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Exp Clin Endocrinol Diabetes 2005; 113(3): 176-181
DOI: 10.1055/s-2005-837521
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

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

I. Schmoelzer1 , A. de Campo1 , H. Pressl1 , H. Stelzl1 , P. Dittrich2 , K. Oettl3 , T. C. Wascher1
  • 1Diabetic Angiopathy Research Group, Department of Internal Medicine, University of Graz, Graz, Austria
  • 2Institute of Pharmacology and Toxicology, University of Graz, Graz, Austria
  • 3Institute of Medical Chemistry, University of Graz, Graz, Austria
Further Information

Publication History

Received: April 23, 2004 First decision: June 21, 2004

Accepted: September 9, 2004

Publication Date:
23 March 2005 (online)

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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.

Key words

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
    CrossrefPubMedGoogle Scholar
  • 2 Ceriello A. The post-prandial state and cardiovascular disease: relevance to diabetes mellitus.  Diabetes Metab Res Rev. 2000;  16 125-132
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 7 Eckel R H. Lipoprotein lipase. A multifactorial enzyme relevant to common metabolic disease.  N Engl J Med. 1989;  320 106-68
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 12 Ginsberg H N. Lipoprotein physiology in nondiabetic and diabetic states.  Diabetes Care. 1991;  14 839-855
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 15 Home P D, Lindholm A, Hylleberg B, Round P. Improved glycemic control with insulin aspart.  Diabetes Care. 1998;  21 1904-1909
    PubMedGoogle Scholar
  • 16 Katsilambros N. Postprandial hypertriglyceridaemia.  Diabet Med. 1995;  12 451-452
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    Google Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 23 Patsch W, Franz S, Schonfeld G. Role of insulin on lipoprotein secretion by cultured rat hepatocytes.  J Clin Invest. 1983;  71 1161-1174
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 26 Pyörälä K, Laakso M, Uusitupa M. Diabetes and atherosclerosis: an epidemiologic view.  Diabetes Metab Res Rev. 1987;  3 463-524
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 33 Zilversmit D B. Atherogenesis: a postprandial phenomenon.  Circulation. 1979;  60 473-485
    CrossrefPubMedGoogle Scholar

Univ.-Prof. Dr. Thomas C. Wascher

Auenbruggerplatz 15

8036 Graz

Austria

Phone: + 43 316 385 80247

Fax: + 43 316 385 3062

Email: thomas.wascher@meduni-graz.at

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