Assessment and Treatment of Cardiometabolic Risk in Adults at Risk for or with Type 2 Diabetes Mellitus

Can J Diabetes 36 (2012) 320e326

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Canadian Journal of Diabetes journal homepage: www.canadianjournalofdiabetes.com

Perspectives in Practice

Assessment and Treatment of Cardiometabolic Risk in Adults at Risk for or with Type 2 Diabetes Mellitus Hwee Teoh PhD a, b, David C.W. Lau MD, PhD, FRCPC c, Kathryn M. Camelon RD, CDE d, Richard E. Gilbert MD, PhD, FRCPC, FRACP a, Stewart B. Harris MD, MPH, FCFP, FACPM e, Philip A. McFarlane MD, PhD, FRCPC f, Rémi Rabasa-Lhoret MD, PhD g, Ehud Ur MB, FRCP h, Lawrence A. Leiter MD, FRCPC, FACP a, * a

Division of Endocrinology and Metabolism, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada Division of Cardiac Surgery, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada Departments of Medicine, Biochemistry and Molecular Biology, and Cardiac Sciences, University of Calgary, Calgary, Alberta, Canada d Department of Allied Health, Clinical Nutrition, University Health Network, Toronto, Ontario, Canada e Centre for Studies in Family Medicine, Department of Family Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada f Division of Nephrology, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada g Platform of Research in Obesity, Diabetes and Metabolism and Department of Nutrition, Institut de Recherches Cliniques de Montréal, Université de Montréal, Montréal, Québec, Canada h Division of Endocrinology, St. Paul’s Hospital and Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada b c

a r t i c l e i n f o

a b s t r a c t

Article history: Received 26 June 2012 Received in revised form 31 August 2012 Accepted 31 August 2012

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:e1ee33). 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. Ó 2012 Canadian Diabetes Association

Keywords: cardiometabolic risk type 2 diabetes mellitus

r é s u m é Mots clés: risque cardiométabolique diabète sucré de type 2

Le risque cardiométabolique (RCM) fait appel à la réflexion collective sur les facteurs de risque traditionnels et émergents qui augmentent le potentiel de la survenue de maladies cardiovasculaires athérogènes ainsi que l’émergence du diabète sucré de type 2. Les données accumulées suggèrent que le syndrome métabolique puisse augmenter de 5 fois le risque de diabète sucré de type 2 et qu’il augmente aussi de manière additionnelle le risque cardiovasculaire calculé selon les algorithmes conventionnels de 1,5 à 2,0 fois. Cet article est un résumé de l’article de principe sur le risque cardiométabolique récemment publié par le groupe de travail interdisciplinaire sur le métabolisme cardiaque (Cardiometabolic Risk Working Group : Can J Cardiol. 2011;27:e1ee33) représenté nationalement. L’objectif de cet article est de passer en revue ce que sont les facteurs de risque émergents, la manière de déterminer si les individus ayant ou étant exposé au risque de diabète sucré de type 2 ont un RCM élevé, et les étapes qui doivent être prises en considération pour une prise en charge optimale et la réduction du RCM chez ces patients. Ó 2012 Canadian Diabetes Association

Introduction

* Address for correspondence: Lawrence A. Leiter, St. Michael’s Hospital Medical Centre, 61 Queen Street East, Suite 6-121Q, Toronto, ON M5C 2T2, Canada. E-mail address: [email protected] (L.A. Leiter). 1499-2671/$ e see front matter Ó 2012 Canadian Diabetes Association http://dx.doi.org/10.1016/j.jcjd.2012.08.009

Cardiometabolic risk (CMR) is an all-encompassing concept that highlights the importance of considering all of the key factors that commonly contribute to the absolute risk of developing cardiovascular (CV) disease as well as type 2 diabetes mellitus (1,2). This

