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Online Library: Diabetes

The following pages provide an overview of the most recent research and clinical studies about the health benefits of micronutrients in fighting diabetes. This collection of scientific facts proves that anyone who privately or publicly questions the health value of micronutrients does not serve YOUR health, or the health of the people, but rather the multi-billion dollar investment 'business with disease' based on patented pharmaceutical drugs.

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Vitamin D Deficiency May be associated with Type 2 Diabetes in HIV Patients

Source: AIDS, 2011; 25(4):525-529

Author: Szep Z, Tebas P, et al

Affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Pennsylvania, USA

Abstract: In a cross-sectional study involving HIV patients in the prospective Modena HIV Metabolic Clinic Cohort, results indicate an association between vitamin D deficiency and risk of type 2 diabetes mellitus. The authors conclude, "Our study demonstrates an association between vitamin D deficiency and type 2 diabetes mellitus."

Vitamin E supplementation may ameliorate oxidative stress in type 1 diabetes mellitus patients

Source: Clinical Laboratory 2011; 57(5-6): 379-86

Author: Gutpa S, Sharma TK, et al.

Affiliation: Department of Biochemistry, J.L.N. Medical College, Ajmer, India.

Abstract: In a study involving 40 children (20 with type 2 diabetes mellitus and the other 20 served as controls), supplementation with vitamin E was found to decrease MDA* and significantly decrease MDA levels and increase GSH. The authors state, "Vitamin E ameliorates oxidative stress in Type 1 Diabetes Mellitus patients and improves antioxidant defense system."

• Malondialdehyde (MDA) is a highly toxic by-product formed in part by lipid oxidation derived free radicals. Many studies have shown that its concentration is increased considerably in diabetes mellitus.
• GSH (Glutathion) is an important chemical that acts as a powerful antioxidant to preserve and protect the brain and other body tissues by protecting them from the damage of free radicals. It also acts to recycle vitamin C & E which also reduce free radicals.

Vitamin D and type 2 diabetes: a systematic review

Source: European Journal of Clinical Nutrition 2011 July 6; [Epub ahead of print]

Author: Mitri J, Muraru MD, et al.

Affiliation: Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center, Boston,USA)

Abstract: In a systematic review and meta-analysis including data from 8 observational cohort studies and 11 randomized controlled trials, intake of more than 500 IU/d vitamin D was found to be associated with a 13% decrease in risk of type 2 diabetes, as compared to intake of less than 200 IU/d. Subjects whose vitamin D status was the highest (more than 25 ng/ml) were found to have a 43% lower risk of developing type 2 diabetes, as compared to those with the lowest vitamin D status (less than 14 ng/ml). In patients with baseline glucose intolerance, vitamin D supplementation was found to improve insulin resistance (in 2 trials), and according to post hoc analyses, in patients with normal glucose tolerance at baseline, vitamin D supplementation did not affect glycemic outcomes (in 8 trials). The authors state, "Vitamin D may play a role in type 2 diabetes; however, to better define the role of vitamin D in the development and progression of type 2 diabetes, high-quality observational studies and RCTs that measure blood 25-hydroxyvitamin D concentration and clinically relevant glycemic outcomes are needed."

Plasma 25-hydroxyvitamin D is independently associated with hemoglobin concentration in male subjects with type 2 diabetes mellitus

Source: International Journal of Endocrinology 2011 (2011) Article ID:362981

Author: Meguro S, Tomita M, et al

Affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan

Abstract: . In a cross-sectional study involving male patients with type 2 diabetes mellitus, hemoglobin concentration was positively associated with BMI*, HbA1c*, estimated glomerular filtration rate, duration of diabetes, serum creatine, and urinary albumin creatinine ratio. The authors state, "Plasma circulating form of vitamin D is significantly associated with hemoglobin concentration in diabetes mellitus independent of the clinical markers for kidney function or nutrition."

• BMI (Body Mass Index) is defined as the individual's body weight divided by the square of his or her height.
• HbA1c (Glycated hemoglobin) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. In diabetes mellitus, higher amounts of glycated hemoglobin, indicating poorer control of blood glucose levels, have been associated with cardiovascular disease, nephropathy, and retinopathy.

Low serum vitamin D is associated with high risk of diabetes in Korean adults

Source: The Journal of Nutrition 2011; 141(8): 1524-8

Author: Choi HS, Kim KA, et al.

Affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Dongguk; University Ilsan Hospital, Goyang-shi, Korea.

Abstract: In a large, population-based survey study involving cross-sectional analyses carried out on data collected from 5,787 Korean adults (2543 men and 3334 women), low serum 25(OH)D* concentrations were associated with an increased risk of diabetes mellitus. Diabetes mellitus was defined as having a fasting plasma glucose of 7 mmol/L or greater or currently using oral hypoglycemic agents or insulin. As compared to subjects with sufficient vitamin D status (25(OH)D of 75 nmol/L or greater), those with serum 25(OH)D concentrations less than 25, 25 to <50, and 50 to <75 nmol/L were found to have ORs* for diabetes mellitus of: 1.73, 1.30, and 1.40. In addition, serum 25(OH)D was inversely associated with HOMA-IR* and positively associated with QUICKI* in overweight or obese subjects. The authors conclude "a low serum vitamin D concentration is associated with a high risk of diabetes mellitus in Korean adults and the concentration is inversely associated with insulin resistance in those who are overweight or obese."

• 25 (OH)D is the chemical description of Vitamin D.
• ORs (Odds ratios) are a common measure of the size of an effect and may be reported in case-control studies, cohort studies, or clinical trials.
• HOMA-IR (Homeostasis Model of Assessment - Insulin Resistance) is calculated using the following formula: fasting Glucose(mmol/L) x fasting Insulin(mU/L) / 22.5.
• QUICKI (quantitative insulin-sensitivity check index) has proven to be a usefull index of insulin resistance during the clinical course of type 2 diabetes mellitus.

