMCID: PMC10136538 DOI: 10.3390/cimb45040205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/15/2023] [Accepted: 03/16/2023] [Indexed: 05/17/2023] Open
Abstract
Many investigations have discovered a connection between statins and magnesium supplements. On one hand, increasing research suggests that chronic hypomagnesemia may be an important factor in the etiology of some metabolic illnesses, including obesity and overweight, insulin resistance and type 2 diabetes mellitus, hypertension, alterations in lipid metabolism, and low-grade inflammation. Chronic metabolic problems seem to be prevented by a high Mg intake combined with diet and/or supplements. On the other hand, it is known that statins lower the frequency of cardiac events, stroke, and mortality, not by lowering LDL-C, but by the capacity to reduce mevalonate formation. That will enhance endothelial function, inhibit vascular smooth muscle cell proliferation and migration and encourage macrophages to promote plaque stability and regression while reducing inflammation. Taking these factors into consideration, we did an extensive analysis of the relevant literature, comparing the effects of Mg2 and statin medications on lipoproteins and, implicitly, on the key enzymes involved in cholesterol metabolism.
Collapse
Affiliation(s)
- Roxana Nartea
- Clinical Department 9, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- National Institute for Rehabilitation, Physical Medicine and Balneoclimatology, 030079 Bucharest, Romania
| | - Brindusa Ilinca Mitoiu
- Clinical Department 9, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Agrippa Ionescu Clinical Emergency Hospital, 077016 Bucharest, Romania
| | - Ioana Ghiorghiu
- Clinical Department 9, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- National Institute for Rehabilitation, Physical Medicine and Balneoclimatology, 030079 Bucharest, Romania
| |
Collapse
|
|
5
|
Oost LJ, Tack CJ, de Baaij JHF. Hypomagnesemia and Cardiovascular Risk in Type 2 Diabetes. Endocr Rev 2022; 44:357-378. [PMID: 36346820 PMCID: PMC10166267 DOI: 10.1210/endrev/bnac028] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 08/22/2022] [Accepted: 11/04/2022] [Indexed: 11/11/2022]
Abstract
Hypomagnesemia is tenfold more common in individuals with type 2 diabetes (T2D), compared to the healthy population. Factors that are involved in this high prevalence are low Mg2+ intake, gut microbiome composition, medication use and presumably genetics. Hypomagnesemia is associated with insulin resistance, which subsequently increases the risk to develop T2D or deteriorates glycaemic control in existing diabetes. Mg2+ supplementation decreases T2D associated features like dyslipidaemia and inflammation; which are important risk factors for cardiovascular disease (CVD). Epidemiological studies have shown an inverse association between serum Mg2+ and the risk to develop heart failure (HF), atrial fibrillation (AF) and microvascular disease in T2D. The potential protective effect of Mg2+ on HF and AF may be explained by reduced oxidative stress, fibrosis and electrical remodeling in the heart. In microvascular disease, Mg2+ reduces the detrimental effects of hyperglycemia and improves endothelial dysfunction. Though, clinical studies assessing the effect of long-term Mg2+ supplementation on CVD incidents are lacking and gaps remain on how Mg2+ may reduce CVD risk in T2D. Despite the high prevalence of hypomagnesemia in people with T2D, routine screening of Mg2+ deficiency to provide Mg2+ supplementation when needed is not implemented in clinical care as sufficient clinical evidence is lacking. In conclusion, hypomagnesemia is common in people with T2D and is both involved as cause, probably through molecular mechanisms leading to insulin resistance, and consequence and is prospectively associated with development of HF, AF and microvascular complications. Whether long-term supplementation of Mg2+ is beneficial, however, remains to be determined.
Collapse
Affiliation(s)
- Lynette J Oost
- Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Cees J Tack
- Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Jeroen H F de Baaij
- Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| |
Collapse
|
|
6
|
Czarniak P, Ahmadizar F, Hughes J, Parsons R, Kavousi M, Ikram M, Stricker BH. Proton pump inhibitors are associated with incident type 2 diabetes mellitus in a prospective population-based cohort study. Br J Clin Pharmacol 2021; 88:2718-2726. [PMID: 34907592 PMCID: PMC9303945 DOI: 10.1111/bcp.15182] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 10/27/2021] [Accepted: 12/02/2021] [Indexed: 12/19/2022] Open
Abstract
Aim To investigate the association between proton pump inhibitors (PPIs) and risk of incident diabetes in a follow‐up study and to investigate its potential mechanisms. Methods A total of 9531 individuals without type 2 diabetes (T2DM) at baseline were included from the Rotterdam Study, a prospective population‐based cohort of 14 926 individuals aged 45 years or older. During the study period (1 April 1997 to 1 January 2012) all incident cases of T2DM were enrolled. We used multivariable linear regression analysis to investigate the associations of baseline PPI use and various serum biomarkers (eg, serum magnesium, insulin‐like growth factor 1) which might modify the association. Thereafter, we excluded prevalent PPI users and performed a Cox proportional hazard regression analysis to explore the time‐varying effect of incident PPI use on T2DM during follow‐up. Results Baseline use of a PPI was associated with increased serum levels of fasting insulin (0.091 pmoL/L, 95% confidence interval [CI] 0.049, 0.133), homeostasis model assessment‐insulin resistance (0.100, 95% CI 0.056, 0.145) and C‐reactive protein (0.29 mg/L, 95% CI 0.198, 0.384), but decreased levels of magnesium (−0.009 mmol/L, 95% CI −0.014, −0.004) and IGF‐1 (−0.805 nmoL/L, 95% CI −1.015, −0.595). After adjustment for risk factors such as physical activity and body mass index/waist‐to‐hip ratio, current use of PPI was associated with an increased risk of incident T2DM (hazard ratio [HR] 1.69, 95% CI 1.36‐2.10). The effect was dose‐dependent with the highest risk (HR 1.88, 95% CI 1.29‐2.75) in those on more than one defined daily dose. Conclusion New users of PPIs during follow‐up had a significantly higher dose‐dependent risk of incident diabetes. We suggest vigilance regarding their potential adverse effect on glucose homeostasis.
Collapse
Affiliation(s)
- Petra Czarniak
- Curtin Medical School, Curtin University, Perth, Western Australia, Australia
| | - Fariba Ahmadizar
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Jeff Hughes
- Curtin Medical School, Curtin University, Perth, Western Australia, Australia
| | - Richard Parsons
- Curtin Medical School, Curtin University, Perth, Western Australia, Australia
| | - Maryam Kavousi
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Mohammad Ikram
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Bruno H Stricker
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
| |
Collapse
|
|
7
|
Magnesium in Aging, Health and Diseases. Nutrients 2021; 13:nu13020463. [PMID: 33573164 PMCID: PMC7912123 DOI: 10.3390/nu13020463] [Citation(s) in RCA: 136] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/26/2021] [Accepted: 01/28/2021] [Indexed: 12/15/2022] Open
Abstract
Several changes of magnesium (Mg) metabolism have been reported with aging, including diminished Mg intake, impaired intestinal Mg absorption and renal Mg wasting. Mild Mg deficits are generally asymptomatic and clinical signs are usually non-specific or absent. Asthenia, sleep disorders, hyperemotionality, and cognitive disorders are common in the elderly with mild Mg deficit, and may be often confused with age-related symptoms. Chronic Mg deficits increase the production of free radicals which have been implicated in the development of several chronic age-related disorders. Numerous human diseases have been associated with Mg deficits, including cardiovascular diseases, hypertension and stroke, cardio-metabolic syndrome and type 2 diabetes mellitus, airways constrictive syndromes and asthma, depression, stress-related conditions and psychiatric disorders, Alzheimer's disease (AD) and other dementia syndromes, muscular diseases (muscle pain, chronic fatigue, and fibromyalgia), bone fragility, and cancer. Dietary Mg and/or Mg consumed in drinking water (generally more bioavailable than Mg contained in food) or in alternative Mg supplements should be taken into consideration in the correction of Mg deficits. Maintaining an optimal Mg balance all through life may help in the prevention of oxidative stress and chronic conditions associated with aging. This needs to be demonstrated by future studies.
Collapse
|
|
8
|
Dominguez LJ, Veronese N, Barbagallo M. Magnesium and Hypertension in Old Age. Nutrients 2020; 13:E139. [PMID: 33396570 PMCID: PMC7823889 DOI: 10.3390/nu13010139] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 12/27/2020] [Accepted: 12/29/2020] [Indexed: 12/15/2022] Open
Abstract
Hypertension is a complex condition in which various actors and mechanisms combine, resulting in cardiovascular and cerebrovascular complications that today represent the most frequent causes of mortality, morbidity, disability, and health expenses worldwide. In recent decades, there has been an exceptional number of experimental, epidemiological, and clinical studies confirming a close relationship between magnesium deficit and high blood pressure. Multiple mechanisms may help to explain the bulk of evidence supporting a protective effect of magnesium against hypertension and its complications. Hypertension increases sharply with advancing age, hence older persons are those most affected by its negative consequences. They are also more frequently at risk of magnesium deficiency by multiple mechanisms, which may, at least in part, explain the higher frequency of hypertension and its long-term complications. The evidence for a favorable effect of magnesium on hypertension risk emphasizes the importance of broadly encouraging the intake of foods such as vegetables, nuts, whole cereals and legumes, optimal dietary sources of magnesium, and avoiding processed foods, which are very poor in magnesium and other fundamental nutrients, in order to prevent hypertension. In some cases, when diet is not enough to maintain an adequate magnesium status, magnesium supplementation may be of benefit and has been shown to be well tolerated.
Collapse
Affiliation(s)
| | | | - Mario Barbagallo
- Geriatric Unit, Department of Medicine, University of Palermo, 90100 Palermo, Italy; (L.J.D.); (N.V.)
| |
Collapse
|
|
9
|
Zimorovat A, Mohammadi M, Ramezani-Jolfaie N, Salehi-Abargouei A. The healthy Nordic diet for blood glucose control: a systematic review and meta-analysis of randomized controlled clinical trials. Acta Diabetol 2020; 57:1-12. [PMID: 31172295 DOI: 10.1007/s00592-019-01369-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 05/14/2019] [Indexed: 12/14/2022]
Abstract
AIMS Investigations on the possible effect of the Nordic diet (ND) on the glycemic control and the risk of diabetes have led to inconsistent results. The present study tried to determine the effect of the ND on the markers of blood glucose control using a systematic review and meta-analysis of randomized controlled clinical trials (RCTs). METHODS Predefined keywords were used to search PubMed, ISI Web of Science, Scopus and Google Scholar up to April 2019. The random effects model was used to compute the overall estimates. RESULTS In total, six RCTs with 618 participants (6-26 weeks of follow-up period) were included in the present study. The meta-analysis revealed that the ND might not have a considerable effect on fasting blood glucose levels [weighted mean difference (WMD) = -0.05 mmol/l, 95% CI - 0.13, 0.01, P = 0.112]. In contrast, the analyses showed that the ND significantly reduces serum insulin concentrations (WMD = -1.12 mU/l, 95% CI - 1.84, - 0.39, P = 0.002) and the homeostasis model assessment for insulin resistance (HOMA-IR) (WMD = - 0.34, 95% CI - 0.53, - 0.14, P = 0.001) compared to control diets. The effect on serum insulin levels was sensitive to one of the included studies. This dietary pattern did not significantly affect 2-h post-prandial blood glucose and Matsuda index. CONCLUSIONS Adherence to the ND might improve serum insulin and HOMA-IR levels; however, this effect was not confirmed for other markers of blood glucose control. Future well-designed and long-term clinical trials are highly recommended.
