title: Phenotypic Characterization of Insulin-Resistant and Insulin-Sensitive Obesity.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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 Musclesen and those in the lower two tertiles were assigned Muscleres. Secondarily, top tertile subjects for endogenous glucose production suppression during the low-dose insulin clamp were deemed Liversen and the remainder Liverres.
  
  
  METHODS
  Clinical and laboratory parameters and visceral, subcutaneous, liver, and pancreatic fat were compared.
  
  
  RESULTS
  Musclesen and Muscleres had similar body mass index and total fat (P > .16), but Musclesen 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. Liversen had lower visceral (P < .01) and liver (P < .01) fat and C-reactive protein (P = .02) than Liverres. 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.
authors.affiliation: Division of Diabetes and Metabolism (D.L.C., A.B.J., D.J.C., D.S.-B., J.R.G.), Garvan Institute of Medical Research and Bioanalytical Mass Spectrometry Facility (A.P.), School of Medical Sciences (A.P., D.S.-B.), Center for Healthy Brain Ageing (A.P.), and Faculty of Medicine (J.R.G.), University of New South Wales, and Department of Radiology (B.M.), and Department of Endocrinology and Diabetes Center (J.R.G.), St Vincent's Hospital, Sydney, New South Wales 2010, Australia; Philips Healthcare (C.L.), Luebeckertordamm 5, 20099 Hamburg, Germany; State Key Laboratory of Pharmaceutical Biotechnology (A.X., J.Z.), University of Hong Kong, Hong Kong; Movelab (C.T., M.T.), Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom; and School of Health Science (A.B.J.), University of Wollongong, Wollongong, New South Wales 2500, Australia.
authors.forename: D L
authors.initials: DL
authors.lastname: Chen
authors.affiliation: Division of Diabetes and Metabolism (D.L.C., A.B.J., D.J.C., D.S.-B., J.R.G.), Garvan Institute of Medical Research and Bioanalytical Mass Spectrometry Facility (A.P.), School of Medical Sciences (A.P., D.S.-B.), Center for Healthy Brain Ageing (A.P.), and Faculty of Medicine (J.R.G.), University of New South Wales, and Department of Radiology (B.M.), and Department of Endocrinology and Diabetes Center (J.R.G.), St Vincent's Hospital, Sydney, New South Wales 2010, Australia; Philips Healthcare (C.L.), Luebeckertordamm 5, 20099 Hamburg, Germany; State Key Laboratory of Pharmaceutical Biotechnology (A.X., J.Z.), University of Hong Kong, Hong Kong; Movelab (C.T., M.T.), Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom; and School of Health Science (A.B.J.), University of Wollongong, Wollongong, New South Wales 2500, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Liess
authors.affiliation: Division of Diabetes and Metabolism (D.L.C., A.B.J., D.J.C., D.S.-B., J.R.G.), Garvan Institute of Medical Research and Bioanalytical Mass Spectrometry Facility (A.P.), School of Medical Sciences (A.P., D.S.-B.), Center for Healthy Brain Ageing (A.P.), and Faculty of Medicine (J.R.G.), University of New South Wales, and Department of Radiology (B.M.), and Department of Endocrinology and Diabetes Center (J.R.G.), St Vincent's Hospital, Sydney, New South Wales 2010, Australia; Philips Healthcare (C.L.), Luebeckertordamm 5, 20099 Hamburg, Germany; State Key Laboratory of Pharmaceutical Biotechnology (A.X., J.Z.), University of Hong Kong, Hong Kong; Movelab (C.T., M.T.), Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom; and School of Health Science (A.B.J.), University of Wollongong, Wollongong, New South Wales 2500, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Poljak
authors.affiliation: Division of Diabetes and Metabolism (D.L.C., A.B.J., D.J.C., D.S.-B., J.R.G.), Garvan Institute of Medical Research and Bioanalytical Mass Spectrometry Facility (A.P.), School of Medical Sciences (A.P., D.S.-B.), Center for Healthy Brain Ageing (A.P.), and Faculty of Medicine (J.R.G.), University of New South Wales, and Department of Radiology (B.M.), and Department of Endocrinology and Diabetes Center (J.R.G.), St Vincent's Hospital, Sydney, New South Wales 2010, Australia; Philips Healthcare (C.L.), Luebeckertordamm 5, 20099 Hamburg, Germany; State Key Laboratory of Pharmaceutical Biotechnology (A.X., J.Z.), University of Hong Kong, Hong Kong; Movelab (C.T., M.T.), Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom; and School of Health Science (A.B.J.), University of Wollongong, Wollongong, New South Wales 2500, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Xu
