Plasma levels of proinsulin and its conversion intermediates are elevated in NIDDM patients. Recent studies have suggested that proinsulin levels are also increased relative to insulin levels in subjects who subsequently develop NIDDM. This may be due to insulin resistance or a defect in proinsulin processing or insulin secretion. If insulin resistance is the trigger, the proinsulinto-insulin ratio would be higher in insulin-resistant subjects than in insulin-sensitive subjects. We examined the association of fasting proinsulin, 32,33 split proinsulin, and the proinsulin-to-insulin ratio with insulin sensitivity (SI), estimated by a frequently sampled intravenous glucose tolerance test and the minimal model in 138 normoglycemic subjects ages 53–61 years. We also investigated the relation of proinsulins and the proinsulin-to-insulin ratio to acute insulin response (AIR). Fasting specific insulin (r = −0.64), intact proinsulin (r = −0.43), and 32,33 split proinsulin (r = −0.54) concentrations were inversely correlated and the proinsulin-to-insulin ratio positively (r = 0.31) correlated with SI (P < 0.001). Fasting specific insulin (r = 0.64), intact proinsulin (r = 0.35), and 32,33 split proinsulin (r = 0.45) concentrations were positively correlated and proinsulin-to-insulin ratio (r = −0.40) inversely correlated with AIR (P < 0.001). The proinsulin-to-insulin ratio increased by increasing levels of SI (quartiles of 5, from low to high: 0.048, 0.078, 0.078, 0.068; P = 0.012) and decreased by increasing SI (quartiles of SI from low to high: 0.088, 0.068, 0.058, 0.058; P = 0.005). These associations were independent of age, sex, BMI, and waist-to-hip ratio. Furthermore, the relation between the proinsulin-to-insulin ratio and AIR was independent of SI In conclusion, in normoglycemic subjects, insulin resistance (low SI was associated with a low rather than a high proinsulin-to-insulin ratio. Subjects who maintained normoglycemia with a low AIR had an increased proinsulin-to-insulin ratio compared with those who needed high to maintain normoglycemia. These results suggest that, in subjects with normal glucose tolerance, insulin resistance does not induce increased proinsulin relative to insulin secretion, but rather is associated with enhanced processing of proinsulin.
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Original Articles|
December 01 1997
The Relation of Proinsulin, Insulin, and Proinsulin-to-Insulin Ratio to Insulin Sensitivity and Acute Insulin Response in Normoglycemic Subjects
Leena Mykkänen;
Leena Mykkänen
Department of Medicine, Division of Clinical Epidemiology, University of Texas Health Science Center at San Antonio
San Antonio, Texas
Department of Medicine, University of Kuopio
Kuopio, Finland
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Steven M Haffner;
Steven M Haffner
Department of Medicine, Division of Clinical Epidemiology, University of Texas Health Science Center at San Antonio
San Antonio, Texas
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C Nick Hales;
C Nick Hales
Department of Biochemistry, University of Cambridge
Cambridge, U.K.
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Tapani Rönnemaa;
Tapani Rönnemaa
Department of Medicine, University of Turku
Turku
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Markku Laakso
Markku Laakso
Department of Medicine, University of Kuopio
Kuopio, Finland
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Address correspondence and reprint requests to Dr. Leena Mykkanen, University of Texas Health Science Center, Division of Clinical Epidemiology, 7703 Floyd Curl Dr., San Antonio, TX 78284. E-mail: [email protected].
Diabetes 1997;46(12):1990–1995
Article history
Received:
February 07 1997
Revision Received:
August 07 1997
Accepted:
August 07 1997
PubMed:
9392485
Citation
Leena Mykkänen, Steven M Haffner, C Nick Hales, Tapani Rönnemaa, Markku Laakso; The Relation of Proinsulin, Insulin, and Proinsulin-to-Insulin Ratio to Insulin Sensitivity and Acute Insulin Response in Normoglycemic Subjects. Diabetes 1 December 1997; 46 (12): 1990–1995. https://doi.org/10.2337/diab.46.12.1990
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