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Identification, pathophysiology, and clinical implications of primary insulin hypersecretion in nondiabetic adults and adolescents.
- Source :
-
JCI insight [JCI Insight] 2018 Dec 20; Vol. 3 (24). Date of Electronic Publication: 2018 Dec 20. - Publication Year :
- 2018
-
Abstract
- Background: Excessive insulin secretion may lead to glucose dysregulation. Our aim was to identify primary (independent of insulin resistance) insulin hypersecretion in subjects with normal glucose tolerance and its role in the progression of dysglycemia.<br />Methods: In 1,168 adults, insulin secretion rate (ISR) and β cell function were estimated by C-peptide modeling during an oral glucose tolerance test (OGTT) and an i.v. glucose tolerance test. Whole-body insulin sensitivity was measured by a hyperinsulinemic-euglycemic clamp. After regressing ISR on insulin sensitivity, subjects in the upper tertile of the distribution of residuals were defined as primary hypersecretors. This approach was applied to a biethnic cohort of 182 obese adolescents, who received an OGTT, a hyperglycemic, and a euglycemic clamp.<br />Results: Adult hypersecretors showed older age, more familial diabetes, sedentary lifestyle, increased fat mass, and worse lipid profile compared with the rest of the cohort, despite virtually identical BMI and insulin sensitivity. Insulin secretion was increased by 53% due to enhanced (+23%) β cell glucose sensitivity. Despite the resulting hyperinsulinemia, glucose tolerance was worse in hypersecretors among both adults and adolescents, coupled with higher indices of liver insulin resistance and increased availability of gluconeogenic substrates. At the 3-year follow-up, adult hypersecretors had increased incidence of impaired glucose tolerance/type 2 diabetes.<br />Conclusion: Primary insulin hypersecretion, independent of insulin resistance, is associated with a worse clinical and metabolic phenotype in adults and adolescents and predicts deterioration of glucose control over time.<br />Funding: The relationship between insulin sensitivity and cardiovascular disease (RISC) Study was partly supported by EU grant QLG1-CT-2001-01252.
- Subjects :
- Adolescent
Adult
Body Mass Index
Child
Diabetes Mellitus, Type 2 metabolism
Glucose metabolism
Glucose Clamp Technique
Glucose Intolerance
Glucose Tolerance Test
Humans
Insulin blood
Insulin Resistance physiology
Insulin-Secreting Cells metabolism
Middle Aged
Prospective Studies
Young Adult
Insulin metabolism
Insulin Secretion physiology
Obesity physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 2379-3708
- Volume :
- 3
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- JCI insight
- Publication Type :
- Academic Journal
- Accession number :
- 30568042
- Full Text :
- https://doi.org/10.1172/jci.insight.124912