authors.affiliation: Division of Diabetes and Metabolism (D.L.C., A.B.J., D.J.C., D.S.-B., J.R.G.), Garvan Institute of Medical Research and Bioanalytical Mass Spectrometry Facility (A.P.), School of Medical Sciences (A.P., D.S.-B.), Center for Healthy Brain Ageing (A.P.), and Faculty of Medicine (J.R.G.), University of New South Wales, and Department of Radiology (B.M.), and Department of Endocrinology and Diabetes Center (J.R.G.), St Vincent's Hospital, Sydney, New South Wales 2010, Australia; Philips Healthcare (C.L.), Luebeckertordamm 5, 20099 Hamburg, Germany; State Key Laboratory of Pharmaceutical Biotechnology (A.X., J.Z.), University of Hong Kong, Hong Kong; Movelab (C.T., M.T.), Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom; and School of Health Science (A.B.J.), University of Wollongong, Wollongong, New South Wales 2500, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of Diabetes and Metabolism (D.L.C., A.B.J., D.J.C., D.S.-B., J.R.G.), Garvan Institute of Medical Research and Bioanalytical Mass Spectrometry Facility (A.P.), School of Medical Sciences (A.P., D.S.-B.), Center for Healthy Brain Ageing (A.P.), and Faculty of Medicine (J.R.G.), University of New South Wales, and Department of Radiology (B.M.), and Department of Endocrinology and Diabetes Center (J.R.G.), St Vincent's Hospital, Sydney, New South Wales 2010, Australia; Philips Healthcare (C.L.), Luebeckertordamm 5, 20099 Hamburg, Germany; State Key Laboratory of Pharmaceutical Biotechnology (A.X., J.Z.), University of Hong Kong, Hong Kong; Movelab (C.T., M.T.), Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom; and School of Health Science (A.B.J.), University of Wollongong, Wollongong, New South Wales 2500, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Thoma
authors.affiliation: Division of Diabetes and Metabolism (D.L.C., A.B.J., D.J.C., D.S.-B., J.R.G.), Garvan Institute of Medical Research and Bioanalytical Mass Spectrometry Facility (A.P.), School of Medical Sciences (A.P., D.S.-B.), Center for Healthy Brain Ageing (A.P.), and Faculty of Medicine (J.R.G.), University of New South Wales, and Department of Radiology (B.M.), and Department of Endocrinology and Diabetes Center (J.R.G.), St Vincent's Hospital, Sydney, New South Wales 2010, Australia; Philips Healthcare (C.L.), Luebeckertordamm 5, 20099 Hamburg, Germany; State Key Laboratory of Pharmaceutical Biotechnology (A.X., J.Z.), University of Hong Kong, Hong Kong; Movelab (C.T., M.T.), Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom; and School of Health Science (A.B.J.), University of Wollongong, Wollongong, New South Wales 2500, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Trenell
authors.affiliation: Division of Diabetes and Metabolism (D.L.C., A.B.J., D.J.C., D.S.-B., J.R.G.), Garvan Institute of Medical Research and Bioanalytical Mass Spectrometry Facility (A.P.), School of Medical Sciences (A.P., D.S.-B.), Center for Healthy Brain Ageing (A.P.), and Faculty of Medicine (J.R.G.), University of New South Wales, and Department of Radiology (B.M.), and Department of Endocrinology and Diabetes Center (J.R.G.), St Vincent's Hospital, Sydney, New South Wales 2010, Australia; Philips Healthcare (C.L.), Luebeckertordamm 5, 20099 Hamburg, Germany; State Key Laboratory of Pharmaceutical Biotechnology (A.X., J.Z.), University of Hong Kong, Hong Kong; Movelab (C.T., M.T.), Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom; and School of Health Science (A.B.J.), University of Wollongong, Wollongong, New South Wales 2500, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Milner
authors.affiliation: Division of Diabetes and Metabolism (D.L.C., A.B.J., D.J.C., D.S.-B., J.R.G.), Garvan Institute of Medical Research and Bioanalytical Mass Spectrometry Facility (A.P.), School of Medical Sciences (A.P., D.S.-B.), Center for Healthy Brain Ageing (A.P.), and Faculty of Medicine (J.R.G.), University of New South Wales, and Department of Radiology (B.M.), and Department of Endocrinology and Diabetes Center (J.R.G.), St Vincent's Hospital, Sydney, New South Wales 2010, Australia; Philips Healthcare (C.L.), Luebeckertordamm 5, 20099 Hamburg, Germany; State Key Laboratory of Pharmaceutical Biotechnology (A.X., J.Z.), University of Hong Kong, Hong Kong; Movelab (C.T., M.T.), Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom; and School of Health Science (A.B.J.), University of Wollongong, Wollongong, New South Wales 2500, Australia.
