calcitriol and Diabetes-Mellitus--Type-2

The potential beneficial effects of supplementing vitamin D or treatment with pharmacological doses of vitamin D in the prevention or cure of diseases like type 1 (T1D) or type 2 diabetes (T2D) remains the subject of debate. Data from epidemiological and association studies clearly indicate a correlation between vitamin D deficiency and a higher prevalence of both forms of diabetes. In animal models, vitamin D deficiency predisposes to type 1 and type 2 diabetes, whereas high doses of vitamin D or its active hormonal form, 1,25-dihydroxyvitamin D, prevent disease. Large scale, randomized, blinded prospective studies however, remain lacking. Here we discuss the current literature on a role for vitamin D in diabetes. We propose, in particular, to avoid vitamin D deficiency in individuals at risk of developing T1D or T2D. Applying international guidelines on supplementation of vitamin D using small daily doses of vitamin D (500-1000IU) may contribute to reduce the burden of diabetes by preventing vitamin D deficiency. Any other recommendations are at present not supported by data.

Topics: Animals; Causality; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dietary Supplements; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Risk Factors; Vitamin D; Vitamin D Deficiency

Reduced monocyte infiltration into the vessel wall and increased macrophage cholesterol efflux are critical components in atherosclerotic plaque regression. During inflammation, monocyte chemotactic protein 1 (MCP-1) signaling activation and cholesterol deposition in macrophages induce endoplasmic reticulum (ER) stress, which promotes an increased inflammatory response. Increased macrophage ER stress shifts macrophages into an M2 macrophage phenotype with increased cholesterol uptake and deposition. In type 2 diabetes, a population with elevated baseline risk of cardiovascular disease (CVD), vitamin D deficiency doubles that risk. We have found that 1,25-dihydroxy vitamin D [1,25(OH)2D] prevents foam cell formation during macrophage differentiation by suppressing ER stress. However, it is unknown whether suppression of ER stress by 1,25(OH)2D decreases monocyte infiltration and reverses atherogenic cholesterol metabolism in previously differentiated, vitamin D-deplete macrophages. We collected peripheral monocytes from type 2 diabetic patients and differentiated them into macrophages under vitamin D-deplete or 1,25(OH)2D-supplemented conditions. 1,25(OH)2D supplementation suppressed macrophage migration in response to MCP-1 and mRNA expression of chemokine (C-C motif) receptor 2 (CCR2), the MCP-1 receptor, compared to vitamin D-deplete cells. Furthermore, inhibition of ER stress with phenyl butyric acid resulted in similar effects even in vitamin D-deplete cells, while induction of ER stress with Thapsigargin under 1,25(OH)2D-supplemented conditions increased macrophage migration and CCR2 expression, suggesting that the effects of vitamin D on migration are mediated through ER stress suppression. To determine whether the detrimental pattern of macrophage cholesterol metabolism in vitamin D depletion is reversible, we assessed cholesterol uptake in macrophages differentiated under vitamin D-deplete conditions as described above, then supplemented with 1,25(OH)2D or maintained in vitamin D-deplete conditions. Cholesterol uptake was decreased in 1,25(OH)2D-supplemented compared to vitamin D-deplete cells, suggesting slowed cholesterol deposition with active vitamin D. 1,25(OH)2D supplementation also suppressed cholesteryl ester formation and enhanced cholesterol efflux in M2 macrophages compared to vitamin D-deplete cells, suggesting facilitation of cholesterol egress in the presence of 1,25(OH)2D. We thus provide further evidence that active vitamin D is an

Topics: Anticholesteremic Agents; Atherosclerosis; Cell Migration Inhibition; Cholesterol; Diabetes Mellitus, Type 2; Endoplasmic Reticulum Stress; Humans; Macrophages; Plaque, Atherosclerotic; Vitamin D

