Biphasic Insulin Aspart Compared to Biphasic Human Insulin Reduces Postprandial Hyperlipidemia in Patients with Type 2 Diabetes

Abstract

Background: Premixed insulin analogues reduce postprandial hyperglycemia in patients with Type 2 diabetes in comparison to premixed regular insulin. Insulin also plays an important role in the regulation of postprandial lipid metabolism. It is known that increased levels of postprandial insulin reduce postprandial hyperlipemia but, on the other hand, no information exists with regard to the possible effect of insulin analogues in comparison to human insulin.

Materials and Methods: 12 subjects (3 men; age 59 ± 5 years; BMI 30.5 ± 5.9 kg/m², duration of diabetes 9 ± 1 years, HbA1c 8.33 ± 1.1 %) already on therapy with premixed insulin were treated either with biphasic human insulin (BHI30) or with biphasic insulin aspart (BIAsp30) (1.3 IU fast acting insulin/12 g KH) in the setting of a standardized test meal. Serum levels of glucose, insulin, C-peptide and triglycerides as well as retinylpalmitate in plasma and chylomicron remnants were determined before and up to 8 hours after the meal.

Results: As was to be expected, therapy with BIAsp30 reduced the maximum increase of postprandial glucose from 7.10 ± 2.00 mmol/l to 5.27 ± 1.83 mmo/l (p = 0.007) compared to BHI30 insulin. In the same way, the maximum increase of triglycerides (from 2.33 ± 1.03 to 1.65 ± 0.69 mmol/l, p = 0.014) was reduced. The AUC 0 - 8 for triglycerides was not significantly influenced (34.20 ± 19.86 vs.31.46 ± 16.21 mmol × 8 h/l) but the incremental area over baseline (AOB 0 - 8) was significantly reduced from 8.02 ± 4.35 to 6.12 ± 3.94 mmol × 8 h/l (p = 0.024).

Conclusions: Compared to conventional human premixed insulin the prandial therapy with biphasic insulin aspart results not only in an improvement of glucose tolerance but also in a significant reduction of postprandial hyperlipemia.