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term is distinct from metabolic syndrome that refers to a more restricted cluster of metabolic abnormalities that increase the relative risk of CV disease and type 2 diabetes (3,4). Most individuals with type 2 diabetes are likely to be at increased CMR (5) and it has been estimated that more than 85% of patients with type 2 diabetes meet the criteria for the metabolic syndrome. Individuals with type 2 diabetes who meet the criteria of the metabolic syndrome have a higher CV risk than those who do not (5). Accordingly, knowledge of a person’s metabolic syndrome status is critical to determining absolute CV risk, even in the individual with type 2 diabetes. It is recommended that both patients at risk for, or with, type 2 diabetes should have their CMR routinely assessed to allow for timely and optimal therapeutic interventions to reduce their CMR. In contrast to diabetes risk engines and CV risk algorithms (e.g. Framingham Risk Score [FRS], Reynolds Risk Score [RRS]), CMR assessment includes both conventional (e.g. dyslipidemia, hypertension, smoking) and newly recognized (e.g. abdominal obesity, ethnicity, inflammatory profile, lifestyle) risk factors. What exactly are the benefits of including these emerging risk factors in risk evaluation and how can healthcare providers optimally identify and manage patients with CMR to reduce both type 2 diabetes and CV disease risk? To answer these questions, the Cardiometabolic Risk Working Group recently published a position paper that provides a Canadian definition of CMR with recommendations, aligned with key existing national guidelines, for CMR assessment, management and treatment of the ethnically diverse Canadian population (1,2). The position paper was reviewed and endorsed by multiple Canadian professional organizations, including the Canadian Diabetes Association (CDA), that have an interest in CMR. A wide spectrum of topics was discussed but this review is confined to those focused on assessing and treating CMR in subjects at risk for or with type 2 diabetes. In the last 4 decades, global morbidity and mortality from CV disease has been declining (6,7) but concerns have been expressed that the epidemic of diabetes and its complications, attributable at least in part to CMR factors, may well reverse these trends (8). In 2011, 366 million people worldwide had diabetes and this number is projected to reach a staggering 552 million by 2030, heralding diabetes as a prominent global health and social burden in the coming decades (9). A similar picture has been painted for Canada where the escalating crisis of obesity, increasingly sedentary lifestyles, an aging population and ethnic diversity is anticipated to propel diagnosed diabetes from 2.5 million in 2010 to 3.7 million in 2020 (10,11). Unless swift changes in lifestyle and therapeutic interventions are implemented, this diabetes tsunami will no doubt elevate the general CMR profile of the Canadian population. There is accumulating evidence that traditional risk engines may underestimate true CV risk in patients at risk for or with type 2 diabetes (12), especially in the setting of the metabolic syndrome. According to the harmonized definition (13), a diagnosis for the metabolic syndrome requires fulfillment of at least three of the following five criteriadincreased waist circumference (ethnic-specific), elevated blood pressure, raised fasting plasma glucose (FPG) level, diminished high-density lipoprotein cholesterol concentration and enhanced circulating triglyceride content (Table 1). Based on the available literature, the current consensus is that the metabolic syndrome confers a 5-fold increase in risk for type 2 diabetes (13) and the calculated absolute CV risk value derived from validated tools such as the FRS or RRS, should be amplified 1.5- to 2.0-fold for individuals with the metabolic syndrome (14e16). The final mathematical product in both cases reflects the CMR profile and should allow for more appropriate evidence-based interventions to be put into practice.

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Table 1 Harmonized definition of the metabolic syndrome Diagnostic criteria Elevated waist circumference Elevated triglycerides or being treated for elevated triglycerides Reduced HDL-C or being treated for reduced HDL-C Elevated blood pressure or being treated with an antihypertensive Elevated FPG or being treated for elevated FPG

Population- and country-specific*
1.7 mmol/L <1.0 mmol/L for males <1.3 mmol/L for females Systolic
130 and/or diastolic
85 mm Hg
5.6 mmol/L

FPG, fasting plasma glucose; HDL-C, high-density lipoprotein cholesterol. Adapted from Alberti et al. (13). * See Table 3.

Cardiometabolic Risk Assessment As shown in Figure 1, consistent with the 2008 CDA clinical practice guidelines (17), the 2009 Canadian Cardiovascular Society Lipid Guidelines (18) and more recently the C-CHANGE initiative (19), the position paper recommends that the following individuals should undergo a CMR assessment: individuals
40 years of age as well as those 18 to 39 years with identifiable traditional CV risk factors, including an overweight or obese phenotype (especially abdominal obesity); of a high risk ethnic background (e.g. Aboriginal Canadian, black and South Asian); practicing unhealthy lifestyle behaviours (e.g. high fat, sugar and/or salt diet, and/or low physical activity); and/or who have a first-degree relative diagnosed with (premature) type 2 diabetes or CV disease. In clinic, in addition to documenting height, weight and body mass index (BMI) (20,21), it is imperative that waist circumference is measured (22,23). BMI and abdominal obesity (4,24,25) should be defined according to ethnic-specific cutoffs as shown in Tables 2 and 3, respectively (13,26). Blood pressure should also be determined and hypertension diagnosed in individuals with readings over the cut-off of 130/80 mm Hg in those with diabetes and 140/ 90 mm Hg in those without. Subsequent to these routine examinations, persons who register abnormal readings for the above-mentioned features should have their FPG and total, high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), triglycerides and, in cases of elevated

Figure 1. General assessment of CMR.

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Table 2 Ethnic specific thresholds for BMI Classification

Underweight Ideal range Overweight Obese I Obese II

Target BMI (kg/m2) Europids

Asians

<18.5 18.5e24.9
25 30e34.9
35

<18.5 18.5e22.9
23 25e29.9
30

Risk of comorbidity

Low Average Increased Moderate Severe

BMI, body mass index. Adapted from WHO Expert Consultation (26).