authors.forename: A B
authors.initials: AB
authors.lastname: Jenkins
authors.affiliation: Division of Diabetes and Metabolism (D.L.C., A.B.J., D.J.C., D.S.-B., J.R.G.), Garvan Institute of Medical Research and Bioanalytical Mass Spectrometry Facility (A.P.), School of Medical Sciences (A.P., D.S.-B.), Center for Healthy Brain Ageing (A.P.), and Faculty of Medicine (J.R.G.), University of New South Wales, and Department of Radiology (B.M.), and Department of Endocrinology and Diabetes Center (J.R.G.), St Vincent's Hospital, Sydney, New South Wales 2010, Australia; Philips Healthcare (C.L.), Luebeckertordamm 5, 20099 Hamburg, Germany; State Key Laboratory of Pharmaceutical Biotechnology (A.X., J.Z.), University of Hong Kong, Hong Kong; Movelab (C.T., M.T.), Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom; and School of Health Science (A.B.J.), University of Wollongong, Wollongong, New South Wales 2500, Australia.
authors.forename: D J
authors.initials: DJ
authors.lastname: Chisholm
authors.affiliation: Division of Diabetes and Metabolism (D.L.C., A.B.J., D.J.C., D.S.-B., J.R.G.), Garvan Institute of Medical Research and Bioanalytical Mass Spectrometry Facility (A.P.), School of Medical Sciences (A.P., D.S.-B.), Center for Healthy Brain Ageing (A.P.), and Faculty of Medicine (J.R.G.), University of New South Wales, and Department of Radiology (B.M.), and Department of Endocrinology and Diabetes Center (J.R.G.), St Vincent's Hospital, Sydney, New South Wales 2010, Australia; Philips Healthcare (C.L.), Luebeckertordamm 5, 20099 Hamburg, Germany; State Key Laboratory of Pharmaceutical Biotechnology (A.X., J.Z.), University of Hong Kong, Hong Kong; Movelab (C.T., M.T.), Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom; and School of Health Science (A.B.J.), University of Wollongong, Wollongong, New South Wales 2500, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Samocha-Bonet
authors.affiliation: Division of Diabetes and Metabolism (D.L.C., A.B.J., D.J.C., D.S.-B., J.R.G.), Garvan Institute of Medical Research and Bioanalytical Mass Spectrometry Facility (A.P.), School of Medical Sciences (A.P., D.S.-B.), Center for Healthy Brain Ageing (A.P.), and Faculty of Medicine (J.R.G.), University of New South Wales, and Department of Radiology (B.M.), and Department of Endocrinology and Diabetes Center (J.R.G.), St Vincent's Hospital, Sydney, New South Wales 2010, Australia; Philips Healthcare (C.L.), Luebeckertordamm 5, 20099 Hamburg, Germany; State Key Laboratory of Pharmaceutical Biotechnology (A.X., J.Z.), University of Hong Kong, Hong Kong; Movelab (C.T., M.T.), Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom; and School of Health Science (A.B.J.), University of Wollongong, Wollongong, New South Wales 2500, Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Greenfield
mesh_terms: D017667:Adipocytes / Q000473:pathology / Q000648:ultrastructure; D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology*; D010179:Pancreas / Q000378:metabolism; D010641:Phenotype; D050151:Subcutaneous Fat / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; D014280:Triglycerides; D002097:C-Reactive Protein