Energy expenditure and body composition in Prader-Willi syndrome

Patients with Prader-Willi syndrome are frequently obese. To determine if obesity is partially explained by a low energy expenditure, we compared total daily energy expenditure, basal metabolic rate, and body composition in Prader-Willi patients with obese controls. Total energy expenditure was measured by doubly labeled water, basal metabolic rate was measured by respiratory gas analysis using an open-system canopy design, and body composition was calculated from total body water determinations using ¹⁸O labeled water. In six Prader-Willi subjects, basal metabolic rates were normal when compared on the basis of fat free mass, but not body surface area or height, weight, and age. Ten Prader-Willi subjects (8 to 24 years-old) had a total daily energy expenditure (± SD) of 1,980 ± 580 kcal/d, which was 47% less than their obese controls (3,700 ± 820 kcal/d). When normalized for their smaller fat free mass and body mass, however, the difference was only 14% (P < .01). The results indicate that the low energy expenditures in Prader-Willi syndrome are mostly due to the small fat free mass in these patients and not due to any difference in energy efficiency at the cellular level. Prader-Willi subjects who had lost weight and were at or near weights appropriate for their heights were still 30% to 40% body fat. Because this excess fat was not evident from skinfold measures, usual anthropometric measures were not reliable indicators of total body fat in these subjects.     

Homozygosity of the Pro12Ala variant of the peroxisome proliferation-activated receptor-γ2 (PPAR-γ2): divergent modulating effects on body mass index in obese and lean Caucasian men

Aims/hypothesis. The objectives of the present investigation were to examine: 1) whether a Pro115Gln variant in the peroxisome proliferator-activated receptor-γ2 (PPAR- γ 2) is associated with juvenile-onset obesity among Danish Caucasianmen and 2) whether the relation of a Pro12Ala polymorphism in PPAR- γ 2 with BMI and long-term weight regulation differ between lean and obese subjects within the same cohort. Methods. The Pro115Gln and Pro112Ala variants were examined using PCR and RFLP in a group of 752 subjects with a Body Mass Index (BMI) of 31.0 kg/m² or more and in 869 non-obese control subjects. Results. We did not find Pro115Gln in any of the 1621 male subjects we examined. Among the males with juvenile-onset obesity, the allelic frequency of the Pro12Ala polymorphism was 14 % (95 % confidence interval: 12–16 %) compared with 16 % (14–17 %) among the non-obese control subjects (NS). Heterozygosity of the codon 12 variant was not associated with differences in BMI or changes in body weight regulation during follow up in lean or obese subjects. In the group of obese subjects, 21 homozygous Ala12Ala carriers had, however, a higher BMI (38.9 ± 5.4 kg/m² (means ± SD) vs 35.5 ± 5.5 kg/m², p = 0.008) and a higher weight gain (0.27 ± 0.24 kg · m^–2· year^–1 vs 0.10 ± 0.24 kg · m^–2· year^–1, p = 0.004), compared with wild-type carriers. Moreover, within the control group of 869 men the 14 homozygous carriers of the variant had a lower BMI (24.4 ± 2.7 kg/m² vs 26.2 ± 3.7 kg/m², p = 0.005) and a slower increase in BMI (0.11 ± 0.11 kg · m^–2· year^–1 vs 0.17 ± 0.11 kg · m^–2· year^–1, p = 0.002) compared with wild-type carriers. Conclusion/interpretation. The codon 12 variant of PPAR- γ 2 is not intrinsically associated with juvenile obesity. The variant may in its homozygous form interact, however, with various combinations of genetic and environmental factors in lean and obese subjects to cause divergent modulating effects on BMI and long-term body weight control. [Diabetologia (1999) 42: 892–895] Received: 22 December 1998 and in revised form: 3 March 1999     

Weight maintenance after a very low calorie diet (VLCD) weight reduction period and the effects of VLCD supplementation: A prospective,randomized, comparative,controlled long-term trial

