OBJECTIVE -To compare effects of different oral hypoglycemic drugs as first-line therapy on lipoprotein subfractions in type 2 diabetes.RESEARCH DESIGN AND METHODS -Sixty overweight type 2 diabetic patients not on lipid-lowering therapy were randomized to metformin, pioglitazone, or gliclazide after a 3-month dietary run-in. Drug doses were uptitrated for 3 months to optimize glycemia and were kept fixed for a further 3 months. LDL subfractions (LDL 1 , LDL 2 , and LDL 3 ) were prepared by density gradient ultracentrifugation at randomization and study end. Triglycerides, cholesterol, total protein, and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. The primary end point was change in proportion of LDL as LDL 3 .RESULTS -HbA 1c , triglycerides, glucose, and cholesterol were comparable across groups at baseline and over time. LDL 3 mass and the LDL 3 -to-LDL ratio fell with pioglitazone (LDL 3 mass 36.2 to 28.0 mg/dl, P Ͻ 0.01; LDL 3 -to-LDL 19.2:13.3%, P Ͻ 0.01) and metformin (42.7 to 31.5 mg/dl, P Ͻ 0.01; 21.3:16.2%, P Ͻ 0.01, respectively) with no change on gliclazide. LDL 3 reductions were associated with reciprocal LDL 1 increases. Changes were independent of BMI, glycemic control, and triglycerides. Total HDL cholesterol increased on pioglitazone (1.28 to 1.36 mmol/l, P ϭ 0.02) but not gliclazide (1.39 to 1.37 mmol/l, P ϭ NS) or metformin (1.26 to 1.18 mmol/l, P ϭ NS), largely due to an HDL 2 increase (0.3 to 0.4 mmol/l, P Ͻ 0.05). HDL 3 cholesterol fell on metformin (0.9 to 0.85 mmol/l, P Ͻ 0.01). On pioglitazone and metformin, the HDL 2 -to-HDL 3 ratio increased compared with no change on gliclazide.CONCLUSIONS -For the same improvement in glycemic control, pioglitazone and metformin produce favorable changes in HDL and LDL subfractions compared with gliclazide in overweight type 2 diabetic patients. Such changes may be associated with reduced atherosclerosis risk and may inform the choice of initial oral hypoglycemic agent. Diabetes Care 27:41-46, 2004P atients with type 2 diabetes are frequently overweight with associated hypertension and a characteristic dyslipidemia with raised triglycerides and low HDL cholesterol. This cluster of abnormalities partly explains their increased risk of macrovascular disease. Targeting and treating the hypertension and dyslipidemia improves long-term outcomes (1-3). However, despite intervention, these patients remain at increased risk, suggesting that other factors contribute.A proportion of the increased risk may be explained by qualitative changes in lipoprotein subfraction. Although LDL cholesterol may not be elevated in type 2 diabetes, the dyslipidemia is characterized by an increased proportion of LDL as small, dense LDL or LDL 3 (4). Increased LDL 3 has been shown to be associated with increased risk of myocardial infarction (5-7). Risk may also be increased by qualitative changes in HDL subfractions (8), with an increased proportion of HDL occurring as smaller, denser HDL 3 , which is believed t...

Objectives-(a) To characterise the lipid profile in psoriatic arthritis and investigate whether there are similarities to the dyslipoproteinaemia reported in rheumatoid arthritis and other inflammatory forms of joint disease; (b) to investigate whether there is an atherogenic lipid profile in psoriatic arthritis, which may have a bearing on mortality. Methods-Fasting lipids, lipoproteins, and their subfractions were measured in 50 patients with psoriatic arthritis and their age and sex matched controls. Results-High density lipoprotein cholesterol (HDL cholesterol) and its third subfraction, HDL 3 cholesterol, were significantly reduced and the most dense subfraction of low density lipoprotein (LDL), LDL 3 , was significantly increased in the patients with psoriatic arthritis. Twenty patients with active synovitis had significantly lower total cholesterol, LDL cholesterol, and HDL 3 cholesterol than their controls. 25% of the patients with psoriatic arthritis had raised Lp(a) lipoprotein levels (>300 mg/l) compared with 19% of controls, but this was not statistically significant. Conclusion-Raised levels of LDL 3 and low levels of HDL cholesterol are associated with coronary artery disease. Such an atherogenic profile in a chronic inflammatory form of arthritis is reported, which may be associated with accelerated mortality.

1. Adrenal and gonadal steroids are derived from cholesterol, which may be derived from plasma lipoproteins or de novo synthesis. 2. Inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG CoA) reductase, the rate limiting enzyme in cholesterol synthesis, may therefore affect steroidogenesis when used as lipid‐lowering agents in hypercholesterolaemia. 3. We have assessed gonadal and adrenal function in subjects with heterozygous familial hypercholesterolaemia (FH) before and after 12 weeks treatment with pravastatin, an HMG CoA reductase inhibitor, or cholestyramine as a control in maximal recommended doses. 4. No changes in measured plasma cortisol responses to tetracosactrin injection were seen in 11 patients on cholestyramine or 12 on pravastatin. 5. No changes were seen in testosterone, sex hormone binding globulin, androstenedione, dehydroepiandrosterone sulphate, oestradiol or 17 alpha‐hydroxyprogesterone. 6. Gonadotrophin levels were unaffected in 10 male subjects on cholestyramine and 7 on pravastatin. 7. Measurements on a subset of subjects continuing to 24 weeks treatment also showed no changes. 8. No adverse effect on adrenal or gonadal function could be demonstrated in patients with familial hypercholesterolaemia on maximal recommended doses of pravastatin.