Abstract

Aims/hypothesisThe aim of the study was to investigate ectopic fat deposition and insulin sensitivity, in a parallel single-blinded randomised controlled trial, comparing Paleolithic diet alone with the combination of Paleolithic diet and exercise in individuals with type 2 diabetes.MethodsThirty-two individuals with type 2 diabetes with BMI 25–40 kg/m2 and 30–70 years of age followed a Paleolithic diet ad libitum for 12 weeks. In addition, study participants were randomised by computer program to either supervised combined exercise training (PD-EX group) or standard care exercise recommendations (PD group). Staff performing examinations and assessing outcomes were blinded to group assignment. Thirteen participants were analysed in each group: hepatic and peripheral insulin sensitivity were measured using the hyperinsulinaemic–euglycaemic clamp technique combined with [6,6-2H2]glucose infusion, and liver fat was assessed by proton magnetic resonance spectroscopy; both analyses were secondary endpoints. Intramyocellular lipid (IMCL) content was measured by magnetic resonance spectroscopy as a secondary analysis. All examinations were performed at Umeå University Hospital, Umeå, Sweden.ResultsBoth study groups showed a median body weight loss of 7 kg. Fat mass decreased by 5.7 kg in the PD group and by 6.5 kg in the PD-EX group. Maximum oxygen uptake increased in the PD-EX group only. Liver fat showed a consistent reduction (74% decrease) in the PD group, while the response in the PD-EX group was heterogeneous (p < 0.05 for the difference between groups). IMCL content of the soleus muscle decreased by 40% in the PD group and by 22% in the PD-EX group (p < 0.05 for the difference between groups). Both groups improved their peripheral and adipose tissue insulin sensitivity, but not their hepatic insulin sensitivity. Plasma fetuin-A decreased by 11% in the PD group (p < 0.05) and remained unchanged in the PD-EX group. Liver fat changes during the intervention were correlated with changes in fetuin-A (rS = 0.63, p < 0.01). Participants did not report any important adverse events caused by the intervention.Conclusions/interpretationA Paleolithic diet reduced liver fat and IMCL content, while there was a tissue-specific heterogeneous response to added exercise training.Trial registrationClinicalTrials.gov NCT01513798FundingSwedish Diabetes Research Foundation, County Council of Västerbotten, Swedish Heart and Lung Foundation, King Gustav V and Queen Victoria’s Foundation

Highlights

  • Fat accumulation outside adipose tissue, i.e. ectopic fat in liver and muscle, is linked to decreased insulin sensitivity and type 2 diabetes [1, 2]

  • We found no betweengroup differences in baseline characteristics except a higher fasting glucose in the PD-EX group (Table 1)

  • Fat mass decreased by 5.7 kg in the PD group and by 6.5 kg in the PD-EX group (Table 1)

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Summary

Introduction

Fat accumulation outside adipose tissue, i.e. ectopic fat in liver and muscle, is linked to decreased insulin sensitivity and type 2 diabetes [1, 2]. Diet-induced weight loss in obese individuals is associated with reduction of fat in liver and skeletal muscle [3,4,5]. This has been linked to improved insulin sensitivity but has not been a universal finding. Two recent studies on obese postmenopausal women found that a Paleolithic diet consumed ad libitum with a moderately decreased carbohydrate intake and a high content of mono- and polyunsaturated fatty acids effectively reduced liver fat [8, 9]. A Paleolithic diet efficiently improved glucose tolerance in overweight individuals and in people with type 2 diabetes [10,11,12]

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