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Context Vitamin D regulates glucose homeostasis pathways, but effects of vitamin D supplementation on β-cell function remain unclear. Objective To investigate the effects of vitamin D3 supplementation on insulin sensitivity and β-cell function. Methods This is a prespecified secondary analysis of the Vitamin D and Type 2 Diabetes study. Overweight/obese adults at high risk for type 2 diabetes (prediabetes) were randomly treated with vitamin D3 4000 IU or matching placebo daily for 24 months. Main Outcome Disposition index (DI), as an estimate of β-cell function, was calculated as the product of Homeostasis Model Assessment 2 indices derived from C-peptide values (HOMA2%Scpep) and C-peptide response during the first 30 minutes of a 75-g oral glucose tolerance test (OGTT). Results Mean age was 60.5 ± 9.8 years and body mass index was 31.9 ± 4.4 kg/m2. Mean serum 25(OH)D level increased from 27.9 ± 10.3 ng/mL at baseline to 54.9 ng/mL at 2 years in the vitamin D group and was unchanged (28.5 ± 10.0 ng/mL) in the placebo group. The baseline DI predicted incident diabetes independent of the intervention. In the entire cohort, there were no significant differences in changes in DI, HOMA2%Scpep, or C-peptide response between the 2 groups. Among participants with baseline 25(OH)D level Conclusions Supplementation with vitamin D3 for 24 months did not improve an OGTT-derived index of β-cell function in people with prediabetes not selected based on baseline vitamin D status; however, there was benefit among those with very low baseline vitamin D status.

Context Observational studies suggest that low vitamin D status may be a risk factor for cancer. Objective In a population with prediabetes and overweight/obesity that is at higher risk of cancer than the general population, we sought to determine if vitamin D supplementation lowers the risk of cancer and precancers. Methods The Vitamin D and type 2 diabetes (D2d) cancer outcomes study (D2dCA) is an ancillary study to the D2d study, which was conducted at 22 academic medical centers in the United States. Participants had prediabetes and overweight/obesity and were free of cancer for the previous 5 years. Participants were randomized to receive vitamin D3 4000 IU daily or placebo. At scheduled study visits (4 times/year), cancer and precancer events were identified by questionnaires. Clinical data were collected and adjudicated for all reported events. Cox proportional hazard models compared the hazard ratio (HR) of incident cancers and precancers between groups. Results Over a median follow-up period of 2.9 years, among 2385 participants (mean age 60 years and 25-hydroxyvitamin D 28 ng/mL), there were 89 cases of cancer. The HR of incident cancer for vitamin D vs placebo was 1.07 (95% CI 0.70, 1.62). Of 241 participants with incident precancers, 239 had colorectal adenomatous polyps. The HR for colorectal polyps for vitamin D vs placebo was 0.83 (95% CI 0.64, 1.07). Conclusion In the D2d population of participants with prediabetes and overweight/obesity, not selected for vitamin D insufficiency, vitamin D supplementation did not have a significant effect on risk of incident cancer or colorectal polyps.

Objective Fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG) from a 75-g oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) can lead to different results when diagnosing prediabetes and diabetes. The Hemoglobin Glycation Index (HGI) quantifies the interindividual variation in glycation resulting in discrepancies between FPG and HbA1c. We used data from the Vitamin D and Type 2 Diabetes (D2d) study to calculate HGI, to identify HGI-associated variables, and to determine how HGI affects prediabetes and diabetes diagnosis. Measurements A linear regression equation [HbA1c (%) = 0.0164 × FPG (mg/dL) + 4.2] was derived using the screening cohort (n = 6829) and applied to calculate predicted HbA1c. This was subtracted from the observed HbA1c to determine HGI in the baseline cohort with 2hPG data (n = 3945). Baseline variables plus prediabetes and diabetes diagnosis by FPG, HbA1c, and 2hPG were compared among low, moderate, and high HGI subgroups. Results The proportion of women and Black/African American individuals increased from low to high HGI subgroups. Mean FPG decreased and mean HbA1c increased from low to high HGI subgroups, consistent with the HGI calculation; however, mean 2hPG was not significantly different among HGI subgroups. Conclusions High HGI was associated with Black race and female sex as reported previously. The observation that 2hPG was not different across HGI subgroups suggests that variation in postprandial glucose is not a significant source of population variation in HGI. Exclusive use of HbA1c for diagnosis will classify more Black individuals and women as having prediabetes compared with using FPG or 2hPG.

The dietary protein requirements of patients with insulin-dependent diabetes mellitus (IDDM) are unknown. We studied the metabolic adaptation of IDDM patients with early nephropathy to therapeutic, low-protein diets. Six patients were studied at baseline and following 1 and 12 weeks of consuming 0.6 g/kg-1 ideal body weight.day-1 protein. Outcome variables included quadriceps muscle strength, body composition, nitrogen balance, and estimates of whole body protein turnover using an infusion of L-[1-13C]leucine. All subjects experienced decreased muscle strength (6.6% decline in maximal torque, P = 0.05) and increased body fatness (11% increase in fat mass, P = 0.03) with no change in total body weight. This was accompanied by an initial 40% decrease in the rate of whole-body leucine oxidation after 1 week of dietary restriction which returned almost to baseline rates by 12 weeks (P less than 0.001, 1 week vs. 12 weeks). Nitrogen balance remained negative throughout the period of protein restriction. We conclude that IDDM subjects with early nephropathy experience protein undernutrition during the first 3 months of the dietary protein restriction currently recommended for the treatment of nephropathy. This may result, in part, from an inability to conserve essential amino acids from oxidative loss over the time period of the study.