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Summary In rodents, lower brown adipose tissue (BAT) activity is associated with greater liver steatosis and changes in the gut microbiome. However, little is known about these relationships in humans. In adults (n = 60), we assessed hepatic fat and cold-stimulated BAT activity using magnetic resonance imaging and the gut microbiota with 16S sequencing. We transplanted gnotobiotic mice with feces from humans to assess the transferability of BAT activity through the microbiota. Individuals with NAFLD (n = 29) have lower BAT activity than those without, and BAT activity is inversely related to hepatic fat content. BAT activity is not related to the characteristics of the fecal microbiota and is not transmissible through fecal transplantation to mice. Thus, low BAT activity is associated with higher hepatic fat accumulation in human adults, but this does not appear to have been mediated through the gut microbiota., Graphical abstract, Highlights Adults with NAFLD have lower brown adipose tissue activity compared with controls Brown adipose tissue (BAT) activity is not linked to fecal gut microbiota BAT activity is not transmissible to mice via fecal transplantation, Ahmed et al. show, using MRI, that higher cold-stimulated BAT activity is linked to lower hepatic fat in 60 adults. BAT activity is not linked to fecal gut microbiota characteristics and is not transmissible to germ-free mice. Gut microbiota does not link BAT activity and liver fat.

Context In rodents, cold exposure induces the activation of brown adipose tissue (BAT) and the induction of intracellular triacylglycerol (TAG) lipolysis. However, in humans, the kinetics of supraclavicular (SCV) BAT activation and the potential importance of TAG stores remain poorly defined. Objective To determine the time course of BAT activation and changes in intracellular TAG using MRI assessment of the SCV (i.e., BAT depot) and fat in the posterior neck region (i.e., non-BAT). Design Cross-sectional. Setting Clinical research center. Patients or Other Participants Twelve healthy male volunteers aged 18 to 29 years [body mass index = 24.7 ± 2.8 kg/m2 and body fat percentage = 25.0% ± 7.4% (both, mean ± SD)]. Intervention(s) Standardized whole-body cold exposure (180 minutes at 18°C) and immediate rewarming (30 minutes at 32°C). Main Outcome Measure(s) Proton density fat fraction (PDFF) and T2* of the SCV and posterior neck fat pads. Acquisitions occurred at 5- to 15-minute intervals during cooling and subsequent warming. Results SCV PDFF declined significantly after only 10 minutes of cold exposure [−1.6% (SE: 0.44%; P = 0.007)] and continued to decline until 35 minutes, after which time it remained stable until 180 minutes. A similar time course was also observed for SCV T2*. In the posterior neck fat (non-BAT), there were no cold-induced changes in PDFF or T2*. Rewarming did not result in a change in SCV PDFF or T2*. Conclusions The rapid cold-induced decline in SCV PDFF suggests that in humans BAT is activated quickly in response to cold and that TAG is a primary substrate.

Background: Diabetes remission due to non-surgical approaches has not been well studied. We investigated induction of diabetes remission following a short-term treatment with insulin glargine, lixisenatide and metformin and changes in exercise and dietary behaviours. Methods: We randomized 160 individuals with type 2 diabetes to (i) 12-week intensive treatment with insulin glargine, lixisenatide, metformin and lifestyle approaches or (ii) standard glycemic management. At 12 weeks, diabetes medications were stopped in patients with HbA1C Results: The intervention significantly reduced the hazard of diabetes relapse (HR 0.57, 95% CI 0.40-0.81; p=0.002). The proportion of participants with diabetes remission was significantly higher in the intervention group compared to the control group at 24 weeks (38% vs. 20%; relative risk RR 1.92 (1.14-3.24)) and at 36 weeks (32% vs. 17%; RR 1.83 (1.03-3.26)), but not at 48 and 64 weeks (RR 1.88 (1.00-3.53) and 2.05 (0.98-4.29), respectively). Conclusion: Short-term intensive treatment targeting normoglycemia and weight loss with insulin glargine, lixisenatide, metformin and lifestyle changes can induce sustained remission of type 2 diabetes. Disclosure N. Mcinnes: Other Relationship; Self; Merck & Co., Inc., Novo Nordisk, Sanofi. J. Yale: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Novo Nordisk Canada Inc., Sanofi, Research Support; Self; Bayer Inc., Speaker’s Bureau; Self; Dexcom, Inc., Medtronic, Merck & Co., Inc., Omnipod. F. Sultan: Employee; Self; Abbott Diabetes. A. C. Smith: None. R. E. Otto: None. D. Sherifali: None. Y. Liu: None. H. C. Gerstein: Advisory Panel; Self; Novo Nordisk Inc., Pfizer Inc., Sanofi, Consultant; Self; Abbott, Covance Inc., Eli Lilly and Company, Kowa Company, Ltd., Sanofi, Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., DKSH, Eli Lilly and Company, Sanofi, Zuellig, Research Support; Self; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Remit-iglarlixi collaborative group: n/a. S. Hall: None. H. A. Lochnan: Research Support; Self; Novo Nordisk Inc., Sanofi. S. B. Harris: Advisory Panel; Self; Abbott Diabetes, Abvance Therapeutics, HLS Therapeutics Inc., Lilly Diabetes, Novo Nordisk A/S, Consultant; Self; Boehringer Ingelheim (Canada) Ltd., mdBriefCase, Other Relationship; Self; American Diabetes Association, AstraZeneca, Novo Nordisk Canada Inc., Sanofi. Z. Punthakee: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Self; AstraZeneca, Lexicon Pharmaceuticals, Inc., Novo Nordisk. R. J. Sigal: Advisory Panel; Self; Novo Nordisk, Research Support; Self; Lexicon Pharmaceuticals, Inc., Novo Nordisk. I. Hramiak: Advisory Panel; Self; AstraZeneca, Bayer Inc., BI-Lilly Joint Venture (Boehringer Ingelheim and Eli Lilly), Dexcom, Inc., Insulet Corporation, Medtronic, Research Support; Self; Eli Lilly and Company, Novo Nordisk, Sanofi. M. Azharuddin: Consultant; Self; Novo Nordisk Canada Inc. J. F. Liutkus: Advisory Panel; Self; Novo Nordisk Canada Inc., Research Support; Self; Bayer Inc., Boehringer Ingelheim (Canada) Ltd., IQVIA, Kowa Research Institute, Inc., Novo Nordisk Canada Inc., Sanofi, Speaker’s Bureau; Self; Novo Nordisk Canada Inc., Stock/Shareholder; Self; Bayer Inc., Novo Nordisk, Pfizer Inc., Stock/Shareholder; Spouse/Partner; Bayer Inc., Eisai Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Canada Inc., Pfizer Inc. Funding Sanofi

Background A recent randomized controlled trial demonstrated that a community-based, telephone-delivered diabetes health coaching intervention was an effective intervention for improving diabetes management. The purpose of the current study was to determine whether this effective intervention is also cost-effective. Methods An economic evaluation, in the form of a cost-utility analysis (CUA), was used to assess the cost-effectiveness of the coaching intervention from a public payer perspective. All direct medical costs, as well as intervention implementation, were included. The outcome of the CUA was the quality adjusted life year (QALY). Uncertainty of cost-effectiveness results were estimated using non-parametric bootstraps of patient-level costs and QALYs in the coaching and control arms. A cost-effectiveness acceptability curve was used to express this uncertainty as the probability that diabetes health coaching is cost-effective across a range of values of willingness to pay (WTP) thresholds for a QALY. Findings The results show that subjects in the coaching arm incurred higher overall costs (Canadian dollars) compared to the control arm ($1,581 vs. $1,086, respectively) and incurred 0.02 more QALYs. The incremental cost-effectiveness ratio of the diabetes health coaching intervention compared to usual care was found to be $35,129/QALY, with probabilities of 67% and 82% that diabetes health coaching would be cost-effective at a willingness to pay threshold of $50,000 per QALY and $100,000 per QALY, respectively. Interpretation A community-based, telephone-delivered diabetes health coaching intervention is cost-effective. Funding We acknowledge the Canadian Institutes for Health Research for funding the trial.

