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Disproportionately Elevated Proinsulin in Pima Indians with Noninsulin-Dependent Diabetes Mellitus*
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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“inefficient proinsulin processing to insulin [77, 78, 79, 80, 81, 82, 83] and a reduction in the release of islet amyloid polypeptide (IAPP), known also as amylin [84, 85, 86, 87], have been observed in established Type 2 diabetes.”
From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [81]
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Metadata
- 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
- 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 › Endocrinology, Diabetes and Metabolism › 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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