1. Case 2: Dyslipidaemia in Type 2 Diabetes Mellitus

2. Page 2 of 8 *DALY; disability-adjusted life years Patient characteristics:  asymptomatic 52 year-old woman  diagnosed with type 2 diabetes mellitus 5 years ago  always was mildly overweight but has remained normotensive  never smoked Physical examination:  weight:71 kg (156 lb)  height: 165 cm (5 ft 5 in)  BMI: 26.3 kg/m 2  blood pressure:110/70 mmHg Case 2: Dyslipidaemia in Type 2 Diabetes Mellitus

3. Page 3 of 8 *DALY; disability-adjusted life years Family history:  Mother: She described her mother, who died in an accident at the age of 50, as also having had “adult-onset” diabetes and as having peripheral vascular complications  Father: The patient’s father died on an MI at the age of 49  Sibling: She has one brother, who is 55 and in apparently good health, although he rarely sees a physician Case 2: Dyslipidaemia in Type 2 Diabetes Mellitus

4. Page 4 of 8 *DALY; disability-adjusted life years Patient history:  She is married and has a 31 year-old daughter and a 29 year-old son, neither of whom has had any health problems; both are normoglycaemic, normotensive, and normolipidaemic  The patient maintains fairly good glycaemic control through scrupulous compliance with a regimen of diet, exercise and glyburide in combination with metformin. Her glycosylated haemoglobin is 6.5% (reference level <6.3%)  She does not drink and her diet is rich in complex carbohydrates and fibre, but she is not a vegetarian Case 2: Dyslipidaemia in Type 2 Diabetes Mellitus

5. Page 5 of 8 *DALY; disability-adjusted life years Lipid profile: The patient’s lipid profile has been closely monitored for only about 1 year. Despite her good glycaemic control and the inclusion of a high-dose statin therapy in her regimen, her fasting lipids have stabilised at average values of:  TC: 150 mg/dl(3.9 mmol/l)  HDL-C: 39 mg/dl(1.0 mmol/l)  TG: 125 mg/dl(1.4 mmol/l)  Calculated LDL-C:86 mg/dl(2.2 mmol/l) Case 2: Dyslipidaemia in Type 2 Diabetes Mellitus

6. Page 6 of 8 What further lipid-lowering therapy would you add to the current statin therapy? Cholestyramine (8 g/day) in a divided dose A fibric acid derivative Ezetimibe 10 mg/day Additional pharmacotherapy not appropriate Recommend adding plant sterols to functional foods in the diet Note: More than one answer may be correct. Case 2: Dyslipidaemia in Type 2 Diabetes Mellitus ABCDEABCDE

7. Page 7 of 8 *DALY; disability-adjusted life years Answer: Although symptoms or signs of atherosclerotic disease are not present, the patient has a high lifetime risk of CHD. She has the typical dyslipidaemia of type 2 diabetes, namely, reduced HDL-C and elevated TG. Type 2 diabetes increases the CHD risk in women 3-7 times, compared to 2- 3 times in men. It nearly eliminates any female premenopausal cardioprotection. Although with statin therapy her lipids are below target levels for high-risk patients (LDL-C <100 mg/dl (<2.5 mmol/l), and TG <150 mg/dl (<1.7 mmol/l)), the patient may benefit from additional LDL-C reduction. Combination therapy with fibric acid derivatives may also be considered. However, adding plant sterols to functional foods further lowers LDL-C by 10-15% even in combination with statin therapy without increasing the risk of side effects in combination therapy. Case 2: Dyslipidaemia in Type 2 Diabetes Mellitus E. Advice to add plant sterols in functional foods to diet

8. Page 8 of 8 *DALY; disability-adjusted life years Evidence: For patients with diabetes, the ADA and NCEP ATPIII recommend decreasing LDL-C below 100 mg/dl (2.6 mmol/l) and TG below 150 mg/dl (1.7 mmol/l). Statins are the first choice of lipid-regulating therapy in patients with diabetes and combined hyperlipidaemia. There is good evidence from large, long-term clinical trials to support significant reductions in rates of CVD clinical events in patients with diabetes, including both coronary and cerebrovascular events. Case 2: Dyslipidaemia in Type 2 Diabetes Mellitus