Omega-3 fatty acids and incident type 2 diabetes: the Singapore Chinese Health Study

Source: The American Journal of Clinical Nutrition 2011; 94(2): 520-526

Author: Diana P Brostow, Andrew O Odegaard, Woon-Puay Koh, et al.

Affiliation: Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, the Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and The Masonic Cancer Center, University of Minnesota, Minneapolis.

Abstract: The objective was to examine the association between total omega-3 Fatty Acids, marine omega-3 (EPA, DHA), nonmarine omega-3 (ALA), and omega-6 (n–6) Fatty Acids and omega-6:omega-3 ratio and risk of type 2 diabetes in a Chinese population in Singapore. Conclusion: Consumption of nonmarine sources (ALA) of omega-3 Fatty Acids is associated with a decreased risk of type 2 diabetes in Chinese Singaporeans.

Plasma omega-3 fatty acids and incident diabetes in older adults

Source: The American Journal of Clinical Nutrition 2011; 94(2): 527-533

Author: Luc Djoussé, Mary L Biggs, Rozenn N Lemaitre et aL

Affiliation: Divisions of Aging and the Department of Epidemiology, University of Washington, Seattle, WA.;University of California San Diego, San Diego; Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston.

Abstract: In this study the authors analyzed data in 3088 older men and women (mean age: 75 y) from the Cardiovascular Health Study (1992–2007). Conclusions: With the use of objective biomarkers, long-chain n−3 Fatty Acids and ALA were not associated with a higher incidence of diabetes. Individuals with the highest concentrations of both types of Fatty Acids had lower risk of diabetes.

Fish, shellfish, and long-chain n−3 fatty acid consumption and risk of incident type 2 diabetes in middle-aged Chinese men and women

Source: The American Journal of Clinical Nutrition 2011; 94(2): 543-551

Author: Raquel Villegas, Yong-Bing Xiang, Tom Elasy et al.

Affiliation: From the Vanderbilt University Medical Center, Nashville, and the Shanghai Cancer Institute, Shanghai, China.

Abstract: Long-chain polyunsaturated n–3 (omega-3) fatty acids, found mainly in fish, have been postulated to reduce type 2 diabetes (T2D) risk. However, the role of long-chain n−3 fatty acids and fish intake in the development of T2D remains unresolved. In this study they examined associations between fish, shellfish, and long-chain n−3 fatty acids and the risk of T2D in a middle-aged Chinese population. This study was a prospective population-based cohort study in 51,963 men and 64,193 women free of T2D, cardiovascular disease, and cancer at baseline with valid dietary information. Dietary intake, physical activity, and anthropometric measurements were collected. Conclusions: An inverse association between fish and shellfish intake and type2 diabetes in women was found. No evidence of a detrimental effect of fish intake in this population was observed.

Effects of vitamin D and calcium supplementation on pancreatic {beta} cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial.

Source: The American journal of clinical nutrition 201;94(2):486-94

Author: Mitri J, Dawson-Hughes B, Hu FB, Pittas AG.

Affiliation: Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center, Boston, MA.

Abstract: A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies, but evidence from trials is lacking. In this study the scientists determined whether vitamin D supplementation, with or without calcium, improved glucose homeostasis in adults at high risk of diabetes. Ninety-two adults were randomly assigned in a 2-by-2 factorial-design, double-blind, placebo-controlled trial to receive either cholecalciferol (Vitamin D; 2000 IU once daily) or calcium carbonate (400 mg twice daily) for 16 wk. The primary outcome was the change in pancreatic β cell function as measured by the disposition index after an intravenous-glucose-tolerance test. Other outcomes were acute insulin response, insulin sensitivity, and measures of glycemia. CONCLUSION: In adults at risk of type 2 diabetes, short-term supplementation with cholecalciferol (Vitamin D) improved β cell function and had a marginal effect on attenuating the rise in Hb A(1c)*. There was no significant difference in any outcomes with calcium compared with no calcium.

• HbA1c (Glycated hemoglobin) is a form of hemoglobin which is measured primarily to identify the damage to this blood cells pigment by elevated plasma glucose concentration over prolonged periods of time. In diabetes mellitus, higher amounts of glycated hemoglobin, indicating poorer control of blood glucose levels, have been associated with cardiovascular disease, nephropathy, and retinopathy.

Plasma vitamin C level, fruit and vegetable consumption, and the risk of new-onset type 2 diabetes mellitus: the European prospective investigation of cancer--Norfolk prospective study.

Source: Archives of internal medicine 2008; 168(14):1493-9

Author: Harding AH, Wareham NJ, Bingham SA, Khaw K, Luben R, Welch A, Forouhi NG.

Affiliation: Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Cambridge, England.

Abstract: Epidemiologic studies suggest that greater consumption of fruit and vegetables may decrease the risk of diabetes mellitus, but the evidence is limited and inconclusive. Plasma vitamin C level is a good biomarker of fruit and vegetable intake, but, to our knowledge, no prospective studies have examined its association with diabetes risk. This study aims to examine whether fruit and vegetable intake and plasma vitamin C level are associated with the risk of incident type 2 diabetes. The authors administered a semiquantitative food frequency questionnaire to men and women from a population-based prospective cohort (European Prospective Investigation of Cancer-Norfolk) study who were aged 40 to 75 years at baseline (1993-1997) when plasma vitamin C level was determined and habitual intake of fruit and vegetables was assessed. During 12 years of follow-up between February 1993 and the end of December 2005, 735 clinically incident cases of diabetes were identified among 21 831 healthy individuals. They reported the odds ratios of diabetes associated with sex-specific quintiles of fruit and vegetable intake and of plasma vitamin C levels. A strong inverse association was found between plasma vitamin C level and diabetes risk. Conclusion: Higher plasma vitamin C level and to a lesser degree, fruit and vegetable intake, was associated with a substantially decreased risk of diabetes. These findings highlight a potentially important public health message on the benefits of a diet rich in fruit and vegetables for the prevention of diabetes.

