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Metabolism. 2016 Jun;65(6):835-42. doi: 10.1016/j.metabol.2016.02.011. Epub 2016 Feb 26.

Hyperglycemic clamp-derived disposition index is negatively associated with metabolic syndrome severity in obese subjects.

Author information

1
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
2
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
3
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.
4
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
5
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
6
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.

Abstract

OBJECTIVE:

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.

RESEARCH DESIGN AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Disposition Index; Insulin secretion; Insulin sensitivity; Metabolic syndrome

PMID:
27173462
PMCID:
PMC4867079
DOI:
10.1016/j.metabol.2016.02.011
[Indexed for MEDLINE]
Free PMC Article

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