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Effects of a Paleolithic diet and exercise on liver fat, muscle fat and insulin sensitivity
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. (Tommy Olsson)ORCID iD: 0000-0001-9016-1139
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Finding ways to reduce risk for obesity-related disorders, including type 2 diabetes and cardiovascular disease, is important. Such approaches can include lifestyle interventions by diet and exercise. Our ancestors in the Paleolithic Era ate a diet based on vegetables, fruit, berries, lean meat, fish, seafood, nuts and eggs. Cereals, dairy products and legumes were not a significant part of the diet before the agricultural revolution, and neither were added sugar or salt. Furthermore, our ancestors were much more physically active compared to the average Western population.

Contemporary hunter-gatherers like the Kitava Islanders and the Greenlandic Inuit eat a diet similar to that of the Paleolithic Era and have a strikingly low frequency of cardiovascular events. Detailed studies of the metabolic effects of the Paleolithic diet, with and without exercise, are therefore warranted.

Impaired insulin sensitivity is a key factor in the development of type 2 diabetes and cardiovascular disease. In this thesis, insulin sensitivity was measured with the gold-standard examination – the hyperinsulinemic– euglycemic clamp – and also with fasting blood samples and the oral glucose tolerance test. We found the fasting index Revised QUICKI to be the best choice if the time-consuming gold-standard examination is not feasible. However, to distinguish insulin sensitivity of different tissues like skeletal muscle, liver and adipose tissue, the hyperinsulinemic–euglycemic clamp is preferred.

In our studies, the Paleolithic diet improved cardiovascular risk factors like overweight, insulin sensitivity, liver fat, triglycerides and blood pressure in obese, postmenopausal women. All study participants decreased liver fat when eating a Paleolithic diet. Six months of Paleolithic diet improved weight, liver fat and triglycerides significantly more than a conventional low-fat diet in obese, postmenopausal women. It was difficult for the women to remain adherent to the Paleolithic diet for 2 years, however, and most cardiovascular risk factors showed some degree of deterioration between 6 and 24 months. In individuals with type 2 diabetes, a Paleolithic diet for 12 weeks improved weight, insulin sensitivity, HbA1c, triglycerides and blood pressure. Exercise training did not improve these cardiovascular risk factors beyond the changes observed with the Paleolithic diet alone. The 12-week Paleolithic diet intervention also reduced muscle fat and liver fat, but exercise training reversed this effect.

A Paleolithic diet has strong effects on fat content in liver and muscle and on insulin sensitivity. Our present results indicate reduced metabolic flexibility in the fat content in liver and muscle tissue among patient with type 2 diabetes, which may improve through diet and exercise intervention. 

Place, publisher, year, edition, pages
Umeå: Umeå University , 2016. , 73 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1839
Keyword [en]
type 2 diabetes, liver fat, Paleolithic diet, exercise training, insulin sensitivity, overweight, intramyocellular lipid content
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:umu:diva-126189ISBN: 978-91-7601-548-3 (print)OAI: oai:DiVA.org:umu-126189DiVA: diva2:1010255
Public defence
2016-10-28, Hörsal 933, trapphus B, Norrlands universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2016-10-07 Created: 2016-10-03 Last updated: 2016-10-06Bibliographically approved
List of papers
1. Strong and persistent effect on liver fat with a Paleolithic diet during a two-year intervention
Open this publication in new window or tab >>Strong and persistent effect on liver fat with a Paleolithic diet during a two-year intervention
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2016 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 5, 747-753 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND/OBJECTIVES: Our objective was to investigate changes in liver fat and insulin sensitivity during a 2-year diet intervention. An ad libitum Paleolithic diet (PD) was compared with a conventional low-fat diet (LFD).

SUBJECTS/METHODS: Seventy healthy, obese, postmenopausal women were randomized to either a PD or a conventional LFD. Diet intakes were ad libitum. Liver fat was measured with proton magnetic resonance spectroscopy. Insulin sensitivity was evaluated with oral glucose tolerance tests and calculated as homeostasis model assessment-insulin resistance (HOMA-IR)/liver insulin resistance (Liver IR) index for hepatic insulin sensitivity and oral glucose insulin sensitivity (OGIS)/Matsuda for peripheral insulin sensitivity. All measurements were performed at 0, 6 and 24 months. Forty-one women completed the examinations for liver fat and were included.

RESULTS: Liver fat decreased after 6 months by 64% (95% confidence interval: 54-74%) in the PD group and by 43% (27-59%) in the LFD group (P<0.01 for difference between groups). After 24 months, liver fat decreased 50% (25-75%) in the PD group and 49% (27-71%) in the LFD group. Weight reduction between baseline and 6 months was correlated to liver fat improvement in the LFD group (rs=0.66, P<0.01) but not in the PD group (rs=0.07, P=0.75). Hepatic insulin sensitivity improved during the first 6 months in the PD group (P<0.001 for Liver IR index and HOMA-IR), but deteriorated between 6 and 24 months without association with liver fat changes.

CONCLUSIONS: A PD with ad libitum intake had a significant and persistent effect on liver fat and differed significantly from a conventional LFD at 6 months. This difference may be due to food quality, for example, a higher content of mono- and polyunsaturated fatty acids in the PD. Changes in liver fat did not associate with alterations in insulin sensitivity.International Journal of Obesity advance online publication, 16 February 2016; doi:10.1038/ijo.2016.4.

