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Cited by 167Pancreatic function and diabetesDiabetes, Cardiovascular Risks, and LipoproteinsDiabetes and associated disorders

Disproportionately Elevated Proinsulin in Pima Indians with Noninsulin-Dependent Diabetes Mellitus*

SAAD, MOHAMMED F., KAHN, STEVEN E., NELSON, ROBERT G., PETTITT, DAVID J., KNOWLER, WILLIAM C., SCHWARTZ, MICHAEL W., KOWALYK, STEPHAN, BENNETT, PETER H. +1 more·1990·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem-70-5-1247
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Abstract

Fasting serum total immunoreactive insulin (IRI), true insulin, and true proinsulin (PI) were measured in 169 Pima Indians. The relationship of these variables to glucose tolerance, obesity, and parental diabetes was studied. Seventy-seven subjects had normal glucose tolerance, 46 had impaired glucose tolerance (IGT), and 46 had noninsulin-dependent diabetes mellitus (NIDDM) by WHO criteria. In subjects with normal glucose tolerance, the geometric mean ratio of PI to IRI (PI/IRI) was 10.8% (arithmetic mean, 12.5%), similar to that reported in other ethnic groups with lower prevalence rates of NIDDM. Parental diabetes had no effect on PI/IRI. Obese persons (body mass index, greater than or equal to 27 kg/m2) with normal glucose tolerance had PI/IRI of 9.3% compared with 16.3% for the nonobese (P less than 0.001), and PI/IRI was negatively correlated with body mass index (r = -0.34; P = 0.002). Proinsulin was disproportionately elevated in NIDDM (geometric mean PI/IRI, 19.9%; arithmetic mean, 23.6%), and the degree of elevation was related to the severity of hyperglycemia, but not the duration of diabetes. Subjects with IGT were more obese and had higher fasting plasma glucose (5.7 vs. 5.2 mmol/L; P = 0.025), true insulin (250 vs. 125 pmol/L; P less than 0.001), and PI concentrations (26 vs. 15 pmol/L; P less than 0.001) than those with normal glucose tolerance but similar mean PI/IRI (9.4 vs. 10.8%; P = 0.4). These findings indicate that Pima Indians with NIDDM have a disproportionate elevation of PI consistent with the hypothesis that beta-cell dysfunction associated with hyperglycemia leads to the release of proinsulin-rich immature granules.

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Authors
SAAD, M. F., KAHN, S. E., NELSON, R. G., PETTITT, D. J., KNOWLER, W. C., SCHWARTZ, M. W., KOWALYK, S., BENNETT, P. H., & PORTE, D.
Affiliations
National Institutes of Health (US)
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
1990-05
Volume
70
Issue
5
Pages
1247-1253
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jcem-70-5-1247
OpenAlex
W2065395239
Cited by
167
References
32
Citations by year
2026: 1 · 2023: 2 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 1
FWCI
10.24
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (2r01dk012829-36)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 12829, DK-17047, P30DK017047)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
proinsulin, type 2 diabetes, Pima Indians, impaired glucose tolerance, obesity, body mass index, beta-cell dysfunction, hyperglycemia, insulin secretion, proinsulin/insulin ratio
MeSH terms
Adolescent, Adult, Aged, Arizona, Blood Glucose, Diabetes Mellitus, Type 2, Fasting, Female, Glucose Tolerance Test, Humans, Indians, North American, Insulin, Male, Middle Aged, Obesity, Proinsulin, Body Mass Index

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