Collapse
Affiliation(s)
- Alireza Zimorovat
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohammad Mohammadi
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nahid Ramezani-Jolfaie
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Amin Salehi-Abargouei
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
| |
Collapse
|
|
10
|
Brey CW, Akbari-Alavijeh S, Ling J, Sheagley J, Shaikh B, Al-Mohanna F, Wang Y, Gaugler R, Hashmi S. Salts and energy balance: A special role for dietary salts in metabolic syndrome. Clin Nutr 2018; 38:1971-1985. [PMID: 30446179 DOI: 10.1016/j.clnu.2018.10.021] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Revised: 10/20/2018] [Accepted: 10/28/2018] [Indexed: 01/01/2023]
Abstract
BACKGROUND Dietary salts sodium (Na+), potassium (K+), magnesium (Mg2+), and calcium (Ca2+) are important in metabolic diseases. Yet, we do not have sufficient understanding on the salts global molecular network in these diseases. In this systematic review we have pooled information to identify the general effect of salts on obesity, insulin resistance and hypertension. AIMS To assess the roles of salts in metabolic disorders by focusing on their individual effect and the network effect among these salts. METHODS We searched articles in PubMed, EMBASE and Google Scholar. We selected original laboratory research, systematic reviews, clinical trials, observational studies and epidemiological data that focused on dietary salts and followed the preferred reporting items for systematic review in designing the present systematic review. RESULTS From the initial search of 2898 studies we selected a total of 199 articles that met our inclusion criteria and data extraction. Alterations in metabolic pathways associated with the sensitivity of sodium, potassium, magnesium and calcium may lead to obesity, hypertension, and insulin resistance. We found that the results of most laboratory research, animal studies and clinical trials are coherent but some research outcome are either inconsistent or inconclusive. CONCLUSION Important of salts in metabolic disorder is evident. In order to assess the effects of dietary salts in metablic diseases, environmental factors, dietary habits, physical activity, and the microbiome, should be considered in any study. Although interest in this area of research continues to grow, the challenge is to integrate the action of these salts in metabolic syndrom.
Collapse
Affiliation(s)
| | - Safoura Akbari-Alavijeh
- Laboratory of Developmental Biology, Center for Vector Biology, Rutgers University, 180 Jones Avenue, New Brunswick, NJ, 08901, USA
| | - Jun Ling
- Department of Basic Sciences, Geisinger Commonwealth School of Medicine, 525 Pine Street, Scranton, PA, 18509, USA
| | - Jordan Sheagley
- Department of Basic Sciences, Geisinger Commonwealth School of Medicine, 525 Pine Street, Scranton, PA, 18509, USA
| | - Bilal Shaikh
- Laboratory of Developmental Biology, Center for Vector Biology, Rutgers University, 180 Jones Avenue, New Brunswick, NJ, 08901, USA
| | | | - Yi Wang
- Laboratory of Developmental Biology, Center for Vector Biology, Rutgers University, 180 Jones Avenue, New Brunswick, NJ, 08901, USA
| | - Randy Gaugler
- Laboratory of Developmental Biology, Center for Vector Biology, Rutgers University, 180 Jones Avenue, New Brunswick, NJ, 08901, USA
| | - Sarwar Hashmi
- Laboratory of Developmental Biology, Center for Vector Biology, Rutgers University, 180 Jones Avenue, New Brunswick, NJ, 08901, USA; Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, & Health, Rutgers University, USA.
| |
Collapse
|
|
11
|
Magnesium upregulates insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide-induced type-2 diabetic rats. Endocr Regul 2018; 52:6-16. [DOI: 10.2478/enr-2018-0002] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Abstract
Objective. We investigated the effects of magnesium supplementation on glucose tolerance, insulin sensitivity, oxidative stress as well as the concentration of insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide induced type-2 diabetic (T2D) rats. Methods. Rats were divided into four groups designated as: 1) control (CTR); 2) diabetic untreated (DU); 3) diabetic treated with 1 mg of Mg/kg diet (Mg1-D); and 4) diabetic treated with 2 mg of Mg/kg diet (Mg2-D). T2D was induced with a single intraperitoneal (i.p.) injection of freshly prepared streptozotocin (55 mg/kg) aft er an initial i.p. injection of nicotinamide (120 mg/kg). Glucose tolerance, insulin sensitivity, lipid profile, malondialdehyde (MAD) and glutathione content, insulin receptors (INSR) and glucose transporter-4 (GLUT4), fasting insulin and glucose levels were measured, and insulin resistance index was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR). Results. Magnesium supplementation improved glucose tolerance and lowered blood glucose levels almost to the normal range. We also recorded a noticeable increase in insulin sensitivity in Mg-D groups when compared with DU rats. Lipid perturbations associated T2D were significantly attenuated by magnesium supplementation. Fasting glucose level was comparable to control values in the Mg-D groups while the HOMA-IR index was significantly lower compared with the DU rats. Magnesium reduced MDA but increased glutathione concentrations compared with DU group. Moreover, INSR and GLUT4 levels were elevated following magnesium supplementation in T2D rats. Conclusion. These findings demonstrate that magnesium may mediate effective metabolic control by stimulating the antioxidant defense, and increased levels of INSR and GLUT4 in diabetic rats.
Collapse
|
|
12
|
Akter S, Eguchi M, Nanri A, Kochi T, Kashino I, Kuwahara K, Hu H, Miki T, Kabe I, Mizoue T. Association of dietary and serum magnesium with glucose metabolism markers: The Furukawa Nutrition and Health Study. Clin Nutr ESPEN 2018; 24:71-77. [PMID: 29576367 DOI: 10.1016/j.clnesp.2018.01.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 01/17/2018] [Indexed: 01/06/2023]
Abstract
BACKGROUND & AIMS Magnesium may play an important role in cardio-metabolic abnormalities, including type 2 diabetes, but epidemiological evidence linking magnesium status to glucose metabolism is limited among Asians. We cross-sectionally examined the association of dietary and serum magnesium with markers of glucose metabolism among Japanese subjects. METHODS Subjects were 1796 workers, aged 18-78 years, who participated in a health survey. Dietary magnesium intake was assessed with a validated brief diet history questionnaire. Serum magnesium concentrations were measured using an enzymatic method. Multivariable linear regression models were used to estimate means of fasting insulin, fasting plasma glucose, homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of β-cell function (HOMA-β), and glycated hemoglobin (HbA1c), with adjustments made for potential confounding variables. RESULTS Dietary magnesium was inversely associated with HOMA-IR (Ptrend = 0.01). Multivariable-adjusted means (95% confidence intervals) of HOMA-IR for the lowest to highest quartiles of dietary magnesium were 0.94 (0.89-0.99), 0.92 (0.88-0.97), 0.88 (0.83-0.92), and 0.86 (0.81-0.90). Serum magnesium concentrations were also inversely associated with HOMA-IR (Ptrend = 0.04) and HbA1c (Ptrend <0.01). Multivariable-adjusted means (95% confidence intervals) for the lowest to highest quartiles of serum magnesium were 0.94 (0.90-0.98), 0.87 (0.83-0.91), 0.90 (0.85-0.95), and 0.86 (0.81-0.92) for HOMA-IR and 5.41 (5.36-5.45), 5.33 (5.28-5.37), 5.30 (5.25-5.36), and 5.28 (5.22-5.35) for HbA1c. Excluding subjects with diabetes did not materially change the association between dietary magnesium and HOMA-IR (Ptrend <0.01), while it attenuated the association of serum magnesium with HOMA-IR (Ptrend = 0.27) and HbA1c (Ptrend = 0.15). CONCLUSIONS The present findings suggest that lower dietary magnesium, but not serum magnesium, is associated with IR in apparently healthy adults.
Collapse
Affiliation(s)
- Shamima Akter
- Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.
| | - Masafumi Eguchi
- Department of Health Administration, Furukawa Electric Corporation, Tokyo, Japan
| | - Akiko Nanri
- Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan; Department of Food and Health Sciences, Fukuoka Women's University, Fukuoka, Japan
| | - Takeshi Kochi
- Department of Health Administration, Furukawa Electric Corporation, Tokyo, Japan
| | - Ikuko Kashino
- Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
| | - Keisuke Kuwahara
- Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan; Teikyo University Graduate School of Public Health, Tokyo, Japan
| | - Huanhuan Hu
- Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
| | - Takako Miki
- Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan; Department of Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Isamu Kabe
- Department of Health Administration, Furukawa Electric Corporation, Tokyo, Japan
| | - Tetsuya Mizoue
- Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
| |
Collapse
|
|
13
|
Verma P, Srivastava RK, Jain D. Association of Lifestyle Risk Factors with Metabolic Syndrome Components: A Cross-sectional Study in Eastern India. Int J Prev Med 2018; 9:6. [PMID: 29441183 PMCID: PMC5801597 DOI: 10.4103/ijpvm.ijpvm_236_17] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2017] [Accepted: 01/05/2018] [Indexed: 12/20/2022] Open
Abstract
Background Approximately 20%-25% of the world adult population and nearly 30% of Indians have metabolic syndrome disorder. Our objective was designed to find out the association between important nutrients and potential lifestyle risk factors such as diet, physical inactivity, and smoking and alcohol consumption with the number of metabolic syndrome components. Methods This was a cross-sectional study. A total of 205 patients of metabolic syndrome were enrolled for this study. Diagnosis of metabolic syndrome was done on the basis of National Cholesterol Education Program Adult Treatment Panel III criteria (NCEP ATP III 2004). Dietary data were collected with the validated food frequency questionnaire and 24 h dietary recall method, and the nutrient intake was calculated with the specially designed software. Results Unhealthy dietary habits were seen more among the participants who had more than 3 risk factors. Results showed the odds of taking >5 times junk foods was 3 times higher (odds ratio [OR]: 2.97; 95% confidence interval [CI]: 1.61-5.47), and sweet dishes was 2.3 times higher (OR: 2.33; 95% CI: 1.28-4.24) among the participants who had 4-5 risk factors. However, milk and dairy products > 4 servings/day (OR: 0.54; 95% CI: 0.175-1.67) and pulses and legumes more than 2 servings/day (OR: 0.57; 95% CI: 0.25-1.29) was protective against hypertension. Mean carbohydrate, saturated fat, and sodium intake was significantly higher in the participants who had 4-5 metabolic risk factors compared to 3 risk factors (P < 0.0001). Conclusions It was concluded that low intake of fruits, vegetables, and higher intake of flesh food and inadequate physical activity significantly associated with the metabolic syndrome risk factors.
Collapse
Affiliation(s)
- Pragya Verma
- Department of Community Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Ratan K Srivastava
- Department of Community Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Dharmendra Jain
- Department of Cardiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| |
Collapse
|
|
14
|
Barbagallo M, Dominguez LJ. Magnesium Role in Health and Longevity. TRACE ELEMENTS AND MINERALS IN HEALTH AND LONGEVITY 2018:235-264. [DOI: 10.1007/978-3-030-03742-0_9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
|
|
15
|
Abstract
Gallstone disease is one of the most common public health problems in the United States. Approximately 10%-20% of the national adult populations currently carry gallstones, and gallstone prevalence is rising. In addition, nearly 750,000 cholecystectomies are performed annually in the United States; direct and indirect costs of gallbladder surgery are estimated to be $6.5 billion. Cholelithiasis is also strongly associated with gallbladder, pancreatic, and colorectal cancer occurrence. Moreover, the National Institutes of Health estimates that almost 3,000 deaths (0.12% of all deaths) per year are attributed to complications of cholelithiasis and gallbladder disease. Although extensive research has tried to identify risk factors for cholelithiasis, several studies indicate that definitive findings still remain elusive. In this review, predisposing factors for cholelithiasis are identified, the pathophysiology of gallstone disease is described, and nonsurgical preventive options are discussed. Understanding the risk factors for cholelithiasis may not only be useful in assisting nurses to provide resources and education for patients who are diagnosed with gallstones, but also in developing novel preventive measures for the disease.