A Diet High in Low-Fat Dairy Products Lowers Diabetes Risk in Postmenopausal Women

Source: Journal of nutrition 2011; 141(11):1969-1974

Author: Margolis KL,Wei F, de Boer IH, et al

Affiliation: HealthPartners Research Foundation, Bloomington, MN, Department of Biostatistics, University of Arkansas for Medical Science, Little Rock, AR, University of Washington, Seattle, WA, Medstar Research Institute, Hyattsville, MD

Abstract: Some previous studies have suggested that consuming dairy products, particularly the low-fat variety, lowers the incidence of type 2 diabetes. However, no study to the knowledge of the authors has focused on an ethnically diverse group of postmenopausal women, a population with a high risk of this disease. The authors conducted a prospective cohort study of 82,076 postmenopausal women enrolled in the Women’s Health Initiative Observational Study who did not report diabetes at enrollment. Total, low-fat, and high-fat dairy product and yogurt intakes were estimated from FFQ at baseline and 3 years of follow-up. Treated diabetes incidence was ascertained from annual follow-up questionnaires. During 8 years of follow-up, 3946 cases of incident treated diabetes were reported. After multivariable adjustment, low-fat dairy product consumption was inversely associated with the risk of type 2 diabetes. RR was roughly 0.5–0.6 in the upper quintiles compared with the lowest quintile (median servings/d, 2.8 in the 5th quintile and 1.5 in the 4th quintile vs. 0.05 in the first quintile; P-trend < 0.001). The inverse relationship was more pronounced in women with a higher BMI. High yogurt consumption was associated with a significant decrease in diabetes risk, whereas there was no relationship between high-fat dairy product consumption and diabetes risk. A diet high in low-fat dairy products is associated with lower diabetes risk in postmenopausal women, particularly those who are obese.

Vitamin D and incidence of diabetes: A prospective cohort study

Source: Clinical Nutrition 2011 Dec 26. [Epub ahead of print]

Author: González-Molero I, Rojo-Martínez G, Morcillo S, Gutiérrez-Repiso C, Rubio-Martín E, Almaraz MC, Olveira G, Soriguer F.

Affiliation: Servicio de Endocrinología y Nutrición, Hospital Universitario Carlos Haya, Málaga, Spain; Ciber de Diabetes y Metabolismo (CIBERDEM), Spain.

Abstract: This study was conducted to investigate the relationship between levels of 25-hydroxyvitamin D and the incidence of type 2 diabetes in a Spanish population. Therefore the authors undertook a population-based prospective study in a population from southern Spain. The first phase of the study (1996-1998) included 1226 individuals. Of this original cohort, 988 persons were reassessed in 2002-2004 and 961 in 2005-2007. Measurements were made of 25-hydroxyvitamin D and intact parathyroid hormone in 2002-2004 and an oral glucose tolerance test was done in three time points. The incidence of diabetes in subjects with 25-hydroxyvitamin D levels =18.5 ng/mL (percentile 25) was 12.4% vs 4.7% in subjects with levels >18.5 ng/mL. The likelihood of having diabetes during the four years of follow-up was significantly lower in the subjects with higher levels of 25-hydroxyvitamin D. None of the subjects with levels higher than 30 ng/mL developed diabetes. Conclusion: In this prospective study, the authors found a significant inverse association between serum 25-hydroxyvitamin D levels and the risk for type 2 diabetes in a population from the south of Spain.

Vitamin D deficiency in obese children and its relationship to glucose homeostasis.

Source: The Journal of clinical endocrinology and metabolism 2012; 97(1):279-85.

Author: Olson ML, Maalouf NM, Oden JD, White PC, Hutchison MR.

Affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Abstract: The aim of the study was to compare the prevalence of vitamin D deficiency in obese and non-overweight children in North Texas, to examine relationships between dietary habits and 25-hydroxyvitamin D [25(OH)D] level in obese children, and to examine the relationship between 25(OH)D level and markers of abnormal glucose metabolism and blood pressure. Using a cross-sectional design, systolic and diastolic blood pressure, dietary information, serum 25(OH)D, fasting glucose and insulin, 2-h glucose from oral glucose tolerance test, hemoglobin A1c, and homeostasis model assessment of insulin resistance were recorded for 411 obese subjects (6-16 yr old) at an obesity referral clinic. 25(OH)D was also obtained from 87 control non-overweight subjects (6-16 yr old). Ninety-two percent of obese subjects had a 25(OH)D level below 75 nmol/liter, and 50% were below 50 nmol/liter. Among non-overweight subjects, these frequencies were 68 and 22%, respectively. 25(OH)D was negatively associated with soda intake, juice intake, and skipping breakfast. 25(OH)D was negatively correlated with homeostasis model assessment of insulin resistance and 2-h glucose after adjustment for body mass index and age but was not correlated with hemoglobin A1c, systolic blood pressure Z score, or diastolic blood pressure Z score. Conclusion: Vitamin D deficiency is common in children in this southern United States location and is significantly more prevalent in obese children. Lower 25(OH)D level is associated with risk factors for type 2 diabetes in obese children.

Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial.

Source: Diabetes Care. 2011 Jan;34(1):14-9.

Author: Salas-Salvadó J, Bulló M, Babio N, Martínez-González MÁ, Ibarrola-Jurado N, Basora J, Estruch R, Covas MI, Corella D, Arós F, Ruiz-Gutiérrez V, Ros E; PREDIMED Study Investigators.

Affiliation: Human Nutrition Unit, Hospital Universitari de Sant Joan, Departament de Bioquímica i Biotecnologia, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.

Abstract: This study was conducted to test the effects of two Mediterranean diet (MedDiet) interventions versus a low-fat diet on incidence of diabetes. This was a three-arm randomized trial in 418 non-diabetic subjects aged 55-80 years recruited in one center (PREDIMED-Reus, northeastern Spain) of the Prevención con Dieta Mediterránea [PREDIMED] study, a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk. Participants were randomly assigned to education on a low-fat diet (control group) or to one of two MedDiets, supplemented with either free virgin olive oil (1 liter/week) or nuts (30 g/day). Diets were ad libitum, and no advice on physical activity was given. The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria. After a median follow-up of 4.0 years, diabetes incidence was 10.1%, 11.0%, and 17.9% in the MedDiet with olive oil group, the MedDiet with nuts group, and the control group, respectively. When the 2 MedDiet groups were pooled and compared with the control group, diabetes incidence was reduced by 52%. In all study arms, increased adherence to the MedDiet was inversely associated with diabetes incidence. Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity. Conclusion: MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk.

