Effect of Vitamin D Supplementation on Kidney Function in Adults with Prediabetes: A Secondary Analysis of a Randomized Trial.

BACKGROUND AND OBJECTIVES: Low serum 25-hydroxyvitamin D (25[OH]D) concentration has been associated with higher levels of proteinuria and lower levels of eGFR in observational studies. In the Vitamin D and Type 2 Diabetes (D2d) study, we investigated the effect of vitamin D supplementation on kidney outcomes in a population with prediabetes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Overweight/obese adults with high risk for type 2 diabetes (defined by meeting two of three glycemic criteria for prediabetes) were randomized to vitamin D3 4000 IU per day versus placebo. Median duration of treatment was 2.9 years (interquartile range 2.0-3.5 years). Kidney outcomes included (1) worsening in Kidney Disease: Improving Global Outcomes (KDIGO ) risk score (low, moderate, high, very high) on two consecutive follow-up visits after the baseline visit and (2) mean changes in eGFR and urine albumin-to-creatinine ratio (UACR). RESULTS: Among 2166 participants (mean age 60 years, body mass index 32 kg/m2, serum 25(OH)D 28 ng/ml, eGFR 87 ml/min per 1.73 m2, UACR 11 mg/g, 79% with hypertension), 10% had moderate, high, or very high KDIGO risk score. Over a median follow-up of 2.9 years, there were 28 cases of KDIGO worsening in the vitamin D group and 30 in the placebo group (hazard ratio, 0.89; 95% confidence interval [95% CI], 0.52 to 1.52]). Mean difference in eGFR from baseline was -1.0 ml/min per 1.73 m2 (95% CI, -1.3 to -0.7) in the vitamin D group and -0.1 ml/min per 1.73 m2 (95% CI, -0.4 to 0.2) in the placebo group; between-group difference was -1.0 ml/min per 1.73 m2 (95% CI, -1.4 to -0.6). Mean difference in UACR was 2.7 mg/g (95% CI, 1.2 to 4.3) in the vitamin D group and 2.0 (95% CI, 0.5 to 3.6) in the placebo group; between-group difference was 0.7 mg/g (95% CI, -1.5 to 2.9). CONCLUSIONS: Among persons with prediabetes, who were not preselected on the basis of serum 25(OH)D concentration, vitamin D supplementation did not affect progression of KDIGO risk scores and did not have a meaningful effect on change in UACR or eGFR.

Vitamin D Supplementation and Prevention of Type 2 Diabetes.

BACKGROUND: Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown. METHODS: We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D3 or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508. RESULTS: A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS: Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, NCT01942694.).

Baseline Characteristics of the Vitamin D and Type 2 Diabetes (D2d) Study: A Contemporary Prediabetes Cohort That Will Inform Diabetes Prevention Efforts.

OBJECTIVE: To describe baseline characteristics of the Vitamin D and Type 2 Diabetes (D2d) study, the first large U.S. diabetes prevention clinical trial to apply current American Diabetes Association (ADA) criteria for prediabetes. RESEARCH DESIGN AND METHODS: This is a multicenter (n = 22 sites), randomized, double-blind, placebo-controlled, primary prevention clinical trial testing effects of oral daily 4,000 IU cholecalciferol (D3) compared with placebo on incident diabetes in U.S. adults at risk for diabetes. Eligible participants were at risk for diabetes, defined as not meeting criteria for diabetes but meeting at least two 2010 ADA glycemic criteria for prediabetes: fasting plasma glucose (FPG) 100-125 mg/dL, 2-h postload glucose (2hPG) after a 75-g oral glucose load 140-199 mg/dL, and/or a hemoglobin A1c (HbA1c) 5.7-6.4% (39-46 mmol/mol). RESULTS: A total of 2,423 participants (45% of whom were women and 33% nonwhite) were randomized to cholecalciferol or placebo. Mean (SD) age was 59 (9.9) years and BMI 32 (4.5) kg/m2. Thirty-five percent met all three prediabetes criteria, 49% met the FPG/HbA1c criteria only, 9.5% met the 2hPG/FPG criteria only, and 6.3% met the 2hPG/HbA1c criteria only. Black participants had the highest mean HbA1c and lowest FPG concentration compared with white, Asian, and other races (P < 0.01); 2hPG concentration did not differ among racial groups. When compared with previous prediabetes cohorts, the D2d cohort had lower mean 2hPG concentration but similar HbA1c and FPG concentrations. CONCLUSIONS: D2d will establish whether vitamin D supplementation lowers risk of diabetes and will inform about the natural history of prediabetes per contemporary ADA criteria.

Total adiponectin, but not inflammatory markers C-reactive protein, tumor necrosis factor-α, interluekin-6 and monocyte chemoattractant protein-1, correlates with increasing glucose intolerance in pregnant Chinese-Americans.

BACKGROUND: Elevated insulin, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 levels and decreased high molecular weight adiponectin (HMW-APN) levels have been reported in Caucasians with gestational diabetes mellitus (GDM). No similar studies have been performed in Chinese women. METHODS: Serum samples were obtained 1 h after a 50-g glucose challenge test (1HGCT) from Chinese-American women at 24-28 gestational weeks and total adiponectin (T-APN), HMW-APN, CRP, TNF-α, IL-6, and MCP-1 concentrations were measured. Correlation coefficients for glucose (1HGCT), HbA1c, insulin, and body mass index (BMI) were calculated against T-APN, HMW-APN, CRP, TNF-α, IL-6, and MCP-1. Significant P-values were determined using Bonferroni adjustments. RESULTS: Women with GDM had higher insulin and 1HGCT and lower T-APN. In addition, T-APN was lower in non-GDM subjects who had 1HGCT ≥135 mg/dL with no abnormal or one abnormal glucose value on the 3-h oral glucose tolerance test. There were no significant differences in HMW-APN and inflammatory marker levels between non-GDM and GDM groups. There were negative correlations between T-APN and 1HGCT, insulin, BMI, and HbA1c, as well as between HMW-APN and 1HGCT, insulin, and BMI. No significant correlations were observed between 1HGCT, HbA1c, insulin, or BMI and CRP, TNF-α, IL-6, or MCP-1. CONCLUSIONS: T-APN is reduced in Chinese women with GDM and those without GDM but with evidence of glucose intolerance. Unlike results reported for Caucasians, Chinese-American women with GDM do not exhibit elevated levels of CRP, TNF-α, IL-6, or MCP-1, possibly because Chinese women are relatively leaner compared with Caucasians.

