Investigating general medication prescription by general practitioners during a 12-month randomized controlled weight loss trial.

Much healthcare expenditure is on pharmaceutical drugs. Expenditure on medications has increased both in absolute terms, and as a proportion of total health expenditure. No previous studies have investigated the prescribing costs by general practitioners when managing patients during a weight loss intervention. This study evaluated the medication costs by individual class during a 1-year study in which 268 participants were randomized to one of two weight loss programmes, either standard care (SC) as defined by national guidelines, or a commercial provider (Weight Watchers) (CP). The baseline body mass index of participants (mean ± standard deviation) was 32.0 ± 2.5 kg m-2 , their body weight was 87.5 ± 11.8 kg, and age 47.4 ± 11.7 years. Weight loss for the SC and CP groups was -2.6 and -6.1 kg, respectively (between group difference; P < 0.0001). The greater weight loss in the CP group compared to SC was accompanied by larger reductions in waist circumference and fat mass. The CP group also had significantly greater improvements than SC in high-density lipoprotein cholesterol. Despite SC participants being prescribed and spending more on medications than the CP group with no better weight or metabolic outcomes, this was not of statistical significance. For both groups the highest proportion of prescriptions (≥30% of medications) was for control of risk factors for cardiovascular disease. In conclusion, this study indicates that obesity treatment via a shared care approach with a CP results in greater weight loss and some better clinical outcomes, but despite lower medication costs overall, this was not significant when compared to SC treatment.

Examining the association between depression and obesity during a weight management programme.

The prevalence of depression in those with obesity is reported to be as high as double that in individuals of normal weight. There is potentially a bi-directional relationship between obesity and depression. Some research has suggested that depression results in weight gain and obesity, and other studies have suggested that those with obesity are more likely to develop depression at a later stage. The aim of this study was to investigate the association of depression symptoms with weight change over a 12-month study. Seventy participants undertook a 3-month lifestyle (diet and exercise) weight loss intervention, and were followed up as part of a 12-month study. Participants completed the Beck Depression Inventory-II (BDI-II) and had their body weight measured throughout the study. Baseline body mass index (BMI) of participants (mean ± standard deviation [SD]) was 31.1 ± 3.9 kg m-2 , body weight was 89.4 ± 16.1 kg, and age was 45.4 ± 11.1 years; 63% of the cohort were female. The mean weight change from baseline to 3 months was -5.2% (±SD 4.3%), and from baseline to 12 months was -4.2% (±SD 6.1%). There was a significant decrease in BDI-II scores over the 12-month study, and a 1-unit decrease in BDI-II score was associated with a further decrease in body weight of -0.4%. The current study indicated that weight loss was associated with improvements in mood for non-clinically depressed individuals with obesity, and these improvements persisted during a period of 3-12 months of follow-up.

Hypoglycaemia in cystic fibrosis in the absence of diabetes: A systematic review.

BACKGROUND: Hypoglycaemia in CF in the absence of diabetes or glucose lowering therapies is a phenomenon that is receiving growing attention in the literature. These episodes are sometimes symptomatic and likely have variable aetiologies. Our first aim was to conduct a systematic review of the literature to determine what is known about hypoglycaemia in CF. Our second aim was to assess evidence based guidelines for management strategies. METHODS: A comprehensive search of databases and guideline compiler entities was performed. Inclusion criteria were primary research articles and evidence based guidelines that referred to hypoglycaemia in CF in the absence of insulin treatment or other glucose lowering therapies. RESULTS: A total of 11 studies (four manuscripts and seven abstracts) and five evidence-based guidelines met the inclusion criteria. Prevalence rates of hypoglycaemia unrelated to diabetes varied between studies (7-69%). Hypoglycaemia was diagnosed during oral glucose tolerance testing or continuous glucose monitoring (CGM). Associations between hypoglycaemia and clinical parameters of BMI, lung function, liver disease and pancreatic insufficiency were measured in some studies. There was no unifying definition of hypoglycaemia in the absence of diabetes. Only two evidence based guidelines reported possible management strategies. CONCLUSION: The systematic review found limited data on this clinical problem and supports the need for high quality methodological studies that are able to describe the experience and the aetiology(ies) of hypoglycaemia in CF.

