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Published in: Diabetologia 6/2005

01-06-2005 | Article

Alterations of lipids and apolipoprotein CIII in very low density lipoprotein subspecies in type 2 diabetes

Authors: Anne Hiukka, Jamila Fruchart-Najib, Eeva Leinonen, Hannele Hilden, Jean-Charles Fruchart, Marja-Riitta Taskinen

Published in: Diabetologia | Issue 6/2005

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Abstract

Aims/hypothesis

Very low density lipoprotein (VLDL) particles are heterogeneous, comprising two main subspecies, VLDL 1 (Sf 60-400) and VLDL 2 (Sf 20-60). The aim of the study was to examine the distribution and composition of VLDL subspecies in type 2 diabetes.

Subjects, materials and methods

We studied the composition and concentration of triglyceride-rich lipoproteins (TRLs) in 217 type 2 diabetic patients and 93 control subjects between 50 and 75 years of age. Lipoprotein subspecies were separated by density-gradient ultracentrifugation. Apolipoprotein (apo) CIII and apo E in plasma and apo CIII in TRL subspecies were measured by nephelometry and apo CII in serum by a commercial kit using a single radial immunodiffusion method.

Results

The concentrations of VLDL 1, VLDL 2 and intermediate density lipoprotein were significantly increased in type 2 diabetes subjects, the change being most marked for VLDL 1. There was a strong linear correlation between VLDL 1 triglycerides and plasma triglycerides in both groups (r=0.879, p<0.001 and r=0.899, p<0.001). Diabetic subjects had markedly higher plasma ratios of apo CII:apo CIII and apo CIII:apo E. Despite elevated plasma apo CIII, type 2 diabetic subjects had a relative deficiency of apo CIII in all TRL subspecies, suggesting profound disturbances of apo CIII metabolism.