Objectives: The Conversations and Reactions Around Severe Hypoglycemia cross-sectional study was conducted to better understand the severe hypoglycemia experiences in persons with diabetes (PWD) and their caregivers (CGs). Methods: Adults with type 1 or type 2 diabetes and CGs were recruited in 8 countries; Canadian cohort data are reported in this study. Insulin-treated PWD who reported a severe hypoglycemic event within the past 3 years and CGs who care for PWD ≥4 years old and who met the criteria were eligible for the study. Participants completed an online survey about their experience with severe hypoglycemia, its treatment and actions during and after severe hypoglycemia. Results: Of the 324 respondents, 139 (43%) reported discussions about severe hypoglycemia with a health-care provider (HCP) at every visit. During the most recent severe hypoglycemic event, the most common actions taken included ingestion of oral carbohydrates and calling emergency medical services; glucagon was rarely used. Despite many respondents (67%) feeling scared because of the most recent severe hypoglycemic event, only 55% (51% with type 1 and 61% with type 2) discussed this event with an HCP. The event affected the mood/emotional status, physical activities and sleep of PWD and CGs. Conclusions: Severe hypoglycemia impacts the emotional and physical status of PWD and CGs. Despite this, many respondents did not report discussions about the most recent severe hypoglycemic event with HCPs. Furthermore

IntroductionPersons of South Asian descent have a higher prevalence of type 2 diabetes mellitus (T2DM). The management of T2DM in the South Asian community has required the support of adult children, potentially impacting the quality of life, diabetes-related knowledge, and risk perception among these caregivers.Research design and methodsTo investigate diabetes-related knowledge, quality of life, risk perception, and actual risk of developing diabetes among South Asian young adults whose parents are living with T2DM. A cross-sectional study was conducted (n=150). An online survey was administered. Data were analyzed with descriptive and inferential statistics.ResultsThere was a statistically significant difference in diabetes-related knowledge between males and females (p=0.002).ConclusionFindings highlight the importance of providing gender-specific and culturally tailored diabetes educational interventions.

To evaluate the epidemiology, presentation and management of hypoparathyroidism in Canada. Hypoparathyroidism is associated with significant morbidity and poor quality of life. We present baseline results from the Canadian National Hypoparathyroidism Registry, a prospective observational study evaluating hypoparathyroidism in Canada. Our study enrolled 130 patients with hypoparathyroidism. Patients were followed every 6 months with clinical and lab assessments. We present baseline data in this manuscript. Seventy percent (91/130) of patients had postsurgical hypoparathyroidism, 30% (39/130) of patients had nonsurgical hypoparathyroidism due to autoimmune, genetic or idiopathic causes, and a molecular diagnosis was confirmed in 11 of these 39 patients. Pseudohypoparathyroidism was confirmed in 4/39 patients, DiGeorge syndrome in 2/39 patients, Barakat syndrome with a mutation in the GATA3 gene in 1/39, and activating mutations of the CASR gene in 3/39 patients with nonsurgical hypoparathyroidism. Renal complications with nephrocalcinosis or nephrolithiasis were present in 27% (14/52) of patients with postsurgical disease and 17% (4/24) of patients with nonsurgical hypoparathyroidism. Basal ganglia calcification was noted on imaging in 15% (n = 5/34) of patients with postsurgical hypoparathyroidism and 37% (n = 7/19) of patients with nonsurgical hypoparathyroidism. Hypercalciuria was more commonly seen in those with renal complications of nephrocalcinosis, nephrolithiasis or CKD, and hyperphosphatemia was more commonly seen in those with basal ganglia calcification. Hospitalization occurred in 28% of those with postsurgical hypoparathyroidism and 46% of those with nonsurgical hypoparathyroidism. Hypoparathyroidism is associated with significant morbidity. Effective strategies to reduce the short-and long-term complications of hypoparathyroidism need to be developed and evaluated.

Health coaching for type 2 diabetes (T2DM) represents a promising addition toward efforts to improve clinical health outcomes and quality of life. The purpose of this study was to evaluate the effect of a 12-month telephone diabetes health coaching (DHC) intervention on glycemic control in persons living with T2DM.In this community-based, randomized, controlled trial, adults with T2DM, glycated hemoglobin (A1C) ≥7.5% and telephone access were assigned to either usual diabetes education (DE) or DHC and access to DE. The primary outcome was change in A1C after 1 year, and secondary outcomes included score on the 19-item Audit of Diabetes-Dependent Quality of Life (ADDQoL-19) instrument and self-care behaviours. Safety was assessed in all participants (NCT02128815 at www.clinicaltrials.gov).Three hundred sixty-five participants (50% females; mean age, 57 years; mean A1C, 8.98%) were randomized to control (DE, n=177) or intervention (DHC, n=188) groups. The A1C level decreased by an absolute amount of 1.8% and 1.3% in the intervention and control groups, respectively. DHC plus DE reduced A1C by 0.49% more than DE alone (95% confidence interval, -0.80 to -0.18; p0.01) and improved ADDQoL-19 scores, with between-group differences for the average weighted score of 0.28 (95% confidence interval, 0.04 to 0.52; p=0.02). There were no differences between groups for proportion of participants having an emergency department visit or hospitalization.Providing frequent telephone-based DHC and access to DE to adults living with T2DM for 1 year supports improvements in glycemic control and quality of life.

Context Celiac disease (CD) is a common comorbidity seen in patients with type 1 diabetes (T1D) and is frequently asymptomatic. As chronic conditions requiring significant lifestyle changes, there are limited reports assessing changes in health-related quality of life (HRQoL) during transition to a gluten-free diet (GFD) in patients with T1D who are asymptomatic for CD. Objective This work aims to prospectively assess HRQoL and health perception in children and adults with T1D and asymptomatic CD after random assignment to GFD vs usual diet. Methods Patients with T1D aged 8 to 45 years without CD symptoms were serologically screened for CD, with positive results confirmed with intestinal biopsy. Participants were randomly assigned in an open-label fashion to a GFD or gluten-containing diet (GCD) for 12 months. Generic and diabetes-specific HRQoL and self-perceived wellness (SPW) were assessed longitudinally. Results A total of 2387 T1D patients were serologically screened. CD was biopsy-confirmed in 82 patients and 51 participants were randomly assigned to a GFD (N = 27) or GCD (N = 24). Excellent adherence to the assigned diets was observed. Overall, no changes in generic (P = .73) or diabetes-specific HRQoL (P = .30), or SPW (P = .41) were observed between groups over 12 months. Hemoglobin A1c (HbA1c) and gastrointestinal symptoms were consistent predictors of HRQoL and SPW. Conclusion HRQoL and SPW were not significantly affected by the adoption of a GFD over 12 months, but worsened with symptom onset and increased HbA1c. Our findings indicate that transition to a GFD can be made successfully in this population without adversely affecting quality of life.

