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Diet-induced weight loss alters hepatic glucocorticoid metabolism in type 2 diabetes mellitus.
Stomby, A, Otten, J, Ryberg, M, Andrew, R, Walker, BR, Olsson, T
European journal of endocrinology. 2020;182(4):447-457
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Cushing syndrome is caused by an overexposure to cortisol and associated with abdominal adiposity, hypertension, dyslipidaemia, insulin resistance and type 2 diabetes mellitus (T2DM), and therefore bears similarities with metabolic syndrome and obesity. Whilst circulating cortisol levels are normal or slightly decreased in obese individuals, they tend to be increased in T2DM. The aim of this study was to investigate associations between obesity and T2DM measures and glucocorticoid metabolism, and any possible effects of a palaeolithic diet (PD) with or without exercise. In this single-blind study (investigators examining patients were blind to intervention), 28 patients with overweight or obesity and T2DM were randomised to either a PD alone or combined with a structured resistance and aerobic exercise programme for 12 weeks. The PD was based on a high intake of vegetables, fruit, lean meat, nuts, egg, fish and seafood, whilst grains, sugar, salt, dairy products and refined fats were reduced. Body mass index, waist circumference, glycaemic control, liver and systemic insulin sensitivity improved in both groups with no statistically significant difference between groups. There was no association between insulin sensitivity and indices of tissue specific glucocorticoid metabolism. PD with and without exercise was associated with increased conversion of the inactive cortisone to the active cortisol through increased activity of the conversion enzyme in the liver, but not with increased urinary excretion of glucocorticoid metabolites. The authors concluded that the results suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction.
Abstract
CONTEXT Altered tissue-specific glucocorticoid metabolism has been described in uncomplicated obesity and type 2 diabetes. We hypothesized that weight loss induced by diet and exercise, which has previously been shown to reverse abnormal cortisol metabolism in uncomplicated obesity, also normalizes cortisol metabolism in patients with type 2 diabetes. OBJECTIVE Test the effects of a diet intervention with added exercise on glucocorticoid metabolism. DESIGN Two groups followed a Paleolithic diet (PD) for 12 weeks with added 180 min of structured aerobic and resistance exercise per week in one randomized group (PDEX). SETTING Umeå University Hospital. PARTICIPANTS Men and women with type 2 diabetes treated with lifestyle modification ± metformin were included. Twenty-eight participants (PD, n = 15; PDEX, n = 13) completed measurements of glucocorticoid metabolism. MAIN OUTCOME MEASURES Changes in glucocorticoid metabolite levels in 24-h urine samples, expression of HSD11B1 mRNA in s.c. adipose tissue and conversion of orally administered cortisone to cortisol measured in plasma. Body composition and insulin sensitivity were measured using a hyperinsulinemic-euglycemic clamp, and liver fat was measured by magnetic resonance spectroscopy. RESULTS Both groups lost weight and improved insulin sensitivity. Conversion of orally taken cortisone to plasma cortisol and the ratio of 5α-THF + 5β-THF/THE in urine increased in both groups. CONCLUSIONS These interventions caused weight loss and improved insulin sensitivity with concomitant increases in the conversion of cortisone to cortisol, which is an estimate of hepatic HSD11B1 activity. This suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction.
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Prevention of Type 2 Diabetes by Lifestyle Changes: A Systematic Review and Meta-Analysis.
Uusitupa, M, Khan, TA, Viguiliouk, E, Kahleova, H, Rivellese, AA, Hermansen, K, Pfeiffer, A, Thanopoulou, A, Salas-Salvadó, J, Schwab, U, et al
Nutrients. 2019;11(11)
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With Type 2 Diabetes growing globally this paper analyses whether T2D is preventable with lifestyle measures including diet. Seven RCTs were included for review with a total of 4090 participants, and 2466 incidents of T2D, and were chosen on the basis that the lifestyle interventions included both physical exercise and diet (typically Mediterranean Diet). They found that diet and lifestyle intervention reduced the risk of T2D by 47%. Sustained risk reduction was also found in follow-up studies up to 10 years later with participants maintaining improved blood glucose control. Lifestyle interventions may also reduce risk factors for cardiovascular disease. Weight reduction was considered a cornerstone of preventing T2D and adherence to lifestyle changes a key element in long term prevention. Dietary foods reviewed include processed meats, white rice and sugars which correlated highly with T2D whilst leafy greens, berries, wholegrains, legumes, dietary fibre and yoghurt correlate with a lower risk of T2D. Dietary patterns of skipping breakfast and snacking correlate higher with T2D. Different criteria for evaluating physical activity estimate that it reduces risk factors by 50%. In conclusion there is high evidence that lifestyle factors which optimise diet, increase physical activity and promote weight reduction are preventative factors for T2D and can be sustained long term.