Considering that the vitamin D receptor as well as the 1-α-hydroxylase enzyme that converts 25-hydroxyvitamin D (25(OH)D) to its active form 1,25-dihydroxyvitamin D have been found in tissues throughout the body, it is likely that vitamin D is important for more than the calcium balance. Accordingly, low serum levels of 25(OH)D have been associated with mortality, cardiovascular disease, type 2 diabetes, hypertension and obesity. Low serum levels of 25(OH)D have also been associated with an unfavourable lipid profile, which could possible explain the relation with cardiovascular disease and mortality. However, the relation between vitamin D and lipids have so far received little attention and is therefore the main focus of the present review. A PubMed search identified 22 cross-sectional studies where serum levels of 25(OH)D and lipids were related and that included a minimum of 500 subjects, and 10 placebo-controlled double-blind intervention studies with vitamin D where more than 50 subjects were included. In all the cross-sectional studies serum 25(OH)D was positively associated with high-density lipoprotein cholesterol (HDL-C) resulting in a favourable low-density lipoprotein cholesterol (LDL-C) (or total cholesterol) to HDL-C ratio. There was also a uniform agreement between studies on a negative relation between serum 25(OH)D and triglycerides (TG). On the other hand, the intervention studies gave divergent results, with some showing a positive and some a negative effect of vitamin D supplementation. However, none of the intervention studies were specifically designed for evaluating the relation between vitamin D and lipids, none had hyperlipemia as an inclusion criterion, and none were sufficiently powered. In only one study was a significant effect seen with an 8% (0.28 mmol/L) increase in serum LDL-C and a 16% (0.22 mmol/L) decrease in serum TG in those given vitamin D as compared to the placebo group. Accordingly, the effect of vitamin D supplementation on serum lipids is at present uncertain. Considering the numerous other promising vitamins and minerals that when properly tested have been disappointing, one should wait for the results of forthcoming vitamin D intervention studies before drawing conclusions on potential beneficial effects of vitamin D.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypertension; Male; Obesity; Randomized Controlled Trials as Topic; Triglycerides; Vitamin D; Vitamin D Deficiency

Type 1 (T1D) and type 2 (T2D) diabetes are considered multifactorial diseases in which both genetic predisposition and environmental factors participate in their development. Many cellular, preclinical, and observational studies support a role for vitamin D in the pathogenesis of both types of diabetes including: (1) T1D and T2D patients have a higher incidence of hypovitaminosis D; (2) pancreatic tissue (more specifically the insulin-producing beta-cells) as well as numerous cell types of the immune system express the vitamin D receptor (VDR) and vitamin D-binding protein (DBP); and (3) some allelic variations in genes involved in vitamin D metabolism and VDR are associated with glucose (in)tolerance, insulin secretion, and sensitivity, as well as inflammation. Moreover, pharmacologic doses of 1,25-dihydroxyvitamin D (1,25(OH)(2)D), the active form of vitamin D, prevent insulitis and T1D in nonobese diabetic (NOD) mice and other models of T1D, possibly by immune modulation as well as by direct effects on beta-cell function. In T2D, vitamin D supplementation can increase insulin sensitivity and decrease inflammation. This article reviews the role of vitamin D in the pathogenesis of T1D and T2D, focusing on the therapeutic potential for vitamin D in the prevention/intervention of T1D and T2D as well as its complications.

Topics: Animals; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Genetic Predisposition to Disease; Glucose Intolerance; Humans; Immune System; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Mice; Pancreatitis; Rats; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein

Hypercalcemia occurs relatively often in dialysis patients. The most common cause of hypercalcemia in dialysis patients is the conventional therapy with calcium and calcitriol. Besides, secondary hyperparathyroidism, low turnover bone diseases, and immobilization are also common causes of hypercalcemia in dialysis patients. Fungal infection associated with hypercalcemia has been infrequently reported. We describe a 71-year-old female woman with end-stage renal disease and diabetes mellitus, who developed severe hypercalcemia. Pulmonary cryptococcosis, with increased concentration of serum 1,25-dihydroxyvitamin D (1,25(OH)2D), was diagnosed. Her serum concentration of calcium and 1,25(OH)2D returned to normal after antifungal treatment. Thus, hypercalcemia was mediated by extrarenal overproduction of 1,25(OH)2D in this patient.