Introduction To evaluate the diagnostic performance of celiac serologic tests in asymptomatic patients with type 1 diabetes (T1D). Methods Patients with T1D asymptomatic for celiac disease were prospectively screened with immunoglobulin A anti-tissue transglutaminase. Test characteristics were calculated and optimal cutoffs for a positive screen determined. Results Two thousand three hundred fifty-three patients were screened and 101 proceeded to biopsy. The positive predictive value of immunoglobulin A anti-tissue transglutaminase at the assay referenced upper limit of normal (30CU) was 85.9%, and the sensitivity and specificity were 100% and 38%, respectively. Discussion Thresholds extrapolated from the general population for the diagnostic evaluation of celiac disease are not suitable for use in asymptomatic T1D patients. Population-specific screening cutoffs are required.

South Asian children and parents have been shown to have a higher risk for cardiovascular disease (CVD) relative to white individuals. To design interventions aimed at addressing the comparatively higher burden in South Asians, a better understanding of attitudes and perspectives regarding CVD-associated behaviors is needed. As a result, we sought to understand knowledge about CVD risk in both children and parents, and attitudes toward physical activity and diet in both the children and parents, including potential cultural influences. In-depth interviews were conducted with 13 South Asian child-and-parent dyads representing a range of child body mass index (BMI) levels, ages, and with both sexes. South Asian children and parents demonstrated good knowledge about CVD prevention; however, knowledge did not always translate into behavior. The influence of social and cultural dynamics on behavior was also highlighted. To ensure that interventions aimed at this population are effective, an understanding of the unique social dynamics that influence diet and physical activity–related behaviors is needed.

OBJECTIVE To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD. RESEARCH DESIGN AND METHODS Asymptomatic patients (8–45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA1c and continuous glucose monitoring over 12 months. RESULTS Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9–8.2%, N = 1,298] vs. 4.7% [95% CI 3.4–5.9%, N = 1,089], P = 0.035) with lower rates of prior CD screening (6.9% vs. 44.2%, P < 0.0001). Fifty-one participants were randomized to a GFD (N = 27) or GCD (N = 24). No HbA1c differences were seen between the groups (+0.14%, 1.5 mmol/mol; 95% CI −0.79 to 1.08; P = 0.76), although greater postprandial glucose increases (4-h +1.5 mmol/L; 95% CI 0.4–2.7; P = 0.014) emerged with a GFD. CONCLUSIONS CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.

OBJECTIVE Epidemiological studies have reported a relationship between severe hypoglycemia, cognitive dysfunction, and dementia in middle-aged and older people with type 2 diabetes. However, whether severe or nonsevere hypoglycemia precedes cognitive dysfunction is unclear. Thus, the aim of this study was to analyze the relationship between hypoglycemia and incident cognitive dysfunction in a group of carefully followed patients using prospectively collected data in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial. RESEARCH DESIGN AND METHODS This prospective cohort analysis of data from a randomized controlled trial included individuals with dysglycemia who had additional cardiovascular risk factors and a Mini-Mental State Examination (MMSE) score ≥24 (N = 11,495). Severe and nonsevere hypoglycemic events were collected prospectively during a median follow-up time of 6.2 years. Incident cognitive dysfunction was defined as either reported dementia or an MMSE score of RESULTS This analysis did not demonstrate an association between severe hypoglycemia and incident cognitive impairment either before (hazard ratio [HR] 1.16; 95% CI 0.89, 1.52) or after (HR 1.00; 95% CI 0.76, 1.31) adjusting for the severe hypoglycemia propensities. Conversely, nonsevere hypoglycemia was inversely related to incident cognitive impairment both before (HR 0.59; 95% CI 0.52, 0.68) and after (HR 0.58; 95% CI 0.51, 0.67) adjustment. CONCLUSIONS Hypoglycemia did not increase the risk of incident cognitive dysfunction in 11,495 middle-aged individuals with dysglycemia.

Background Myocardial injury after non-cardiac surgery (MINS) is the most common perioperative cardiovascular complication and is independently associated with 30-day mortality. We aimed to assess the association between preoperative glucose concentration and postoperative MINS and mortality. Methods The VISION study is a prospective cohort study done at 12 centres in eight countries. Patients aged 45 years or older who required at least one overnight hospital admission for non-cardiac surgery were enrolled from Aug 6, 2007, to Jan 11, 2011. In the GlucoVISION analysis, we assessed the relations between preoperative casual or fasting glucose concentration and MINS within 3 days after surgery using logistic regression, and 30-day mortality using Cox proportional regression, in people with and without diabetes. Findings 11954 patients were included in this analysis, of whom 2809 (23%) had diabetes. Within the first three postoperative days, MINS occurred in 813 (7%) patients. 249 (2%) patients died by day 30. More patients with diabetes had MINS (odds ratio [OR] 1.98 [95% CI 1.70-2.30]; p

The prevalence of hypertension in children is increasing globally. Addressing this will require a robust understanding of associated risk factors. To this end, we conducted a systematic review to identify correlates of elevated blood pressure (BP) in children. Literature searches were conducted using pre-defined search terms from three academic databases. The abstract and full text of identified studies were screened for eligibility by two independent reviewers. A total of 100 studies were included in this systematic review. An assessment tool was first used to assess study quality; a narrative synthesis was then performed. We found a broad range of physiological, social and behavioural factors associated with elevated BP in children. The most common correlate observed was adiposity, suggesting that childhood obesity may be implicated in the increased prevalence of hypertension observed in children. However, the broad range of other factors identified underscores the multi-factorial aetiology of hypertension. Data from a broad range of studies showed that the correlates of hypertension in children are multi-factorial. Therefore, approaches aimed at preventing hypertension must in turn be multi-factorial to ensure that the burden of hypertension in childhood is addressed.

Diabetes is often poorly managed in hospitals. This study assessed the level of adherence to current Canadian practice guidelines for inpatient pharmacologic management of type 2 diabetes and whether it affected the frequency of hyperglycemia or hypoglycemia.Retrospectively, we assessed the first 3 days of routine inpatient capillary blood glucose measurement (CBGM) records for hyperglycemia (8 mmol/L fasting,10 mmol/L nonfasting) and hypoglycemia (4 mmol/L) in adults with drug-treated type 2 diabetes admitted to internal medicine without metabolic decompensation or nil per os (NPO) status at 2 hospitals during October through December 2014. Patients, divided according to their admission orders into guideline-adherent versus guideline-nonadherent groups were compared for frequency of hyperglycemia and hypoglycemia. Factors predicting guideline adherence were assessed.Of 150 patients with diabetes who were admitted, 108 met entry criteria. A total of 89 patients received guideline-based care (82%), whereas 19 patients did not (18%). Charlson index and preadmission medications did not predict guideline-based care, but admitting physicians' seniority did (junior, senior resident, attending physician; p=0.05). In the adherent group, 43% of CBGMs were hyperglycemic, versus 64% in the nonadherent group (p=0.01). For hypoglycemia, proportions were 2% versus 1%, respectively (p=0.21).Adherence to guidelines for inpatient type 2 diabetes management is good and may be greater with more training. Hyperglycemia was more common in patients who did not receive guideline-based care. Hypoglycemia was uncommon and did not appear to be more common in the guideline-adherent group, although numbers were small. These results may alleviate physicians' fear that providing adequate insulin to hospitalized patients may cause hypoglycemia.

