Unsupervised Exercise Training Was Not Found to Improve the Metabolic Health or Phenotype over a 6-Month Dietary Intervention: A Randomised Controlled Trial with an Embedded Economic Analysis

Abstract Ectopic fat leads to metabolic health problems. This research aimed to assess the effectiveness of a hypocaloric diet intervention together with an unsupervised exercise training program in comparison with a hypocaloric diet alone to reduce ectopic fat deposition. Sixty-one premenopausal women with overweight or obesity participated in this controlled trial and were each randomised into either a usual care group (hypocaloric diet) or intervention group (hypocaloric diet + unsupervised exercise training). Ectopic fat deposition, metabolic parameters, incremental costs from a societal perspective and incremental quality-adjusted life years (QALYs) were assessed before, during and after the six-month intervention period. In the total sample, there was a significant decrease in visceral adipose tissue (VAT: -18.88 cm2, 95% CI -11.82 to -25.95), subcutaneous abdominal adipose tissue (SAT: -46.74 cm2, 95% CI -29.76 to -63.18), epicardial fat (ECF: -14.50 cm3, 95% CI -10.9 to -18.98) and intrahepatic lipid content (IHL: -3.53%, 95% CI -1.72 to -5.32). Consequently, an "adapted" economic analysis revealed a non-significant decrease in costs and an increase in QALYs after the intervention. No significant differences were found between groups. A multidisciplinary lifestyle approach seems successful in reducing ectopic fat deposition and improving the metabolic risk profile in women with overweight and obesity. The addition of unsupervised exercise training did not further improve the metabolic health or phenotype over the six months. Keywords: body fat distribution; ectopic fat; exercise; overweight

Unsupervised Exercise Training Was Not Found to Improve the Metabolic Health or Phenotype over a 6-Month Dietary Intervention: A Randomised Controlled Trial with an Embedded Economic Analysis

Abstract Ectopic fat leads to metabolic health problems. This research aimed to assess the effectiveness of a hypocaloric diet intervention together with an unsupervised exercise training program in comparison with a hypocaloric diet alone to reduce ectopic fat deposition. Sixty-one premenopausal women with overweight or obesity participated in this controlled trial and were each randomised into either a usual care group (hypocaloric diet) or intervention group (hypocaloric diet + unsupervised exercise training). Ectopic fat deposition, metabolic parameters, incremental costs from a societal perspective and incremental quality-adjusted life years (QALYs) were assessed before, during and after the six-month intervention period. In the total sample, there was a significant decrease in visceral adipose tissue (VAT: -18.88 cm2, 95% CI -11.82 to -25.95), subcutaneous abdominal adipose tissue (SAT: -46.74 cm2, 95% CI -29.76 to -63.18), epicardial fat (ECF: -14.50 cm3, 95% CI -10.9 to -18.98) and intrahepatic lipid content (IHL: -3.53%, 95% CI -1.72 to -5.32). Consequently, an "adapted" economic analysis revealed a non-significant decrease in costs and an increase in QALYs after the intervention. No significant differences were found between groups. A multidisciplinary lifestyle approach seems successful in reducing ectopic fat deposition and improving the metabolic risk profile in women with overweight and obesity. The addition of unsupervised exercise training did not further improve the metabolic health or phenotype over the six months. Keywords: body fat distribution; ectopic fat; exercise; overweight

Weight loss and ethnicity: a cohort study of the effects induced by a very low calorie diet.