Abstract. Objectives . To evaluate the efficacy of a structured very low calorie diet (VLCD) weight reduction/weight maintenance behaviour programme on weight maintenance in obese patients (BMI ≥ 30 kg/m²). Design . Prospective, randomized, controlled intervention trial. Setting . University out-patient obesity clinic. Subjects . A total of 114 obese patients from the waiting list were invited to participate in the structured weight reduction/weight maintenance programme lasting for 64 weeks. Sixty patients agreed to participate. Intervention . All 60 patients were placed on a Cambridge 330 kcal day^-1diet during the first 12 weeks. Fifty-two were subsequently randomized to either a well balanced hypocaloric diet (1600 kcal day^-1), of which 220 kcal were provided by two sachets of Cambridge diet (group 1), or the same energy provided by the same principal diet (group 2) during the following 52-week weight maintenance period. Main outcome measures . During the VLCD period, the mean body weight decreased significantly from 112.4 ± 19.8 to 91.6 ± 17.7 kg (P < 0.0001). Seventy-one per cent of the weight loss was fat. During the weight maintenance period the average body weight increased significantly in group 1: 8.0 ± 8.2 vs. 12.3 ± 9.7 kg in group 2 (P < 0.0001). After the 64-week treatment period the mean body weight in group 1 was 93.7 ± 18.1 kg and significantly lower compared to 109.9 ± 23.8 kg in group 2 (P = 0.008). Compliance was high: 87% completed the VLCD period and 75% completed the whole 64-week treatment programme. Conclusion . Very low calorie diet as part of the dietary allowance during the weight maintenance programme partly prevents weight regain. This finding can be translated into practical treatment recommendations.     

A low-calorie diet improves endothelium-dependent vasodilation in obese patients with essential hypertension

BackgroundBoth obesity and hypertension are associated with endothelial dysfunction. The purpose of this study was to investigate the effects of a low-calorie diet on endothelial function in obese patients with essential hypertension.MethodsWe measured forearm blood flow (FBF) during intra-arterial infusion of acetylcholine (ACh; 7.5, 15, 30 μg/min), an index of endothelium-dependent vasodilation, and isosorbide dinitrate (ISDN; 0.75, 1.5, 3.0 μg/min), an index of endothelium-independent vasodilation, in obese patients with essential hypertension before and after 2 weeks on a low-calorie diet (800 kcal/d). The study included 11 obese hypertensive Japanese patients (mean body mass index, 30.8 ± 3.6 kg/m²). Fifteen healthy Japanese normotensive individuals were recruited as a control group.ResultsIn obese patients with hypertension, the response of FBF to ACh was attenuated compared to healthy individuals (P < .001). Caloric restriction reduced body weight from 77.5 ± 15.0 to 73.2 ± 13.5 kg (P < .01), the mean blood pressure from 118.4 ± 8.7 to 105.7 ± 8.5 mm Hg (P < .01), fasting plasma insulin from 85.8 ± 22.8 to 64.8 ± 27.0 pmol/L (P < .05), serum total cholesterol from 5.30 ± 0.76 to 4.67 ± 0.58 mmol/L (P < .05), and low density lipoprotein cholesterol from 3.80 ± 0.48 to 3.29 ± 0.44 mmol/L (P < .05). Basal FBF was similar before and after weight reduction. Caloric restriction enhanced the response of FBF to ACh (P < .05), but did not alter the response to ISDN. The intra-arterial infusion of N^G-monomethyl-l-arginine (8 μmol/min), a nitric oxide synthase inhibitor, decreased the enhanced ACh-induced blood flow response induced by caloric restriction.ConclusionsThe present findings suggest that the caloric restriction improves endothelial-dependent vasodilation through an increased release of nitric oxide in obese hypertensive patients.     

Peritoneal Dialysis in Class 2-3 Obesity—A Single-Center Experience

Extreme obesity may hamper successful peritoneal dialysis (PD) delivery. Among our PD patients, we have identified 15 markedly obese (class 2-3 obesity: body mass index [BMI] ≥35 kg/m²) and 20 lean (BMI: 20-25 kg/m²) dialysis patients and reviewed multiple clinical, laboratory and dialysis-related parameters. Extreme outliers of obesity (BMI > 40; 6 subjects) received detailed review. Although weight (P < 0.0001) and BMI (P < 0.0001) differed significantly, weekly Kt/V (obese versus lean: 2.05 ± 0.51 versus 2 ± 0.36), creatinine clearance (86.8 ± 44.8 versus 70 ± 30.4 L/1.73 m²) or residual renal functions were not statistically different. Total daily PD exchange volumes were similar (11.2 ± 2.5 L versus 10.4 ± 2.5 L, P = 0.378). Serum albumin, calcium, phosphorus, hemoglobin and parathyroid hormone levels did not differ, either. Analogous results have been obtained for extremely obese subjects (BMI 44.3 ± 4.2 kg/m²; range: 40.2-51.6). Our study shows only limited effect of class ≥2 obesity for successful PD in this predominantly African American cohort.     