triglycerides, apolipoprotein B (if available) in place of LDL-C, analyzed. This battery of tests allows for absolute CV risk to be enumerated via the FRS or the RRS and CMR to be estimated with the 1.5 to 2.0 multiplication factor. The sequence of steps to be taken to quantify CMR is summarized in Figure 2. Patients who are deemed to have an elevated CMR should undergo further laboratory investigations that may include, as appropriate, glycated hemoglobin (A1C) or a 75 g oral glucose tolerance test (in those with FPG levels between 6.1 and 6.9 mmol/L or in those with a FPG between 5.6 and 6.0 mmol/L plus one or more risk factors), renal function, hepatic enzymes, a 12-lead resting electrocardiogram and/or exercise stress test and/or highsensitive C-reactive protein (hs-CRP). Management of Cardiometabolic Risk Vascular protective measures are essential for all patients with CMR (27,28) and health behaviour modification, including increased physical activity, reduced caloric intake and smoking cessation, is recommended as the first-line treatment strategy (17,18,24,29). Given that diabetes is a key element for the presentation of elevated CMR, a reduction in diabetes risk will likely also result in a decrease in CMR. The United States Diabetes Prevention Program (30), the Finnish Diabetes Prevention Study (31) and the Chinese Da Qing Study (32) have collectively demonstrated that intensive health behaviour intervention is effective in preventing or delaying the development of diabetes in people with impaired glucose tolerance (IGT). Maintaining or improving fitness has also been associated with a lower risk of all-cause and CV disease mortality (33). Furthermore, it has been repeatedly shown that the use of structured health behavioural interventions can in some cases decrease diabetes risk more successfully (30e32) and cost effectively than some pharmacologic interventions (30,34). Implementation of a regular and sustained (30 to 60 minutes on most days of the week) dynamic physical aerobic activity program of moderate intensity over every day activities is advocated but short high intensity bouts of resistance training can also provide significant metabolic benefits (35,36). Where possible, access to an exercise specialist (kinesiologist) is encouraged to help reinforce the take home message and may result in increased adherence and extended weight loss maintenance (37,38). Single sessions of

Table 3 Ethnic specific thresholds for waist circumference Country/ethnic group Europids South Asians, Chinese, Japanese Ethnic South and Central Americans Sub-Saharan Africans Eastern Mediterranean and Middle East (Arab) populations Adapted from Alberti et al. (13).

Male
94 cm; female
80 cm Male
90 cm; female
80 cm Use South Asian recommendations until more specific data are available Use European recommendations until more specific data are available Use European recommendations until more specific data are available

Figure 2. Quantification of CMR.

exercise have reportedly produced appreciable reductions in FPG readings in persons with very high plasma glucose levels (39) and improved insulin resistance (40). Adherence to a comprehensive and continuous exercise program significantly reduces the risk of type 2 diabetes and CV disease, improves CMR risk factors (blood pressure, lipid profile) and also allows some recovery of metabolic control in those with type 2 diabetes (41e44). Whether or not health behaviour interventions influence the incidence of CV events in patients with established type 2 diabetes remains unknown although data from the ongoing Look AHEAD (Action for Health in Diabetes) trial will provide some insight (44). Dietary modifications leading to negative energy balance should be promoted because reductions in body weight and improvements in several metabolic parameters have been reported in patients with type 2 diabetes after such sessions (17,18,29,44). Nutrition counselling should be performed by a registered dietitian, if possible. Caloric restriction (w500e1000 kcal deficit per day) significantly reduces CMR in part due to decreases in abdominal obesity (44e46). Notably in people with type 2 diabetes, caloric reduction together with increased physical activity, can not only result in clinically significant weight loss but also an improvement in fitness, glycemic, lipid and blood pressure control and accordingly less related pharmacotherapy (41,44,47,48). Aside from reducing caloric content, food quality also has some important implications (49,50). For instance, newer guidelines recommend limiting sugar-sweetened beverages as they may promote weight gain and independent of obesity, increase the risk of type 2 diabetes and CV disease (51). In the Diabetes Prevention Program IGT subjects failing to reduce weight but improving food quality demonstrated a reduced risk for type 2 diabetes and therefore attention should be paid to food quality as well as quantity. Because daily sodium intake is closely linked with the hypertensive phenotype, salt restriction is encouraged and a DASH (Dietary Approaches to Stop Hypertension) like diet is recommended (52). Specifically, adults should aim to cut down their dietary sodium to 1500 mg/day, 1300 mg/day and 1200 mg/day if they are age 50 and under, 51 to 70, and older than 70 years, respectively (29). Notably, early intensive lifestyle management is also associated with psychological improvements (53) and may reduce the risk of diabetes-specific complications such as retinopathy (54). Modest weight loss of 5% to 10% not only significantly reduces diabetes risk (A1C levels) but also improves surrogate CV markers (blood pressure, lipid profile) in individuals with type 2 diabetes (44). Additionally, each kilogram of weight lost due to caloric restriction alone is associated with an approximately 1.0 cm

