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Randomized Controlled Trial
. 2018 Jul;61(7):1548-1559.
doi: 10.1007/s00125-018-4618-y. Epub 2018 Apr 26.

A Heterogeneous Response of Liver and Skeletal Muscle Fat to the Combination of a Paleolithic Diet and Exercise in Obese Individuals With Type 2 Diabetes: A Randomised Controlled Trial

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Free PMC article
Randomized Controlled Trial

A Heterogeneous Response of Liver and Skeletal Muscle Fat to the Combination of a Paleolithic Diet and Exercise in Obese Individuals With Type 2 Diabetes: A Randomised Controlled Trial

Julia Otten et al. Diabetologia. .
Free PMC article

Abstract

Aims/hypothesis: The 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.

Methods: Thirty-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.

Results: Both 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/interpretation: A Paleolithic diet reduced liver fat and IMCL content, while there was a tissue-specific heterogeneous response to added exercise training.

Trial registration: ClinicalTrials.gov NCT01513798 FUNDING: Swedish Diabetes Research Foundation, County Council of Västerbotten, Swedish Heart and Lung Foundation, King Gustav V and Queen Victoria's Foundation.

Keywords: Exercise; Hyperinsulinaemic–euglycaemic clamp; Insulin sensitivity; Intramyocellular fat; Liver fat; Nutrition; Obesity; Paleolithic diet; Proton magnetic resonance spectroscopy; Weight loss.

Conflict of interest statement

The authors declare that there is no duality of interest associated with this manuscript.

Figures

Fig. 1
Fig. 1
CONSORT flow diagram
Fig. 2
Fig. 2
Insulin clearance during 12 weeks of intervention in the PD and PD-EX groups. *p < 0.05 for the within-group change over time from baseline to 12 weeks. p < 0.05 for the intervention effect between the PD group and the PD-EX group
Fig. 3
Fig. 3
IMCL content of the soleus muscle (a) and liver fat (b) during 12 weeks of intervention in the PD and PD-EX groups. IMCL is normalised to the creatine concentration of the muscle. **p < 0.01, ***p < 0.001 for the within-group change over time from baseline to 12 weeks. p < 0.05 for the intervention effect between the PD group and the PD-EX group
Fig. 4
Fig. 4
Plasma fetuin-A levels during 12 weeks of intervention in the PD and PD-EX groups. *p < 0.05 for the within-group change over time from baseline to 12 weeks
Fig. 5
Fig. 5
Association between change in liver fat and change in plasma fetuin-A during the intervention

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