Exercise training decreases pancreatic fat content and improves beta cell function regardless of baseline glucose tolerance: a randomised controlled trial

Abstract

Aims/hypothesis: Pancreatic fat accumulation may contribute to the development of beta cell dysfunction. Exercise training improves whole-body insulin sensitivity, but its effects on pancreatic fat content and beta cell dysfunction are unclear. The aim of this parallel-group randomised controlled trial was to evaluate the effects of exercise training on pancreatic fat and beta cell function in healthy and prediabetic or type 2 diabetic participants and to test whether the responses were similar regardless of baseline glucose tolerance.

Methods: Using newspaper announcements, a total of 97 sedentary 40-55-year-old individuals were assessed for eligibility. Prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes were defined by ADA criteria. Of the screened candidates, 28 healthy men and 26 prediabetic or type 2 diabetic men and women met the inclusion criteria and were randomised into 2-week-long sprint interval or moderate-intensity continuous training programmes in a 1:1 allocation ratio using random permuted blocks. The primary outcome was pancreatic fat, which was measured by magnetic resonance spectroscopy. As secondary outcomes, beta cell function was studied using variables derived from OGTT, and whole-body insulin sensitivity and pancreatic fatty acid and glucose uptake were measured using positron emission tomography. The measurements were carried out at the Turku PET Centre, Finland. The analyses were based on an intention-to-treat principle. Given the nature of the intervention, blinding was not applicable.

Results: At baseline, the group of prediabetic or type 2 diabetic men had a higher pancreatic fat content and impaired beta cell function compared with the healthy men, while glucose and fatty acid uptake into the pancreas was similar. Exercise training decreased pancreatic fat similarly in healthy (from 4.4% [3.0%, 6.1%] to 3.6% [2.4%, 5.2%] [mean, 95% CI]) and prediabetic or type 2 diabetic men (from 8.7% [6.0%, 11.9%] to 6.7% [4.4%, 9.6%]; p = 0.036 for time effect) without any changes in pancreatic substrate uptake (p ≥ 0.31 for time effect in both insulin-stimulated glucose and fasting state fatty acid uptake). In prediabetic or type 2 diabetic men and women, both exercise modes similarly improved variables describing beta cell function.

Conclusions/interpretation: Two weeks of exercise training improves beta cell function in prediabetic or type 2 diabetic individuals and decreases pancreatic fat regardless of baseline glucose tolerance. This study shows that short-term training efficiently reduces ectopic fat within the pancreas, and exercise training may therefore reduce the risk of type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT01344928 FUNDING: This study was funded by the Emil Aaltonen Foundation, the European Foundation for the Study of Diabetes, the Finnish Diabetes Foundation, the Orion Research Foundation, the Academy of Finland (grants 251399, 256470, 281440, and 283319), the Ministry of Education of the State of Finland, the Paavo Nurmi Foundation, the Novo Nordisk Foundation, the Finnish Cultural Foundation, the Hospital District of Southwest Finland, the Turku University Foundation, and the Finnish Medical Foundation.

Keywords: Beta cell function; Exercise training; High-intensity interval training; Moderate-intensity continuous training; Pancreatic fat content; Pancreatic metabolism; Prediabetes; Type 2 diabetes.

Fig. 1

Participant flow diagram. The analyses were carried out using intention-to-treat principle and hence included all the randomised participants. T2DM, type 2 diabetes mellitus

Fig. 2

Pancreatic fat content in healthy and prediabetic or type 2 diabetic men at baseline (a), before and after the training intervention when participants were grouped into healthy and prediabetic or type 2 diabetic men (b), and before and after the training intervention when men were grouped according to low (≤6.2%) and high (>6.2%) pancreatic fat at baseline (c). The shaded area in (a) denotes normal pancreatic fat content (≤6.2%). (b, c) Square root transformation was performed to calculate model-based means and 95% CI. Circles, healthy men; squares, prediabetic men; triangles, type 2 diabetic men; white symbols, before exercise intervention; black symbols, after exercise intervention. T2DM, type 2 diabetes mellitus. *p ≤ 0.05, ***p ≤ 0.001 for baseline difference between the groups; ^†p ≤ 0.05 for time effect; ^‡‡‡p ≤ 0.001 time effect for men with high pancreatic fat content

Fig. 3

ISR (a) and potentiation (b) during 2 h OGTTs in healthy and prediabetic or type 2 diabetic men before and after the training intervention. The shaded area in (a) denotes ISR_early (0–30 min), which increased only in healthy men (p = 0.006 for the time effect in healthy men). There were non-significant differences in the potentiation of insulin secretion between prediabetic or type 2 diabetic men and healthy men (p = 0.083 for time effect for the potentiation factor ratio in prediabetic or type 2 diabetic men). White circles, healthy men before the exercise intervention; black circles, healthy men after the exercise intervention; white squares, prediabetic or type 2 diabetic men before the exercise intervention; black squares, prediabetic or type 2 diabetic men after the exercise intervention