Accumulation of cervical and chin subcutaneous adipose tissues (SAT) represent known phenotypes of obesity. We aimed to evaluate the sensitivity of these fat storages to long-term weight-loss ...directed lifestyle-intervention and to assess their relations to bodily-adiposity, insulin-resistance, and cardiometabolic risk; We randomly assigned 278 participants with abdominal-obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets +/- physical-activity. All participants underwent an 18 month whole-body magnetic resonance imaging follow-up, from which we assessed cervical and chin SAT-areas; Participants (age = 48 years; 90% men; body-mass-index = 30.9 kg/m
) had an 18-month adherence-rate of 86%. Cervical-SAT and chin-SAT decreased after 6-months (-13.1% and -5.3%, respectively,
< 0.001). After 18-months only cervical-SAT remained decreased compared to baseline (-5%,
< 0.001). Cervical and chin-SAT 18-month changes were associated with changes in weight (r = 0.70, r = 0.66 respectively; <0.001 for both) and visceral-adipose-tissue (VAT; r = 0.35, r = 0.42 respectively; <0.001 for both). After adjustment to VAT, waist-circumference, or weight-changes, chin-SAT 18-month reduction was associated with favorable changes in fasting-glucose (β = 0.10;
= 0.05), HbA1c (β = 0.12;
= 0.03), and homeostasis-model-assessment-of-insulin-resistance (β = 0.12;
= 0.03). Cervical-SAT 18-month reduction was associated with decreased triglycerides (β = 0.16;
= 0.02) and leptin (β = 0.19;
= 0.01) independent of VAT; Cervical and chin-SATs are dynamic fat depots that correspond with weight-loss and are associated with changes in cardiometabolic profile. In long-term, chin-SAT displays a larger rebound compared with cervical-SAT. Chin-SAT accumulation is associated with in insulin-resistance, independent of central obesity. (ClinicalTrials identifier NCT01530724).
Recommendations for moderate alcohol consumption remain controversial, particularly in type 2 diabetes mellitus (T2DM). Long-term randomized, controlled trials (RCTs) are lacking.
To assess ...cardiometabolic effects of initiating moderate alcohol intake in persons with T2DM and whether the type of wine matters.
2-year RCT (CASCADE CArdiovaSCulAr Diabetes & Ethanol trial). (ClinicalTrials.gov: NCT00784433).
Ben-Gurion University of the Negev-Soroka Medical Center and Nuclear Research Center Negev, Israel.
Alcohol-abstaining adults with well-controlled T2DM.
Patients were randomly assigned to 150 mL of mineral water, white wine, or red wine with dinner for 2 years. Wines and mineral water were provided. All groups followed a Mediterranean diet without caloric restriction.
Primary outcomes were lipid and glycemic control profiles. Genetic measurements were done, and patients were followed for blood pressure, liver biomarkers, medication use, symptoms, and quality of life.
Of the 224 patients who were randomly assigned, 94% had follow-up data at 1 year and 87% at 2 years. In addition to the changes in the water group (Mediterranean diet only), red wine significantly increased high-density lipoprotein cholesterol (HDL-C) level by 0.05 mmol/L (2.0 mg/dL) (95% CI, 0.04 to 0.06 mmol/L 1.6 to 2.2 mg/dL; P < 0.001) and apolipoprotein(a)1 level by 0.03 g/L (CI, 0.01 to 0.06 g/L; P = 0.05) and decreased the total cholesterol-HDL-C ratio by 0.27 (CI, -0.52 to -0.01; P = 0.039). Only slow ethanol metabolizers (alcohol dehydrogenase alleles ADH1B*1 carriers) significantly benefited from the effect of both wines on glycemic control (fasting plasma glucose, homeostatic model assessment of insulin resistance, and hemoglobin A1c) compared with fast ethanol metabolizers (persons homozygous for ADH1B*2). Across the 3 groups, no material differences were identified in blood pressure, adiposity, liver function, drug therapy, symptoms, or quality of life, except that sleep quality improved in both wine groups compared with the water group (P = 0.040). Overall, compared with the changes in the water group, red wine further reduced the number of components of the metabolic syndrome by 0.34 (CI, -0.68 to -0.001; P = 0.049).
Participants were not blinded to treatment allocation.
This long-term RCT suggests that initiating moderate wine intake, especially red wine, among well-controlled diabetics as part of a healthy diet is apparently safe and modestly decreases cardiometabolic risk. The genetic interactions suggest that ethanol plays an important role in glucose metabolism, and red wine's effects also involve nonalcoholic constituents.
European Foundation for the Study of Diabetes.
Trials comparing the effectiveness and safety of weight-loss diets are frequently limited by short follow-up times and high dropout rates.
In this 2-year trial, we randomly assigned 322 moderately ...obese subjects (mean age, 52 years; mean body-mass index the weight in kilograms divided by the square of the height in meters, 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non-restricted-calorie.