Fast versus slow weight loss: development process and rationale behind the dietary interventions for the TEMPO Diet Trial.

OBJECTIVE AND METHODS: Finding effective solutions to curb the obesity epidemic is a great global public health challenge. The need for long-term follow-up necessitates weight loss trials conducted in real-world settings, outside the confines of tightly controlled laboratory or clinic conditions. Given the complexity of eating behaviour and the food supply, this makes the process of designing a practical dietary intervention that stands up to scientific rigor difficult. Detailed information about the dietary intervention itself, as well as the process of developing the final intervention and its underlying rationale, is rarely reported in scientific weight management publications but is valuable and essential for translating research into practice. Thus, this paper describes the design process and underlying rationale behind the dietary interventions in an exemplar weight loss trial - the TEMPO Diet Trial (Type of Energy Manipulation for Promoting optimal metabolic health and body composition in Obesity). This trial assesses the long-term effects of fast versus slow weight loss on adiposity, fat free mass, muscle strength and bone density in women with obesity (body mass index 30-40 kg m-2) that are 45-65 years of age, postmenopausal and sedentary. RESULTS AND CONCLUSIONS: This paper is intended as a resource for researchers and/or clinicians to illustrate how theoretical values based on a hypothesis can be translated into a dietary weight loss intervention to be used in free-living women of varying sizes.

The determinants of glycemic responses to diet restriction and weight loss in obesity and NIDDM.

OBJECTIVE: To examine the mechanisms by which weight loss improves glycemic control in overweight subjects with NIDDM, particularly the relationships between energy restriction, improvement in insulin sensitivity, and regional and overall adipose tissue loss. RESEARCH DESIGN AND METHODS: Hyperinsulinemic glucose clamps were performed in 20 subjects (BMI = 32.0 +/- 0.5 [SEM] kg/m2, age = 48.4 +/- 2.7 years) with normal glucose tolerance (NGT) (n = 10) or mild NIDDM (n = 10) before and on the 4th (d4) and 28th (d28) days of a reduced-energy (1,100 +/- 250 [SD] kcal/day) formula diet. Body composition changes were assessed by dual energy x-ray absorptiometry and insulin secretory changes were measured by insulin response to intravenous glucose before and after weight loss. RESULTS: In both groups, energy restriction (d4) reduced fasting plasma glucose (FPG) (delta FPG: NGT = -0.4 +/- 0.2 mmol/l and NIDDM = -1.1 +/- 0.03 mmol/l, P = 0.002), which was independently related to reduced carbohydrate intake (partial r = 0.64, P = 0.003). There was a marked d4 increase in percent of insulin suppression of hepatic glucose output (HGO) in both groups (delta HGO suppression: NGT = 28 +/- 15% and NIDDM = 32 +/- 8%, P = 0.002). By d28, with 6.3 +/- 0.4 kg weight loss, FPG was further reduced (d4 vs. d28) in NIDDM only (P = 0.05), and insulin sensitivity increased in both groups (P = 0.02). Only loss of abdominal fat related to improvements in FPG (r = 0.51, P = 0.03) and insulin sensitivity after weight loss (r = 0.48, P = 0.05). In contrast to insulin action, there were only small changes in insulin secretion. CONCLUSIONS: Both energy restriction and weight loss have beneficial effects on insulin action and glycemic control in obesity and mild NIDDM. The effect of energy restriction is related to changes in individual macronutrients, whereas weight loss effects relate to changes in abdominal fat.

Beneficial effect on average lipid levels from energy restriction and fat loss in obese individuals with or without type 2 diabetes.