Topics: Aged; Cryptococcosis; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Hypercalcemia; Kidney Failure, Chronic; Lung Diseases, Fungal; Renal Dialysis; Vitamin D

Although both vitamin D deficiency and obesity are highly prevalent in the UAE, the role of vitamin D metabolites in mediating obesity-related adverse health effects is not clear. We aimed to assess the role of vitamin D metabolites as potential mediators in the association between obesity, inflammation and metabolic risk factors.. 277 participants who were part of a randomized controlled trial had their assessment that included clinical, anthropometric and physical activity data at baseline and at 6 months. Blood and urine samples were taken for measurements of serum 25(OH)D, 25(OH)D metabolites including 25(OH)D3), 25(OH)D2), 1,25(OH)2D3, 3-Epi-D3), metabolic and inflammatory markers and related biochemical variables. Multiple regression analysis used to assess the role of 25(OH)D metabolites in mediating the effect of increasing body mass index (BMI) on inflammation and metabolic risk factors.. Overall, 277 participants with complete 6 months follow up with a mean (±SD) age of 41 ± 12 and 204 (74%) female were included in the study. Blood pressure, inflammatory, metabolic and lipid profile markers significantly increased in overweight and obese subjects compared to subjects with normal BMI both at baseline and at 6 months (p < 0.05). 25(OH)D revealed significant association with age, gender, HbA1c and type 2 diabetes (p < 0.05). No statistically significant changes in any of 25(OH)D metabolites assessed. Multivariate analysis revealed significant and independent associations between BMI and important inflammatory and metabolic risk factors (p < 0.05). No similar association observed with 25(OH)D metabolites.. Although we found significant association between 25(OH)D and prevalence of type 2 diabetes, we found no evidence however to support a role of 25(OH)D metabolites in mediating the effect of BMI on inflammatory or metabolic risk factors.

Topics: 25-Hydroxyvitamin D 2; Adult; Body Mass Index; Calcifediol; Calcitriol; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Multivariate Analysis; Obesity; Risk Factors; Vitamin D; Vitamin D Deficiency

Sodium glucose cotransporter-2 (SGLT2) inhibitors are the most recently approved class of drugs for type 2 diabetes and provide both glycemic efficacy and cardiovascular risk reduction. A number of safety issues have been identified, including treatment-emergent bone fractures. To understand the overall clinical profile, these safety issues must be balanced against an attractive efficacy profile. Our study was designed to investigate pathophysiological mechanisms mediating treatment-emergent adverse effects on bone health.. We conducted a single-blind randomized crossover study in hospitalized healthy adults (n = 25) receiving either canagliflozin (300 mg/d) or placebo for 5 days. The primary end-point was the drug-induced change in AUC for plasma intact fibroblast growth factor 23 (FGF23) immunoactivity between 24 and 72 hours.. Canagliflozin administration increased placebo-subtracted mean levels of serum phosphorus (+16%), plasma FGF23 (+20%), and plasma parathyroid hormone (PTH) (+25%), while decreasing the level of 1,25-dihydroxyvitamin D (-10%). There was substantial interindividual variation in the magnitude of each of these pharmacodynamic responses. The increase in plasma FGF23 was correlated with the increase in serum phosphorus, and the decrease in plasma 1,25-dihydroxyvitamin D was correlated with the increase in plasma FGF23.. Canagliflozin induced a prompt increase in serum phosphorus, which triggers downstream changes in FGF23, 1,25-dihydroxyvitamin D, and PTH, with potential to exert adverse effects on bone health. These pharmacodynamic data provide a foundation for future research to elucidate pathophysiological mechanisms of adverse effects on bone health, with the objective of devising therapeutic strategies to mitigate the drug-associated fracture risk.. ClinicalTrial.gov (NCT02404870).. Supported by the Intramural Program of NIDDK.

