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Efficacy of a 2-Month Very Low-Calorie Ketogenic Diet (VLCKD) Compared to a Standard Low-Calorie Diet in Reducing Visceral and Liver Fat Accumulation in Patients With Obesity.
Cunha, GM, Guzman, G, Correa De Mello, LL, Trein, B, Spina, L, Bussade, I, Marques Prata, J, Sajoux, I, Countinho, W
Frontiers in endocrinology. 2020;11:607
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Excess fat in the liver, known as non-alcoholic fatty liver disease (NAFLD), has been shown to increase the risk of chronic diseases such as type 2 diabetes. Standard treatment regimens consist of low-calorie (LC) diets and exercise, however these may be ineffective at reversing fat accumulation in the liver. A very low-calorie ketogenic diet (VLCKD) has been proposed as an alternative treatment for NAFLD. This randomised control pilot study of 39 individuals with obesity aimed to compare LC diet and VLCKD on fat accumulation and indicators for NAFLD for two months. The results showed greater weight loss, abdominal fat reduction, liver fat reduction and improvements in liver function with VLCKD compared to the LC diet. Cholesterol was significantly reduced by both diets. However liver stiffness remained unchanged. The authors concluded that VLCKD was more successful at reducing liver fat and abdominal fat accumulation than current standard therapy and has the potential to improve NAFLD. Health care professionals could use this study to improve liver and abdominal fat loss in patients with obesity to improve NAFLD, when standard therapy has been inadequate.
Abstract
Background: Currently the treatment of non-alcoholic fatty liver disease (NAFLD) is based on weight loss through lifestyle changes, such as exercise combined with calorie-restricted dieting. Objectives: To assess the effects of a commercially available weight loss program based on a very low-calorie ketogenic diet (VLCKD) on visceral adipose tissue (VAT) and liver fat content compared to a standard low-calorie (LC) diet. As a secondary aim, we evaluated the effect on liver stiffness measurements. Methods: Open, randomized controlled, prospective pilot study. Patients were randomized and treated either with an LC or a VLCKD and received orientation and encouragement to physical activity equally for both groups. VAT, liver fat fraction, and liver stiffness were measured at baseline and after 2 months of treatment using magnetic resonance imaging. Paired t-tests were used for comparison of continuous variables between visits and unpaired test between groups. Categorical variables were compared using the χ2-test. Pearson correlation was used to assess the association between VAT, anthropometric measures, and hepatic fat fraction. A significance level of the results was established at p < 0.05. Results: Thirty-nine patients (20 with VLCKD and 19 with LC) were evaluated at baseline and 2 months of intervention. Relative weight loss at 2 months was -9.59 ± 2.87% in the VLCKD group and -1.87 ± 2.4% in the LC group (p < 0.001). Mean reductions in VAT were -32.0 cm2 for VLCKD group and -12.58 cm2 for LC group (p < 0.05). Reductions in liver fat fraction were significantly more pronounced in the VLCKD group than in the LC group (4.77 vs. 0.79%; p < 0.005). Conclusion: Patients undergoing a VLCKD achieved superior weight loss, with significant VAT and liver fat fraction reductions when compared to the standard LC diet. The weight loss and rapid mobilization of liver fat demonstrated with VLCKD could serve as an effective alternative for the treatment of NAFLD. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04322110.
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Impact of changes in physical activity or BMI on risk of heart failure in women - the prospective population study of women in Gothenburg.
Halldin, AK, Lissner, L, Lernfelt, B, Björkelund, C
Scandinavian journal of primary health care. 2020;38(1):56-65
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Heart failure (HF) is a severe and progressive condition with poor prognosis. Obesity is a risk factor for HF. The aim of this study was to investigate the impact of change in physical activity or change in body mass index on the risk of later developing HF in women without a previous diagnosis of HF. This study is prospective longitudinal study which includes 1749 healthy women from the Prospective Population Study of Women in Gothenburg. Results indicate that gaining weight in early middle age is more harmful than gaining weight later in life, with regard to the risk of developing HF later in life. Furthermore, reduced risk of future HF in healthy women may be achieved by remaining physically active from young middle age and throughout life or by increasing the level of physical activity. Authors conclude that the role of physical activity in preventing the development of obesity must be taken into account.
