title: Impact of obesity on insulin action in volunteers with normal glucose tolerance: demonstration of a threshold for the adverse effect of obesity.
abstract: We examined whether obesity must first exceed a critical threshold before it begins to impair insulin action in volunteers with normal glucose tolerance. Forty-nine healthy volunteers, whose ideal body weight ranged from 80-240%, underwent euglycemic clamps during sequential insulin infusions of 0.4, 1.0, and 10 mU/kg.min. Insulin sensitivity was assessed by estimation of the plasma insulin concentration that produced half-maximal glucose disposal (EC50). Glucose disposal during the highest insulin infusion was used as an index of maximal insulin responsiveness. There was a significant correlation between body mass index and insulin sensitivity (EC50) best fitted by a straight line that broke at a body mass index of 26.8 kg/m2 (P less than 0.05). Below this breakpoint (26.8 kg/m2), there was no significant correlation (r = 0.1), whereas above the breakpoint there was a strong positive correlation (r = 0.8; P less than 0.001) between EC50 and body mass index. In contrast, insulin responsiveness was not significantly correlated with body mass index (r = 0.1). We conclude that insulin sensitivity for glucose disposal is impaired in human subjects with normal glucose tolerance who exceed a critical threshold of obesity, which corresponds to an ideal body weight of 120%. This threshold is consistent with the nonlinear (J-shaped) relationship between obesity and its other adverse health consequences, and may have important implications for desirable weight goals.
authors.affiliation: Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee 37232.
authors.forename: P J
authors.initials: PJ
authors.lastname: Campbell
authors.forename: J E
authors.initials: JE
authors.lastname: Gerich
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics*; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose