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

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. 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). 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). 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.

Kim SH ，Brodsky IG ，Chatterjee R ，Kashyap SR ，Knowler WC ，Liao E ，Nelson J ，Pratley R ，Rasouli N ，Vickery EM ，Sarnak M ，Pittas AG ，D2d Research Group ，D2d Research Group collaborators ... -  《-》

Vitamin D Supplementation and Prevention of Type 2 Diabetes.

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. 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. 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. 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.).

Pittas AG ，Dawson-Hughes B ，Sheehan P ，Ware JH ，Knowler WC ，Aroda VR ，Brodsky I ，Ceglia L ，Chadha C ，Chatterjee R ，Desouza C ，Dolor R ，Foreyt J ，Fuss P ，Ghazi A ，Hsia DS ，Johnson KC ，Kashyap SR ，Kim S ，LeBlanc ES ，Lewis MR ，Liao E ，Neff LM ，Nelson J ，O'Neil P ，Park J ，Peters A ，Phillips LS ，Pratley R ，Raskin P ，Rasouli N ，Robbins D ，Rosen C ，Vickery EM ，Staten M ，D2d Research Group ... -  《-》

Effect of Vitamin D and Omega-3 Fatty Acid Supplementation on Kidney Function in Patients With Type 2 Diabetes: A Randomized Clinical Trial.

de Boer IH ，Zelnick LR ，Ruzinski J ，Friedenberg G ，Duszlak J ，Bubes VY ，Hoofnagle AN ，Thadhani R ，Glynn RJ ，Buring JE ，Sesso HD ，Manson JE ... -  《-》

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

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. 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). 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. D2d will establish whether vitamin D supplementation lowers risk of diabetes and will inform about the natural history of prediabetes per contemporary ADA criteria.

LeBlanc ES ，Pratley RE ，Dawson-Hughes B ，Staten MA ，Sheehan PR ，Lewis MR ，Peters A ，Kim SH ，Chatterjee R ，Aroda VR ，Chadha C ，Neff LM ，Brodsky IG ，Rosen C ，Desouza CV ，Foreyt JP ，Hsia DS ，Johnson KC ，Raskin P ，Kashyap SR ，O'Neil P ，Phillips LS ，Rasouli N ，Liao EP ，Robbins DC ，Pittas AG ，D2d Research Group ... -  《-》

Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials.

Pittas AG ，Kawahara T ，Jorde R ，Dawson-Hughes B ，Vickery EM ，Angellotti E ，Nelson J ，Trikalinos TA ，Balk EM ... -  《-》