Elsevier

Translational Research

Volume 158, Issue 5, November 2011, Pages 276-281
Translational Research

Original Article
Vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose

https://doi.org/10.1016/j.trsl.2011.05.002Get rights and content

Vitamin D has in vitro and in vivo effects on β cells and insulin sensitivity. Vitamin D deficiency (VDD) has been associated with the onset and progression of type 2 diabetes mellitus (DM-2). However, studies involving supplementation of vitamin D in subjects with previously established diabetes have demonstrated inconsistent effects on insulin sensitivity. The aim of this open-label study was to assess the effects of high-dose vitamin D3 supplementation on insulin sensitivity in subjects with VDD and impaired fasting glucose. We studied 8 subjects with VDD and prediabetes with the modified, frequently sampled intravenous glucose tolerance (mFSIGT) test before and after vitamin D supplementation. Vitamin D3 was administered as 10,000 IU daily for 4 weeks. The mFSIGT was analyzed with MinMod Millennium (purchased from Dr. Richard Bergman, Keck School of Medicine of USC, Los Angeles, Calif) to obtain estimates of acute insulin response to glucose (AIRg), insulin sensitivity (SI), and disposition index (DI). We found that AIRg decreased (P = 0.011) and SI increased (P = 0.012) after a intervention with vitamin D. If these findings are repeated in a randomized, double-blind study, the results indicate that orally administered high-dose vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose and suggests that high-dose vitamin D3 supplementation might provide an inexpensive public health measure in preventing, or at least delaying, the progression from impaired fasting glucose to diabetes.

Section snippets

Study participants

Study participants were recruited through primary care and endocrinology clinics affiliated with Hennepin County Medical Center and the University of Minnesota (Minneapolis, Minn). Participants included adults, ages 18 to 65, with fasting glucose levels ≥100 mg/dL but less than 126 mg/dL, and serum 25-OH vitamin D levels ≤30 ng/mL. We used this latter concentration as patients with values less than this are stated to be at increased risk for the development of type 2 diabetes.1 Exclusion

Methods

The consent form and process were approved by the Institutional Review Boards at the University of Minnesota and Hennepin County Medical Center. The research was carried out according to the principles of the Declaration of Helsinki. Qualified subjects presented to the GCRC after an overnight 12-h fast. Two intravenous catheters were established, 1 for blood samples and another for administration of insulin and glucose. Baseline laboratories (performed at the University of Minnesota Clinical

Results

Eleven subjects provided consent and completed preintervention and postintervention assessment with the mFSIGT. However, vitamin D measurements were reported only after completion of all testing. Consequently, 3 subjects were excluded from analysis as they were not VDD at baseline. Therefore, 8 eligible subjects (3 men and 5 women) who completed the study were used for the final analysis.

Table I gives the patient characteristics, pre- and post-25-hydroxyvitamin D levels, pre- and post-PTH

Discussion

The influence of vitamin D on beta cell function and insulin sensitivity has been demonstrated in animal and in vitro studies. In human studies, a strong correlation exists between VDD and reduced insulin sensitivity.14 However, the therapeutic usefulness of these findings has been difficult to demonstrate. Interventional trials using vitamin D supplementation in subjects with existing type 2 diabetes have shown no overall improvement in beta cell function or insulin resistance.6, 11, 12 These

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      Recently, the effect of vitamin D supplementation on prediabetes has been reported. Studies have found that vitamin D supplementation was associated with improved beta cell function [12] and insulin sensitivity [13] among persons who were at high risk for diabetes but not in individuals with normal fasting glucose at baseline. Several randomized control trials (RCTs) have been conducted to evaluate the effect of vitamin D supplementation on subjects with type 2 diabetes, but the findings of these trials have been inconsistent.

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    Supported by a grant-in-aid from the Minneapolis Research Foundation and by Grant T32 DK007203 from the National Institutes of Health.

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