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Canadian Journal of Cardiology

CardioDiabetes: Core Competencies for Cardiovascular Clinicians in a Rapidly Evolving Era of Type 2 Diabetes Management

Open AccessPublished:July 19, 2018DOI:https://doi.org/10.1016/j.cjca.2018.07.010

      Abstract

      A sea change in the management of diabetes is occurring with the publication of clinical trials showing unequivocal cardiovascular (CV) protection through the use of certain antihyperglycemic agents. This change is similar to the change that occurred when lipid lowering with statins was first shown to have CV benefits, an event necessitating changes in training and the proactive treatment of lipids by CV specialists. As was the case then, many CV specialists currently feel poorly equipped to address diabetes with this new information even though diabetes is common in CV practice. The purpose of this overview is to provide an updated, comprehensive, and evidence-based CV protection plan for patients with type 2 diabetes, intended specifically for cardiologists and vascular medicine specialists. We attempt to elucidate a set of “CardioDiabetes” core competencies by merging the CV-relevant elements of the Diabetes Canada 2018 guidelines within a framework of comprehensive vascular protection as supported by other CV guidelines. We review the rationale for measuring hemoglobin A1C, understanding its use for establishing a diagnosis and for monitoring treatment. We also provide a brief review of the medications most important for a CV specialist to know. We provide useful memory aids and a succinct set of reminders and tips (“ABCDEFR’S”) that can serve as a comprehensive checklist in the clinic and help to motivate trainees and clinicians to consult the original guideline source documents to enrich their knowledge and improve treatment in this rapidly changing arena.

      Résumé

      Un changement de paradigme s’opère dans la prise en charge du diabète suivant la publication d’essais cliniques démontrant la protection cardiovasculaire (CV) sans équivoque que procurent certains antihyperglycémiants. Ce changement rappelle celui qui s’est produit lorsque les bienfaits CV du traitement hypolipémiant par les statines ont été démontrés pour la première fois, ce qui avait entraîné des changements en matière de formation et amené les spécialistes de la médecine CV à adopter une conduite proactive dans le traitement des troubles lipidiques. Comme ce fut le cas alors, beaucoup de spécialistes de la médecine CV se sentent actuellement mal outillés pour traiter le diabète dans ce nouveau contexte, même si cette pathologie est fréquente dans le cadre de leur pratique. Dans le présent article de survol, nous proposons un plan de protection CV à jour, complet et fondé sur des données probantes répondant spécifiquement aux besoins des cardiologues et des spécialistes de la médecine vasculaire en matière de prise en charge du diabète de type 2. Nous tentons d’élucider une série de compétences « cardiodiabétiques » de base en fusionnant les éléments CV pertinents des lignes directrices de 2018 de Diabète Canada dans une démarche de protection vasculaire globale étayée par d’autres lignes directrices en médecine CV. Nous abordons les fondements de la mesure de l’hémoglobine glyquée et les principes de son utilisation pour les besoins du diagnostic de la maladie et de la surveillance du traitement. En outre, nous passons brièvement en revue les principaux médicaments offrant un intérêt certain pour les spécialistes de la médecine CV. Enfin, nous présentons des aide-mémoire et une brève liste de rappels et de conseils susceptibles de constituer une liste de contrôle exhaustive en clinique et d’inciter les stagiaires et les cliniciens à consulter les lignes directrices originales pour enrichir leurs connaissances et améliorer le traitement dans un contexte qui évolue rapidement.
      Type 2 diabetes (T2D) is a major risk factor for cardiovascular (CV) morbidity and mortality. This writing group has previously summarized practical issues in the diagnosis and management of diabetes
      • Mancini G.B.J.
      • Cheng A.Y.
      • Connelly K.
      • et al.
      Diabetes for cardiologists: practical issues in diagnosis and management.
      and provided a brief summary of some of the key diabetes pharmacotherapies of relevance to cardiologists.
      • Fitchett D.
      • Cheng A.
      • Connelly K.
      • et al.
      A practical guide to the use of glucose-lowering agents with cardiovascular benefit or proven safety.
      The purpose of this overview is to provide an updated, comprehensive, and evidence-based CV protection plan for patients with T2D. We attempt to elucidate a set of “CardioDiabetes” core competencies by emphasizing the Diabetes Canada 2018 guidelines while integrating them within a framework of comprehensive vascular protection as outlined in guidelines relevant to CV practice
      Diabetes Canada Clinical Practice Guidelines Expert Committee
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      2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult.
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      (Table 1). Given that recently completed CV outcome trials showing CV safety or superiority are for agents approved for T2D, our scope is to address the care of nonpregnant adults with T2D likely to be encountered by CV clinicians and the recommendations most critical for cardiology practice. The original guidelines remain the source documents for more detailed and critical analyses of levels and grades of evidence underlying the general principles emphasized in this practical review.
      Table 1Summary of CardioDiabetes core competencies: the “ABCDEFR’S”
      Core competency issuesQuick tips and reminders
      AA1CUse A1C
      A1C may not be appropriate in special circumstances (eg, thalassemia, pregnancy, etc.).
      (or FPG) as an initial screening test (Fig. 3)

      Confirmed A1C ≥ 6.5% = T2D

      A1C 6.0% to 6.4% = prediabetes
      A1C goal is ≤7.0% (≤6.5% to reduce retinopathy and nephropathy; relax goals in frail, functionally dependent patients)Initiate healthy lifestyle behaviours

      Metformin is the initial drug of choice if eGFR ≥ 30 mL/min/1.73 m2.
      Insulin may be required if A1C is very high or if there is metabolic decompensation. The original guidelines remain the source documents for more detailed discussion of any of the “ABCDEFR’S.”


