Online-only article: The risks of hypercholesterolaemia in diabetes

Successful control of blood lipid levels is even more important in patients with diabetes, says Dr Colin Kenny.

NICE guidance recommends simvastatin in all patients with type-2 diabetes over the age of 40 (Photograph: SPL)
NICE guidance recommends simvastatin in all patients with type-2 diabetes over the age of 40 (Photograph: SPL)

Diabetes mellitus is an important and common metabolic disorder, where there is chronic hyperglycemia, which in turn can lead to disturbances of carbohydrate, fat and protein metabolism. The condition results from defects of insulin secretion, insulin action or a combination of both.

In type-1 diabetes there is often a sudden onset due to an almost complete lack of endogenous insulin production. In type-2 diabetes the blood sugar can rise more slowly and the condition may have a multifactorial cause, including genetic predisposition; an unhealthy, calorie-dense diet; lack of physical activity and increasing weight, especially distributed around the abdomen.

Both types of diabetes may be associated with the development of long-term organ damage, including retinopathy, nephropathy and neuropathy, as well as being particularly associated with a high risk of cardiovascular, cerebrovascular and peripheral artery disease.

The number of people with type-2 diabetes around the world is predicted to increase from 171 million in 2000 to 366 million by 2030. The World Health Organization estimates that there are around 1.8 million people living with diabetes mellitus in the UK, with numbers expected to rise to 2.7 million by 2030.

The third edition of the International Diabetes Federation (IDF) Atlas suggests UK prevalence of diabetes is 3.9 per cent in the 20-79 year age group, of whom it is conventional to assume 85 per cent have type-2 diabetes.

Abnormal lipid profile
People with type-2 diabetes have a characteristic disturbance called diabetic dyslipidaemia. It consists of elevated serum triglycerides, low HDL- and high LDL-cholesterol. This profile in turn leads to a 2-4 fold increase in the risk of developing cardiovascular disease.1

Atherosclerosis in people with type-2 diabetes is often more severe and diffuse than in people without diabetes, and in turn both morbidity and mortality rates are higher,2 with 60-80 per cent of people with type-2 diabetes dying from macrovascular complications.3

Role for diet and lifestyle
People with diabetes should be given lifestyle and dietary advice in a form sensitive to their individual needs. While there should be emphasis on general population dietetic measures, people with diabetes should be encouraged to have a diet that includes carbohydrate from fruits, vegetables, wholegrains and pulses. There should be emphasis on the inclusion of low fat dairy products and oily fish, and control of saturated and trans-fatty acid intake.

Another important aspect of lifestyle modification is to encourage increasing physical activity. Studies assessing the association between physical activity and the risk of cardiovascular mortality among diabetic patients indicate regular physical activity is associated with reduced CVD and total morality.4 The promotion of physical activity is recommended for the primary and secondary prevention of cardiovascular disease and complications in diabetic patients.

Medication for hypercholesterolaemia
Diet and lifestyle advice should form the cornerstone of type-2 diabetes management, but on its own may be insufficient to achieve contemporary targets. This is recognised in the latest NICE guidance, which suggests that nearly all patients with type-2 diabetes are at high cardiovascular risk. In some cases this may be enough to justify statin therapy without further assessment.

The guidance also emphasises other therapies that may be used in addition to cholesterol-modifying drugs to ameliorate CV risk. These include blood glucose lowering, blood pressure lowering, and anti-platelet therapies. These in turn should be intensified according to cardiovascular risk assessment. Quantifying the degree of cardiovascular risk in diabetes may be complex, as many people with diabetes are already at high risk, and this can vary with age and ethnicity.

The NICE guidance suggests managing nearly all patients with type-2 diabetes as having a 10-year cardiovascular risk >20 per cent. This is appropriate, particularly as outcome from MI is known to be worse for those with diabetes, and preventive therapy therefore more cost-effective.

Statin therapy has immerged as a very important intervention in people with type-2 diabetes. A number of large clinical trials have included sub groups of patients with diabetes. These have helped to establish an important role for statins as effective agents in both primary and secondary prevention of coronary artery disease.

In the Heart Protection Study (HPS), type-2 diabetes was an independent predictor of benefit from statin therapy as simvastatin 40mg.5

The CARDS study, in patients with type-2 diabetes and at least one other CHD risk factor, showed a 37 per cent relative reduction in major coronary events and a 48 per cent relative reduction in stroke with atorvastatin.6 A meta-analysis of lipid-lowering trials in diabetes have concluded that cholesterol reduction in type-2 diabetes appears to cost-effective.7 For GPs and their teams the current target for total cholesterol in patients with diabetes in the GMS quality and outcome framework is 5mmmol/l.

The latest NICE guidance recommends simvastatin 40mg in all patients with type-2 diabetes over the age of 40, with annual review and escalating dosage of simvastatin as needed. It is suggested that if there is existing or newly-diagnosed cardiovascular disease, or if there is an increased albumin excretion rate, to achieve a total cholesterol level below 4.0mmol/l (and HDL-cholesterol not exceeding 1.4mmol/l) or an LDL-cholesterol level below 2.0mmol/l. NICE also recommends fibrates in addition to statins where triglycerides remain high, but is more cautious about the use of nicotinic acid and omega 3 fish oils.

Conclusion
The epidemic of diabetes is an urgent and growing problem, which needs multifactorial interventions to both prevent and treat the condition. Patients with diabetes have a distinctive lipid profile which leaves them at considerable added risk of cardiovascular events. Dietary and lifestyle measures are important interventions.

Large recent trials and associated guidance suggests an initial risk stratification, and then active consideration of statin therapy, with additional therapy as needed, in patients with diabetes over 40 years of age, to help prevent the considerable cardiovascular risk and attendant morbidity and mortality from the condition.

This article has been published online only and is exclusive to Healthcare Republic. Dr Kenny is a general practitioner in Dromore, Co Down.

VIEW OUR ONLINE HEALTHY CHOLESTEROL LIFESTYLES RESOURCE CENTRE

References
1. Wei M, Gaskill SP, Haffner SM, Stern MP. Effects of diabetes and level of glycemia on all-cause and cardiovascular mortality. The San Antonio Heart Study. Diabetes Care 1998; 21: 1,167-72.

2. Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF.. Lifetime risk for diabetes mellitus in the United States. JAMA 2003; 290: 1,884-90.

3. Henry RR. Preventing cardiovascular complications of type 2 diabetes: focus on lipid management. Clinical Diabetes 2001; 19: 113-20.

4. Hayes L, White M, Unwin N, Bhopal R, Fischbacher C, Harland J, Alberti KG. Patterns of physical activity and relationship with risk markers for cardiovascular disease and diabetes in Indian, Pakistani, Bangladeshi and European adults in a UK population. J Public Health Med 2002; 24: 170-8.

5. Collins R, Armitage J, Parish S, Sleigh P, Peto R; Heart Protection Study Collaborative Group. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 5693 people with diabetes. Lancet 2003; 361: 2005-16.

6. un HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH; CARDS investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin in type 2 diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364: 685-96.

7. Vijan S, Howard RA. Pharmacologic lipid lowering therapy in type 2 diabetes: background paper for the American College of Physicians. Annals of Internal Medicine 2004; 140: 650-8.

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