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Diabetologia. 2018 Mar;61(3):681-687. doi: 10.1007/s00125-017-4511-0. Epub 2017 Dec 1.

Adapting to insulin resistance in obesity: role of insulin secretion and clearance.

Author information

1
Department of Obstetrics and Gynaecology, CHA Bundang Medical Centre, CHA University, Seongnam, South Korea.
2
Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon Hospital, Bucheon, South Korea.
3
Division of Endocrinology, Gerontology and Metabolism, Department of Medicine, Stanford University Medical Center, 300 Pasteur Drive, Room S025, Stanford, CA, 94305-5103, USA.
4
Division of Endocrinology, Gerontology and Metabolism, Department of Medicine, Stanford University Medical Center, 300 Pasteur Drive, Room S025, Stanford, CA, 94305-5103, USA. sunhkim@stanford.edu.

Abstract

AIMS/HYPOTHESIS:

The aim of this study was to quantify the relative contributions of increased insulin secretion rate (ISR) and decreased insulin clearance rate (ICR) in the compensatory hyperinsulinaemia characteristic of insulin-resistant individuals without diabetes.

METHODS:

Obese (BMI ≥30 kg/m2) individuals without diabetes (n = 91) were identified from a registry of volunteers. Volunteers underwent the following measurements: oral glucose tolerance; insulin resistance (steady-state plasma glucose [SSPG] concentration during the insulin suppression test [IST]); ISR (using the graded glucose infusion test [GGIT]); and ICR (using the IST and GGIT). Participants were stratified into tertiles based on SSPG concentration: SSPG-1(insulin-sensitive); SSPG-2 (intermediate); and SSPG-3 (insulin-resistant).

RESULTS:

There were no differences in BMI and waist circumference among the SSPG tertiles. Serum alanine aminotransferase concentrations were higher in the SSPG-2 and SSPG-3 groups compared with the SSPG-1 group (p = 0.02). Following an oral glucose challenge, there was a progressive increase in the total integrated insulin response from the most insulin-sensitive to the most insulin-resistant tertiles (p < 0.001). Following intravenous glucose, the SSPG-3 group had significantly greater integrated glucose (median [interquartile range], 32.9 [30.8-36.3] mmol/l × h) and insulin responses (1711 [1476-2223] mmol/l × h) compared with the SSPG-1 group (30.3 [28.8-32.9] mmol/l × h, p = 0.04, and 851 [600-1057] pmol/l × h, p < 0.001, respectively). Furthermore, only the SSPG-3 group had significant changes in both ISR and ICR (p < 0.001). In the SSPG-2 group, only the ICR was significantly decreased compared with the SSPG-1 group. Therefore, ICR progressively declined during the IST with increasing insulin resistance (SSPG-1, 0.48 [0.41-0.59]; SSPG-2, 0.43 [0.39-0.50]; SSPG-3, 0.34 [0.31-0.40]).

CONCLUSIONS/INTERPRETATION:

While both increases in ISR and decreases in ICR compensate for insulin resistance, decreases in ICR may provide the first adaptation to decreased insulin sensitivity.

KEYWORDS:

Hyperinsulinaemia; Insulin clearance rate; Insulin resistance; Insulin secretion rate; Obesity

PMID:
29196782
PMCID:
PMC6095137
DOI:
10.1007/s00125-017-4511-0
[Indexed for MEDLINE]
Free PMC Article

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