      Reassess in 3 mo and use add-on medications as per Figures 3 and 4
      Antiplatelet agentsUse for secondary preventionDo not use routinely for primary preventionASA 81 mg (clopidogrel 75 mg if ASA intolerant)
      Acute coronary syndromesTreat as per ACS guidelines
      • Teo K.K.
      • Cohen E.
      • Buller C.
      • et al.
      Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology/Canadian Society of Cardiac Surgery position statement on revascularization—multivessel coronary artery disease.
      • Welsh R.C.
      • Travers A.
      • Huynh T.
      • Cantor W.J.
      Canadian Cardiovascular Society Working G. Canadian Cardiovascular Society Working Group: providing a perspective on the 2007 focused update of the American College of Cardiology and American Heart Association 2004 guidelines for the management of ST elevation MI.


      ACS is an important time to screen for unrecognized T2D (Fig. 2)
      Hyperglycemia should be managed to attain blood glucose 7.0-10.0 mmol/L using locally developed algorithms incorporating basal + bolus + corrective insulin dosages and implemented by specifically trained personnelASA + ticagrelor/prasugrel preferred over ASA + clopidogrel if feasible

      Consider ASA + prasugrel if undergoing percutaneous coronary intervention, clopidogrel naïve, <75 years old, >65 kg, and no history of stroke; or, consider ASA + ticagrelor if no history of stroke and no extreme bradycardia.

      In high-risk patients with average or low bleeding risk, prolong dual antiplatelet therapy for up to 3 y with ASA + lower dose ticagrelor
      AFTreat as per AF guidelines
      • Macle L.
      • Cairns J.
      • Leblanc K.
      • et al.
      2016 focused update of the Canadian Cardiovascular Society guidelines for the management of AF.
      T2D is a strong predictor of stroke in AF and, as a component of risk algorithms, renders such patients eligible for OACNovel oral anticoagulant preferred over warfarin in nonvalvular AF
      BBlood pressure<130/80 mm HgPreference for ACEI/ARB particularly if there is evidence of either hypertension- or T2D-induced end-organ damage (eg, left ventricular hypertrophy, nephropathy/albuminuria, retinopathy, neuropathy)Preference for combinations (ACEI/ARB + dihydropyridine CCBs; ACEI/ARB + thiazide/thiazide-like diuretics if higher risk features are absent)
      CCholesterolTreat as per CCS dyslipidemia guidelines
      • Anderson T.J.
      • Gregoire J.
      • Pearson G.J.
      • et al.
      2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult.
      (CVD or microvascular complications, >40 years old, >30 years old with 15-y duration of T2D)
      Statin should be initiated regardless of baseline LDL-C. Elevated LDL-C should be reduced to values consistently <2.0 mmol/L or by ≥50%.Ezetimibe may be warranted to achieve goals. PCSK9i’s may be warranted in the presence of CVD or familial hypercholesterolemia to achieve goals
      DDietWarranted for patients with T2D or prediabetesIf body mass index ≥25 kg/m2 encourage 5% to 10% weight lossProfessional dietary counselling ideal if feasible and accessible
      DrivingConsider proximity to ACS or coronary artery bypass grafting, syncope, arrhythmias, internal cardioverter defibrillator implantation, valve disease, ejection fraction, and New York Heart Association Class, hypertrophic cardiomyopathySpecial restrictions and considerations such as self-monitoring of blood glucose apply to patients using insulin and/or insulin secretagoguesAssessment of hypoglycemic episodes may warrant consideration of alternative AHAs or relaxation of A1C targets if appropriate
      EExerciseWarranted for patients with T2D or prediabetes who are able to exerciseRest electrocardiogram warranted. Determine if pre-exercise program functional testing is warranted (see “S” - Screening for CAD, below)150 min/wk of aerobic exercise and, ideally, incorporation of resistance exercise (initial training by an exercise specialist if feasible and accessible)
      FFailure (heart failure)Therapies are similar as for patients without T2D including beta blockers, RAAS blockers, or sacubitril/valsartanIf eGFR > 30 mL/min/1.73 m2 metformin is the initial drug of choice for T2D. Consider SGLT2i (empagliflozin/canagliflozin) to reduce hospitalization for heart failure

      Avoid or use caution with saxagliptin

      Avoid thiazolidinedione class
      Care required with respect to dosage and dose escalation in the presence of impaired renal function. Check eGFR, electrolytes within 2 wk of drug additions or dosage changes. Use of SGLT2i requires reassessment of diuretic doses
      RRenal functionAll medications require dosing with respect to baseline renal function. See Figure 6 for key antihyperglycemic agent dosage adjustmentsRenoprotection can be achieved with ACEI/ARBs particularly in the setting of hypertension and/or albuminuria