National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-117538 (URN)10.1038/ijo.2016.4 (DOI)000377616500003 ()26786351 (PubMedID)
Funder
Swedish Research Council, K2011-12237-15-6
Available from: 2016-03-01 Created: 2016-03-01 Last updated: 2017-12-12Bibliographically approved
2. Benefits of a Paleolithic diet with and without supervised exercise on fat mass, insulin sensitivity, and glycemic control: a randomized controlled trial in individuals with type 2 diabetes
Open this publication in new window or tab >>Benefits of a Paleolithic diet with and without supervised exercise on fat mass, insulin sensitivity, and glycemic control: a randomized controlled trial in individuals with type 2 diabetes
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2017 (English)In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 33, no 1, e2828Article in journal (Refereed) Published
Abstract [en]

Background

Means to reduce future risk for cardiovascular disease in subjects with type 2 diabetes are urgently needed.

Methods

Thirty-two patients with type 2 diabetes (age 59 ± 8 years) followed a Paleolithic diet for 12 weeks. Participants were randomized to either standard care exercise recommendations (PD) or 1-h supervised exercise sessions (aerobic exercise and resistance training) three times per week (PD-EX).

Results

For the within group analyses, fat mass decreased by 5.7 kg (IQR: −6.6, −4.1; p < 0.001) in the PD group and by 6.7 kg (−8.2, −5.3; p < 0.001) in the PD-EX group. Insulin sensitivity (HOMA-IR) improved by 45% in the PD (p < 0.001) and PD-EX (p < 0.001) groups. HbA1c decreased by 0.9% (−1.2, −0.6; p < 0.001) in the PD group and 1.1% (−1.7, −0.7; p < 0.01) in the PD-EX group. Leptin decreased by 62% (p < 0.001) in the PD group and 42% (p < 0.001) in the PD-EX group. Maximum oxygen uptake increased by 0.2 L/min (0.0, 0.3) in the PD-EX group, and remained unchanged in the PD group (p < 0.01 for the difference between intervention groups). Male participants decreased lean mass by 2.6 kg (−3.6, −1.3) in the PD group and by 1.2 kg (−1.3, 1.0) in the PD-EX group (p < 0.05 for the difference between intervention groups).

Conclusions

A Paleolithic diet improves fat mass and metabolic balance including insulin sensitivity, glycemic control, and leptin in subjects with type 2 diabetes. Supervised exercise training may not enhance the effects on these outcomes, but preserves lean mass in men and increases cardiovascular fitness.

Keyword
type 2 diabetes, Paleolithic diet, diet intervention, exercise, glycosyl-ated haemoglobin A, insulin sensitivity, leptin
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-126188 (URN)10.1002/dmrr.2828 (DOI)000397102800010 ()
Available from: 2016-10-03 Created: 2016-10-03 Last updated: 2017-11-30Bibliographically approved
3. Exercise Training Reverses the Effect of a Paleolithic Diet on Liver Fat and Intramyocellular Lipid Content in Patients with Type 2 Diabetes
Open this publication in new window or tab >>Exercise Training Reverses the Effect of a Paleolithic Diet on Liver Fat and Intramyocellular Lipid Content in Patients with Type 2 Diabetes
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(English)Manuscript (preprint) (Other academic)
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-126185 (URN)
Available from: 2016-10-03 Created: 2016-10-03 Last updated: 2016-10-03
4. Surrogate measures of insulin sensitivity vs the hyperinsulinaemic-euglycaemic clamp: a meta-analysis
Open this publication in new window or tab >>Surrogate measures of insulin sensitivity vs the hyperinsulinaemic-euglycaemic clamp: a meta-analysis
2014 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, no 9, 1781-1788 p.Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis We aimed to identify which surrogate index of insulin sensitivity has the strongest correlation with the reference measurement, the hyperinsulinaemic-euglycaemic clamp (HEC), to determine which surrogate measure should be recommended for use in large-scale studies. Methods A literature search (1979-2012) was conducted to retrieve all articles reporting bivariate correlations between the HEC and surrogate measures of insulin sensitivity (in fasting samples or during the OGTT). We performed a random effects meta-analysis for each surrogate measure to integrate the correlation coefficients of the different studies. Results The OGTT-based surrogate measures with the strongest pooled correlations (r) to the HEC were the Stumvoll metabolic clearance rate (Stumvoll MCR; r=0.70 [95% CI 0.61, 0.77], n=5), oral glucose insulin sensitivity (OGIS; r=0.70 [0.57, 0.80], n=6), the Matsuda index (r=0.67 [0.61, 0.73], n=19), the Stumvoll insulin sensitivity index (Stumvoll ISI; r=0.67 [0.60, 0.72], n=8) and the Gutt index (r=0.65 [0.60, 0.69], n=6). The fasting surrogate indices that correlated most strongly with the HEC and had narrow 95% CIs were the revised QUICKI (r=0.68 [0.58, 0.77], n=7), the QUICKI (r=0.61 [0.55, 0.65], n=35), the log HOMA-IR (r=-0.60 [-0.66, -0.53], n=22) and the computer generated HOMA of insulin sensitivity (HOMA-%S; r=0.57 [0.46, 0.67], n=5). Conclusions/interpretation The revised QUICKI fasting surrogate measure appears to be as good as the OGTT-based Stumvoll MCR, OGIS, Matsuda, Stumvoll ISI and Gutt indices for estimating insulin sensitivity. It can therefore be recommended as the most appropriate index for use in large-scale clinical studies.

Place, publisher, year, edition, pages
Springer, 2014
Keyword
Glucose, Hyperinsulinaemic-euglycaemic clamp, Insulin, Insulin sensitivity, Meta-analysis, Surrogate markers
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-92899 (URN)10.1007/s00125-014-3285-x (DOI)000340050800006 ()
Available from: 2014-09-18 Created: 2014-09-09 Last updated: 2017-12-05Bibliographically approved

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