Vitamin D supplementation for the prevention of type 2 diabetes in overweight adults: study protocol for a randomized controlled trial

Abstract

BackgroundDespite Australia’s sunny climate, low vitamin D levels are increasingly prevalent. Sun exposure is limited by long working hours, an increase in time spent indoors, and sun protection practices, and there is limited dietary vitamin D fortification. While the importance of vitamin D for bone mineralization is well known, its role as a protective agent against chronic diseases, such as type 2 diabetes and cardiovascular disease, is less understood. Observational and limited intervention studies suggest that vitamin D might improve insulin sensitivity and secretion, mainly via its anti-inflammatory properties, thereby decreasing the risk of development and progression of type 2 diabetes. The primary aim of this trial is to investigate whether improved plasma concentrations of 25-hydroxyvitamin D (25(OH)D), obtained through vitamin D supplementation, will increase insulin sensitivity and insulin secretion. A secondary aim is to determine whether these relationships are mediated by a reduction in underlying subclinical inflammation associated with obesity.Methods/DesignFifty overweight but otherwise healthy nondiabetic adults between 18 and 60 years old, with low vitamin D levels (25(OH)D < 50 nmol/l), will be randomly assigned to intervention or placebo. At baseline, participants will undergo a medical review and anthropometric measurements, including dual X-ray absorptiometry, an intravenous glucose tolerance test, muscle and fat biopsies, a hyperinsulinemic euglycemic clamp, and questionnaires assessing diet, physical activity, sun exposure, back and knee pain, and depression. The intervention group will receive a first dose of 100,000 IU followed by 4,000 IU vitamin D (cholecalciferol) daily, while the placebo group will receive apparently identical capsules, both for a period of 16 weeks. All measurements will be repeated at follow-up, with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion for the intervention group compared with the placebo group. Secondary outcome measures will compare changes in anthropometry, cardiovascular risk factors, and inflammatory markers.DiscussionThe trial will provide much needed clinical evidence on the impact of vitamin D supplementation on insulin resistance and secretion and its underlying mechanisms, which are relevant for the prevention and management of type 2 diabetes.Trial registrationClinicaltrials.gov ID: NCT02112721.

Higher glomerular filtration rate is related to insulin resistance but not to obesity in a predominantly obese non-diabetic cohort

“…Insulin sensitivity was measured during a hyperinsulinemic-euglycemic clamp, performed as per our published protocol19. In brief, after an overnight fast, we collected baseline blood and tested plasma glucose levels at 0 minute, after which the clamp was initiated by an intravenous bolus injection of insulin (9 mU/kg).…”

Plasma Phospholipids with Long‐Chain Polyunsaturated Fatty Acids and Dihydroceramides at the Crossroads of Iron Stores and Insulin Resistance

“…A comprehensive description of data collection and analysis has been previously described . In brief, after 10–12 h overnight fast, participants underwent an OGTT and basal and 2 h glucose levels were analyzed.…”

“…Glucose Metabolism Parameters: A comprehensive description of data collection and analysis has been previously described. [42] In brief, after 10-12 h overnight fast, participants underwent an OGTT and basal and 2 h glucose levels were analyzed. Insulin was measured from fasting venous blood samples using a simultaneous immunoenzymatic sandwich assay (DXI ultrasensitive insulin assay, Beckman Coulter, Australia).…”

Is There a Relation Between Serum Vitamin D Level and Microvascular Comlications in Type 2 Diabetes?

“…[17] Research indicates that diabetes prevention focusing on change-of-lifestyle interventions is likely to be cost-saving. [18] In light of new information that vitamin D might improve insulin sensitivity and secretion [19] , we aimed to investigate the relationship between vitamin D and metabolic parameters and microvascular complications in T2DM patients. For this purpose, this study evaluated each of the 206 T2DM patients for microvascular complications and vitamin D level, in addition to routine metabolic parameters.…”