      Empagliflozin and canagliflozin have been shown to reduce renal disease progression. Liraglutide and semaglutide have been shown to reduce albuminuria
      Extra caution is required in patients with T2D during acute illnesses and/or when unable to eat and hydrate properly. Drug cessation may be warranted under these situations (see Table 3), but hyperglycemia should be avoided through monitoring and/or use of other agents as warranted
      RetinopathyNot a contraindication for use of thrombolytic therapyFenofibrate may be used to slow progression of retinopathy, but this therapy has not been shown to reduce CV risk. It is generally warranted only to help address severe hypertriglyceridemia (TG ≥ 10 mmol/L)Reinforce yearly eye examination with fundoscopy
      RevascularizationPatients with T2D are at higher riskWith non-ST elevation ACS and high-risk features, an early invasive approach to reduce recurrent coronary events is warranted unless contraindicatedPatients with multivessel and/or complex coronary anatomy should be considered for coronary artery bypass grafting
      SSmoking cessationConcomitant T2D and smoking imparts extremely high-risk CVD and T2D complicationsAssess for readiness to quit in all patients who smoke and access smoking cessation support programsHospitalized smokers warrant interventions for smoking cessation during the period of hospitalization and ongoing follow-up
      Screening for CADResting electrocardiogram if >40 y; or if >30 y and T2DM > 15-y duration or if there are other traditional risk factorsPatients >40 and planning to undertake very vigorous or prolonged exercise should have resting ECG and be considered for exercise testingTesting for underlying coronary artery disease should be assessed as per CCS Stable Ischemic Heart Disease guidelines as appropriate and particularly in the presence of typical or atypical cardiac symptoms; the presence of resting electrocardiographic abnormalities; the presence of noncoronary atherosclerosis (eg, peripheral arterial disease) or events (eg, stroke/transient ischemic attack); the presence of coronary calcium score >400 Agatston units
      Sex-specific issuesFemales contemplating pregnancy or who are pregnant require specialized T2D careConcomitant CVD requires specialized CV care in coordination with T2D careStatins, fibrates, ACEI/ARBs should be stopped before or as soon as possible during pregnancy and during breast feeding
      Erectile dysfunction occurs especially commonly with CVD and T2DM comorbidityPhosphodiesterase-5 inhibitors are first line of treatment but cannot be used concomitantly with nitratesFailure of phosphodiesterase-5 inhibitors may warrant specialist assessment of hypogonadism
      This is a succinct summary for consideration of routine care in uncomplicated situations.
      A1C, haemoglobin A1C; ACEI, angiotensin converting enzyme inhibitor; ACS, acute coronary syndrome; AF, atrial fibrillation; AHA, antihyperglycemic agents; ARB, angiotensin receptor blocker; ASA, acetylsalicylic acid; CAD, coronary artery disease; CCB, calcium channel blocker; CCS, Canadian Cardiovascular Society; CV, cardiovascular; CVD, cardiovascular disease; ECG, electrocardiogram; eGFR, estimated glomerular filtration rate; FPG, fasting plasma, glucose; LDL-C, low-density lipoprotein-cholesterol; OAC, oral anticoagulant; PCSK9i, proprotein convertase subtilisin kexin 9 inhibitor; RAAS, renin angiotensin aldosterone system; SGLT2i, sodium-glucose cotransporter-2 inhibitor; T2D, type 2 diabetes; T2DM, type 2 diabetes mellitus; TG, triglycerides.
      A1C may not be appropriate in special circumstances (eg, thalassemia, pregnancy, etc.).
      Insulin may be required if A1C is very high or if there is metabolic decompensation. The original guidelines remain the source documents for more detailed discussion of any of the “ABCDEFR’S.”

      CardioDiabetes: Why CV Clinicians Should Be More Proactive in Preventing, Diagnosing, and Managing T2D

      A multifactorial approach addressing healthy lifestyle, glycemic control, blood pressure (BP) control, dyslipidemia management, and other CV protective measures effectively lowers the risk of serious complications and mortality and prolongs life expectancy for individuals with diabetes.
      • Gaede P.
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      Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial.
      • Clement M.
      • Filteau P.
      • Harvey B.
      • et al.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: organization of diabetes care.
      CV clinicians recognize that T2D is a marker of risk when evaluating the need for anticoagulation for stroke prevention in atrial fibrillation (AF), type of coronary revascularization, appropriate BP and lipid goals, and overall risk stratification. But recent developments support a more proactive role in ensuring optimal glycemic and vascular protection using appropriate antihyperglycemic agents (AHAs). Randomized clinical trials have identified certain AHAs that offer CV protection, compared with placebo in the context of standard diabetes care (Fig. 1).
      • Zinman B.
      • Wanner C.
      • Lachin J.M.
      • et al.
      Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.
      • Neal B.
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      • et al.
      Canagliflozin and cardiovascular and renal events in type 2 diabetes.
      • Marso S.P.
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      • et al.
      Liraglutide and cardiovascular outcomes in type 2 diabetes.
      • Marso S.P.
      • Bain S.C.
      • Consoli A.
      • et al.
      Semaglutide and cardiovascular outcomes in patients with type 2 diabetes.
      The mechanisms of CV benefit remain to be defined but do not appear to be linked predominantly to A1C reduction. In addition, there is greater awareness of the association between increased mortality and severe or symptomatic hypoglycemia.
      • Yale J.F.
      • Paty B.
      • Senior P.A.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: hypoglycemia.
      Finally, Diabetes Canada has recently promoted the general principle of avoiding hypoglycemia and weight gain, the latter relevant to overall CV risk and patient adherence.
      • Wharton S.
      • Pedersen S.D.
      • Lau D.C.W.
      • Sharma A.M.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: weight management in diabetes.
      Thus, CV clinicians should be aware of the optimal choice of AHAs for patients with or at risk of cardiovascular disease (CVD).
      Figure thumbnail gr1
      Figure 1Summary of hazard ratios for events of interest as reported in recent trials showing either CV superiority or safety. Cells shaded in green indicate statistically significant results. *Although statistically significant, a superiority analysis was not pre-specified in this safety trial; #effects predominantly on albuminuria. CANVAS, CANagliflozin cardioVascular Assessment Study; CV, cardiovascular; EMPA-REG, Empagliflozin Cardiovascular Outcome Event Trial in T2D Patients (EMPA-REG OUTCOME); LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; MACE, major adverse cardiac events (CV death, nonfatal MI, or stroke); MI, myocardial infarction; SUSTAIN-6, Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes.
      T2D is often diagnosed when macrovascular disease is already present or CV risk is already augmented. Nearly half of patients seen in either elective or emergency CV settings have unrecognized dysglycemia.
      • Mancini G.B.J.
      • Cheng A.Y.
      • Connelly K.
      • et al.
      Diabetes for cardiologists: practical issues in diagnosis and management.
      • Bartnik M.
      • Ryden L.
      • Ferrari R.
      • et al.
      The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe. The Euro Heart Survey on diabetes and the heart.
      Previously unrecognized prediabetes and T2D were recently identified in 1 in 3 referrals for elective angioplasty, and these patients had a 2.2-fold augmented hazard for adverse CV events compared with referrals without dysglycemia.
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      • Kok M.M.
      • Sattar N.
      • et al.
      “Silent” diabetes and clinical outcome after treatment with contemporary drug-eluting stents: the BIO-RESORT Silent Diabetes study.
      Moreover, increased CV risk (ie, macrovascular risk and early macrovascular disease) occurs at an A1C level below the threshold for diagnosis (6.5%), a threshold signalling increased risk of retinopathy.
      • Gerstein H.C.
      Dysglycemia and cardiovascular risk in the general population.
      • Punthakee Z.
      • Goldenberg R.
      • Katz P.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome.
      Thus, cardiologists are in a key position not only to optimize care of patients with known T2D but also to recognize new cases and to identify patients with prediabetes (A1C 6.0% to 6.4%) who are at increased CV risk. General screening and diagnostic categories are summarized in Figure 2.
      • Punthakee Z.
      • Goldenberg R.
      • Katz P.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome.
      • Ekoe J.M.
      • Goldenberg R.
      • Katz P.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: screening for diabetes in adults.
      Figure thumbnail gr2
      Figure 2Screening for type 2 diabetes in adults. If both fasting plasma glucose (FPG) and A1C are available but discordant, use the test that appears furthest to the right side of the algorithm. *Consider 75-g oral glucose tolerance test if there is an additional risk factor. **Consider 75-g oral glucose tolerance test.
      Reproduced from Ekoe et al.
      • Ekoe J.M.
      • Goldenberg R.
      • Katz P.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: screening for diabetes in adults.
      with permission from Elsevier.
      Of admissions for acute coronary syndrome (ACS), 15% to 35% have diabetes,
      • Ovbiagele B.
      • Markovic D.
      • Fonarow G.C.
      Recent US patterns and predictors of prevalent diabetes among acute MI patients.
      and up to 15% have previously unrecognized diabetes.
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      • Kober L.
      • et al.
      Newly diagnosed and previously known diabetes mellitus and 1-year outcomes of acute MI: the VALsartan In Acute MI (VALIANT) trial.
      More than two-thirds of people with myocardial infarction (MI) have either diabetes or prediabetes including impaired glucose tolerance or impaired fasting glucose.
      • Bartnik M.
      • Ryden L.
      • Ferrari R.
      • et al.
      The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe. The Euro Heart Survey on diabetes and the heart.
      • Norhammar A.
      • Tenerz A.
      • Nilsson G.
      • et al.
      Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study.
      Cardiologists should be prepared to provide acute management of hyperglycemia in those patients (Fig. 3).
      • Tardif J.C.
      • L'Allier P.L.
      • Fitchett D.H.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: management of acute coronary syndromes.
      However, fasting plasma glucose can be elevated transiently in the first 2 days after ACS and is unreliable for establishing a diagnosis of diabetes as would also be the case during other significant illnesses causing “stress” hyperglycemia (eg, pneumonia).
      • Tardif J.C.
      • L'Allier P.L.
      • Fitchett D.H.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: management of acute coronary syndromes.
      But these responses may alert practitioners to underlying dysglycemia. Although impaired glucose tolerance is the predominant glucose abnormality in ACS,
      • Bartnik M.
      • Ryden L.
      • Ferrari R.
      • et al.
      The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe. The Euro Heart Survey on diabetes and the heart.
      an oral glucose tolerance test is not indicated and may also be unreliable if performed within 4 to 5 days of the event.
      • Tardif J.C.
      • L'Allier P.L.
      • Fitchett D.H.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: management of acute coronary syndromes.
      Thus, in an acute setting, the most pragmatic approach is to use an A1C test as outlined in Figure 3.
      Figure thumbnail gr3
      Figure 3Screening for type 2 diabetes in acute coronary syndromes (ACS). BG, blood glucose; CBG, capillary blood glucose; CBGM, CBG monitoring; PG, plasma glucose.