Abstract
Prevention of type 2 diabetes (T2D) is a great challenge worldwide. The aim of this evidence synthesis was to summarize the available evidence in order to update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy. We conducted a systematic review and, where appropriate, meta-analyses of randomized controlled trials (RCTs) carried out in people with impaired glucose tolerance (IGT) (six studies) or dysmetabolism (one study) to answer the following questions: What is the evidence that T2D is preventable by lifestyle changes? What is the optimal diet (with a particular focus on diet quality) for prevention, and does the prevention of T2D result in a lower risk of late complications of T2D? The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to assess the certainty of the trial evidence. Altogether seven RCTs (N = 4090) fulfilled the eligibility criteria and were included in the meta-analysis. The diagnosis of incident diabetes was based on an oral glucose tolerance test (OGTT). The overall risk reduction of T2D by the lifestyle interventions was 0.53 (95% CI 0.41; 0.67). Most of the trials aimed to reduce weight, increase physical activity, and apply a diet relatively low in saturated fat and high in fiber. The PREDIMED trial that did not meet eligibility criteria for inclusion in the meta-analysis was used in the final assessment of diet quality. We conclude that T2D is preventable by changing lifestyle and the risk reduction is sustained for many years after the active intervention (high certainty of evidence). Healthy dietary changes based on the current recommendations and the Mediterranean dietary pattern can be recommended for the long-term prevention of diabetes. There is limited or insufficient data to show that prevention of T2D by lifestyle changes results in a lower risk of cardiovascular and microvascular complications.
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A Pecan-Rich Diet Improves Cardiometabolic Risk Factors in Overweight and Obese Adults: A Randomized Controlled Trial.
McKay, DL, Eliasziw, M, Chen, CYO, Blumberg, JB
Nutrients. 2018;10(3)
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There has been a global rise in cardiovascular disease (CVD) and type 2 diabetes mellitus (TD2M) and dietary risk factors are a known contributor. While evidence has shown that an increased intake of tree nuts is associated with a reduced risk of disease indicators, there is limited research specifically on the effects of pecans. The aim of this randomised crossover trial was to assess the impact of pecan consumption on biomarkers related to CVD and T2DM risk in 26 overweight or obese women. Participants consumed a pecan-rich diet with an iso-caloric control diet of similar fat and fibre content, but absent in nuts, for four weeks with a two-week washout period. This trial demonstrated that displacing a portion of saturated fat in the typical American diet with pecans has a protective effect for CVD and TD2M. Based on these results, the authors recommend using dietary change as a first-line approach to disease prevention and management and suggest further studies be done to better understand potential benefits and associated mechanisms.
Abstract
Evidence from observational and intervention studies has shown a high intake of tree nuts is associated with a reduced risk of cardiovascular disease (CVD), mortality from type 2 diabetes (T2DM), and all-cause mortality. However, there is limited data regarding their effects on indicators of cardiometabolic risk other than hypercholesterolemia, and little is known about the demonstrable health benefits of pecans (Carya illinoensis (Wangenh.) K.Koch). We conducted a randomized, controlled feeding trial to compare the effects of a pecan-rich diet with an isocaloric control diet similar in total fat and fiber content, but absent nuts, on biomarkers related to CVD and T2DM risk in healthy middle-aged and older adults who are overweight or obese with central adiposity. After 4 weeks on a pecan-rich diet, changes in serum insulin, insulin resistance (HOMA-IR) and beta cell function (HOMA-β) were significantly greater than after the control diet (p < 0.05). Pecan consumption also lowered the risk of cardiometabolic disease as indicated by a composite score reflecting changes in clinically relevant markers. Thus, compared to the control diet, the pecan intervention had a concurrent and clinically significant effect on several relevant markers of cardiometabolic risk.
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A whole-grain diet reduces peripheral insulin resistance and improves glucose kinetics in obese adults: A randomized-controlled trial.
