| 11. |
- Otten, Julia, 1973-, et al.
(författare)
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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
- 2017
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 33:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMeans to reduce future risk for cardiovascular disease in subjects with type 2 diabetes are urgently needed.MethodsThirty-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).ResultsFor 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).ConclusionsA 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.
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| 12. |
- Otten, Julia, 1973-
(författare)
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Effects of a Paleolithic diet and exercise on liver fat, muscle fat and insulin sensitivity
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 13. |
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| 14. |
- Otten, Julia, 1973-, et al.
(författare)
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Exercise Training Adds Cardiometabolic Benefits of a Paleolithic Diet in Type 2 Diabetes Mellitus
- 2019
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Ingår i: Journal of the American Heart Association. - : Wiley-Blackwell. - 2047-9980. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: The accumulation of myocardial triglycerides and remodeling of the left ventricle are common features in type 2 diabetes mellitus and represent potential risk factors for the development of diastolic and systolic dysfunction. A few studies have investigated the separate effects of diet and exercise training on cardiac function, but none have investigated myocardial changes in response to a combined diet and exercise intervention. This 12-week randomized study assessed the effects of a Paleolithic diet, with and without additional supervised exercise training, on cardiac fat, structure, and function.Methods and Results: Twenty-two overweight and obese subjects with type 2 diabetes mellitus were randomized to either a Paleolithic diet and standard-care exercise recommendations ( PD ) or to a Paleolithic diet plus supervised exercise training 3 hours per week ( PD - EX ). This study includes secondary end points related to cardiac structure and function, ie, myocardial triglycerides levels, cardiac morphology, and strain were measured using cardiovascular magnetic resonance, including proton spectroscopy, at baseline and after 12 weeks. Both groups showed major favorable metabolic changes. The PD - EX group showed significant decreases in myocardial triglycerides levels (-45%, P=0.038) and left ventricle mass to end-diastolic volume ratio (-13%, P=0.008) while the left ventricle end-diastolic volume and stroke volume increased significantly (+14%, P=0.004 and +17%, P=0.008, respectively). These variables were unchanged in the PD group.Conclusions: Exercise training plus a Paleolithic diet reduced myocardial triglycerides levels and improved left ventricle remodeling in overweight/obese subjects with type 2 diabetes mellitus.Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01513798.
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| 15. |
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| 16. |
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| 17. |
- Otten, Julia, 1973-, et al.
(författare)
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Fasting C-peptide at type 2 diabetes diagnosis is an independent risk factor for total and cancer mortality
- 2022
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Ingår i: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 38:3
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We assessed the association between insulin resistance and blood glucose concentrations at type 2 diabetes diagnosis and future development of diabetes-related complications and mortality.Materials and Methods: This retrospective cohort study included 864 individuals with type 2 diabetes (median age 60 years) whose fasting C-peptide and HbA1c were measured at diabetes diagnosis. The median follow-up time until death or study end was 16.4 years (interquartile range 13.3−19.6). The association between C-peptide and mortality/complications was estimated by Cox regression adjusted for sex, age at diabetes diagnosis, smoking, hypertension, BMI, total cholesterol, and HbA1c. C-peptide and HbA1c were converted to Z scores before the Cox regression analysis.Results: An increase by one standard deviation in fasting C-peptide at diabetes diagnosis was associated with all-cause (hazard ratio [HR] 1.33; 95% confidence intervals [CI] 1.12–1.58; p = 0.001) and cancer mortality (HR 1.51; 95% CI 1.13–2.01; p = 0.005) in the fully adjusted model. An increase by one standard deviation in HbA1c at diabetes diagnosis was associated with all-cause mortality (HR 1.24; 95% CI 1.07–1.44; p = 0.005), major cardiovascular events (HR 1.20; 95% CI 1.04–1.39; p = 0.015), stroke (HR 1.36; 95% CI 1.09–1.70; p = 0.006), and retinopathy (HR 1.54; 95% CI 1.34–1.76; p < 0.0001) in the fully adjusted model.Conclusions: Fasting C-peptide at type 2 diabetes diagnosis is an independent risk factor for total and cancer-related mortality. Thus, treatment of type 2 diabetes should focus not only on normalising blood glucose levels but also on mitigating insulin resistance.
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| 18. |
- Otten, Julia, 1973-, et al.