      Individualization of Targets and Goals

      A1C targets should be individualized to reduce complications while maintaining safety.
      • Tardif J.C.
      • L'Allier P.L.
      • Fitchett D.H.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: management of acute coronary syndromes.
      One of the main roles of cardiologists should be to recognize the appropriate A1C goal, determine if it has been achieved, and assess side effects, particularly hypoglycemia.
      • Yale J.F.
      • Paty B.
      • Senior P.A.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: hypoglycemia.
      For the vast majority of patients with or without CVD, the A1C target is ≤7.0%, which has been shown to reduce microvascular complications and also macrovascular complications over a long period of time.
      UK Prospective Diabetes Study (UKPDS) Group
      Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).
      The Diabetes Control and Complications Trial Research Group
      The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.
      • Holman R.R.
      • Paul S.K.
      • Bethel M.A.
      • Matthews D.R.
      • Neil H.A.W.
      10-year follow-up of intensive glucose control in type 2 diabetes.
      • Nathan D.M.
      • Cleary P.A.
      • Backlund J.Y.
      • et al.
      Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes.
      Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes.
      • Patel A.
      • MacMahon S.
      • et al.
      Advance Collaborative Group
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      • Hayward R.A.
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      • Wiitala W.L.
      • et al.
      Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes.
      In a minority of patients (eg, functional dependency, recurrent severe hypoglycemia, hypoglycemia unawareness, limited life expectancy, dementia, or frailty), a higher A1C (up to 8.5%) is appropriate.
      • Imran S.A.
      • Agarwal G.
      • Bajaj H.S.
      • Ross S.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: targets for glycemic control.
      Finally, A1C ≤ 6.5% is endorsed in early, uncomplicated cases to further reduce the risk of retinopathy and nephropathy in T2D if achieved without hypoglycemia.
      A1C should generally be measured every 3 months to ensure that glycemic goals are being achieved or every 6 months once target is consistently maintained.
      • Imran S.A.
      • Agarwal G.
      • Bajaj H.S.
      • Ross S.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: targets for glycemic control.
      Cardiologists should inquire if their patient is using self-monitored blood glucose testing, particularly if they are on insulin or other medications associated with hypoglycemia. Although the act of testing does not by itself improve glycemic control, actions undertaken based on the self-monitored blood glucose results facilitate self-management.