Abstract
Objective: To longitudinally evaluate the impact of change in physical activity or change in body mass index (BMI) over time on the risk of developing heart failure (HF) in women without a previous diagnosis of HF.Design and setting: Longitudinal, observational, prospective study of women in Gothenburg, Sweden. Data on BMI and level of physical activity were collected from examinations 1968-1992 and hospital diagnoses and mortality data were ascertained from 1980 to 2012.Subjects: Data were obtained from 1749 women included in the Prospective Population Study of Women in Gothenburg.Main outcome measures: Hazard ratio (HR) for HF was calculated, using a Cox regression model.Results: Women with stable high physical activity during 1968-1980 and 1980-1992 reduced their risk of subsequent HF compared to the non-active women (for 1968-1980 HR 0.66, 95% Confidence Interval (CI) 0.44-0.99 and for 1980-1992 HR 0.47, 95% CI 0.29-0.74). Women with increasing levels of physical activity during 1980-1992 reduced their risk of HF compared to the non-active women (HR 0.40, 95% CI 0.22-0.72). Increase in BMI from overweight to obesity during 1968-1980 predicted increased risk of developing HF (HR 1.93, 95% CI 1.18-3.14).Conclusions: Reduced risk of future HF in healthy women may be achieved by remaining physically active from young middle age and throughout life or by increasing the level of physical activity. This is particularly important for sedentary women in middle age. The role of physical activity in preventing the development of obesity must be taken into account.Key pointsA sedentary lifestyle and obesity are risk factors for developing heart failure (HF) in women.The risk of developing HF may be reduced by increasing the level of activity in sedentary middle-aged women.For younger women, avoiding obesity is most important to reduce the risk of later HF.Primary care has a key role in guiding women towards the most effective lifestyle changes to prevent development of HF.
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Effect of a Nutritional and Behavioral Intervention on Energy-Reduced Mediterranean Diet Adherence Among Patients With Metabolic Syndrome: Interim Analysis of the PREDIMED-Plus Randomized Clinical Trial.
Sayón-Orea, C, Razquin, C, Bulló, M, Corella, D, Fitó, M, Romaguera, D, Vioque, J, Alonso-Gómez, ÁM, Wärnberg, J, Martínez, JA, et al
JAMA. 2019;322(15):1486-1499
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Excess caloric intake and poor nutritional quality are associated with overweight and obesity. A traditional Mediterranean diet has been shown to reduce all-cause mortality, and in particular to reduce risk of cardiovascular disease, type 2 diabetes mellitus and overweight. The aim of this randomised, prospective, single-blinded study was to evaluate the effectiveness of an intensive lifestyle intervention programme in 6874 overweight or obese men and women with metabolic syndrome in Spain. The intervention group was advised on an energy-reduced Mediterranean diet and exercise and received behavioural support, with initial group sessions and interviews, and monthly follow-up phone calls for one year. The control group received advice on a Mediterranean diet and usual care, with 6 monthly follow-ups. After 12 months, the more intensively counselled patients showed a significantly better adherence to an energy-reduced Mediterranean diet than the control group. They had greater reductions in refined grains, pastries, red and processed meats and greater increases in vegetable, fruit and nut consumption than the control group. The intervention group had also better improvements in cardiovascular risk factors.