Digoxin disposition in obesity: Clinical pharmacokinetic investigation

Olgoxin pharmacokinetics were studied in 16 obese (mean ± SD weight, 100.2 ± 36.8 kg) and 13 control (64.6 ± 10.5 kg) subjects. all subjects had normal renal function and no other coexisting disease. After administration of 0.75 mg digoxin by intravenous intusion, multiple plasma samples obtained over the 96 hours following infusion were analyzed for digoxin concentration by radloimmunoassay. Pharmacokinetic parameters were determined by weighted iterative nonlinear least squares regression analysis. Elimination half-life ($\text{t}\text{1}\text{2}$) was not different between obese and control groups (35.6 ± 10.5 vs 41.2 ± 16.7 hours). Absolute volume of distribution (Vd) also was not different (981 ± 301 vs 937 ± 397 liters), nor was total clearance of digoxin (328 ± 82 vs 278 ± 87 ml/min). Elimination $\text{t}\text{1}\text{2}$ was significantly negatively correlated with clearance among all subjects (r = ?0.46; p < 0.01). Using percent ideal body weight (IBW) as a measure of obesity, no correlation was found between percent IBW and Vd (r = 0.03). Thus digoxin is simllarly distributed into IBW in obese and normal weight subjects, and there is no significant distribution of digoxin into excese body weight over IBW. In addition, there is no difference in total metabolic clearance or elimination half-life between obese and control subjects. Digoxin loading and maintenance dosage should be calculated on the basis of IBW, which reflects lean body mass, rather than TBW, which reflects adipose tissue weight in addition to lean body mass.     

Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity

Aims: People with type 2 diabetes mellitus (T2DM) are characterized by reduced incretin effect and inappropriate glucagon levels. We evaluated α and β‐cell responses to oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion (IIGI) in lean and obese persons with T2DM or normal glucose tolerance (NGT) to elucidate the impact of obesity on the incretin effect and incretin hormone and glucagon responses. Methods: Four hour 50‐g OGTT and IIGI were performed in (i) Eight obese patients with T2DM [mean body mass index (BMI): 37 (range: 35–41) kg/m²]; (ii) Eight obese subjects with NGT [BMI: 33 (35–38) kg/m²]; (iii) Eight lean patients with T2DM [BMI: 24 (22–25) kg/m²]; and (iv) Eight lean healthy subjects [BMI: 23 (20–25) kg/m²]. Results: The incretin effect was significantly (p < 0.05) reduced in patients with T2DM {obese: 7 ± 7% [mean ± standard error of the mean (SEM)]; lean: 29 ± 8%; p = 0.06)} and was lower in obese subjects (41 ± 4%) than in lean subjects with NGT (53 ± 4%; p < 0.05). Obese subjects with NGT were also characterized by elevated fasting plasma glucagon levels, but the inappropriate glucagon responses to OGTT found in the T2DM patients were not evident in these subjects. Conclusions: Our findings suggest that reduced incretin effect and fasting hyperglucagonaemia constitute very early steps in the pathophysiology of T2DM detectable even in obese people who despite their insulin‐resistant state have NGT.     

Weight loss leads to a marked decrease in nonresting energy expenditure in ambulatory human subjects

The extent to which the resting and nonresting components of 24-hour energy expenditure decrease after weight reduction has not been prospectively assessed in ambulatory, weight-stable, reduced-obese humans. Accordingly, 24-hour energy expenditure was estimated as the weight-stabilizing (+/- 50 g/d) daily caloric intake of a defined liquid diet in a cross-sectional study of ten reduced-obese subjects after a 23.2% +/- 9.4% weight loss and 18 obese subjects at baseline weight. A regression analysis demonstrated an 18% decrease in the mean daily energy requirement of the reduced-obese subjects compared with that of subjects of the same relative body weight who had never dieted. Strong linear relationships were noted between estimated 24-hour energy expenditure and fat-free mass (FFM), and between resting metabolic rate (RMR) and FFM in the subjects at baseline weight. In six reduced-obese men, the 24-hour energy expenditure was only 75.7% +/- 5.6% of the value predicted by regression analysis for the decreased FFM. In these six subjects the RMR was 97.4% +/- 7.5% of that predicted for the decreased FFM, suggesting that essentially all the energy savings relative to FFM in the reduced-obese state occurred in nonresting energy expenditure. In a subsequent group of seven subjects studied longitudinally before and after a 21.5% +/- 2.3% weight loss, the decrease in nonresting energy expenditure accounted for 582 +/- 276 kcal/d or 71% of the decrease in estimated 24-hour energy expenditure. These data suggest a decrease in the nonresting energy expenditure of ambulatory reduced-obese individuals, which is greater than previously appreciated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Psychosocial and Cardiometabolic Health of Patients With Differing Body Mass Index Completing Cardiac Rehabilitation