Topics: Adult; Canagliflozin; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fractures, Bone; Healthy Volunteers; Humans; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Placebos; Sodium-Glucose Transporter 2 Inhibitors; Vitamin D

Relative to European Americans, African Americans have lower 25-hydroxyvitamin D (25OHD) and vitamin D binding protein (VDBP) concentrations, higher 1,25-dihydroxyvitamin D (1,25(OH)2D3) concentrations and bone mineral density (BMD), and paradoxically reduced burdens of calcified atherosclerotic plaque (subclinical atherosclerosis). To identify genetic factors contributing to vitamin D and BMD measures, association analysis of >14M variants was conducted in a maximum of 697 African American-Diabetes Heart Study participants with type 2 diabetes (T2D). The most significant association signals were detected for VDBP on chromosome 4; variants rs7041 (β = 0.44, SE = 0.019, P = 9.4x10-86) and rs4588 (β = 0.17, SE = 0.021, P = 3.5x10-08) in the group-specific component (vitamin D binding protein) gene (GC). These variants were found to be independently associated. In addition, rs7041 was also associated with bioavailable vitamin D (BAVD; β = 0.16, SE = 0.02, P = 3.3x10-19). Six rare variants were significantly associated with 25OHD, including a non-synonymous variant in HSPG2 (rs116788687; β = -1.07, SE = 0.17, P = 2.2x10-10) and an intronic variant in TNIK (rs143555701; β = -1.01, SE = 0.18, P = 9.0x10-10), both biologically related to bone development. Variants associated with 25OHD failed to replicate in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Evaluation of vitamin D metabolism and bone mineral density phenotypes in an African American population enriched for T2D could provide insight into ethnic specific differences in vitamin D metabolism and bone mineral density.

Topics: Aged; Black or African American; Bone Density; Diabetes Mellitus, Type 2; Female; Genome-Wide Association Study; Humans; Male; Middle Aged; Polymorphism, Genetic; Vitamin D; Vitamin D-Binding Protein

The association between low vitamin D status and the development of type 2 diabetes mellitus is well established; however, intervention trials that increased serum vitamin D (through ultraviolet B exposure or dietary supplementation) provide mixed outcomes. Recent evidence suggests that metabolites directly related to vitamin D receptor activation-1α,25-dihydroxyvitamin D

Topics: Adult; Aged; Asian People; Calcifediol; Diabetes Mellitus, Type 2; Female; Glucose; Homeostasis; Humans; Insulin Resistance; Insulin Secretion; Intra-Abdominal Fat; Male; Middle Aged; Oxygen; Oxygen Consumption; Triglycerides; Vitamin D; Vitamin D Deficiency

Abnormal neutrophils are involved in many chronic endocrine diseases, including type 2 diabetes mellitus (T2DM), and in periodontitis (PD), which is a chronic inflammatory disease in which neutrophils play a vital role. The p38 mitogen-activated protein kinase (MAPK) signaling pathway participates in the apoptosis of many inflammatory cells. Additionally, 1,25-dihydroxyvitamin-D3 (1,25VitD3) as a regulator can induce responses to infection and tumor cell apoptosis. However, the effect of 1,25VitD3 in the pathogenic relationship between T2DM and PD remains unclear. The aim of this study was to assess the effect of 1,25VitD3 on neutrophil apoptosis in patients with T2DM and PD and the p38-MAPK-relevant signaling pathway mechanism in this process in vitro.. Neutrophils were stained with Wright's stain, and apoptosis was detected by flow cytometry and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. Apoptosis- and p38-related mRNAs and proteins were examined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting and ELISA. The internal relationships were analyzed using a linear regression equation and Pearson's correlation coefficient.. The highest rate of neutrophil apoptosis occurred in cultures treated with 10 mol/L 1,25VitD3 in the T2DM-PD group. The apoptosis rate in the T2DM-PD-p38 inhibitor group was higher than that in the healthy control group. Western blot, ELISA and qRT-PCR results showed that the mRNA and protein expression profiles of Caspase-3 and Bax were highly up-regulated and that Bcl-2 was down-regulated in the T2DM-PD-p38 inhibitor group. The expression levels of apoptotic mRNAs and proteins in the T2DM and T2DM-PD groups were significantly higher than those in the T2DM-p38 and T2DM-PD-p38 inhibitor groups. 1,25VitD3-induced neutrophil apoptosis and phosphorylated p38 (p-p38) expression were partially inhibited by the p38 inhibitor. Expression levels of apoptosis-related genes and p-p38 in neutrophils were positively associated with increasing concentrations of 1,25VitD3. p-p38 protein expression was positively associated with the level of serum 1,25VitD3.. 1,25VitD3 could promote peripheral blood neutrophil apoptosis in patients with T2DM and PD through activation of the p38-MAPK signaling pathway in vitro.

