Higher C-Peptide Level During Glucose Clamp Is Associated With Muscle Insulin Resistance in Nonobese Japanese Men

Hideyoshi Kaga; Yoshifumi Tamura; Kageumi Takeno; Saori Kakehi; Yuki Someya; Takashi Funayama; Yasuhiko Furukawa; Ruriko Suzuki; Daisuke Sugimoto; Satoshi Kadowaki; Miho Nishitani-Yokoyama; Kazunori Shimada; Hiroyuki Daida; Shigeki Aoki; Adria Giacca; Akio Kanazawa; Ryuzo Kawamori; Hirotaka Watada

doi:10.1210/js.2019-00167

Higher C-Peptide Level During Glucose Clamp Is Associated With Muscle Insulin Resistance in Nonobese Japanese Men

J Endocr Soc. 2019 Jul 23;3(10):1847-1857. doi: 10.1210/js.2019-00167. eCollection 2019 Oct 1.

Authors

Hideyoshi Kaga¹, Yoshifumi Tamura^{1

2}, Kageumi Takeno^{1

2}, Saori Kakehi^{1

2}, Yuki Someya², Takashi Funayama¹, Yasuhiko Furukawa¹, Ruriko Suzuki¹, Daisuke Sugimoto¹, Satoshi Kadowaki¹, Miho Nishitani-Yokoyama³, Kazunori Shimada^{2

3}, Hiroyuki Daida^{2

3}, Shigeki Aoki^{2

4}, Adria Giacca⁵, Akio Kanazawa¹, Ryuzo Kawamori^{1

2}, Hirotaka Watada^{1

2

6

7}

Affiliations

¹ Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
² Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
³ Department of Cardiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
⁴ Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
⁵ Departments of Physiology and Medicine, Institute of Medical Science and Banting and Best Diabetes Centre, University of Toronto, Toronto, Canada.
⁶ Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate School of Medicine, Tokyo, Japan.
⁷ Center for Identification of Diabetic Therapeutic Targets, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Abstract

Context: Circulating C-peptide is generally suppressed by exogenous insulin infusion. However, steady-state serum C-peptide (SS_SC) levels during hyperinsulinemic-euglycemic clamp in obese subjects are higher than in healthy subjects, which may contribute to hyperinsulinemia to compensate for insulin resistance. Even in healthy subjects, interindividual variations in SS_SC levels are present; however, the characteristics of subjects with high SS_SC levels in those populations have not been fully elucidated.

Objective: To investigate the clinical parameters associated with interindividual variations in SS_SC levels in apparently healthy, nonobese Japanese men.

Design and participants: We studied 49 nonobese (BMI < 25 kg/m²), healthy Japanese men. We evaluated SS_SC and insulin sensitivity using hyperinsulinemic-euglycemic clamp with tracer. Intrahepatic lipid (IHL) was measured using proton magnetic resonance spectroscopy.

Results: We divided subjects into high and low SS_SC groups based on the median SS_SC value and compared their clinical parameters. Compared with the low SS_SC group, the high SS_SC group had IHL accumulation, impaired muscle insulin sensitivity, reduced insulin clearance, and hyperinsulinemia during a 75-g oral glucose tolerance test (OGTT). All of these factors were significantly correlated with SS_SC.

Conclusions: In healthy, nonobese men, higher SS_SC was associated with impaired muscle insulin sensitivity, IHL accumulation, and hyperinsulinemia during OGTT. These findings suggest that higher endogenous insulin secretion during hyperinsulinemia, along with reduced insulin clearance, may be an early change to maintain metabolic status in the face of moderate muscle insulin resistance, even in healthy, nonobese men.

Keywords: feedback inhibition of insulin secretion; hyperinsulinemia; insulin resistance; nonobese.