BackgroundIt remains unclear whether cardiac rehabilitation (CR) provides similar benefits to patients with varying levels of body mass index (BMI). We assessed the psychosocial and cardiometabolic health of patients with increased BMI who completed CR.MethodsThe records of 582 patients who completed a 3-month outpatient CR program were analyzed. On the basis of their BMI at baseline, patients were categorized as normal (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), obese (30.0-34.9 kg/m²), or severely obese (≥ 35.0 kg/m²). Analysis of covariance was used to compare health-related quality of life (ie, Physical Component Summary [PCS] and Mental Component Summary scores), anxiety, depression, and cardiometabolic health indicators between BMI categories after CR.ResultsAt baseline, patients with severe obesity, when compared with those with normal BMI, had lower PCS scores (39.7 ± 8.5 vs 44.4 ± 8.4, P < 0.001), elevated levels of anxiety (7.0 ± 3.7 vs 4.8 ± 3.2, P = 0.001) and depression (5.5 ± 4.4 vs 3.4 ± 3.7, P < 0.001), higher glycated hemoglobin A1C (6.5 ± 1.1 vs 5.6 ± 0.7%, P < 0.001) and triglycerides (1.6 ± 0.5 vs 1.1 ± 0.4 mmol/L, P < 0.001), and lower high-density lipoprotein cholesterol (1.1 ± 0.3 vs 1.2 ± 0.4 mmol/L, P = 0.006). After CR, notwithstanding a greater percent weight reduction in obesity (−3.5% ± 6.9% vs +1.1% ± 7.0%, P = 0.002) and severe obesity (−6.5% ± 6.9% vs +1.1% ± 7.0%, P < 0.001), smaller improvements in PCS scores were seen in the obese (4.1 ± 7.4 vs 6.9 ± 7.6, P = 0.011) and severely obese (4.1 ± 7.6 vs 6.9 ± 7.6, P = 0.039) when compared with those with normal BMI.ConclusionsPoorer psychosocial and cardiometabolic health at baseline coupled with smaller improvements in the PCS score suggest that patients with obesity and severe obesity will benefit from enhanced care in the CR setting.     

Carbohydrate intake and short-term regulation of leptin in humans

Summary The response of serum leptin to short (4 days) and prolonged (28 days) energy restriction (50 % reduction in energy intake) was determined in 18 (9 male, 9 female) moderately obese humans (body mass index 32.0 ± 0.6 kg/m² mean ± SEM), 9 of whom had mild non-insulin-dependent diabetes mellitus (NIDDM). Body composition was assessed before and at the end of the energy restriction using DEXA. The subjects lost a measured 2.6 ± 0.4 kg of body fat after 28 days and an estimated 0.3 kg at 4 days. Serum leptin fell to 64 ± 3 % of baseline levels at day 4 and further to 46 ± 4 % at day 28. In a multiple correlation analysis, the change in leptin concentration at day 4 was significantly related to the change in dietary carbohydrate intake (partial r = 0.68, p < 0.005) but not to changes in fat (r = 0.12) or protein (r = 0.02) intakes. There was a 1 : 1 relationship between the changes in leptin and dietary carbohydrate (regression slope = 1.0 ± 0.3). Gender, or the presence of NIDDM had no effects on these responses. This pronounced fall in serum leptin in association with reduced carbohydrate intake before substantial loss of body fat suggests a role for leptin in defending the body's carbohydrate stores and implicates leptin in the satiating effects of carbohydrate. Dietary or other interventions which maintain leptin levels during weight reduction may lead to improvements in weight loss. [Diabetologia (1997) 40: 348–351] Received: 29 October 1996 and in revised form: 16 December 1996     

Antihypertensive effect of α- and β-adrenergic blockade in obese and lean hypertensive subjects

