PPAR activation lipid metabolism Diabetic dyslipidaemia Lipid profiles
PPAR activation & lipid metabolism
Diabetic dyslipidaemia Lipid profiles and hyperinsulinaemia in newly diagnosed type 2 diabetic patients Type 2 diabetes Control p HDL-C (mmol/L) 1. 07 1. 34 <0. 05 Triglycerides (mmol/L) 2. 41 1. 60 <0. 05 LDL-C (mmol/L) 4. 49 4. 17 NS Total-C (mmol/L) 6. 43 6. 7 NS Fasting insulin (m. U/L) 24. 8 15. 4 0. 003 Niskanen L et al. Diabetes Care 1998; 21: 1861 -9
Effects of pioglitazone vs gliclazide addition to metformin on dyslipidaemia Triglycerides 30. 00 10. 00 TC / HDL ratio 7 2 0. 00 -10. 00 -7 -6 p<0. 001 -20. 00 -23 -30. 00 LDL cholesterol 22 20. 00 % change from baseline after 2 yrs HDL cholesterol p<0. 001 Pioglitazone + Metformin Gliclazide + Metformin -10 -17 p<0. 001 Betteridge DJ, Verges B. Diabetologia 2005; 48: 2477 -81
Changes in dyslipidaemic profile with TZDs * Change from baseline to endpoint (%) after 24 weeks * †* †* Mean baseline mmol/L Mean endpoint mmol/L Triglycerides 2. 9 2. 7 2. 3 2. 8 HDL-C 1. 0 1. 15 1. 08 Non-HDL-C 4. 0 4. 1 4. 6 *p<0. 05 vs baseline; † p<0. 001 between treatment groups Goldberg RB et al. Diabetes Care 2005; 28: 1547– 1554 Goldberg RB et al. Circulation 2005; 111: 1727– 1728
Sulfonylurea + TZD or metformin: Comparison of lipid and renal effects N = 639 with poorly controlled DM 2 † Change after 52 wks (%) † ‡ * Pioglitazone 15– 45 mg + sulfonylurea † Metformin 850– 2550 mg + sulfonylurea *P = 0. 008, †P < 0. 001, ‡P = NS Hanefeld M et al. Diabetes Care. 2004; 27: 141 -7.
TZDs and metformin reduce risk of MI Case-control study of insulin-sensitizing therapy and first MI in patients with type 2 diabetes n Monotherapy Metformin TZD Combination therapy TZD + sulfonylurea Metformin + sulfonylurea Insulin-sensitizing Sulfonylurea drugs monotherapy Patients Controls 38 87 0. 01 7 19 0. 03 7 18 0. 04 40 62 0. 19 0 *Adjusted for age, sex, BMI, ACE inhibitor use, history of hypertension or hypercholesterolemia P 0. 2 0. 4 0. 6 0. 8 1. 0 1. 2 Odds ratio for MI (95% CI)* Sauer WH et al. Am J Cardiol. 2006; 97: 651 -4.
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