We aimed to determine whether British Asians of Indian or Pakistani descent differed in their baseline characteristics and in response to a twelve-week, very-low-calorie diet (VLCD). We then assessed whether or not a VLCD had a different effect on Asians and Caucasians, in terms of changes in weight and waist circumference. Weight loss was achieved using a nutritionally-complete VLCD with an average daily intake of 550kcal, using greater than or equal to 50g protein, greater than or equal to 50g carbohydrate, mean 15.9g fats, and greater than or equal to 100% of the recommended daily allowances (RDA) for key vitamins and minerals. The VLCD was used alongside a unique behaviour-change programme, called LighterLife (LL). Data were analysed for Asians who were recruited onto LL in 2009/2010, and for whom twelve-week weight change information was available. Waist circumference data were available for a subset of Asians, including age, body mass index and gender. These were matched to a Caucasian population and compared by independent t-test. No differences were observed between the Indian and Pakistani group for baseline measurements or weight change at twelve weeks. Caucasians had a greater percent excess body weight loss (%EBWL) than Asians at twelve weeks (72.4 ± 22.1 vs 48.9 ± 18.0, p < 0.0001). However, Asians had a greater waist circumference reduction per kilogram of weight loss when compared to Caucasians (1.16 ± 0.7 vs 0.95 ± 0.3, p = 0.037). It appears that, despite a greater %EBWL for Caucasians, Asians had a greater waist circumference reduction per kilogram of weight loss using a VLCD approach for a twelve-week period

Pasireotide can induce sustained decreases in urinary cortisol and provide clinical benefit in patients with Cushing’s disease: results from an open-ended, open-label extension trial

International audiencePurpose Report the efficacy and safety of pasireotide sc in patients with Cushing's disease during an open-ended, open-label extension to a randomized, double-blind, 12-month, Phase III study. Methods 162 patients entered the core study. 58 patients who had mean UFC B ULN at month 12 or were bene-fiting clinically from pasireotide entered the extension. Patients received the same dose of pasireotide as at the end of the core study (300–1,200 lg bid). Dose titration was permitted according to efficacy or drug-related adverse events. Results 40 patients completed 24 months' treatment. Of the patients who entered the extension, 50.0 % (29/58) and 34.5 % (20/58) had controlled UFC (UFC B ULN) at months 12 and 24, respectively. The mean percentage decrease in UFC was 57.3 % (95 % CI 40.7–73.9; n = 52) and 62.1 % (50.8–73.5; n = 33) after 12 and 24 months' treatment, respectively. Improvements in clinical signs of Cushing's disease were sustained up to month 24. The most frequent drug-related adverse events in patients who received C1 dose of pasireotide (n = 162) from core baseline until the 24-month cut-off were diarrhea (55.6 %), nausea (48.1 %), hyperglycemia (38.9 %), and cholelithi-asis (31.5 %). No new safety issues were identified during the extension. Conclusions Reductions in mean UFC and improvements in clinical signs of Cushing's disease were maintained over 24 months of pasireotide treatment. The safety profile of pasireotide is typical for a somatostatin analogue, except for the frequency and degree of hyperglycemia; patients should be monitored for changes in glucose homeostasis. Pasireotide represents the first approved pituitary-targeted treatment for patients with Cushing's disease.-1) contains supplementary material, which is available to authorized users

Echocardiographic Evidence for Valvular Toxicity of Benfluorex: A Double-Blind Randomised Trial in Patients with Type 2 Diabetes Mellitus

OBJECTIVES: REGULATE trial was designed to compare the efficacy and safety of benfluorex versus pioglitazone in type 2 diabetes mellitus (DM) patients. METHODS: Double-blind, parallel-group, international, randomised, non-inferiority trial. More than half of the 196 participating centres were primary care centres. Patients eligible had type 2 DM uncontrolled on sulfonylurea. 846 were randomised. They received study treatment for 1 year. 423 patients were allocated to benfluorex (150 to 450 mg/day) and 423 were allocated to pioglitazone (30 to 45 mg/day). Primary efficacy criterion was HbA(1c). Safety assessment included blinded echocardiographic evaluation of cardiac and valvular status. RESULTS: At baseline, patients were 59.1 ± 10.5 years old with HbA1c 8.3 ± 0.8%, and DM duration 7.1 ± 6.0 years. During the study, mean HbA1c significantly decreased in both groups (benfluorex: from 8.30 ± 0.80 to 7.77 ± 1.31 versus pioglitazone: from 8.30 ± 0.80 to 7.45 ± 1.30%). The last HbA1c value was significantly lower with pioglitazone than with benfluorex (p<0.001) and non-inferiority of benfluorex was not confirmed (p = 0.19). Among the 615 patients with assessable paired echocardiography (310 benfluorex, 305 pioglitazone), 314 (51%) had at least one morphological valvular abnormality and 515 (84%) at least one functional valvular abnormality at baseline. Emergent morphological abnormalities occurred in 8 patients with benfluorex versus 4 with pioglitazone (OR 1.99), 95% CI (0.59 to 6.69). Emergent regurgitation (new or increased by one grade or more) occurred more frequently with benfluorex (82 patients, 27%) than with pioglitazone (33 patients, 11%) (OR 2.97), 95% CI (1.91 to 4.63) and were mainly rated grade 1; grade 2 (mild) was detected in 2 patients with benfluorex and 3 with pioglitazone. There was no moderate or severe regurgitation. CONCLUSION: After 1 year of exposure, our results show a 2.97 fold increase in the incidence of valvular regurgitation with benfluorex and provide evidence for the valvular toxicity of this drug