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decrease in waist circumference (55,56). When insufficient weight loss necessary to reduce CMR is achieved, however, adjunctive pharmacotherapy and bariatric surgery may be considered. Weight loss medications, such as orlistat should only be prescribed in association with a weight-reducing diet and increased physical activity (57). However, patients with a BMI
30 kg/m2 or those with a BMI
27 kg/m2 plus CV risk factors and/or IGT may be prescribed weight loss medications if their decrease in weight is <0.5 kg per week after lifestyle changes have been attempted for 3 to 6 months (57). Bariatric surgery is a treatment option indicated for people with a BMI
40 kg/m2 or a BMI
35 kg/m2 with comorbid conditions (21,24). Surgery may not only result in significant and sustained weight loss, but may also lead to dramatic amelioration of diabetes, improvement in blood pressure and dyslipidemia and, most notably, reduction in all-cause, CV and cancer mortality (58). Traditional CV disease risk factors should be managed with pharmacotherapy as per current guidelines (17,18,29). However, consistent with the school of thought that a multifaceted approach is optimal for managing CMR, when treating one risk factor, it is ideal that one should not select a treatment that will worsen a different risk factor. The recommended treatment goals and therapeutic routes are summarized in Table 4. With respect to dyslipidemia, statin therapy reduces adverse CV risk in persons with diabetes irrespective of their baseline LDL-C values (59). The current CDA guidelines recommend that in patients with diabetes, statins, in addition to behavioural health changes, be used in all men over the age of 45, women over the age of 50, and younger individuals with additional risk (17). Patients with known CV disease, a high FRS (>20% chance of having a heart attack or dying from heart disease within 10 years), IGT and those at intermediate risk displaying multiple CMR factors, LDL-C levels >3.5 mmol/L or hs-CRP >2.0 mg/L should commence concomitant behavioural health changes and statin therapy immediately. The therapeutic goal for LDL-C in these patients is <2.0 mmol/L or at least a 50% reduction in LDL-C levels or an optional alternative

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treatment target of <0.8 g/L for apolipoprotein B. Individuals at intermediate risk may need to undergo additional tests to ascertain if they need to be pharmacologically managed for increased CMR. Those with low FRS values need only be observed and statin therapy initiated if their LDL-C levels climb beyond 5.0 mmol/L. Cholesterol absorption inhibitors, fibrates, or niacin can be introduced if patients fail to achieve therapeutic goals despite taking optimal doses of statins. With respect to glycemic management in those individuals with type 2 diabetes, pharmacotherapy as per the 2008 CDA guidelines (17) should generally be initiated only if suboptimal results have been obtained after 3 to 6 months of structured health behavioural changes. The primary therapeutic goal is an A1C level of 7.0% although this target must be individualized. Metformin is typically the initial antihyperglycemic agent of choice but dual therapy comprising metformin with another class of antihyperglycemic agent or insulin monotherapy or combination therapy can be attempted in individuals with an A1C reading of
9.0%. With respect to hypertension, the recent recommendations of the 2012 Canadian Hypertension Education Program (CHEP), developed in conjunction with the CDA, should be followed (29). Specifically, the patient should aim for more physical activity, weight and waist loss, a healthy diet including reduced sodium and moderate alcohol consumption, stress reduction and smoking cessation. Patients with diabetes, with or without elevated CMR, should be treated to a blood pressure of <130/80 mm Hg. In individuals where CMR is associated with dysglycemia, it may be prudent to use antihypertensive agents associated with improved glucose metabolism (i.e. renin angiotensin aldosterone system [RAAS] inhibitors) or those that are metabolically neutral (i.e. calcium channel blockers) (60e62). Thiazide diuretics should not be used as first line therapy as they are associated with an increased risk for the development of new diabetes (63). With respect to smoking, counselling on smoking cessation should be the initial step. When and where appropriate, group

Table 4 CMR management and treatment targets Dyslipidemia

Diabetes*

Hypertensiony

Target LDL-C: <2.0 mmol/L or Y
50% Optional target ApoB: <0.8 g/L

Target A1C 7.0% but must be individualized

Initiate behavioural changes (with pharmacotherapy if necessary)  Regular exercise (3e5 days/week; 30e60 min/day), including resistance training  Improve diet quality Thresholds for pharmacotherapy  High risk: initiate statin treatment immediately  Intermediate risk:  If LDL-C >3.5 mmol/L, initiate statin treatment  If hs-CRP >2 mg/L, start on statin (if age appropriate)  If multiple CMR factors, initiate statin treatment  Low risk: observe and if LDL-C >5.0 mmol/L, initiate statin treatment Recommended pharmacotherapeutic approach  Statins

Initiate behavioural changes  Regular exercise (3e5 days/week; 30e60 min/day), including resistance training  Improve diet quality

Target BP <140/90 mm Hg or 130/80 mm Hg in patients with type 2 diabetes mellitus or chronic kidney disease Initiate behavioural changes  Regular exercise (3e5 days/week; 30e60 min/day), including resistance training  Improve diet quality including salt restriction

If not reaching therapeutic goals despite optimal doses:  Add cholesterol absorption inhibitor

If still not at therapeutic goals:  Add niacin

Threshold for pharmacotherapy  If A1C > 6.5 to 7.0% after behavioural changes are made, consider pharmacotherapy as per 2008 CDA CPG

Threshold for pharmacotherapy  If BP not at target after behavioural changes are made, consider pharmacotherapy as per 2012 CHEP CPG

Recommended pharmacotherapeutic approach  Metformin

Recommended pharmacotherapeutic approach  Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers

 Add a-glucosidase inhibitor, dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 agonist, insulin, meglitinide, sulfonylurea, thiazolidinedione or weight loss agent

 Add calcium channel blockers

 Add third antihyperglycemic agent

 Add small doses of diuretic

A1C, glycated hemoglobin; ApoB, apolipoprotein B; BP, blood pressure; CDA, Canadian Diabetes Association; CHEP, Canadian Hypertension Education Program; CMR, cardiometabolic risk; CPG, clinical practice guidelines; hs-CRP, high-sensitive C-reactive protein; LDL-C, low-density lipoprotein cholesterol. * If A1C
9%, consider initiating metformin with another class or initiate insulin. y If BP
20/10 mm Hg above target, consider initial combination therapy.