The rate of adherence to a study diet was 95.4% at 1 year and 84.6% at 2 years. The Mediterranean-diet group consumed the largest amounts of dietary fiber and had the highest ratio of monounsaturated to saturated fat (P<0.05 for all comparisons among treatment groups). The low-carbohydrate group consumed the smallest amount of carbohydrates and the largest amounts of fat, protein, and cholesterol and had the highest percentage of participants with detectable urinary ketones (P<0.05 for all comparisons among treatment groups). The mean weight loss was 2.9 kg for the low-fat group, 4.4 kg for the Mediterranean-diet group, and 4.7 kg for the low-carbohydrate group (P<0.001 for the interaction between diet group and time); among the 272 participants who completed the intervention, the mean weight losses were 3.3 kg, 4.6 kg, and 5.5 kg, respectively. The relative reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol was 20% in the low-carbohydrate group and 12% in the low-fat group (P=0.01). Among the 36 subjects with diabetes, changes in fasting plasma glucose and insulin levels were more favorable among those assigned to the Mediterranean diet than among those assigned to the low-fat diet (P<0.001 for the interaction among diabetes and Mediterranean diet and time with respect to fasting glucose levels).
Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions. (ClinicalTrials.gov number, NCT00160108.)
Decreased dietary meat may deplete iron stores, as plant-derived iron bioavailability is typically limited.
We explored the effect of a low-meat Mediterranean (green-MED) diet, supplemented with ...Wolffia globosa duckweed (Mankai: rich in protein and iron) as a food source for humans, on iron status. We further examined the iron bioavailability of Mankai in rats.
Two hundred and ninety-four abdominally obese/dyslipidemic mean age = 51.1 y; body mass index (kg/m2) = 31.3; 88% men nonanemic participants were randomly assigned to physical activity (PA), PA + MED diet, or PA + green-MED diet. Both isocaloric MED groups consumed 28 g walnuts/d and the low-meat green-MED group further consumed green tea (800 mL/d) and Mankai (100 g green shake/d). In a complementary animal experiment, after 44 d of an iron deficiency anemia–inducing diet, 50 female rats (age = 3 wk; Sprague Dawley strain) were randomly assigned into: iron-deficient diet (vehicle), or vehicle + iso-iron: ferrous gluconate (FG) 14, Mankai 50, and Mankai 80 versions (1.7 mg · kg−1 · d−1 elemental iron), or FG9.5 and Mankai 50-C version (1.15 mg · kg−1 · d−1 elemental iron). The specific primary aim for both studies was changes in iron homeostasis parameters.
After 6 mo of intervention, iron status trajectory did not differ between the PA and PA + MED groups. Hemoglobin modestly increased in the PA + green-MED group (0.23 g/dL) compared with PA (−0.1 g/dL; P < 0.001) and PA + MED (−0.1 g/dL; P < 0.001). Serum iron and serum transferrin saturation increased in the PA + green-MED group compared with the PA group (8.21 μg/dL compared with −5.23 μg/dL and 2.39% compared with −1.15%, respectively; P < 0.05 for both comparisons), as did folic acid (P = 0.011). In rats, hemoglobin decreased from 15.7 to 9.4 mg/dL after 44 d of diet-induced anemia. After depletion treatment, the vehicle-treated group had a further decrease of 1.3 mg/dL, whereas hemoglobin concentrations in both FG and Mankai iso-iron treatments similarly rebounded (FG14: +10.8 mg/dL, Mankai 50: +6.4 mg/dL, Mankai 80: +7.3 mg/dL; FG9.5: +5.1 mg/dL, Mankai 50-C: +7.1 mg/dL; P < 0.05 for all vs. the vehicle group).
In humans, a green-MED low-meat diet does not impair iron homeostasis. In rats, iron derived from Mankai (a green-plant protein source) is bioavailable and efficient in reversal of anemia. This trial was registered at clinicaltrials.gov as NCT03020186.
Unlike visceral adipose tissue (VAT), the association between subcutaneous adipose tissue (SAT) and obesity-related morbidity is controversial. In patients with type 2 diabetes, we assessed whether ...this variability can be explained by a putative favorable, distinct association between abdominal superficial SAT (SSAT) (absolute amount or its proportion) and cardiometabolic parameters.
We performed abdominal magnetic resonance imaging (MRI) in 73 patients with diabetes (mean age 58 years, 83% were men) and cross-sectionally analyzed fat distribution at S1-L5, L5-L4, and L3-L2 levels. Patients completed food frequency questionnaires, and subgroups had 24-h ambulatory blood pressure monitoring and 24-h ambulatory electrocardiography.
