International Task Force for Prevention of Coronary Heart Disease

International Task Force for Prevention of
Coronary Heart Disease

CORONARY HEART DISEASE: REDUCING THE RISK

3.6 Management of coronary risk factors in patients with diabetes mellitus

Careful diabetic control is essential. The goal is to maintain the values of glycosylated HbA1c below 7.0% ⁵⁰. Reduction of other cardiovascular risk factors is also very important in diabetic patients. This includes the following instruments:

Correction of overweight and obesity by decreasing energy intake and by taking suitable aerobic exercise. This is essential to improve the control of diabetes and of associated coronary risk factors, particularly in the obese type 2 diabetic patient. In insulin-treated patients a programme for weight reduction requires special experience, particularly for older patients. Aerobic (endurance) exercise improves insulin sensitivity in skeletal muscle, lowers circulating triglyceride levels and increases HDL-cholesterol.
A diet similar to the lipid-lowering diet, with carbohydrate intake of 55% of total calories, and with emphasis on complex carbohydrates, fruits, vegetables and soluble fibre. Refined and processed simple sugar is severely restricted. Total fat intake should be <30% of daily energy, with reduction in the intake of saturated fat to less than 7%. Moderate consumption of polyunsaturated and, in particular, monounsaturated fats (olive or rapeseed oil) should be encouraged. Total cholesterol intake should be restricted to < 300 mg/day.
Stop smoking: in diabetics, smoking is associated with a fourfold increase in risk of CHD. For this reason, stopping smoking is mandatory.
Pharmacological means, if necessary: in patients with mild diabetes, a two- to four-month trial of life style modification should be attempted before pharmaceutical treatment is initiated. However, in patients with severe metabolic derangement, preexisting CHD or diabetic complications, pharmacological means should be employed without delay to achieve strict diabetic control.

Pharmacological measures may be need in addition to diet and physical exercise to achieve glycaemic control include insulin, sulfonylureas, biguanides (e.g. metformin), alpha glucosidase inhibitors (e.g. acarbose), and the new thiazolidinediones (insulin-sensitizers). In type 1 diabetes, intensive insulin therapy has been shown, in a long-term follow-up study, to reduce the incidence of microvascular complications significantly; there was also a decline in macrovascular complications, though this failed to reach statistical significance due to the small number of events observed. Information on glycaemic control and incidence of cardiovascular disease in type 2 diabetes is scanty. The results from the UK Prospective Diabetes Study will become available late in 1998. In a small study in Kumamoto (Japan), intensive insulin therapy in type 2 diabetics significantly reduced microvascular complications, with a non-significant 54% reduction in cardiovascular events ^50a.

Most type 2 diabetics are deficient in insulin and sulfonylureas are a rational initial choice of drug. They have the advantages of a clear mechanism of action, low cost, and well-defined adverse effects. Unfortunately, their effect is not always maintained in the long term. Metformin, a biguanide compound, increases sensitivity to endogenous insulin and reduces plasma glucose and insulin concentrations in obese type 2 diabetics. It is not effective in the absence of endogenous insulin. Metformin reduces lipolysis and plasma free fatty acid concentrations and, compared with sulfonylureas, produces a greater improvement in the lipid profile. Acarbose, an alpha-glucosidase inhibitor, lowers blood glucose by interfering the intestinal digestion of carbohydrates. The primary benefits are a reduction in postprandial glycaemia and a decrease in the extremes between maximal and minimal postprandial glucose levels. Acarbose can be used in both type 1 and type 2 diabetics, its main drawback being flatulence and abdominal discomfort. Thiazolidinediones have been shown to be improve insulin resistance adn dyslipidaemia in type 2 diabetes. Their safety profile and efficacy in reducing cardiovascular complications have yet to be established in long-term trials.

Glycaemic control influences lipid levels in diabetics. The prevalence of lipid abnormalities in type 1 diabetics depends on the degree of glycaemic control. In well controlled subjects , plasma lipid levels are similar to nondiabetic subjects, while poorly controlled individuals (often in some degree of ketoacidosis) show hypertriglyceridaemia or even chylomicronaemia. Intensive insulin therapy may decrease elevated plasma cholesterol and LDL-cholesterol and in some cases is associated with increased HDL-cholesterol. In a large trial, there was less dyslipidaemia in the intensively treated group compared to the standard treatment group50b. Some type 1 diabetic patients, however, have an increased cholesterol to triglyceride ratio in VLDL particles which may not resolve with intensive glucose control by insulin. In these cases, the composition of lipoproteins may remain abnormal in spite of tight glycaemic control with intensive insulinization.

The lipid abnormalities most characteristic of type 2 diabetes are increased triglyceride and decreased HDL-cholesterol levels, with an excess of small, dense LDL particles. In addition to glycaemic control, other factors such as obesity, insulin resistance, renal disease and microalbuminuria affect lipid levels in these patients. Glycaemic control, whether by insulin or oral agents, improves, diabetic dyslipidaemia, especially hypertriglyceridaemia. Often, the magnitude of the triglyceride lowering is related to the degree of improved glycaemic control obtained, but the effect on HDL-cholesterol is more variable. It is possible that improved glycaemic control with insulin may have a greater effect on HDL-cholesterol than improved glycaemic control with sulfonylureas. <>p Regular monitoring of plasma lipids including cholesterol and HDL-cholesterol should be part of the management of diabetes.

Lipid-lowering drugs should be considered if lipid abnormalities persist despite the measures described above. Fibrates are mostly used for combined hyperlipidaemia. They should be used with care or not at all in the presence of diabetic nephropathy or renal insufficiency. Statins are effective when elevated cholesterol and LDL predominate and can effectively lower triglyceride levels as well. They can be used in the presence of nephrotic syndrome. The recommended target lipid levels in diabetic patients are shown in Table 13.

Table 13: Suggested target lipid levels in diabetic patients.

	No evidence of macrovascular disease	Evidence of macrovascular disease
LDL-C	< 130 mg/dl (3.4 mmol/L)	< 100 mg/dl (2.6 mmol/L)
Triglyceride	< 150 mg/dl (1.8 mmol/L)	< 150 mg/dl (1.8 mmol/L)
HDL-C	> 35 mg/dl (0.9 mmol/L)	> 35 mg/dl (0.9 mmol/L)

No evidence of

macrovascular disease

Evidence of

macrovascular disease

LDL-C

< 130 mg/dl (3.4 mmol/L)

< 100 mg/dl (2.6 mmol/L)

Triglyceride

< 150 mg/dl (1.8 mmol/L)

HDL-C

> 35 mg/dl (0.9 mmol/L)

Good control of hypertension is also essential in diabetics (see section 3.5, Management of hypertension). Subgroup analysis of data from the HOT Study ^48a showed significantly and progressively lower incidence of major cardiovascular events with lower target diastolic blood pressure in diabetic hypertensives. This finding supports the concept of the need for aggressive intervention against high blood pressure in diabetics. Low-dose thiazides and b-blockers are suitable first-line agents for treatment of hypertension in diabetics. If these agents produce or exacerbate hyperlipidaemia, or if they worsen diabetic control, they should be replaced by antihy-pertensive agents that have no adverse metabolic side-effect, such as ACE-inhibitors, calcium channel blockers or a3.5.3.3, Angiotensin converting enzyme (ACE)-inhibitors).