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therapy can be introduced and/or if necessary, coupled with medication support through nicotine replacement, bupropion or varenicline. Special Considerations The increasingly diverse nature of the Canadian population has meant that the “one-size-fits-all” mentality for assessing and treating CMR must be revisited and refined. The Study of Health Assessment and Risk in Ethnic groups (SHARE) provided solid evidence that Canadian residents of different ethnic origins display diverse CMR factors and appear to have disparate susceptibilities to CMR-related derangements (64). For instance, the relationship between percentage body fat and body mass index is ethnic specific (Table 2) so calculations based on ethnic-specific cut-off values should be used to define overweight (26), abdominal obesity (13), CV risk and CMR. From a CMR plus diabetes identification standpoint, 2 Canadian subpopulations warrant special mentioning. South Asians, currently Canada’s largest visible minority group, demonstrate a high prevalence of type 2 diabetes, IGT, CV disease, obesity, dyslipidemia and hypertension as well as more abnormalities of the emerging factors (64e68). Aboriginal Canadians also show a high incidence of type 2 diabetes, CV disease, (abdominal) obesity and smoking (64,69e73). Ethnicity, culture and social factors are believed to contribute to the clustering of CMR factors in these 2 groups. In contrast, Canadians of Chinese (64,67) and black (17,67) origin exhibit less metabolic disorders but appear to be more prone to hypertension, especially the latter. Outside of ethnicity, the highest rates of diabetes are found within the lower income quintiles (74) and some of the traditional and emerging risk factors appear to be elevated in these socially disadvantaged groups (75). The management of these special groups with health behaviour changes and pharmacotherapy merits certain considerations. Socio-economic and cultural status have a significant impact on lifestyle prescription and implementation (76). Inasmuch as South Asians and Aboriginal Canadians are more susceptible to diabetes, antihypertensive agents that may improve glucose metabolism (i.e. RAAS inhibitors) or that are metabolically neutral (i.e. calcium channel blockers) may be preferable as first-line therapy. On the other hand, RAAS inhibitors may not be ideal for managing hypertension in blacks as they are typically less responsive to this class of antihypertensive drugs (63). Health Canada recommends lowering the starting dose of certain statins in Asian patients (77) as some studies have suggested that statins are more efficacious in Asian vs. non-Asian populations (78e81). However, recent data suggest that because people of South Asian origin derive similar lipid effects from some statins as white populations (82,83), dose adjustment may not be necessary across all Asian populations. Implementation Strategies The Cardiometabolic Risk Working Group has undertaken the following strategies to disseminate the message of appropriately assessing and treating CMR:  CMR-focused workshops were presented at the 2011 Canadian Cardiovascular Congress and the 2011 Family Medicine Forum.  CMR-focused supplements in the Medical Post (circulated on January 31, 2012) and L’actualite médicale (circulated on March 13, 2012).  A bilingual mobile application, designed for the iOS (iPhone and iPad), Blackberry and Android platforms as well as a webbased application (www.cmrapp.com), which provides an overview of CMR and includes a CMR calculator.  A CMR-focused slide kit for physicians.