The purpose of this study was to determine the contribution of the adrenergic system in mediating hypertension in obese and lean patients. Thirteen obese, hypertensive patients with a body mass index (BMI) ≥28 kg/m² (obese) and nine lean patients with a BMI ≤25 kg/m² (lean) were recruited. After a 1-week washout period, participants underwent daytime ambulatory blood pressure monitoring (ABPM). Participants were then treated with the α-adrenergic antagonist doxazosin, titrating to 4 mg QHS in 1 week. In the next week, the β-adrenergic antagonist atenolol was added at an initial dose of 25 mg/day and titrated to 50 mg/day within 1 week. One month after the addition of atenolol, all patients underwent a second ABPM session.There were no differences between the obese and lean subjects in baseline systolic (SBP), diastolic (DBP), or mean arterial pressures (MAP) measured by office recording or ABPM. However, obese subjects had higher heart rates than lean subjects (87.5 ± 2.4 v 76.8 ± 4.9 beats/min). After 1 month of treatment with the adrenergic blockers, obese patients had a significantly lower SBP (130.0 ± 2.5 v 138.9 ± 2.1 mm Hg, P = .02) and MAP (99.6 ± 2.3 v 107.0 ± 1.5 mm Hg, P = .02) than lean patients. Obese patients also tended to have a lower DBP than lean patients (84.3 ± 2.5 v 90.9 ± 1.6 mm Hg, P = .057), but there was no significant difference in heart rate after 1 month of adrenergic blockade.These results indicate that blood pressure is more sensitive to adrenergic blockade in obese than in lean hypertensive patients and suggest that increased sympathetic activity may be an important factor in the maintenance of hypertension in obesity.     

Similarity in Gallstone Formation from 900 kcal/day Diets Containing 16 g vs 30 g of Daily Fat (Evidence that Fat Restriction Is Not the Main Culprit of Cholelithiasis During Rapid Weight Reduction)

Diets containing essentially no fat, 1-2 g fatper day, have resulted in cholesterol gallstones.Greater fat may result in less gallbladder stasis. Dogallstones form with greater fat content? We studied 272 moderately obese subjects who had normalgallbladder ultrasonograms. The 900 kcal/day liquiddiets contained either 16 g fat (N = 94) or 30 g fat (N= 178) each day for 13 weeks. A second gallbladderultrasound was performed. Sixteen of 94 (17.0%) of the16-g fat group developed stones with a weight loss of 18(±7) kg and a body mass index (BMI) decrease of6 (±2) kg/m². Twenty of 178 (11.2%) ofthe 30-g fat group developed stones (P = 0.18, no differencein stone formation) with similar weight loss of 20(±7) kg (P = 0.08) and BMI decrease of 7(±2) kg/m² (P = 0.04). Substantial fatfor rapid weight-reducing diets resulted in gallstone formation. Sinceexperiments have shown that our higher fat diet,containing 10 g fat per meal, results in maximalgallbladder emptying, cholelithiasis from rapid weightloss may not be solely attributable to gallbladderstasis.     

The COVID-19 lockdown as an opportunity to change lifestyle and body weight in people with overweight/obesity and diabetes: Results from the national French COVIDIAB cohort

Background and aimsTo analyze lifestyle habits and weight evolution during the COVID-19 pandemic-associated lockdown, in diabetes and overweight/obesity patients (body mass index (BMI) [25–29.9] and ≥30 kg/m², respectively).Methods and resultsWe collected information on participants’ characteristics and behavior regarding lifestyle before and during the lockdown, through the CoviDIAB web application, which is available freely for people with diabetes in France. We stratified the cohort according to BMI (≥25 kg/m² vs < 25 kg/m²) and examined the determinants of weight loss (WL), WL > 1 kg vs no-WL) in participants with a BMI ≥25 kg/m², in both univariate and multivariate analyses.Of the 5280 participants (mean age, 52.5 years; men, 49%; diabetes, 100% by design), 69.5% were overweight or obese (mean BMI, 28.6 kg/m² (6.1)). During the lockdown, patients often quit or decreased smoking; overweight/obese participants increased alcohol consumption less frequently as compared with normal BMI patients. In addition, overweight/obese patients were more likely to improve other healthy behaviors on a larger scale than patients with normal BMI: increased intake of fruits and vegetables, reduction of snacks intake, and reduction of total dietary intake. WL was observed in 18.9% of people with a BMI ≥25 kg/m², whereas 28.6% of them gained weight. Lifestyle favorable changes characterized patients with WL.ConclusionsA significant proportion of overweight/obese patients with diabetes seized the opportunity of lockdown to improve their lifestyle and to lose weight. Identifying those people may help clinicians to personalize practical advice in the case of a recurrent lockdown.     