Collapse
|
|
16
|
Kim Y, Keogh JB, Clifton PM. Consumption of red and processed meat and refined grains for 4weeks decreases insulin sensitivity in insulin-resistant adults: A randomized crossover study. Metabolism 2017; 68:173-183. [PMID: 28183449 DOI: 10.1016/j.metabol.2016.12.011] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Revised: 10/12/2016] [Accepted: 12/19/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Red and processed meat and refined grains are associated with an increased risk of type 2 diabetes. Interventions are limited. We hypothesized that a diet high in red and processed meat and refined grains (HMD) would decrease insulin sensitivity compared to a diet high in whole grains, nuts, dairy and legumes with no red meat (HWD). METHODS Forty-nine subjects without diabetes [15 men and 34 women, age, 35.6±15.7 years, body mass index (BMI), 27±5.9kg/m2] underwent two 4-week weight-stable dietary interventions in a randomized crossover design. The insulin sensitivity index (ISI) was calculated from the last 30min of a continuous low-dose insulin (25mU/kg·h) and glucose (4mg/kg·min) infusion test (LDIGIT 120-150min) at the end of each diet. RESULTS The population fell into two very discrete groups: those with a very low insulin response in the LDIGIT 120-150min on HMD (Group 1<56pmol/L, n=24), and those with relatively normal insulin responses (Group 2>56pmol/L, n=25). Group 2 had significantly higher insulin concentrations [(median and interquartile range) 153, 180 for HMD vs. 123, 149pmol/L for HWD; P=0.019] and glucose concentrations [(mean±standard deviation) 7.4±1.3 for HMD vs.6.7±1.2mmol/L for HWD; P=0.05], resulting in a significantly decreased ISI [(median and interquartile range) 21.1, 34.2 for HMD vs. 31.6, 39.4 for HWD; P=0.014] compared to HWD. Log ISI after HMD was significantly correlated with BMI (r=-0.5; P=0.009), fat mass (r=-0.55; P=0.004) and self-reported activity levels (r=-0.45; P=0.024). CONCLUSIONS A dietary pattern high in red and processed meat and refined grains decreased insulin sensitivity compared to a dietary pattern high in whole grains, nuts, dairy products and legumes only in relatively insulin-resistant adults.
Collapse
Affiliation(s)
- Yoona Kim
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
| | - Jennifer B Keogh
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
| | - Peter M Clifton
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
| |
Collapse
|
|
17
|
Upala S, Jaruvongvanich V, Wijarnpreecha K, Sanguankeo A. Hypomagnesemia and mortality in patients admitted to intensive care unit: a systematic review and meta-analysis. QJM 2016; 109:453-459. [PMID: 27016536 DOI: 10.1093/qjmed/hcw048] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Reports of mortality due to magnesium dysregulation in the critical care setting are controversial. We performed a systematic review and meta-analysis to evaluate the association between hypomagnesemia and mortality in patients admitted to the intensive care unit. METHODS Eligible studies assessing the association between hypomagnesemia or hypermagnesemia and mortality in the critical care setting were comprehensively searched in MEDLINE and EMBASE from their inception to September 2015. Inclusion criteria were published observational studies in adults who were admitted to the intensive or critical care setting with initial serum magnesium measurement. We used the definition of abnormal magnesium level defined by each study. Primary outcome was all-cause mortality. We performed meta-analysis using random-effects model and calculated pooled effect estimate of outcome comparing between hypomagnesemia and normal magnesium category. RESULTS From 30 full-text articles, 6 studies involving 1550 participants were included in the meta-analysis. There was a statistically significant higher risk of mortality in critically ill patients who had hypomagnesemia with RR of 1.90 (95% CI: 1.48-2.44, P < 0.001, I(2 )=( )63.5%). Risk for needing mechanical ventilation was also higher in the hypomagnesemia group with RR of 1.65 (95% CI: 1.12-2.43, P = 0.01, I(2 )=( )84%). Length of ICU stay was also higher in the hypomagnesemia group with mean difference of 4.1 days (95% CI: 1.16-7.04, P = 0.01). CONCLUSION The findings of this meta-analysis indicate hypomagnesemia is associated with higher mortality, the need of mechanical ventilation and also the length of ICU stay in patients admitted to ICU.
Collapse
Affiliation(s)
- Sikarin Upala
- From the 1 Department of Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY, USA
- Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | | | - Karn Wijarnpreecha
- From the 1Department of Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY, USA
| | - Anawin Sanguankeo
- From the 1 Department of Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY, USA
- Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| |
Collapse
|
|
18
|
Moghadam SK, Bahadoran Z, Mirmiran P, Tohidi M, Azizi F. Association between Dietary Acid Load and Insulin Resistance: Tehran Lipid and Glucose Study. Prev Nutr Food Sci 2016; 21:104-9. [PMID: 27390726 PMCID: PMC4935236 DOI: 10.3746/pnf.2016.21.2.104] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Accepted: 04/20/2016] [Indexed: 11/28/2022] Open
Abstract
In the current study, we investigated the longitudinal association between dietary acid load and the risk of insulin resistance (IR) in the Tehranian adult population. This longitudinal study was conducted on 925 participants, aged 22~80 years old, in the framework of the third (2006~2008) and fourth (2009~2011) phases of the Tehran Lipid and Glucose Study. At baseline, the dietary intake of subjects was assessed using a validated semi-quantitative food frequency questionnaire, and the potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores were calculated at baseline. Fasting serum insulin and glucose were measured at baseline and again after a 3-year of follow-up; IR was defined according to optimal cut-off values. Multiple logistic regression models were used to estimate the risk of IR according to the PRAL and NEAP quartile categories. Mean age and body mass index of the participants were 40.3 years old of 26.4 kg/m2, respectively. Mean PRAL and NEAP scores were −11.2 and 35.6 mEq/d, respectively. After adjustment for potential confounders, compared to the lowest quartile of PRAL and NEAP, the highest quartile was accompanied with increased risk of IR [odds ratio (OR)=2.81, 95% confidence interval (CI)=1.32~5.97 and OR=2.18, 95% CI=1.03 ~4.61, respectively]. Our findings suggest that higher acidic dietary acid-base load, defined by higher PRAL and NEAP scores, may be a risk factor for the development of IR and related metabolic disorders.
Collapse
Affiliation(s)
- Sajjad Khalili Moghadam
- Students' Research Committee, Shahid Beheshti University of Medical Sciences, Tehran 19395-4763, Iran; Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19395-4763, Iran
| | - Zahra Bahadoran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19395-4763, Iran
| | - Parvin Mirmiran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19395-4763, Iran
| | - Maryam Tohidi
- Prevention of Metabolic Disorder Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19395-4763, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19395-4763, Iran
| |
Collapse
|
|
19
|
Abstract
Over the past decades, hypomagnesemia (serum Mg(2+) <0.7 mmol/L) has been strongly associated with type 2 diabetes mellitus (T2DM). Patients with hypomagnesemia show a more rapid disease progression and have an increased risk for diabetes complications. Clinical studies demonstrate that T2DM patients with hypomagnesemia have reduced pancreatic β-cell activity and are more insulin resistant. Moreover, dietary Mg(2+) supplementation for patients with T2DM improves glucose metabolism and insulin sensitivity. Intracellular Mg(2+) regulates glucokinase, KATP channels, and L-type Ca(2+) channels in pancreatic β-cells, preceding insulin secretion. Moreover, insulin receptor autophosphorylation is dependent on intracellular Mg(2+) concentrations, making Mg(2+) a direct factor in the development of insulin resistance. Conversely, insulin is an important regulator of Mg(2+) homeostasis. In the kidney, insulin activates the renal Mg(2+) channel transient receptor potential melastatin type 6 that determines the final urinary Mg(2+) excretion. Consequently, patients with T2DM and hypomagnesemia enter a vicious circle in which hypomagnesemia causes insulin resistance and insulin resistance reduces serum Mg(2+) concentrations. This Perspective provides a systematic overview of the molecular mechanisms underlying the effects of Mg(2+) on insulin secretion and insulin signaling. In addition to providing a review of current knowledge, we provide novel directions for future research and identify previously neglected contributors to hypomagnesemia in T2DM.
Collapse
Affiliation(s)
- Lisanne M M Gommers
- Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
| | - Joost G J Hoenderop
- Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
| | - René J M Bindels
- Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
| | - Jeroen H F de Baaij
- Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, U.K.
| |
Collapse
|
|
20
|
Barbagallo M, Dominguez LJ. Magnesium and type 2 diabetes. World J Diabetes 2015; 6:1152-1157. [PMID: 26322160 PMCID: PMC4549665 DOI: 10.4239/wjd.v6.i10.1152] [Citation(s) in RCA: 126] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Revised: 06/29/2015] [Accepted: 08/17/2015] [Indexed: 02/05/2023] Open
Abstract
Type 2 diabetes is frequently associated with both extracellular and intracellular magnesium (Mg) deficits. A chronic latent Mg deficit or an overt clinical hypomagnesemia is common in patients with type 2 diabetes, especially in those with poorly controlled glycemic profiles. Insulin and glucose are important regulators of Mg metabolism. Intracellular Mg plays a key role in regulating insulin action, insulin-mediated-glucose-uptake and vascular tone. Reduced intracellular Mg concentrations result in a defective tyrosine-kinase activity, postreceptorial impairment in insulin action and worsening of insulin resistance in diabetic patients. A low Mg intake and an increased Mg urinary loss appear the most important mechanisms that may favor Mg depletion in patients with type 2 diabetes. Low dietary Mg intake has been related to the development of type 2 diabetes and metabolic syndrome. Benefits of Mg supplementation on metabolic profiles in diabetic patients have been found in most, but not all clinical studies and larger prospective studies are needed to support the potential role of dietary Mg supplementation as a possible public health strategy in diabetes risk. The aim of this review is to revise current evidence on the mechanisms of Mg deficiency in diabetes and on the possible role of Mg supplementation in the prevention and management of the disease.
Collapse
|
|
21
|
Variation in macro and trace elements in progression of type 2 diabetes. ScientificWorldJournal 2014; 2014:461591. [PMID: 25162051 PMCID: PMC4138889 DOI: 10.1155/2014/461591] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Accepted: 06/30/2014] [Indexed: 12/12/2022] Open
Abstract
Macro elements are the minerals of which the body needs more amounts and are more important than any other elements. Trace elements constitute a minute part of the living tissues and have various metabolic characteristics and functions. Trace elements participate in tissue and cellular and subcellular functions; these include immune regulation by humoral and cellular mechanisms, nerve conduction, muscle contractions, membrane potential regulations, and mitochondrial activity and enzyme reactions. The status of micronutrients such as iron and vanadium is higher in type 2 diabetes. The calcium, magnesium, sodium, chromium, cobalt, iodine, iron, selenium, manganese, and zinc seem to be low in type 2 diabetes while elements such as potassium and copper have no effect. In this review, we emphasized the status of macro and trace elements in type 2 diabetes and its advantages or disadvantages; this helps to understand the mechanism, progression, and prevention of type 2 diabetes due to the lack and deficiency of different macro and trace elements.
