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This study assessed the efficacy of insulin degludec/liraglutide (IDegLira) vs insulin glargine U100 (IGlar) across categories of baseline glycated haemoglobin (HbA1c; ≤7.5%, >7.5% to ≤8.5% and >8.5%), body mass index (BMI

OBJECTIVE Emerging evidence suggests that peripheral neuropathy begins in the early stages of diabetes pathogenesis. Our objective was to describe the prevalence of peripheral neuropathy and nerve dysfunction according to glucose tolerance and metabolic syndrome status and examine how these conditions are associated with neurological changes in individuals at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS We studied 467 individuals in the longitudinal PROMISE (Prospective Metabolism and Islet Cell Evaluation) cohort. Peripheral neuropathy was defined by Michigan Neuropathy Screening Instrument (MNSI) scores (>2), and the severity of nerve dysfunction was measured objectively by vibration perception thresholds (VPTs) using a neurothesiometer. Metabolic syndrome was defined using the International Diabetes Federation/American Heart Association harmonized criteria. RESULTS The prevalence of peripheral neuropathy was 29%, 49%, and 50% for normal glycemia, prediabetes, and new-onset diabetes, respectively (P < 0.001 for trend). The mean VPT was 6.5 V for normal glycemia, 7.9 V for prediabetes, and 7.6 V for new-onset diabetes (P = 0.024 for trend). Prediabetes was associated with higher MNSI scores (P = 0.01) and VPTs (P = 0.004) versus normal glycemia, independent of known risk factors. Additionally, progression of glucose intolerance over 3 years predicted a higher risk of peripheral neuropathy (P = 0.007) and nerve dysfunction (P = 0.002). Metabolic syndrome was not independently associated with MNSI scores or VPTs. CONCLUSIONS In individuals with multiple risk factors for diabetes, prediabetes was associated with similar risks of peripheral neuropathy and severity of nerve dysfunction as new-onset diabetes. Prediabetes, but not metabolic syndrome, was independently associated with both the presence of peripheral neuropathy and the severity of nerve dysfunction.

Aims The long-term efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, was evaluated over 104 weeks in patients aged 55–80 years with type 2 diabetes mellitus (T2DM) inadequately controlled on a stable antihyperglycaemic agent regimen. Methods In this randomized, double-blind, phase III study, patients received canagliflozin 100 or 300 mg or placebo once daily during a 26-week core period (N = 714) and a 78-week extension period (n = 624). Efficacy endpoints at week 104 included change from baseline in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and systolic blood pressure, and percent change from baseline in body weight and fasting plasma lipids. Safety was assessed by adverse event (AE) reports. Results At week 104, canagliflozin 100 and 300 mg were associated with reductions in HbA1c versus placebo (−0.32 and −0.43% vs 0.17%, respectively; overall mean baseline, 7.7%) and more patients achieved HbA1c

Our aim was to determine the longitudinal associations of individual NEFA with the pathogenesis of diabetes, specifically with differences in insulin sensitivity and beta cell function over 6 years in a cohort of individuals who are at risk for diabetes. In the Prospective Metabolism and Islet Cell Evaluation (PROMISE) longitudinal cohort, 477 participants had serum NEFA measured at the baseline visit and completed an OGTT at three time points over 6 years. Outcome variables were calculated using the OGTT values. At each visit, insulin sensitivity was assessed using the HOMA2 of insulin sensitivity (HOMA2-%S) and the Matsuda index, while beta cell function was assessed using the insulinogenic index over HOMA-IR (IGI/IR) and the insulin secretion-sensitivity index-2 (ISSI-2). Generalised estimating equations were used, adjusting for time, waist, sex, ethnicity, baseline age, alanine aminotransferase (ALT) and physical activity. NEFA were analysed as both concentrations (nmol/ml) and proportions (mol%) of the total fraction. Participants’ (73% female, 70% with European ancestry) insulin sensitivity and beta cell function declined by 14–21% over 6 years of follow-up. In unadjusted models, several NEFA (e.g. 18:1 n-7, 22:4 n-6) were associated with lower insulin sensitivity, however, nearly all of these associations were attenuated in fully adjusted models. In adjusted models, total NEFA, 16:0, 18:1 n-9 and 18:2 n-6 (as concentrations) were associated with 3.7–8.0% lower IGI/IR and ISSI-2, while only 20:5 n-3 (as mol%) was associated with 7.7% higher HOMA2-%S. Total NEFA concentration was a strong predictor of lower beta cell function over 6 years. Our results suggest that the association with beta cell function is due to the absolute size of the serum NEFA fraction, rather than the specific fatty acid composition.

Insulin is the most effective therapy for achieving optimal glycemic control; however, many patients with type 2 diabetes on an intensified treatment regimen fail to achieve the recommended HbA1c target (1,2) and face the risk of adverse effects such as hypoglycemia and weight gain (3). The addition of sodium–glucose cotransporter 2 (SGLT2) inhibitors to a regimen of insulin therapy in this patient population has the potential to mitigate insulin-related weight gain and risk of hypoglycemia, with the added benefit of insulin dose reduction (4). Randomized controlled trials (RCTs) have shown improved clinical outcomes of SGLT2 inhibitors as monotherapy and as an add-on to oral and insulin therapy, but there is a paucity of real-world (RW) studies evaluating similar outcomes. Data extracted from WebDR (5) was used to evaluate the RW clinical impact of SGLT2 inhibitors (initiation of canagliflozin or dapagliflozin between February 2014 and December 2016) as an add-on to insulin therapy in patients with type 2 diabetes not achieving glycemic targets (those with HbA1c >7% [>53 mmol/mol]). Empagliflozin was excluded because of inadequate sample size. Ethical approval …

Objectives In order to scale-up successful innovations, more evidence is needed to evaluate programs that attempt to address the rising prevalence of diabetes and the associated burdens on patients and the healthcare system. This study aimed to assess the construct and content validity of the Diabetes Evaluation Framework for Innovative National Evaluations (DEFINE), a tool developed to guide the evaluation, design and implementation with built-in knowledge translation principles. Methods A modified Delphi method, including 3 individual rounds (questionnaire with 7-point agreement/importance Likert scales and/or open-ended questions) and 1 group round (open discussion) were conducted. Twelve experts in diabetes, research, knowledge translation, evaluation and policy from Canada (Ontario, Quebec and British Columbia) and Australia participated. Quantitative consensus criteria were an interquartile range of ≤1. Qualitative data were analyzed thematically and confirmed by participants. An importance scale was used to determine a priority multi-level indicator set. Items rated very or extremely important by 80% or more of the experts were reviewed in the final group round to build the final set. Results Participants reached consensus on the content and construct validity of DEFINE, including its title, overall goal, 5-step evaluation approach, medical and nonmedical determinants of health schematics, full list of indicators and associated measurement tools, priority multi-level indicator set and next steps in DEFINE's development. Conclusions Validated by experts, DEFINE has the right theoretic components to evaluate comprehensively diabetes prevention and management programs and to support acquisition of evidence that could influence the knowledge translation of innovations to reduce the burden of diabetes.

Many investments have been made to help address the rising prevalence and associated costs of diabetes, but there has been minimal evaluation to assess their value. A comprehensive literature review and five expert committee meetings were conducted to iteratively conceptualize and develop a Diabetes Evaluation Framework (DEFINE). Building on existing frameworks, DEFINE provides an evidence-based approach for evaluating diabetes. The framework is focused on guiding evaluation, building robust evidence, and fostering knowledge translation. DEFINE promotes comprehensive evaluation of initiatives targeting diabetes prevention and management, and will facilitate policy innovations to reduce the burden of diabetes. Plusieurs investissements ont ete deployes pour lutter contre la prevalence croissante du diabete et ses couts aff erents, mais peu d’efforts pour evaluer leurs benefi ces. Une recension exhaustive de la litterature et cinq reunions d’un comite d’experts ont eu lieu pour concevoir et developper de facon iterative un cadre d’evaluation du diabete. Baptise DEFINE, ce cadre base sur des modeles existants s’avere une methode fondee sur des donnees probantes pour evaluer le diabete. Le cadre vise a orienter l’evaluation, etablir des donnees probantes, et faciliter le transfert de connaissances. DEFINE vise la promotion de l’evaluation comprehensive des initiatives ciblant la prevention et la gestion du diabete et facilite les innovations politiques aidant a reduire le fardeau du diabete.

The majority of diabetes care in Canada is provided within the primary healthcare setting. It is delivered in a variety of models ranging from the physician working in a solo fee-for-service practice to an interprofessional team setting with specialist collaboration. To augment diabetes-related health services, the Ontario government has provided substantial funding to support community diabetes education programs. These models and initiatives are improving diabetes outcomes, and continued evolution of these programs can provide even greater outcomes. The St. Joseph's Primary Care Diabetes Support Program (SJHC PCDSP) is an innovative model that incorporates multidisciplinary allied health professionals together with physician support to provide care for more than 3000 patients in London, Ontario, Canada. It embodies the Canadian Diabetes Association (CDA)'s Organizations of Care recommendations to combine patient education and self-management with active medical support at each clinic encounter, all while embodying the tenets of primary care. A brief review of primary healthcare reform is provided to explain how the SJHC PCDSP combines features of current models in a unique format so as to deliver exceptional patient care. By providing a detailed description of the services delivered at the SJHC PCDSP, it is hoped that both specialists and primary care providers consider using and adapting approaches to diabetes management based on this innovative model to optimize their practices.

OBJECTIVE Diabetes self-management is universally regarded as a foundation of diabetes care. We determined whether comparable glycemic control could be achieved by self-titration versus physician titration of a once-daily bolus insulin dose in patients with type 2 diabetes who are unable to achieve optimal glycemia control with a basal insulin. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes, an HbA1c level >7% (53 mmol/mol), and either nocturnal hypoglycemia episodes or an insufficient basal insulin glargine level (with or without oral agents) to achieve a fasting plasma glucose level ≤6 mmol/L (108 mg/dL) were studied. Participants all had bolus insulin glulisine added at breakfast and were allocated to either algorithm-guided patient self-titration or physician titration. The primary outcome was an HbA1c level ≤7% (53 mmol/mol) without severe hypoglycemia. RESULTS After a mean (SD) follow-up of 159.4 days (36.2 days), 28.4% of participants in the self-titration arm vs. 21.2% in the physician titration arm achieved an HbA1c level of ≤7% (53 mmol/mol) without severe hypoglycemia (between-group absolute difference 7.2%; 95% CI −3.2 to 17.7). The lower end of this 95% confidence interval was within the predetermined noninferiority boundary of −5% (P noninferiority = 0.011). CONCLUSIONS In stable patients with type 2 diabetes who are receiving doses of basal insulin glargine who require bolus insulin, a simple bolus insulin patient-managed titration algorithm is as effective as a physician-managed algorithm.

ObjectiveThe aim of this study was to investigate the impact of hypoglycemia according to severity and time of onset on health-related quality of life (HRQoL) in a Canadian population.MethodsTime trade-off (TTO) methodology was used to estimate health utilities associated with hypoglycemic events in a representative sample of the Canadian population. A global analysis conducted in the United Kingdom, Canada, Germany and Sweden has been published. The present Canadian analysis focuses on 3 populations: general, type 1 and type 2 diabetes. Using a web-based survey, participants (>18 years) assessed the utility of 13 different health states (severe, non-severe, daytime and nocturnal hypoglycemia at different frequencies) using a scale from 1 (perfect health) to 0 (death). The average disutility value for each type of event was calculated.ResultsOf 2258 participants, 1696 completers were included in the analysis. A non-severe nocturnal hypoglycemic event was associated with a significantly greater disutility than a non-severe daytime event (−0.0076 vs. −0.0056, respectively; p=0.05), while there was no statistically significant difference between severe nocturnal and severe daytime events (−0.0616 vs. −0.0592; p=0.76). Severe hypoglycemia was associated with greater disutility than non-severe hypoglycemia (p

OBJECTIVE Short leg length, a marker of early childhood deprivation, has been used in studies of the association of early life conditions with adult chronic disease risk. The objective of this study was to determine the cross-sectional associations of leg length with measures of insulin sensitivity and β-cell function. RESEARCH DESIGN AND METHODS Subjects (n = 462) at risk for type 2 diabetes were recruited into the PROspective Metabolism and ISlet cell Evaluation (PROMISE) longitudinal cohort. Leg length was calculated from sitting and standing height at the 3-year clinical examination. Glucose tolerance status was determined using an oral glucose tolerance test. Insulin sensitivity was assessed using homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda insulin sensitivity index (ISI), while the insulinogenic index over HOMA-IR (IGI/IR) and the insulin secretion sensitivity index 2 (ISSI-2) determined β-cell function. Multiple linear regression analysis was conducted, adjusting for covariates including age, sex, ethnicity, family history of diabetes, waist, and weight. RESULTS Leg length and leg-to-height ratio were significantly associated with HOMA-IR (β = −0.037, β = −10.49, respectively; P < 0.0001), ISI (β = 0.035, β = 8.83, respectively; P < 0.0001), IGI/IR (β = 0.021, P < 0.05; β = 7.60, P < 0.01, respectively), and ISSI-2 (β = 0.01, P < 0.03; β = 3.34, P < 0.01, respectively) after adjustment for covariates. The association of shorter leg length with lower insulin sensitivity was most evident for those with high waist circumferences. CONCLUSIONS Shorter legs were independently associated with lower insulin sensitivity and β-cell function, suggesting that early childhood deprivation may increase the risk of developing diabetes.