Topics: Apoptosis; Culture Techniques; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Flow Cytometry; Humans; Male; MAP Kinase Signaling System; Neutrophils; p38 Mitogen-Activated Protein Kinases; Periodontitis; Real-Time Polymerase Chain Reaction; RNA, Messenger; Vitamin D

To determine the interrelationships between body composition, glycemic control and vitamin D status in an ambulatory population with diabetes (DM) and chronic kidney disease (CKD).. Adult (18-80 years) patients (n=60) with DM and stage 1-4 CKD were recruited from the Northern Alberta Renal Program. Outcome variables included body composition (absolute/regional fat (FM)/lean soft tissue/total mass, percent fat/lean/fat-free (FFM) mass), glycemic control (glycated hemoglobin (HbA1c)), vitamin D intake (dietary/supplemental) and vitamin D status (25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D)) measured by validated methodologies. Sarcopenia was determined as an appendicular skeletal mass/height(2) less than 7.26 kg/m(2) (males) and 5.45 kg/m(2) (females).. Suboptimal HbA1c (>7%), 25(OH)D (<50 nmol/l) and 1,25(OH)2D (<43 pmol/l) concentrations were present in 57, 8 and 11% of participants. Ten percent of subjects had sarcopenia. Gender/age/DM type, not CKD, significantly influenced regional/whole body composition. Females, older participants and those with type 2 DM had higher %FM. No significant interrelationships between vitamin D status and glycemic control were observed (P>0.05). Serum 25(OH)D concentrations were inversely associated with arm lean soft tissue/FFM/total mass, weight, appendicular skeletal mass, lean soft tissue/height(2), FFM/height(2), appendicular skeletal mass/height(2) and body mass index (P<0.05). Sarcopenia occurred more frequently in patients with 25(OH)D concentrations ⩾100 nmol/l. Regional/whole body %FM was inversely related to 1,25(OH)2D, not 25(OH)D.. Body composition, not glycemic control, is associated with vitamin D status in an ambulatory population of adults with DM and CKD.

Topics: Adult; Aged; Alberta; Blood Glucose; Body Composition; Body Mass Index; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Sarcopenia; Vitamin D; Vitamin D Deficiency