OBJECTIVE: The risk of cardiovascular disease in type 2 diabetes is greater than is accounted for by conventional risk factors. We investigated whether energy restriction or modest fat loss improved the lipid profile in obese subjects with and without type 2 diabetes. The relationship of site of adipose tissue loss to lipid changes was also examined. RESEARCH DESIGN AND METHODS: Lipid levels were measured in 18 subjects with normal glucose tolerance (NGT) (n = 9, BMI = 31.5 +/- 0.8 [SEM] kg/m2) or type 2 diabetes (n = 9, BMI = 31.8 +/- 0.7) before and on the 4th (d4) and 28th (d28) days of a hypocaloric formula diet. Body composition was assessed with dual energy X-ray absorptiometry on d0 and d28. RESULTS: Mean daily energy intake during the diet was 1,100 +/- 60 kcal (33% protein, 38% carbohydrate, and 29% fat). Mean weight loss was 6.2 +/- 0.4 kg. Initial lipid profiles were similar in subjects with or without diabetes, and diabetes did not affect the responses. Dietary intervention resulted in early (d4) and late (d28) changes. Energy restriction (d4) reduced VLDL cholesterol and total triglyceride (TG) concentrations and increased LDL particle size. LDL TG, and LDL apolipoprotein B (apoB) concentrations. Reduction in central abdominal fat (but not other body fat) was correlated with a less atherogenic lipid profile: delta abdominal fat versus delta LDL free cholesterol, r = 0.65, P = 0.006 and versus delta apoB, r = 0.64, P = 0.008. CONCLUSIONS: Even in obese subjects with an average lipid profile, modest weight loss reduces atherogenicity, independently of type 2 diabetes, and abdominal fat loss is specifically related to such improvements.

Do ketogenic diets really suppress appetite? A systematic review and meta-analysis.

Very-low-energy diets (VLEDs) and ketogenic low-carbohydrate diets (KLCDs) are two dietary strategies that have been associated with a suppression of appetite. However, the results of clinical trials investigating the effect of ketogenic diets on appetite are inconsistent. To evaluate quantitatively the effect of ketogenic diets on subjective appetite ratings, we conducted a systematic literature search and meta-analysis of studies that assessed appetite with visual analogue scales before (in energy balance) and during (while in ketosis) adherence to VLED or KLCD. Individuals were less hungry and exhibited greater fullness/satiety while adhering to VLED, and individuals adhering to KLCD were less hungry and had a reduced desire to eat. Although these absolute changes in appetite were small, they occurred within the context of energy restriction, which is known to increase appetite in obese people. Thus, the clinical benefit of a ketogenic diet is in preventing an increase in appetite, despite weight loss, although individuals may indeed feel slightly less hungry (or more full or satisfied). Ketosis appears to provide a plausible explanation for this suppression of appetite. Future studies should investigate the minimum level of ketosis required to achieve appetite suppression during ketogenic weight loss diets, as this could enable inclusion of a greater variety of healthy carbohydrate-containing foods into the diet.

The effects of high-fat feeding on physical function and skeletal muscle extracellular matrix.

Skeletal muscle extracellular matrix (ECM) remodelling has been proposed as a feature of the pathogenic milieu associated with obesity and metabolic dysfunction. Whether muscle ECM is associated with impaired physical function in obese conditions is unknown. C57BL/6 mice were fed a high-fat diet (HFD) or chow for 5, 10 and 25 weeks. Non-invasive physiological tests (hang wire, hang mesh and grip strength) to assess neuromuscular function and motor co-ordination were performed. Genes related to ECM structure (COL1, COL3, COL6A2, SPARC), growth factors (TGFB1, TGFB2, CTGF, VEGF) and muscle function (DMD (Dp147), CPN3, DAG1) were measured in gastrocnemius muscle using real-time PCR and COL1, 3 and 6 protein were measured by western immunoblot. Compared with chow, HFD mice had two to six-fold lower muscle strength (hang wire test; raw data and multiplied by body weight) at all time-points (P<0.001) and two-fold lower hang mesh and grip strength at 10 weeks (P<0.05). At 5 weeks, COL1, COL3 and COL6 gene expression, but not protein levels were three to eight-fold lower in HFD compared with chow. In the HFD group at 5 weeks, greater COL3 and 6 gene expression were associated with poorer hang wire performance. For the first time, our results demonstrate links between muscle ECM structure and physical function in obesity.

