Most studies agree that TZDs increase HDL-cholesterol by 10-14 percent, decrease free fatty acids and contribute to the increase in size of small-dense LDL molecules, which has a beneficial effect on the risk for atherosclerosis. Moreover, they do exert a mild hypotriglyceridaemic effect when the triglycerides are > 200 mg/dl (2.3 mmol/L). It should also be mentioned that modern pharmaceutical research is directed towards the development of products that are simultaneously PPAR-g and-a agonists, affecting both the metabolism of glucose and lipids.
A 48 year old woman with a 10 year history of Type 2 DM that has been treated for six years with metformin (at an escalating dose reaching 850 mg three times per day during the last year), presents to the Diabetes Clinic for a regular visit. She feels well and denies any dyspnoea, orthopnoea or ankle oedema, or any undesirable effect of metformin. Her weight is stable, as is her diet (roughly 1,400 kcal/day). Because of her work she does not exercise regularly, except for walking 300 metres every day. Her dietary habits and her activities have not altered during the last 7-8 years, and she does not predict that she will be able to exercise more in the future, because of family and professional responsibilities. She does not smoke. On physical examination there are no murmurs in her heart, no jugular distention, or lower extremity oedema. Her liver edge is palpable and soft. She has a body mass index of 30kg/m2 and slight hypertension (recent measurement 146/88 mmHg), for which she receives an angiotensin converting enzyme inhibitor. Her renal and liver function tests are normal. She has been treated with a statin for two years and the recent levels of total cholesterol are 213 mg/dl (5.51 mmol/L), of HDL-cholesterol 42 mg/dl (1.09 mmol/L), LDL-cholesterol 131 mg/dl (3.39 mmol/L)
and triglycerides 199 mg/dl (2.25 mmol/L). Usual morning fasting blood glucose levels are 140-160 mg/dl (7.8-8.9 mmol/L) and post-prandial 200-230 mg/dl (11.1 -12.8 mmol/L). Her glycosylated haemoglobin level is 8.4 percent, increased by 1.2 percent from the previous measurement five months ago. Her urine albumin excretion rate is at the upper limits of normal (27 mg/24 h). An abdominal ultrasound showed fatty infiltration of the liver, but the remainder of the abdominal organs are without abnormalities. The patient was advised to have a stricter diet and more exercise and was prescribed a small dose of a thiazide diuretic as well as rosiglitazone at a dose of 4 mg per day.
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