Vitamin D binding protein (DBP) is an important determinant of bioavailable vitamin D (BAVD) and may provide clues to racial variation in osteoporosis and atherosclerosis.. The objective was to assess relationships between DBP, BAVD, 25-hydroxyvitamin D (25OHD), and 1,25 di-hydroxyvitamin D (1,25OH2D) with kidney, bone, adipose, and atherosclerosis phenotypes in African Americans with type 2 diabetes.. Cross-sectional (N = 545) and longitudinal (N = 288; mean 5.1 ± 0.9-year follow-up) relationships between vitamin D concentrations with renal phenotypes, vertebral bone mineral density, aorto-iliac, coronary artery, and carotid artery calcified plaque (CP), and adipose tissue volumes were studied.. African American-Diabetes Heart Study.. Participants were 56.7% female with mean ± standard deviation (sd) age 55.6 ± 9.6 years, diabetes duration 10.3 ± 8.2 years, and eGFR 90.9 ± 22.1 ml/min/1.73 m(2).. None.. Associations tested between vitamin D and the previously mentioned phenotypes adjusting for age, sex, African ancestry proportion, diabetes duration, statins, smoking, changes in estimated glomerular filtration rate, body mass index, hemoglobin A1c, and blood pressure.. 1,25OH2D was inversely associated with change in coronary artery CP (parameter estimate [β] -0.005, standard error [SE] 0.002; P = .037), with a trend for change in carotid artery CP (β -0.007, SE 0.004; P = .074). Further adjustment for renin-aldosterone-system blockade revealed inverse association between 1,25OH2D and change in albuminuria (β -0.004, SE 0.002; P = .037). DBP, BAVD, and 25OHD did not associate significantly with changes in albuminuria, CP, or bone mineral density. BAVD was inversely associated with visceral, subcutaneous, intermuscular, and pericardial adipose volumes.. In contrast to BAVD and 25OHD, only 1,25OH2D levels were significantly and inversely associated with changes in subclinical atherosclerosis and albuminuria in African Americans, suggesting potential beneficial effects.

Topics: Aged; Albuminuria; Atherosclerosis; Black or African American; Bone Density; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Vitamin D; Vitamin D-Binding Protein

To examine the associations between serum 25-hydroxyvitamin D (25OHD) levels and the active vitamin D metabolite, 1,25-hydroxyvitamin D (1,25OHD), with type 2 diabetes mellitus (DM) in community-living men aged 70 and older.. Cross-sectional.. A population-based, cross-sectional analysis of the baseline phase of the Concord Health and Ageing in Men Project (CHAMP), a large epidemiological study conducted in Sydney between January 2005 and May 2007.. Community dwelling men aged 70 and older taking part in CHAMP (N = 1,659).. Serum 25OHD and 1,25OHD levels, presence of DM, age, country of birth, season of blood collection, sun exposure, body mass index, vitamin D supplement use, statin use, income, measures of health, depression, activity of daily living disabilities, parathyroid hormone, estimated glomerular filtration rate, phosphate, and calcium.. The prevalence of DM was 20.0%. There was a significant association between low 25OHD and 1,25OHD levels and DM that remained after adjustment for a wide range of confounders and covariates of clinical significance such as comorbidity, renal function, calciotropic hormones, and medications.. 25OHD and 1,25OHD levels were associated with DM. The independent association between serum 25OHD and 1,25OHD concentrations and DM raises the question of whether each of the two vitamin D metabolites may influence DM through different biological mechanisms and pathways.

Topics: Aged; Aged, 80 and over; Australia; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Humans; Logistic Models; Male; Vitamin D

We aimed to examine associations among serum 25-hydroxyvitamin D (25OHD) levels, 1,25-dihyroxyvitamin D (1,25OHD) levels, vitamin D receptor (VDR) polymorphisms, and renal function based on estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.. In a cross-sectional study of 410 patients, chronic kidney disease (CKD) stage assessed by eGFR was compared with 25OHD, 1,25OHD, and VDR FokI (rs10735810) polymorphisms by an ordered logistic regression model adjusted for the following confounders: disease duration, calendar month, use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers or statins, and serum calcium, phosphate, and intact parathyroid hormone levels.. 1,25OHD levels, rather than 25OHD levels, showed seasonal oscillations; peak levels were seen from May to October and the lowest levels were seen from December to February. These findings were evident in patients with CKD stage 3 ~ 5 but not stage 1 ~ 2. eGFR was in direct proportion to both 25OHD and 1,25OHD levels (P<0.0001), but it had stronger linearity with 1,25OHD (r = 0.73) than 25OHD (r = 0.22) levels. Using multivariate analysis, 1,25OHD levels (P<0.001), but not 25OHD levels, were negatively associated with CKD stage. Although FokI polymorphisms by themselves showed no significant associations with CKD stage, a significant interaction between 1,25OHD and FokITT was observed (P = 0.008). The positive association between 1,25OHD and eGFR was steeper in FokICT and CC polymorphisms (r = 0.74) than FokITT polymorphisms (r = 0.65).. These results suggest that higher 1,25OHD levels may be associated with better CKD stages in patients with type 2 diabetes and that this association was modified by FokI polymorphisms.