Aim To investigate the cardiometabolic risk (CMR) assessment and management patterns for individuals with and without type 2 diabetes mellitus (T2DM) in Canadian primary care practices. Methods Between April 2011 and March 2012, physicians from 9 primary care teams and 88 traditional non-team practices completed a practice assessment on the management of 2461 patients >40 years old with no clinical evidence of cardiovascular disease and diagnosed with at least one of the following risk factor—T2DM, dyslipidaemia or hypertension. Results There were 1304 individuals with T2DM and 1157 without. Pharmacotherapy to manage hyperglycaemia, dyslipidaemia and hypertension was widely prescribed. Fifty-eight percent of individuals with T2DM had a glycated haemoglobin (HbA1c) ≤7.0%. Amongst individuals with dyslipidaemia, median low-density lipoprotein cholesterol (LDL-C) was 1.8 mmol/l for those with T2DM and 2.8 mmol/l for those without. Amongst individuals with hypertension, 30% of those with T2DM achieved the

To gain insight into the current management of patients with type 2 diabetes mellitus by Canadian primary care physicians.A total of 479 primary care physicians from across Canada submitted data on 5123 type 2 diabetes patients whom they had seen on a single day on or around World Diabetes Day, November 14, 2012.Mean glycated hemoglobin (A1C) was 7.4%, low-density lipoprotein (LDL-C) was 2.1 mmol/L and blood pressure (BP) was 128/75 mm Hg. A1C ≤7.0% was met by 50%, LDL-C ≤2.0 mmol/L by 57%, BP130/80 mm Hg by 36% and the composite triple target by 13% of patients. Diet counselling had been offered to 38% of patients. Of the 87% prescribed antihyperglycemic agents, 18% were on 1 non-insulin antihyperglycemic agent (NIAHA) (85% of which was metformin), 15% were on 2 NIAHAs, 6% were on ≥3 NIAHAs, 19% were on insulin only and 42% were on insulin + ≥1 NIAHA(s). Amongst the 81% prescribed lipid-lowering therapy, 88% were on monotherapy (97% of which was a statin). Among the 83% prescribed antihypertensive agents, 39%, 34%, 21% and 6% received 1, 2, 3 and3 drugs, respectively, with 59% prescribed angiotensin-converting enzyme inhibitors and 35% angiotensin II receptor blockers.The Diabetes Mellitus Status in Canada survey highlights the persistent treatment gap associated with the treatment of type 2 diabetes and the challenges faced by primary care physicians to gain glycemic control and global vascular protection in these patients. It also reveals a higher use of insulin therapy in primary care practices relative to previous surveys. Practical strategies aimed at more effectively managing type 2 diabetes patients are urgently needed.

CONTEXT Vitamin D may play a role in the aetiology of the metabolic syndrome (MetS), yet the majority of previous studies have been cross-sectional, and the limited number of prospective studies has yielded inconsistent results. OBJECTIVE To examine the prospective association of vitamin D [25-hydroxyvitamin D, 25(OH)D] with MetS in a multi-ethnic cohort of adults in Ontario, Canada. DESIGN Nondiabetic individuals with pre-existing MetS risk factors were recruited for participation in the PROspective Metabolism and ISlet cell Evaluation (PROMISE) cohort study, a longitudinal study of the determinants of insulin resistance and MetS. METHODS Of the 654 participants enrolled at baseline, 489 attended a 3-year follow-up visit. There were 301 participants eligible for the analysis of 25(OH)D with incident MetS (age 49·2 ± 9·3 years old, 75·4% female), after excluding 188 (38·5%) prevalent MetS cases at baseline. Longitudinal change in MetS components was assessed in the entire follow-up cohort. RESULTS There were 76 (15·5%) participants who developed MetS over the 3-years of follow-up. Multivariate logistic regression analyses indicated a decreased risk of MetS at follow-up per standard deviation increase in baseline 25(OH)D after adjustment for sociodemographics, season, baseline and change in supplement use and physical activity and insulin resistance (OR = 0·63, 95% CI 0·44-0·90). Multivariate linear regression analyses revealed a significant inverse association of baseline 25(OH)D with fasting glucose at follow-up (β = -0·0005, P = 0·025). CONCLUSIONS There was a significant inverse association of baseline 25(OH)D with incident MetS, which may be partly driven by its association with glucose homoeostasis.

All the basal insulin products currently available have suboptimal pharmacokinetic (PK) properties, with none reliably providing a reproducible and peakless pharmacodynamic (PD) effect that endures over 24 h from once-daily dosing. Insulin degludec is a novel acylated basal insulin with a unique mechanism of protracted absorption involving the formation of a depot of soluble multihexamer chains after subcutaneous injection. PK/PD studies show that insulin degludec has a very long duration of action, with a half-life exceeding 25 h. Once-daily dosing produces a steady-state profile characterized by a near-constant effect, which varies little from injection to injection in a given patient. Clinically, insulin degludec has been shown consistently to carry a lower risk of nocturnal hypoglycaemia than once-daily insulin glargine, in both basal+bolus and basal-only insulin regimens. The constancy of the steady-state profile of insulin degludec also means that day-to-day irregularities at the time of injection have relatively little PD influence, thereby offering the possibility of greater treatment flexibility for patients. © 2012 Blackwell Publishing Ltd.

Aims To compare the safety and efficacy of a simpler titration algorithm for insulin degludec/liraglutide (IDegLira) with that used in previous DUAL trials in insulin-naive patients with type 2 diabetes. Research design and methods This 32-week, open-label, non-inferiority trial randomized adults with type 2 diabetes uncontrolled on metformin ± pioglitazone to receive IDegLira, titrated either once weekly, based on the mean of 2 pre-breakfast plasma glucose (PG) readings (n = 210), or twice weekly, based on the mean of 3 pre-breakfast PG readings (n = 210). Results Mean HbA1c decreased from 8.2% (65 mmol/mol) to 6.1% (43 mmol/mol) with once-weekly titration and from 8.1% (65 mmol/mol) to 6.0% (42 mmol/mol) with twice-weekly titration; non-inferiority was confirmed (estimated treatment difference: 0.12% [−0.04; 0.28]95% CI , 1.30 mmol/mol [−0.41; 3.01]95% CI ). Approximately 90% of patients achieved HbA1c

Patients with type 2 diabetes mellitus (T2DM) are unlikely to maintain glycemic control with monotherapy, and will eventually require therapy with multiple antihyperglycemic agents (AHAs). Combination therapy regimens with multiple AHAs may be complex and negatively impact patient adherence. Fixed-dose combinations (FDCs) are used successfully for management of numerous chronic diseases. Areas covered: This article includes a brief overview of the add-on approach of current treatment guidelines for T2DM and reviews the evidence supporting the utility of oral FDCs in the treatment of T2DM, including recently developed oral FDCs (2010-2016). Benefits regarding safety and tolerability, adherence and cost are also discussed. Finally, the barriers limiting the use of FDCs and how these barriers may be overcome are addressed. Expert commentary: Therapeutic strategies including FDCs need to be implemented on a larger scale. FDCs have the potential to simplify treatment regimens, improve adherence and provide long-term glycemic control.

Context:Specific serum fatty acid (FA) profiles predict the development of incident type 2 diabetes; however, limited longitudinal data exist exploring their role in the progression of insulin sensitivity (IS) and β-cell function.Objective:To examine the longitudinal associations of the FA composition of serum phospholipid (PL) and cholesteryl ester (CE) fractions with IS and β-cell function over 6 years.Design:The Prospective Metabolism and Islet Cell Evaluation (PROMISE) cohort is a longitudinal observational study, with clinic visits occurring every 3 years. Three visits have been completed, totaling 6 years of follow-up.Setting:Individuals (n = 477) at risk for diabetes recruited from the general population in London and Toronto, Canada.Main Outcome Measures:Values from an oral glucose tolerance test were used to compute 1/HOMA-IR and the Matsuda index for IS, the insulinogenic index over HOMA-IR, and the insulin secretion-sensitivity index-2 for β-cell function. Thin-layer chromatograph and gas chromatograph quantified FA. Generalized estimating equations were used for the analysis.Results:IS and β-cell function declined by 8.3–19.4% over 6 years. In fully adjusted generalized estimating equation models, PL cis-vaccenate (18:1n-7) was positively associated with all outcomes, whereas γ-linolenate (GLA; 18:3n-6) and stearate (18:0) were negatively associated with IS. Tests for time interactions revealed that PL eicosadienoate (20:2n-6) and palmitate (16:0) and CE dihomo-γ-linolenate (20:3n-6), GLA, and palmitate had stronger associations with the outcomes after longer follow-up.Conclusions:In a Canadian population at risk for diabetes, we found that higher PL stearate and GLA and lower cis-vaccenic acid predicted consistently lower IS and β-cell function over 6 years.

Background Type 2 diabetes mellitus is a growing concern worldwide, particularly in Indigenous communities, which have undergone a marked nutrition transition characterized by reduced intakes of traditional foods and increased intakes of market foods. Few studies have assessed the relationships between differing dietary patterns and risk for type 2 diabetes in Indigenous communities in Canada. The objective of the study was to characterize dietary patterns using factor analysis (FA) and to relate these patterns to the incidence of type 2 diabetes after 10 years of follow up in a First Nations community in Ontario, Canada. Methods We conducted a prospective analysis of 492 participants in the SLHDP who did not have diabetes at baseline (1993 to 1995) and were followed for 10 years. A food-frequency questionnaire was administered, and FA was used to identify patterns of food consumption. Multivariate logistic regression analyses determined associations of food patterns with incident type 2 diabetes, adjusting for sociodemographic and lifestyle confounders. Results At follow up, 86 participants had developed incident type 2 diabetes. FA revealed 3 prominent dietary patterns: Balanced Market Foods, Beef and Processed Foods and Traditional Foods. After adjustment for age, sex, waist circumference, interleukin-6 and adiponectin, the Beef and Processed Foods pattern was associated with increased risk for incident type 2 diabetes (OR=1.38; 95% CI 1.02, 1.86). In contrast, the Balanced Market Foods and Traditional Foods Patterns were not significantly associated with type 2 diabetes. Conclusions Dietary interventions should encourage reduced consumption of unhealthful market foods, in combination with improvements in local food environments so as to increase access to healthful foods and reduce food insecurity in Indigenous communities.

Cardiometabolic risk (CMR) refers to the collective consideration of traditional and emerging risk factors that amplify the potential of developing atherogenic cardiovascular disease, as well as the emergence of type 2 diabetes mellitus. Cumulative data suggest that the metabolic syndrome confers a 5-fold increase in risk for type 2 diabetes mellitus and also increases the cardiovascular risk calculated by conventional algorithms by an additional 1.5- to 2.0-fold. This article is a summary of the recently published position article on cardiometabolic risk by the nationally represented inter-disciplinary Cardiometabolic Risk Working Group (Can J Cardiol. 2011;27:e1–e33). The objective of this article is to review what the emerging risk factors are, how to determine if individuals at risk for or with type 2 diabetes mellitus have elevated CMR and the steps that should be taken to optimally manage and reduce CMR in these patients.

Objective To determine the visit and patient factors associated with specialist referral for patients with type 2 diabetes mellitus. Methods The sample consisted of 9443 patient-physician visits from 8 family practice groups in southwestern and central Ontario. The generalized estimating equations approach was used for fitting logistic regression models to the referral data from patients' visits. Results The odds of referral decreased if a visit occurred with a female patient and if an albumin-creatinine ratio measurement was not available at the visit. A 1 year increase in the number of years with the family physician resulted in a lower odds of referral. The odds of referral increased if the patient had a specialist appointment in the previous 2 years, if lifestyle counselling occurred and if a neuropathy examination was carried out. Conclusion Further research should assess the influence of visit level factors on decision making. Guidelines for specialist referral should also be considered.

Diabet. Med. 29, e180–e183 (2012) Abstract Aims To compare the prevalence of diabetes in pregnancy, pregnancy care and adverse pregnancy outcomes in on-reserve First Nations women vs. non-First Nations women in Ontario, Canada. Methods A retrospective population-based cohort study was performed. All 487 368 live singleton hospital deliveries between 1 April 2002 and 31 March 2010 were identified. Outcomes were defined by linking mothers and infants to provincial healthcare administrative databases. Results Diabetes in pregnancy was more prevalent in First Nations women (10.3 vs. 6.0%). They received less pregnancy care and had higher rates of adverse outcomes than non-First Nations women with diabetes. Conclusions First Nations women are at a higher risk of diabetes in pregnancy and adverse outcomes. This highlights the need for increased care for pregnant First Nations women.