      Comprehensive Therapy of T2D From a CV Perspective

      Nutrition and physical activity

      People with prediabetes or T2D should ideally be referred to a registered dietician. If the body mass index is ≥25 kg/m2, a 5% to 10% weight loss goal is recommended. Simple walking programs are suitable for patients without exertional symptoms. At least 150 minutes per week of aerobic exercise is recommended, with the addition of at least 2 or 3 sessions per week of resistance exercise when possible.
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      • et al.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: physical activity and diabetes.
      Supervised exercise interventions improve A1C,
      • Umpierre D.
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      • et al.
      Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis.
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      • Ribeiro J.P.
      Volume of supervised exercise training impacts glycaemic control in patients with type 2 diabetes: a systematic review with meta-regression analysis.
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      • Boule N.G.
      Effect of aerobic exercise intensity on glycemic control in type 2 diabetes: a meta-analysis of head-to-head randomized trials.
      triglycerides, and cholesterol
      • Balducci S.
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      • Cardelli P.
      • et al.
      Effect of high- versus low-intensity supervised aerobic and resistance training on modifiable cardiovascular risk factors in type 2 diabetes; the Italian Diabetes and Exercise Study (IDES).
      in people with T2D. In people with type 2, or type 1 diabetes, regular physical activity and/or moderate-to-high cardiorespiratory fitness are associated in cohort studies with reductions in CV and overall mortality.
      • Sluik D.
      • Buijsse B.
      • Muckelbauer R.
      • et al.
      Physical activity and mortality in individuals with diabetes mellitus: a prospective study and meta-analysis.
      • Gregg E.W.
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      Relationship of walking to mortality among US adults with diabetes.
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      • Barengo N.C.
      • et al.
      Physical activity, cardiovascular risk factors, and mortality among Finnish adults with diabetes.
      • Moy C.S.
      • Songer T.J.
      • LaPorte R.E.
      • et al.
      Insulin-dependent diabetes mellitus, physical activity, and death.
      • Tikkanen-Dolenc H.
      • Waden J.
      • Forsblom C.
      • et al.
      Frequent and intensive physical activity reduces risk of cardiovascular events in type 1 diabetes.
      • Church T.S.
      • LaMonte M.J.
      • Barlow C.E.
      • Blair S.N.
      Cardiorespiratory fitness and body mass index as predictors of cardiovascular disease mortality among men with diabetes.
      • Hu F.B.
      • Stampfer M.J.
      • Solomon C.
      • et al.
      Physical activity and risk for cardiovascular events in diabetic women.
      It should be emphasized that even lesser amounts of exercise are important and that a reduction in sedentary time on top of exercise is important as well. Patients on medications associated with hypoglycemia, particularly insulin, will require specialized recommendations regarding timing of exercise sessions with meals, carbohydrate supplementation, and dosing of AHAs.

      Key antihyperglycemic agents

      Sequential use of AHAs is depicted in Figure 4. This figure does not include consideration of metabolic decompensation, which will require the use of insulin supplemented by other medications.
      • Lipscombe L.
      • Booth G.
      • Butalia S.
      • et al.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: pharmacologic glycemic management of type 2 diabetes in adults.
      Figure thumbnail gr4
      Figure 4Simplified flow diagram for the selection of add-on antihyperglycemic agents. Semaglutide is shown in brackets because the superiority endpoint was not prespecified. CV, cardiovascular; DPP-4, dipeptidyl peptidase-4; GLP-1 RA, glucagon-like peptide-1 receptor agonists; SGLT2, sodium-glucose cotransporter-2; TZD, thiazolidinedione.
      Adapted from Lipscombe et al.
      • Lipscombe L.
      • Booth G.
      • Butalia S.
      • et al.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: pharmacologic glycemic management of type 2 diabetes in adults.
      with permission from Elsevier.
      Metformin is typically used initially, in conjunction with healthy lifestyle modifications, or at 3 months after diagnosis if glycemic targets are not achieved using healthy lifestyle changes. Metformin has low risks of hypoglycemia and weight gain, the advantage of long-term experience, and low cost. If A1C values are ≥1.5% above goal at diagnosis, initiating metformin in combination with a second AHA is recommended to increase the likelihood of achieving A1C goals. Goals should be attained expeditiously within 3 to 6 months through either dose adjustments to metformin and/or addition of other AHAs. Simultaneous use of agents within the same class and/or from different classes but with similar mechanisms of action (eg, dipeptidyl peptidase-4 [DPP-4] inhibitors, and glucagon-like peptide-1 receptor agonists [GLP-1 RAs], both incretins; sulphonylureas and meglitinides, both insulin secretagogues) is not recommended at this time.
      Accordingly, although CV clinicians should be familiar with metformin and all other AHAs used by their patients, they should prioritize the use of agents with CV superiority or safety, no or rare hypoglycemia, avoidance of weight gain, positive effects on heart failure (HF) outcomes and evidence for renal protection (Fig. 5). Currently, AHAs with proven CV superiority include two GLP-1 RAs (liraglutide, semaglutide) and two sodium-glucose cotransporter-2 (SGLT2) inhibitors (empagliflozin, canagliflozin). DPP-4 inhibitors (alogliptin, sitagliptin, saxagliptin) show CV safety, but saxagiptin was associated with greater risk of HF. Some reduce BP (eg, SGLT2 inhibitors and GLP-1 RAs) so reassessment of BP medications, particularly diuretics, is often needed. Other general issues and practical tips are summarized in Table 2.
      • Lipscombe L.
      • Booth G.
      • Butalia S.
      • et al.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: pharmacologic glycemic management of type 2 diabetes in adults.
      Note that CV studies are pending regarding dapagliflozin and ertugliflozin (SGLT2 inhibitors), albiglutide and dulaglutide (GLP-1 RAs), and linagliptin (DPP-4 inhibitor).
      Figure thumbnail gr5
      Figure 5Short list of add-on antihyperglycemic agents showing CV superiority or safety. CV, cardiovascular; DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1; SGLT2, sodium-glucose cotransporter-2.
      Table 2General consideration for use of classes with at least 1 agent with demonstrated CV superiority or safety
      Adapted from the paper by Lipscombe et al.
      • Lipscombe L.
      • Booth G.
      • Butalia S.
      • et al.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: pharmacologic glycemic management of type 2 diabetes in adults.
      with permission from Elsevier.
      ClassOther therapeutic considerations
      GLP-1 RAsRequires subcutaneous injection