Lidocaine disposition in obesity

Fourteen obese men (mean weight 124 ± 8 kg (± standard error of the mean), percent ideal body weight (IBW) 169 ± 10%), 11 obese women (96 ± 6 kg; 174 ± 11% IBW), 19 control men (69 ± 1 kg; 93 ± 2% IBW), and 12 control women (59 ± 2 kg; 102 ± 3% IBW), all of similar age and without clinical or laboratory evidence of cardiac or renal dysfunction, received a single 25-mg intravenous dose of lidocaine. Elimination half-life was markedly prolonged in obese compared with control men (2.69 ± 0.2 vs 1.62 ± 0.06 hour, p < 0.001) and in obese compared with control women (2.95 ± 0.1 vs 2.08 ± 0.06 hour, p <0.01). This was not the result of a change in clearance (men, obese vs control: 1,427 ± 117 vs 1,346 ± 86 ml/min, difference not significant, [NS]; women: 1,089 ± 83 vs 1,162 ± 84 ml/min, NS), but rather of an increased absolute volume of distribution (Vd) in obese men (325 ± 29 vs 186 ± 12 liters, p <0.001) and obese women (264 ± 20 vs 209 ± 15 liters, p <0.025). Vd corrected for total body weight was unchanged in obesity for both men (2.67 ± 0.22 vs 2.71 ± 0.18 1/kg, NS) and women (2.88 ± 0.31 vs 3.57 ± 0.25, NS), suggesting that lidocaine Vd increases in parallel with body weight in both sexes. Because lidocaine clearance is determined mainly by hepatic blood flow, these findings suggest that extremes of body weight do not change hepatic blood flow. However, lidocaine distribution is markedly increased in obese subjects of either sex, and is distributed to the same extent into excess body weight as into IBW. Lidocaine loading doses in obese persons should be calculated based on total body weight, but infusion rate should not be changed.     

Reductions in Blood Pressure Following Energy Restriction for Weight Loss Do Not Rebound after Re-Establishment of Energy Balance in Overweight and Obese Subjects

Objective.?The objective of the present study was to elucidate the separate effects of energy restriction and weight loss on blood pressure (BP) and to assess the relationship between sodium intake, weight loss, and BP.?Methods.?Two hundred and eight overweight and obese subjects (age: 52.4 ± 0.8 yrs; BMI 33.6 ± 0.3 kg/m²) completed a weight loss diet program consisting of 8–12 weeks of moderate energy restriction (ER; ～30% energy deficit, unrestricted salt intake) and four weeks of energy balance (EB). Body weight and BP were measured at baseline, the midpoint, and the end of ER and after EB. 24-hr Na+ excretion was measured at baseline and at the end of EB.?Results. Overall, body weight reduced progressively by 7.0 ± 0.2 kg (7.5%; p?<?0.001) with the hypocaloric diet. BP fell substantially during the first phase of ER (?5.7 ± 0.7/?2.6 ± 0.4 mmHg, p = 0.001), corresponding to a 4.5 ± 0.2 kg weight reduction, with no further BP changes during the second phase of ER, despite further weight loss (2.4 ± 0.1 kg). During EB, BP remained stable. The hypotensive effects of caloric restriction and weight loss were similar across clinical subgroups defined by age, sex, diabetes, insulin sensitivity, and hypertensive status. BP responses to weight loss were independent of 24-hr urinary Na+ excretion. 24-hr urinary Na+ excretion was similar at baseline and at the end of EB (146.5 ± 5.3 vs. 146.9 ± 5.3 mmol/24-hr).?Conclusion.?The hypotensive effects of caloric restriction do not rebound upon return to eucaloric intake at a reduced body weight, and a high sodium intake does not appear to alter the hypotensive effects of weight loss. This reinforces the clinical importance of weight loss and supports the recommendation that strategies for promoting long-term weight loss should become the primary focus of dietary efforts to control BP in overweight patients.     

