Prevention of type 2 diabetes

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

This report covers recent results of two randomized clinical trials in prevention of type 2 diabetes: the Vitamin D and Type 2 Diabetes (D2d) Study and the Diabetes Prevention Program Outcomes Study (DPPOS). D2d Vitamin D supplementation and kidney function. Low serum 25-hydroxyvitamin D (25OHD) concentration has been associated with higher levels of proteinuria and lower levels of eGFR in observational studies. In the 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. 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). 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). In conclusion, 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. Predictive properties of tests for prediabetes. Using screening results from the D2d study, we assessed whether meeting both fasting plasma glucose (FPG) and HbA1c criteria for prediabetes in people at high risk indicates with near certainty the presence of dysglycemia on repeat testing. HbA1c and FPG were measured at screening visit 1; FPG, HbA1c and 2 h plasma glucose (2hPG) were measured at screening visit 2 (a median of 21 days later); participants classified as having normal glucose regulation (all 3 tests in normal range), prediabetes or diabetes (at least 1 of 3 tests in diabetes range). Of 1271 participants who met both FPG and HbA1c criteria for prediabetes at screening visit 1, 98.6% exhibited dysglycemia (defined as prediabetes or diabetes) on repeat testing (84.5% were classified as having prediabetes, 14.1% were reclassified as having diabetes). Of those with diabetes, 62.6% were identified by 2hPG alone. In conclusion, combined measurement of FPG and HbA1c is a reliable and reproducible measure to identify presence of dysglycemia among people at high risk. On-treatment vitamin D serum concentrations and diabetes incidence. Post-randomization biases may influence the estimate of efficacy of supplemental vitamin D in diabetes prevention trials. In the Vitamin D and Type 2 Diabetes (D2d) study, repeated measures of serum 25-hydroxyvitamin D 25(OH)D level provided an opportunity to test whether intratrial vitamin D exposure affected diabetes risk and whether the effect was modified by trial assignment (vitamin D vs. placebo). The D2d study compared the effect of daily supplementation with 100 g (4,000 units) of vitamin D3 versus placebo on new-onset diabetes in adults with prediabetes. Intratrial vitamin D exposure was calculated as the cumulative rolling mean of annual serum 25(OH)D measurements. Hazard ratios for diabetes among participants who had intratrial 25(OH)D levels of <50, 75-99, 100-124, and 125 nmol/L were compared with those with levels of 50-74 nmol/L (the range considered adequate by the National Academy of Medicine) in the entire cohort and by trial assignment. There was an interaction of trial assignment with intratrial 25(OH)D level in predicting diabetes risk (interaction P = 0.018). The hazard ratio for diabetes for an increase of 25 nmol/L in intratrial 25(OH)D level was 0.75 (95% CI 0.68-0.82) among those assigned to vitamin D and 0.90 (0.80-1.02) among those assigned to placebo. The hazard ratios for diabetes among participants treated with vitamin D who maintained intratrial 25(OH)D levels of 100-124 and 125 nmol/L were 0.48 (0.29-0.80) and 0.29 (0.17-0.50), respectively, compared with those who maintained a level of 50-74 nmol/L. Daily vitamin D supplementation to maintain a serum 25(OH)D level 100 nmol/L is a promising approach to reducing the risk of diabetes in adults with prediabetes. DPPOS Effect of physical activity (PA) in diabetes prevention. Across the Diabetes Prevention Program (DPP) follow-up, cumulative diabetes incidence remained lower in the lifestyle compared with the placebo and metformin randomized groups and could not be fully explained by weight. Collection of self-reported PA (yearly) with cross-sectional objective PA (in follow-up) allowed for examination of PA and its long-term impact on diabetes prevention. Yearly self-reported PA and diabetes assessment and oral glucose tolerance test results (fasting glucose semiannually) were collected for 3,232 participants with one accelerometry assessment 11-13 years after randomization (n = 1,793). Mixed models determined PA differences across treatment groups. The association between PA and diabetes incidence was examined using Cox proportional hazards models. There was a 6% decrease (Cox proportional hazard ratio 0.94 95% CI 0.92, 0.96; P < 0.001) in diabetes incidence per 6 MET-h/week increase in time-dependent PA for the entire cohort over an average of 12 years (controlled for age, sex, baseline PA, and weight). In conclusion, PA was inversely related to incident diabetes in the entire cohort across the study, with cross-sectional accelerometry results supporting these findings. This highlights the importance of PA within lifestyle intervention efforts designed to prevent diabetes and urges health care providers to consider both PA and weight when counseling high-risk patients. Assessing gene-lifestyle intervention interactions in DPP. We tested whether diabetes genetic risk modifies the association of successful lifestyle changes with incident diabetes. We studied 823 individuals randomized to the intensive lifestyle intervention (ILS) arm of the DPP who were diabetes-free 1 year after enrolment. We tested additive and multiplicative interactions of a 67-variant diabetes genetic risk score (GRS) with achievement of three ILS goals at 1 year (7% weight loss, 150 minutes/week of moderate leisure-time physical activity, and/or a goal for self-reported total fat intake) on the primary outcome of incident diabetes over 3 years of follow-up. A lower GRS and achieving each or all three ILS goals were each associated with lower incidence of diabetes (all P < 0.05). Additive interactions were significant between the GRS and achievement of the weight loss goal (P < 0.001), physical activity goal (P = 0.02), and all three ILS goals (P < 0.001) for diabetes risk. Achievement of all three ILS goals was associated with 1.8 (95% CI 0.3, 3.4), 3.1 (95% CI 1.5, 4.7), and 3.9 (95% CI 1.6, 6.2) fewer diabetes cases/100-person-years in the first, second and third GRS tertiles (P < 0.001 for trend). Multiplicative interactions between the GRS and ILS goal achievement were significant for the diet goal (P < 0.001), but not for weight loss (P = 0.18) or physical activity (P = 0.62) goals. Genetic risk may identify high-risk subgroups for whom successful lifestyle modification is associated with greater absolute reduction in the risk of incident diabetes.