Women had higher %SSAT (37 vs. 23% in men; P < 0.001) despite a similar mean waist circumference. Fasting plasma glucose (P = 0.046) and HbA(1c) (P = 0.006) were both lower with increased tertile of absolute SSAT. In regression models adjusted for age, waist circumference, and classes of medical treatments used in this patient population, increased %SSAT was significantly associated with decreased HbA(1c) (β = -0.317; P = 0.013), decreased daytime ambulatory blood pressure (β = -0.426; P = 0.008), and increased HDL cholesterol (β = 0.257; P = 0.042). In contrast, increased percent of deep SAT (DSAT) was associated with increased HbA(1c) (β = 0.266; P = 0.040) and poorer heart rate variability parameters (P = 0.030). Although total fat and energy intake were not correlated with fat tissue distribution, increased intake of trans fat tended to be associated with total SAT (r = 0.228; P = 0.05) and DSAT (r = 0.20; P = 0.093), but not with SSAT.
Abdominal SAT is composed of two subdepots that associate differently with cardiometabolic parameters. Higher absolute and relative distribution of fat in abdominal SSAT may signify beneficial cardiometabolic effects in patients with type 2 diabetes.
Summary Background & aims Data regarding the role of kidney adiposity, its clinical implications, and its dynamics during weight-loss are sparse. We investigated the effect of long-term weight-loss ...induced intervention diets on dynamics of renal-sinus-fat, an ectopic fat depot, and %renal-parenchymal-fat, lipid accumulation within the renal parenchyma. Methods We randomized 278 participants with abdominal obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets, with or without exercise. We quantified renal-sinus-fat and %renal-parenchymal-fat by whole body magnetic-resonance-imaging. Results Participants (age = 48 years; 89% men; body-mass-index = 31 kg/m2 ) had 86% retention to the trial after 18 months. Both increased renal-sinus-fat and %renal-parenchymal-fat were directly associated with hypertension, and with higher abdominal deep-subcutaneous-adipose-tissue and visceral-adipose-tissue (p of trend < 0.05 for all) after adjustment for body weight. Higher renal-sinus-fat was associated with lower estimated-glomerular-filtration-rate and with higher microalbuminuria and %HbA1C beyond body weight. After 18 months of intervention, overall renal-sinus-fat (−9%; p < 0.05 vs. baseline) but not %renal-parenchymal-fat (−1.7%; p = 0.13 vs. baseline) significantly decreased, and similarly across the intervention groups. Renal-sinus-fat and %renal-parenchymal-fat changes were correlated with weight-loss per-se (p < 0.05). In a model adjusted for age, sex, and visceral-adipose-tissue changes, 18 months reduction in renal-sinus-fat associated with decreased pancreatic, hepatic and cardiac fats (p < 0.05 for all) and with decreased cholesterol/high-density lipoprotein-cholesterol (HDL-c) (β = 0.13; p = 0.05), triglycerides/HDL-c (β = 0.13; p = 0.05), insulin (β = 0.12; p = 0.05) and gamma glutamyl transpeptidase (β = 0.24; p = 0.001), but not with improved renal function parameters or blood pressure. Decreased intake of sodium was associated with a reduction in %renal-parenchymal-fat, after adjustment for 18 months weight-loss (β = 0.15; p = 0.026) and hypertension (β = 0.14; p = 0.04). Conclusions Renal-sinus-fat and renal-parenchymal-fat are fairly related to weight-loss. Decreased renal-sinus-fat is associated with improved hepatic parameters, independent of changes in weight or hepatic fat, rather than with improved renal function or blood pressure parameters. ClinicalTrials.govIdentifier NCT01530724.
The progression of carotid-plaque volume in patients with type 2 diabetes is common. Previous observational studies showed an association between moderate alcohol and reduced risk of coronary ...disease. We examined whether consuming moderate wine affects the progression of carotid atherosclerosis.
In the CASCADE (CArdiovaSCulAr Diabetes and Ethanol), a 2-year randomized controlled trial, we randomized abstainers with type 2 diabetes were to drink 150 ml of either red wine, white wine, or water, provided for 2 years. In addition, groups were guided to maintain a Mediterranean diet. We followed 2-year changes in carotid total plaque volume (carotid-TPV) and carotid vessel wall volume (carotid-VWV), using three-dimensional ultrasound.
Carotid images were available from 174 of the 224 CASCADE participants (67% men; age = 59 yr; HbA1C = 6.8%). Forty-five percent had detectable plaque at baseline. After 2 years, no significant progression in carotid-TPV was observed (water, -1.4 (17.0) mm
, CI (-2.7, 5.5), white-wine, -1.2 (16.9) mm
, CI (-3.8, 6.2), red wine, -1.3 (17.6) mm
, CI (-3.4, 6.0; p = 0.9 between groups)). In post hoc analysis, we divided the 78 participants with detectable baseline carotid plaque into tertiles. Those with the higher baseline plaque burden, whom were assigned to drink wine, reduced their plaque volume significantly after 2 years, as compared to baseline. Two-year reductions in Apo(B)/Apo(A) ratio(s) were independently associated with regression in carotid-TPV (β = 0.4; p < 0.001). Two-year decreases in systolic blood pressure were independently associated with regression in carotid-VWV (β = 0.2; p = 0.005).