Topics: Adult; Aged; Aged, 80 and over; Deoxyribonucleases, Type II Site-Specific; Diabetes Mellitus, Type 2; Female; Genetic Predisposition to Disease; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Kidney Function Tests; Logistic Models; Male; Middle Aged; Polymorphism, Genetic; Receptors, Calcitriol; Seasons; Vitamin D; Young Adult

To investigate the relationship between Erythropoietin (EPO) and 1,25-dihydroxyvitamin D levels, and tubular damage in patients with diabetes mellitus (DM) without persistent microalbuminuria.. We measured serum EPO and 1,25-dihydroxyvitamin D levels and tubular injury markers such as urinary N-acetyl-beta-d-glucosaminidase (NAG) and retinol binding protein (RBP) levels in 41 non-diabetic controls, 40 patients with Type 1 and 40 with Type 2 DM.. Median serum EPO levels were lower in Type 1 (2.57 mIU/ml: p<0.001) and Type 2 DM (5.69 mIU/ml: p=0.044) than in controls (8.76 mIU/ml), though haemoglobin levels did not differ. Median 1,25-dihydroxyvitamin D levels were lower in Type 1 (41.0 pmol/l: p=0.001) and Type 2 DM (41.8 pmol/l: p=0.035) than in controls (56.1 pmol/l), though serum creatinine, calcium, phosphate and PTH levels did not differ. Median RBP excretion was higher in Type 2 DM (0.35 mg/l vs. 0.23 mg/l: p=0.013) than in controls. Median NAG excretion was higher in Type 1 DM (1,079 micromol/h vs.1,030 micromol/h: p=0.048) compared to controls.. Tubulo-interstitial damage with low levels of EPO and 1,25-dihydroxyvitamin D occurs early in Type 1 and Type 2 DM before persistent microalbuminuria.

Topics: Adult; Albuminuria; Blood Glucose; Blood Pressure; Creatinine; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Erythropoietin; Female; Glycated Hemoglobin; Humans; Kidney Tubules; Male; Middle Aged; Reference Values; Vitamin D; Young Adult

Cardiovascular disease is the leading cause of death among those with diabetes mellitus. Vitamin D deficiency is associated with an increased risk of cardiovascular disease in this population. To determine the mechanism by which vitamin D deficiency mediates accelerated cardiovascular disease in patients with diabetes mellitus, we investigated the effects of active vitamin D on macrophage cholesterol deposition.. We obtained macrophages from 76 obese, diabetic, hypertensive patients with vitamin D deficiency (25-hydroxyvitamin D <80 nmol/L; group A) and 4 control groups: obese, diabetic, hypertensive patients with normal vitamin D (group B; n=15); obese, nondiabetic, hypertensive patients with vitamin D deficiency (group C; n=25); and nonobese, nondiabetic, nonhypertensive patients with vitamin D deficiency (group D; n=10) or sufficiency (group E; n=10). Macrophages from the same patients in all groups were cultured in vitamin D-deficient or 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] -supplemented media and exposed to modified low-density lipoprotein cholesterol. 1,25(OH)(2)D(3) suppressed foam cell formation by reducing acetylated or oxidized low-density lipoprotein cholesterol uptake in diabetic subjects only. Conversely, deletion of the vitamin D receptor in macrophages from diabetic patients accelerated foam cell formation induced by modified LDL. 1,25(OH)(2)D(3) downregulation of c-Jun N-terminal kinase activation reduced peroxisome proliferated-activated receptor-gamma expression, suppressed CD36 expression, and prevented oxidized low-density lipoprotein-derived cholesterol uptake. In addition, 1,25(OH)(2)D(3) suppression of macrophage endoplasmic reticulum stress improved insulin signaling, downregulated SR-A1 expression, and prevented oxidized and acetylated low-density lipoprotein-derived cholesterol uptake.. These results identify reduced vitamin D receptor signaling as a potential mechanism underlying increased foam cell formation and accelerated cardiovascular disease in diabetic subjects.

