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Disproportionately elevated proinsulin in Pima Indians with noninsulin-dependent diabetes mellitus.
J Clin Endocrinol Metab. 1990 May; 70(5):1247-53.JC

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.

Authors+Show Affiliations

Diabetes and Arthritis Epidemiology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85014.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2186054

Citation

Saad, M F., et al. "Disproportionately Elevated Proinsulin in Pima Indians With Noninsulin-dependent Diabetes Mellitus." The Journal of Clinical Endocrinology and Metabolism, vol. 70, no. 5, 1990, pp. 1247-53.
Saad MF, Kahn SE, Nelson RG, et al. Disproportionately elevated proinsulin in Pima Indians with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1990;70(5):1247-53.
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. (1990). Disproportionately elevated proinsulin in Pima Indians with noninsulin-dependent diabetes mellitus. The Journal of Clinical Endocrinology and Metabolism, 70(5), 1247-53.
Saad MF, et al. Disproportionately Elevated Proinsulin in Pima Indians With Noninsulin-dependent Diabetes Mellitus. J Clin Endocrinol Metab. 1990;70(5):1247-53. PubMed PMID: 2186054.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Disproportionately elevated proinsulin in Pima Indians with noninsulin-dependent diabetes mellitus. AU - Saad,M F, AU - Kahn,S E, AU - Nelson,R G, AU - Pettitt,D J, AU - Knowler,W C, AU - Schwartz,M W, AU - Kowalyk,S, AU - Bennett,P H, AU - Porte,D,Jr PY - 1990/5/1/pubmed PY - 2001/3/28/medline PY - 1990/5/1/entrez SP - 1247 EP - 53 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 70 IS - 5 N2 - 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. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/2186054/Disproportionately_elevated_proinsulin_in_Pima_Indians_with_noninsulin_dependent_diabetes_mellitus_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem-70-5-1247 DB - PRIME DP - Unbound Medicine ER -