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Phenotypic Characterization of Insulin-Resistant and Insulin-Sensitive Obesity

Lookup NU author(s): Christian Thoma, Professor Mike TrenellORCiD

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Abstract

Context: Whereas insulin resistance and obesity coexist, some obese individuals remain insulin sensitive.Objective: We examined phenotypic and metabolic factors associated with insulin sensitivity in both muscle and liver in obese individuals.Design and Participants: Sixty-four nondiabetic obese adults (29 males) underwent hyperinsulinemic (15 and 80 mU/m(2) . min)-euglycemic clamps with deuterated glucose. Top tertile subjects for glucose infusion rate during the high-dose insulin clamp were assigned Muscle(sen) and those in the lower two tertiles were assigned Muscle(res). Secondarily, top tertile subjects for endogenous glucose production suppression during the low-dose insulin clamp were deemed Liver(sen) and the remainder Liver(res).Main Outcomes Measures: Clinical and laboratory parameters and visceral, subcutaneous, liver, and pancreatic fat were compared.Results: Muscle(sen) and Muscle(res) had similar body mass index and total fat (P > .16), but Muscle(sen) had lower glycated hemoglobin (P < .001) and systolic (P = .01) and diastolic (P = .03) blood pressure (BP). Despite similar sc fat (P = 1), Musclesen had lower visceral (P < .001) and liver (P < .001) fat. Liver(sen) had lower visceral (P < .01) and liver (P < .01) fat and C-reactive protein (P = .02) than Liver(res). When subjects were grouped by both glucose infusion rate during the high-dose insulin clamp and endogenous glucose production suppression, insulin sensitivity at either muscle or liver conferred apparent protection from the adverse metabolic features that characterized subjects insulin resistant at both sites. High-density lipoprotein-cholesterol, 1-hour glucose, systolic BP, and triglycerides explained 54% of the variance in muscle insulin sensitivity.Conclusions: Obese subjects who were insulin sensitive at muscle and/or liver exhibited favorable metabolic features, including lower BP, liver and visceral adiposity. This study identifies factors associated with, and possibly contributing to, insulin sensitivity in obesity.


Publication metadata

Author(s): Chen DL, Liess C, Poljak A, Xu A, Zhang J, Thoma C, Trenell M, Milner B, Jenkins AB, Chisholm DJ, Samocha-Bonet D, Greenfield JR

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Endocrinology & Metabolism

Year: 2015

Volume: 100

Issue: 11

Pages: 4082-4091

Print publication date: 01/11/2015

Online publication date: 17/09/2015

Acceptance date: 14/09/2015

ISSN (print): 0021-972X

ISSN (electronic): 1945-7197

Publisher: The Endocrine Society

URL: http://dx.doi.org/10.1210/jc.2015-2712

DOI: 10.1210/jc.2015-2712


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