Vitamin D, insulin sensitivity, and cardiometabolic risk in children

Abstract

Background: The childhood obesity epidemic has increased the prevalence of cardiometabolic disease and pre-diabetes prevalence. Vitamin D’s role in diabetes and cardiometabolic disease is an emerging, extraskeletal function that has been explored via mechanistic research, as well as observational and intervention studies, predominantly in adults. Objective: To review the relevant literature, report the effects of vitamin D supplementation on glycemia and insulin sensitivity in apparently healthy children, and examine the cross-sectional relationship between serum vitamin D and cardiometabolic risk in overweight children. Methods: The intervention trial includes black and white early pubertal (N = 320) males (aged 10 to 13 years) and females (aged 9 to 12 years) who participated in a 12-week randomized, triple masked, multi-site, five-dose (0, 400, 1,000, 2000, and 4,000 IU vitamin D3) placebo-controlled trial. The cross-sectional study includes 222 sedentary, overweight children (aged 7-11 years, 58% female, 58% black, 86% obese). Anthropometry, body composition, and biochemical indices related to serum vitamin D status, glucose-insulin homeostasis, and cardiometabolic risk were examined in both studies. Results: The vitamin D intervention did not significantly alter glycemia or insulin sensitivity over 12-weeks. Glucose, insulin, and insulin resistance increased, while insulin sensitivity decreased, over the 12-weeks, likely attributable to organic pubertal maturation phenomena. Lower serum vitamin D concentrations were associated with multiple cardiometabolic risk factors, insulin resistance, and adipokines and associated with an increase in cardiometabolic disease risk, however, model adjustment with visceral adipose tissue attenuated all of these relationships. Conclusions: We report novel findings from the first pediatric vitamin D intervention to examine effects on glycemia and insulin sensitivity. In this trial, the apparently healthy, vitamin D sufficient status of our children, are key facets that may have contributed to our null finding. Furthermore, we may have avoided the glucose-insulin homeostatic alterations induced by pubertal growth if we had examined a pre- or post-pubertal population. Our cross-sectional findings highlight the important mediating role of visceral adiposity in the vitamin D-cardiometabolic disease relationship. Future, rigorously designed trials are warranted to elucidate the causal effect of vitamin D on cardiovascular disease and diabetes, with particular attention paid to pediatric populations with higher cardiometabolic risk and vitamin D insufficiency.