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Disproportionately elevated proinsulin levels reflect the degree of impaired B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus.
J Clin Endocrinol Metab. 1998 Feb; 83(2):604-8.JC

Abstract

An increased proportion of fasting proinsulin (PI) relative to immunoreactive insulin (IRI; increased PI/IRI) occurs in noninsulin-dependent diabetes mellitus (NIDDM). To determine whether the magnitude of the increase in PI/IRI is an indicator of the degree of reduced B cell secretory capacity, we measured fasting plasma glucose, PI, IRI, and PI/IRI and related them to maximal B cell secretory capacity (AIRmax) in 9 subjects with NIDDM [age, 61 +/- 3 yr; body mass index (BMI), 27.5 +/- 1.3 kg/m2; duration of NIDDM, 10.8 +/- 1.8 yr; mean +/- SEM] and in 10 healthy subjects matched for age and BMI (age, 61 +/- 6 yr; BMI, 27.9 +/- 1.5 kg/m2). AIRmax was quantified as the incremental insulin response to i.v. arginine at maximal glycemic potentiation (plasma glucose > 25 mmol/L). Mean fasting plasma glucose was 13.7 +/- 1.4 mmol/L (range, 7.5-18.3 mmol/L) in NIDDM subjects and 5.0 +/- 0.1 mmol/L in the controls. Fasting PI was higher in NIDDM (33.1 +/- 5.2) than in controls (9.4 +/- 2.5 pmol/L; P < 0.01), but IRI levels were similar (93.4 +/- 10.9 vs. 82.8 +/- 23.4 pmol/L; P = NS). The PI/IRI ratio was significantly elevated in NIDDM compared to control subjects (35.9 +/- 4.1% vs. 12.8 +/- 0.8%; P < 0.01). After elevation of the glucose level to 30.3 +/- 0.4 mmol/L (NIDDM) and 30.3 +/- 0.5 mmol/L (controls), AIRmax was quantified as 622 +/- 71 pmol/L in NIDDM and 1997 +/- 315 pmol/L in controls, (P < 0.001). The PI/IRI ratio correlated inversely with AIRmax in the NIDDM patients (r = -0.76; P < 0.01). We conclude that the magnitude of the elevation in fasting PI/IRI is related to the reduction in AIRmax. Thus, the fasting PI/IRI ratio appears to be a marker of the degree of reduced AIRmax in NIDDM.

Authors+Show Affiliations

Division of Metabolism, Endocrinology, and Nutrition, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA. mroder@login.dknet.dkNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9467581

Citation

Røder, M E., et al. "Disproportionately Elevated Proinsulin Levels Reflect the Degree of Impaired B Cell Secretory Capacity in Patients With Noninsulin-dependent Diabetes Mellitus." The Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 2, 1998, pp. 604-8.
Røder ME, Porte D, Schwartz RS, et al. Disproportionately elevated proinsulin levels reflect the degree of impaired B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1998;83(2):604-8.
Røder, M. E., Porte, D., Schwartz, R. S., & Kahn, S. E. (1998). Disproportionately elevated proinsulin levels reflect the degree of impaired B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. The Journal of Clinical Endocrinology and Metabolism, 83(2), 604-8.
Røder ME, et al. Disproportionately Elevated Proinsulin Levels Reflect the Degree of Impaired B Cell Secretory Capacity in Patients With Noninsulin-dependent Diabetes Mellitus. J Clin Endocrinol Metab. 1998;83(2):604-8. PubMed PMID: 9467581.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Disproportionately elevated proinsulin levels reflect the degree of impaired B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. AU - Røder,M E, AU - Porte,D,Jr AU - Schwartz,R S, AU - Kahn,S E, PY - 1998/2/19/pubmed PY - 2001/3/28/medline PY - 1998/2/19/entrez SP - 604 EP - 8 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 83 IS - 2 N2 - An increased proportion of fasting proinsulin (PI) relative to immunoreactive insulin (IRI; increased PI/IRI) occurs in noninsulin-dependent diabetes mellitus (NIDDM). To determine whether the magnitude of the increase in PI/IRI is an indicator of the degree of reduced B cell secretory capacity, we measured fasting plasma glucose, PI, IRI, and PI/IRI and related them to maximal B cell secretory capacity (AIRmax) in 9 subjects with NIDDM [age, 61 +/- 3 yr; body mass index (BMI), 27.5 +/- 1.3 kg/m2; duration of NIDDM, 10.8 +/- 1.8 yr; mean +/- SEM] and in 10 healthy subjects matched for age and BMI (age, 61 +/- 6 yr; BMI, 27.9 +/- 1.5 kg/m2). AIRmax was quantified as the incremental insulin response to i.v. arginine at maximal glycemic potentiation (plasma glucose > 25 mmol/L). Mean fasting plasma glucose was 13.7 +/- 1.4 mmol/L (range, 7.5-18.3 mmol/L) in NIDDM subjects and 5.0 +/- 0.1 mmol/L in the controls. Fasting PI was higher in NIDDM (33.1 +/- 5.2) than in controls (9.4 +/- 2.5 pmol/L; P < 0.01), but IRI levels were similar (93.4 +/- 10.9 vs. 82.8 +/- 23.4 pmol/L; P = NS). The PI/IRI ratio was significantly elevated in NIDDM compared to control subjects (35.9 +/- 4.1% vs. 12.8 +/- 0.8%; P < 0.01). After elevation of the glucose level to 30.3 +/- 0.4 mmol/L (NIDDM) and 30.3 +/- 0.5 mmol/L (controls), AIRmax was quantified as 622 +/- 71 pmol/L in NIDDM and 1997 +/- 315 pmol/L in controls, (P < 0.001). The PI/IRI ratio correlated inversely with AIRmax in the NIDDM patients (r = -0.76; P < 0.01). We conclude that the magnitude of the elevation in fasting PI/IRI is related to the reduction in AIRmax. Thus, the fasting PI/IRI ratio appears to be a marker of the degree of reduced AIRmax in NIDDM. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/9467581/Disproportionately_elevated_proinsulin_levels_reflect_the_degree_of_impaired_B_cell_secretory_capacity_in_patients_with_noninsulin_dependent_diabetes_mellitus_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem.83.2.4544 DB - PRIME DP - Unbound Medicine ER -