OBJECTIVE To examine the prospective associations of baseline vitamin D [25-hydroxyvitamin D; 25(OH)D] with insulin resistance (IR), β-cell function, and glucose homeostasis in subjects at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS We followed 489 subjects, aged 50 ± 10 years, for 3 years. At baseline and follow-up, 75-g oral glucose tolerance tests (OGTTs) were administered. IR was measured using the Matsuda index (ISOGTT) and the homeostasis model assessment of IR (HOMA-IR), β-cell function was determined using both the insulinogenic index divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2), and glycemia was assessed using the area under the glucose curve (AUCglucose). Regression models were adjusted for age, sex, ethnicity, season, and baseline value of the outcome variable, as well as baseline and change in physical activity, vitamin D supplement use, and BMI. RESULTS Multivariate linear regression analyses indicated no significant association of baseline 25(OH)D with follow-up ISOGTT or HOMA-IR. There were, however, significant positive associations of baseline 25(OH)D with follow-up IGI/IR (β = 0.005, P = 0.015) and ISSI-2 (β = 0.002, P = 0.023) and a significant inverse association of baseline 25(OH)D with follow-up AUCglucose (β = −0.001, P = 0.007). Progression to dysglycemia (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes) occurred in 116 subjects. Logistic regression analyses indicated a significant reduced risk of progression with higher baseline 25(OH)D (adjusted odds ratio 0.69 [95% CI 0.53–0.89]), but this association was not significant after additional adjustment for baseline and change in BMI (0.78 [0.59–1.02]). CONCLUSIONS Higher baseline 25(OH)D independently predicted better β-cell function and lower AUCglucose at follow-up, supporting a potential role for vitamin D in type 2 diabetes etiology.

Process measures are heavily relied on to assess physician performance/quality of diabetes control. A unique primary care electronic medical record-health administrative database linkage found no clinically meaningful relationship between control (HbA1c value) and number of tests performed, casting doubt on the usefulness in diabetes performance and quality of care assessment.

OBJECTIVE In the Canadian Normoglycemia Outcome Evaluation (CANOE) trial, low-dose rosiglitazone/metformin reduced the risk of diabetes in subjects with impaired glucose tolerance by 66% over a median of 3.9 years. We evaluate the temporal changes in glycemic control, insulin sensitivity, and β-cell function during this trial. RESEARCH DESIGN AND METHODS CANOE participants (n = 207) underwent annual oral glucose tolerance testing, enabling temporal comparison of glycemia, insulin sensitivity (Matsuda index), and β-cell function (insulin secretion-sensitivity index-2 [ISSI-2]) between the rosiglitazone/metformin and placebo arms. RESULTS Glycemic parameters and insulin sensitivity improved in the rosiglitazone/metformin arm in year 1, but deteriorated in the years thereafter as in the placebo arm. Generalized estimating equation analysis confirmed that both insulin sensitivity and β-cell function decreased over time (Matsuda: β = −0.0515, P < 0.0001; ISSI-2: β = −6.6507, P < 0.0001), with no significant time-by-treatment interaction (Matsuda: P = 0.57; ISSI-2: P = 0.22). CONCLUSIONS Despite preventing incident diabetes, low-dose rosiglitazone/metformin did not modify the natural history of worsening insulin resistance and β-cell dysfunction.

Aims The aim of this cross-sectional study was to document the clinical management of type 2 diabetes and related complications in Canada's First Nations. Methods Patients were randomly selected from 19 communities. Data from charts from consenting patients were collected. Results Of 885 patients, 63.3% were female, mean age was 54.9 years and mean duration of T2DM was 11.2 years. Mean A1C was 8.2%; 61.1% of patients had an A1C >7.0%; mean LDL was 2.4 mmol/L; 92.6% had dyslipidemia; mean systolic BP was 132 mmHg; mean diastolic BP was 76 mmHg; 92.0% had hypertension. Lipid-lowering medications were prescribed to 62.9% of those with dyslipidemia and an LDL-C >2.0 mmol/L. Of hypertensive patients, 15.8% were not on an antihypertensive agent. For vascular protection, 55.1% were on a statin, 72.1% on an ACE inhibitor or ARB, and 64.5% on an anticoagulant. Smoking was documented in 39.4%, 92.1% were overweight/obese; 55.1% had chronic kidney disease, and 13.3% had coronary artery disease. Conclusions Major care gaps were revealed, with most patients not achieving glycemic, lipid and BP targets. Over half of this relatively young cohort had established microvascular disease. Macrovascular disease rates may increase dramatically due to the high prevalence of risk factors.

Objectives To evaluate vascular protection treatment patterns and attainment of the 2003 Canadian Diabetes Association's recommended targets in ambulatory patients with type 2 diabetes. Methods Between 2005 and 2006, 3002 outpatients with type 2 diabetes were enrolled by 229 primary health care settings across Canada. Baseline characteristics, therapeutic regimens and treatment success – defined as the achievement of a blood pressure (BP) of 130/80mmHg or lower, glycosylated hemoglobin (A1C) of 7% or lower, low-density lipoprotein cholesterol (LDL-C) lower than 2.5mmol/L and total cholesterol/ high-density lipoprotein cholesterol ratio lower than 4.0 – are reported. Results Overall, 46% of individuals had a BP that was above the Canadian Diabetes Association's recommended target. Of these, 11% were untreated, 28% were receiving monotherapy, 38% were not receiving an angiotensin-converting enzyme inhibitor and 16% were not receiving either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Optimal A1C levels were achieved in 53% of patients. Of those who did not attain A1C targets, 3% were not on glucose-lowering pharmacotherapy and 27% were receiving monotherapy. A total of 74% of patients were treated with statins. Overall, 64% and 62%, respectively, met the target LDL-C and the target total cholesterol/high-density lipoprotein cholesterol ratio. Statins were not prescribed to 43% of patients with LDL-C above target. Antiplatelet therapy was implemented in 81% of patients. In total, 21% achieved the combined targets for BP, A1C and LDL-C. Interpretation A substantial proportion of patients did not achieve guideline-recommended targets and were not receiving evidence-based therapy for vascular protection two years after publication of the Canadian guidelines. More research is warranted, and novel and effective strategies must be tested and implemented to correct this ongoing treatment gap.

Background: Expanding evidence indicates that apolipoprotein B (apo B) is superior to LDL cholesterol as a marker of vascular disease. Although traditional lipid measures are known to predict type 2 diabetes, limited data are available regarding apo B. We assessed the association of apo B with incident type 2 diabetes and compared it with traditional lipid variables as a risk predictor in aboriginal Canadians. Methods: Of an initial cohort of 606 individuals without diabetes in 1993–1995, 540 were contacted for the 10-year follow-up evaluation in 2003–2005. Fasting and 2-h postload glucose concentrations were obtained at baseline and follow-up to determine incident type 2 diabetes. Baseline fasting serum lipids were measured with standard laboratory procedures. Results: The cumulative 10-year incidence of type 2 diabetes was 17.5%. High concentrations of apo B, triglycerides, and LDL cholesterol, and low concentrations of HDL cholesterol were individually associated with incident type 2 diabetes in univariate analyses. Comparing C statistics of univariate models showed apo B to be a superior determinant of incident diabetes compared with LDL (P = 0.026) or HDL (P = 0.004) cholesterol. With multivariate adjustment including waist circumference, apo B (odds ratio, 1.50; 95% CI, 1.11–2.02) and triglycerides (odds ratio, 1.49; 95% CI, 1.12–1.98) remained associated with incident diabetes, whereas LDL and HDL cholesterol became nonsignificant. Conclusions: The association of plasma apo B with incident type 2 diabetes and its better prediction of risk compared with LDL or HDL cholesterol suggest the potential for the use of apo B in type 2 diabetes risk communication and prevention.

