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Type 2 diabetes T2DM is considered epidemic in the developed world, and is rapidly increasing in the developing world. Since , there has been a near quadrupling of the number of adults with diabetes worldwide to an estimated million in [1]. Because diabetes affects the whole body vascular system, there is a significant burden of vascular complications directly attributable to diabetes. Although the rates of diabetes-related complications are declining, the burden of disease remains high due to the increasing prevalence of diabetes [2]. The tremendous burden of diabetes and its complications on the population make it imperative that all health care practitioners understand the vascular effects of diabetes as well as evidence-based interventions that can mitigate them.

In this review, we present an approach to the assessment, prevention, and treatment of cardiovascular disease in patients with T2DM. He is obese and a smoker, has no other health issues, and is taking no medications.

Cardiovascular Risk Factor Control in Type 2 Diabetes Mellitus and New Trial Evidence

He is sent for routine bloodwork and his A1c and fasting glucose are elevated and are diagnostic for diabetes. He returns to the clinic to discuss his results. There are many risk scores and risk calculators available for assessing cardiovascular risk.

Exercise ECG stress testing should be reserved for patients who can exercise and who have a normal resting electrocardiogram, but given the widespread availability and greater specificity of ECG stress testing when combined with an imaging modality, exercise ECG testing should mainly be utilized to assess exercise response and functional ability as indicators of overall prognosis. Poor prognostic indicators include inability to exercise beyond 5 METS, fall in systolic blood pressure with exercise, development of exercise-induced angina, and chronotropic incompetence inability to increase heart rate appropriately in response to exercise.

Cardiovascular Risk Factor Control in Type 2 Diabetes Mellitus and New Trial Evidence

If the patient cannot exercise, pharmacologic stress should be used. Fasting lipid panel, including HDL, LDL, triglycerides and total cholesterol levels should be assessed at the time of diagnosis, at the initial medical evaluation, and at least every 5 years thereafter. A lipid panel should also be obtained immediately before initiating statin therapy.

Once a patient is taking a statin, testing for LDL cholesterol may be considered on an individual basis e. Serum creatinine and urine albumin-to-creatinine ratio if urine dipstick is negative for proteinuria. Common conditions that coexist with diabetes, such as hypertension and dyslipidemia, largely contribute to increased risk of cardiovascular disease in this patient population, and treatment should be pursued with a global approach, addressing these comorbidities aggressively in diabetic patients.

Hypertension is a common comorbidity of diabetes and contributes to increased risk of both microvascular and macrovascular disease. Blood pressure BP control should be pursued in diabetic patients in concert with the recommendations of the ADA:. The prevalence of lipid abnormalities is increased in diabetic patients, contributing to the increased incidence of cardiovascular disease seen in these patients. Lifestyle modification is an essential part of lipid management in diabetic patients, and should focus on reduction in the intake of saturated fat, trans fat, and cholesterol, increase of dietary?

All diabetic patients with overt atherosclerotic cardiovascular disease ASCVD or those above the age of 40 plus additional risk factors for ASCVD should be treated with a statin, regardless of baseline lipid levels. For patients of all ages with diabetes and atherosclerotic cardiovascular disease, high-intensity statin therapy should be added to lifestyle therapy Level A recommendation. For patients with diabetes aged 40—75 years without additional atherosclerotic cardiovascular disease risk factors, consider using moderate-intensity statin and lifestyle therapy Level A recommendation.

For patients with diabetes aged 40—75 years with additional atherosclerotic cardiovascular disease risk factors, consider using high-intensity statin and lifestyle therapy Level B recommendation. Intensity of statin therapy should be adjusted based on individual patient response to medication e. At the present time, there is no convincing data that treatment of low HDL and elevated triglycerides results in incremental CVD risk reduction when the LDL is at target on statin therapy.

Furthermore, combination therapy is associated with an increased risk of transaminitis, myositis and rhabdomyolysis. Therefore, treatment of low HDL or elevated triglycerides is not recommended at this time. The ADA proposes optimal targets for glycemic control but each target must be individualized to the needs of each patient and their disease factors. Recent randomized control trials of intensive targeting HbA1c of less than 6. A modest, but significant, benefit in reducing cardiovascular disease outcomes, primarily nonfatal MI, was observed in a pooled analysis of these three trials.

Nevertheless, intensive glycemic control needs to be balanced against the increased risk of hypoglycemic events, which were increased in the intensive glycemic arms of all of these trials. Smoking cessation is an essential part of cardiovascular disease risk reduction in diabetic patients and should be an integral component in comprehensive diabetes management.

The presence or absence of diabetes should not influence the decision process with respect to coronary reperfusion in patients with AMI. Specifically, in diabetic patients with ST segment elevation myocardial infarction STEMI , an immediate revascularization strategy should be pursued, preferably with percutaneous coronary intervention PCI , or thrombolytic therapy if PCI is unavailable in a timely manner. However, diabetic patients tend to have better outcomes with PCI compared to fibrinolysis.

