Browsing by Author "Mather, K. J."

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    Changes in Weight and Glucose Can Protect Against Progression in Early Diabetes Independent of Improvements in β-Cell Function
    (Oxford University Press, 2016-11) Patel, Y. R.; Kirkman, M. S.; Considine, R. V.; Hannon, T. S.; Mather, K. J.; Medicine, School of Medicine
    Reductions in fasting glucose, via reductions in weight, provided protection from progressive dysglycemia in EDIP. Lifestyle change can contribute importantly to glycemic control in early diabetes.
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    Effects of Acarbose to Delay Progression of Carotid Intima-Media Thickness in Early Diabetes
    (Wiley, 2013) Patel, Y. R.; Kirkman, M. S.; Considine, R. V.; Hannon, T. S.; Mather, K. J.; Medicine, School of Medicine
    Background: The anti-diabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes. Methods: The Early Diabetes Intervention Program was a randomized trial of acarbose versus placebo in 219 participants with early diabetes characterized by glucose values over 11.1 mmol/L 2 h after a 75 g oral glucose load and a mean HbA1c of 6.3%. IMT was measured at baseline and yearly. Follow-up was discontinued if participants progressed to the study glucose endpoints; IMT readings were available for a median of 2 years, with 72 subjects followed for 5 years. Results: Progressive increases in IMT were seen in both treatment groups, but progression was reduced in participants randomized to acarbose (p = 0.047). In age, sex and smoking-adjusted analyses, IMT progression was associated with greater fasting and oral glucose tolerance test-excursion glucose, fasting insulin, cholesterol and glycated low-density lipoprotein concentrations. IMT progression was reduced with study-related changes in weight, insulin and non-esterified fatty acids; these features were more strongly associated with reduced IMT progression than acarbose treatment. Despite strong associations of baseline glycemia with IMT progression, study-related changes in glucose were not important determinants of IMT progression. Conclusions: Acarbose can delay progression of carotid intima-media thickness in early diabetes defined by an oral glucose tolerance test. Glucose, weight, insulin and lipids contributed to risk of progression but reductions in glycemia were not major determinants of reduced rate of IMT progression. Vascular benefits of acarbose may be independent of its glycemic effects.
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    Steroid Sex Hormones, Sex Hormone–Binding Globulin, and Diabetes Incidence in the Diabetes Prevention Program.
    (The Endocrine Society, 2015-10) Mather, K. J.; Kim, C.; Christophi, C. A.; Aroda, V. R.; Knowler, W. C.; Edelstein, S. E.; Florez, J. C.; Labrie, F.; Kahn, S. E.; Goldberg, R. B.; Barrett-Connor, E.; Department of Medicine, IU School of Medicine
    Context:: Steroid sex hormones and SHBG may modify metabolism and diabetes risk, with implications for sex-specific diabetes risk and effects of prevention interventions. Objective:: This study aimed to evaluate the relationships of steroid sex hormones, SHBG and SHBG single-nucleotide polymorphisms (SNPs) with diabetes risk factors and with progression to diabetes in the Diabetes Prevention Program (DPP). Design and Setting:: This was a secondary analysis of a multicenter randomized clinical trial involving 27 U.S. academic institutions. Participants:: The study included 2898 DPP participants: 969 men, 948 premenopausal women not taking exogenous sex hormones, 550 postmenopausal women not taking exogenous sex hormones, and 431 postmenopausal women taking exogenous sex hormones. Interventions:: Participants were randomized to receive intensive lifestyle intervention, metformin, or placebo. Main Outcomes:: Associations of steroid sex hormones, SHBG, and SHBG SNPs with glycemia and diabetes risk factors, and with incident diabetes over median 3.0 years (maximum, 5.0 y). Results:: T and DHT were inversely associated with fasting glucose in men, and estrone sulfate was directly associated with 2-hour post-challenge glucose in men and premenopausal women. SHBG was associated with fasting glucose in premenopausal women not taking exogenous sex hormones, and in postmenopausal women taking exogenous sex hormones, but not in the other groups. Diabetes incidence was directly associated with estrone and estradiol and inversely with T in men; the association with T was lost after adjustment for waist circumference. Sex steroids were not associated with diabetes outcomes in women. SHBG and SHBG SNPs did not predict incident diabetes in the DPP population. Conclusions:: Estrogens and T predicted diabetes risk in men but not in women. SHBG and its polymorphisms did not predict risk in men or women. Diabetes risk is more potently determined by obesity and glycemia than by sex hormones.