Conclusions/interpretation

The elevation of VLDL 1 triglycerides is the major determinant of plasma triglyceride concentration in normal subjects and in type 2 diabetic individuals. Both apo CIII and apo E metabolism are disturbed in type 2 diabetes.
Literature
1.
go back to reference Lehto S, Ronnemaa T, Haffner SM, Pyorala K, Kallio V, Laakso M (1997) Dyslipidemia and hyperglycemia predict coronary heart disease events in middle-aged patients with NIDDM. Diabetes 46:1354–1359PubMed Lehto S, Ronnemaa T, Haffner SM, Pyorala K, Kallio V, Laakso M (1997) Dyslipidemia and hyperglycemia predict coronary heart disease events in middle-aged patients with NIDDM. Diabetes 46:1354–1359PubMed
2.
go back to reference Turner RC, Millns H, Neil HA et al (1998) Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom prospective diabetes study (UKPDS: 23) [comment]. BMJ 316:823–828PubMed Turner RC, Millns H, Neil HA et al (1998) Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom prospective diabetes study (UKPDS: 23) [comment]. BMJ 316:823–828PubMed
3.
go back to reference Taskinen MR (2003) Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 46:733–749CrossRefPubMed Taskinen MR (2003) Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 46:733–749CrossRefPubMed
4.
go back to reference Criqui MH, Heiss G, Cohn R et al (1993) Plasma triglyceride level and mortality from coronary heart disease. N Engl J Med 328:1220–1225CrossRefPubMed Criqui MH, Heiss G, Cohn R et al (1993) Plasma triglyceride level and mortality from coronary heart disease. N Engl J Med 328:1220–1225CrossRefPubMed
5.
go back to reference Hokanson JE, Austin MA (1996) Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 3:213–219PubMed Hokanson JE, Austin MA (1996) Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 3:213–219PubMed
6.
go back to reference Avins AL, Neuhaus JM (2000) Do triglycerides provide meaningful information about heart disease risk? Arch Intern Med 160:1937–1944CrossRefPubMed Avins AL, Neuhaus JM (2000) Do triglycerides provide meaningful information about heart disease risk? Arch Intern Med 160:1937–1944CrossRefPubMed
7.
go back to reference Bos G, Dekker JM, Nijpels G et al (2003) A combination of high concentrations of serum triglyceride and non-high-density-lipoprotein-cholesterol is a risk factor for cardiovascular disease in subjects with abnormal glucose metabolism—The Hoorn study. Diabetologia 46:910–916CrossRefPubMed Bos G, Dekker JM, Nijpels G et al (2003) A combination of high concentrations of serum triglyceride and non-high-density-lipoprotein-cholesterol is a risk factor for cardiovascular disease in subjects with abnormal glucose metabolism—The Hoorn study. Diabetologia 46:910–916CrossRefPubMed
8.
go back to reference Packard CJ, Shepherd J (1997) Lipoprotein heterogeneity and apolipoprotein B metabolism. Arterioscler Thromb Vasc Biol 17:3542–3556PubMed Packard CJ, Shepherd J (1997) Lipoprotein heterogeneity and apolipoprotein B metabolism. Arterioscler Thromb Vasc Biol 17:3542–3556PubMed
9.
go back to reference Malmstrom R, Packard CJ, Caslake M et al (1997) Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM. Diabetologia 40:454–462CrossRefPubMed Malmstrom R, Packard CJ, Caslake M et al (1997) Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM. Diabetologia 40:454–462CrossRefPubMed
10.
go back to reference Jong MC, Hofker MH, Havekes LM (1999) Role of ApoCs in lipoprotein metabolism: functional differences between ApoC1, ApoC2, and ApoC3. Arterioscler Thromb Vasc Biol 19:472–484PubMed Jong MC, Hofker MH, Havekes LM (1999) Role of ApoCs in lipoprotein metabolism: functional differences between ApoC1, ApoC2, and ApoC3. Arterioscler Thromb Vasc Biol 19:472–484PubMed
11.