Conclusions Type 2 diabetes, a major health socio-economic issue for Canada (10), is expected to continue being a national burden as obesity, a precursor of type 2 diabetes, affects over 1 in 4 adults in Canada (11). Because both type 2 diabetes and (abdominal) obesity are considered key factors of the CMR phenotype, CMR in Canadian adults will likely rise in parallel. Although the cause of elevated CMR is multifactorial, the consensus is that health behaviour interventions coupled with a multidisciplinary approach is necessary to adequately prevent and treat CMR factors. Primary healthcare teams that comprise physicians, nurses, kinesiologists, registered dietitians and, if possible, psychologists with the common goal of addressing CMR in the patients would allow for optimal healthcare delivery. Finally, ethnic-specific risk factors must be considered to appropriately evaluate all individuals in the dynamic Canadian demographic. Author Disclosures HT has no conflicts of interest to declare; DCWL has received honouraria or research support from Abbott, Allergan, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Novo Nordisk, Pfizer, Roche and Sanofi; KMC is a consultant and advisory board member for Abbott; REG has received honouraria or research support from AstraZeneca, BristolMyers Squibb, Merck, Novartis and Sanofi; SBH has received honouraria or research support from AstraZeneca, BoehringerIngelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck, Novo Nordisk, Pfizer, Sanofi and Roche; PAM has received honouraria or research support from Abbott, Amgen Inc, AstraZeneca, Biovail, Bristol-Myers Squibb, Boehringer-Ingleheim, GlaxoSmithKline, Merck, Novartis, Novo Nordisk, Ortho-Biotech, Otsuka, Reata, Sanofi and Takeda; RR-L has received honouraria or research support from Abbott, AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Merck, Novartis, Novo Nordisk and Sanofi; EU has received honouraria or research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Novo Nordisk and Sanofi; LAL has received honouraria or research support from Abbott, AstraZeneca, BristolMyers Squibb, Boehringer-Ingelheim, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi and Servier. Author Contributions HT and LAL drafted the manuscript. HT, DCWL, KMC, REG, SBH, PAM, RR-L, EU and LAL contributed to discussion, revised the manuscript and gave final approval of the version to be submitted and published. References 1. Leiter LA, Fitchett DH, Gilbert RE, et al. Identification and management of cardiometabolic risk in Canada: a position paper by the cardiometabolic risk working group (executive summary). Can J Cardiol 2011;27:124e31. 2. Leiter LA, Fitchett DH, Gilbert RE, et al. Cardiometabolic risk in Canada: a detailed analysis and position paper by the cardiometabolic risk working group. Can J Cardiol 2011;27:e1e33. 3. Despres JP, Cartier A, Cote M, et al. The concept of cardiometabolic risk: Bridging the fields of diabetology and cardiology. Ann Med 2008;40:514e23. 4. Després JP, Lemieux I, Bergeron J, et al. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol 2008;28:1039e49. 5. Alexander CM, Landsman PB, Teutsch SM, et al. NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 2003;52:1210e4. 6. Ford ES, Capewell S. Proportion of the decline in cardiovascular mortality disease due to prevention versus treatment: public health versus clinical care. Annu Rev Public Health 2011;32:5e22. 7. Luepker RV, Berger AK. Is acute myocardial infarction disappearing? Circulation 2010;121:1280e2.

H. Teoh et al. / Can J Diabetes 36 (2012) 320e326 8. Gregg EW, Cheng YJ, Saydah S, et al. Trends in death rates among U.S. adults with and without diabetes between 1997 and 2006: findings from the national health interview survey. Diabetes Care 2012;35:1252e7. 9. Whiting DR, Guariguata L, Weil C, et al. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011;94: 311e21. 10. Canadian Diabetes Association. An economic tsunami: the cost of diabetes in Canada. 2009. (available online at http://www.diabetes.ca/documents/getinvolved/FINAL_Economic_Report.pdf). Accessed December 2009. 11. The Public Health Agency of Canada and the Canadian Institute for Health Information. Obesity in Canada. 2011. (available online at https://secure.cihi.ca/ estore/productFamily.htm?locale¼en&pf¼PFC1636). Accessed 7 February 2012. 12. Tong PC, Kong AP, So WY, et al. The usefulness of the International Diabetes Federation and the National Cholesterol Education Program’s Adult Treatment Panel III definitions of the metabolic syndrome in predicting coronary heart disease in subjects with type 2 diabetes. Diabetes Care 2007;30: 1206e11. 13. Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009;120:1640e5. 14. Galassi A, Reynolds K, He J. Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. Am J Med 2006;119:812e9. 15. Gami AS, Witt BJ, Howard DE, et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol 2007;49:403e14. 16. Mottillo S, Filion KB, Genest J, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol 2010;56: 1113e32. 17. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2008;32: S1e201. 18. Genest J, McPherson R, Frohlich J, et al. 2009 Canadian Cardiovascular Society/ Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adultd2009 recommendations. Can J Cardiol 2009;25:567e79. 19. Tobe SW, Stone JA, Brouwers M, et al. Harmonization of guidelines for the prevention and treatment of cardiovascular disease: the C-CHANGE Initiative. CMAJ 2011;183:E1135e50. 20. Health Canada. Canadian Guidelines for Body Weight Classification in Adults, edited by Office of Nutrition Policy and Promotion. Ottawa: Health Canada; 2003. p. H49e179/2003E. 21. Poirier P, Alpert MA, Fleisher LA, et al. Cardiovascular evaluation and management of severely obese patients undergoing surgery: a science advisory from the American Heart Association. Circulation 2009;120:86e95. 22. Canadian Cardiometabolic Risk Working Group. Identification and management of cardiometabolic risk in Canada (Mobile Application), Toronto, ON, Canada. 2012. www.cmrapp.com 23. International Chair on Cardiometabolic Risk of Université Laval. Waist circumference measurement guidelines. In: International Chair on Cardiometabolic Risk of Université Laval, editor. Myhealthywaist.org. Québec City, Québec, Canada, 2012. 24. Lau DC, Douketis JD, Morrison KM, et al. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary]. CMAJ 2007;176:S1e13. 25. Després JP, Tchernof A. Classification of overweight and obesity. In: 2006 Canadian clinical practice guidelines on management and prevention of obesity in adults and children. CMAJ 2007;176:21e6. 26. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363: 157e63. 27. Berger JS, Jordan CO, Lloyd-Jones D, et al. Screening for cardiovascular risk in asymptomatic patients. J Am Coll Cardiol 2010;55:1169e77. 28. Paras E, Mancini GB, Lear SA. The relationship of three common definitions of the metabolic syndrome with sub-clinical carotid atherosclerosis. Atherosclerosis 2008;198:228e36. 29. Canadian Hypertension Education Program. The 2012 CHEP Recommendations for the Management of Hypertension, edited by Canadian Hypertension Education Program Executive: Hypertension Canada, 2012. 30. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346:393e403. 31. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343e50. 32. Pan XR, Li GW, Hu YH, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 1997;20:537e44. 33. Lee DC, Sui X, Artero EG, et al. Long-term effects of changes in cardiorespiratory fitness and body mass index on all-cause and cardiovascular disease mortality in men: the Aerobics Center Longitudinal Study. Circulation 2011;124: 2483e90.