The impact of obesity on balance control in community-dwelling older women

Older individuals have impaired balance control, particularly those that are frail and/or have sensory deprivations. Obese individuals show faster body sway during upright stance than normal weight individuals, suggesting that they also have difficulty controlling balance even if they do not have the same sensory issues as the older people. Therefore, the objective of this study was to examine if obesity is associated to a decreased balance control in older women. Postural sway of normal weight (n?=?15, age?=?70.8?±?5.5 years; BMI?=?22.2?±?1.9 kg/m²), overweight (n?=?15, age?=?71.7?±?4.3 years; BMI?=?27.3?±?1.3 kg/m²), and obese (n?=?15, age?=?71.1?±?4.3 years; BMI?=?33.1?±?3.4 kg/m²) women was measured with a force platform for normal quiet stance lasting for 30 s in opened and closed eyes conditions. The obese group oscillated at a faster speed than the normal weight group (vision 0.99?±?0.29 cm/s vs. 0.70?±?0.16 cm/s, p?<?0.01; no vision 1.43?±?0.50 cm/s vs. 0.87?±?0.23 cm/s, p?<?0.01). The obese group exhibited greater range in both axes without vision compared to the normal weight group (p?<?0.05). When observing sway density parameters, the obese group also spent less time in stability zones (2 mm radius area in which the center of pressure is relatively stable), and the distance between these stability zones are greater than the normal weight group in both visual conditions (p?<?0.01 and p?<?0.05, respectively). Obesity clearly affects postural control in older women. Our results suggest that obesity has a negative impact on the capacity of older woman to adequately use proprioceptive information for posture control. As postural instability or balance control deficits are identified as a risk factor for falling, our results also suggest that obesity in older women could be considered as another potential contributing factor for falling.     

Early and longer term effects of gastric bypass surgery on tissue-specific insulin sensitivity and beta cell function in morbidly obese patients with and without type 2 diabetes

Aims/hypothesis

Bariatric surgery consistently induces remission of type 2 diabetes. We tested whether there are diabetes-specific mechanisms in addition to weight loss.

Methods

We studied 25 morbidly obese patients (BMI 51.7?±?1.5?kg/m² [mean?±?SEM]), 13 with non-insulin-treated type 2 diabetes (HbA_1c 7.1?±?0.5% [54?±?5?mmol/mol]), before and at 2?weeks and 1?year after Roux-en-Y gastric bypass (RYGB). Lean (n?=?8, BMI 23.0?±?0.5?kg/m²) and obese (n?=?14) volunteers who were BMI-matched (36.0?±?1.2) to RYGB patients at 1?year after surgery served as controls. We measured insulin-stimulated glucose disposal (M) and substrate utilisation (euglycaemic clamp/indirect calorimetry), endogenous glucose production (EGP) by 6,6-[²H₂]glucose, lipolysis (rate of appearance of [²H₅]glycerol) and beta cell function (acute insulin response to i.v. glucose [AIR] as determined by C-peptide deconvolution).

Results

At baseline, all obese groups showed typical metabolic abnormalities, with M, glucose oxidation and non-oxidative disposal impaired, and EGP, lipolysis, lipid oxidation and energy expenditure increased. Early after RYGB plasma glucose and insulin levels, and energy expenditure had decreased, while lipid oxidation increased, with M, EGP and AIR unchanged. At 1?year post-RYGB (BMI 34.4?±?1.1?kg/m²), all diabetic patients were off glucose-lowering treatment and mean HbA_1c was 5.4?±?0.14% (36?±?2?mmol/mol) (p?=?0.03 vs baseline); AIR also improved significantly. In all RYGB patients, M, substrate oxidation, EGP, energy expenditure and lipolysis improved in proportion to weight loss, and were therefore similar to values in obese controls, but still different from those in lean controls.

Conclusions/interpretation

In morbidly obese patients, RYGB has metabolic effects on liver, adipose tissue, muscle insulin sensitivity and pattern of substrate utilisation; these effects can be explained by energy intake restriction and weight loss, the former prevailing early after surgery, the latter being dominant in the longer term.     

Leptin and norepinephrine plasma concentrations during glucose loading in normotensive and hypertensive obese women