go back to reference Marcoux C, Tremblay M, Fredenrich A, Davignon J, Cohn JS (2001) Lipoprotein distribution of apolipoprotein C-III and its relationship to the presence in plasma of triglyceride-rich remnant lipoproteins. Metabolism 50:112–119CrossRefPubMed Marcoux C, Tremblay M, Fredenrich A, Davignon J, Cohn JS (2001) Lipoprotein distribution of apolipoprotein C-III and its relationship to the presence in plasma of triglyceride-rich remnant lipoproteins. Metabolism 50:112–119CrossRefPubMed
12.
go back to reference Campos H, Perlov D, Khoo C, Sacks FM (2001) Distinct patterns of lipoproteins with apoB defined by presence of apoE or apoC-III in hypercholesterolemia and hypertriglyceridemia. J Lipid Res 42:1239–1249PubMed Campos H, Perlov D, Khoo C, Sacks FM (2001) Distinct patterns of lipoproteins with apoB defined by presence of apoE or apoC-III in hypercholesterolemia and hypertriglyceridemia. J Lipid Res 42:1239–1249PubMed
13.
go back to reference van Dijk KW, Rensen PC, Voshol PJ, Havekes LM (2004) The role and mode of action of apolipoproteins CIII and AV: synergistic actors in triglyceride metabolism? Curr Opin Lipidol 15:239–246CrossRefPubMed van Dijk KW, Rensen PC, Voshol PJ, Havekes LM (2004) The role and mode of action of apolipoproteins CIII and AV: synergistic actors in triglyceride metabolism? Curr Opin Lipidol 15:239–246CrossRefPubMed
14.
go back to reference Briones ER, Mao SJ, Palumbo PJ, O’Fallon WM, Chenoweth W, Kottke BA (1984) Analysis of plasma lipids and apolipoproteins in insulin-dependent and noninsulin-dependent diabetics. Metabolism 33:42–49CrossRefPubMed Briones ER, Mao SJ, Palumbo PJ, O’Fallon WM, Chenoweth W, Kottke BA (1984) Analysis of plasma lipids and apolipoproteins in insulin-dependent and noninsulin-dependent diabetics. Metabolism 33:42–49CrossRefPubMed
15.
go back to reference Stalenhoef AF, Demacker PN, Lutterman JA, van’t Laar A (1982) Apolipoprotein C in type 2 (non-insulin-dependent) diabetic patients with hypertriglyceridaemia. Diabetologia 22:489–491CrossRefPubMed Stalenhoef AF, Demacker PN, Lutterman JA, van’t Laar A (1982) Apolipoprotein C in type 2 (non-insulin-dependent) diabetic patients with hypertriglyceridaemia. Diabetologia 22:489–491CrossRefPubMed
16.
go back to reference Pan XR, Cheung MC, Walden CE, Hu SX, Bierman EL, Albers JJ (1986) Abnormal composition of apoproteins C-I, C-II, and C-III in plasma and very-low-density lipoproteins of non-insulin-dependent diabetic. Chinese Clin Chem 32:1914–1920 Pan XR, Cheung MC, Walden CE, Hu SX, Bierman EL, Albers JJ (1986) Abnormal composition of apoproteins C-I, C-II, and C-III in plasma and very-low-density lipoproteins of non-insulin-dependent diabetic. Chinese Clin Chem 32:1914–1920
17.
go back to reference Ishibashi S, Yamada N, Shimano H, Takaku F, Akanuma Y, Murase T (1989) Composition of very-low-density lipoproteins in non-insulin-dependent diabetes mellitus. Clin Chem 35:808–812PubMed Ishibashi S, Yamada N, Shimano H, Takaku F, Akanuma Y, Murase T (1989) Composition of very-low-density lipoproteins in non-insulin-dependent diabetes mellitus. Clin Chem 35:808–812PubMed
18.
go back to reference Gervaise N, Garrigue MA, Lasfargues G, Lecomte P (2000) Triglycerides, apo C3 and Lp B:C3 and cardiovascular risk in type II diabetes. Diabetologia 43:703–708CrossRefPubMed Gervaise N, Garrigue MA, Lasfargues G, Lecomte P (2000) Triglycerides, apo C3 and Lp B:C3 and cardiovascular risk in type II diabetes. Diabetologia 43:703–708CrossRefPubMed
19.
go back to reference Luc G, Fievet C, Arveiler D et al (1996) Apolipoproteins C-III and E in apoB- and non-apoB-containing lipoproteins in two populations at contrasting risk for myocardial infarction: the ECTIM study. J Lipid Res 37:508–517PubMed Luc G, Fievet C, Arveiler D et al (1996) Apolipoproteins C-III and E in apoB- and non-apoB-containing lipoproteins in two populations at contrasting risk for myocardial infarction: the ECTIM study. J Lipid Res 37:508–517PubMed
20.
go back to reference Sacks FM, Alaupovic P, Moye LA et al (2000) VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial. Circulation 102:1886–1892PubMed Sacks FM, Alaupovic P, Moye LA et al (2000) VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial. Circulation 102:1886–1892PubMed