Background Type 1 diabetes is a common chronic disease. Poor health outcomes are often noted after transfer to adult health care. It is important to determine the predictors of such outcomes to decrease the morbidity and mortality. Methods This retrospective study included patients followed ≥1year pre-transfer and ≥1 year post-transfer to adult care in a Canadian tertiary diabetes center. Data including demographics, education, comorbidity and pediatric diabetes management-related factors were analyzed as possible independent predictors of adult HbA1c, number of adult diabetes-related hospitalization and clinic visits. Results A total of 102 youth were followed to a mean age of 21.8 ± 1.5 years. Predictors of mean adult HbA1c were presence of any comorbidity (0.71%; 95%CI 0.15-1.27; p = 0.01), and pediatric HbA1c (0.67% per 1%; 95%CI 0.51-0.84; p

Digital, Background: Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. Methods: REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952. Findings: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m2 (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1-5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77-0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68-0·87; p, Ciencias Médicas y de la Salud

Digital, Background Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A1c (HbA1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. Methods This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. Findings Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA1c 7·2% [IQR 6·6–8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1–5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79–0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80–1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p, Ciencias Médicas y de la Salud

ObjectiveWe sought to explore various correlates of blood pressure (BP) and hypertension, and to identify the most important aggregate combination of correlates for BP in South Asian children.DesignCross-sectional studySettingCommunity-based recruitment in two Canadian citiesParticipantsSouth Asian children (n=762) provided a range of physiological, lifestyle and social variables. BP was assessed using an automated device. Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and BP were transformed to z-scores using published standards.Outcome measuresLinear and logistic regression analyses were used to explore associations between the range of variables with BP z-scores and hypertension while stepwise regression was used to identify aggregate factors that provided explanatory capacity for systolic BP (SBP) and diastolic BP (DBP) z-scores.ResultsA range of variables were associated with BP z-score and hypertension in unadjusted analysis. On adjustment for confounders, the association between age (β=−0.054, 95% CI=−0.078 to 0.029), female sex (β=−0.208, 95% CI=−0.350 to –0.067), height (β=0.022, 95% CI=0.011 to 0.033), weight (β=0.047, 95% CI=0.040 to 0.055), BMI z-score (β=0.292, 95% CI=0.249 to 0.336), WC z-score (β=0.273, 95% CI=0.219 to 0.326), WHtR z-score (β=0.289, 95% CI=0.236 to 0.342), heart rate (β=0.016, 95% CI=0.010 to 0.022), child’s perception of body image (β=0.183, 95% CI=0.128 to 0.239) and grip strength (β=0.025, 95% CI=0.007 to 0.043) with SBP z-score remained. In stepwise regression, age, sex, BMI z-score, heart rate and weight accounted for 30% of the variance of SBP z-score, while age, BMI z-score, heart rate and daily fast food intake accounted for 23% of the DBP z-score variance.ConclusionOur findings suggest that variables, such as age, sex, height, adiposity and heart rate, provide stronger explanatory capacity to BP variance and hypertension risk than other variables in South Asian children.

The Canadian National Hypoparathyroidism Registry (CNHR) was formed in 2014 and enrolment of prevalent and incident cases began following approval by McMaster University Ethics Review Board. Objective(s): • identify the etiology and presenting symptoms of patients with hypoPTH. • assess differences in presentation based on etiology of the disease. • compare parameters of calcium homeostasis amongst those developing complications of nephrolithiasis or nephrocalcinosis and those without complications. • assess fracture risk in Canadian patients with hypoPTH. Material and Methods: 118 patients aged >18 years registered in the CNHR were reviewed as per the following inclusion criteria: 1. Chronic HypoPTH (low PTH in the presence of low serum calcium total or ionized below normal reference range for at least 6 months prior to enrolment) 2. HypoPTH (including post-surgery) requiring calcium/calcitriol replacement to maintain normal calcium (total or ionized calcium level for at least 6 months prior to enrolment 3. Pseudohypoparathyroidism with elevated PTH and low serum calcium (total or ionized) normal vitamin D and hyperphosphatemia were included. We reviewed etiology, clinical presentation, biochemical profile, management strategies, markers of skeletal health including fractures, bone mineral density (BMD), fracture risk and complications including nephrolithiasis/nephrocalcinosis, and basal ganglia calcification. Results: Most patients (72%) had postsurgical hypoparathyroidism, followed by idiopathic/autoimmune disease (25%) and pseudohypoparathyroidism (3%). The mean age of onset was 42.0 years, with mean duration of follow-up of 4 years. All patients were taking calcium supplements (100%); calcitriol was taken by 82.2% and 6 patients were receiving parathyroid hormone. Nephrolithiasis or nephrocalcinosis were present in 24.6% of treated patients despite a mean calcium phosphate product

Background The effect on cardiovascular outcomes of withholding angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in chronic users before noncardiac surgery is unknown. Methods In this international prospective cohort study, the authors analyzed data from 14,687 patients (including 4,802 angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users) at least 45 yr old who had in-patient noncardiac surgery from 2007 to 2011. Using multivariable regression models, the authors studied the relationship between withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and a primary composite outcome of all-cause death, stroke, or myocardial injury after noncardiac surgery at 30 days, with intraoperative and postoperative clinically important hypotension as secondary outcomes. Results Compared to patients who continued their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, the 1,245 (26%) angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users who withheld their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the 24 h before surgery were less likely to suffer the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1,245 [12.0%] vs. 459/3,557 [12.9%]; adjusted relative risk, 0.82; 95% CI, 0.70 to 0.96; P = 0.01) and intraoperative hypotension (adjusted relative risk, 0.80; 95% CI, 0.72 to 0.93; P < 0.001). The risk of postoperative hypotension was similar between the two groups (adjusted relative risk, 0.92; 95% CI, 0.77 to 1.10; P = 0.36). Results were consistent across the range of preoperative blood pressures. The practice of withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers was only modestly correlated with patient characteristics and the type and timing of surgery. Conclusions Withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers before major noncardiac surgery was associated with a lower risk of death and postoperative vascular events. A large randomized trial is needed to confirm this finding. In the interim, clinicians should consider recommending that patients withhold angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers 24 h before surgery.

Background: The role of high density lipoprotein-raising interventions in addition to statin therapy in patients with diabetes remains controversial. Chronic kidney disease (CKD) is a strong modifier of cardiovascular (CV) outcomes. We therefore investigated the impact of CKD status at baseline on outcomes in patients with diabetes randomized to standard statin or statin plus fenofibrate treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial. Methods: Among 5,464 participants in the ACCORD lipid trial, 3,554 (65%) were free of CKD at baseline, while 1,910 (35%) had mild to moderate CKD. Differences in CV outcomes during follow-up between CKD and non-CKD subgroups were examined. In addition, the effect of fenofibrate as compared to placebo on CV outcomes was examined for both subgroups. Results: All CV outcomes were 1.4-3 times higher among patients with CKD as compared to non-CKD patients. In patients with CKD, the addition of fenofibrate had no effect on any of the primary or secondary outcomes. In patients without CKD, however, the addition of fenofibrate was associated with a significant 36% reduction of CV mortality (hazards ratio [HR] 0.64; 95% CI 0.42-0.97; p value for treatment interaction p value treatment interaction Conclusions: For patients with type 2 diabetes at high CV risk but no CKD, fenofibrate therapy added to statin reduced the CV mortality and the rate of fatal and non-fatal CHF.

Background Recent evidence suggests that fostering strategies to enable youth with chronic health conditions to work towards gradual self-management of their health is key in successful transition to adult healthcare. To date, there is limited research on self-management promotion for youth. The purpose of this study is to explore self-management from the perspectives of youth, parents and healthcare providers in transition to adult healthcare. Methods Part of a larger longitudinal transition (TRACE-2009–2013) study, interpretive phenomenology was used to explore the meaning of the lived experiences and perceptions of youth, parents, and healthcare providers about transition to adult healthcare. Purposeful sampling was utilized to select youth with a range of chronic health conditions from the TRACE cohort (spanning 20 diagnoses including developmental disabilities and chronic conditions), their parents and healthcare providers. Results The emerging three themes were: increasing independence of youth; parents as safety nets and healthcare providers as enablers and collaborators. The findings indicate that the experiences of transitioning youth, parents and service providers are interconnected and interdependent. Conclusions Results support a dynamic and developmentally appropriate approach when working with transitioning youth and parents in practice. As youth depend on parents and healthcare providers for support in taking charge of their own health, parents and healthcare providers must work together to enable youth for self-management. At a policy level, adequate funding, institutional support and accreditation incentives are recommended to allow for designated time for healthcare providers to foster self-management skills in transitioning youth and parents.

