Skip to main content
Erschienen in: Diabetologia 9/2006

01.09.2006 | Article

Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes

verfasst von: N. Matikainen, S. Mänttäri, A. Schweizer, A. Ulvestad, D. Mills, B. E. Dunning, J. E. Foley, M.-R. Taskinen

Erschienen in: Diabetologia | Ausgabe 9/2006

Einloggen, um Zugang zu erhalten

Abstract

Aims/hypothesis

We assessed the effects of vildagliptin, a novel dipeptidyl peptidase IV inhibitor, on postprandial lipid and lipoprotein metabolism in patients with type 2 diabetes.

Subjects, materials and methods

This was a single-centre, randomised, double-blind study in drug-naive patients with type 2 diabetes. Patients received vildagliptin (50 mg twice daily, n=15) or placebo (n=16) for 4 weeks. Triglyceride, cholesterol, lipoprotein, glucose, insulin, glucagon and glucagon-like peptide-1 (GLP-1) responses to a fat-rich mixed meal were determined for 8 h postprandially before and after 4 weeks of treatment.

Results

Relative to placebo, 4 weeks of treatment with vildagliptin decreased the AUC0–8h for total trigyceride by 22±11% (p=0.037), the incremental AUC0–8h (IAUC0–8h) for total triglyceride by 85±47% (p=0.065), the AUC0–8h for chylomicron triglyceride by 65±19% (p=0.001) and the IAUC0–8h for chylomicron triglyceride by 91±28% (p=0.002). This was associated with a decrease in chylomicron apolipoprotein B-48 (AUC0–8h, −1.0±0.5 mg l−1 h, p=0.037) and chylomicron cholesterol (AUC0–8h, −0.14±0.07 mmol l−1 h, p=0.046). Consistent with previous studies, 4 weeks of treatment with vildagliptin also increased intact GLP-1, suppressed inappropriate glucagon secretion, decreased fasting and postprandial glucose, and decreased HbA1c from a baseline of 6.7% (change, −0.4±0.1%, p<0.001), all relative to placebo.