21.
go back to reference Onat A, Hergenc G, Sansoy V et al (2003) Apolipoprotein C-III, a strong discriminant of coronary risk in men and a determinant of the metabolic syndrome in both genders. Atherosclerosis 168:81–89CrossRefPubMed Onat A, Hergenc G, Sansoy V et al (2003) Apolipoprotein C-III, a strong discriminant of coronary risk in men and a determinant of the metabolic syndrome in both genders. Atherosclerosis 168:81–89CrossRefPubMed
22.
go back to reference Santamarina-Fojo S (1992) Genetic dyslipoproteinemias: role of lipoprotein lipase and apolipoprotein C-II. Curr Opin Lipidol 3:186–195 Santamarina-Fojo S (1992) Genetic dyslipoproteinemias: role of lipoprotein lipase and apolipoprotein C-II. Curr Opin Lipidol 3:186–195
23.
go back to reference Clavey V, Lestavel-Delattre S, Copin C, Bard JM, Fruchart JC (1995) Modulation of lipoprotein B binding to the LDL receptor by exogenous lipids and apolipoproteins CI, CII, CIII, and E. Arterioscler Thromb Vasc Biol 15:963–971PubMed Clavey V, Lestavel-Delattre S, Copin C, Bard JM, Fruchart JC (1995) Modulation of lipoprotein B binding to the LDL receptor by exogenous lipids and apolipoproteins CI, CII, CIII, and E. Arterioscler Thromb Vasc Biol 15:963–971PubMed
24.
go back to reference Ji ZS, Dichek HL, Miranda RD, Mahley RW (1997) Heparan sulfate proteoglycans participate in hepatic lipase and apolipoprotein E-mediated binding and uptake of plasma lipoproteins, including high density lipoproteins. J Biol Chem 272:31285–31292CrossRefPubMed Ji ZS, Dichek HL, Miranda RD, Mahley RW (1997) Heparan sulfate proteoglycans participate in hepatic lipase and apolipoprotein E-mediated binding and uptake of plasma lipoproteins, including high density lipoproteins. J Biol Chem 272:31285–31292CrossRefPubMed
25.
go back to reference Mensenkamp AR, Jong MC, van Goor H et al (1999) Apolipoprotein E participates in the regulation of very low density lipoprotein–triglyceride secretion by the liver. J Biol Chem 274:35711–35718CrossRefPubMed Mensenkamp AR, Jong MC, van Goor H et al (1999) Apolipoprotein E participates in the regulation of very low density lipoprotein–triglyceride secretion by the liver. J Biol Chem 274:35711–35718CrossRefPubMed
26.
go back to reference Heeren J, Grewal T, Laatsch A et al (2003) Recycling of apoprotein E is associated with cholesterol efflux and high-density lipoprotein internalization. J Biol Chem 278:14370–14378CrossRefPubMed Heeren J, Grewal T, Laatsch A et al (2003) Recycling of apoprotein E is associated with cholesterol efflux and high-density lipoprotein internalization. J Biol Chem 278:14370–14378CrossRefPubMed
27.
go back to reference Keech AC, Field Study Investigators T (2004) The need for a large-scale trial of fibrate therapy in diabetes: the rationale and design of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study ISRCTN64783481. Cardiovasc Diabetol 3:9CrossRefPubMed Keech AC, Field Study Investigators T (2004) The need for a large-scale trial of fibrate therapy in diabetes: the rationale and design of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study ISRCTN64783481. Cardiovasc Diabetol 3:9CrossRefPubMed
28.
go back to reference World Health Organisation (1999) Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO consultation: Part I. Diagnosis and classification of diabetes mellitus. World Health Organisation, Geneva, pp 1–65 World Health Organisation (1999) Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO consultation: Part I. Diagnosis and classification of diabetes mellitus. World Health Organisation, Geneva, pp 1–65
29.
go back to reference Taskinen MR, Kuusi T, Helve E, Nikkila EA, Yki-Jarvinen H (1988) Insulin therapy induces antiatherogenic changes of serum lipoproteins in noninsulin-dependent diabetes. Arteriosclerosis 8:168–177PubMed Taskinen MR, Kuusi T, Helve E, Nikkila EA, Yki-Jarvinen H (1988) Insulin therapy induces antiatherogenic changes of serum lipoproteins in noninsulin-dependent diabetes. Arteriosclerosis 8:168–177PubMed