Vitamin D levels predict all-cause and cardiovascular disease mortality in subjects with the metabolic syndrome: the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.

Source: Diabetes Care. 2012 May;35(5):1158-64.

Author: Thomas GN, ó Hartaigh B, Bosch JA, Pilz S, Loerbroks A, Kleber ME, Fischer JE, Grammer TB, Böhm BO, März W.

Affiliation: Public Health, Epidemiology and Biostatistics, University of Birmingham, Birmingham, UK.

Abstract: Optimal vitamin D levels are associated with reduced cardiovascular and all-cause mortality. The authors investigated whether optimal 25-hydroxyvitamin D (25[OH]D) is protective in individuals with the metabolic syndrome. The Ludwigshafen Risk and Cardiovascular Health (LURIC) study is a cohort study of subjects referred for coronary angiography between 1997 and 2000, from which 1,801 with the metabolic syndrome were investigated. Mortality was tracked for a median of 7.7 years. Multivariable survival analysis was used to estimate the association between 25(OH)D levels and mortality. Most subjects (92%) had suboptimal levels of 25(OH)D (<75 nmol/L), with 22.2% being severely deficient (<25 nmol/L). During follow-up, 462 deaths were recorded, 267 (57.8%) of which were cardiovascular in origin. After full adjustment, including the metabolic syndrome components, those with optimal 25(OH)D levels showed a substantial reduction in all-cause and cardiovascular disease mortality compared with those with severe vitamin D deficiency. For specific cardiovascular disease mortality, there was a strong reduction for sudden death and congestive heart failure, but not for myocardial infarction. The reduction in mortality was dose-dependent for each of these causes. Conclusion: Optimal 25(OH)D levels substantially lowered all-cause and cardiovascular disease mortality in subjects with the metabolic syndrome. These observations call for interventional studies that test whether vitamin D supplementation provides a useful adjunct in reducing mortality in these subjects.

Lower vitamin D status is more common among Saudi adults with diabetes mellitus type 1 than in non-diabetics

Source: http://www.ncbi.nlm.nih.gov/pubmed/24517121

Author: Al-Daghri NM, et al.

Affiliation: Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Saudi Arabia

Abstract: Vitamin D deficiency is an increasingly recognized comorbidity in patients with type 1 diabetes mellitus (DMT1), suggesting that vitamin D deficiency might play a role in DMT1. The researchers aimed to determine and compare the vitamin D status of Saudi adults with and without DMT1. A total of 60 Saudi adults with DMT1 from the Diabetes Clinics and 60 non-DM, healthy controls were included in the study. The mean age for those with DMT1 was 25.9 +/- 16.1 years versus 36.7 +/- 3.6 years among the controls. The study measured serum 25-hydroxy vitamin D (25OHD), calcium, cholesterol, blood glucose, HDL, and triglycerides and compared the results between the DMT1 group and control subjects. Both the DMT1 and healthy groups had vitamin D deficiency. The mean levels of 25OHD were significantly lower in the DMT1 adults than in the controls (28.1 +/- 1.4 nmol/L versus 33.4 +/- 1.6 nmol/L). In the DMT1 adults, 66.7% were mildly, 31.7% moderately, and 3.3% severely vitamin D deficient as compared with 41.7% (mildly), 31.7% (moderately), and 5% (severely) in the control group. Overall, 100% of the DMT1 adults and 78% of the healthy children were vitamin D deficient. Conclusion: The prevalence of vitamin D deficiency among DMT1 adults was relatively high. Therefore, screening for vitamin D deficiency and supplementation for this population should be warranted.

Serum vitamin-D predicts insulin resistance in individuals with prediabetes

Source: http://www.ncbi.nlm.nih.gov/pubmed/24521626

Author: Dutta D, et al.

Affiliation: Department of Endocrinology & Metabolism, Institute of Postgraduate Medical Education & Research & SSKM Hospital, Kolkata, India.

Abstract: Patients with diabetes and vitamin-D insufficiency have increased insulin resistance. Similar observations among individuals with prediabetes are not well documented. The aim of this study was to find the occurrence of vitamin-D insufficiency/deficiency among individuals with prediabetes and to evaluate the relationship between vitamin-D status and insulin resistance. 157 individuals with prediabetes who fulfilled all the inclusion and exclusion criteria underwent clinical examination, anthropometric measurements (waist circumference, waist-hip ratio, waist-height ratio) and blood sampling after overnight fast for estimation of fasting blood glucose, fasting insulin, 25(OH)vitamin-D, intact parathyroid hormone (iPTH) and lipid profile. One hour post 75 g glucose (1hPG) blood glucose during oral glucose tolerance test was measured. Vitamin-D deficiency/insufficiency was found in 115 (73.25%) individuals with prediabetes. Severe vitamin-D deficiency (<10 ng/ml) was seen in 14.65 per cent individuals. Individuals with the lowest vitamin-D levels (<10 ng/ml) had the highest insulin resistance. Serum 25(OH)D had a statistically significant inverse correlation with insulin resistance, and positive correlation with insulin sensitivity, after adjusting for BMI and HbA1c. There was no correlation between vitamin-D status and estimated beta cell mass. The mean waist-height ratio among individuals with prediabetes was 0.57 (normal<0.5) indicating a high risk of cardiovascular morbidity. Individuals with elevated 1hPG(>155 mg/dl) had significantly higher BMI and worse insulin resistance, and 1hPG correlated well with 2 hour post glucose blood glucose. The researchers concluded that vitamin-D deficiency/insufficiency may have some role in the development/worsening of insulin resistance in individuals with prediabetes in India who have a high cardiovascular risk.