Patterns of medication initiation in newly diagnosed diabetes mellitus: quality and cost implications.

Currently, 25 million Americans are known to have diabetes, with an additional 7 million cases believed to be undiagnosed. It is estimated that direct and indirect costs of diabetes top $200 billion. Due to the significant health and financial burdens associated with diabetes, it is imperative that this disease be treated quickly and aggressively. In 2009, the American Diabetes Association and the European Association for the Study of Diabetes developed a consensus statement regarding the treatment of type 2 diabetes, citing lifestyle modification and metformin as the preferred first line therapies. In this study, the authors looked at prescription claims data for adults who were newly initiated on oral hypoglycemic monotherapy between January 1, 2006, and December 31, 2008, to determine if initiation patterns changed over time, to evaluate how well the treatment guidelines were being followed, and to assess the economic consequences of prescribing patterns by drug class for both patients and insurers. The results showed that over the course of the study period the proportion of patients initially treated with metformin increased, whereas those receiving sulfonylureas as first-line therapy decreased. Thiazolidinediones experienced the greatest decrease, falling from 20% to 8%, while prescriptions for dipeptidyl peptidase-4 inhibitors increase from 0-7%. Over a 6-month period, patients taking metformin or sulfonylureas paid approximately $38 to $40 in co-pays while insurance paid about $77. Patients taking other agents paid approximately $130 in co-pays and insurance paid over $500. The authors concluded that based its cost and safety profile, metformin should be the first line drug therapy for patients with newly diagnosed type 2 diabetes. This CME multimedia activity, which is part of a 2-part multimedia activity on the management and treatment of diabetes, contains a video presentation and is available through the website of The American Journal of Medicine at http://amjmed.com/content/multimedia. Click on "Patterns of Medication Initiation in Newly Diagnosed Diabetes Mellitus: Quality and Cost Implications" to access this part of the multimedia program.

Management of type 2 diabetes: new and future developments in treatment.

To date, six classes of oral medication have been approved by the U.S. Food and Drug Administration for the treatment of type 2 diabetes and several new agents are in the pipeline. In 2009, the American Diabetes Association and the European Association for the Study of Diabetes developed a consensus statement regarding the treatment of type 2 diabetes, citing lifestyle modification and metformin as the preferred first line therapies. In addition to the currently available drugs, several new agents have recently been introduced or are in the development pipeline. Incretin therapies include both glucagon-like peptide-1 (GLP-1) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors. Non-incretin beta cell stimulants still in development include glucokinase activators, G-protein-coupled receptors, and anti-inflammatory and anti-oxidant therapies. Additional agents that target glucose synthesis include glucose-6-phosphatase and glycogen phosphorylase. Other new agents target metabolic syndrome, which is often the first clinical condition that presents in patients at risk for type 2 diabetes. Finally, for obese patients who are unable to lose weight through diet and exercise, weight-loss surgery is an option that should be discussed with their physicians. This CME multimedia activity, which is part of a 2-part multimedia activity on the management and treatment of diabetes, contains a video presentation and is available through the website of The American Journal of Medicine at http://amjmed.com/content/multimedia. Click on "Management of Type 2 Diabetes: New and Future Developments in Treatment" to access this part of this multimedia program.

Lack of effect of subtherapeutic vitamin D treatment on glycemic and lipid parameters in Type 2 diabetes: A pilot prospective randomized trial.

BACKGROUND: Epidemiological studies suggest a higher prevalence of metabolic syndrome and its components among individuals with vitamin D deficiency. The aim of the present study was to determine whether vitamin D treatment improves glucose control and insulin sensitivity in Type 2 diabetes mellitus (T2DM). METHODS: Subjects with T2DM and serum 25-hydroxyvitamin D (25(OH)D) concentrations <25 ng/mL were randomized to receive 400 IU (Group 1) or 1200 IU (Group 2) cholecalciferol for 4 months. Fasting plasma glucose, glycosylated hemoglobin (HbA1c), Quantitative Insulin Sensitivity Check Index (QUICKI), serum lipid levels and serum adiponectin were measured at baseline and at 4 months. RESULTS: Mean 25(OH)D levels increased in both groups (from 17.6±1.5 to 25.5±1.8 ng/mL in Group 1 and from 15.6±1.4 to 27.4±2.4 ng/mL in Group 2; P≤0.001 vs baseline for each group). No significant differences were noted in fasting plasma glucose, HbA1c, QUICKI, serum adiponectin, and lipid levels compared with baseline within groups or between the two groups. CONCLUSIONS: In the present pilot study, conventional vitamin D treatment at a level improving, but not optimizing, serum 25(OH)D did not improve glycemia, insulin sensitivity, or lipid profile. However, diabetes and lipids were relatively well controlled at baseline. Future studies should be designed to achieve optimal concentrations of serum 25(OH)D (at least >32 ng/mL) and should include subjects showing more abnormal parameters of glycemia, lipid, and insulin sensitivity at baseline.