This paper outlines ways to maximize response rates to surveys by summarizing the most relevant literature to date and demonstrating how these techniques have resulted in consistently high rates of return in family practice research. We describe the methodology used in recent surveys of physicians conducted by the Centre for Studies in Family Medicine through its Thames Valley Family Practice Research Unit, located in London, Ontario, Canada and funded by the Ontario Ministry of Health and Long-Term Care. The identification and implementation of these techniques to maximize response rates is critical, as primary health care researchers often rely on information gathered through questionnaires to study physicians' practice profiles, experiences and attitudes. Four separate and distinct mailed surveys of physicians using a modified Dillman approach were conducted from 2001 to 2004. The sampling strategies, topics, types of questions and response formats of these surveys varied. The first survey did not use any incentives or recorded delivery/registered mail and received a response rate of 48%. In sharp contrast, the other three surveys obtained responses rates of 76%, 74%, 74%, respectively, achieved through the use of gift certificates and recorded delivery/registered mail. Sending a survey by recorded delivery/registered mail tends to result in the survey package being given priority in the physicians' incoming mail at the practice. Gift certificates partially compensate physicians for time spent completing the survey and recognition of the time required is appreciated. The response rates achieved provide strong evidence to support the use of monetary incentives and recorded delivery/registered mail (along with the Dillman approach) in survey research. It is anticipated that this evidence will be used by other researchers to justify requests for funding to cover the costs associated with incentives and recorded delivery/registered mail. We recommend the use of these strategies to maximize response rates and improve the quality of this type of primary health care research.

Objectives To measure knowledge of Israeli low back pain (LBP) clinical practice guidelines among different subgroups of primary care doctors, prior to designing an intervention programme to enhance guideline adherence in practice. Study design Confidential mailed survey questionnaire. Setting Family practices in the Haifa and western Galilee district, Israel. Participants Random sample of 163 primary care doctors. A total of 134 doctors (82%) completed the questionnaire. Main outcome measures A Multiple Choice Questionnaire measuring knowledge of the LBP guidelines. Instrument reliability and inter-item reliability were tested in a pilot phase. Content validity was assured by having the Israeli LBP guideline authors involved in a consensus procedure. Results Distribution of test scores significantly differentiated professional levels and background variables, demonstrating the instrument reliability. Cronbach’s alpha was above 0.91. The average test score was 67.7 [standard deviation (SD) 16.2], family doctors had average scores of 75.2 (SD 9.8), general practitioners (GPs) 57.9 (SD 19) and family practice residents 67.4 (SD 13.2). The difference between the test average scores of family doctors, GPs and residents was significant (P

Introduction and objective The world's Indigenous peoples are experiencing an unprecedented epidemic of type 2 diabetes [T2DM] but little has been published describing the complications burden. The objective of this paper was to conduct a systematic review of T2DM complications in Indigenous populations worldwide. Methods A literature review was conducted using PubMed and EMBASE to examine available complications data. Country, Indigenous population, authors, publication year, total sample size, Indigenous sample size, age, methodology, and prevalence of nephropathy, end-stage renal disease, retinopathy, neuropathy, lower extremity amputations, cardiovascular disease, hospitalizations and mortality due to diabetes were recorded. Results One-hundred and eleven studies were selected. Results revealed a disproportionate burden of disease complications among all Indigenous peoples regardless of their geographic location. Complication rates were seen to vary widely across Indigenous groups. Discussion Gaps were found in the published literature on complications among Indigenous populations, especially those living in underdeveloped countries. These gaps may be in part due to the challenges caused by varying operational practices, research methodologies, and definitions of the term Indigenous, making documentation of rates among these peoples problematic. Comprehensive surveillance applying standardized definitions and methodologies is needed to design targeted prevention and disease management strategies for Indigenous peoples with T2DM.

Objective. To describe determinants of diet-related behavior and physical activity in First Nations for development of culturally appropriate diabetes prevention programs. Design. Cross-sectional 24-hour dietary recalls (n=129), random household risk factor surveys of primary food preparers/shoppers (n=133), and accelerometry (n=81) were assessed in First Nations adults. Setting. Nine Anishinaabe (Ojibwe and Oji-Cree) First Nations in northwestern Ontario, Canada. Results. Descriptive statistics (mean, SD, range) were calculated for all outcomes (dietary intake, psychosocial determinants of diabetes risk factors, dietary behaviors, physical activity, and body mass index, BMI) and t-tests were performed to examine differences in means between remote and semi-remote communities. Regression models adjusting for sociodemographic factors were also fit for the outcome measures. Respondents reported high-energy intake (2676 and 2060 kcal/day for men and women, respectively) and acquired higher fat/higher sugar/l...

OBJECTIVE—The aim of this study was to investigate associations of adiponectin, leptin, C-reactive protein (CRP), interleukin (IL)-6, and serum amyloid A (SAA), individually or in combinations, with risk of incident type 2 diabetes in an Aboriginal Canadian population. RESEARCH DESIGN AND METHODS—Of the 606 Sandy Lake Health and Diabetes Project cohort subjects who were free of diabetes at baseline, 540 (89.1%) participated in 10-year follow-up assessments. Concentrations of fasting adiponectin, leptin, CRP, IL-6, SAA, and covariates were measured at baseline. Fasting glucose and a 75-g oral glucose tolerance test were obtained at baseline and follow-up to determine incident type 2 diabetes, defined as clinically diagnosed type 2 diabetes or as fasting plasma glucose ≥7.0 mmol/l or 2-h postload plasma glucose ≥11.1 mmol/l at follow-up. RESULTS—Low adiponectin, high leptin, and low adiponectin-to-leptin ratio at baseline were associated with increased risk of incident type 2 diabetes after adjustment for age, sex, triglycerides, HDL cholesterol, hypertension, and impaired glucose tolerance (odds ratio 0.63 [95% CI 0.48–0.83], 1.50 [1.02–2.21], and 0.54 [0.37–0.77], respectively). When the models were additionally adjusted for waist circumference or BMI, however, only low adiponectin remained significantly associated with increased incident diabetes (0.68 [0.51–0.90]). Combinations of leptin, CRP, IL-6, and/or SAA with adiponectin, assessed using either the ratio or joint effects, did not improve diabetes prediction. CONCLUSIONS—Low baseline adiponectin is associated with increased risk of incident type 2 diabetes independent of leptin, CRP, IL-6, SAA, and metabolic syndrome variables including obesity.