Abstract
Importance: High-quality dietary patterns may help prevent chronic disease, but limited data exist from randomized trials about the effects of nutritional and behavioral interventions on dietary changes. Objective: To assess the effect of a nutritional and physical activity education program on dietary quality. Design, Setting, and Participants: Preliminary exploratory interim analysis of an ongoing randomized trial. In 23 research centers in Spain, 6874 men and women aged 55 to 75 years with metabolic syndrome and no cardiovascular disease were enrolled in the trial between September 2013 and December 2016, with final data collection in March 2019. Interventions: Participants were randomized to an intervention group that encouraged an energy-reduced Mediterranean diet, promoted physical activity, and provided behavioral support (n = 3406) or to a control group that encouraged an energy-unrestricted Mediterranean diet (n = 3468). All participants received allotments of extra-virgin olive oil (1 L/mo) and nuts (125 g/mo) for free. Main Outcomes and Measures: The primary outcome was 12-month change in adherence based on the energy-reduced Mediterranean diet (er-MedDiet) score (range, 0-17; higher scores indicate greater adherence; minimal clinically important difference, 1 point). Results: Among 6874 randomized participants (mean [SD] age, 65.0 [4.9] years; 3406 [52%] men), 6583 (96%) completed the 12-month follow-up and were included in the main analysis. The mean (SD) er-MedDiet score was 8.5 (2.6) at baseline and 13.2 (2.7) at 12 months in the intervention group (increase, 4.7 [95% CI, 4.6-4.8]) and 8.6 (2.7) at baseline and 11.1 (2.8) at 12 months in the control group (increase, 2.5 [95% CI, 2.3-2.6]) (between-group difference, 2.2 [95% CI, 2.1-2.4]; P < .001). Conclusions and Relevance: In this preliminary analysis of an ongoing trial, an intervention that encouraged an energy-reduced Mediterranean diet and physical activity, compared with advice to follow an energy-unrestricted Mediterranean diet, resulted in a significantly greater increase in diet adherence after 12 months. Further evaluation of long-term cardiovascular effects is needed. Trial Registration: isrctn.com Identifier: ISRCTN89898870.
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Comparison of the Effects of Fasting Glucose, Hemoglobin A1c, and Triglyceride-Glucose Index on Cardiovascular Events in Type 2 Diabetes Mellitus.
Su, WY, Chen, SC, Huang, YT, Huang, JC, Wu, PY, Hsu, WH, Lee, MY
Nutrients. 2019;11(11)
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Cardiovascular disease generally refers to the narrowing or blockage of the arteries of the heart, which can lead to a heart attack or stroke and is the major cause of death in individuals with type 2 diabetes. Identifying individuals with type 2 diabetes who are at high risk of developing cardiovascular disease could ensure better management of these patients. This retrospective observational study of 3524 individuals with type 2 diabetes aimed to investigate if the amount of sugar found in the blood over the last few months, known as haemaglobin A1c (HbA1c) can predict cardiovascular disease in individuals with type 2 diabetes. In addition, the study looked at the triglyceride-glucose (TyG) index and its relationship to cardiovascular disease outcomes. The results showed that several factors were associated with cardiovascular disease, however of main note was that the TyG index and the amount of sugar in the blood following a fast were associated with increased cardiovascular events in individuals with type 2 diabetes, but HbA1c was not. It was concluded that TyG and the blood sugar level could be used to allow early identification and management of type 2 diabetics to prevent cardiovascular events. Clinicians could use this study to justify the use of measuring the TyG index and blood sugar levels as a predictor for cardiovascular events to ensure that patients are managed not only for type 2 diabetes but also to reduce their risk of cardiovascular events in the future.
Abstract
The triglyceride-glucose (TyG) index has been correlated with insulin resistance. We aim to investigate the role of the TyG index on cardiovascular (CV) events in type 2 diabetes mellitus and compare the roles of fasting glucose, hemoglobin A1c, and the TyG index in predicting CV events. This retrospective study enrolled 3524 patients with type 2 diabetes from the Kaohsiung Medical University Research Database in 2009 in this longitudinal study and followed them until 2015. The TyG index was calculated as log (fasting triglyceride level (mg/dL) × fasting glucose level (mg/dL)/2). CV events included myocardial infarction, unstable angina, stroke, hospitalization for coronary artery disease, peripheral artery disease, and CV-related death. The association between variables and CV events was assessed using a multivariable stepwise Cox proportional hazard analysis. Two hundred and fifteen CV events (6.1%) were recorded during a follow-up period of 5.93 years. The multivariable stepwise analysis showed that high fasting glucose (HR, 1.007; p < 0.001) and a high TyG index (HR, 1.521; p = 0.004) but not hemoglobin A1c or triglycerides were associated with a higher rate of CV events. Adding fasting glucose and the TyG index to the basic model improved the predictive ability of progression to a CV event (p < 0.001 and p = 0.018, respectively), over that of hemoglobin A1c (p = 0.084) and triglyceride (p = 0.221). Fasting glucose and the TyG index are useful parameters and stronger predictive factors than hemoglobin A1c and triglyceride for CV events and may offer an additional prognostic benefit in patients with type 2 diabetes.
