- Diagnosis and Classification of Diabetes
- Initial Assessment and Criteria for Specialist Referral
- Glycaemic Control in Type 2 Diabetes - Oral Hypoglycaemic Agents
- Indications for Insulin in Type 2 Diabetes
- Hypertension
- Dyslipidaemia
- Aspirin Therapy in Diabetes
- Retinopathy
- Nephropathy
- Neuropathy and Foot Ulcers
- Sexual Dysfunction in Men
- Diabetes in Pregnancy and Pre-conception Guidance
6. Dyslipidaemia
- Please also refer to NICE Guideline H: Management of Type 2 Diabetes - management of blood pressure and blood lipids
Patients with diabetes mellitus are at increased risk for cardiovascular disease. In one study, for example, patients with type 2 diabetes without a prior myocardial infarction were at the same risk for myocardial infarction and cardiac mortality as non-diabetic patients who had had a prior myocardial infarction (20 and 19 percent, respectively). These data suggest that cardiovascular risk factors in diabetic patients should be treated as aggressively as in non-diabetic patients with a previous myocardial infarction.
Lipid Abnormalities – The serum lipid abnormalities differ somewhat in patients with type 1 and type 2 diabetes.
• The lipid pattern in patients with type 1 diabetes is largely related to glycaemic control. The Diabetes Control and Complications Trial (DCCT) found that patients with type 1 diabetes who were in reasonable glycaemic control had similar serum lipid values to normal subjects except for young women, who had somewhat higher serum total cholesterol and lower high-density-lipoprotein (HDL) cholesterol concentrations. In comparison, poor glycaemic control is associated with hypertriglyceridaemia and, in some patients, high serum low-density-lipoprotein (LDL) cholesterol and low HDL cholesterol concentrations.
• Among patients with type 2 diabetes, insulin resistance, relative insulin deficiency, and obesity are associated with hypertriglyceridaemia, low serum HDL cholesterol concentrations, and occasionally high serum LDL cholesterol and lipoprotein(a) values. The hypertriglyceridaemia results from both increased substrate availability (glucose and free fatty acids) and decreased lipolysis of very low-density lipoprotein (VLDL) triglyceride. This pattern of lipid abnormalities can be detected before the onset of overt hyperglycaemia and is thought to be due in part to hyperinsulinaemia
For any serum lipoprotein concentration, diabetic patients have more coronary disease than non-diabetic patients. This increase in risk may be due in part to qualitative differences in the lipoprotein fractions or to the presence of other proatherosclerotic metabolic changes such as lipoprotein(a) and oxidised LDL.
Rationale For Lipid Lowering Therapy – The preceding observations suggest that lipid-lowering therapy would be beneficial in some patients with diabetes. Although no trials have been performed specifically in these patients, subgroup analysis of lipid-lowering trials has demonstrated benefit.
Secondary Prevention of Coronary Heart Disease – Two trials suggested that lipid lowering is beneficial in patients with coronary disease (secondary prevention) who have either diabetes or impaired glucose tolerance. The 4S trial(Scandinavian Simvastatin Survival Study) consisted of 4444 patients with coronary disease (angina pectoris or prior myocardial infarction) and hyperlipidaemia. In the subset of 202 patients with diabetes (mostly type 2), those who were treated with Simvastatin had a lower incidence of major cardiovascular events, similar to the non-diabetic patients.
The CARE (Cholesterol and Recurrent Events) trial involved 4159 patients with a history of a myocardial infarction in the previous two years who had "average" serum total, LDL, and HDL cholesterol concentrations, respectively, of 5.4, 3.6, and 1.0 mmol/L). The patients were randomly assigned to Pravastatin or placebo; 586 (14 percent) had diabetes and 342 (8 percent) had impaired glucose tolerance as defined by fasting blood glucose concentrations between 6.1 to 6.9mmol/L. The patients with impaired glucose tolerance had a higher rate of cardiac events than those with blood glucose concentrations less than 6.1mmol/L. The event rate decreased with Pravastatin compared to placebo (relative risk reduction for primary endpoint was 23 percent).
Neither of these trials evaluated the efficacy of treating hypertriglyceridaemia, the most common lipid abnormality in patients with diabetes. Whether correction of isolated hypertriglyceridaemia is beneficial remains unproven, even in non-diabetic patients.
Primary Prevention Of Coronary Heart Disease – A separate issue is the treatment of hyperlipidaemia for primary prevention (ie, in patients without clinical evidence of coronary disease). Two major trials using a statin have demonstrated benefit in non-diabetic patients with hypercholesterolaemia. It is argued from these studies that there is clear support for treatment of high serum cholesterol concentrations in all diabetic patients to reduce the risk of CHD. There is also preliminary clinical evidence that lipid lowering may slow the rate of progression of diabetic nephropathy.
Goal values – Although diabetic patients may have a variety of lipoprotein abnormalities, the primary target of therapy in clinical trials has been LDL cholesterol.
Current practice at the Royal Free Hospital is to suggest a target of total cholesterol of 5.0mmol/L and LDL of 3.0mmol/l in primary prevention. In secondary prevention a target LDL of 2.6mmol/L should be targeted. Strong consideration should be given to drug treatment of significant hypertriglyceridaemia greater than 4.5mmol/L. The lack of data on the magnitude of benefit of LDL-cholesterol lowering therapy in older patients suggests that clinical judgment be applied to patients with diabetes who are over age 65 years and have no additional CHD risk factors other than age.
Lipid-lowering therapy – Appropriate therapy begins with diet (including monounsaturated fats), weight reduction, exercise, and improvement in glycaemic control. In many patients, however, some degree of dyslipidaemia persists and drug therapy is necessary.
Statins and Fibrates – The drug of choice is a statin (Pravastatin 40mg, Simvastatin 40mg, Atorvastatin 10mg) in patients with hypercholesterolaemia and mild hypertriglyceridaemia, or a fibric acid derivative (such as Bezafibrate or Fenofibrate) in patients with marked hypertriglyceridaemia. Among the statins, Atorvastatin may be advantageous because it lowers serum triglyceride concentrations effectively in patients with diabetes and Fluvastatin may be preferred if there is renal impairment. The value of hypolipidaemic drugs other than statins and fibric acid derivatives in patients with type 2 diabetes is uncertain.