Insulin therapy in people with type 2 diabetes:opportunities and challenges?

Given the continued interest in defining the optimal management of individuals with type 2 diabetes, the Editor of Diabetes Care convened a working party of diabetes specialists to examine this topic in the context of insulin therapy. This was prompted by recent new evidence on the use of insulin in such people. The group was aware of evidence that the benefits of insulin therapy are still usually offered late, and thus the aim of the discussion was how to define the optimal timing and basis for decisions regarding insulin and to apply these concepts in practice. It was noted that recent evidence had built upon that of the previous decades, together confirming the benefits and safety of insulin therapy, albeit with concerns about the potential for hypoglycemia and gain in body weight. Insulin offers a unique ability to control hyperglycemia, being used from the time of diagnosis in some circumstances, when metabolic control is disturbed by medical illness, procedures, or therapy, as well as in the longer term in ambulatory care. For those previously starting insulin, various other forms of therapy can be added later, which offer complementary effects appropriate to individual needs. Here we review current evidence and circumstances in which insulin can be used, consider individualized choices of alternatives and combination regimens, and offer some guidance on personalized targets and tactics for glycemic control in type 2 diabetes

Visceral, subcutaneous abdominal adiposity and liver fat content distribution in normal glucose tolerance, impaired fasting glucose and/or impaired glucose tolerance

Q1Q1Objectives: To examine the specific distribution of liver fat content, visceral and subcutaneous adiposity in normal glucose tolerance (NGT/NGT), isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT) and combined conditions (IFG+IGT), as well as with newly diagnosed type 2 diabetes (nT2D). Design: Multicenter, international observational study: cross-sectional analysis. Subjects: Two thousand five hundred and fifteen patients (50.0% women, 54.5% non-Caucasian) without previously known diabetes were recruited from 29 countries. Abdominal fat distribution was measured by computed tomography (CT). Liver fat was estimated using the CT-liver mean attenuation. Results: Compared with NGT/NGT patients, increased visceral adiposity was found in iIFG, iIGT, IFG+IGT and nT2D; estimated liver fat progressively increased across these conditions. A one-s.d. increase in visceral adiposity was associated with an increased risk of having iIFG (men: odds ratio (OR) 1.41 (95% confidence interval (CI) 1.15–1.74), women: OR 1.62 (1.29–2.04)), iIGT (men: OR 1.59 (1.15–2.01), women: OR 1.30 (0.96–1.76)), IFG+IGT (men: OR 1.64 (1.27–2.13), women: OR 1.83 (1.36–2.48)) and nT2D (men: OR 1.80 (1.35–2.42), women: OR 1.73 (1.25–2.41)). A one-s.d. increase in estimated liver fat was associated with iIGT (men: OR 1.46 (1.12–1.90), women: OR 1.81 (1.41–2.35)), IFG+IGT (men: OR 1.42 (1.14–1.77), women: OR 1.74 (1.35–2.26)) and nT2D (men: OR 1.77 (1.40–2.27), women: OR 2.38 (1.81–3.18)). Subcutaneous abdominal adipose tissue showed an inverse relationship with nT2D in women (OR 0.63 (0.45–0.88)). Conclusions: Liver fat was associated with iIGT but not with iIFG, whereas visceral adiposity was associated with both. Liver fat and visceral adiposity were associated with nT2D, whereas subcutaneous adiposity showed an inverse relationship with nT2D in women