All patients who have sustained a MI should be administered aspirin indefinitely, regardless of the presence or absence of diabetes.

In patients who sustain an NSTEMI and are treated with medical therapy, P2Y12 inhibitor such as clopidogrel or ticagrelor, but not prasugrel, should be administered in addition to aspirin for at least 1 year. In patients with diabetes and prior MI 1—3 years before , adding ticagrelor to aspirin significantly reduces the risk of recurrent ischemic events including cardiovascular and coronary heart disease death. While there are no clear data on mortality benefit in diabetic patients in the setting of STEMI, a mortality benefit in diabetic patients was reported in a meta-analysis of six randomized trials in the setting of NSTEMI day mortality of 6.

However, recent randomized controlled clinical trials of aspirin for primary prevention of CVD in diabetic patients have failed to demonstrate a significant reduction in risk of cardiovascular disease outcomes.

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Aspirin should be utilized for secondary prevention in patients with known cardiovascular disease Level A recommendation. In patients with documented allergy to aspirin and a strong indication for antiplatelet therapy, clopidogrel should be used as a substitute, at a dose of 75 mg Level B recommendation. ACE inhibitor therapy is recommended to reduce the risk of future cardiovascular events in diabetic patients with cardiovascular disease.

When used after an acute coronary syndrome ACS , ACE inhibitors reduce infarct size, limit ventricular remodeling, and reduce mortality; they also may provide substantial benefit in diabetic patients even compared to non-diabetic patients who sustain an ACS. ACE inhibitors should be administered long-term in diabetic patients after an ACS, provided that there are no contraindications to continued use i. Beta blockers are an important medical therapy in the treatment of cardiovascular disease in diabetic patients, and particularly in the setting of ACS, as they have been shown to reduce the incidence of recurrent ischemia and repeat infarction, reduce infarct size and improve mortality.

While there has been concern that beta blockers may mask hypoglycemic symptoms, which has historically resulted in underuse of beta blockers in diabetics, this concern has not been borne out in clinical trials. In contrast, diabetic patients may derive even greater benefit from beta blockers. Beta blockers should be used for the treatment of patients who have sustained a MI provided there are no contraindications present i.

Serum potassium levels should be monitored closely during treatment, particularly with concomitant use of ACE inhibitor therapy, due to increased risk of hyperkalemia. Recently published cardiovascular outcome trials have provided evidence for the first time that supports the use of antihyperglycemic agents in mitigating cardiovascular risk in patients with type 2 diabetes with cardiovascular disease or at high risk for cardiovascular disease.

Management of Common Comorbidities of Diabetes |

The FDA recently added a new indication for empagliflozin, to reduce the risk of cardiovascular death in adults with type 2 diabetes and cardiovascular disease. Whether other SGLT2 inhibitors will have the same effect in high-risk patients and whether empagliflozin or other SGLT2 inhibitors will have a similar effect in lower-risk patients with diabetes remains unknown. For example, the CVD risk associated with lipid and BP levels is continuous; hence, specific targets are somewhat arbitrary and should be used as a guide to treatment, and not as a mandatory requirement.

Table 8 can be used when developing a management plan for patients. The risks associated with the effort required to reach a particular target, as opposed to achieving a near-target value, may outweigh any small absolute benefit.


Any reduction in risk factor values will be associated with some benefit. Treat simultaneously with lipid-lowering and BP-lowering unless contraindicated or clinically inappropriate. Consider withdrawal of therapy for people who make profound lifestyle changes.

Approaches to Reducing CVD Risk in Type 2 Diabetes

Review response 6—12 weekly until sufficient improvement or maximum tolerated dose achieved. Lifestyle changes in nutrition, physical activity and smoking status fundamentally underpin a comprehensive approach to CVD risk minimisation.

Lifestyle changes show excellent cost-effectiveness in lowering the burden of disease and remain the basis for the management of all CVD risk levels. Lifestyle modification. This section on antihypertensive interventions to reduce cardiovascular risk provides further discussion of BP targets. BP-lowering therapy in people with diabetes should preferentially include an angiotensin converting enzyme inhibitor ACEI or angiotensin receptor blocker ARB. Lowering BP reduces cardiovascular events and all-cause mortality in people with type 2 diabetes in the same manner as for the general population.

While no difference is noted between different classes of BP-lowering therapy for CVD outcomes, there is clear evidence that in people with type 2 diabetes, antihypertensive therapy with an angiotensin receptor blocker ARB or angiotensin-converting enzyme inhibitor ACEI decreases the rate of progression of albuminuria, promotes regression to normoalbuminuria and may reduce the risk of decline in renal function. The target levels for BP therapy have been based on little direct trial evidence.

As always, treatment targets should be individualised and people with diabetes monitored for side effects from the use of medications to achieve lower targets. GPs should consider treatable secondary causes of raised blood lipids before commencing drug therapy.