Collapse
|
|
22
|
Telfer SJ. Fluoroquinolone antibiotics and type 2 diabetes mellitus. Med Hypotheses 2014; 83:263-9. [PMID: 24947193 DOI: 10.1016/j.mehy.2014.05.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2013] [Accepted: 05/21/2014] [Indexed: 10/25/2022]
Abstract
Exposure to fluoroquinolone antibiotics is postulated as a risk factor for subsequent development of type 2 diabetes. It is hypothesized that fluoroquinolones induce an intracellular magnesium deficit that can lead to insulin resistance. A temporal correlation is reported between the rate of outpatient prescription of quinolones and the incidence of diabetes during the period 1980-2011 with a lag of approximately two years (R(2)=0.86, P<10(-9)). The increase in incidence of diabetes after 1990 and the recent decrease in the number of new cases are both reflected in the fluoroquinolone prescription rates. A geographical correlation is reported (adj. R(2)=0.7, P<0.0001) between rates of increase in prevalence of diabetes in each U.S. state and a model using only local rates of outpatient fluoroquinolone prescription, local rates of increase in the prevalence of obesity, and local rates of population growth as predictor variables. Prescription rates of non-quinolone antibiotics correlated less well with the local rates of increase in prevalence of diabetes. The data are consistent with fluoroquinolone exposure predisposing an individual to develop diabetes with a probability that strongly depends upon factors that also lead to an increase in obesity. According to the hypothesis, much of the increase in the incidence of type 2 diabetes in the U.S. from 1990 to the present can be attributed to fluoroquinolone exposure.
Collapse
Affiliation(s)
- Stephen J Telfer
- E Ink Corporation, 1000 Technology Park Drive, Billerica, MA 01821, USA.
| |
Collapse
|
|
23
|
Jindal V. Neurodegeneration as a primary change and role of neuroprotection in diabetic retinopathy. Mol Neurobiol 2014; 51:878-84. [PMID: 24826918 DOI: 10.1007/s12035-014-8732-7] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2014] [Accepted: 04/29/2014] [Indexed: 02/06/2023]
Abstract
Diabetic retinopathy (DR) was earlier recognized as a vascular disease, but nowadays, it is considered as a neurovascular disorder. Neuronal death is the primary change which leads to various vascular changes which are visible to an ophthalmologist. But these changes are feature of an advanced disease and can affect vision at any moment of time. There are various evidences which suggests that glutamate excitotoxicity, hyperhomocysteinemia, kynurenic acid, and erythro-poietin plays important role in causation of retinal ganglionic cell apoptosis in diabetic patients. Adaptive optics, a new imaging technique, also showed that loss of photoreceptors (specialized neurons) is the early change in diabetic retinopathy. These changes suggest DR as a neurovascular disorder. Neuroprotective agents also showed good results in delaying progression of DR especially memantine, insulin receptor activation, and neurotrophic factors. More research in this field will help us to find novel therapeutic measures for DR, which can delay or even stop progression of DR at a very early stage.
Collapse
Affiliation(s)
- Vishal Jindal
- , H. No. 102 GHS 51 sector 20, Panchkula, Haryana, India,
| |
Collapse
|
|
24
|
Hruby A, Meigs JB, O'Donnell CJ, Jacques PF, McKeown NM. Higher magnesium intake reduces risk of impaired glucose and insulin metabolism and progression from prediabetes to diabetes in middle-aged americans. Diabetes Care 2014; 37:419-27. [PMID: 24089547 PMCID: PMC3898748 DOI: 10.2337/dc13-1397] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To assess 7-year associations between magnesium intake and incident prediabetes and/or insulin resistance (IR), and progression from these states to type 2 diabetes. RESEARCH DESIGN AND METHODS In 2,582 community-dwelling participants 26-81 years old at baseline, magnesium intake and risk of incident "metabolic impairment," defined as impaired fasting glucose (FG) (≥5.6 to <7.0 mmol/L), impaired glucose tolerance (2-h postload glucose ≥7.8 to <11.1 mmol/L), IR, or hyperinsulinemia (≥90th percentile of homeostasis model assessment of IR or fasting insulin, respectively), was estimated among those with normal baseline status, and risk of incident diabetes was estimated among those with baseline metabolic impairment. In participants without incident diabetes, we examined magnesium intake in relation to 7-year changes in fasting and postload glucose and insulin, IR, and insulin sensitivity. RESULTS After adjusting for age, sex, and energy intake, compared with those with the lowest magnesium intake, those with the highest intake had 37% lower risk of incident metabolic impairment (P trend = 0.02), and in those with baseline metabolic impairment, higher intake was associated with 32% lower risk of incident diabetes (P trend = 0.05). In the combined population, the risk in those with the highest intake was 53% (P trend = 0.0004) of those with the lowest intake. Adjusting for risk factors and dietary fiber attenuated associations in the baseline normal population but did not substantially affect associations in the metabolically impaired. Higher magnesium intake tended to associate with lower follow-up FG and IR, but not fasting insulin, postload values, or insulin sensitivity. CONCLUSIONS Magnesium intake may be particularly beneficial in offsetting risk of developing diabetes among those at high risk. Magnesium's long-term associations with non-steady-state (dynamic) measures deserve further research.
Collapse
|
|
25
|
Hruby A, McKeown NM, Song Y, Djoussé L. Dietary magnesium and genetic interactions in diabetes and related risk factors: a brief overview of current knowledge. Nutrients 2013; 5:4990-5011. [PMID: 24322525 PMCID: PMC3875916 DOI: 10.3390/nu5124990] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Revised: 11/18/2013] [Accepted: 11/27/2013] [Indexed: 12/15/2022] Open
Abstract
Nutritional genomics has exploded in the last decade, yielding insights—both nutrigenomic and nutrigenetic—into the physiology of dietary interactions and our genes. Among these are insights into the regulation of magnesium transport and homeostasis and mechanisms underlying magnesium’s role in insulin and glucose handling. Recent observational evidence has attempted to examine some promising research avenues on interaction between genetics and dietary magnesium in relation to diabetes and diabetes risk factors. This brief review summarizes the recent evidence on dietary magnesium’s role in diabetes and related traits in the presence of underlying genetic risk, and discusses future potential research directions.
Collapse
Affiliation(s)
- Adela Hruby
- Department of Nutrition, Harvard School of Public Health, 677 Huntington Avenue, Building 2, Boston, MA 02115, USA; E-Mail:
| | - Nicola M. McKeown
- Nutritional Epidemiology Program, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, 9th Floor, Boston, MA 02111, USA; E-Mail:
| | - Yiqing Song
- Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, 714 N. Senate Avenue, Indianapolis, IN 46202, USA; E-Mail:
| | - Luc Djoussé
- Division of Aging, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 1620 Tremont Street, 3rd Floor, Boston, MA 02120, USA
- Boston Veterans Affairs Healthcare System, Boston, MA 02130, USA
- Author to whom correspondence should be addressed; E-Mail: ; Tel.: +1-617-525-7591; Fax: +1-617-525-7739
| |
Collapse
|
|
26
|
Promotion and selection by serum growth factors drive field cancerization, which is anticipated in vivo by type 2 diabetes and obesity. Proc Natl Acad Sci U S A 2013; 110:13927-31. [PMID: 23908399 DOI: 10.1073/pnas.1312831110] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Individuals suffering from type 2 diabetes or obesity exhibit a significant increase in the incidence of various types of cancer. It is generally accepted that those conditions arise from overnutrition and a sedentary lifestyle, which lead to insulin resistance characterized by overproduction of insulin acting as a growth factor. There is a consensus based largely on epidemiological data that chronic overproduction of insulin is responsible for the increased incidence of cancer. A model system in culture of NIH 3T3 cells induces the collective effects of serum growth factors on progression through the stages of field cancerization. It shows that the driving force of progression is promotion of cell growth under selection at high cell density, with no requirement for exogenous carcinogenic agents. The early effect is gradual selection among many preexisting, low-penetrance preneoplastic mutations or stable epigenetic variants, followed by sporadic, high-penetrance transforming variants, all dependent on endogenous processes. The significance of the results for cancer in diabetic and obese individuals is that the initial stages of the process involve multiorgan metabolic interactions that produce a systemic insulin resistance with chronic overproduction of insulin and localized field cancerization. Hypomagnesemia is prevalent in the foregoing metabalo/systemic disorders, and may also provide a selective microenvironment for tumor development.
Collapse
|
|
27
|
Hruby A, Ngwa JS, Renström F, Wojczynski MK, Ganna A, Hallmans G, Houston DK, Jacques PF, Kanoni S, Lehtimäki T, Lemaitre RN, Manichaikul A, North KE, Ntalla I, Sonestedt E, Tanaka T, van Rooij FJA, Bandinelli S, Djoussé L, Grigoriou E, Johansson I, Lohman KK, Pankow JS, Raitakari OT, Riserus U, Yannakoulia M, Zillikens MC, Hassanali N, Liu Y, Mozaffarian D, Papoutsakis C, Syvänen AC, Uitterlinden AG, Viikari J, Groves CJ, Hofman A, Lind L, McCarthy MI, Mikkilä V, Mukamal K, Franco OH, Borecki IB, Cupples LA, Dedoussis GV, Ferrucci L, Hu FB, Ingelsson E, Kähönen M, Kao WHL, Kritchevsky SB, Orho-Melander M, Prokopenko I, Rotter JI, Siscovick DS, Witteman JCM, Franks PW, Meigs JB, McKeown NM, Nettleton JA. Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 CHARGE Consortium Studies. J Nutr 2013; 143:345-53. [PMID: 23343670 PMCID: PMC3713023 DOI: 10.3945/jn.112.172049] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = -0.009 mmol/L (95% CI: -0.013, -0.005), P < 0.0001] and insulin [-0.020 ln-pmol/L (95% CI: -0.024, -0.017), P < 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted.
