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- Title
Disproportionately Elevated Proinsulin Levels Reflect the Degree of Impaired B Cell Secretory Capacity in Patients with Noninsulin-Dependent Diabetes Mellitus.
- Authors
RØDER, MICHAEL E.; PORTE JR., DANIEL; SCHWARTZ, ROBERT S.; KAHN, STEVEN E.
- 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 iv 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.
- Publication
Journal of Clinical Endocrinology & Metabolism, 1998, Vol 83, Issue 2, p604
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/jc.83.2.604