Explore the vast range of titles available.

Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability. Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT. There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT. FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.

Oded Bar-Or (deceased), Professor Emeritus of Pediatrics, McMaster University, and Director of the Children's Exercise and Nutrition Centre, Chedoke Hospital, Hamilton Health Sciences, Hamilton, Ont.; Daniel Birch, Associate Professor, Department of Surgery, University of Alberta, Edmonton, Alta.; Simon Biron, Professor of Surgery and Director, General Surgery Division, Laval University, and Head, Department of Surgery, Laval Hospital, Laval, Que.; Robert R.M. Dent, Director, Weight Management Clinic, Ottawa Hospital, Ottawa, Ont.; [Jean-Pierre Chanoine] Després, Chair and Professor of Human Nutrition, Department of Sciences of Food and Nutrition, Laval University, and Director of Research, Cardiology, Québec Heart Institute, Laval Hospital Research Centre, Sainte-Foy, Que.; Denis Drouin, Clinical Professor of Family Medicine, Faculty of Medicine, Laval University, Québec, Que.; Diane T. Finegood, Scientific Director, Canadian Institutes of Health Research Institute of Nutrition, Metabolism and Diabetes, and Professor of Kinesiology, School of Kinesiology, Simon Fraser University, Bumaby, BC; Dominique R. Carrel, Professor of Medicine and Director, Department of Nutrition, Université de Montréal, Hôtel-Dieu - Centre hospitalier de l'Université de Montréal, Montréal, Que.; Linda Gillis, Children's Exercise and Nutrition Centre, McMaster Children's Hospital, Hamilton, Ont.; Michael Grace, Professor Emeritus of Surgery, University of Western Ontario, London, Ont.; Rhona Hanning, Associate Professor, Department of Health Studies and Gerontology, Faculty of Applied Health Sciences, University of Waterloo, Waterloo, Ont.; Peter T. Katzmarzyk, Associate Professor, School of Kinesiology and Health Studies and Department of Community Health and Epidemiology, Queen's University. Kingston, Ont.; Claire LeBlanc, Associate Professor of Pediatrics, University of Ottawa, Children's Hospital of Eastern Ontario. Ottawa, Ont.; Lawrence A. Leiter, Professor of Medicine and Nutritional Sciences, University of Toronto, and Head, Division of Endocrinology and Metabolism, St. Michael's Hospital, Toronto, Ont.; Rena Mendelson, Professor of Nutrition, Department of Nutritional Sciences, Ryerson University, Toronto, Ont.; Linda McCargar, Professor, Department of Agriculture, Food and Nutritional Science, Faculty of Agriculture, Forestry and Home Economics, and Director, Human Nutrition Research Centre, University of Alberta, Edmonton, Alta.; Terri L Paul, Assistant Professor of Medicine, University of Western Ontario, and endocrinologist, St. Joseph's Health Centre, London, Ont.; Denis Prud'homme, Dean, Faculty of Health Sciences, University of Ottawa, and Behavioural and Metabolic Research Unit, Montfort Hospital, Ottawa, Ont.; Kim Raine, Director and Professor, Centre for Health Promotion Studies, University of Alberta, Edmonton, Alta.; Bruce A. Reeder, Professor and Head, Department of Community Health and Epidemiology, University of Saskatchewan, and staff, Department of Family Medicine, Royal University Hospital, Saskatoon, Sask.; Elizabeth A.C. Sellers, Assistant Professor of Pediatrics and Child Health, section of Pediatric Endocrinology, University of Manitoba, Winnipeg Children's Hospital, Winnipeg, Man.; Mark S. Tremblay, Professor, College of Kinesiology, University of Saskatchewan, and Senior Scientific Director on Health Measurement, Statistics Canada, Ottawa, Ont.; Michael VaIKs, Associate Professor of Psychology, Dalhousie University, and psychologist, Queen Elizabeth Il Health Sciences Centre, Halifax, NS; Vlvienne A. Vance, Department of Health Studies and Gerontology, Faculty of Applied Health Sciences, University of Waterloo, Waterloo, Ont.; Elinor Wilson, Chief Executive Officer, Canadian Public Health Association, Ottawa, Ont.