ObjectiveGiven the South Asian phenotype of higher body fat at similar body mass index (BMI) relative to Caucasians, we sought to explore the association between prominent adiposity indicators with blood pressure (BP) and hypertension, to compare the accuracy of these indicators in estimating hypertension, and to provide cut-off values associated with adverse hypertension risk in South Asian children.DesignCross-sectional study.SettingCommunity-based recruitment in two Canadian cities (Hamilton and Surrey).ParticipantsSouth Asian children (n=762) were recruited from two Canadian cities. Waist circumference, waist to height ratio and BMI were determined. Body fat percentage was assessed by bioelectrical impedance analysis and BP was assessed using an automated device. All variables (except body fat percentage) were transformed to z-scores using published standards.Outcome measuresLinear and Poisson regression was used to explore associations between the adiposity indicators with BP z-score and hypertension. Receiver operating curve (ROC) analysis was used to explore the strength of the adiposity indicators in estimating hypertension risk and sex-stratified optimal adiposity cut-off values associated with hypertension risk.ResultsSignificant associations were detected in adjusted and unadjusted models between the adiposity indicators with BP z-score and hypertension (pConclusionOur results show associations between adiposity indicators with BP and hypertension and suggests that South Asian children might be at adverse risk of hypertension at levels of adiposity considered normal.

Diet and South Asian ethnicity are both associated with early onset of cardiovascular risk factors. Among youth of South Asian origin, little is known about the role of culture in determining healthy dietary patterns. We aimed to assess dietary patterns and their relationships with acculturation to Western and traditional lifestyles among South Asian youth in Canada.The Research in Cardiovascular Health - Lifestyles, Environments and Genetic Attributes in Children and Youth (RICH LEGACY) study targeted South Asian children and adolescents aged 7-8 and 14-15 years in two Canadian cities. In this cross-sectional study, acculturation questionnaires and food frequency questionnaires were administered to assess the correlations between Western and traditional culture scores, immigration status (generation and length of residency) in Canada and intake frequency of various foods.Among 759 youth, those who ate fruits and vegetables more often consumed dairy and whole grains more often (all r = 0.17-0.22, all p 0.001), while those who ate fast food more often consumed meat, sweets and sugared drinks more often (all r 0.24-0.38, all p 0.001). Traditional culture scores were weakly positively correlated with whole grain intake frequency (r = 0.12, p = 0.001), and negatively with meat intake frequency (r = -0.14, p 0.001). Western culture scores positively correlated with high intake frequency of meat (r = 0.23, p 0.001), fast food (r = 0.14, p 0.001) and sweets (r = 0.14, p 0.001).Children who are more acculturated with Western lifestyle consumed foods associated with increased metabolic risk. However, whether this eating pattern translates into increased risk of obesity and cardiovascular diseases needs to be further explored.

Objectives The Diabetes Health Coaching Trial was a single-blind, randomized controlled trial designed to evaluate the effect of a 1-year telephone-based diabetes health-coaching intervention for community-dwelling adults living with type 2 diabetes mellitus. It concerned glycated hemoglobin levels, self-care behaviours and cost-effectiveness. The purpose of this article is to describe the rationale, design and participants' characteristics. Methods The eligibility criteria were: 1) adults ≥18 years of age; 2) a diagnosis of type 2 diabetes; 3) glycated hemoglobin levels of ≥7.5% 6 months before randomization; 4) the ability to read, write and understand English; and 5) having telephone access. Participants were randomized to either usual diabetes education or diabetes education plus diabetes health coaching. Results From May 2016 to December 2017, 365 participants were randomized into the trial. At baseline, the mean age was 57.9 (11.78) years, the mean duration of diabetes was 8.69 (8.54) years, the mean glycated hemoglobin level was 8.98 (1.58) %, and the mean body mass index was 35.03 (8.07) kg/m2. Conclusions The baseline characteristics of the participants were equally distributed across the intervention and control groups. The Diabetes Health Coaching Trial is in a position to evaluate a potential treatment alternative and approach for type 2 diabetes and examined the effect of the intervention on clinical outcomes, self-care behaviours and cost-effectiveness.

Background: Significant variability is reported as to the presence and quality of gastrointestinal (GI) symptoms in patients with type 1 diabetes (T1D). Objective: To assess reported GI symptoms and associated comorbidities in adults and children with T1D. Methods: The Gastrointestinal Symptom Scale (GISS) and a Visual Analog Scale (VAS) were used to assess GI symptom type and severity in 2,370 patients with T1D aged 8-45 years as part the screening phase of the Celiac Disease and Diabetes Dietary Intervention and Evaluation Trial (CD-DIET). Co-morbidities, including diabetes-related complications, were extracted from clinical records. The presence and severity of GI symptoms and relationships with demographic, clinical and other diabetes-related factors were evaluated. Results: Overall, 1368 adults (57.7%) aged 19-45 years and 1002 (42.3%) pediatric patients aged 8-18 years were studied. At least one GI symptom was reported in 34.1% of adults as compared with 21.7% of children (p Conclusions: In this large screening study in a contemporary T1D cohort, significant differences were found between age groups with more frequent GI symptoms in adults. Significant associations were observed between GI symptoms and diabetes complications along with diabetes duration. Disclosure F.H. Mahmud: None. E. Nunes de Melo: None. A.B. Clarke: None. E. Assor: None. A. Parikh: None. A. Advani: Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH. Other Relationship; Self; Boehringer Ingelheim GmbH. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc.. B.R. Shah: None. C.S. Zuijdwijk: None. C. McDonald: None. D. Mack: None. D. Koltin: None. E. Hsieh: None. E.M. Szentgyorgyi: None. F. Saibil: None. G. Mukerji: None. H.A. Lochnan: Research Support; Self; Amylin Pharmaceuticals, Boston Therapeutics, Inc., Sanofi. J. Gilbert: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Sanofi. K. Bax: None. M.L. Lawson: None. M.D. Beaton: Advisory Panel; Self; Takeda Canada Inc., Janssen Pharmaceuticals, Inc., AbbVie Inc.. N.A. Saloojee: None. O. Lou: None. P.H. Gallego: None. R.L. Houlden: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., AstraZeneca, Eli Lilly and Company. R. Aronson: Other Relationship; Self; Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Sanofi, AstraZeneca. Research Support; Self; Eli Lilly and Company, Becton, Dickinson and Company, Merck & Co., Inc., Senseonics, Boehringer Ingelheim Pharmaceuticals, Inc.. S.E. Kirsch: None. W.G. Paterson: None. Z. Punthakee: Research Support; Self; Amgen, Astra Zeneca/Bristol Myers Squibb, Lexicon, Merck, NovoNordisk, Sanofi. Speaker's Bureau; Self; Abbott, Astra Zeneca/Bristol Myers Squibb, Boehringer Ingelheim/Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Sanofi. Advisory Panel; Self; Astra Zeneca/Bristol Myers Squibb, Boehringer Ingelheim/Eli Lilly, Dexcom, Janssen, Medtronic, NovoNordisk, Pfizer, Sanofi. M.A. Marcon: None.