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What is the effect of a Mediterranean compared with a Fast Food meal on the exercise induced adipokine changes? A randomized cross-over clinical trial.
Silva, D, Moreira, R, Beltrão, M, Sokhatska, O, Montanha, T, Pizarro, A, Garcia-Larsen, V, Villegas, R, Delgado, L, Moreira, P, et al
PloS one. 2019;14(4):e0215475
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Unhealthy dietary intake and sedentary behaviour in a genetically susceptible individual have been associated with adipokine dysregulation (adipokines are small proteins secreted by the fat tissue) resulting both in adverse metabolic and immune responses. The aim of this study was to evaluate the effect of a Mediterranean (MdM) compared with a Fast Food (FFM) iso-energy meal on the acute exercise-induced adipokine changes. The study is a double-blind randomised crossover clinical trial. Participants (n = 46) were randomly assigned to the intervention order in a double-blinded fashion, stratified by asthma diagnosis. Outcomes were measured blinded to the participant’s allocation order. Results indicate that MdM may blunt the adipsin (an adipokine) immediate response and potentiate its exercise induced increase in comparison with a FFM. MdM slightly attenuated the exercise induced cortisol increase. Authors conclude that their findings highlight the importance of the pre-exercise dietary intake on both the immune and metabolic response to acute exercise.
Abstract
BACKGROUND Adipose tissue-derived adipokines are pro-inflammatory cytokines involved in metabolic-related diseases and can be influenced by diet and exercise. We aimed to compare the effect of a Mediterranean (MdM) compared with Fast Food (FFM) meal on the exercise induced adipokines changes. METHODS In a double blinded cross over trial, 46 participants were randomly assigned to one of two standardized iso-energy pre-exercise meals: FFM or MdM-type. Three hours after each meal, participants completed a treadmill exercise test (EC). Serum adiponectin, resistin, PAI-1, lipocalin-2/NGAL and adipsin were determined by Luminex magnetic bead immunoassay. Wilcoxon signed rank test compared changes before/after meal and before/after EC and a linear mixed model evaluated the effect of meals on the adipokine response to exercise, adjusted for confounders. RESULTS Thirty-nine participants (mean age of 25, with a standard deviation of 5 years) completed the trial (56% females). For both interventions, a significant reduction of adipsin after each meal and a significant increase of lipocalin, PAI-1, adipsin and resistin, after exercise was observed. When exercise was preceded by a MdM meal a higher increase in adipsin levels was seen. CONCLUSION Acute exercise induced an increase of circulatory levels of adipsin, resistin, lipocalin and PAI-1, but not adiponectin. A pre-exercise Mediterranean meal potentiated the increase of adipsin after the exercise test, which possibly relates to the immune regulatory role of adipsin. These changes suggest a cross-talk between the immune and metabolic immediate response to exercise and its modulation by the pre-exercise diet composition.
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Effect of an Intensive Lifestyle Intervention on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial.
Johansen, MY, MacDonald, CS, Hansen, KB, Karstoft, K, Christensen, R, Pedersen, M, Hansen, LS, Zacho, M, Wedell-Neergaard, AS, Nielsen, ST, et al
JAMA. 2017;318(7):637-646
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First-line treatment of Type 2 diabetes includes diet, physical activity, and weight loss prior to or in parallel with initiation of medication. The aim of this study was to examine whether an intensive lifestyle intervention results in equivalent blood sugar control compared with standard care. A secondary aim was to test whether an intensive lifestyle intervention leads to a reduction in glucose-lowering medication in participants with Type 2 diabetes. The study was a randomized, assessor-blind clinical study of 98 adults with Type 2 diabetes diagnosed for less than 10 years. The participants were randomly assigned (2:1; stratified by sex) to the lifestyle group (n = 64) or the standard care group (n = 34). Results show that an intensive lifestyle intervention did not achieve comparable blood sugar control in comparison with standard care, however, the former led to a substantial and parallel reduction in glucose-lowering medication. The authors conclude that even though a lifestyle intervention compared to standard care did not result in the expected glycaemic control, it was still in a direction consistent with benefit.