      GI side effects (nausea, vomiting, diarrhea; usually self-limited)

      Gallstone disease

      Contraindicated with personal/family history of medullary thyroid cancer or multiple endocrine neoplasia-2
      SGLT2 inhibitorsHypotension

      Increased urinary frequency, genital infections (eg, vaginitis, balanitis), urinary tract infections (usually limited to initial phase of therapy)

      Dose-related increases in LDL-C

      Caution with renal dysfunction, loop diuretics, in the elderly

      Dapagliflozin not to be used if there is a history of bladder cancer

      Rare diabetic ketoacidosis (may occur with no hyperglycemia)

      Increased risk of fractures and amputations with canagliflozin
      DPP-4 inhibitorsRare joint pains

      Caution/avoid saxagliptin in heart failure
      CV, cardiovascular; DPP-4, dipeptidyl peptidase-4; GLP-1 RA, glucagon-like peptide-1 receptor agonists; GI, gastrointenstinal; LDL-C, low-density lipoprotein-cholesterol; SGLT2, sodium-glucose cotransporter-2.
      Some insulin preparations have demonstrated CV safety but are associated with weight gain or hypoglycemia (eg, insulin glargine and degludec). Thus, insulin prescriptions should be initiated and monitored by diabetes specialists in all nonurgent situations. Weight gain and HF associated with the use of thiazolidinediones make this class unattractive for routine cardiology use. Patients may be taking other classes not associated with hypoglycemia (acarbose and orlistat), but these have not been shown yet in randomized clinical trials to have CV superiority or safety in patients with T2D. This applies also to insulin secretagogues (meglitinides and sulphonylureas), which are often associated with hypoglycemia and should not be initiated or recommended by cardiologists. Even agents not associated with hypoglycemia may precipitate hypoglycemia if added to insulin or insulin secretagogues. Their addition may require a reduction in the dose of insulin or insulin secretagogues. Cardiologists asked to assess CV suitability for driving or flying must recognize if the patient is using AHAs associated with hypoglycemia, because this situation may warrant a recommendation for switching AHAs and/or education for use of self-monitoring of blood glucose.
      • Houlden R.L.
      • Berard L.
      • Lakoff J.M.
      • Woo V.
      • Yale J.F.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: diabetes and driving.
      • Simpson C.
      • Dorian P.
      • Gupta A.
      • et al.
      Assessment of the cardiac patient for fitness to drive: drive subgroup executive summary.
      Renal function (see also the Renal issues and renoprotection section) at the time of initiation and while on therapy must be considered (Fig. 6).
      • Lipscombe L.
      • Booth G.
      • Butalia S.
      • et al.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: pharmacologic glycemic management of type 2 diabetes in adults.
      If SGLT2 inhibitors are initiated, the dosage of diuretics, particularly loop diuretics, needs to be reconsidered.
      Figure thumbnail gr6
      Figure 6Key antihyperglycemic agents and renal function. CKD, chronic kidney disease; DPP-4, dipeptidyl peptidase-4; eGFR, estimated glomerular filtration rate; GLP-1, glucagon-like peptide-1; SGLT2, sodium-glucose cotransporter-2.
      Adapted from Lipscombe et al.
      • Lipscombe L.
      • Booth G.
      • Butalia S.
      • et al.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: pharmacologic glycemic management of type 2 diabetes in adults.
      with permission from Elsevier.
      Sick day medication management (ie, management of medications when patients are unable to eat or are at high risk of dehydration) is important to avoid hypoglycemia, acute kidney injury, or other complications. The medications that should possibly be held during dehydrating illness are commonly used in cardiology and therefore CV clinicians should reinforce that teaching (Table 3).
      • Lipscombe L.
      • Booth G.
      • Butalia S.
      • et al.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: pharmacologic glycemic management of type 2 diabetes in adults.
      Diabetes Canada Clinical Practice Guidelines Expert Committee
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: sick-day medication list.
      Table 3Two alternate mnemonics to assist in remembering list of “sick day” medications that may require reduction or temporary cessation when patients are unable to hydrate or take in calories
      SADMANS from Lipscombe et al
      • Lipscombe L.
      • Booth G.
      • Butalia S.
      • et al.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: pharmacologic glycemic management of type 2 diabetes in adults.
      and Diabetes Canada
      Diabetes Canada Clinical Practice Guidelines Expert Committee
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: sick-day medication list.
      reproduced with permission from Elsevier.
      “SADMANS”“NO BP”
      • S = Sulphonylureas
      • A = ACEI
      • D = Diuretics, direct renin inhibitors
      • M = Metformin
      • A = ARB
      • N = Nonsteroidal anti-inflammatory drugs
      • S = SGLT2 inhibitors
      • N = NSAIDs
      • O = Oral antihyperglycemic agents (metformin, sulphonylureas, SGLT2 inhibitors)
      • BP = RAAS blockers, diuretics
      Note that in some circumstances insulin may be the only feasible medication that is safe for controlling hyperglycemia during severe, acute illnesses.
      ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BP, blood pressure; NSAID, nonsteroidal anti-inflammatory drug; RAAS, renin angiotensin aldosterone system; SGLT2, sodium-glucose cotransporter-2 inhibitor.

      Antiplatelet agents and acute coronary syndromes

      Diabetes and hyperglycemia are independent predictors of increased short- and long-term mortality, recurrent MI, and HF in patients with acute MI. Acetylsalicylic acid (ASA) is recommended in patients with T2D requiring secondary prevention but is not recommended routinely in patients requiring only primary prevention.
      • Stone J.A.
      • Houlden R.L.
      • Lin P.
      • Udell J.A.
      • Verma S.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: cardiovascular protection in people with diabetes.
      Clopidogrel is appropriate in patients with ASA intolerance. Patients with ACS and T2D should generally be treated in the same fashion as patients without T2D, but ASA with prasugrel or ticagrelor are preferred over ASA with clopidogrel. After a year of dual antiplatelet therapy, those at very high risk of recurrent ischemic events and at average or low bleeding risk should be considered for dual treatment up to 3 years with ticagrelor 60 mg twice daily.
      • Teo K.K.
      • Cohen E.
      • Buller C.
      • et al.
      Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology/Canadian Society of Cardiac Surgery position statement on revascularization—multivessel coronary artery disease.
      • Mehta S.R.
      • Bainey K.R.
      • Cantor W.J.
      • et al.
      2018 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Focused Update of the guidelines for the use of antiplatelet therapy.
      • Tardif J.C.
      • L'Allier P.L.
      • Fitchett D.H.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: management of acute coronary syndromes.