Background: Celiac Disease (CD) is more common in individuals with type 1 diabetes (T1D) and is frequently asymptomatic. Despite this association, evidence as to the impact and diagnostic accuracy of CD screening is limited in asymptomatic patients with T1D. Objective: To describe CD serology and biopsy positivity rates in T1D patients screened as part of the Celiac Disease and Diabetes Dietary Intervention and Evaluation Trial (CD-DIET). Methods: Prospective data from patients, aged 8-45 years, with T1D screened at 22 sites across Ontario, Canada as part of CD-DIET were analyzed with respect to demographics, clinical symptoms and CD status. Serological and biopsy-confirmed rates of CD were evaluated. Results: Overall, 2585 patients were approached and 2386 patients completed serological testing using tissue transglutaminase antibodies. The sample included 1298 (54.4%) adults, aged 19-45 years, and 1088 (45.6%) pediatric subjects, aged 8-18 years. Mean age was 23.1 ± 10.3 years, 49.2% female, with mean duration of diabetes 12.2 ± 9.0 years. A small number of screened patients (N=45) were symptomatic for CD as per study criteria with clinical GI symptoms (n=39), osteoporosis (n=2), apthous ulcers (n=1), weight loss (n=1), and/or anemia (n=2). Overall, 140 asymptomatic patients were serologically positive for CD. A positive CD serology rate of 7.2% (94/1298) was seen in adults as compared to 4.2% (46/1088) in pediatric subjects (p=0.0064). Endoscopy was completed in 104 patients and CD was subsequently confirmed using duodenal biopsy in 54/71 adults (76.1%) and 28/33 pediatric patients (84.8%), with overall biopsy positivity rates of 4.2% and 2.6% respectively (p=0.034). Conclusions: Significant differences were observed in CD serology and biopsy positivity, with higher rates seen in adults as compared with children with T1D, which may be due to increasing risk of autoimmune co-morbidities with age as well as many adults being naïve to celiac disease screening. Disclosure F.H. Mahmud: None. A.B. Clarke: None. K.C. Joachim: None. E. Assor: None. A. Parikh: None. A. Advani: Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH. Other Relationship; Self; Boehringer Ingelheim GmbH. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc.. B.R. Shah: None. C.S. Zuijdwijk: None. C. McDonald: None. D. Mack: None. D. Koltin: None. E. Hsieh: None. E.M. Szentgyorgyi: None. F. Saibil: None. G. Mukerji: None. H.A. Lochnan: Research Support; Self; Amylin Pharmaceuticals, Boston Therapeutics, Inc., Sanofi. J. Gilbert: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Sanofi. K. Bax: None. M.L. Lawson: None. M.D. Beaton: Advisory Panel; Self; Takeda Canada Inc., Janssen Pharmaceuticals, Inc., AbbVie Inc.. N.A. Saloojee: None. O. Lou: None. P.H. Gallego: None. R.L. Houlden: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., AstraZeneca, Eli Lilly and Company. R. Aronson: Other Relationship; Self; Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Sanofi, AstraZeneca. Research Support; Self; Eli Lilly and Company, Becton, Dickinson and Company, Merck & Co., Inc., Senseonics, Boehringer Ingelheim Pharmaceuticals, Inc.. S.E. Kirsch: None. W.G. Paterson: None. Z. Punthakee: Research Support; Self; Amgen, Astra Zeneca/Bristol Myers Squibb, Lexicon, Merck, NovoNordisk, Sanofi. Speaker's Bureau; Self; Abbott, Astra Zeneca/Bristol Myers Squibb, Boehringer Ingelheim/Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Sanofi. Advisory Panel; Self; Astra Zeneca/Bristol Myers Squibb, Boehringer Ingelheim/Eli Lilly, Dexcom, Janssen, Medtronic, NovoNordisk, Pfizer, Sanofi. M.A. Marcon: None.

Background: As related autoimmune conditions, celiac disease (CD) is more common in individuals with type 1 diabetes (T1D) and is frequently asymptomatic. Despite this association, evidence as to the diagnostic accuracy of screening as well as the potential benefits or harms of screening for CD is limited in asymptomatic patients with T1D. Methods: T1D patients, aged 8-45 years, were serologically screened for CD at multiple centers across Ontario, Canada as part of the Celiac Disease and Diabetes Dietary Intervention and Evaluation Trial (CD-DIET). Patients were deemed asymptomatic on the basis of the absence of GI symptoms, weight changes, anemia and other CD-related clinical features. Screening was conducted in 2,386 patients using chemiluminescent (CL, BioFlash™) and/or ELISA (Celikey™) tissue transglutaminase (TTG) IgA assays, yielding 140 positives. Of these, 104 patients had a duodenal biopsy with CD confirmation (Marsh ≥2). Receiver operating characteristic (ROC) curve analysis was conducted and positive predictive values (PPV) of available screening tests for CD were evaluated. Results: CL and ELISA data were available for 100/104 and 36/104 patients, respectively. The area under the curve of the ROC for CL TTG was 0.918, while the PPV using the manufacturer referenced upper limit (RUL) of 30 CU was 85.9% (95% CI: 82.3-90.8%). According to our data, an optimal cut-off of 156.5 CU, or 5.2 times the RUL, showed an improved PPV of 95.8% (95% CI: 92.4-100.0%). With respect to ELISA TTG, the PPV was 94.4% at the RUL of 8 U/ml and reached to 100% at the optimal cut-off determined by our analysis of 58.7 U/ml, which translates to 7.3 times the RUL. Conclusion: Results from serologic CL and ELISA TTG assays that were greater than 5 times the reported upper limit showed a high PPV for biopsy-confirmed CD in asymptomatic adult and pediatric T1D patients, which may help guide diagnostic evaluation in this population. Disclosure M. Gould: None. F.H. Mahmud: None. A.B. Clarke: None. E. Assor: None. A. Parikh: None. A. Advani: Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH. Other Relationship; Self; Boehringer Ingelheim GmbH. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc.. B.R. Shah: None. C.S. Zuijdwijk: None. C. McDonald: None. D. Mack: None. D. Koltin: None. E. Hsieh: None. E.M. Szentgyorgyi: None. F. Saibil: None. G. Mukerji: None. H.A. Lochnan: Research Support; Self; Amylin Pharmaceuticals, Boston Therapeutics, Inc., Sanofi. J. Gilbert: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Sanofi. K. Bax: None. M.L. Lawson: None. M.D. Beaton: Advisory Panel; Self; Takeda Canada Inc., Janssen Pharmaceuticals, Inc., AbbVie Inc.. N.A. Saloojee: None. O. Lou: None. P.H. Gallego: None. R.L. Houlden: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., AstraZeneca, Eli Lilly and Company. R. Aronson: Other Relationship; Self; Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Sanofi, AstraZeneca. Research Support; Self; Eli Lilly and Company, Becton, Dickinson and Company, Merck & Co., Inc., Senseonics, Boehringer Ingelheim Pharmaceuticals, Inc.. S.E. Kirsch: None. W.G. Paterson: None. Z. Punthakee: Research Support; Self; Amgen, Astra Zeneca/Bristol Myers Squibb, Lexicon, Merck, NovoNordisk, Sanofi. Speaker's Bureau; Self; Abbott, Astra Zeneca/Bristol Myers Squibb, Boehringer Ingelheim/Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Sanofi. Advisory Panel; Self; Astra Zeneca/Bristol Myers Squibb, Boehringer Ingelheim/Eli Lilly, Dexcom, Janssen, Medtronic, NovoNordisk, Pfizer, Sanofi. M.A. Marcon: None.

