Abstract
Introduction: Patients with diabetes mellitus type 2 are characterized by a typical dyslipoproteinemia.
Improvement in glucose control usually also ameliorates this dyslipoproteinemia. It
is unclear whether different antidiabetic strategies differ in their effects on the
lipid profile. Particularly, it is unknown whether glitazones improve lipid values
independently of their effects on glucose metabolism.
Methods: Ten patients well controlled on sulfonylureas (HbA1c 6.9 ± 0.5 %) with diabetic dyslipoproteinemia
were treated with additional pioglitazone (30 mg/d) for 3 months. Every 4 weeks the
sulfonylurea dose was adjusted to keep HbA1c and fasting glucose constant. Before
and after 3 months of pioglitazone therapy lipid metabolism was determined in detail
(cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol, VLDL-triglycerides,
lipoprotein(a), LDL-subtype distribution by isopycnic density gradient ultracentrifugation).
Results: Although glucose control remained unchanged (HbA1c 6.9 ± 0.5 % vs. 6.8 ± 0.6 %; fasting
glucose concentration 7.7 ± 1.1 vs. 7.3 ± 1.3 mmol/l) we observed a significant reduction
in triglyceride concentration (1.9 ± 0.6 vs. 1.4 ± 0.5 mmol/l, - 26 %, p < 0.01),
a significant increase in HDL-cholesterol concentration (1.2 ± 0.2 vs. 1.4 ± 0.2 mmol/l,
+ 14 %, p < 0.05), a significant decrease in LDL/HDL-ratio (3.03 ± 0.77 vs. 2.51 ±
0.61, - 24 %, p < 0.05) and non-significant improvements in total cholesterol, LDL-cholesterol,
VLDL-triglycerides, and VLDL-cholesterol concentrations. The LDL-subtype profile improved
(significant reduction [- 20 %] in small dense LDL).
Conclusions: This pilot study indicates that at comparable fasting glucose concentration and at
comparable HbA1c value pioglitazone is superior to sulfonylureas concerning the improvement
of diabetic dyslipoproteinemia. Whether this relates to indirect effects (improvement
in insulin sensitivity) or direct effects (stimulation of PPARα) remains to be determined.
Key words
Diabetic dyslipoproteinemia - glitazone - LDL-subtype - small dense LDL - thiazolidinedione
References
- 1
Beckmann J A, Creager M A, Libby P.
Diabetes and atherosclerosis epidemiology, pathophysiology, and management.
JAMA.
2002;
287
2570-2581
- 2
Camp H S.
Thiazolidinediones in diabetes: current status and future outlook.
Curr Opin Investig Drugs.
2003;
4
406-411
- 3
Chapman M J, Goldstein S, Lagrange D, Laplaud P M.
A density gradient ultracentrifugal procedure for the isolation of the major lipoprotein
classes from human serum.
J Lipid Res.
1981;
22
339-358
- 4
Goeke B. on behalf of the German Pioglitazone Study Group .
Improved glycemic control and lipid profile in a randomized study of pioglitazone
compared with acarbose in patients with type 2 diabetes mellitus.
Treat Endocrinol.
2002;
1
329-336
- 5
Hanefeld M, Brunetti P, Schernthaner G, Mattews D, Charbonnel B.
One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea
plus metformin in patients with type 2 diabetes.
Diab Care.
2004;
27
141-147
- 6
Keating G M, Ormrod D.
Micronised fenofibrate: an updated review of its clinical efficacy in the management
of dyslipidaemia.
Drugs.
2002;
62
1909-1944
- 7
Lawrence J, Reid J, Taylor G, Stirling C, Reckless J.
Favorable effects of pioglitazone and metformin compared with gliclazide on lipoprotein
subfractions in overweight patients with early type 2 diabetes.
Diab Care.
2004;
27
41-46
- 8
Satoh N, Ogawa Y, Usui T, Tagami T, Kono S, Uwaugi H, Sugiyama H, Sugawara A, Yamada K,
Shimatsu A, Kuzuya H, Nakao K.
Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of
the responsiveness to its antidiabetic effect.
Diab Care.
2003;
26
2493-2499
- 9
Schamberger B M, Geiss H C, Ritter M M, Schwandt P, Parhofer K G.
Influence of LDL-apheresis on LDL-subtypes in patients with coronary heart disease
and severe hyperlipoproteinemia.
J Lipid Res.
2000;
41
727-733
- 10
Shelness G S, Sellers J A.
Very-low-density lipoprotein assembly and secretion.
Curr Opin Lipidol.
2001;
2
151-157
- 11
Taskinen M R.
Diabetic dyslipidaemia: from basic research to clinical practice.
Diabetologia.
2003;
46
733-749
- 12
Winkler K, Konrad T, Fullert S, Friedrich I, Destani R, Baumstark M W, Krebs K, Wieland H,
März W.
Pioglitazone reduces atherogenic dense LDL particles in nondiabetic patients with
arterial hypertension: a double-blind, placebo-controlled study.
Diab Care.
2003;
26
2588-2594
MD Klaus G. Parhofer
Medical Department II - Großhadern
University of Munich
Marchioninistraße 15
81377 Munich
Germany
Phone: + 498970953010
Fax: + 49 89 70 95 88 79
Email: Klaus.Parhofer@med.uni-muenchen.de