Malin, SK, Kullman, EL, Scelsi, AR, Haus, JM, Filion, J, Pagadala, MR, Godin, JP, Kochhar, S, Ross, AB, Kirwan, JP
Metabolism: clinical and experimental. 2018;82:111-117
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Literature shows that dietary whole-grain intake is associated with a lower incidence of type 2 diabetes. The aim of the study was to investigate the association between a whole-grain diet and insulin resistance and glucose use in individuals at risk for type 2 diabetes. The study was a randomized, double-blind, controlled crossover trial involving fourteen middle-aged, obese adults at risk for diabetes. Randomisation was carried out prior to metabolic testing. Results indicate that whole-grain intake as part of a mixed-meal diet significantly improved post-prandial (after a meal) glucose metabolism in middle-aged obese adults. Furthermore, both whole-grain and refined-grain interventions induced about 3–6% weight and fat loss. Authors conclude that whole-grain intake effectively promotes glycaemic control by improving insulin action.
Abstract
BACKGROUND Whole-grain intake is associated with lower risk of type 2 diabetes but the mechanisms are unclear. PURPOSE We tested the hypothesis that a WG diet reduces insulin resistance and improves glucose use in individuals at risk for type 2 diabetes compared with an isocaloric-matched refined-grain diet. METHODS A double-blind, randomized, controlled, crossover trial of 14 moderately obese adults (Age, 38 ± 2 y; BMI, 34.0 ± 1.1 kg/m2). Insulin resistance and glucose metabolism was assessed using an oral glucose tolerance test combined with isotopic tracers of [6,6-2H2]-glucose and [U-13C]-glucose, and indirect calorimetry. Peripheral and hepatic insulin resistance was assessed as 1/(rate of disposal/insulin), and endogenous glucose rates of appearance (Ra) iAUC60-240 × insulin iAUC60-240, respectively. Both diets met ADA nutritional guidelines and contained either whole-grain (50 g per 1000 kcal) or equivalent refined-grain. All food was provided for 8 wk. with an 8-10 wk. washout period between diets. RESULTS Post-prandial glucose tolerance, peripheral insulin sensitivity, and metabolic flexibility (insulin-stimulated - fasting carbohydrate oxidation) improvements were greater after whole-grain compared to the refined-grain diet (P < 0.05). Compared to baseline, body fat (~2 kg) and hepatic Ra insulin resistance was reduced by both diets, while fasting glucose and exogenous glucose-meal were unchanged after both interventions. Changes in peripheral insulin resistance and metabolic flexibility correlated with improved glucose tolerance (P < 0.05). CONCLUSION Whole-grains reduced diabetes risk and the mechanisms appear to work through reduced post-prandial blood glucose and peripheral insulin resistance that were statistically linked to enhanced metabolic flexibility.
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The Association between Breakfast Skipping and Body Weight, Nutrient Intake, and Metabolic Measures among Participants with Metabolic Syndrome.
Zhang, L, Cordeiro, LS, Liu, J, Ma, Y
Nutrients. 2017;9(4)
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There is conflicting evidence on the benefits of either skipping breakfast versus the idea that breakfast is the most important meal of the day. This study examines the effects of skipping breakfast on weight loss in a group of 240 participants diagnosed as having Metabolic syndrome (MetS). The study looked at data from a diet trial looking at the effects of a high fibre diet or the American Heart Association diet on MetS, in which they all also monitored breakfast eating patterns, to see if there was any change to body weight, nutrient intakes, and selected metabolic measures. The study lasted one year, and dietary recalls were collected throughout. The results showed that at the start of the trial 32.9% of the participants self-reported regularly skipped breakfast and generally they had lower levels of vitamins B1, B3 and folate intake. They also had a higher fat intake compared to those who ate breakfast. However, at the end of the year there was no statistical differences between those who ate and those who skipped breakfast when it came to the other metabolic parameters of weight, BMI, weight circumference, blood pressure, cholesterol, and fasting glucose. Interestingly at the end of the trial only 14% reported skipping breakfast suggesting that participants had the intention to change their eating patterns because of having participated in the trial. The study concluded that skipping breakfast alone was not enough to influence MetS.
Abstract
The effect of skipping breakfast on health, especially in adults, remains a controversial topic. A secondary data analysis was conducted to examine associations between breakfast eating patterns and weight loss, nutrient intake, and metabolic parameters among participants with metabolic syndrome (MetS) (n = 240). Three randomly selected 24-h dietary recalls were collected from each participant at baseline and at the one-year visit. Skipped breakfast was seen in 32.9% at baseline and in 17.4% at the one-year visit, respectively. At baseline, after adjustment for demographics and physical activity, participants who ate breakfast had a higher thiamin, niacin, and folate intake than did breakfast skippers (p < 0.05); other selected parameters including body weight, dietary quality scores, nutrient intake, and metabolic parameters showed no significant differences between the two groups (p ≥ 0.05). From baseline to one year, after adjustment for covariates, mean fat intake increased by 2.7% (95% confidence intervals (CI): -1.0, 6.5%) of total energy in breakfast skippers in comparison to the 1.2% decrease observed in breakfast eaters (95% CI: -3.4, 1.1%) (p = 0.02). Mean changes in other selected parameters showed no significant differences between breakfast skippers and eaters (p > 0.05). This study did not support the hypothesis that skipping breakfast has impact on body weight, nutrient intakes, and selected metabolic measures in participants with MetS.