Background: The prevalence of childhood obesity is increasing globally. This has severe implications for cardiometabolic risk including hypertension. South Asian children are particularly vulnerable given their unique phenotype which results in higher body fat at similar body mass index (BMI) levels compared to Europeans. As a result, we sought to explore the association between adiposity indicators and blood pressure, and to compare the strength of these indicators in determining hypertension in South Asian children and adolescents. Methods: Children ages 7-8 and 14-15 with South Asian origin were recruited from two Canadian cities. They were then assessed for height, weight and waist circumference (WC). Waist to height ratio (WHtR), and BMI were calculated. Body fat percentage was determined by bioelectrical impedance analysis. Blood pressure (BP) was assessed three times using an automated device. All variables (except body fat percentage) were transformed to z-scores using published standards. Unadjusted and adjusted (age, sex, household income, exposure to bullying or violence) logistic regression was used to explore associations between adiposity and hypertension. Subsequently, area under the curve (AUC) analysis was used to explore the strength of the adiposity metrics in determining hypertension. Results: This study consisted of 306 boys and 402 girls (n=762) with mean age 9.5 (S.D 3.2) years. Significant association were detected in unadjusted models between the adiposity indicators with systolic and diastolic hypertension (p Conclusion: Significant associations were observed between adiposity indicators and hypertension. Moreover, the adiposity indicators were observed to be strong predictors of hypertension in AUC analysis. This highlights the relationship between adiposity and hypertension, and suggests that BMI, WC, WHtR and body fat percentage are good indicators of hypertension in South Asian children.

Background: Persons with chronic kidney disease (CKD) represent a population prone to cardiovascular disease (CVD) but vulnerable to adverse medication effects. We assessed the impact of intensive antihypertensive therapy on the cerebrovascular and other CVD outcomes in high-risk patients with type 2 diabetes and baseline CKD. Methods: Using current guideline criteria, 1,726 (36.9%) of 4,678 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure (BP) arm had mild to moderate CKD (CKD1-3B) at baseline. Participants of this study were randomized to intensive (systolic Results: Total cerebrovascular events were significantly higher in participants with baseline CKD (0.66%/year) compared with participants free of CKD (0.28%/year). A significantly higher rate of events was observed in CKD participants. Intensive antihypertensive therapy in participants without CKD at baseline resulted in a 55% significant reduction of any stroke (hazard ratio 0.447; 95% CI 0.227-0.880) and a 50% reduction of non-fatal stroke (hazard ratio 0.498; 95% CI 0.250-0.993). In participants with CKD at baseline, the occurrence of any stroke was reduced by 38% (hazard ratio 0.623; 95% CI 0.361-1.074) and non-fatal stroke by 36% (hazard ratio 0.642; 95% CI 0.361-1.142). Test for interaction was NS between the 2 groups. Changes in other CVD outcomes did not reach statistical significance. Conclusions: These findings suggest that intensive antihypertensive therapy offers significant cerebrovascular protection in diabetic participants without CKD at baseline, but significant benefit to patients with CKD cannot be excluded.

Objectives:The purpose of this study was to understand perceived benefits, facilitators, disadvantages, and barriers for physical activity among South Asian adolescents in India and Canada.Methods:Thirteen focus group discussions with South Asian (origin) adolescent boys and girls of different nutritional status and socioeconomic status in rural and urban India and urban Canada.Results:Across the groups, fitness and ‘energy’ were perceived to be major benefits of physical activity. In India, better academic performance was highlighted, while health benefits were well detailed in Canadian groups. In all settings, friends, family, and teachers were perceived as facilitators of as well as barriers to physical activity. Lack of a safe space to play was a major concern for urban adolescents, while academic pressures and preference for other sedentary recreational activities were common barriers across all groups. Girls were less likely than boys to be interested in physical activity, with girls’ participation in India further limited by societal restrictions.Conclusions:The study suggests key areas for promotion of physical activity among South Asian adolescents: balance between academic pressure and opportunities for physical activity, especially in India; urban planning for a built environment conducive to physical activity; and gender-sensitive programming to promote girls’ activity which also addresses culture-specific barriers.

Objectives. To determine (1) whether intramuscular adipose tissue (IntraMAT) differs between women with and without type 2 diabetes and (2) the association between IntraMAT and mobility and strength.Methods. 59 women ≥ 65 years with and without type 2 diabetes were included. A 1-Tesla MRI was used to acquire images of the leg. Timed-up-and-go (TUG) and grip strength were measured. Regression was used to determine associations between the following: (1) type 2 diabetes and IntraMAT (covariates: age, ethnicity, BMI, waist : hip ratio, and energy expenditure), (2) IntraMAT and TUG (covariates: diabetes, age, BMI, and energy expenditure), and (3) IntraMAT and grip strength (covariates: diabetes, age, height, and lean mass).Results. Women with diabetes had more IntraMAT. After adjustment, IntraMAT was similar between groups (diabetes mean [SD] = 13.2 [1.4]%, controls 11.8 [1.3]%,P=0.515). IntraMAT was related to TUG and grip strength, but the relationships became nonsignificant after adjustment for covariates (difference/percent IntraMAT [95% CI]: TUG = 0.041 seconds [−0.079–0.161],P=0.498, grip strength = −0.144 kg [−0.335–0.066],P=0.175).Conclusions. IntraMAT alone may not be a clinically important predictor of functional mobility and strength; however, whether losses in functional mobility and strength are promoted by IntraMAT accumulation should be explored.

OBJECTIVE The effect of hypoglycemia related to treatment of type 2 diabetes mellitus (T2DM) on brain structure remains unclear. We aimed to assess whether symptomatic severe hypoglycemia is associated with brain atrophy and/or white matter abnormalities. RESEARCH DESIGN AND METHODS We included T2DM participants with brain MRI from the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) trial. Symptomatic severe hypoglycemia was defined as blood glucose RESULTS Of the 503 T2DM participants (mean age, 62 years) with successful baseline and 40-month brain MRI, 28 had at least one HA episode during the 40-month follow-up. Compared with participants without HA, those with HA had marginally significant less atrophy (less decrease in TBV) from baseline to 40 months (−9.55 [95% CI −15.21, −3.90] vs. −15.38 [95% CI −16.64, −14.12], P = 0.051), and no significant increase of AWM volume (2.06 [95% CI 1.71, 2.49] vs. 1.84 [95% CI 1.76, 1.91], P = 0.247). In addition, no unexpected local signal changes or volume loss were seen on hypoglycemic participants’ brain MRI scans. CONCLUSIONS Our study suggests that hypoglycemia related to T2DM treatment may not accentuate brain pathology, specifically brain atrophy or white matter abnormalities.

Background: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study’s four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. Methods: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated “abnormal” laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. Results: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors’ diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96–5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6–41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. Conclusion: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

Source Citation D’Aiuto F, Gkranias N, Bhowruth D, et al; TASTE Group. Systemic effects of periodontitis treatment in patients with type 2 diabetes: a 12 month, single-centre, investigator-masked, ...

To examine the relationship of cognitive performance to exposure to insulin (INS) and thiazolidinediones (TZD) in the ACCORD-MIND cohort.Participants (55-80years) with type 2 diabetes (T2D), hemoglobin A1c (HbA1c)7.5% (58mmol/mol), and a high risk of cardiovascular events were randomly assigned to receive intensive control targeting HbA1c to6.0% (42mmol/mol) or a standard strategy targeting HbA1c to 7.0%-7.9% (53-63mmol/mol). The Digit Symbol Substitution Test (DSST) was assessed at baseline and at 20 and 40months. Exposure to INS was calculated as average daily dose/kg of body weight; exposure to rosiglitazone (ROS) was calculated as days of ROS prescription in the intervals preceding the 20- and 40-month DSSTs.At baseline, INS use was associated with reduced DSST performance, but not after controlling for comorbidities and lab values. There was no relationship between use of a TZD and DSST performance on at baseline. ROS but not INS exposure was associated with greater decline in DSST performance over 40months in subjects randomized to the intensive but not the standard group.Exposure to a TZD may increase cognitive decline in some patients with T2D. However, these results may be confounded by unexplained differences between participants.