Lower vitamin D levels at first trimester are associated with higher risk of developing gestational diabetes mellitus.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24526261

Author: Lacroix M, et al.

Affiliation: Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.

Abstract: The progressive increase of insulin resistance observed in pregnancy contributes to the pathophysiology of gestational diabetes mellitus (GDM). There is controversy whether vitamin D deficiency contributes to abnormal glycemic regulation in pregnancy. Researchers tested the associations between first trimester 25-hydroxyvitamin D (25OHD) levels and: 1) the risk of developing GDM; 2) insulin resistance/sensitivity, beta cell function and compensation indices in a large population-based prospective cohort of pregnant women. Participants (n = 655) were seen at first (6-13 weeks) and second (24-28 weeks) trimesters for blood samples. At first trimester, 25OHD levels were measured. At second trimester, glucose and insulin were measured 3 times during the oral glucose tolerance test to estimate insulin resistance (HOMA-IR), beta cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUCins/gluc) and beta cell compensation (ISSI-2). Based on IADPSG criteria, 54 participants (8.2 %) developed GDM. Lower first trimester 25OHD levels were associated with higher risk of developing GDM even after adjustment for vitamin D confounding factors and GDM risk factors. Lower first trimester 25OHD levels were associated with higher HOMA-IR, lower Matsuda index and lower ISSI-2. After adjustment for confounders, no significant association with HOMA-B and AUCins/gluc was found. The study results suggest that low levels of 25OHD at first trimester are (1) an independent risk factor for developing GDM and (2) associated with insulin resistance at second trimester.

Oral Magnesium Supplementation Decreases C-reactive Protein Levels in Subjects with Prediabetes and Hypomagnesemia: A Clinical Randomized Double-blind Placebo-controlled Trial.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24814039

Author: Simental-Mendía LE, et al.

Affiliation: Biomedical Research Unit, Mexican Social Security Institute, Durango, Mexico; The Research Group on Diabetes, Durango, Mexico.

Abstract: It has been suggested that magnesium deficiency is associated with the triggering of acute phase response, which may contribute to type 2 diabetes and cardiovascular disease risk. The researchers undertook this study to determine whether oral magnesium supplementation modifies serum levels of high-sensitivity C-reactive protein (hsCRP) in apparently healthy subjects with prediabetes and hypomagnesemia. A total of 62 men and non-pregnant women aged 18-65 year, with new diagnosis of prediabetes and hypomagnesemia were enrolled in a clinical double-blind placebo-controlled trial and randomly allocated to receive either magnesium chloride or NaHCO3 0.1% solution, once daily for 3 months. At basal conditions, anthropometric and biochemical variables were similarly distributed in both groups. At the end of follow-up, participants who received magnesium chloride showed higher serum magnesium levels and lower hsCRP levels compared with participants in the control group. Conclusion: Oral magnesium supplementation decreases hsCRP levels in apparently healthy subjects with prediabetes and hypomagnesemia.

Diabetes and Curcumin

Effect of turmeric and curcumin on oxidative stress and antioxidant enzymes in streptozotocin-induced diabetic rat

Source: Medical Science Monitor 2007; 13(12):BR286-92

Author: Suryanarayana P, Satyanarayana A, Balakrishna N, Kumar PU, Reddy GB

Affiliation: Department of Biochemistry, National Institute of Nutrition, Hyderabad, India.

Abstract: There is increasing evidence that complications related to diabetes are associated with increased oxidative stress. Curcumin, an active principle of turmeric*, has several biological properties, including antioxidant activity. The protective effect of curcumin and turmeric on streptozotocin* (STZ)-induced oxidative stress in various tissues of rats was studied. Three-month-old Wistar-NIN rats were made diabetic by injecting STZ (35 mg/kg body weight) intraperitoneally and fed either only the AIN-93* diet or the AIN-93 diet containing 0.002% or 0.01% curcumin or 0.5% turmeric for a period of eight weeks. After eight weeks the levels of oxidative stress parameters and activity of antioxidant enzymes were determined in various tissues. STZ-induced hyperglycemia resulted in increased lipid peroxidation and protein carbonyls in red blood cells and other tissues and altered antioxidant enzyme activities. Interestingly, feeding curcumin and turmeric to the diabetic rats controlled oxidative stress by inhibiting the increase in TBARS* and protein carbonyls and reversing altered antioxidant enzyme activities without altering the hyperglycemic state in most of the tissues. Conclusion: Turmeric and curcumin appear to be beneficial in preventing diabetes-induced oxidative stress in rats despite unaltered hyperglycemic status.

* Turmeric is a spice grown in India and other tropical regions of Asia.
* Streptozotocin (Streptozocin, STZ, Zanosar) is a naturally occurring chemical that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. It is used in medicine for treating certain cancers of the Islets of Langerhans and used in medical research to produce an animal model for Type 1 diabetes.
* "AIN" stands for "American Institute of Nutrition," which is now known as the America Society for Nutritional Sciences. They have published purified diet formulas that are well-accepted and respected in the scientific community as sound general nutrition for laboratory rodents.
* TBARS - Thiobarbituric Acid Reactive Substances - are formed as a byproduct of lipid peroxidation (i.e. as degradation products of fats).

Diabetes and Kidney Disease

Resveratrol retards progression of diabetic nephropathy through modulations of oxidative stress, proinflammatory cytokines, and AMP-activated protein kinase*.

Source: Journal of biomedical sciences 2011; 18(1):47

Author: Chang CC, Chang CY, Wu YT, Huang JP, Yen TH, Hung LM

Affiliation: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taiwan.