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Favourable effects of consuming a Palaeolithic-type diet on characteristics of the metabolic syndrome: a randomized controlled pilot-study.
Boers, I, Muskiet, FA, Berkelaar, E, Schut, E, Penders, R, Hoenderdos, K, Wichers, HJ, Jong, MC
Lipids in health and disease. 2014;13:160
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The prevalence of metabolic syndrome (MetS) is increasing rapidly worldwide and is a major risk factor for type 2 diabetes (DM2) and cardiovascular disease (CVD). Modern lifestyle-induced insulin resistance and chronic systemic low grade inflammation are considered at the root of the MetS. Therefore, dietary patterns of our Palaeolithic ancestors may be ideal for prevention and treatment of metabolic disorders since they are thought to be in line with the evolution of human physiology and metabolism. The aim of this randomized controlled pilot study was to assess the efficacy of a Palaeolithic-type diet in improving the characteristics of MetS, compared to a diet based on healthy eating guidelines. The study included 34 participants with MetS who consumed their allocated diets for two weeks. Efforts were made to prevent weight loss so that any favourable effects could be explained by the dietary intervention and not by the positive health effects of weight loss. The findings of this study showed that the Palaeolithic-type diet significantly lowered blood pressure, total cholesterol and triglycerides, as well as improved HDL-cholesterol, compared to the reference diet. The participants in the Palaeolithic diet intervention also had fewer characteristics of MetS and a tendency to higher insulin sensitivity at the end of the study. Despite efforts to keep body-weight stable, more weight was lost by the participants in the Palaeolithic group. No changes were observed in the secondary outcomes of inflammation, intestinal permeability and salivary cortisol, which the authors explain by the short duration of the intervention and the attempt to prevent weight loss. The authors conclude that future studies should take full additional advantage of the greater weight loss with the Palaeolithic diet, which may be more satiating than other diets, hence allowing weight loss to happen.
Abstract
BACKGROUND The main goal of this randomized controlled single-blinded pilot study was to study whether, independent of weight loss, a Palaeolithic-type diet alters characteristics of the metabolic syndrome. Next we searched for outcome variables that might become favourably influenced by a Paleolithic-type diet and may provide new insights in the pathophysiological mechanisms underlying the metabolic syndrome. In addition, more information on feasibility and designing an innovative dietary research program on the basis of a Palaeolithic-type diet was obtained. METHODS Thirty-four subjects, with at least two characteristics of the metabolic syndrome, were randomized to a two weeks Palaeolithic-type diet (n = 18) or an isoenergetic healthy reference diet, based on the guidelines of the Dutch Health Council (n = 14). Thirty-two subjects completed the study. Measures were taken to keep bodyweight stable. As primary outcomes oral glucose tolerance and characteristics of the metabolic syndrome (abdominal circumference, blood pressure, glucose, lipids) were measured. Secondary outcomes were intestinal permeability, inflammation and salivary cortisol. Data were collected at baseline and after the intervention. RESULTS Subjects were 53.5 (SD9.7) year old men (n = 9) and women (n = 25) with mean BMI of 31.8 (SD5.7) kg/m2. The Palaeolithic-type diet resulted in lower systolic blood pressure (-9.1 mmHg; P = 0.015), diastolic blood pressure (-5.2 mmHg; P = 0.038), total cholesterol (-0.52 mmol/l; P = 0.037), triglycerides (-0.89 mmol/l; P = 0.001) and higher HDL-cholesterol (+0.15 mmol/l; P = 0.013), compared to reference. The number of characteristics of the metabolic syndrome decreased with 1.07 (P = 0.010) upon the Palaeolithic-type diet, compared to reference. Despite efforts to keep bodyweight stable, it decreased in the Palaeolithic group compared to reference (-1.32 kg; P = 0.012). However, favourable effects remained after post-hoc adjustments for this unintended weight loss. No changes were observed for intestinal permeability, inflammation and salivary cortisol. CONCLUSIONS We conclude that consuming a Palaeolithic-type diet for two weeks improved several cardiovascular risk factors compared to a healthy reference diet in subjects with the metabolic syndrome. TRIAL REGISTRATION Nederlands Trial Register NTR3002.