Objective: To assess efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus (vs) insulin glargine 100 U/mL (Gla-100) in North American and non-North American people with type 2 diabetes mellitus on different background therapies.Methods: A patient-level meta-analysis of three international studies (EDITION 1, 2 and 3) was performed to examine glycemic control and hypoglycemia over 6 months in 2496 participants including 1420 participants in a North American sub-population (Gla-300, N=700; Gla-100, N=720). Endpoints included change in glycated hemoglobin (HbA1c), percentage of patients at target HbA1c at Month 6, incidence and rate of hypoglycemic events, change in body weight and insulin dose, as well as incidence of adverse events.Results: Mean change in HbA1c was comparable for Gla-300 and Gla100 in both regions (P=0.8347 for treatmentby- subgroup interaction). There were no regional differences in the percentage of participants achieving target HbA1c 0.1). North American participants treated with Gla-300 gained less weight than North American participants treated with Gla-100 (least squares mean change 0.64 kg vs 1.15 kg), whereas in non-North American participants the change in weight tended to be similar in both treatment groups (0.36 kg vs 0.32 kg). Treatment with Gla-300 and Gla-100 was well tolerated in both regions.Conclusion: Gla-300 provided comparable glycemic control to Gla-100 with consistently less hypoglycemia at any time of day and during the night, regardless of the region (North America/outside North America).

Introduction Dietary patterns have contributed to the rising prevalence of overweight and obesity among Indian adolescents. Yet there are limited studies on their perspectives on healthy eating. The purpose of this study was to understand perceptions and attitudes of Indian-origin adolescents in India and Canada that may contribute to healthy eating behaviour. Methods Qualitative data collection and analysis of 13 focus group discussions (FGD) was conducted among 34 boys and 39 girls (total number of participants: 73) of different weight and socioeconomic status (SES) in rural and urban India, and urban Canada aged 11–18 years. Results All adolescents perceived homemade foods, and foods high in vitamins, minerals and fiber as healthy. Rural Indian adolescents also identified contaminant-free food as important. Opinions differed regarding the health value of consuming meat, and amongst Canadian adolescents, the health impact of Western versus Indian diets. Identified benefits of healthy eating included improved energy for Indians, and disease prevention for Canadians and urban Indians. Identified barriers across all settings included peers; and availability, access and affordability of unhealthy foods. Urban Indians and Canadian girls also reported academic stress and lack of time as barriers. Canadian girls reported limited parental supervision during mealtimes as an additional barrier. Facilitators to healthy eating included parents, friends and personal preferences for healthy foods. Conclusion This study suggests potential targets for family-based and school-based education programs and policies to improve dietary habits of Indian and Indo-Canadian adolescents which include, culturally focused nutrition education and guidelines, academic stress management strategies, parental education, food hygiene regulations and restriction on the sale and advertising of unhealthy foods.

Context Medical strategies targeting remission of type 2 diabetes have not been systematically studied. Objective This trial assessed the feasibility, safety, and potential to induce remission of a short-term intensive metabolic strategy. Design A randomized, parallel, open-label pilot trial with 83 participants followed for 52 weeks. Setting Ambulatory care. Participants Patients with type 2 diabetes of up to 3 years in duration. Interventions Participants were randomized to: (1) an 8-week intensive metabolic intervention, (2) a 16-week intensive metabolic intervention, or (3) standard diabetes care. During the intensive intervention period, weight loss and normoglycemia were targeted using lifestyle approaches and treatment with metformin, acarbose, and insulin glargine. Diabetes drugs were then discontinued in the intervention groups and participants were followed for hyperglycemic relapse. Primary outcome On-treatment normoglycemia. Results At 8 weeks, 50.0% of the 8-week intervention group vs 3.6% of controls achieved normoglycemia on therapy [relative risk (RR), 14.0; 95% confidence interval (CI), 1.97 to 99.38), and at 16 weeks, these percentages were 70.4% in the 16-week group and 3.6% in controls (RR, 19.7; 95% CI, 2.83 to 137.13). Twelve weeks after completion of the intervention, 21.4% of the 8-week group compared with 10.7% of controls (RR, 2.00; 95% CI, 0.55 to 7.22) and 40.7% of the 16-week group compared with 14.3% of controls (RR, 2.85; 95% CI, 1.03 to 7.87) met hemoglobin A1C criteria for complete or partial diabetes remission. Conclusions A short course of intensive lifestyle and drug therapy achieves on-treatment normoglycemia and promotes sustained weight loss. It may also achieve prolonged, drug-free diabetes remission and strongly supports ongoing studies of novel medical regimens targeting remission.

Objective Adults with type 2 diabetes mellitus (DM) have an elevated fracture risk despite normal areal bone mineral density (aBMD). The study objective was to compare trabecular bone microarchitecture of postmenopausal women with type 2 DM and women without type 2 DM. Methods An extremity 1T magnetic resonance imaging system was used to acquire axial images (195 × 195 × 1,000 μm3 voxel size) of the distal radius of women recruited from outpatient clinics or by community advertisement. Image segmentation yielded geometric, topologic, and stereologic outcomes, i.e., number and size of trabecular bone network holes (marrow spaces), endosteal area, trabecular bone volume fraction, nodal and branch density, and apparent trabecular thickness, separation, and number. Lumbar spine (LS) and proximal femur BMD were measured with dual x-ray absorptiometry. Microarchitectural differences were assessed using linear regression and adjusted for percent body fat, ethnicity, timed up-and-go test, Charlson Index, and calcium and vitamin D intake; aBMD differences were adjusted for body mass index (BMI). Results Women with type 2 DM (n = 30, mean ± SD age 71.0 ± 4.8 years) had larger holes (+13.3%; P = 0.001) within the trabecular bone network than women without type 2 DM (n = 30, mean ± SD age 70.7 ± 4.9 years). LS aBMD was greater in women with type 2 DM; however, after adjustment for BMI, LS aBMD did not differ between groups. Conclusion In women with type 2 DM, the average hole size within the trabecular bone network at the distal radius is greater compared to controls. This may explain the elevated fracture risk in this population.

Type 1 diabetes (T1D) negatively influences skeletal muscle health; however, its effect on muscle satellite cells (SCs) remains largely unknown. SCs from samples from rodents (Akita) and human subjects with T1D were examined to discern differences in SC density and functionality compared with samples from their respective control subjects. Examination of the Notch pathway was undertaken to investigate its role in changes to SC functionality. Compared with controls, Akita mice demonstrated increased muscle damage after eccentric exercise along with a decline in SC density and myogenic capacity. Quantification of components of the Notch signaling pathway revealed a persistent activation of Notch signaling in Akita SCs, which could be reversed with the Notch inhibitor DAPT. Similar to Akita samples, skeletal muscle from human subjects with T1D displayed a significant reduction in SC content, and the Notch ligand, DLL1, was significantly increased compared with control subjects, supporting the dysregulated Notch pathway observed in Akita muscles. These data indicate that persistent activation in Notch signaling impairs SC functionality in the T1D muscle, resulting in a decline in SC content. Given the vital role played by the SC in muscle growth and maintenance, these findings suggest that impairments in SC capacities play a primary role in the skeletal muscle myopathy that characterizes T1D.