Fahim Abbasi1, Christine Blasey2, David Feldman3, Michael P Caulfield4, Feras M Hantash4, Gerald M Reaven5. 1. Divisions of Cardiovascular Medicine and fahim@stanford.edu. 2. Department of Psychiatry, Stanford University School of Medicine, Stanford, CA; and. 3. Endocrinology, Gerontology, and Metabolism, Department of Medicine, and. 4. Quest Diagnostics Nichols Institute, San Juan Capistrano, CA. 5. Divisions of Cardiovascular Medicine and.
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.
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.
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