325

34. Ramachandran A, Snehalatha C, Yamuna A, et al. Cost-effectiveness of the interventions in the primary prevention of diabetes among Asian Indians: within-trial results of the Indian Diabetes Prevention Programme (IDPP). Diabetes Care 2007;30:2548e52. 35. Cornelissen VA, Fagard RH, Coeckelberghs E, et al. Impact of resistance training on blood pressure and other cardiovascular risk factors: a meta-analysis of randomized, controlled trials. Hypertension 2011;58:950e8. 36. Gibala MJ, Little JP, Macdonald MJ, et al. Physiological adaptations to lowvolume, high-intensity interval training in health and disease. J Physiol 2012; 590:1077e84. 37. Dale KS, McAuley KA, Taylor RW, et al. Determining optimal approaches for weight maintenance: a randomized controlled trial. CMAJ 2009;180:E39e46. 38. Lawton BA, Rose SB, Elley CR, et al. Exercise on prescription for women aged 40-74 recruited through primary care: two year randomised controlled trial. BMJ 2008;337:a2509. 39. Thompson PD, Crouse SF, Goodpaster B, et al. The acute versus the chronic response to exercise. Med Sci Sports Exerc 2001;33:S438e45. 40. Devlin JT, Hirshman M, Horton ED, et al. Enhanced peripheral and splanchnic insulin sensitivity in NIDDM men after single bout of exercise. Diabetes 1987;36: 434e9. 41. Pi-Sunyer X, Blackburn G, Brancati FL, et al. Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care 2007;30:1374e83. 42. Janiszewski PM, Ross R. Physical activity in the treatment of obesity: beyond body weight reduction. Appl Physiol Nutr Metab 2007;32:512e22. 43. Kujala UM, Jokelainen J, Oksa H, et al. Increase in physical activity and cardiometabolic risk profile change during lifestyle intervention in primary healthcare: 1-year follow-up study among individuals at high risk for type 2 diabetes. BMJ Open 2011;1:e000292. 44. The Look AHEAD Research Group. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med 2010;170: 1566e75. 45. Rejeski WJ, Ip EH, Bertoni AG, et al. Lifestyle change and mobility in obese adults with type 2 diabetes. N Engl J Med 2012;366:1209e17. 46. Wadden TA, Neiberg RH, Wing RR, et al. Four-year weight losses in the Look AHEAD study: factors associated with long-term success. Obesity (Silver Spring) 2011;19:1987e98. 47. Unick JL, Beavers D, Jakicic JM, et al. Effectiveness of lifestyle interventions for individuals with severe obesity and type 2 diabetes: results from the Look AHEAD trial. Diabetes Care 2011;34:2152e7. 48. Wing RR, Lang W, Wadden TA, et al. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care 2011;34:1481e6. 49. Kastorini CM, Milionis HJ, Esposito K, et al. The effect of Mediterranean diet on metabolic syndrome and its components: a meta-analysis of 50 studies and 534,906 individuals. J Am Coll Cardiol 2011;57:1299e313. 50. Pegklidou K, Nicolaou I, Demopoulos VJ. Nutritional overview on the management of type 2 diabetes and the prevention of its complications. Curr Diabetes Rev 2010;6:400e9. 51. Malik VS, Popkin BM, Bray GA, et al. Sugar-sweetened beverages, obesity, type 2 diabetes mellitus, and cardiovascular disease risk. Circulation 2010;121:1356e64. 52. Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med 2001;344:3e10. 53. Ruusunen A, Voutilainen S, Karhunen L, et al. How does lifestyle intervention affect depressive symptoms? Results from the Finnish Diabetes Prevention Study. Diabet Med 2012;29:e126e32. 54. Gong Q, Gregg EW, Wang J, et al. Long-term effects of a randomised trial of a 6year lifestyle intervention in impaired glucose tolerance on diabetes-related microvascular complications: the China Da Qing Diabetes Prevention Outcome Study. Diabetologia 2011;54:300e7. 55. Dansinger ML, Gleason JA, Griffith JL, et al. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA 2005;293:43e53. 56. Ross R, Dagnone D, Jones PJ, et al. Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial. Ann Intern Med 2000;133:92e103. 57. Sharma AM, Douketis JD. Pharmacotherapy for obesity: adults. In: 2006 Canadian clinical practice guidelines on management and prevention of obesity in adults and children. CMAJ 2007;176:66e71. 58. Sjostrom L, Narbro K, Sjostrom CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357:741e52. 59. Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008;371:117e25. 60. Dagenais GR, Pogue J, Fox K, et al. Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials. Lancet 2006;368:581e8. 61. Dagenais GR, Gerstein HC, Holman R, et al. Effects of ramipril and rosiglitazone on cardiovascular and renal outcomes in people with impaired glucose tolerance or impaired fasting glucose: results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial. Diabetes Care 2008; 31:1007e14. 62. Holman RR, Haffner SM, McMurray JJ, et al. Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med 2010;362:1463e76.