30.
go back to reference Taskinen MR, Packard CJ, Shepherd J (1990) Effect of insulin therapy on metabolic fate of apolipoprotein B-containing lipoproteins in NIDDM. Diabetes 39:1017–1027PubMed Taskinen MR, Packard CJ, Shepherd J (1990) Effect of insulin therapy on metabolic fate of apolipoprotein B-containing lipoproteins in NIDDM. Diabetes 39:1017–1027PubMed
31.
go back to reference Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275PubMed Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275PubMed
32.
go back to reference Havekes LM, de Knijff P, Beisiegel U, Havinga J, Smit M, Klasen E (1987) A rapid micromethod for apolipoprotein E phenotyping directly in serum. J Lipid Res 28:455–463PubMed Havekes LM, de Knijff P, Beisiegel U, Havinga J, Smit M, Klasen E (1987) A rapid micromethod for apolipoprotein E phenotyping directly in serum. J Lipid Res 28:455–463PubMed
33.
go back to reference Schonfeld G, George PK, Miller J, Reilly P, Witztum J (1979) Apolipoprotein C-II and C-III levels in hyperlipoproteinemia. Metabolism 28:1001–1010CrossRefPubMed Schonfeld G, George PK, Miller J, Reilly P, Witztum J (1979) Apolipoprotein C-II and C-III levels in hyperlipoproteinemia. Metabolism 28:1001–1010CrossRefPubMed
34.
go back to reference Havel RJ, Kotite L, Vigne JL et al (1980) Radioimmunoassay of human arginine-rich apolipoprotein, apoprotein E: concentration in blood plasma and lipoproteins as affected by apoprotein E-3 deficiency. J Clin Invest 66:1351–1362PubMed Havel RJ, Kotite L, Vigne JL et al (1980) Radioimmunoassay of human arginine-rich apolipoprotein, apoprotein E: concentration in blood plasma and lipoproteins as affected by apoprotein E-3 deficiency. J Clin Invest 66:1351–1362PubMed
35.
go back to reference Guerin M, Le Goff W, Lassel TS, Van Tol A, Steiner G, Chapman MJ (2001) Atherogenic role of elevated CE transfer from HDL to VLDL(1) and dense LDL in type 2 diabetes: impact of the degree of triglyceridemia. Arterioscler Thromb Vasc Biol 21:282–288PubMed Guerin M, Le Goff W, Lassel TS, Van Tol A, Steiner G, Chapman MJ (2001) Atherogenic role of elevated CE transfer from HDL to VLDL(1) and dense LDL in type 2 diabetes: impact of the degree of triglyceridemia. Arterioscler Thromb Vasc Biol 21:282–288PubMed
36.
go back to reference Garvey WT, Kwon S, Zheng D et al (2003) Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes 52:453–462PubMed Garvey WT, Kwon S, Zheng D et al (2003) Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes 52:453–462PubMed
37.
go back to reference McEneny J, O’Kane MJ, Moles KW et al (2000) Very low density lipoprotein subfractions in type II diabetes mellitus: alterations in composition and susceptibility to oxidation. Diabetologia 43:485–493CrossRefPubMed McEneny J, O’Kane MJ, Moles KW et al (2000) Very low density lipoprotein subfractions in type II diabetes mellitus: alterations in composition and susceptibility to oxidation. Diabetologia 43:485–493CrossRefPubMed
38.
go back to reference Taskinen MR, Beltz WF, Harper I et al (1986) Effects of NIDDM on very-low-density lipoprotein triglyceride and apolipoprotein B metabolism: studies before and after sulfonylurea therapy. Diabetes 35:1268–1277PubMed Taskinen MR, Beltz WF, Harper I et al (1986) Effects of NIDDM on very-low-density lipoprotein triglyceride and apolipoprotein B metabolism: studies before and after sulfonylurea therapy. Diabetes 35:1268–1277PubMed
39.
go back to reference James RW, Pometta D (1991) The distribution profiles of very low density and low density lipoproteins in poorly-controlled male, type 2 (non-insulin-dependent) diabetic patients. Diabetologia 34:246–252CrossRefPubMed James RW, Pometta D (1991) The distribution profiles of very low density and low density lipoproteins in poorly-controlled male, type 2 (non-insulin-dependent) diabetic patients. Diabetologia 34:246–252CrossRefPubMed