The objective was to compare the impact on treatment satisfaction (TS) and quality of life (QoL) of early insulinization with glargine versus adjusting oral antidiabetic drug (OAD) therapy in people with Type 2 diabetes with uncontrolled glycemia. TS and QoL were assessed at baseline, weeks 12 and 24 within the Canadian INSIGHT, a randomized 24-week trial of Type 2 patients. A total of 366 patients randomized to either the insulin glargine arm (n=182) or the adjusted OAD therapy arm (n=184) completed both questionnaires. At baseline, TS and QoL were similar in both groups. A1c reduction was greater in the insulin glargine arm. TS improved from baseline in both treatment arms; however, there was greater increase with insulin glargine+OAD. Perceived frequency of hypoglycemia and hypoglycemia were lower at week 24, with no differences between the two groups. Perceived frequency of hyperglycemia improved with glargine at week 12, and no difference was found at 24 weeks. Finally, QoL improved in both groups, but significantly more with glargine at both weeks 12 and 24. Improving glucose control by adding insulin glargine to OAD therapy had a positive impact on TS and general QoL without complaints related to hypoglycemia.

Purpose Current low back pain (LBP) clinical guidelines have helped to summarize the scientific evidence and research, but have failed to provide tools and guide family physicians (FPs). The purpose of this study is to identify barriers and facilitators for the implementation of LBP guidelines from family FPs’ perspective. Methods A qualitative focus group study of FPs in the north of Israel. Purposeful sampling was used to recruit participants, all of them board-certified FPs. Four focus groups were created, and discussions were taped, transcribed and analysed for major themes. Results Focus groups findings have expanded the understanding of the intellectual and mental challenges faced by Israeli FPs caring for LBP patients and highlighted the many obstacles to implementing LBP guidelines. Physicians’ decision-making, pertaining to LBP, functions on three levels simultaneously: the physicians’ agenda based on familiarity with the guidelines; their need to remain grounded in the context of the specific patient–doctor relationship; and the constraints and demands of the physician’s workplace, medical system and environment. Conclusions Despite an overall positive attitude towards LBP guideline implementation, FPs found it hard to come to terms with the conflicting dimensions of LBP patient care. The patient–doctor interaction determined the outcome of the encounter, whether it complied with the guidelines and whether the encounter leads to a healing process or to a vicious circle of unnecessary utilization of services.

Serum concentration of cystatin C, a marker of glomerular filtration, has been associated with incident cardiovascular disease (CVD), although the pathophysiology underlying this association remains unclear. As North American Aboriginal populations are experiencing high prevalence rates of CVD in early adulthood, evaluation of cardiovascular (CV) risk factors in Aboriginal children may provide insight into the early pathophysiology of vascular disease. In this context, we sought to determine whether cystatin C is associated with CV risk factors in Aboriginal youth. Serum concentrations of cystatin C were assessed in a population-based study of a Canadian Aboriginal community, involving 230 children aged 10-19 years. Cystatin C was higher in the 41 children with pediatric metabolic syndrome (MetS) (defined using an age- and gender-specific version of Adult Treatment Panel III criteria) than in the 189 children free of MetS (0.87 vs 0.81 mg/l, p = 0.0026). After adjustment for age, gender, and glomerular filtration rate (estimated using the Schwartz formula), cystatin C was (1) positively correlated with waist circumference, body mass index, systolic blood pressure, triglycerides, fasting insulin, and leptin (all r >/= 0.18, p < 0.05), and (2) inversely related to high-density lipoprotein (HDL) cholesterol (r = -0.21, p = 0.0023). These associations, however, were attenuated with further adjustment for insulin resistance, as measured by the homeostasis model assessment (HOMA-IR). On multivariate analysis, waist circumference emerged as a positive independent determinant of cystatin C, whereas female gender and age were negative correlates. Cystatin C levels progressively increased in association with the number of metabolic syndrome component disorders coexistent within an individual (trend p = 0.0072). In summary, increased cystatin C is associated with an enhanced CV risk factor profile in Aboriginal youth and may be an early event in the natural history of vascular disease.

Epidemic rates of diabetes among Native North Americans demand novel solutions. Zhiiwaapenewin Akino'maagewin: Teaching to Prevent Diabetes was a community-based diabetes prevention program based in schools, food stores and health offices in seven First Nations in northwestern Ontario, Canada. Program interventions in these three institutions included implementation of Grades 3 and 4 healthy lifestyles curricula; stocking and labeling of healthier foods and healthy recipes cooking demonstrations and taste tests; and mass media efforts and community events held by health agencies. Qualitative and quantitative process data collected through surveys, logs and interviews assessed fidelity, dose, reach and context of the intervention to evaluate implementation and explain impact findings. School curricula implementation had moderate fidelity with 63% delivered as planned. Store activities had moderate fidelity: availability of all promoted foods was 70%, and appropriate shelf labels were posted 60% of the time. Cooking demonstrations were performed with 71% fidelity and high dose. A total of 156 posters were placed in community locations; radio, cable TV and newsletters were utilized. Interviews revealed that the program was culturally acceptable and relevant, and suggestions for improvement were made. These findings will be used to plan an expanded trial in several Native North American communities.

OBJECTIVE To report on the out-of-pocket expenses incurred by insulin- treated patients to manage blood glucose levels. METHODS This retrospective study in insulin-using adults with type 1 or type 2 diabetes was conducted between July 7 and December 12, 2003, in 4 Canadian centres, using a patient self-administered questionnaire and medical charts. The questionnaire collected data regarding duration of diabetes; duration of insulin therapy; type of diabetes; source of payment for insulin, oral antihyperglycemic agents and test strips (i.e. insurance company [with % coverage], government, self); average cost per month to treat hypoglycemia; frequency of self-monitoring of blood glucose and insulin injections; and frequency of diabetes-related visits to healthcare professionals. RESULTS All 335 patients enrolled completed the study; 202 (60.3%) had type 1 diabetes and 133 (39.7%) had type 2 diabetes; 29 patients (8.6%; 27 type 1 and 2 type 2 diabetes patients) used pump therapy. The mean out-of-pocket cost per person for all patients was $2.21 daily or $807 annually ($891 for type 1 and $679 for type 2 diabetes). Insulin pump users had higher annual average costs than non-pump users ($1309 vs. $797). At 39.2% of total expenses, glucose monitoring test strips accounted for the greatest cost, followed by management of hypoglycemia (26.1%), insulin (15.8%), syringes and needles (11.7%), and insulin pump and supplies (3.9%). CONCLUSIONS This study provides direct data confirming that the costs of managing blood glucose are significant for people with diabetes treated with insulin. Ensuring that people with diabetes do not receive compromised care because of financial constraints is a challenge that will require a coordinated and thoughtful response from healthcare providers, all levels of government, the insurance industry, formulary listing bodies and patient advocacy groups.