326

H. Teoh et al. / Can J Diabetes 36 (2012) 320e326

63. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981e97. 64. Anand SS, Yusuf S, Vuksan V, et al. Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic groups (SHARE). Lancet 2000;356: 279e84. 65. Gupta M, Brister S. Is South Asian ethnicity an independent cardiovascular risk factor? Can J Cardiol 2006;22:193e7. 66. Brister SJ, Hamdulay Z, Verma S, et al. Ethnic diversity: South Asian ethnicity is associated with increased coronary artery bypass grafting mortality. J Thorac Cardiovasc Surg 2007;133:150e4. 67. Leenen FH, Dumais J, McInnis NH, et al. Results of the Ontario survey on the prevalence and control of hypertension. CMAJ 2008;178:1441e9. 68. Gupta M, Doobay AV, Singh N, et al. Risk factors, hospital management and outcomes after acute myocardial infarction in South Asian Canadians and matched control subjects. CMAJ 2002;166:717e22. 69. Anand SS, Yusuf S, Jacobs R, et al. Risk factors, atherosclerosis, and cardiovascular disease among Aboriginal people in Canada: the Study of Health Assessment and Risk Evaluation in Aboriginal Peoples (SHARE-AP). Lancet 2001;358:1147e53. 70. Ley SH, Harris SB, Connelly PW, et al. Adipokines and incident type 2 diabetes in an Aboriginal Canadian [corrected] population: the Sandy Lake Health and Diabetes Project. Diabetes Care 2008;31:1410e5. 71. Green C, Blanchard JF, Young TK, et al. The epidemiology of diabetes in the Manitoba-registered First Nation population: current patterns and comparative trends. Diabetes Care 2003;26:1993e8. 72. Harris SB, Naqshbandi M, Bhattacharyya O, et al. Major gaps in diabetes clinical care among Canada’s First Nations: results of the CIRCLE study. Diabetes Res Clin Pract 2011;92:272e9.

73. Naqshbandi M, Harris SB, Esler JG, et al. Global complication rates of type 2 diabetes in Indigenous peoples: A comprehensive review. Diabetes Res Clin Pract 2008;82:1e17. 74. Hux JE, Tang M. Patterns of prevalence and incidence of diabetes. In: Hux J, Booth G, Slaughter P, Laupacis A, editors. Diabetes in Ontario. An ICES Practice Atlas. Institute for Clinical Evaluative Sciences; 2003. p. 1.1e1.18. 75. Anand SS, Razak F, Davis AD, et al. Social disadvantage and cardiovascular disease: development of an index and analysis of age, sex, and ethnicity effects. Int J Epidemiol 2006;35:1239e45. 76. Booth DA, Booth P. Targeting cultural changes supportive of the healthiest lifestyle patterns. A biosocial evidence-base for prevention of obesity. Appetite 2011;56:210e21. 77. Health Canada. Association of CRESTOR (rosuvastatin) with muscle related adverse eventsdAstraZeneca Canada Inc. Health Products and Food Branch, editors. Ottawa: Health Canada, 2005. 78. Liao JK. Safety and efficacy of statins in Asians. Am J Cardiol 2007;99:410e4. 79. Matsuzawa Y, Kita T, Mabuchi H, et al. Sustained reduction of serum cholesterol in low-dose 6-year simvastatin treatment with minimum side effects in 51,321 Japanese hypercholesterolemic patients. Circ J 2003;67:287e94. 80. Wu CC, Sy R, Tanphaichitr V, et al. Comparing the efficacy and safety of atorvastatin and simvastatin in Asians with elevated low-density lipoproteincholesterolda multinational, multicenter, double-blind study. J Formos Med Assoc 2002;101:478e87. 81. Yamamoto A, Arakawa K, Sasaki J, et al. Clinical effects of rosuvastatin, a new HMG-CoA reductase inhibitor, in Japanese patients with primary hypercholesterolemia: an early phase II study. J Atheroscler Thromb 2002;9:48e56. 82. Gupta M, Braga MF, Teoh H, et al. Statin effects on LDL and HDL cholesterol in South Asian and white populations. J Clin Pharmacol 2009; 49:831e7. 83. Deedwania PC, Gupta M, Stein M, et al. Comparison of rosuvastatin versus atorvastatin in South-Asian patients at risk of coronary heart disease (from the IRIS Trial). Am J Cardiol 2007;99:1538e43.