Low circulating 25-hydroxyvitamin D concentrations are associated with defects in insulin action and insulin secretion in persons with prediabetes

Abstract

Background: Individuals with prediabetes mellitus (PreDM) and low circulating 25-hydroxyvitamin D [25(OH)D] are at increased risk of type 2 diabetes mellitus (T2DM).

Objective: We aimed to determine whether low 25(OH)D concentrations are associated with defects in insulin action and insulin secretion in persons with PreDM.

Methods: In this cross-sectional study, we stratified 488 nondiabetic subjects as having PreDM or normal fasting glucose (NFG) and a 25(OH)D concentration ≤20 ng/mL (deficient) or >20 ng/mL (sufficient). We determined insulin resistance by steady state plasma glucose (SSPG) concentration and homeostasis model assessment of insulin resistance (HOMA-IR) and insulin secretion by homeostasis model assessment of β-cell function (HOMA-β). We compared insulin resistance and secretion measures in PreDM and NFG groups; 25(OH)D-deficient and 25(OH)D-sufficient groups; and PreDM-deficient, PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups, adjusting for age, sex, race, body mass index, multivitamin use, and season.

Results: In the PreDM group, mean SSPG concentration and HOMA-IR were higher and mean HOMA-β was lower than in the NFG group (P < 0.001 for all comparisons). In the 25(OH)D-deficient group, mean SSPG concentration was higher (P < 0.001), but neither mean HOMA-IR nor HOMA-β was significantly different from that in the 25(OH)D-sufficient group. In the PreDM-deficient subgroup, mean (95% CI) SSPG concentration was higher (P < 0.01) than in the PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups [192 (177-207) mg/dL vs. 166 (155-177) mg/dL, 148 (138-159) mg/dL, and 136 (127-144) mg/dL, respectively]. Despite greater insulin resistance, mean HOMA-β was not significantly higher in the PreDM-deficient subgroup than in the PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups [98 (85-112) vs. 91 (82-101), 123 (112-136), and 115 (106-124), respectively].

Conclusion: Subjects with PreDM and low circulating 25(OH)D concentrations are the subgroup of nondiabetic individuals who are the most insulin resistant and have impaired β-cell function, attributes that put them at enhanced risk of T2DM.

Keywords: 25-hydroxyvitamin D; HOMA-IR; HOMA-β; insulin resistance; insulin secretion; prediabetes.

FIGURE 1

Insulin resistance (SSPG concentration and HOMA-IR) and insulin secretion (HOMA-β) in individuals with PreDM or NFG divided on the basis of 25(OH)D status. Values are arithmetic means (SSPG concentration) or geometric means (HOMA-IR and HOMA-β) and their 95% CIs (error bars). Higher values of SSPG concentration (A) and HOMA-IR (B) indicate increased insulin resistance and lower values of HOMA-β (C) indicate decreased β-cell function. In each panel, the P value denotes the overall difference in means among the 4 subgroups by 1-factor ANCOVA, adjusted for age, sex, race, BMI, multivitamin use, and season. Pairs of means without a common letter differ, P < 0.05 by least-significant-difference pairwise comparison test. FPG concentration ≥100 mg/dL, PreDM, and <100 mg/dL, NFG. 25(OH)D concentration ≤20 ng/mL, 25(OH)D deficient, and >20 ng/mL, 25(OH)D sufficient. Deficient, 25(OH)D deficient; HOMA-β, homeostasis model assessment of β-cell function; NFG, normal fasting glucose; PreDM, prediabetes mellitus; SSPG, steady state plasma glucose; sufficient, 25(OH)D sufficient; 25(OH)D, 25-hydroxyvitamin D.