Abstract: Diabetic nephropathy (DN) has been recognized as the leading cause of end-stage renal disease. Resveratrol (RSV), a polyphenolic compound, has been indicated to possess an insulin-like property in diabetes. In the present study, the authors aimed to investigate the renoprotective effects of RSV and delineate its underlying mechanism in early-stage DN. In this study the protective effects of RSV on DN were evaluated in streptozotocin (STZ)-induced diabetic rats. The plasma glucose, creatinine, and blood urea nitrogen were significantly elevated in STZ-induced diabetic rats. RSV treatment markedly ameliorated hyperglycemia and renal dysfunction in STZ-induced diabetic rats. The diabetes-induced superoxide anion and protein carbonyl levels were also significantly attenuated in RSV-treated diabetic kidney. The AMPK protein phosphorylation* and expression levels were remarkably reduced in diabetic renal tissues. In contrast, RSV treatment significantly rescued the AMPK protein expression and phosphorylation compared to non-treated diabetic group. Additionally, hyperglycemia markedly enhanced renal production of proinflammatory cytokine* IL-1β*. RSV reduced IL-1β but increased TNF-α* and IL-6 levels in the diabetic kidneys.Conclusion: The findings of this study suggest that RSV protects against oxidative stress, exhibits concurrent proinflammation and anti-inflammation, and up-regulates AMPK expression and activation, which may contribute to its beneficial effects on the early stage of DN.

* 5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme that plays a role in cellular energy homeostasis. It is expressed in a number of tissues, including the liver, brain, and skeletal muscle. The net effect of AMPK activation is stimulation of hepatic fatty acid oxidation and ketogenesis, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipolysis and lipogenesis, stimulation of skeletal muscle fatty acid oxidation and muscle glucose uptake, and modulation of insulin secretion by pancreatic beta-cells.
* Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes.
* Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication.
* IL-1β is a member of the interleukin 1 cytokine family. This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis.
* Tumor necrosis factor-alpha (TNF-A) is an inflammatory cytokine.

Resveratrol protects diabetic kidney by attenuating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via Nrf2-Keap1* signaling.

Source: Biochimica et biophysica acta 2011; 1812(7):719-31

Author: Palsamy P, Subramanian S.

Affiliation: Department of Biochemistry, University of Madras, India.

Abstract: Hyperglycemia-mediated oxidative stress plays a crucial role in the progression of diabetic nephropathy. Hence, the present study was hypothesized to explore the renoprotective nature of resveratrol by assessing markers of oxidative stress, proinflammatory cytokines and antioxidant competence in streptozotocin-nicotinamide-induced diabetic rats. Oral administration of resveratrol to diabetic rats showed a significant normalization on the levels of creatinine clearance, plasma adiponectin, C-peptide and renal superoxide anion, hydroxyl radical, nitric oxide, TNF-α, IL-1β, IL-6 and NF-κB p65 subunit and activities of renal aspartate transaminase, alanine transaminase and alkaline phosphatase in comparison with diabetic rats. The altered activities of renal aldose reductase, sorbitol dehydrogenase and glyoxalase-I and elevated level of serum advanced glycation end products in diabetic rats were also reverted back to near normalcy. Further, resveratrol treatment revealed a significant improvement in superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase activities and vitamins C and E, and reduced glutathione levels, with a significant decline in lipid peroxides, hydroperoxides and protein carbonyls levels in diabetic kidneys. Similarly, mRNA and protein analyses substantiated that resveratrol treatment notably normalizes the renal expression of Nrf2/Keap1and its downstream regulatory proteins in the diabetic group of rats. Histological and ultrastructural observations also evidenced that resveratrol effectively protects the kidneys from hyperglycemia-mediated oxidative damage. These findings demonstrated the renoprotective nature of resveratrol by attenuating markers of oxidative stress in renal tissues of diabetic rats.

* Nrf2-Keap1 defines a physiologically important stress response mechanism.

Resveratrol ameliorates early diabetic nephropathy associated with suppression of augmented TGF-β/smad* and ERK1/2* signaling in streptozotocin-induced diabetic rats.

Source: Chemico-biological interactions 2011; 190(1):45-53

Author: Chen KH, Hung CC, Hsu HH, Jing YH, Yang CW, Chen JK.

Affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taiwan.

Abstract: Diabetic nephropathy (DN) is the major cause of end-stage renal disease. The early changes in DN are characterized by an increased in kidney size, glomerular volume, and kidney function, followed by the accumulation of glomerular extracellular matrix, increased urinary albumin excretion (UAE), glomerular sclerosis, and tubular fibrosis. Resveratrol (RSV) has been shown to ameliorate hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats. In the present study, the authors examined the beneficial effects of RSV on DN and explored the possible mechanism of RSV action. Male Sprague-Dawley rats were injected with streptozotocin at 65mg/kg body weight. The induction of diabetes mellitus (DM) was confirmed by a fasting plasma glucose level ≥300mg/dL and symptoms of polyphagia and polydipsia. The DM rats were treated with or without RSV at 0.75mg/kg body weight 3 times a day for 8 weeks. Animals were sacrificed and kidney histology was examined by microscopy. Urinary albumin excretion, glomerular hypertrophy and expressions of fibronectin, collagen IV, and TGF-β in the glomeruli were alleviated in RSV-treated DM rats, but not in untreated DM rats. In addition, RSV treatment reduced the thickness of the glomerular basement membrane (GBM) to the original thickness and increased nephrin expressions to normal levels in DM rats. Moreover, RSV inhibited phosphorylation of smad2, smad3 and ERK1/2 in diabetic rat kidneys. This is the first report showing that RSV alleviates early glomerulosclerosis in DN through TGF-β/smad and ERK1/2 inhibition. In addition, podocyte* injuries of diabetic kidneys are lessened by RSV.

* Transforming growth factor beta (TGF-β) is a protein that controls proliferation, cellular differentiation, and other functions in most cells. It plays a role in immunity, cancer, heart disease, diabetes.
* Extracellular-signal-regulated kinases (ERKs) or classical MAP kinases are widely expressed protein kinase intracellular signaling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells. Many different stimuli, including growth factors, cytokines, virus infection, and carcinogens, activate the ERK pathway.
* Podocytes (or visceral epithelial cells) are cells in the Bowman's capsule in the kidneys that wrap around the capillaries of the glomerulus. The Bowman's capsule filters blood, holding back large molecules such as proteins, and passing through small molecules such as water, salts, and sugar, as the first step in forming urine.

