Diabetes UK.

Aims/hypothesisType 2 diabetes is regarded as inevitably progressive, with irreversible beta cell failure. The hypothesis was tested that both beta cell failure and insulin resistance can be reversed by dietary restriction of energy intake.MethodsEleven people with type 2 diabetes (49.5 ± 2.5 years, BMI 33.6 ± 1.2 kg/m2, nine male and two female) were studied before and after 1, 4 and 8 weeks of a 2.5 MJ (600 kcal)/day diet. Basal hepatic glucose output, hepatic and peripheral insulin sensitivity and beta cell function were measured. Pancreas and liver triacylglycerol content was measured using three-point Dixon magnetic resonance imaging. An age-, sex- and weight-matched group of eight non-diabetic participants was studied.ResultsAfter 1 week of restricted energy intake, fasting plasma glucose normalised in the diabetic group (from 9.2 ± 0.4 to 5.9 ± 0.4 mmol/l; p = 0.003). Insulin suppression of hepatic glucose output improved from 43 ± 4% to 74 ± 5% (p = 0.003 vs baseline; controls 68 ± 5%). Hepatic triacylglycerol content fell from 12.8 ± 2.4% in the diabetic group to 2.9 ± 0.2% by week 8 (p = 0.003). The first-phase insulin response increased during the study period (0.19 ± 0.02 to 0.46 ± 0.07 nmol min−1 m−2; p < 0.001) and approached control values (0.62 ± 0.15 nmol min−1 m−2; p = 0.42). Maximal insulin response became supranormal at 8 weeks (1.37 ± 0.27 vs controls 1.15 ± 0.18 nmol min−1 m−2). Pancreatic triacylglycerol decreased from 8.0 ± 1.6% to 6.2 ± 1.1% (p = 0.03).Conclusions/interpretationNormalisation of both beta cell function and hepatic insulin sensitivity in type 2 diabetes was achieved by dietary energy restriction alone. This was associated with decreased pancreatic and liver triacylglycerol stores. The abnormalities underlying type 2 diabetes are reversible by reducing dietary energy intake.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence Newcastle University ePrints -eprint.ncl.ac.uk Lean MEJ,

BackgroundLifestyle interventions focusing on weight loss remain the cornerstone of non-alcoholic fatty liver disease (NAFLD) management. Despite this, the weight losses achieved in research trials are not easily replicated in the clinic and there is an urgent need for therapies independent of weight loss. Aerobic exercise is not well sustained and the effectiveness of the better tolerated resistance exercise upon liver lipid and mediators of liver lipid has not been assessed.MethodsSedentary adults with clinically defined NAFLD were assigned to 8 weeks of resistance exercise (n=11) or continued normal treatment (n=8).Results8 weeks of resistance exercise elicited a 13% relative reduction in liver lipid (14.0±9.1 vs 12.2±9.0; p<0.05). Lipid oxidation (submaximal RQ ∆ −0.020±0.010 vs −0.004±0.003; p<0.05), glucose control (−12% vs +12% change AUC; p<0.01) and homeostasis model assessment insulin resistance (5.9±5.9 to 4.6±4.6 vs 4.7±2.1 to 5.1±2.5; p<0.05) were all improved. Resistance exercise had no effect on body weight, visceral adipose tissue volume, or whole body fat mass (p>0.05).ConclusionThis is the first study to demonstrate that resistance exercise specifically improves NAFLD independent of any change in body weight. These data demonstrate that resistance exercise may provide benefit for the management for non-alcoholic fatty liver, and the long-term impact of this now requires evaluation.