title: Hyperglycemic clamp-derived disposition index is negatively associated with metabolic syndrome severity in obese subjects.
abstract: Metabolic syndrome is associated with insulin resistance and increased future risk of type 2 diabetes. This study investigates the relationship between insulin secretion, insulin resistance and individual metabolic syndrome components in subjects without a prior diagnosis of diabetes.
  
  
  
  We assessed insulin secretion during hyperglycemic clamps by infusing dextrose to maintain hyperglycemia (200mg/dL), followed by L-arginine administration. Studies in 98 individuals (mean age 45.3±1.2years, 56% female, 22% African-American, 49% with metabolic syndrome) were analyzed. We tested the association between the number of metabolic syndrome components and individual outcome variables using linear mixed-effects models to adjust for potential confounding effects of age, sex, and race.
  
  
  
  Insulin sensitivity index was reduced in the presence of 1 or more metabolic syndrome components. Insulin sensitivity was independently associated with age, waist circumference, male gender and decreased HDL cholesterol. The acute insulin response was greater with two or more metabolic syndrome components, and late glucose-stimulated and L-arginine-stimulated insulin responses exhibited a similar trend. In contrast, the disposition index, a measure of beta cell compensation for insulin resistance, was linearly lower with the number of metabolic syndrome components, and was negatively associated with age, Caucasian race, waist circumference, fasting glucose, and decreased HDL cholesterol.
  
  
  
  The insulin secretory response in metabolic syndrome is inadequate for the worsening insulin sensitivity, as demonstrated by a decline in disposition index. A dysfunctional insulin secretory response is evident in non-diabetic individuals and worsens with accumulation of metabolic syndrome components.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Sapna S
authors.initials: SS
authors.lastname: Shah
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Ramirez
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA.
authors.forename: Alvin C
authors.initials: AC
authors.lastname: Powers
authors.affiliation: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Cyndya A
authors.initials: CA
authors.lastname: Shibao
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: James.Luther@Vanderbilt.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Luther
mesh_terms: D000328:Adult; D000367:Age Factors; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D012720:Severity of Illness Index; D012737:Sex Factors; D055105:Waist Circumference
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: Disposition Index; Insulin secretion; Insulin sensitivity; Metabolic syndrome