Conclusions/interpretation

Treatment with vildagliptin for 4 weeks improves postprandial plasma triglyceride and apolipoprotein B-48-containing triglyceride-rich lipoprotein particle metabolism after a fat-rich meal. The mechanisms underlying the effects of this dipeptidyl peptidase IV inhibitor on postprandial lipid metabolism remain to be explored.
Literatur
1.
Zurück zum Zitat Mari A, Sallas WM, He YL et al (2005) Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed β-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab 90:4888–4894PubMedCrossRef Mari A, Sallas WM, He YL et al (2005) Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed β-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab 90:4888–4894PubMedCrossRef
2.
Zurück zum Zitat Ahrén B, Landin-Olsson M, Jansson P-A et al (2004) Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab 89:2078–2084PubMedCrossRef Ahrén B, Landin-Olsson M, Jansson P-A et al (2004) Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab 89:2078–2084PubMedCrossRef
3.
Zurück zum Zitat Qin X, Shen H, Liu M et al (2005) GLP-1 reduces intestinal lymph flow, triglyceride absorption, and apolipoprotein production in rats. Am J Physiol Gastrointest Liver Physiol 288:G943–G949PubMedCrossRef Qin X, Shen H, Liu M et al (2005) GLP-1 reduces intestinal lymph flow, triglyceride absorption, and apolipoprotein production in rats. Am J Physiol Gastrointest Liver Physiol 288:G943–G949PubMedCrossRef
4.
Zurück zum Zitat Wasada T, McCorkle K, Harris V et al (1981) Effect of gastric inhibitory polypeptide on plasma levels of chylomicron triglycerides in dogs. J Clin Invest 68:1106–1107PubMedCrossRef Wasada T, McCorkle K, Harris V et al (1981) Effect of gastric inhibitory polypeptide on plasma levels of chylomicron triglycerides in dogs. J Clin Invest 68:1106–1107PubMedCrossRef
5.
Zurück zum Zitat Ebert R, Nauck M, Creutzfeldt W (1991) Effect of exogenous or endogenous gastric inhibitory polypeptide (GIP) on plasma triglyceride responses in rats. Horm Metab Res 23:517–521PubMedCrossRef Ebert R, Nauck M, Creutzfeldt W (1991) Effect of exogenous or endogenous gastric inhibitory polypeptide (GIP) on plasma triglyceride responses in rats. Horm Metab Res 23:517–521PubMedCrossRef
6.
Zurück zum Zitat Taskinen M-R (2003) Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 46:733–749PubMedCrossRef Taskinen M-R (2003) Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 46:733–749PubMedCrossRef
7.
Zurück zum Zitat De Man FHAF, Cabezas MC, Van Barlingen HHJJ, Erkelens DW, de Bruin TWA (1996) Triglyceride-rich lipoproteins in non-insulin-dependent diabetes mellitus: post-prandial metabolism and relation to premature atherosclerosis. Eur J Clin Invest 26:89–108PubMedCrossRef De Man FHAF, Cabezas MC, Van Barlingen HHJJ, Erkelens DW, de Bruin TWA (1996) Triglyceride-rich lipoproteins in non-insulin-dependent diabetes mellitus: post-prandial metabolism and relation to premature atherosclerosis. Eur J Clin Invest 26:89–108PubMedCrossRef
8.
Zurück zum Zitat Mero N, Malmstrom R, Steiner G, Taskinen MR, Syvanne M (2000) Postprandial metabolism of apolipoprotein B-48- and B-100-containing particles in type 2 diabetes mellitus: relations to angiographically verified severity of coronary artery disease. Atherosclerosis 150:167–177PubMedCrossRef Mero N, Malmstrom R, Steiner G, Taskinen MR, Syvanne M (2000) Postprandial metabolism of apolipoprotein B-48- and B-100-containing particles in type 2 diabetes mellitus: relations to angiographically verified severity of coronary artery disease. Atherosclerosis 150:167–177PubMedCrossRef
9.
Zurück zum Zitat Ahrén B, Gomis R, Standl E, Mills D, Schweizer A (2004) Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care 27:2874–2880PubMedCrossRef Ahrén B, Gomis R, Standl E, Mills D, Schweizer A (2004) Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care 27:2874–2880PubMedCrossRef
10.
Zurück zum Zitat Mero N, Syvanne M, Eliasson B, Smith U, Taskinen MR (1997) Postprandial elevation of ApoB-48-containing triglyceride-rich particles and retinyl esters in normolipemic males who smoke. Arterioscler Thromb Vasc Biol 17:2096–2102PubMed Mero N, Syvanne M, Eliasson B, Smith U, Taskinen MR (1997) Postprandial elevation of ApoB-48-containing triglyceride-rich particles and retinyl esters in normolipemic males who smoke. Arterioscler Thromb Vasc Biol 17:2096–2102PubMed
11.
Zurück zum Zitat Karpe F, Hamsten A (1994) Determination of apolipoproteins B-48 and B-100 in triglyceride-rich lipoproteins by analytical SDS-PAGE. J Lipid Res 35:1311–1317PubMed Karpe F, Hamsten A (1994) Determination of apolipoproteins B-48 and B-100 in triglyceride-rich lipoproteins by analytical SDS-PAGE. J Lipid Res 35:1311–1317PubMed
12.
Zurück zum Zitat Havekes LM, de KP, Beisiegel U et al (1987) A rapid micromethod for apolipoprotein E phenotyping directly in serum. J Lipid Res 28:455–463PubMed Havekes LM, de KP, Beisiegel U et al (1987) A rapid micromethod for apolipoprotein E phenotyping directly in serum. J Lipid Res 28:455–463PubMed
13.