Carbohydrate intake and short-term regulation of leptin in humans.

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.

Importance of early insulin levels on prandial glycaemic responses and thermogenesis in non-insulin-dependent diabetes mellitus.

To examine the effect of different profiles of insulin administration on glycaemia and thermogenesis, we studied 10 subjects with mild non-insulin-dependent diabetes mellitus on four occasions after a standard mixed meal: (1) with no supplementary insulin (control), (2) with intravenous insulin (1.8U over 15 min = short), (3) as for short but extended over 30 min to simulate the normal initial rise in portal vein insulin levels (medium), (4) as for medium with additional insulin to normalize the profile from 30-60 min (3.6U over 60 min, long). All studies in which supplemental insulin was administered lowered the integrated glucose response above baseline versus the control study (short 76%, medium 71%, and long 56% of control, p = 0.003). The insulin infusions also increased the non-protein respiratory quotient in the first hour following the meal (0.82 +/- 0.01 (control) vs 0.87 +/- 0.01 (short), 0.86 +/- 0.01 (medium) and 0.87 +/- 0.01 (long), p = 0.003) and augmented thermogenesis (7.6 +/- 1.5 (control) vs 10.5 +/- 2.9 (short), 13.0 +/- 1.9 (medium) and 13.2 +/- 2.8% (long), p = 0.02). Total integrated insulin area above baseline was significantly greater in the long study (short 121, medium 111 vs long 179% of control, p = 0.02). Thus the greatest glycaemic benefit in relation to insulinaemia was obtained with the two shorter insulin infusions (short and medium). In conclusion, this study confirms the role of early prandial insulin secretion (or delivery) in limiting prandial glycaemia in NIDDM and increasing thermogenesis and highlights the pivotal role of the timing of elevation of insulin levels in modulating hyperglycaemia and hyperinsulinaemia.

Fat oxidation, body composition and insulin sensitivity in diabetic and normoglycaemic obese adults 5 years after weight loss.

OBJECTIVE: To investigate whether normal glucose-tolerant and type II diabetic overweight adults differ in response to weight regain with regard to substrate oxidation and metabolic parameters. METHODS: A total of 15 overweight-obese subjects: seven normal glucose tolerant (NGT) and eight with type II diabetes (DM) were restudied 5 y after significant weight loss. Prediet, after 28 days calorie restriction and at 5 y, subjects were characterised for weight, height, waist-to-hip ratio (WHR) and body composition by dual-energy X-ray absorptiometry. Fasting glucose, insulin, leptin and lipid levels were measured and subjects underwent euglycaemic-hyperinsulinaemic clamp (insulin 0.25 U/kg/h for 150 min). Indirect calorimetry was performed resting and in the final 30 min of the clamp. Dietary assessment was by 4-day diet-diary. RESULTS: Both NGT and DM groups regained weight at 5 y and were not different to prediet. Total body fat (%) and WHR were higher at 5 y compared to prediet in both groups. Fasting glucose was increased in NGT subjects at 5 y, and fasting insulin was higher in both groups at 5 y compared to prediet. Insulin sensitivity (GIR) was similar at 5 y compared to prediet, but at 5 y DM subjects were more insulin resistant than NGT subjects. At 5 y, both DM and NGT groups had significantly reduced basal fat oxidation and no significant suppression of fat oxidation with insulin. Clamp respiratory quotient levels at 5 y were significantly higher in NGT compared to DM subjects. CONCLUSION: Reduced basal fat oxidation, and reduced variation in substrate oxidation in response to insulin develop with fat regain and fasting hyperinsulinaemia in both NGT and DM obese adults.