Abstract
Importance: It is unclear whether a lifestyle intervention can maintain glycemic control in patients with type 2 diabetes. Objective: To test whether an intensive lifestyle intervention results in equivalent glycemic control compared with standard care and, secondarily, leads to a reduction in glucose-lowering medication in participants with type 2 diabetes. Design, Setting, and Participants: Randomized, assessor-blinded, single-center study within Region Zealand and the Capital Region of Denmark (April 2015-August 2016). Ninety-eight adult participants with non-insulin-dependent type 2 diabetes who were diagnosed for less than 10 years were included. Participants were randomly assigned (2:1; stratified by sex) to the lifestyle group (n = 64) or the standard care group (n = 34). Interventions: All participants received standard care with individual counseling and standardized, blinded, target-driven medical therapy. Additionally, the lifestyle intervention included 5 to 6 weekly aerobic training sessions (duration 30-60 minutes), of which 2 to 3 sessions were combined with resistance training. The lifestyle participants received dietary plans aiming for a body mass index of 25 or less. Participants were followed up for 12 months. Main Outcomes and Measures: Primary outcome was change in hemoglobin A1c (HbA1c) from baseline to 12-month follow-up, and equivalence was prespecified by a CI margin of ±0.4% based on the intention-to-treat population. Superiority analysis was performed on the secondary outcome reductions in glucose-lowering medication. Results: Among 98 randomized participants (mean age, 54.6 years [SD, 8.9]; women, 47 [48%]; mean baseline HbA1c, 6.7%), 93 participants completed the trial. From baseline to 12-month follow-up, the mean HbA1c level changed from 6.65% to 6.34% in the lifestyle group and from 6.74% to 6.66% in the standard care group (mean between-group difference in change of -0.26% [95% CI, -0.52% to -0.01%]), not meeting the criteria for equivalence (P = .15). Reduction in glucose-lowering medications occurred in 47 participants (73.5%) in the lifestyle group and 9 participants (26.4%) in the standard care group (difference, 47.1 percentage points [95% CI, 28.6-65.3]). There were 32 adverse events (most commonly musculoskeletal pain or discomfort and mild hypoglycemia) in the lifestyle group and 5 in the standard care group. Conclusions and Relevance: Among adults with type 2 diabetes diagnosed for less than 10 years, a lifestyle intervention compared with standard care resulted in a change in glycemic control that did not reach the criterion for equivalence, but was in a direction consistent with benefit. Further research is needed to assess superiority, as well as generalizability and durability of findings. Trial Registration: clinicaltrials.gov Identifier: NCT02417012.
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Changes in Visceral Adiposity, Subcutaneous Adiposity, and Sex Hormones in the Diabetes Prevention Program.