We performed this study to investigate whether changes in plasma glucose, insulin, and norepinephrine concentrations during an oral glucose tolerance test (OGTT) are associated with changes in plasma leptin levels in normotensive and hypertensive obese women. Plasma insulin, glucose, norepinephrine, and leptin concentrations were evaluated at the baseline and during OGTT in normotensive women (NT-Ob, N = 24, mean age 38.3 ± 1.8 years, body mass index [BMI] 37.9 ± 1.1 kg/m²) and hypertensive (HT-Ob, N = 25, mean age 37.7 ± 1.9 years, BMI 39.4 ± 1.3 kg/m²) obese women, and in a group of normal-weight women (controls, N = 20, mean age 38.3 ± 1.3 years, BMI 23.1 ± 0.4 kg/m²). The OGTT caused a significant increase in plasma leptin concentrations in both NT-Ob and HT-Ob groups, whereas no such change was detectable in control subjects. Area under curve (AUC) for plasma leptin showed a direct correlation with norepinephrine AUC in both NT-Ob (r = 0.73, P = .001) and HT-Ob (r = 0.74, P = .001) group, which was still detectable in multivariate analysis (P = .014 and P = .017, respectively). Our study confirms that glucose loading increases circulating leptin concentrations in obese women, and demonstrates the existance of an association between leptin and norepinephrine changes during OGTT in both normotensive and hypertensive obese women. We hypothesize that this association may reflect the lack of leptin suppression by catecholamines or a direct leptin-induced sympathoactivation. These findings suggest that leptin could be relevant in the regulation of blood pressure in obese women.     

Body mass index is associated with prognosis in Japanese elderly patients with atrial fibrillation: an observational study from the outpatient clinic

The relationship between body mass index (BMI) and the prognosis of elderly patients with atrial fibrillation (AF) is unknown. We aimed to examine the association of body weight with the clinical outcomes among Japanese elderly patients with a history of documented AF. This observational study of AF patients from an outpatients clinic in Nagoya University Hospital included 413 patients ≥70 years old (99 obese: BMI ≥25 kg/m²; 256 normal weight: BMI 18.5–24.9 kg/m²; and 58 underweight patients: BMI <18.5 kg/m²). The mean age was 77.5 ± 5.6 years. During a mean follow-up of 19.0 months, all-cause death occurred in 23 patients (obese 1 %, normal weight 5.1 %, and underweight 16 %). The major adverse events including all-cause death, stroke or transient ischemic attack, heart failure requiring admission, and acute coronary syndrome were observed in 53 patients (obese 5.1 %, normal weight 13 %, and underweight 26 %). After adjusting for confounding factors, the underweight group had a significantly greater risk for all-cause death [hazard ratio (HR) 2.91, 95 % confidence interval (CI) 1.12–7.60, p = 0.029], and major adverse events (HR 2.45, 95 % CI 1.25–4.78, p = 0.009) than the normal weight group. In contrast, the obese group had a better prognosis in major adverse events compared with the normal weight group (HR 0.34, 95 % CI 0.13–0.89, p = 0.029). In conclusion, lower BMI was independently associated with poor outcomes among older AF patients. The association between obesity and better prognosis in elderly AF patients was also found.     

Circulating angiotensin II is associated with body fat accumulation and insulin resistance in obese subjects with type 2 diabetes mellitus

Adipocytes express all components of the renin-angiotensin system, and the renin-angiotensin system is involved in obesity and insulin resistance. Circulating angiotensin II (Ang II) is detectable in blood, but its significance in human obesity remains unknown. The aim of this study was to investigate plasma Ang II in obese patients with type 2 diabetes mellitus (T2D) and the change during weight loss. Fifty Japanese obese subjects with T2D (body weight, 75.0 ± 14.1 kg; body mass index, 29.1 ± 3.7 kg/m²; visceral fat area [VFA], 169.3 ± 54.3 cm²; hemoglobin A_1c, 7.6% ± 1.5%) were enrolled. The subjects were prescribed a diet of daily caloric intake of 20 kcal/kg for 24 weeks. Plasma Ang II was measured by radioimmunoassay. Leptin, adiponectin, and lipoprotein lipase mass in preheparin serum were also measured as adipocyte-derived factors. After 24 weeks of weight reduction diet, the mean body weight, VFA, and hemoglobin A_1c decreased significantly by 2.3%, 7.0%, and 8.3%, respectively. The mean plasma Ang II decreased by 24% (P < .0001) and correlated with body weight both at baseline (r = 0.425, P = .0018) and at 24 weeks (r = 0.332, P = .0181). The change in Ang II correlated with changes in body weight (r = 0.335, P = .0167) and VFA (r = 0.329, P = .0191). The change in Ang II also correlated positively with change in leptin (r = 0.348, P = .0127) and tended to correlate negatively with change in lipoprotein lipase mass in preheparin serum (r = −0.260, P = .0683), which is a marker of insulin sensitivity. Plasma Ang II is associated with body weight, decreases during weight loss, and is associated with markers of insulin resistance in obese subjects with T2D.