Background The SUSTAIN 6 trial demonstrated that once-weekly semaglutide (0.5 and 1.0 mg) significantly reduced major adverse cardiovascular (CV) events (MACE) vs placebo in subjects with type 2 diabetes (T2D) and high CV risk. The effects of gender, age and baseline CV risk on outcomes are important considerations for further study. Methods Subjects were grouped according to gender, age (50–65 years and > 65 years), and CV risk profile at baseline (prior myocardial infarction [MI] or stroke vs no prior MI or stroke, and established CV disease [CVD] vs CV risk factors alone, including subjects with chronic kidney disease). Time to MACE and its individual components (CV death, nonfatal MI, nonfatal stroke), hospitalization for unstable angina or heart failure, and revascularization (coronary and peripheral) were analyzed for all subgroups. Additional analyses were performed for gender and age to investigate change from baseline in HbA 1c and body weight, as well as tolerability. Results A total of 3297 subjects were included. The majority of subjects (60.7%) were male; 43% were > 65 years of age; 41.5% had a history of MI or stroke; and 76.8% had established CVD. Compared with placebo, semaglutide reduced the risk of the first occurrence of MACE and each MACE component consistently across all subgroups (gender, age, and baseline CV risk profile). Revascularizations, HbA 1c and body weight were also reduced consistently across all subgroups compared with placebo. Gastrointestinal adverse events in all treatment groups were more common among women than men, but rates of premature treatment discontinuation were similar for both genders. Conclusions In this post hoc analysis of SUSTAIN 6, once-weekly semaglutide vs placebo reduced the risk of MACE in all subjects included in the trial, regardless of gender, age, or baseline CV risk profile. Trial registry Clinicaltrials.gov, Identifying number: NCT01720446, Date of registration: October 29, 2012

Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people with type 2 diabetes. ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high HbA 1c concentrations (>7·5%), and cardiovascular disease (or ≥2 cardiovascular risk factors) were randomly assigned by central randomisation to intensive (target haemoglobin A 1c [HbA 1c] of <6·0%) or standard (7·0–7·9%) glycaemic therapy. In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291·7 μmol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or compliance to therapies. ACCORD is registered with ClinicalTrials.gov, number NCT00000620. 10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the standard group (HR 1·00, 95% CI 0·88–1·14; p=1·00), and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 (0·96, 0·89–1·02; p=0·19). Results were similar at study end (first composite outcome 556 of 5119 vs 586 of 5115 [HR 0·95, 95% CI 0·85–1·07, p=0·42]; and second 1956 of 5119 vs 2046 of 5115, respectively [0·95, 0·89–1·01, p=0·12]). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of albuminuria and some measures of eye complications and neuropathy. Six secondary measures at study end favoured intensive therapy (p<0·05). Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycaemia. US National Institutes of Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; and General Clinical Research Centers.

Over the last decade, several new antihyperglycemic medications have been introduced including those associated with a lower hypoglycemia risk. We aimed to investigate how these medications are being prescribed to older adults in our region. We conducted population-based cross-sectional analyses of older adults (mean age 75 years) with treated diabetes in Ontario, Canada from 2002 until 2013, to examine the percentage prescribed insulin, sulphonylureas, alpha-glucosidase inhibitors, metformin, thiazolidinediones, meglitinides, and dipeptidyl peptidase-4 inhibitors. Over the study period, we also examined their hospital encounters for hypoglycemia (emergency room or inpatient encounter). The mean age of treated patients increased slightly over the study quarters and the proportion that were women declined. With the exception of chronic kidney disease, cancer, dementia, and neuropathy, the percentage with a comorbidity appeared to decline. The percentage of treated patients prescribed metformin, gliclazide and dipeptidyl peptidase-4 inhibitors increased as did combination therapy. Glyburide and thiazolidinedione prescriptions declined, and insulin use remained stable. In those with newly treated diabetes, the majority were prescribed metformin, with smaller percentages prescribed insulin and other oral agents. Although the absolute number of treated patients with a hypoglycemia encounter increased until mid-2006 and then decreased, the overall percentage with an encounter declined over the study period (0.8% with an event in the first quarter, 0.4% with an event in the last quarter). Antihyperglycemic medications with safer profiles are being increasingly prescribed to older adults. In this setting there has been a decrease in the percentage of treated patients with a hospital encounter for hypoglycemia.

IntroductionSuboptimal screening for diabetic eye disease is a major cause of preventable vision loss. Screening barriers include mydriasis and the extra time patients need to attend dedicated eye screening appointments. In the Clearsight trial, we are testing whether screening by non-mydriatic ultra-wide field (NM UWF) imaging on the day patients attend their diabetes outpatient clinic visit improves detection of clinically important eye disease compared with usual screening.Methods and analysisPatients with diabetes due for a screening eye exam by the 2013 Canadian Diabetes Association (CDA) practice guidelines are being randomised to on-site screening by NM UWF imaging on the day of their clinic visit or to usual screening where, per CDA guidelines, they are encouraged to arrange an exam by an optometrist. The primary outcome is actionable eye disease (AED) based on a need for referral to ophthalmology and/or increased ocular surveillance. The primary analysis will use an intention-to-screen approach that compares the proportions of detected AED between on-site and usual screening groups under a superiority hypothesis in favour of on-site screening. With 740 randomised participants, the study will have 80% power to detect ≥5% absolute increase in the AED rate among on-site screening versus usual screening participants. This difference translates into a number-needed-to-screen by on-site screening of 20 to detect 1 additional person with AED.Ethics and disseminationThe protocol was approved by the institutional review board of Western University. The findings of the trial will be disseminated directly to participants and through peer-reviewed publications and conference presentations.Trial registration numberClinicalTrials.Gov NCT02579837 (registered 16 October 2015).Protocol issue date18 November 2015.

Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability. Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT. There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT. FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.

Improving adherence to insulin treatment for better glycemic control remains a challenge in the management of diabetes. New technological aids are required to help support adherence. This study evaluated preference for the NovoPen(®) 5 (NP5), a durable insulin pen with memory function, compared with the HumaPen Luxura(®) (HPL) among patients with diabetes and health care professionals. This crossover, multicenter usability study included insulin pen-experienced patients with diabetes and health care professionals treating patients with diabetes in Canada, China, and Germany. Participants evaluated NP5 and HPL in a randomized order by performing handling tasks in a usability test related to everyday use during a face-to-face interview. Tasks, pens, and preferences were assessed by completing a questionnaire comprised of rating and open-ended questions relating to confidence in everyday diabetes management. Overall, 300 patients with diabetes and 150 health care professionals participated in the study. Significantly more participants preferred NP5 (81%) to HPL (18%) (P < 0.001). Also, 82% of patients with diabetes had more confidence in NP5 for managing their daily injections versus 11% with HPL (P < 0.001), and 7% had no preference. Memory function was most helpful in giving patients with diabetes confidence about when they last injected (63%), how much insulin they last injected (62%) and improving diabetes management (55%). Participants gave higher ratings to NP5 than to HPL on all parameters relating to performing an injection (ease of handling, satisfaction when using the pen, convenience of using the pen day-to-day, quality of the pen, and the extent to which the pen meets their needs; P < 0.05 for all comparisons). NP5 was preferred to HPL by most participants. Significantly more patients with diabetes had more confidence for managing daily insulin injections when using NP5, the pen with a memory function.

The addition of sitagliptin to usual care in patients with type 2 diabetes and cardiovascular disease was not associated with any change in the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events. Good glycemic control among patients with type 2 diabetes reduces the risk of diabetes-related microvascular complications. 1 – 3 Many antihyperglycemic agents are licensed for the treatment of type 2 diabetes, but questions regarding the long-term cardiovascular safety of some of these agents have been raised. 4 , 5 International regulatory agencies have responded by requiring that new antihyperglycemic agents not only show glucose-lowering ability but also are not associated with clinically meaningful increases in rates of major adverse cardiovascular events. 6 , 7 Sitagliptin, an orally administered dipeptidyl peptidase 4 (DPP-4) inhibitor, prolongs the action of incretin hormones, including glucagon-like peptide 1 and glucose-dependent insulinotropic . . .

Abstract Objective To examine diabetes remission following a short-term intensive metabolic intervention combining lifestyle and glucose-lowering approaches. Methods We conducted an open-label, randomized controlled trial in 154 patients with type 2 diabetes up to 8 years in duration on 0 to 2 glucose-lowering medications. Participants were randomized to (a) a 12-week intensive intervention comprising lifestyle approaches and treatment with insulin glargine, metformin, and dapagliflozin or (b) standard diabetes care. At 12 weeks, diabetes medications were discontinued in participants with hemoglobin A1c (HbA1C) < 7.3% (56 mmol/mol). Participants were then followed for diabetes relapse until 64 weeks. The primary outcome was complete or partial diabetes remission (HbA1C < 6.5% [48 mmol/mol] off chronic diabetes drugs) at 24 weeks. Main secondary outcomes were complete or partial diabetes remission at 36, 48, and 64 weeks. Results The primary outcome was achieved in 19 (24.7%) intervention group participants and 13 (16.9%) control group participants at 24 weeks (relative risk [RR] 1.5; 95% confidence interval [CI], 0.8-2.7). The relative risks of remission at 36, 48, and 64 weeks were 2.4 (95% CI, 1.2-5.0), 2.1 (95% CI, 1.0-4.4), and 1.8 (95% CI, 0.7-4.7), respectively. In an exploratory analysis, the intervention reduced the hazard of diabetes relapse with overt hyperglycemia by 43% (hazard ratio 0.57; 95% CI, 0.39-0.81). Conclusions Our primary outcome of diabetes remission at 24 weeks was not statistically significantly different. However, our overall results suggest that some patients with early type 2 diabetes are able to achieve sustained diabetes remission following a short-term intensive intervention. Further studies are needed to optimize the combined therapeutic approach used.