No progression in carotid-TPV was observed. In subgroup analyses, those with the greatest plaque burden assigned to drink wine may have had a small regression of plaque burden.
To generate evidence-based conclusions about the effect of wine consumption on weight gain and abdominal fat accumulation and distribution in patients with type 2 diabetes.
In the 2-year randomized ...controlled CASCADE (CArdiovaSCulAr Diabetes & Ethanol) trial, patients following a Mediterranean diet were randomly assigned to drink 150 ml of mineral water, white wine or red wine with dinner for 2 years. Visceral adiposity and abdominal fat distribution were measured in a subgroup of sixty-five participants, using abdominal MRI.
Ben-Gurion University of the Negev, Soroka-Medical Center and the Nuclear Research Center Negev, Israel.
Alcohol-abstaining adults with well-controlled type 2 diabetes.
Forty-eight participants (red wine, n 27; mineral water, n 21) who completed a second MRI measurement were included in the 2-year analysis. Similar weight losses (sd) were observed: red wine 1·3 (3·9) kg; water 1·0 (4·2) kg (P=0·8 between groups). Changes (95 % CI) in abdominal adipose-tissue distribution were similar: red wine, visceral adipose tissue (VAT) -3·0 (-8·0, 2·0) %, deep subcutaneous adipose tissue (DSAT) +5·2 (-1·1, 11·6) %, superficial subcutaneous adipose tissue (SSAT) -1·9 (-5·0, 1·2) %; water, VAT -3·2 (-8·9, 2·5) %, DSAT +2·9 (-2·8, 8·6) %, SSAT -0·15 (-3·3, 2·9) %. No changes in antidiabetic medication and no substantial changes in energy intake (+126 (sd 2889) kJ/d (+30·2 (sd 690) kcal/d), P=0·8) were recorded. A 2-year decrease in glycated Hb (β=0·28, P=0·05) was associated with a decrease in VAT.
Moderate wine consumption, as part of a Mediterranean diet, in persons with controlled diabetes did not promote weight gain or abdominal adiposity.
Summary Background & Aims We aimed to assess the association between the distinct abdominal sub-depots and resting energy expenditure (REE). Methods We performed magnetic resonance imaging (MRI) to ...quantify abdominal visceral-adipose-tissue (VAT), deep-subcutaneous-adipose-tissue (deep-SAT), and superficial-subcutaneous-adipose-tissue (superficial-SAT). We measured REE by indirect-calorimetry. Non-exercise activity thermogenesis (NEAT) 1-3 metabolic equivalents (METs) and exercise thermogenesis (activities of 4+METS ) were estimated based on 6-days of accelerometry to assess total physical activity energy expenditure (PAEE). Results We studied 282 participants: 249 men mean age=47.4 years, body-mass-index (BMI) =31 kg/m2 , mean VAT proportion from total abdominal fat=34.5%, mean superficial-SAT proportion from total abdominal fat=24.3% and 33 women (mean age=51.2 years, BMI=30.1 kg/m2 , mean VAT proportion from total abdominal fat=22.8%, mean superficial-SAT proportion from total abdominal fat=37.8%). As expected, women had lower REE by 32.4% (1,488±234 kcal/day vs. 1,971±257 kcal/day; p<0.01) and lower REE/kg by 8% (19.6 ±3 kcal/kg vs. 21.2 ±2 kcal/kg; p<0.01) than men. Exercise and total PAEE were positively associated with REE/kg (p<0.01 for both) and a positive correlation between NEAT and REE/kg was borderline (p=0.056). Participants, in whom abdominal VAT was the dominant proportional depot, had higher REE (1,964±297 kcal/day vs. 1,654±352 kcal/day; p<0.01) and higher REE\kg (22.2±2.3 kcal/kg/day vs. 19.6±2.5 kcal/kg/day; p<0.01) than participants in whom superficial-SAT was the largest proportional depot. In multivariate models, adjusted for age, gender and residual BMI, increased VAT proportion was independently associated with higher REE (β=0.181; p=0.05). Likewise, increased VAT proportion (β=0.482; p<0.01) remained independently associated with higher REE/kg. In this model younger age (β=-0.329; p<0.01) was associated with higher REE/kg. Conclusions Abdominal fat distribution patterns are associated with varying levels of resting energy expenditure, potentially reflecting different metabolic rates of adipose sub-depots and providing an anatomic/anthropometric link to physiological obese sub-phenotypes.
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