Marked weight loss reduces lean body mass and quadriceps thickness. It is unclear whether muscle loss varies according to the method of weight loss.
This study compared the association of surgical ...versus nonsurgical weight loss with change in vastus medialis (VM) properties in obese adults.
Twenty obese patients (body mass index ≥ 30 kg/m(2)) who lost weight via laparoscopic gastric banding were matched for weight loss with obese patients who lost weight nonsurgically. The thickness and fat infiltration of VM were assessed at baseline and a mean of 2.4 years later.
After adjusting for confounders, the annual change in VM thickness was -2.9% in the surgical group and -.5% for the nonsurgical group (P = .02). There was also a tendency toward an increased risk for VM fat infiltration to be reduced when weight loss occurred nonsurgically (OR 5.1, 95% CI .8-32.8; P = .09).
Compared with nonsurgical weight loss, laparoscopic gastric banding was associated with greater VM muscle thickness loss. Relative to laparoscopic gastric banding, there was also a tendency toward an increased risk for VM fat infiltration to be reduced with nonsurgical weight loss. Close attention to preserving muscle properties at the knee when significant amounts of weight loss have occurred is required. Physical therapy may be important in the management of patients after laparoscopic gastric banding in an attempt to preserve skeletal muscle mass.
Increased glucose production is associated with fasting hyperglycaemia in type 2 diabetes but whether or not it causes glucose intolerance is unclear. This study sought to determine whether a primary ...defect in gluconeogenesis (GNG) resulting in elevated glucose production is sufficient to induce glucose intolerance in the absence of insulin resistance and impaired insulin secretion. Progression of glucose intolerance was assessed in phosphoenolpyruvate carboxykinase (PEPCK) transgenic rats, a genetic model with a primary increase in GNG. Young (4–5 weeks of age) and adult (12–14 weeks of age) PEPCK transgenic and Piebald Virol Glaxo (PVG/c) control rats were studied. GNG, insulin sensitivity, insulin secretion and glucose tolerance were assessed by intraperitoneal and intravascular substrate tolerance tests and hyperinsulinaemic/euglycaemic clamps. Despite elevated GNG and increased glucose appearance, PEPCK transgenic rats displayed normal glucose tolerance due to adequate glucose disposal and robust glucose-mediated insulin secretion. Glucose intolerance only became apparent in the PEPCK transgenic rats following the development of insulin resistance (both hepatic and peripheral) and defective glucose-mediated insulin secretion. Taken together, a single genetic defect in GNG leading to increased glucose production does not adversely affect glucose tolerance. Insulin resistance and impaired glucose-mediated insulin secretion are required to precipitate glucose intolerance in a setting of chronic glucose oversupply.
Hypogonadism is the most frequent hormonal deficiency in individuals with Prader‐Willi syndrome (PWS). This often necessitates testosterone treatment, but limited data are available to guide ...testosterone treatment in adult men with PWS. We aimed to evaluate the serum testosterone concentrations and adverse effects of testosterone treatment in individuals with PWS attending a specialist obesity management service. A retrospective audit was undertaken at Austin Health, Melbourne between January 2010 and April 2021. Main outcome measures were testosterone formulation and dose, serum total testosterone concentration, and prevalence of polycythemia and behavioral disturbance. Data were available for eight individuals with median baseline age 19 years (range, 19–42) and BMI 37 kg/m2 (range, 27–71). Six men had obstructive sleep apnea; none were smokers. Baseline testosterone concentration was 1.8 nmol/L (IQR, 1.1–3.3) with hematocrit 0.43. Testosterone formulations were intramuscular testosterone undecanoate (TU) 1000 mg (n = 5), transdermal testosterone gel 50 mg daily (n = 1), and oral TU 80–120 mg daily (n = 2). Median total testosterone concentration was 9.7 nmol/L (IQR, 8.5–14.7). Nine of 25 (36%) hematocrit results in six patients measured >0.50 (range, 0.50–0.56). Intramuscular TU was well tolerated and was the only formulation to achieve serum total testosterone concentrations in the adult male reference range. Worsening behavioral disturbance resulted in treatment discontinuation in one individual. Our experience reinforces the need to regular monitoring of hematocrit in men with PWS treated with testosterone. However, a worsening of behavior problems was uncommon in this series.
Department of Medicine, University of Melbourne, Royal Melbourne
Hospital, Parkville, Victoria 3050, Australia
High-fat feeding has been shown to cause hepatic insulin
resistance. The aims of this ...study were to investigate the biochemical steps responsible for enhanced gluconeogenesis as a result of increased
dietary fat intake and the site or sites at which the antihyperglycemic
agent metformin acts to inhibit this process. Male Hooded Wistar rats
were fed either a standard chow diet (5% fat by weight) or a high-fat
diet (60% fat by weight) for 14 days with or without metformin. Total
endogenous glucose production and gluconeogenesis were determined using
6- 3 Hglucose and U- 14 Calanine,
respectively. Gluconeogenic enzyme activity and, where appropriate,
protein and mRNA levels were measured in liver tissues. The high-fat
diet increased endogenous glucose production (21.9 ± 4.4 vs.