Collapse
Affiliation(s)
- Adela Hruby
- Tufts University Friedman School of Nutrition Science and Policy, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA
| | - Julius S. Ngwa
- Department of Biostatistics, Boston University School of Public Health, Boston, MA
| | - Frida Renström
- Department of Nutrition, Harvard School of Public Health, Boston, MA,Department of Clinical Sciences, Lund University, Malmö, Sweden,Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Mary K. Wojczynski
- Department of Genetics, Washington University School of Medicine, St. Louis, MO
| | - Andrea Ganna
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Göran Hallmans
- Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden
| | - Denise K. Houston
- Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC
| | - Paul F. Jacques
- Tufts University Friedman School of Nutrition Science and Policy, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA
| | - Stavroula Kanoni
- Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK,Department of Nutrition and Dietetics, Harokopio University of Athens, Athens, Greece
| | - Terho Lehtimäki
- Fimlab Laboratories and University of Tampere, School of Medicine, and Tampere University Hospital, Tampere, Finland
| | - Rozenn N. Lemaitre
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA
| | - Ani Manichaikul
- Center for Public Health Genomics, and Division of Biostatistics and Epidemiology, Department of Public Health Sciences, University of Virginia, Charlottesville, VA
| | - Kari E. North
- Department of Epidemiology and Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC
| | - Ioanna Ntalla
- Clinical Research Branch, National Institute on Aging, Baltimore, MD
| | - Emily Sonestedt
- Department of Clinical Sciences, Lund University, Malmö, Sweden
| | - Toshiko Tanaka
- Clinical Research Branch, National Institute on Aging, Baltimore, MD
| | - Frank J. A. van Rooij
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands,Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging, Leiden, The Netherlands
| | | | - Luc Djoussé
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Massachusetts Veterans Epidemiology and Research Information Center and Geriatric Research, Education, and Clinical Center, Boston Veterans Affairs Healthcare System, Boston, MA
| | - Efi Grigoriou
- Department of Nutrition and Dietetics, Harokopio University of Athens, Athens, Greece
| | | | - Kurt K. Lohman
- Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC
| | - James S. Pankow
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN
| | - Olli T. Raitakari
- Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, and Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
| | - Ulf Riserus
- Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden
| | - Mary Yannakoulia
- Department of Nutrition and Dietetics, Harokopio University of Athens, Athens, Greece
| | - M. Carola Zillikens
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands,Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging, Leiden, The Netherlands,Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Neelam Hassanali
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
| | - Yongmei Liu
- Division of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC
| | - Dariush Mozaffarian
- Department of Epidemiology and Nutrition, Harvard School of Public Health, Boston, MA; Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | | | - Ann-Christine Syvänen
- Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - André G. Uitterlinden
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands,Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging, Leiden, The Netherlands,Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Jorma Viikari
- Department of Medicine, University of Turku, and Turku University Hospital, Turku, Finland
| | - Christopher J. Groves
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
| | - Albert Hofman
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands,Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging, Leiden, The Netherlands
| | - Lars Lind
- Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden
| | - Mark I. McCarthy
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK,Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK
| | - Vera Mikkilä
- Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland
| | - Kenneth Mukamal
- Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA
| | - Oscar H. Franco
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands,Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging, Leiden, The Netherlands
| | - Ingrid B. Borecki
- Department of Genetics, Washington University School of Medicine, St. Louis, MO
| | - L. Adrienne Cupples
- Department of Biostatistics, Boston University School of Public Health, Boston, MA,Framingham Heart Study, Framingham, MA
| | - George V. Dedoussis
- Department of Nutrition and Dietetics, Harokopio University of Athens, Athens, Greece
| | - Luigi Ferrucci
- Clinical Research Branch, National Institute on Aging, Baltimore, MD
| | - Frank B. Hu
- Department of Nutrition, Harvard School of Public Health, Boston, MA
| | - Erik Ingelsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Mika Kähönen
- Department of Clinical Physiology, Tampere University Hospital, and University of Tampere, Tampere, Finland
| | - W. H. Linda Kao
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
| | | | | | - Inga Prokopenko
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK,Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
| | - Jerome I. Rotter
- Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - David S. Siscovick
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA,Department of Epidemiology, University of Washington, Seattle, WA
| | - Jacqueline C. M. Witteman
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands,Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging, Leiden, The Netherlands
| | - Paul W. Franks
- Department of Nutrition, Harvard School of Public Health, Boston, MA,Department of Clinical Sciences, Lund University, Malmö, Sweden,Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - James B. Meigs
- Harvard Medical School and General Medicine Division, Clinical Epidemiology and Diabetes Research Units, Massachusetts General Hospital, Boston, MA; and
| | - Nicola M. McKeown
- Tufts University Friedman School of Nutrition Science and Policy, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA,To whom correspondence should be addressed. E-mail:
| | - Jennifer A. Nettleton
- Division of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health at The University of Texas Health Science Center–Houston, Houston, TX
| |
Collapse
|
|
28
|
|
|
29
|
Doşa MD, Hangan LT, Crauciuc E, Galeş C, Nechifor M. Influence of therapy with metformin on the concentration of certain divalent cations in patients with non-insulin-dependent diabetes mellitus. Biol Trace Elem Res 2011; 142:36-46. [PMID: 20567934 DOI: 10.1007/s12011-010-8751-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2010] [Accepted: 06/07/2010] [Indexed: 12/15/2022]
Abstract
Research was performed on a group of 30 patients with non-insulin-dependent diabetes mellitus (NIDDM), who never received antidiabetic medication before, and on a group of 17 healthy adults. The patients were administered treatment with metformin, 1,000 mg/day. Plasmatic and urinary concentration of magnesium have been measured, copper and zinc along with the concentrations of glucose, HDL, LDL, cholesterol, tryglicerides, HbA1c, and total erythrocyte magnesium, in advance and after 3 months of treatment. Data showed significant differences in the NIDDM group vs the control group: for plasma magnesium-1.95 ± 0.19 vs 2.20 ± 0.18 mg/dl, p < 0.001; urine magnesium-237.28 ± 34.51 vs 126.25 ± 38.22 mg/24 h, p < 0.001; erythrocyte magnesium-5.09 ± 0.63 vs 6.38 ± 0.75 mg/dl, p < 0.001; plasma zinc-67.56 ± 6.21 vs 98.41 ± 20.47 μg/dl, p < 0.001; urine zinc-1,347.54 ± 158.24 vs 851.65 ± 209.75 μg/24 h, p < 0.001; plasma copper-111.91 ± 20.98 vs 96.33 ± 8.56 μg/dl, p < 0.001; and urine copper-51.70 ± 23.79 vs 36.00 ± 11.70 μg/24 h, p < 0.05. Treatment with metformin for 3 months modified significant erythrocyte magnesium-5.75 ± 0.61 vs 5.09 ± 0.63 mg/dl, p < 0.001 and urine magnesium-198.27 ± 27.07 vs 237.28 ± 34.51 mg/24 h, p < 0.001, whereas it did not modify significant the plasmatic and urinary concentration of the other cations. The erythrocyte magnesium concentration was inversely correlated with HbA1c (r = -0.438, p = 0.015). The plasma level of copper was positively correlated with HbA1c (r = 0.517, p < 0.003), tryglicerides (r = 0.534, p < 0.003), and cholesterol (r = 0.440, p < 0.05), and the plasma level of zinc was inversely correlated with glycemia (r = -0.399, p = 0.029). Our data show a significant action of metformin therapy, by increasing the total intraerythrocyte magnesium concentration and decreasing the urinary magnesium elimination, positively correlated with the decrease of glycemia and HbA1c in NIDDM patients.
Collapse
Affiliation(s)
- Monica Daniela Doşa
- Pharmacology Department, School of Medicine, Ovidius University of Constanţa, Romania.
| | | | | | | | | |
Collapse
|
|
30
|
Souto G, Donapetry C, Calviño J, Adeva MM. Metabolic acidosis-induced insulin resistance and cardiovascular risk. Metab Syndr Relat Disord 2011; 9:247-53. [PMID: 21352078 DOI: 10.1089/met.2010.0108] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Microalbuminuria has been conclusively established as an independent cardiovascular risk factor, and there is evidence of an association between insulin resistance and microalbuminuria, the former preceding the latter in prospective studies. It has been demonstrated that even the slightest degree of metabolic acidosis produces insulin resistance in healthy humans. Many recent epidemiological studies link metabolic acidosis indicators with insulin resistance and systemic hypertension. The strongly acidogenic diet consumed in developed countries produces a lifetime acidotic state, exacerbated by excess body weight and aging, which may result in insulin resistance, metabolic syndrome, and type 2 diabetes, contributing to cardiovascular risk, along with genetic causes, lack of physical exercise, and other factors. Elevated fruits and vegetables consumption has been associated with lower diabetes incidence. Diseases featuring severe atheromatosis and elevated cardiovascular risk, such as diabetes mellitus and chronic kidney failure, are typically characterized by a chronic state of metabolic acidosis. Diabetic patients consume particularly acidogenic diets, and deficiency of insulin action generates ketone bodies, creating a baseline state of metabolic acidosis worsened by inadequate metabolic control, which creates a vicious circle by inducing insulin resistance. Even very slight levels of chronic kidney insufficiency are associated with increased cardiovascular risk, which may be explained at least in part by deficient acid excretory capacity of the kidney and consequent metabolic acidosis-induced insulin resistance.
Collapse
Affiliation(s)
- Gema Souto
- Clinical Center of the National Institutes of Health, Washington, District of Columbia, USA
| | | | | | | |
Collapse
|
|
31
|
Pimentel GD, Zemdegs JCS, Theodoro JA, Mota JF. Does long-term coffee intake reduce type 2 diabetes mellitus risk? Diabetol Metab Syndr 2009; 1:6. [PMID: 19825198 PMCID: PMC2761298 DOI: 10.1186/1758-5996-1-6] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2009] [Accepted: 09/16/2009] [Indexed: 01/28/2023] Open
Abstract
This review reports the evidence for a relation between long-term coffee intake and risk of type 2 diabetes mellitus. Numerous epidemiological studies have evaluated this association and, at this moment, at least fourteen out of eighteen cohort studies revealed a substantially lower risk of type 2 diabetes mellitus with frequent coffee intake. Moderate coffee intake (>/=4 cups of coffee/d of 150 mL or >/=400 mg of caffeine/d) has generally been associated with a decrease in the risk of type 2 diabetes mellitus. Besides, results of most studies suggest a dose-response relation, with greater reductions in type 2 diabetes mellitus risk with higher levels of coffee consumption. Several mechanisms underlying this protective effect, as well as the coffee components responsible for this association are suggested. Despite positive findings, it is still premature to recommend an increase in coffee consumption as a public health strategy to prevent type 2 diabetes mellitus. More population-based surveys are necessary to clarify the long-term effects of decaffeinated and caffeinated coffee intake on the risk of type 2 diabetes mellitus.
Collapse
Affiliation(s)
- Gustavo D Pimentel
- Department of Physiology, Division of Nutrition Physiology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil
| | - Juliane CS Zemdegs
- Department of Physiology, Division of Nutrition Physiology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil
| | - Joyce A Theodoro
- Department of Nutrition, Nutrition and Health Sciences Institute, Campinas, Brazil
| | - João F Mota
- Department of Physiology, Division of Nutrition Physiology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil
| |
Collapse
|
|
32
|
Hirschler V, Oestreicher K, Beccaria M, Hidalgo M, Maccallini G. Inverse association between insulin resistance and frequency of milk consumption in low-income Argentinean school children. J Pediatr 2009; 154:101-5. [PMID: 18692202 DOI: 10.1016/j.jpeds.2008.06.036] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2008] [Revised: 05/19/2008] [Accepted: 06/20/2008] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To determine the association between milk consumption, lifestyle, components of the metabolic syndrome, and insulin resistance in school children. STUDY DESIGN Students (n = 365 [175M]) age 10 +/- 2.3 years from 2 poor suburbs of Buenos Aires were examined for body mass index, waist circumference, blood pressure, and Tanner stage in April 2007. Fasting concentrations of lipids, insulin, and glucose were determined. Mothers completed questionnaires about their children's lifestyle. RESULTS Approximately 14.0% of the children were obese, and 12.1% were overweight by use of norms from the Centers for Disease Control and Prevention. Half were at Tanner I. Mean values of waist circumference, systolic blood pressure, insulin resistance, and insulin were higher as subjects consumed more glasses of milk. Multiple regression analysis with insulin resistance as the dependent variable showed that there was a significant and positive association with triglyceridemia (beta = 0.007) and waist circumference (beta = 0.024), and a negative association with milk consumption (beta = -0.135) adjusted for blocks walked daily, TV viewing, soft drink consumption, parental educational level, sex, age, high-density lipoprotein (HDL) cholesterol, and systolic blood pressure (R(2) = 0.27). CONCLUSIONS Increased milk consumption was associated with greater insulin sensitivity, suggesting that it might reduce the risk of type 2 diabetes.