Type 2 diabetes - insulin aspart - postprandial hyperlipidemia

References

• 1 Cavallero E, Dachte C, Neuflor D, Wirquin E, Mathe D, Jacotot B. Postprandial amplification of lipoprotein abnormalities in controlled type II diabetic subjects: relationship to postprandial lipemia and C-peptide/glucagon levels.  Metabolism. 1994;  43 270-278
• 2 Ceriello A. The post-prandial state and cardiovascular disease: relevance to diabetes mellitus.  Diabetes Metab Res Rev. 2000;  16 125-132
• 3 Charbonell B, Balarac N, Cazeneuve B, Augendre-Ferran F, Drouin P. Which are the insulin treatment regimens used in the “Schema Survey”.  Diabetes Metab. 2001;  27 591-597
• 4 Chen Y D, Swami S, Skrowronski R, Coulston A M, Reaven G M. Differences in postprandial lipemia between patients with normal glucose tolerance and noninsulin-dependent diabetes mellitus.  J Clin Endocrinol Metab. 1993;  76 172-177
• 5 Cortner J A, Coates P M, Le N A. et al . Kinetics of chylomicron remnant clearance in normal and in hyperlipoproteinemic subjects.  J Lipid Res. 1987;  28 195-206
• 6 De Man F HA, Cabezas M C, Van Barlingen H HJJ, Erkelens D W, De Bruin T WA. Triglyceride-rich lipoproteins in NIDDM, postprandial metabolism and relation to premature atherosclerosis.  Eur J Clin Invest. 1996;  26 89-108
• 7 Eckel R H. Lipoprotein lipase. A multifactorial enzyme relevant to common metabolic disease.  N Engl J Med. 1989;  320 106-68
• 8 Fontbonne A, Eschwege E, Cambien F. et al . Hypertriglyceridaemia as a risk factor of coronary artery disease mortality in subjects with impaired glucose tolerance or diabetes. Results from the Paris Prospective Study.  Diabetologia. 1989;  32 300-304
• 9 Geltner C H, Lechleitner M, Föger B, Ritsch A, Drexel H, Patsch J R. Insulin improves fasting and postprandial lipemia in type II diabetes.  EJIM. 2002;  13 256-263
• 10 Gibbons G F, Brown A M, Wiggins D, Rease R. The roles of insulin and fatty acids in the regulation of hepatic very-low-density lipoprotein assembly.  J R Soc Med. 2002;  95 (Suppl 42) 23-32
• 11 Ginsberg H N, Illingworth D R. Postprandial dyslipidemia: an atherogenic disorder common in patients with diabetes mellitus.  Am J Cardiol. 2001;  88 9H-15H
• 12 Ginsberg H N. Lipoprotein physiology in nondiabetic and diabetic states.  Diabetes Care. 1991;  14 839-855
• 13 Hermansen K, Colombo M, Storgaard H, Ostergaard A, Kolendorf K, Madsbad S. Improved postprandial glycemic control with biphasic insulin aspart relative to biphasic insulin lispro and biphasic human insulin in patients with type II diabetes.  Diabetes Care. 2002 a;  25 883-888
• 14 Hermansen K, Vaaler S, Madsbad S, Dalgaard M, Zander M, Begtru K, Soendetgaard K. Postprandial glycemic control with biphasic insulin aspart in patients with type I diabetics.  Metabolism. 2002 b;  51 896-900
• 15 Home P D, Lindholm A, Hylleberg B, Round P. Improved glycemic control with insulin aspart.  Diabetes Care. 1998;  21 1904-1909
• 16 Katsilambros N. Postprandial hypertriglyceridaemia.  Diabet Med. 1995;  12 451-452
• 17 Krasinski S D, Cohn J S, Russel R M, Schaefer E J. Postprandial plasma vitamin A metabolism in humans: a reassessment of the use of plasma retinyl esters as markers for intestinally derived chylomicrons and their remnants.  Metabolism. 1990;  39 357-365
• 18 Lewis G F, Uffelman K D, Szeto L W, Steiner G. Effects of acute hyperinsulinemia on VLDL triglyceride and VLDL apoB production in normal weight and obese individuals.  Diabetes. 1993;  42 833-842
• 19 Lindholm A, McEwen J, Riis A P. Improved postprandial glycemic control with insulin aspart: a randomized double-blind cross-over trial in type 1 diabetes.  Diabetes Care. 1999;  22 801-805
• 20 Matthews D R, Hosker J P, Rudenski A S, Naylor B A, Treacher D F, Turner R C. Homeostasis model assessment. Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
• 21 McNamara J R, Paulesh K S, Nakajima K, Cupples L A, Wilson P WF, Ordovas J M, Schaefer E J. Remnant-like particle (RLP) cholesterol is an independent cardiovascular disease risk factor in women: results from the Framingham Heart sStudy.  Atherosclerosis. 2001;  154 229-236
• 22 Patsch J R, Miesenböck G, Hopferwieser T. et al . The relationship of triglyceride metabolism and coronary heart disease: studies in the postprandial state.  Arterioscler Thromb Vasc Biol. 1992;  12 1336-1345
• 23 Patsch W, Franz S, Schonfeld G. Role of insulin on lipoprotein secretion by cultured rat hepatocytes.  J Clin Invest. 1983;  71 1161-1174
• 24 Patsch W, Gotto A M, Patsch J R. Effects of insulin on lipoprotein secretion in rat hepatocyte cultures.  J Biol Chem. 1986;  21 9603-9606
• 25 Potts J L, Fisher R M, Humphreys S M, Gibbson G F, Fray K N. Separation of lipoprotein fractions by ultracentrifugation: investigation of analytic recovery with sequential flotation and density gradient procedures.  Clinica Chimica Acta. 1994;  230 215-220
• 26 Pyörälä K, Laakso M, Uusitupa M. Diabetes and atherosclerosis: an epidemiologic view.  Diabetes Metab Res Rev. 1987;  3 463-524
• 27 Roach P, Yue L, Arora V. Improved postprandial glycemic control during treatment with Humalog Mix25, a novel protamine-based insulin lispro formulation: Humalog Mix25 Study Group.  Diabetes Care. 1999;  22 1258-1261
• 28 Schaefer E J, Mc Namara J R, Shah P K, Nakajima K, Cupples L A, Ordovas J M, Wilson P W. Elevated remnant-like particle cholesterol and triglyceride levels in diabetic men and women in the Framingham Offspring Study.  Diabetes Care. 2002;  25 989-994
• 29 Skrapari I, Perrea D, Ionnidis I, Karabina S AP, Elisaf M, Tselepis A D, Karagiannacos P, Katsilambros N. Glibenclamide improves postprandial hypertriglyceridaemia in type II diabetic patients by reducing chylomicrons but not the very low-density lipoprotein subfraction levels.  Diabet Med. 2001;  18 781-785
• 30 Sowell A L, Huff D L, Yeager P R, Caudill S P, Gunter E W. Retinol, alpha-tocopherol, lutein/zeaxantin, beta-cryptoxanthin, lycobene, alpha-carotene, trans-beta-carotene and four retinylesters in serum determined simultaneously by reversed-phase HPLC with multiwavelengh detection.  Clin Chem. 1994;  40 411-416
• 31 Sprecher D L, Knauer S L, Black D M. Chylomicron-retinyl palmitate clearance in type I hyperlipidemic families.  J Clin Invest. 1991;  88 985-994
• 32 Syvänne M, Hilden H, Taskinen M R. Abnormal metabolism of postprandial lipoproteins in patients with non-insulin dependent diabetes mellitus is not related to coronary artery disease.  J Lipid Res. 1994;  35 15-26
• 33 Zilversmit D B. Atherogenesis: a postprandial phenomenon.  Circulation. 1979;  60 473-485