40.
go back to reference Steiner G, Tkac I, Uffelman KD, Lewis GF (1998) Important contribution of lipoprotein particle number to plasma triglyceride concentration in type 2 diabetes. Atherosclerosis 137:211–214CrossRefPubMed Steiner G, Tkac I, Uffelman KD, Lewis GF (1998) Important contribution of lipoprotein particle number to plasma triglyceride concentration in type 2 diabetes. Atherosclerosis 137:211–214CrossRefPubMed
41.
go back to reference Manzato E, Zambon A, Lapolla A et al (1993) Lipoprotein abnormalities in well-treated type II diabetic patients. Diabetes Care 16:469–475PubMed Manzato E, Zambon A, Lapolla A et al (1993) Lipoprotein abnormalities in well-treated type II diabetic patients. Diabetes Care 16:469–475PubMed
42.
go back to reference Gabor J, Spain M, Kalant N (1980) Composition of serum very-low-density and high-density lipoproteins in diabetes. Clin Chem 26:1261–1265PubMed Gabor J, Spain M, Kalant N (1980) Composition of serum very-low-density and high-density lipoproteins in diabetes. Clin Chem 26:1261–1265PubMed
43.
go back to reference Lee SJ, Moye LA, Campos H, Williams GH, Sacks FM (2003) Hypertriglyceridemia but not diabetes status is associated with VLDL containing apolipoprotein CIII in patients with coronary heart disease. Atherosclerosis 167:293–302CrossRefPubMed Lee SJ, Moye LA, Campos H, Williams GH, Sacks FM (2003) Hypertriglyceridemia but not diabetes status is associated with VLDL containing apolipoprotein CIII in patients with coronary heart disease. Atherosclerosis 167:293–302CrossRefPubMed
44.
go back to reference Batal R, Tremblay M, Barrett PH et al (2000) Plasma kinetics of apoC-III and apoE in normolipidemic and hypertriglyceridemic subjects. J Lipid Res 41:706–718PubMed Batal R, Tremblay M, Barrett PH et al (2000) Plasma kinetics of apoC-III and apoE in normolipidemic and hypertriglyceridemic subjects. J Lipid Res 41:706–718PubMed
45.
go back to reference Kashyap ML, Srivastava LS, Chen CY et al (1977) Radioimmunoassay of human apolipoprotein CII: a study in normal and hypertriglyceridemic subjects. J Clin Invest 60:171–180PubMed Kashyap ML, Srivastava LS, Chen CY et al (1977) Radioimmunoassay of human apolipoprotein CII: a study in normal and hypertriglyceridemic subjects. J Clin Invest 60:171–180PubMed
46.
go back to reference Chan DC, Watts GF, Redgrave TG, Mori TA, Barrett PH (2002) Apolipoprotein B-100 kinetics in visceral obesity: associations with plasma apolipoprotein C-III concentration. Metabolism 51:1041–1046CrossRefPubMed Chan DC, Watts GF, Redgrave TG, Mori TA, Barrett PH (2002) Apolipoprotein B-100 kinetics in visceral obesity: associations with plasma apolipoprotein C-III concentration. Metabolism 51:1041–1046CrossRefPubMed
47.
go back to reference Cohn JS, Patterson BW, Uffelman KD, Davignon J, Steiner G (2004) Rate of production of plasma and very-low-density lipoprotein (VLDL) apolipoprotein C-III is strongly related to the concentration and level of production of VLDL triglyceride in male subjects with different body weights and levels of insulin sensitivity. J Clin Endocrinol Metab 89:3949–3955CrossRefPubMed Cohn JS, Patterson BW, Uffelman KD, Davignon J, Steiner G (2004) Rate of production of plasma and very-low-density lipoprotein (VLDL) apolipoprotein C-III is strongly related to the concentration and level of production of VLDL triglyceride in male subjects with different body weights and levels of insulin sensitivity. J Clin Endocrinol Metab 89:3949–3955CrossRefPubMed
Metadata
Title
Alterations of lipids and apolipoprotein CIII in very low density lipoprotein subspecies in type 2 diabetes
Authors
Anne Hiukka
Jamila Fruchart-Najib
Eeva Leinonen
Hannele Hilden
Jean-Charles Fruchart
Marja-Riitta Taskinen
Publication date
01-06-2005
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 6/2005
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-005-1753-z

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