Collapse
|
|
33
|
Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Long-term effect of magnesium consumption on the risk of symptomatic gallstone disease among men. Am J Gastroenterol 2008; 103:375-82. [PMID: 18076730 DOI: 10.1111/j.1572-0241.2007.01696.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Magnesium deficiency can cause dyslipidemia and insulin hypersecretion, which may facilitate gallstone formation. However, the effect of long-term consumption of magnesium on the risk of gallstone disease is unknown. METHODS We prospectively studied magnesium consumption and risk of gallstone disease in a cohort of 42,705 U.S. men from 1986 to 2002. Magnesium consumption was assessed using a validated semiquantitative food frequency questionnaire. Newly diagnosed gallstone disease was ascertained biennially. RESULTS We documented 2,195 incident cases of symptomatic gallstones during 560,810 person-years of follow-up. The age-adjusted relative risks (RRs) for men with total magnesium intake and dietary magnesium, when the highest and lowest quintiles were compared, were 0.67 (95% confidence interval [CI] 0.59-0.77, P for trend <0.0001) and 0.67 (CI 0.59-0.76, P for trend <0.0001), respectively. After adjusting for multiple potential confounding variables, when extreme quintiles were compared, the multivariate RR of total magnesium intake (RR 0.72, CI 0.61-0.86, P for trend = 0.006) and dietary magnesium (RR 0.68, CI 0.57-0.82, P for trend = 0.0006) remained significant with a dose-response relationship. CONCLUSIONS Our findings suggest a protective role of magnesium consumption in the prevention of symptomatic gallstone disease among men.
Collapse
Affiliation(s)
- Chung-Jyi Tsai
- Division of Digestive Diseases and Nutrition, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA
| | | | | | | |
Collapse
|
|
34
|
He K, Song Y, Belin RJ, Chen Y. Magnesium intake and the metabolic syndrome: epidemiologic evidence to date. ACTA ACUST UNITED AC 2007; 1:351-5. [PMID: 17679786 DOI: 10.1111/j.1559-4564.2006.05702.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The importance of magnesium intake in relation to the metabolic syndrome has been increasingly recognized. Magnesium is an essential mineral, critical for a number of metabolic functions in the human body. The major dietary sources of magnesium intake include whole grains, legumes, nuts, and green leafy vegetables. Animal studies indicate a pivotal role of magnesium in glucose homeostasis and insulin secretion and action. Experimental and clinical studies suggest that magnesium intake may be inversely related to the risk of hypertension and type 2 diabetes mellitus, and may decrease blood triglyceride and increase high-density lipoprotein cholesterol levels. The purpose of this brief review is to summarize the epidemiologic data relating magnesium to the metabolic syndrome and to discuss the potential mechanisms.
Collapse
Affiliation(s)
- Ka He
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
| | | | | | | |
Collapse
|
|
35
|
Ford ES, Li C, McGuire LC, Mokdad AH, Liu S. Intake of dietary magnesium and the prevalence of the metabolic syndrome among U.S. adults. Obesity (Silver Spring) 2007; 15:1139-46. [PMID: 17495189 DOI: 10.1038/oby.2007.628] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE Limited data suggest that people with the metabolic syndrome have lower intakes or circulating concentrations of magnesium than those who do not have the syndrome. The aim of this study was to examine the associations between dietary intake of magnesium and the prevalence of the metabolic syndrome in a nationally representative sample of U.S. adults. RESEARCH METHODS AND PROCEDURES We used data for 7669 participants > or =20 years of age of the Third National Health and Nutrition Examination Survey (1988 to 1994). The metabolic syndrome was defined using the criteria of the National Cholesterol Education Program. Magnesium intake was determined from a single dietary 24-hour recall. RESULTS The unadjusted prevalences of the metabolic syndrome were 29.0% (quintile of lowest magnesium intake), 27.5%, 25.8%, 23.9%, and 21.8% for increasing quintiles of magnesium intake (p for trend = 0.002). After multiple adjustment, the odds ratios for the second through the fifth quintiles (highest intake) of magnesium intake among all participants included in the analysis were 0.84 [95% confidence interval (CI): 0.58, 1.23], 0.76 (95% CI: 0.54, 1.07), 0.62 (95% CI: 0.40, 0.98), and 0.56 (95% CI: 0.34, 0.92), respectively (p for trend = 0.029). The associations were similar for men and women. DISCUSSION Our results showing an inverse association between dietary magnesium intake and the prevalence of the metabolic syndrome add to the evidence that adequate magnesium intake or a diet rich in magnesium may be important for maintaining good cardiometabolic health.
Collapse
Affiliation(s)
- Earl S Ford
- Centers for Disease Control and Prevention, 4770 Buford Highway, MS K66, Atlanta, GA 30341, USA.
| | | | | | | | | |
Collapse
|
|
36
|
Barbagallo M, Dominguez LJ. Magnesium metabolism in type 2 diabetes mellitus, metabolic syndrome and insulin resistance. Arch Biochem Biophys 2007; 458:40-7. [PMID: 16808892 DOI: 10.1016/j.abb.2006.05.007] [Citation(s) in RCA: 217] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2006] [Revised: 05/10/2006] [Accepted: 05/24/2006] [Indexed: 12/13/2022]
Abstract
Type 2 diabetes is characterized by cellular and extracellular Mg depletion. Epidemiologic studies showed a high prevalence of hypomagnesaemia and lower intracellular Mg concentrations in diabetic subjects. Insulin and glucose are important regulators of Mg metabolism. Intracellular Mg plays a key role in regulating insulin action, insulin-mediated-glucose uptake and vascular tone. Reduced intracellular Mg concentrations result in a defective tyrosine-kinase activity, post-receptorial impairment in insulin action, and worsening of insulin resistance in diabetic patients. Mg deficit has been proposed as a possible underlying common mechanism of the "insulin resistance" of different metabolic conditions. Low dietary Mg intake is also related to the development of type 2 diabetes. Benefits of Mg supplementation on metabolic profile in diabetic subjects have been found in most, but not all clinical studies, and larger prospective studies are needed to support the potential role of dietary Mg supplementation as a possible public health strategy in diabetes risk.
Collapse
Affiliation(s)
- Mario Barbagallo
- Institute of Internal Medicine and Geriatrics, University of Palermo, Italy.
| | | |
Collapse
|
|
37
|
Rumawas ME, McKeown NM, Rogers G, Meigs JB, Wilson PWF, Jacques PF. Magnesium Intake Is Related to Improved Insulin Homeostasis in the Framingham Offspring Cohort. J Am Coll Nutr 2006; 25:486-92. [PMID: 17229895 DOI: 10.1080/07315724.2006.10719563] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Higher dietary intake of magnesium may protect against development of type 2 diabetes. The aim of this study was to examine the association between dietary magnesium intake and metabolic risk factors for diabetes. METHODS We examined cross-sectional associations between magnesium intake and fasting glucose and insulin, 2-hour post-challenge plasma glucose and insulin, and insulin resistance assessed by the homeostasis model (HOMA-IR) in 1223 men and 1485 women without diabetes from the Framingham Offspring cohort. Magnesium intake was assessed by a food frequency questionnaire and magnesium intake was categorized into quintile categories. Geometric mean insulin, glucose, 2-hour post challenge plasma glucose and insulin concentrations and HOMA-IR were estimated across quintile categories of magnesium intake using Generalized Linear Models. RESULTS After adjustment for potential confounding factors, magnesium intake was inversely associated with fasting insulin (mean: 29.9 vs 26.7 microU/mL in the lowest vs highest quintiles of magnesium intake; P trend <0.001), post-glucose challenge plasma insulin (86.4 vs 72 microU/mL; P trend <0.001), and HOMA-IR (7.0 vs 6.2; P trend <0.001). No significant association was found between magnesium intake and fasting glucose or 2-hour post challenge glucose. CONCLUSIONS Improved insulin sensitivity may be one mechanism by which higher dietary magnesium intake may reduce the risk of developing type 2 DM.
Collapse
Affiliation(s)
- Marcella E Rumawas
- Nutritional Epidemiology Program, JM USDA HNRC at Tufts University, Boston, MA 02111-1524, USA
| | | | | | | | | | | |
Collapse
|
|
38
|
van Dam RM, Hu FB, Rosenberg L, Krishnan S, Palmer JR. Dietary calcium and magnesium, major food sources, and risk of type 2 diabetes in U.S. black women. Diabetes Care 2006; 29:2238-43. [PMID: 17003299 DOI: 10.2337/dc06-1014] [Citation(s) in RCA: 150] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Inverse associations between magnesium and calcium intakes and risk of type 2 diabetes have been reported for studies in predominantly white populations. We examined magnesium, calcium, and major food sources in relation to type 2 diabetes in African-American women. RESEARCH DESIGN AND METHODS This is a prospective cohort study including 41,186 participants of the Black Women's Health Study without a history of diabetes who completed validated food frequency questionnaires at baseline. During 8 years of follow-up (1995-2003), we documented 1,964 newly diagnosed cases of type 2 diabetes. RESULTS The multivariate-adjusted hazard ratio of type 2 diabetes for the highest compared with the lowest quintile of intake was 0.69 (95% CI 0.59-0.81; P trend <0.0001) for dietary magnesium and 0.86 (0.74-1.00; P trend = 0.01) for dietary calcium. After mutual adjustment, the association for calcium disappeared (hazard ratio 1.04 [95% CI 0.88-1.24]; P trend = 0.88), whereas the association for magnesium remained. Daily consumption of low-fat dairy (0.87 [0.76-1.00]; P trend = 0.04) and whole grains (0.69 [0.60-0.79]; P trend <0.0001) were associated with a lower risk of type 2 diabetes compared with a consumption less than once a week. After mutual adjustment, the hazard ratio was 0.81 (0.68-0.97; P trend = 0.02) for magnesium and 0.73 (0.63-0.85; P trend <0.0001) for whole grains. CONCLUSIONS These findings indicate that a diet high in magnesium-rich foods, particularly whole grains, is associated with a substantially lower risk of type 2 diabetes in U.S. black women.
Collapse
Affiliation(s)
- Rob M van Dam
- Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA.
| | | | | | | | | |
Collapse
|
|
39
|
Sales CH, Pedrosa LDFC. Magnesium and diabetes mellitus: Their relation. Clin Nutr 2006; 25:554-62. [PMID: 16690176 DOI: 10.1016/j.clnu.2006.03.003] [Citation(s) in RCA: 94] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2005] [Revised: 02/08/2006] [Accepted: 03/18/2006] [Indexed: 12/15/2022]
Abstract
The aim of this review was to elaborate a synthesis about the discussions on magnesium and diabetes mellitus, in the last 14 years. The magnesium deficiency has been associated with chronic diseases, amongst them, diabetes mellitus. Epidemiological studies had shown low levels of magnesium ingestion in the general population, as well as a relation between the ingestion of food rich in magnesium and the reduction of diabetes installation and its complications. Hypomagnesemia is frequently present in diabetic patients, however there is not an exact elucidation of the mechanism of magnesium deficiency in diabetes mellitus. On the other hand, in the presence of this illness, it is observed that inadequate metabolic control can affect the corporal concentrations of magnesium, developing hypomagnesemia, which may be still directly related with some micro and macrovascular complications observed in diabetes, as cardiovascular disease, retinopathy and neuropathy. This way, the chronic complications of diabetes can appear precociously. Based on this, the supplementation with magnesium has been suggested in patients with diabetes mellitus who have proven hypomagnesemia and the presence of its complications.