Topics: Adult; Animals; CD36 Antigens; Cells, Cultured; Cholesterol; Diabetes Mellitus, Type 2; Female; Foam Cells; Humans; JNK Mitogen-Activated Protein Kinases; Lipoproteins, LDL; Macrophages; Male; Mice; Mice, Mutant Strains; Middle Aged; Obesity; PPAR gamma; Receptors, Calcitriol; Scavenger Receptors, Class A; Signal Transduction; Vitamin D; Vitamin D Deficiency

Because it has been reported that vitamin D, given to mother or infant, can prevent type I diabetes in children, that diabetes is more common in adults with low serum vitamin D and that insulin secretion and action are related to vitamin D levels in healthy young adults we examined the relationship between serum vitamin D metabolites and fasting serum glucose in patients attending our outpatient clinics.. Retrospective examination of convenience sample of postmenopausal women attending our osteoporosis clinics.. A total of 753 postmenopausal women attending a university hospital outpatient clinic and not on any treatment known to affect glucose metabolism.. Body weight and height, serum 25-hydroxyvitamin D [25(OH)D], serum 1,25-dihydroxyvitamin D [1,25(OH)2D], serum PTH and fasting serum glucose.. On simple correlation fasting serum glucose was a positive function of age (P < 0.05), weight (P < 0.001) and body mass index (BMI) (P < 0.001) and a negative function of serum 25(OH)D (P < 0.001), but it was not significantly related to either serum 1,25(OH)2D, PTH or creatinine. When fasting serum glucose was regressed simultaneously on age, BMI and 25(OH)D, glucose was still an inverse function of 25(OH)D (P = 0.006).. Fasting serum glucose increased as 25(OH)D levels fell throughout the range of serum 25(OH)D measured but the greatest increase was observed in those with 25(OH)D below 40 nmol/l.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; Calcifediol; Creatinine; Diabetes Mellitus, Type 2; Fasting; Female; Humans; Middle Aged; Parathyroid Hormone; Postmenopause; Regression Analysis; Risk Factors; Vitamin D; White People

To investigate whether there is a relationship between serum 1,25 dihydroxy vitamin D3 [1,25(OH)2D3], which is an inhibitor of angiogenesis, concentrations and severity of diabetic retinopathy (DR).. Serum 1,25(OH)2D3, 25 hydroxy vitamin D [25(OH)D] and parathormone (PTH) concentrations were measured in diabetic patients (n = 66) and nondiabetic healthy subjects (n = 20).. The mean serum 1,25(OH)2D3 concentration in diabetic patients was lower than that in nondiabetics (57.3+/-21.44 vs. 89.4+/-18.01 pmol/L, p<0.001); mean 1,25(OH)2D3 concentrations fell with increasing severity of DR [being 63.4+/-17.26 pmol/L for background DR (BDR), 47.7+/-13.27 pmol/L for preproliferative DR (pre-PDR), and 43.1+/-19.45 pmol/L for proliferative DR (PDR)]. Compared with the control group, serum 25(OH)D concentrations were found to be decreased in diabetic patients (p<0.001). There were negative correlations between 1,25(OH)2D3 and age (r = -0.331, p<0.01) and duration of diabetes (r = -0.255, p<0.05).. From these findings, it was found that there was an inverse relationship between the severity of the retinopathy, i.e., neovascularization, and serum 1,25(OH)2D3 concentrations, being the lowest in PDR and the highest in diabetic patients without retinopathy (NDR) patients. The measurement of serum 1,25(OH)2D3 concentrations might be helpful to predict severity of DR in patients with diabetes mellitus.

Topics: Age Factors; Angiogenesis Inhibitors; Calcifediol; Calcium; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Predictive Value of Tests; Vitamin D