32.2 ± 4.8 µmol · kg 1 · min 1 ,
P < 0.05) and alanine gluconeogenesis (4.5 ± 0.9 vs. 9.6 ± 1.9 µmol · kg 1 · min 1 ,
P < 0.05). Metformin reduced both endogenous glucose
production (32.2 ± 4.8 vs. 16.1 ± 2.1 µmol · kg 1 · min 1 ,
P < 0.05) and alanine gluconeogenesis (9.6 ± 1.9 vs. 4.7 ± 0.8 µmol · kg 1 · min 1 ,
P < 0.05) after high-fat feeding. These changes were
reflected in liver fructose-1,6-bisphosphatase protein levels (4.5 ± 0.9 vs. 9.6 ± 1.9 arbitrary units, P < 0.05 chow vs. high-fat feeding; 9.5 ± 1.9 vs. 4.7 ± 0.8 arbitrary units, P < 0.05 high fat fed in the absence
vs. presence of metformin) but not in changes to the activity of other
gluconeogenic enzymes. There was a significant positive correlation
between alanine gluconeogenesis and fructose-1,6-bisphosphatase protein
levels ( r = 0.56, P < 0.05). Therefore,
excess supply of dietary fat stimulates alanine gluconeogenesis via an
increase in fructose-1,6-bisphosphatase protein levels. Metformin
predominantly inhibits alanine gluconeogenesis by preventing the
fat-induced changes in fructose-1,6-bisphosphatase levels.
endogenous glucose production; fructose-1,6-bisphosphatase; fat
feeding; hepatic insulin resistance
Off-label drugs for obesity Morgan, Andy; Sturgiss, Liz; Proietto, Joseph
Australian prescriber,
08/2022, Letnik:
45, Številka:
4
Journal Article
Recenzirano
Odprti dostop
A Cochrane review of their long-term effects in people with hypertension found only one randomised trial reporting cardiovascular outcomes. ...they should mandate safety studies with long-term use. ......we have a 3.8-year safety study showing that liraglutide improves cardiovascular outcomes in patients with type 2 diabetes.4 A two-year study of patients with diabetes and established cardiovascular disease showed that semaglutide once weekly reduced cardiovascular events.5Another two-year study concluded that a combination of phentermine and topiramate maintained weight loss and improved cardiovascular and metabolic variables and decreased rates of incident diabetes compared to placebo.6 A study to assess cardiovascular safety for naltrexone/bupropion was terminated early following an interim analysis after 25% and 50% of expected cardiovascular events had occurred.
Summary
The prevalence of women of child‐bearing age with obesity continues to rise at an alarming rate. This has significant implications for both the short‐term and long‐term health of mother and ...offspring. Given the paucity of evidence‐based literature in this field, the preconception management of women with obesity is highly variable both between institutions and around the world. This systematic review aims to evaluate studies that inform us about the role of preconception weight loss in the fertility and pregnancy outcomes of women with obesity. Current therapeutic interventions are discussed, with a specific focus on the suitability of weight loss interventions for women with obesity planning pregnancy. There are significant knowledge gaps in the current literature; these are discussed and areas for future research are explored.
CONTEXT Observational studies suggest that surgically induced loss of weight may be effective therapy for type 2 diabetes. OBJECTIVE To determine if surgically induced weight loss results in better ...glycemic control and less need for diabetes medications than conventional approaches to weight loss and diabetes control. DESIGN, SETTING, AND PARTICIPANTS
Unblinded randomized controlled trial conducted from December 2002 through December 2006 at the University Obesity Research Center in Australia, with general community recruitment to established treatment programs. Participants were 60 obese patients (BMI >30 and <40)
with recently diagnosed (<2 years) type 2 diabetes.
INTERVENTIONS Conventional diabetes therapy with a focus on weight loss by lifestyle change vs laparoscopic adjustable gastric banding with conventional diabetes care. MAIN OUTCOME MEASURES
Remission of type 2 diabetes (fasting glucose level <126
mg/dL 7.0 mmol/L and glycated hemoglobin HbA1c value <6.2% while taking no glycemic therapy). Secondary measures included weight and components of the metabolic syndrome. Analysis was by intention-to-treat.
RESULTS
Of the 60 patients enrolled, 55 (92%) completed the 2-year follow-up.
Remission of type 2 diabetes was achieved by 22 (73%) in the surgical group and 4 (13%) in the conventional-therapy group. Relative risk of remission for the surgical group was 5.5 (95% confidence interval,
2.2-14.0). Surgical and conventional-therapy groups lost a mean (SD)
of 20.7% (8.6%) and 1.7% (5.2%) of weight, respectively, at 2 years (P < .001). Remission of type 2 diabetes was related to weight loss (R2 = 0.46, P < .001) and lower baseline HbA1c levels (combined R2 = 0.52, P < .001). There were no serious complications in either group.