Collapse
Affiliation(s)
- Cristiane Hermes Sales
- Departamento de Nutrição, Universidade Federal do Rio Grande do Norte, UFRN, Centro de Ciências da Saúde, Av. General Cordeiro de Farias, s/n, Petrópolis, Natal-RN, 59010-180, Brazil
| | | |
Collapse
|
|
40
|
Fung TT, Manson JE, Solomon CG, Liu S, Willett WC, Hu FB. The association between magnesium intake and fasting insulin concentration in healthy middle-aged women. J Am Coll Nutr 2006; 22:533-8. [PMID: 14684759 DOI: 10.1080/07315724.2003.10719332] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE We assessed the association between magnesium intake and fasting insulin levels in a large cohort of women. METHODS Female nurses free of diabetes, cardiovascular diseases and cancer from the Nurses Health Study provided blood samples between 1989-1990. We selected a sub-sample of 219 women for this analysis. Magnesium intake was assessed by a food frequency questionnaire in 1990 and categorized into quartiles. Cross-sectional geometric means of fasting insulin concentrations by quartiles of magnesium intake were obtained with Generalized Linear Model and adjusted for several risk factors and lifestyle characteristics. RESULTS After adjustment for age, body mass index (BMI), total energy, physical activity, hours per week spent sitting outside work, alcohol intake, smoking, and family history of diabetes, magnesium intake was inversely associated with fasting insulin concentration. The multivariate adjusted geometric mean for women in the lowest quartile of magnesium intake was 11.0 microU/mL and 9.3 microU/mL among those in the highest quartile of magnesium intake (p for trend = 0.04). The inverse association remained when we considered magnesium from only food sources. CONCLUSION Higher magnesium intake is associated with lower fasting insulin concentrations among women without diabetes. Because lower fasting insulin concentrations generally reflect greater insulin sensitivity, these findings provide a mechanism through which higher dietary magnesium intake may reduce the risk of developing type 2 diabetes mellitus.
Collapse
Affiliation(s)
- Teresa T Fung
- Department of Nutrition, Simmons College, 300 The Fenway, Boston, MA 02215, USA.
| | | | | | | | | | | |
Collapse
|
|
41
|
Mitsopoulos E, Griveas I, Zanos S, Anagnostopoulos K, Giannakou A, Pavlitou A, Sakellariou G. Increase in serum magnesium level in haemodialysis patients receiving sevelamer hydrochloride. Int Urol Nephrol 2006; 37:321-8. [PMID: 16142565 DOI: 10.1007/s11255-004-7135-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND Clinical studies have shown that sevelamer hydrochloride improves lipid profiles and attenuates the progression of the cardiovascular calcifications in haemodialysis patients. It is known that both of these properties are associated with increased magnesium levels. The effect of sevelamer on serum magnesium level is not well documented. The aim of this study was to determine the effects of sevelamer treatment on serum magnesium in haemodialysis patients and to assess the association of magnesium levels with lipid profiles and intact parathyroid hormone (iPTH). METHODS Phosphate binders were discontinued during a two week washout period. Forty-seven patients, whose serum phosphate was greater than 6.0 mg/dl at the end of washout, received sevelamer hydrochloride for eight weeks. The patients were then washed off sevelamer for another two weeks. RESULTS Mean serum phosphorus concentration declined from 7.5 +/- 1.3 to 6.4 +/- 1.2 mg/dl (P < 0.001), mean serum magnesium levels increased from 2.75 +/- 0.35 to 2.90 +/- 0.41 mg/dl (P < 0.001) and median serum iPTH levels decreased from 297 to 213 pg/ml (P=0.001) during the eight weeks of sevelamer treatment. After the two week post-treatment washout phosphorus levels increased to 7.3 +/- 1.3 mg/dl (P < 0.001), magnesium levels were reduced to 2.77 +/- 0.39 mg/dl (P < 0.001) and iPTH levels increased to 240 pg/ml (P=0.012). No change was observed in serum calcium levels during the sevelamer treatment period and the subsequent washout period. The mean decline in total and low density lipoprotein (LDL) cholesterol during sevelamer treatment was 16.3 and 28.3 (P < 0.001), respectively. The mean increase in high density lipoprotein (HDL) cholesterol and in apolipoprotein A1 was 2.9 +/- 5.8 mg/dl (P=0.004) and 6.8 +/- 11.1 mg/dl (P=0.001), respectively. Multivariate analysis showed that the rise in serum magnesium concentration significantly correlated with reductions in iPTH levels (r=-0.40, P=0.016), but did not have any significant correlation with the changes in lipid profiles. CONCLUSIONS Our findings indicate that patients on haemodialysis receiving sevelamer have a significant increase in serum magnesium concentrations. This increase in serum magnesium is associated with reduction in iPTH levels. The changes in lipid profiles of these patients however are not related to changes in serum magnesium levels.
Collapse
|
|
42
|
He K, Liu K, Daviglus ML, Morris SJ, Loria CM, Van Horn L, Jacobs DR, Savage PJ. Magnesium Intake and Incidence of Metabolic Syndrome Among Young Adults. Circulation 2006; 113:1675-82. [PMID: 16567569 DOI: 10.1161/circulationaha.105.588327] [Citation(s) in RCA: 234] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background—
Studies suggest that magnesium intake may be inversely related to risk of hypertension and type 2 diabetes mellitus and that higher intake of magnesium may decrease blood triglycerides and increase high-density lipoprotein (HDL) cholesterol levels. However, the longitudinal association of magnesium intake and incidence of metabolic syndrome has not been investigated.
Methods and Results—
We prospectively examined the relations between magnesium intake and incident metabolic syndrome and its components among 4637 Americans, aged 18 to 30 years, who were free from metabolic syndrome and diabetes at baseline. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III definition. Diet was assessed by an interviewer-administered quantitative food frequency questionnaire, and magnesium intake was derived from the nutrient database developed by the Minnesota Nutrition Coordinating Center. During the 15 years of follow-up, 608 incident cases of the metabolic syndrome were identified. Magnesium intake was inversely associated with incidence of metabolic syndrome after adjustment for major lifestyle and dietary variables and baseline status of each component of the metabolic syndrome. Compared with those in the lowest quartile of magnesium intake, multivariable-adjusted hazard ratio of metabolic syndrome for participants in the highest quartile was 0.69 (95% confidence interval [CI], 0.52 to 0.91;
P
for trend <0.01). The inverse associations were not materially modified by gender and race. Magnesium intake was also inversely related to individual component of the metabolic syndrome and fasting insulin levels.
Conclusions—
Our findings suggest that young adults with higher magnesium intake have lower risk of development of metabolic syndrome.
Collapse
Affiliation(s)
- Ka He
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
| | | | | | | | | | | | | | | |
Collapse
|
|
43
|
Jensen MK, Koh-Banerjee P, Franz M, Sampson L, Grønbaek M, Rimm EB. Whole grains, bran, and germ in relation to homocysteine and markers of glycemic control, lipids, and inflammation 1. Am J Clin Nutr 2006; 83:275-83. [PMID: 16469984 DOI: 10.1093/ajcn/83.2.275] [Citation(s) in RCA: 161] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Intake of whole grains is inversely associated with risk of diabetes and ischemic heart disease in observational studies. The lower risk associated with high whole-grain intakes may be mediated through improvements in glycemic control, lipid profiles, or reduced inflammation. OBJECTIVE The aim was to examine whether the intake of whole grains, bran, and germ is related to homocysteine, plasma markers of glycemic control (fasting insulin, hemoglobin A1c, C-peptide, and leptin), lipids (total cholesterol, triacylglycerol, HDL cholesterol, and LDL cholesterol), and inflammation (C-reactive protein, fibrinogen, and interleukin 6). DESIGN This was a cross-sectional study of the relations of whole grains, bran, and germ intakes with homocysteine and markers of glycemic control, lipids, and inflammation in 938 healthy men and women. RESULTS Whole-grain intake was inversely associated with homocysteine and markers of glycemic control. Compared with participants in the bottom quintile of whole-grain intake, participants in the highest quintile had 17%, 14%, 14%, and 11% lower concentrations of homocysteine (P < 0.01), insulin (P = 0.12), C-peptide (P = 0.03), and leptin (P = 0.03), respectively. Inverse associations were also observed with total cholesterol (P = 0.02), HDL cholesterol (P = 0.05), and LDL cholesterol (P = 0.10). Whole-grain intake was not associated with the markers of inflammation. Whole-grain intake was most strongly inversely associated with markers of glycemic control in this population. CONCLUSION The results suggest a lower risk of diabetes and heart disease in persons who consume diets high in whole grains.
Collapse
Affiliation(s)
- Majken K Jensen
- Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
| | | | | | | | | | | |
Collapse
|
|
44
|
McCarty MF. PKC-mediated modulation of L-type calcium channels may contribute to fat-induced insulin resistance. Med Hypotheses 2006; 66:824-31. [PMID: 16307847 DOI: 10.1016/j.mehy.2004.08.034] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2004] [Accepted: 08/27/2004] [Indexed: 01/01/2023]
Abstract
Increased intracellular free calcium [Ca2+]i has been noted in adipocytes, platelets, and leukocytes of subjects with insulin resistance syndrome or allied disorders. In rodent studies, measures which increase [Ca2+]i in adipocytes and skeletal muscle are associated with impaired insulin signaling, attributable at least in part to diminished ability of insulin to activate phosphoserine phosphatase-1 (PP-1). In fat-fed insulin resistant rats, pre-treatment with a drug that selectively chelates intracellular calcium eliminates about half of the decrement in insulin-stimulated glucose uptake induced by fat feeding; since this chelator does not influence the insulin sensitivity of chow-fed rats, it is reasonable to suspect that fat feeding boosts [Ca2+]i in skeletal muscle, and that this effect is partially responsible for the associated reduction in insulin sensitivity. Clinical insulin resistance is associated with increased levels of triglycerides and other fatty acid metabolites in muscle fibers; this can give rise to diacylglycerol-mediated activation of PKC, which in turn compromises insulin signaling by triggering kinase cascades that phosphorylate IRS-1 on key serine residues. Yet there is also evidence that, in skeletal muscle, PKC activity up-regulates the function of L-type calcium channels, increasing their maximal conductance while left-shifting their voltage dependence. Thus, the PKC activation associated with fat overexposure might be expected to boost basal [Ca2+]i in skeletal muscle, potentially impeding insulin-mediated activation of PP-1. This hypothesis is consistent with several clinical studies demonstrating that long-acting inhibitors of L-type calcium channels can improve insulin sensitivity in overweight hypertensives; it should be readily testable in rodent models of fat-induced insulin resistance. Since parathyroid hormone can act on adipocytes and muscle to boost [Ca2+]i, mild secondary hyperparathyroidism associated with low calcium intakes and poor vitamin D status may contribute to insulin resistance, consistent with certain clinical and epidemiological findings. Magnesium, often thought of as a mild calcium antagonist, appears to have favorable effects on insulin sensitivity and risk for diabetes, and recent evidence indicates that increases of intracellular magnesium within the physiological range can diminish calcium influx through phosphorylated L-type calcium channels. It will be of interest to determine whether calcium antagonism does indeed underlie the favorable influence of good magnesium status on insulin function. A report that chromium picolinate can induce the plasmalemmal Ca2+-ATPase in smooth muscle cells, raises the possibility that modulation of calcium transport might play a role in the insulin-sensitizing efficacy of bioactive chromium.