Ameliorative potential of resveratrol on proinflammatory cytokines, hyperglycemia mediated oxidative stress, and pancreatic beta-cell dysfunction in streptozotocin-nicotinamide-induced diabetic rats.

Source: Journal of cellular physiology 2010; 224(2):423-32

Author: Palsamy P, Subramanian S.

Affiliation: Department of Biochemistry, University of Madras, India.

Abstract: Chronic exposure of pancreatic beta-cells to supraphysiologic glucose causes adverse beta-cell dysfunction. Thus, the present study was aimed to investigate the hypothesis that oral administration of resveratrol attenuates hyperglycemia, proinflammatory cytokines and antioxidant competence and protects beta-cell ultrastructure in streptozotocin-nicotinamide-induced diabetic rats. Oral administration of resveratrol (5 mg/kg body weight) to diabetic rats for 30 days showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), TNF-alpha, IL-1beta, IL-6, NF-kappaB p65 unit and nitric oxide (NO) with concomitant elevation in plasma insulin. Further, resveratrol treated diabetic rats elicited a notable attenuation in the levels of lipid peroxides, hydroperoxides and protein carbonyls in both plasma and pancreatic tissues. The diminished activities of pancreatic superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione-S-transferase (GST) as well as the decreased levels of plasma ceruloplasmin, vitamin C, vitamin E and reduced glutathione (GSH) in diabetic rats were reverted to near normalcy by resveratrol administration. Based on histological and ultrastructural observations, it is first-time reported that the oral administration of resveratrol may effectively rescue beta-cells from oxidative damage without affecting their function and structural integrity. The results of the present investigation demonstrated that resveratrol exhibits significant antidiabetic potential by attenuating hyperglycemia, enhancing insulin secretion and antioxidant competence in pancreatic beta-cells of diabetic rats.

Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats

Source: Clinical and experimental pharmacology and physiology 2006; 33(10): 940-5

Author: Sharma S, Kulkarni SK, Chopra K.

Affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.

Abstract: Chronic hyperglycemia in diabetes leads to the overproduction of free radicals and evidence is increasing that these contribute to the development of diabetic nephropathy. Among the spices, turmeric (Curcuma longa) is used as a flavoring and coloring agent in the Indian diet every day and is known to possess anti-oxidant properties. The present study was designed to examine the effect of curcumin, a yellow pigment of turmeric, on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. Four weeks after STZ injection, rats were divided into four groups, namely control rats, diabetic rats and diabetic rats treated with curcumin (15 and 30 mg/kg, p.o.) for 2 weeks. Renal function was assessed by creatinine, blood urea nitrogen, creatinine and urea clearance and urine albumin excretion. Oxidative stress was measured by renal malonaldehyde, reduced glutathione and the anti-oxidant enzymes superoxide dismutase and catalase. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria and a decrease in bodyweight compared with age-matched control rats. After 6 weeks, diabetic rats also exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance and proteinuria, along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Chronic treatment with curcumin significantly attenuated both renal dysfunction and oxidative stress in diabetic rats. These results provide confirmatory evidence of oxidative stress in diabetic nephropathy and point towards the possible anti-oxidative mechanism being responsible for the nephroprotective action of curcumin.

Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats

Source: Pharmacology 2006;76(2):69-75

Author: Sharma S, Anjaneyulu M, Kulkarni SK, Chopra K.

Affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, India.

Abstract: Diabetic nephropathy is a serious microvascular complication and one of the main causes of end-stage renal disease. Various studies have revealed that increased oxidative stress is a major pathophysiological mechanism which is involved in the etiology of diabetic nephropathy. Resveratrol, a polyphenolic phytoalexin present in red wine, is known to possess potent antioxidant properties and thus the authors aimed to examine its effect on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. After 4 weeks of STZ injection, rats were divided into four groups: the control rats, diabetic rats and diabetic rats treated with resveratrol (5 and 10 mg/kg, orally) respectively from week 4 up till week 6. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The levels of the renal oxidative stress markers malonaldehyde and glutathione and the antioxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. STZ-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in body weight compared with age-matched control rats. After 6 weeks, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance, and proteinuria along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key antioxidant enzymes. Treatment with resveratrol significantly attenuated renal dysfunction and oxidative stress in diabetic rats. The present study reinforces the important role of oxidative stress in diabetic kidney and points towards the possible antioxidative mechanism being responsible for the renoprotective action of resveratrol.

Quercetin, an anti-oxidant bioflavonoid, attenuates diabetic nephropathy in rats

Source: Clin Exp Pharmacol Physiol. 2004; 31(4): 244-8

Author: Anjaneyulu M, Chopra K.

Affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.

Abstract: Diabetic nephropathy is an important microvascular complication and one of the main causes of end-stage renal disease. Many in vivo and in vitro studies have indicated that oxidative stress is one of the major pathophysiological mechanisms involved in the development of diabetic nephropathy. In the present study, the authors examined the effect of an anti-oxidant bioflavonoid quercetin on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Sprague-Dawley rats with a single intravenous injection of STZ (45 mg/kg). Four weeks after STZ injection, quercetin (10 mg/kg per day) was given orally for 4 weeks in both control and diabetic rats. Plasma glucose levels and bodyweights were measured at 4 and 8 weeks after the STZ injection. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The renal oxidative stress marker malonaldehyde, glutathione levels and the anti-oxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in bodyweight compared with age-matched control rats. After 8 weeks, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance, and proteinuria along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Treatment with quercetin significantly attenuated renal dysfunction and oxidative stress in diabetic rats. These results confirm the role of oxidative stress in the development of diabetic nephropathy and point to the possible anti-oxidative mechanism being responsible for the nephroprotective action of quercetin.

Diabetes and Resveratrol

Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients.

Source: Br J Nutr. 2011; 9:1-7

Author: Brasnyó P, Molnár GA, Mohás M, Markó L, Laczy B, Cseh J, Mikolás E, Szijártó IA, Mérei A, Halmai R, Mészáros LG, Sümegi B, Wittmann I.