      Atrial fibrillation

      The odds ratio is 1.4 for men and 1.6 for women for the development of AF in the setting of diabetes.
      • Benjamin E.J.
      • Levy D.
      • Vaziri S.M.
      • et al.
      Independent risk factors for AF in a population-based cohort. The Framingham Heart study.
      But this association diminishes with age and may not be present past age of 75.
      • Pallisgaard J.L.
      • Schjerning A.M.
      • Lindhardt T.B.
      • et al.
      Risk of AF in diabetes mellitus: a nationwide cohort study.
      The increased risk is multifactorial and may be related to MI, left ventricular dysfunction, diabetic cardiomyopathy, and chronic oxidative stress causing tissue inflammation leading to fibrosis of atrial tissue, conducting pathways and ventricular tissue. In addition, as many as 1/5 persons with T2D who suffer MI may develop AF. T2D causes a significantly increased risk of stroke/thromboembolic events as reflected in contemporary AF stroke risk calculators.
      • Macle L.
      • Cairns J.
      • Leblanc K.
      • et al.
      2016 focused update of the Canadian Cardiovascular Society guidelines for the management of AF.
      • Gage B.F.
      • Waterman A.D.
      • Shannon W.
      • et al.
      Validation of clinical classification schemes for predicting stroke: results from the national registry of AF.
      Oral anticoagulants, with a preference for novel oral anticoagulants over warfarin, are indicated.
      • Macle L.
      • Cairns J.
      • Leblanc K.
      • et al.
      2016 focused update of the Canadian Cardiovascular Society guidelines for the management of AF.

      BP control

      People with diabetes, explicitly excluded from the Systolic Blood Pressure Intervention Trial (SPRINT) trial, should be treated to achieve a BP < 130/80 mm Hg.
      • Nerenberg K.A.
      • Zarnke K.B.
      • Leung A.A.
      • et al.
      Hypertension Canada’s 2018 guidelines for diagnosis, risk assessment, prevention, and treatment of hypertension in adults and children.
      • Leung A.A.
      • Nerenberg K.
      • Daskalopoulou S.S.
      • et al.
      Hypertension Canada’s 2016 Canadian Hypertension Education Program guidelines for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension.
      • Tobe S.W.
      • Gilbert R.E.
      • Jones C.
      • et al.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: treatment of hypertension.
      The SPRINT Research Group
      A randomized trial of intensive versus standard blood-pressure control.
      For persons with CV disease or chronic kidney disease, including albuminuria, or with CV risk factors in addition to diabetes and hypertension, an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) is recommended as initial therapy. If target BP levels are not achieved with standard-dose monotherapy, additional agents should be used. For persons in whom combination therapy with an ACEI or ARB is being considered, a dihydropyridine calcium channel blocker is preferable to a thiazide/thiazide-like diuretic.

      Cholesterol management

      The beneficial effects of lowering low-density lipoprotein cholesterol with statin therapy apply equally well to people with and without diabetes.
      • Anderson T.J.
      • Gregoire J.
      • Pearson G.J.
      • et al.
      2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult.
      • Mancini G.B.J.
      • Hegele R.A.
      • Leiter L.A.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: dyslipidemia.
      The goal for people with diabetes is low-density lipoprotein cholesterol consistently <2.0 mmol/L or > 50% reduction from baseline (or non–high-density lipoprotein cholesterol <2.6 mmol/L or apolipoprotein B <0.8 g/L). This should be achieved with healthy lifestyle changes and statin monotherapy. The addition of other lipid-lowering medications, such as ezetimibe or proprotein convertase subtilisin kexin 9 inhibitor, may be considered. With fasting triglyceride >10.0 mmol/L, glycemic control should be optimized, healthy lifestyle interventions (eg, weight management, alcohol avoidance, etc.) should be implemented, and a fibrate should be added to reduce the risk of pancreatitis.

      Heart failure

      Diabetes is associated with the increased prevalence of HF with either reduced or preserved ejection fraction. Moreover, diabetes can cause HF independently of ischemic heart disease or hypertension by causing a diabetic cardiomyopathy.
      The SPRINT Research Group
      A randomized trial of intensive versus standard blood-pressure control.
      In nearly every HF trial, diabetes is present in over one-third of subjects, and although this subset has increased risk, they derive greater absolute benefit as compared with people without diabetes.
      • Ghali J.K.
      • Boehmer J.
      • Feldman A.M.
      • et al.
      Influence of diabetes on cardiac resynchronization therapy with or without defibrillator in patients with advanced heart failure.
      • Fantoni C.
      • Regoli F.
      • Ghanem A.
      • et al.
      Long-term outcome in diabetic heart failure patients treated with cardiac resynchronization therapy.
      Accordingly, individuals with diabetes and HF should receive the same HF therapies as those without diabetes.
      • Ezekowitz J.A.
      • O'Meara E.
      • McDonald M.A.
      • et al.
      2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of heart failure.
      • Connelly K.A.
      • Gilbert R.E.
      • Liu P.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: treatment of diabetes in people with heart failure.
      Serum electrolytes and creatinine, BP and body weight, and HF symptoms and signs should be monitored within 7 to 10 days of any initiation or titration of therapy of ACEIs or ARBs or use of sacubitril/valsartan. HF in patients with T2D is more frequently complicated by renal disease and a propensity for hyperkalemia. If the estimated glomerular filtration rate is <60 mL/min and/or if combined renin angiotensin aldosterone system blockade is employed, starting doses should be halved and uptitration should be more gradual. For A1C management, metformin remains first line but should be temporarily withheld if renal function acutely worsens, and should be discontinued if renal function significantly and chronically worsens (<30 mL/min/1.73 m2). Thiazolidinediones should be avoided, but SGLT2 inhibitors (empagliflozin or canagliflozin) may be added to reduce the risk of hospitalizations for HF in those with clinical CVD and estimated glomerular filtration rate >30 mL/min/1.73 m2.
      • Ezekowitz J.A.
      • O'Meara E.
      • McDonald M.A.
      • et al.
      2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of heart failure.
      • Connelly K.A.
      • Gilbert R.E.
      • Liu P.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: treatment of diabetes in people with heart failure.