CONCLUSIONS
Participants randomized to surgical therapy were more likely to achieve remission of type 2 diabetes through greater weight loss.
These results need to be confirmed in a larger, more diverse population and have long-term efficacy assessed.
TRIAL REGISTRATION
actr.org Identifier: ACTRN012605000159651
Leptin is produced in proportion to body fat mass and can act on the brain to induce satiety and regulate adipose tissue mass; factors other than adipose tissue mass may influence circulating leptin ...concentrations.
We explored the possibility that short-term, moderately high-fat diets induce weight gain by producing inappropriately low circulating leptin concentrations.
Female Hooded Wistar rats were fed either a moderately high-fat diet or control diet. Body weight, energy intake, body composition, and fasting plasma leptin were compared after 4 and 14 wk of dietary treatment.
After 4 wk, abdominal fat mass was 38% greater in rats fed the high-fat diet than in those fed the control diet (P < 0.01). However, plasma leptin concentrations were 24% lower in animals fed the high-fat diet (P < 0.05), resulting in significantly lower plasma leptin concentrations per unit abdominal fat mass than in control animals (P < 0.005). From 4 to 14 wk, animals fed the high-fat diet gained twice as much weight and consumed 32 kJ/d more than controls (both P < 0.05). At 14 wk, plasma leptin concentrations per unit abdominal fat mass were 27% lower in rats fed the high-fat diet (P = 0.058) and there was a significant negative association between leptin concentrations per unit abdominal fat mass and body weight (r = 0.44, P < 0.05).
In the short term, a moderately high-fat diet is associated with lower than expected circulating leptin concentrations, which correlate with a higher body weight. A high-fat diet may therefore contribute to weight gain by reducing leptin secretion in adipose tissue.
Purpose
Prader-Willi syndrome (PWS) is characterised by childhood-onset hyperphagia and obesity however limited data are available to guide treatment of obesity in this population. We aimed to ...evaluate the safety, tolerability, and efficacy of intensive medical weight loss interventions (very-low-energy diets VLED and/or pharmacotherapy) in individuals with PWS attending a specialist obesity management service.
Methods
A retrospective audit was undertaken of individuals with PWS attending the Austin Health Weight Control Clinic between January 2010-April 2021. Main outcome measures were weight outcomes, duration of use, and adverse effects.
Results
Data were available for 18 patients, of whom 15 were treated with intensive weight loss interventions. Median (interquartile range, IQR) age at baseline was 20 years (19–32) with median body weight 90 kg (75–118) and BMI 37 kg/m
2
(30–51). Median weight loss during VLED (
n
= 7) was 14 kg (1–20 kg) over 60 weeks. Median weight loss with phentermine-topiramate (
n
= 7) was 17 kg (IQR 9–19 kg) over 56 weeks. Median weight loss with liraglutide 0.6–3 mg (
n
= 7), prescribed with topiramate in 3 individuals, was 9 kg (2–14 kg) over 96 weeks. Naltrexone-bupropion resulted in weight loss in 2 of 4 individuals. Thirteen individuals achieved ≥10% weight loss but only 5 individuals maintained ≥10% weight loss at last follow-up. Five individuals discontinued pharmacotherapy due to adverse effects.
Conclusions
VLED and pharmacotherapy can achieve substantial weight loss in some individuals with PWS though non-adherence results in substantial weight regain. Adverse effects were ascribed to phentermine and topiramate, whereas liraglutide was well-tolerated in this population.
The prevalence of type 2 diabetes is rapidly increasing, with severe socioeconomic impacts. Excess lipid deposition in peripheral tissues impairs insulin sensitivity and glucose uptake, and has been ...proposed to contribute to the pathology of type 2 diabetes. However, few treatment options exist that directly target ectopic lipid accumulation. Recently it was found that vascular endothelial growth factor B (VEGF-B) controls endothelial uptake and transport of fatty acids in heart and skeletal muscle. Here we show that decreased VEGF-B signalling in rodent models of type 2 diabetes restores insulin sensitivity and improves glucose tolerance. Genetic deletion of Vegfb in diabetic db/db mice prevented ectopic lipid deposition, increased muscle glucose uptake and maintained normoglycaemia. Pharmacological inhibition of VEGF-B signalling by antibody administration to db/db mice enhanced glucose tolerance, preserved pancreatic islet architecture, improved β-cell function and ameliorated dyslipidaemia, key elements of type 2 diabetes and the metabolic syndrome. The potential use of VEGF-B neutralization in type 2 diabetes was further elucidated in rats fed a high-fat diet, in which it normalized insulin sensitivity and increased glucose uptake in skeletal muscle and heart. Our results demonstrate that the vascular endothelium can function as an efficient barrier to excess muscle lipid uptake even under conditions of severe obesity and type 2 diabetes, and that this barrier can be maintained by inhibition of VEGF-B signalling. We propose VEGF-B antagonism as a novel pharmacological approach for type 2 diabetes, targeting the lipid-transport properties of the endothelium to improve muscle insulin sensitivity and glucose disposal.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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