Affiliation: 2nd Department of Internal Medicine and Nephrological Center, Faculty of Medicine, University of Pécs, Pacsirta Street 1, Pécs H-7624, Hungary.

Abstract: Although resveratrol has widely been studied for its potential health benefits, little is known about its metabolic effects in humans. Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action. The present study shows for the first time that resveratrol improves insulin sensitivity in humans, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin signaling via the Akt pathway.

High dietary magnesium intake is associated with low insulin resistance in the Newfoundland population.

Source: http://www.ncbi.nlm.nih.gov/pubmed/23472169

Author: Cahill F, Shahidi M, Shea J, Wadden D, Gulliver W, Randell E, Vasdev S, Sun G.

Affiliation: Division of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.

Abstract: Magnesium plays a role in glucose and insulin homeostasis and evidence suggests that magnesium intake is associated with insulin resistance (IR). However, data is inconsistent and most studies have not adequately controlled for critical confounding factors. The study investigated the association between magnesium intake and IR in normal-weight (NW), overweight (OW) and obese (OB) along with pre- and post- menopausal women. A total of 2295 subjects (590 men and 1705 women) were recruited from the CODING study. Dietary magnesium intake was computed from the Willett Food Frequency Questionnaire (FFQ). Adiposity (NW, OW and OB) was classified by body fat percentage (%BF) measured by Dual-energy X-ray absorptiometry according to the Bray criteria. Multiple regression analyses were used to test adiposity-specific associations of dietary magnesium intake on insulin resistance adjusting for caloric intake, physical activity, medication use and menopausal status. Subjects with the highest intakes of dietary magnesium had the lowest levels of circulating insulin, HOMA-IR, and HOMA-ß and subjects with the lowest intake of dietary magnesium had the highest levels of these measures, suggesting a dose effect. Multiple regression analysis revealed a strong inverse association between dietary magnesium with IR. In addition, adiposity and menopausal status were found to be critical factors revealing that the association between dietary magnesium and IR was stronger in OW and OB along with Pre-menopausal women. Conclusion: The results of this study indicate that higher dietary magnesium intake is strongly associated with the attenuation of insulin resistance and is more beneficial for overweight and obese individuals in the general population and pre-menopausal women. Moreover, the inverse correlation between insulin resistance and dietary magnesium intake is stronger when adjusting for %BF than BMI.

Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients.

Source: http://www.ncbi.nlm.nih.gov/pubmed/23561637

Author: Breslavsky A, Frand J, Matas Z, Boaz M, Barnea Z, Shargorodsky M.

Affiliation: Department of Medicine, Wolfson Medical Center, Israel.

Abstract: Vitamin D supplementation has the potential to alleviate the cardiovascular damage in diabetic patients. The present study was designed to evaluate long term impact of high doses of vitamin D on arterial properties, glucose homeostasis, adiponectin and leptin in patients with type 2 diabetes mellitus. In randomized, placebo-controlled study 47 diabetic patients were assigned into two groups: Group 1 received oral daily supplementation with vitamin D at a dose of 1000 U/day for 12 months. Group 2 received matching placebo capsules. Blood sampling for metabolic parameters, including fasting glucose, lipid profile, HbA1C, insulin, hs-CRP, 25 OH Vit D, adiponectin and leptin was performed at baseline and at the end of the study. Insulin resistance was assessed by homeostasis model assessment (HOMA-IR). Central aortic augmentation index (AI) was evaluated using SphygmoCor. The two groups were similar at baseline in terms of hemodynamic parameters. After 12 months, AI decreased significantly during the treatment period in patients received vitamin D and did not change in placebo group. Glucose homeostasis parameters, leptin as well as leptin adiponectin ratio did not change in both groups. 25 OH Vit D level significantly increased and circulating adiponectin marginally increased during 12 month treatment period in active treatment and did not change in placebo group. Conclusion: High doses of vitamin D supplementation in diabetic patients was associated with significant decrease in AI during one year treatment.

Diabetes and Vasculopathy

Resveratrol ameliorates vasculopathy in STZ-induced diabetic rats: role of AGE-RAGE* signaling.

Source: Diabetes/metabolism research and reviews 2010; 26(3):212-22

Author: Jing YH, Chen KH, Yang SH, Kuo PC, Chen JK

Affiliation: Department of Physiology, College of Medicine, Chang Gung University, Taiwan.

Abstract: Resveratrol (RSV) has been shown to ameliorate hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats. In the present study, the authors examined the beneficial effects of RSV on diabetes mellitus (DM)-induced vasculopathy and explored its possible mechanism. Male Sprague-Dawley rats were injected with streptozotocin at 65 mg/kg body weight The induction of DM was confirmed by a fasting plasma glucose level > or = 300 mg/dL and symptoms of polyphagia and polydipsia. The DM rats were treated with or without RSV at 0.75 mg/kg body weight three times a day for 4-8 weeks. Animals were sacrificed and vessel wall histology was examined by microscopy. The vascular smooth muscle cell activation was assessed by the medial thickness, collagen deposition, and the expressions receptor for advanced glycation end product, NF-kappaB*, proliferation cell nuclear antigen, and the levels of Erk1/2 phosphorylation. In RSV-treated DM rats, the vascular wall thickening, collagen deposition/cross-linking, and vascular permeability were all alleviated compared with that of the untreated DM rats. The vascular smooth muscle cell of the RSV-treated rats was characterized with less proliferation, lower NF-kappaB, and Erk1/2 activation, decreased proliferation cell nuclear antigen and receptor for advanced glycation end product expression. Moreover, the plasma fructosamine was significantly reduced in RSV-treated DM rats. Conclusion: RSV alleviated DM-induced vasculopathy through attenuation of advanced glycation end product-receptor for advanced glycation end product-NF-kappaB signaling pathway.

* Studies revealed advanced glycation end products (AGE) as the major environmental account for vascular cell derangement characteristic of diabetes and the receptor for AGE (RAGE) as the major genic factor that responds to them.
* NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls the transcription of DNA. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κB plays a key role in regulating the immune response to infection (kappa light chains are critical components of immunoglobulins). Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development.