(författare)
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Insulin resistance at type 2 diabetes diagnosis, not impaired beta cell function, is associated with total mortality
- 2020
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 63:SUPPL 1, s. S41-S41
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: We investigated the separate effects of insulin resistance and beta cell function at the diagnosis of type 2 diabetes on the development of mortality and diabetes complications.Materials and methods: This cohort study included 864 individuals with type 2 diabetes (median age 60 years) in whom fasting glucose and fasting C-peptide were measured at diabetes diagnosis. Insulin resistance was estimated by HOMA-%S and beta cell function by HOMA-%B. Four groups were created based on the median HOMA-%S and HOMA-%B values: group 1, high insulin resistance and preserved beta cell function; group 2, high insulin resistance and impaired beta cell function; group 3, low insulin resistance and preserved beta cell function; group 4, low insulin resistance and impaired beta cell function (reference group). Mortality and diabetes complications were registered with a follow-up of 15 years. The associations between the four groups and mortality/complications were estimated by Cox regression adjusted for gender and age at diabetes diagnosis in model 1, and also for smoking, hypertension, BMI, and total cholesterol in model 2. In the figure a Kaplan-Meier plot is displayed not including adjustments for confounding factors.Results: Total mortality in the four groups is displayed in the figure. Both groups with high insulin resistance had higher total mortality (group 1: HR 1.58, 95% CI 1.06−2.36; group 2: HR 1.85, 95% CI 1.20-2.84) than group 4. Fasting C-peptide, as a continuous variable, was independently associated with total mortality (HR 1.29, 95% CI 1.11−1.49) and cancer mortality (HR 1.42, 95% CI 1.09−1.84).Conclusion: Insulin resistance was an independent risk factor for total mortality. Thus, treatment of type 2 diabetes should focus not only on normalizing blood glucose levels, but also reducing insulin resistance.
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| 19. |
- Otten, Julia, 1973-, et al.
(författare)
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Postprandial levels of GLP-1, GIP and glucagon after 2 years of weight loss with a Paleolithic diet: A randomised controlled trial in healthy obese women
- 2019
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Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 180:6, s. 417-427
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate how weight loss by different diets impacts postp randial levels of glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon. Methods: In this single-centre, parallel group 2-year trial, 70 healthy postmenopausal obese women were randomised to the Paleolithic diet or a healthy control diet based on Nordic Nutrition Recommendations. Both diets were without calorie restriction. The primary outcome was the change in fat mass. Here, secondary analyses on GLP-1, GIP and glucagon measured during an OGTT are described. Results: In the Paleolithic diet group, mean weight loss compared to ba seline was 11% at 6 months and 10% at 24 months. In the control diet group, mean weight loss was 6% a fter 6 and 24 months (P = 0.0001 and P = 0.049 for the comparison between groups at 6 and 24 months respectively). Compared to baseline, the mean incremental area under the curve (iAUC) for GLP-1 increased by 34 and 45% after 6 and 24 months in the Paleolithic diet group and increased by 59% after 24 months in the control diet group. The mean iAUC for GIP increased only in the Paleolithic diet group. The area under the curve (AUC) for glucagon increas ed during the first 6 months in both groups. The fasting glucagon increase correlated with the β-hydroxybutyrate increase. Conclusions: Weight loss caused an increase in postprandial GLP-1 levels and a further rise occurred during weight maintenance. Postprandial GIP levels increased only after the Paleolithic diet. Reduced postprandial glucagon suppression may be caused by a catabolic state. © 2019 European Society of Endocrinology Printed in Great Britain.
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| 20. |
- Otten, Julia, 1973-, et al.
(författare)
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The liver-alpha-cell axis after a mixed meal and during weight loss in type 2 diabetes
- 2021
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Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 10:9, s. 1101-1110
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Glucagon and amino acids may be regulated in a feedback loop called the liver-alpha-cell axis with alanine or glutamine as suggested signal molecules. We assessed this concept in individuals with type 2 diabetes in the fasting state, after ingestion of a protein-rich meal, and during weight loss. Moreover, we investigated if postprandial glucagon secretion and hepatic insulin sensitivity were related.Methods: This is a secondary analysis of a 12-week weight-loss trial (Paleolithic diet ± exercise) in 29 individuals with type 2 diabetes. Before and after the intervention, plasma glucagon and amino acids were measured in the fasting state and during 180 min after a protein-rich mixed meal. Hepatic insulin sensitivity was measured using the hyperinsulinemic-euglycemic clamp with [6,6-2H2]glucose as a tracer.Results: The postprandial increase of plasma glucagon was associated with the postprandial increase of alanine and several other amino acids but not glutamine. In the fasted state and after the meal, glucagon levels were negatively correlated with hepatic insulin sensitivity (rS = −0.51/r = −0.58, respectively; both P < 0.05). Improved hepatic insulin sensitivity with weight loss was correlated with decreased postprandial glucagon response (r = −0.78; P < 0.001).Conclusions: Several amino acids, notably alanine, but not glutamine could be key signals to the alpha cell to increase glucagon secretion. Amino acids may be part of a feedback mechanism as glucagon increases endogenous glucose production and ureagenesis in the liver. Moreover, postprandial glucagon secretion seems to be tightly related to hepatic insulin sensitivity.
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