Kim, C, Dabelea, D, Kalyani, RR, Christophi, CA, Bray, GA, Pi-Sunyer, X, Darwin, CH, Yalamanchi, S, Barrett-Connor, E, Golden, SH, et al
The Journal of clinical endocrinology and metabolism. 2017;102(9):3381-3389
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It is not currently known to what extent changes in different types of fat stores (visceral fat that surrounds organs and subcutaneous fat that sits under the surface of the skin) relate to changes in sex hormones. This study was a secondary analysis of a randomised controlled trial including 555 individuals. It examined whether changes to visceral and subcutaneous fat were associated with changes in sex hormones (DHEA, testosterone, oestrogen and sex hormone binding globulin - SHBG) among overweight individuals with glucose intolerance under the care of a diabetes program. Participants were randomly assigned to an intensive lifestyle modification programme (goals for weight reduction and 150 mins exercise weekly), medication (metformin) or placebo for 12 months. The authors found that among men, reductions in both types of fat were associated with significant increases in total testosterone and SHBG. Among women, reductions in both types of fat were associated with increases in SHBG and associations with estrone differed by menopausal status. No associations were found between changes in fat stores and estradiol or DHEA. The authors conclude that weight loss may affect sex hormone profiles via reductions in visceral and subcutaneous fat. -
Abstract
Context: The degree to which changes in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) relate to corresponding changes in plasma sex steroids is not known. Objective: We examined whether changes in VAT and SAT areas assessed by computed tomography were associated with changes in sex hormones [dehydroepiandrosterone sulfate (DHEAS), testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG)] among Diabetes Prevention Program participants. Design: Secondary analysis of a randomized trial. Participants: Overweight and glucose-intolerant men (n = 246) and women (n = 309). Interventions: Intensive lifestyle change with goals of weight reduction and 150 min/wk of moderate intensity exercise or metformin administered 850 mg twice a day or placebo. Main Outcome Measures: Associations between changes in VAT, SAT, and sex hormone changes over 1 year. Results: Among men, reductions in VAT and SAT were both independently associated with significant increases in total testosterone and SHBG in fully adjusted models. Among women, reductions in VAT and SAT were both independently associated with increases in SHBG and associations with estrone differed by menopausal status. Associations were similar by race/ethnicity and by randomization arm. No significant associations were observed between change in fat depot with change in estradiol or DHEAS. Conclusions: Among overweight adults with impaired glucose intolerance, reductions in either VAT and SAT were associated with increased total testosterone in men and higher SHBG in men and women. Weight loss may affect sex hormone profiles via reductions in visceral and subcutaneous fat.
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A comparative controlled trial comparing the effects of yoga and walking for overweight and obese adults.
Telles, S, Sharma, SK, Yadav, A, Singh, N, Balkrishna, A
Medical science monitor : international medical journal of experimental and clinical research. 2014;20:894-904
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Walking and yoga are types of exercise that may be useful for weight loss. The aim of this study was to compare the effects of yoga and walking on the biochemistry, body composition, balance and strength in overweight people. 68 Indian adults who were overweight or obese were allocated to either yoga or walking twice a day for 15 days. Both groups were given the same plant-based diet providing 1,650 kcal/day Both groups showed similar and significant decreases in body mass index (BMI), waist and hip circumference, lean mass, body water and total cholesterol over the 15 days. The yoga group increased serum leptin and decreased LDL cholesterol. The walking group decreased serum adiponectin and triglycerides. Since there was no control group, it was not possible to attribute the changes to the yoga or walking, rather than the diet. The authors concluded that both yoga and walking improved anthropometric variables and serum lipid profile in overweight and obese people, and that these interventions may be useful in treating obesity.
Abstract
BACKGROUND Walking and yoga have been independently evaluated for weight control; however, there are very few studies comparing the 2 with randomization. MATERIAL AND METHODS The present study compared the effects of 90 minutes/day for 15 days of supervised yoga or supervised walking on: (i) related biochemistry, (ii) anthropometric variables, (iii) body composition, (iv) postural stability, and (v) bilateral hand grip strength in overweight and obese persons. Sixty-eight participants, of whom 5 were overweight (BMI ≥25 kg/m2) and 63 were obese (BMI ≥30 kg/m2; group mean age ±S.D., 36.4±11.2 years; 35 females), were randomized as 2 groups - (i) a yoga group and (ii) a walking group - given the same diet. RESULTS All differences were pre-post changes within each group. Both groups showed a significant (p<0.05; repeated measures ANOVA, post-hoc analyses) decrease in: BMI, waist circumference, hip circumference, lean mass, body water, and total cholesterol. The yoga group increased serum leptin (p<0.01) and decreased LDL cholesterol (p<0.05). The walking group decreased serum adiponectin (p<0.05) and triglycerides (p<0.05). CONCLUSIONS Both yoga and walking improved anthropometric variables and serum lipid profile in overweight and obese persons. The possible implications are discussed.