Collapse
Affiliation(s)
- Mark F McCarty
- Natural Alternatives International, 1185 Linda Vista Dr., San Marcos, CA 92078, USA.
| |
Collapse
|
|
45
|
Rodríguez-Hernández H, Gonzalez JL, Rodríguez-Morán M, Guerrero-Romero F. Hypomagnesemia, insulin resistance, and non-alcoholic steatohepatitis in obese subjects. Arch Med Res 2005; 36:362-6. [PMID: 15950075 DOI: 10.1016/j.arcmed.2005.03.008] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2004] [Accepted: 01/03/2005] [Indexed: 12/18/2022]
Abstract
BACKGROUND Epidemiological evidence shows a strong relationship between decreased serum magnesium levels (DSML) and insulin resistance. As nonalcoholic steatohepatitis (NASH) seems to be related to insulin resistance, the aim of this study was to determine the potential relationship between DSML and NASH in obese subjects. METHODS We compared obese individuals with the diagnosis of diabetes, insulin-resistance, and non-insulin resistance to a control group of non-obese, non-insulin-resistant subjects. Participants were required to have negative viral markers and negligible alcohol intake. Other liver diseases and well-known causes for decreasing of magnesium were exclusion criteria. A liver biopsy was performed in subjects with aspartate aminotransferase (AST) and alanine aminotransferease (ALT) levels > or =40 IU/mL. RESULTS Of the 60 obese subjects, 20 were non-insulin resistant, 20 were insulin resistant, and 20 were type 2 diabetics. Twenty subjects were in the control group. Eleven (33.3%) diabetics, 14 (42.4%) insulin-resistant subjects, and 8 (24.2%) non-insulin-resistant subjects underwent liver biopsies. Diagnosis of NASH was established in 29 (36.2%) individuals. Subjects with the diagnosis of NASH exhibited lower serum magnesium levels of 1.7 +/- 0.2 mg/dL (0.70 +/- 0.08 mmol/L), and those with fibrosis showed the lowest serum magnesium concentration at 1.5 +/- 0.3 mg/dL (0.62 +/- 0.12 mmol/L). Multiple regression analysis adjusted by age showed that low serum magnesium concentration was independently related to a high HOMA-IR index (OR 7.6, CI 95% 2.1-11.2; p <0.0001) and that a high HOMA-IR index was related to NASH (OR 6.5, CI 95% 1.5-8.8; p <0.01). After adjusting for age and a high HOMA-IR index, hypomagnesemia remained independently related to NASH (OR 1.4, CI 95% 1.1-5.4; p <0.05). CONCLUSIONS The results of this study demonstrate an independent relationship between DSML and NASH.
Collapse
|
|
46
|
Azadbakht L, Mirmiran P, Esmaillzadeh A, Azizi F. Dairy consumption is inversely associated with the prevalence of the metabolic syndrome in Tehranian adults. Am J Clin Nutr 2005; 82:523-30. [PMID: 16155263 DOI: 10.1093/ajcn.82.3.523] [Citation(s) in RCA: 95] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Although previous studies showed some benefits from dairy consumption with respect to obesity and insulin resistance syndrome, epidemiologic data on the association between dairy intakes and metabolic syndrome are sparse. OBJECTIVE The objective was to evaluate the relation between dairy consumption and metabolic syndrome in Tehranian adults. DESIGN Dairy consumption and features of metabolic syndrome were assessed in a population-based cross-sectional study of 827 subjects (357 men and 470 women) aged 18-74 y. Metabolic syndrome was defined according to guidelines of the Adult Treatment Panel III. Multivariate logistic regression adjusted for lifestyle and nutritional confounders was used in 4 models. RESULTS Mean (+/-SD) consumption of milk, yogurt, and cheese was 0.7 +/- 0.2, 1.06 +/- 0.6, and 0.9 +/- 0.3 servings/d, respectively. Subjects in the highest quartile of dairy consumption had lower odds of having enlarged waist circumference [odds ratio (OR) by quartile: 1, 0.89, 0.74, 0.63; P for trend < 0.001], hypertension (OR by quartile: 1, 0.88, 0.79, 0.71; P for trend < 0.02), and metabolic syndrome (OR by quartile: 1, 0.83, 0.74, 0.69; P for trend < 0.02). The values of ORs became weaker after further adjustment for calcium intake. CONCLUSION Dairy consumption is inversely associated with the risk of having metabolic syndrome. It seems that this relation is somewhat attributed to calcium.
Collapse
Affiliation(s)
- Leila Azadbakht
- Endocrine Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
| | | | | | | |
Collapse
|
|
47
|
Azadbakht L, Mirmiran P, Esmaillzadeh A, Azizi F. Dairy consumption is inversely associated with the prevalence of the metabolic syndrome in Tehranian adults. Am J Clin Nutr 2005. [DOI: 10.1093/ajcn/82.3.523] [Citation(s) in RCA: 245] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Leila Azadbakht
- From the Endocrine Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
| | - Parvin Mirmiran
- From the Endocrine Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
| | - Ahmad Esmaillzadeh
- From the Endocrine Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- From the Endocrine Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
48
|
Huerta MG, Roemmich JN, Kington ML, Bovbjerg VE, Weltman AL, Holmes VF, Patrie JT, Rogol AD, Nadler JL. Magnesium deficiency is associated with insulin resistance in obese children. Diabetes Care 2005; 28:1175-81. [PMID: 15855585 DOI: 10.2337/diacare.28.5.1175] [Citation(s) in RCA: 151] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Magnesium deficiency has been associated with insulin resistance (IR) and increased risk for type 2 diabetes in adults. This study was designed to determine whether obese children exhibit serum or dietary magnesium deficiency and its potential association with IR. RESEARCH DESIGN AND METHODS We studied 24 obese nondiabetic children (BMI > or =85th percentile) and 24 sex- and puberty-matched lean control subjects (BMI <85th percentile). We measured serum magnesium, indexes of insulin sensitivity, dietary magnesium intake (using a food frequency questionnaire), and body composition (by air displacement plethysmography). RESULTS Serum magnesium was significantly lower in obese children (0.748 +/- 0.015 mmol/l, means +/- SE) compared with lean children (0.801 +/- 0.012 mmol/l) (P = 0.009). Serum magnesium was inversely correlated with fasting insulin (r(s) = -0.36 [95% CI -0.59 to -0.08]; P = 0.011) and positively correlated with quantitative insulin sensitivity check index (QUICKI) (0.35 [0.06-0.58]; P = 0.015). Dietary magnesium intake was significantly lower in obese children (obese: 0.12 +/- 0.004 vs. lean: 0.14 +/- 0.004 mg/kcal; P = 0.003). Dietary magnesium intake was inversely associated with fasting insulin (-0.43 [-0.64 to -0.16]; P = 0.002) and directly correlated with QUICKI (0.43 [0.16-0.64]; P = 0.002). CONCLUSIONS The association between magnesium deficiency and IR is present during childhood. Serum magnesium deficiency in obese children may be secondary to decreased dietary magnesium intake. Magnesium supplementation or increased intake of magnesium-rich foods may be an important tool in the prevention of type 2 diabetes in obese children.
Collapse
Affiliation(s)
- Milagros G Huerta
- University of Virginia, Department of Pediatrics, Box 800386, Charlottesville, VA 22908, USA.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
49
|
McCarty MF. Magnesium may mediate the favorable impact of whole grains on insulin sensitivity by acting as a mild calcium antagonist. Med Hypotheses 2005; 64:619-27. [PMID: 15617878 DOI: 10.1016/j.mehy.2003.10.034] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2003] [Accepted: 10/17/2003] [Indexed: 12/15/2022]
Abstract
Recent epidemiology has linked high consumption of whole grains with reduced risk for diabetes, coronary disease, stroke, and various types of cancer; there is reason to suspect that improved insulin sensitivity is largely responsible for this protection. This phenomenon may be partially explained by the lower glycemic indices of some whole grain food products in comparison to their fiber-depleted analogs. Nonetheless, the fact that whole wheat flour promotes insulin sensitivity relative to white flour--and yet has a near-identical glycemic index--suggests that certain nutrients or phytochemicals in whole wheat, depleted by the refining process, promote preservation of insulin sensitivity. Magnesium is a likely candidate in this regard; magnesium deficiency promotes insulin resistance in rodents and in humans, whereas supplemental magnesium has been found to prevent type 2 diabetes in rodent models of this syndrome, and to improve the insulin sensitivity of elderly or diabetic humans. Magnesium-rich diets as well as above-average serum magnesium are associated with reduced diabetes risk in prospective epidemiology, and with greater insulin sensitivity in cross-sectional studies; moreover, other types of magnesium-rich foods--dairy products, legumes, and nuts--have been linked to decreased diabetes risk in prospective studies. The biochemical role of magnesium in support of insulin function is still poorly understood. In light of evidence that magnesium can function as a mild natural calcium antagonist, it is interesting to note suggestive evidence that increases in intracellular free calcium may compromise the insulin responsiveness of adipocytes and skeletal muscle, and may indeed play a pathogenic role in the insulin resistance syndrome. Thus, it is proposed that some or all of the favorable impact of good magnesium status on insulin function may reflect antagonism of the induction or effects of increased intracellular free calcium. Further research concerning the potential health benefits of long-term magnesium supplementation is clearly warranted. These considerations, however, should not detract from efforts to better inform the public regarding the strong desirability of choosing whole grain products in preference to refined grains.
Collapse
Affiliation(s)
- Mark F McCarty
- Pantox Laboratories, 4622 Santa Fe Street, San Diego, CA 92109, USA.
| |
Collapse
|
|
50
|
Demigné C, Sabboh H, Rémésy C, Meneton P. Protective effects of high dietary potassium: nutritional and metabolic aspects. J Nutr 2004; 134:2903-6. [PMID: 15514249 DOI: 10.1093/jn/134.11.2903] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Potassium (K+) requirements have been largely overlooked because severe deficiencies are uncommon due to the ubiquity of this element in foods. However, a transition toward modern ("Westernized") diets has led to a substantial decline of K+ intake compared with traditional food habits, and a large fraction of the population might now have suboptimal K+ intake. A high K+ intake was demonstrated to have protective effects against several pathologic states affecting the cardiovascular system, kidneys, and bones. Additionally, fruits and vegetables contain K/organic anion salts (malate, citrate), which exert alkalinizing effects, through KHCO(3)(-) generation, which serves to neutralize fixed acidity in urine. Low-grade metabolic acidosis, when not properly controlled, may exacerbate various catabolic processes (bone Ca++ mobilization, proteolysis), especially in the elderly. Fruits and vegetables are therefore receiving great attention in a strategy to increase the nutritional value of meals while reducing energy density and intake. The need to ensure a 2.5- to 3.5-g daily K+ supply from fruits and vegetables represents a strong rationale for the "5-10 servings per day" recommendations.
Collapse
Affiliation(s)
- Christian Demigné
- Metabolic Diseases and Micronutriments Unit, INRA Theix/CRNH Clermont-Ferrand, 63122 St-Genes-Champanelle, France.
| | | | | | | |
Collapse
|