      Renal issues and renoprotection

      In addition to the renoprotective benefits of ACEI/ARBs, Figure 1, Figure 4, and 5 emphasize the potential addition of newer AHAs for reducing either progression of “hard” renal endpoints or reduction of albuminuria.
      • Nerenberg K.A.
      • Zarnke K.B.
      • Leung A.A.
      • et al.
      Hypertension Canada’s 2018 guidelines for diagnosis, risk assessment, prevention, and treatment of hypertension in adults and children.
      • McFarlane P.
      • Cherney D.
      • Gilbert R.E.
      • Senior P.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: chronic kidney disease in diabetes.
      Dosing according to renal function is critical for some agents and summarized in Figure 6.
      • Lipscombe L.
      • Booth G.
      • Butalia S.
      • et al.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: pharmacologic glycemic management of type 2 diabetes in adults.
      Furthermore, when evaluating patients unable to hydrate or take in calories, some agents may require reduction or temporary cessation of AHAs as summarized using the sick-day mnemonics in Table 3.

      Revascularization

      Revascularization decisions in patients with diabetes are complex. But in many scenarios, coronary artery bypass grafting is favoured over percutaneous coronary intervention (PCI) for patients with T2D relative to the general population based on improved long-term outcomes of death, MI, and repeat revascularization despite an early stroke excess.
      • Fox K.A.
      • Clayton T.C.
      • Damman P.
      • et al.
      Long-term outcome of a routine versus selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome a meta-analysis of individual patient data.
      These results are generally extrapolated to the higher risk ACS population with diabetes in the setting of non–ST-elevation-ACS and complex coronary anatomy. Therefore, coronary artery bypass grafting with the use of internal thoracic artery bypass should be the preferred revascularization modality over complex PCI with the provision that patient characteristics (such as frailty, cerebrovascular disease, among others) are considered. PCI with newer generation drug-eluting stents may be acceptable for people with less extensive disease (ie, single-vessel disease or 2-vessel disease without involvement of the left anterior descending artery and those with a SYNTAX score ≤ 22) if symptoms or quality of life issues on medical therapy dictate the addition of revascularization.
      • Teo K.K.
      • Cohen E.
      • Buller C.
      • et al.
      Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology/Canadian Society of Cardiac Surgery position statement on revascularization—multivessel coronary artery disease.
      • Mancini G.B.
      • Gosselin G.
      • Chow B.
      • et al.
      Canadian Cardiovascular Society guidelines for the diagnosis and management of stable ischemic heart disease.
      • Verma S.
      • Farkouh M.E.
      • Yanagawa B.
      • et al.
      Comparison of coronary artery bypass surgery and percutaneous coronary intervention in patients with diabetes: a meta-analysis of randomised controlled trials.
      In people with diabetes and ST-elevation-ACS, the selection of the reperfusion modality (primary PCI vs fibrinolysis) should not differ from people with STE-ACS without diabetes; ocular haemorrhage in people with diabetic retinopathy is extremely rare and should not limit the use of fibrinolysis when it is indicated.
      • Tardif J.C.
      • L'Allier P.L.
      • Fitchett D.H.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: management of acute coronary syndromes.

      Conclusions

      With the addition of other topics not discussed above (screening for coronary artery disease,
      • Poirier P.
      • Bertrand O.F.
      • Leipsic J.
      • et al.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: screening for the presence of cardiovascular disease.
      smoking cessation,
      • Pipe A.L.
      • Eisenberg M.J.
      • Gupta A.
      • et al.
      Smoking cessation and the cardiovascular specialist: Canadian Cardiovascular Society Position Paper.
      and sex-specific issues
      • Bebb R.
      • Millar A.
      • Brock G.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: sexual dysfunction and hypogonadism in men with diabetes.
      • Feig D.S.
      • Berger H.
      • Donovan L.
      • et al.
      Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada: diabetes and pregnancy.
      ) Table 1 can serve as a checklist of areas of competence with practical, quick tips and reminders for the cardiologist or CV clinician taking care of routine patients with T2D and CVD. The interplay of multiple guideline recommendations applied to this patient population represents what we propose as core competencies for CV clinicians and trainees as we enter an exciting new era of management of T2D. Regarding T2D itself, CV clinicians should:
      • understand how to identify prediabetes and T2D mainly through measuring and understanding the use of A1C;
      • be aware of standard, initial therapy with metformin in routine patients;
      • generally aim for an A1C ≤ 7%;
      • become familiar and competent with drugs that are not associated with hypoglycemia and that have proven CV superiority and/or CV safety and to add them or advocate adding them according to key patient characteristics based mainly on the presence or absence of established CVD;
      • undertake these actions in conjunction with the primary care physician and/or an endocrinologist; and
      • recognize that achievement of A1C goals using insulin should not generally be performed in the ambulatory setting by cardiologists.

      Funding Sources

      This work was supported by the Canadian subsidiaries of Astra Zeneca , Boehringer Ingelheim , Janssen, Merck & Co , and Novo Nordisk through unrestricted educational grants to the University of British Columbia . Bridge Medical Communications was hired to facilitate the travel arrangements and logistical needs for a single working meeting to review content. The manuscript is the sole creation of the authors.

      Disclosures

      Please see Supplemental Appendix S1 for conflict of interest disclosures.

      Supplementary Material

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