Aims Insulin is generally withheld until people with Type 2 diabetes are unresponsive to other therapies. However, its potential advantages suggest that it could be added earlier to achieve glycaemic goals; this possibility was tested in a clinical trial. Methods Consenting adults aged 18–80 years with Type 2 diabetes for at least 6 months, HbA 1c of 7.5–11%, and on 0, 1 or 2 oral agents, were randomized to one of two therapeutic approaches for 24 weeks: evening insulin glargine plus self-titration by 1 unit/day if the fasting plasma glucose (FPG) was > 5.5 mmol/l; or conventional therapy with physician adjustment of oral glucose-lowering agents if capillary FPG levels were > 5.5 mmol/l. The primary outcome was the first achievement of two consecutive HbA 1c levels ≤ 6.5%. Results Two hundred and six participants were allocated to glargine and 199 to oral agents. Compared with control subjects, participants receiving glargine: (i) were 1.68 times more likely to achieve two consecutive HbA 1c levels ≤ 6.5% (95% CI 1.00–2.83; P = 0.049); (ii) reduced their HbA 1c by 1.55 vs. 1.25% ( P = 0.005), achieving adjusted means of 7.0 vs. 7.2% ( P = 0.0007); (iii) had lower FPG ( P = 0.0001), non-high-density lipoprotein (HDL) cholesterol ( P = 0.02) and triglycerides ( P = 0.02); (iv) had greater increases in treatment satisfaction ( P = 0.045); and (v) had a 1.9-kg greater increase in weight ( P < 0.0001). No differences in hypoglycaemia were noted. Conclusions Adding insulin glargine is more likely to achieve a lower HbA 1c level than conventional therapy with oral agents. Diabet. Med. 23, 736–742 (2006)

Objective: To examine lifestyle factors associated with metabolic syndrome (MetS) and to explore the relationships between MetS and non-traditional cardiovascular disease risk factors [adiponectin, leptin, C-reactive protein (CRP), interleukin-6 (IL-6), and serum amyloid A (SAA)] in an isolated Aboriginal Canadian community. Research Methods and Procedures: Data were obtained from 360 non-diabetic adults participating in a population-based study of Aboriginal Canadians. Fasting samples were drawn for glucose, insulin, lipids, adiponectin, leptin, CRP, IL-6, and SAA. Percentage body fat was measured using bioelectrical impedance analysis. Past year physical activity and fitness level were assessed. MetS was diagnosed according to the criteria of the National Cholesterol Education Program, the World Health Organization, and the International Diabetes Federation. Results: The results showed that older age, higher percentage body fat, and lower fitness levels were associated with increased odds of MetS regardless of MetS definition and subject gender. Past year physical activity was independently related with the World Health Organization-MetS in male subjects. Subjects with MetS had significantly higher leptin, CRP, IL-6, and SAA levels and lower adiponectin levels; however, only adiponectin remained significantly low after adjustment for age and percentage body fat. Discussion: The study showed that higher percentage body fat and lower physical activity and fitness were associated with a higher prevalence of MetS in this Aboriginal community and that hypoadiponectinemia was independently associated with MetS.

BACKGROUND There exists a considerable gap between best practice as rec-ommended by diabetes guidelines and actual practice. The objective of this study was to determine the level of care being provided to patients with type 2 diabetes by family physicians in group practices in 4 regions of Canada. METHODS Baseline characteristics from a cluster-randomized trial using chart audits were recorded to assess glycemic control and rates of physician adherence to guidelines-recommended practice. Intracluster correlation coefficients (ICCs) were calculated using the physician practice as the cluster. RESULTS Fifty-six physicians in 16 group practices provided 549 charts. Glycosylated hemoglobin (A1C) was measured in 71.8% of patients (mean: 7.7%). A total of 82.3% received antihyperglycemic medication, but only 35.3% achieved an A1C INTERPRETATION Despite high rates of screening for glycemia and macrovascu-lar complications, treatment was not sufficiently intensive for most patients. Family physicians performed poorly in microvascular complication screening.

The prevalence rates of type 2 diabetes (T2DM) and coronary heart disease (CHD) in Ontario Oji-Cree are among the world's highest. Since metabolic syndrome (MetS) increases risk of T2DM and CHD, we characterized prevalence and putative genetic determinants of MetS in Oji-Cree.In 515 adult (or = 18 years old) and 115 adolescent (18 years old) Oji-Cree subjects, using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, we determined that 29.9% of Oji-Cree adults, and 43.4% of adultsor = 35 years of age, had MetS. Furthermore, 33.9 and 8.7% of female Oji-Cree adults and adolescents, respectively, had MetS. Increased waist girth and depressed HDL cholesterol were the most prevalent individual MetS components, while increased blood pressure was least prevalent. AGT T174M, GNB3 825CT, and APOC3 -455TC genotypes were significantly associated with MetS (P = 0.018, 0.0056, and 0.029, respectively) for female adults, whereas FABP2 A54T genotype was associated with MetS (P = 0.040) for female adolescents.The high MetS prevalence in Oji-Cree adults, especially women, is consistent with their high risk of T2DM and CHD. Functional polymorphisms in three candidate genes for plasma lipoproteins and blood pressure were associated with MetS in adult Oji-Cree. Furthermore, several female adolescents met the adult MetS criteria, suggesting that the genesis of MetS begins in youth, especially among aboriginal females.

Aim: Subclinical inflammation has been proposed as a pathophysiologic mechanism linking obesity with vascular and metabolic disease. Native North American populations are experiencing high prevalence rates of both (i) childhood obesity and (ii) adult cardiovascular disease (CVD) and type 2 diabetes. Thus, we sought to determine whether subclinical inflammation is an early complication of obesity in Native children. Methods: Serum concentrations of the inflammatory biomarker C-reactive protein (CRP) were assessed in a population-based, cross-sectional study of the Sandy Lake Oji-Cree community of Northern Ontario, Canada, involving 228 children aged 10–19 years (mean age 14.8). Results: Median CRP in this population was 0.5 mg/l (interquartile range 0.18–1.79 mg/l). CRP levels were higher than age-matched reference data from the Third National Health and Nutrition Examination Survey (NHANES III). Importantly, fully 15.8% of the children of this community had CRP concentrations between 3 and 10 mg/l, a range that identifies adults at high risk of CVD. Moreover, increasing CRP concentration in this paediatric population was associated with an enhanced CV risk profile, consisting of increased adiposity, higher insulin resistance, worsening lipid profile (higher total cholesterol, triglycerides, low-density lipoprotein cholesterol, apolipoprotein B and total cholesterol : high-density-lipoprotein cholesterol ratio), increased leptin and decreased adiponectin. On multivariate analysis, waist circumference and interleukin-6 (IL-6) emerged as independent determinants of CRP concentration. Conclusion: Subclinical inflammation is an early complication of childhood obesity in Native children and may foreshadow an increased burden of CVD and type 2 diabetes in the future.