Zurück zum Zitat Sluiter WJ, Erkelens DW, Reitsma WD, Doorenbos H (1976) Glucose tolerance and insulin release, a mathematical approach. I. Assay of the beta-cell response after oral glucose loading. Diabetes 25:241–244PubMedCrossRef Sluiter WJ, Erkelens DW, Reitsma WD, Doorenbos H (1976) Glucose tolerance and insulin release, a mathematical approach. I. Assay of the beta-cell response after oral glucose loading. Diabetes 25:241–244PubMedCrossRef
14.
Zurück zum Zitat Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462–1470PubMedCrossRef Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462–1470PubMedCrossRef
15.
Zurück zum Zitat Cohn JS, McNamara JR, Krasinski SD, Russell RM, Schaefer EJ (1989) Role of triglyceride-rich lipoproteins from the liver and intestine in the etiology of postprandial peaks in plasma triglyceride concentration. Metabolism 38:484–490PubMedCrossRef Cohn JS, McNamara JR, Krasinski SD, Russell RM, Schaefer EJ (1989) Role of triglyceride-rich lipoproteins from the liver and intestine in the etiology of postprandial peaks in plasma triglyceride concentration. Metabolism 38:484–490PubMedCrossRef
16.
Zurück zum Zitat Adiels M, Taskinen MR, Packard C et al (2006) Overproduction of large VLDL particles is driven by increased liver fat content in man. Diabetologia 49:755–765PubMedCrossRef Adiels M, Taskinen MR, Packard C et al (2006) Overproduction of large VLDL particles is driven by increased liver fat content in man. Diabetologia 49:755–765PubMedCrossRef
17.
Zurück zum Zitat Maggs DG, Buchanan TA, Burant CF et al (1998) Metabolic effects of troglitazone monotherapy in type 2 diabetes mellitus. A randomised, double-blind, placebo-controlled trial. Ann Intern Med 128:176–185PubMed Maggs DG, Buchanan TA, Burant CF et al (1998) Metabolic effects of troglitazone monotherapy in type 2 diabetes mellitus. A randomised, double-blind, placebo-controlled trial. Ann Intern Med 128:176–185PubMed
18.
Zurück zum Zitat Tan GD, Fielding BA, Currie JM et al (2005) The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes. Diabetologia 48:83–95PubMedCrossRef Tan GD, Fielding BA, Currie JM et al (2005) The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes. Diabetologia 48:83–95PubMedCrossRef
19.
Zurück zum Zitat van Wijk JP, de Koning EJ, Castro CM, Rabelink TJ (2005) Rosiglitazone improves postprandial triglyceride and free fatty acid metabolism in type 2 diabetes. Diabetes Care 28:844–849PubMedCrossRef van Wijk JP, de Koning EJ, Castro CM, Rabelink TJ (2005) Rosiglitazone improves postprandial triglyceride and free fatty acid metabolism in type 2 diabetes. Diabetes Care 28:844–849PubMedCrossRef
20.
Zurück zum Zitat Majali KA, Cooper MB, Staels B et al (2006) The effect of sensitisation to insulin with pioglitazone on fasting and postprandial lipid metabolism, lipoprotein modification by lipases, and lipid transfer activities in type 2 diabetic patients. Diabetologia 49:527–537PubMedCrossRef Majali KA, Cooper MB, Staels B et al (2006) The effect of sensitisation to insulin with pioglitazone on fasting and postprandial lipid metabolism, lipoprotein modification by lipases, and lipid transfer activities in type 2 diabetic patients. Diabetologia 49:527–537PubMedCrossRef
21.
Zurück zum Zitat Jeppesen J, Zhou MY, Chen YD, Reaven GM (1994) Effect of metformin on postprandial lipemia in patients with fairly to poorly controlled NIDDM. Diabetes Care 17:1093–1099PubMedCrossRef Jeppesen J, Zhou MY, Chen YD, Reaven GM (1994) Effect of metformin on postprandial lipemia in patients with fairly to poorly controlled NIDDM. Diabetes Care 17:1093–1099PubMedCrossRef
22.
Zurück zum Zitat Abbasi F, Chu JW, McLaughlin T et al (2004) Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus. Metabolism 53:159–164PubMedCrossRef Abbasi F, Chu JW, McLaughlin T et al (2004) Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus. Metabolism 53:159–164PubMedCrossRef
23.
Zurück zum Zitat Jeppesen J, Zhou MY, Chen YD, Reaven GM (1994) Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM. Diabetologia 37:781–787PubMedCrossRef Jeppesen J, Zhou MY, Chen YD, Reaven GM (1994) Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM. Diabetologia 37:781–787PubMedCrossRef
24.
Zurück zum Zitat Vakkilainen J, Mero N, Schweizer A, Foley JE, Taskinen MR (2002) Effects of nateglinide and glibenclamide on postprandial lipid and glucose metabolism in type 2 diabetes. Diabetes Metab Res Rev 18:484–490PubMedCrossRef Vakkilainen J, Mero N, Schweizer A, Foley JE, Taskinen MR (2002) Effects of nateglinide and glibenclamide on postprandial lipid and glucose metabolism in type 2 diabetes. Diabetes Metab Res Rev 18:484–490PubMedCrossRef
25.
Zurück zum Zitat Nauck MA, Niedereichholz U, Ettler R et al (1997) Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol Endocrinol Metab 273:E981–E988 Nauck MA, Niedereichholz U, Ettler R et al (1997) Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol Endocrinol Metab 273:E981–E988
26.
Zurück zum Zitat Schirra J, Goke B (2005) The physiological role of GLP-1 in human: incretin, ileal brake or more? Regul Pept 128:109–115PubMedCrossRef Schirra J, Goke B (2005) The physiological role of GLP-1 in human: incretin, ileal brake or more? Regul Pept 128:109–115PubMedCrossRef
27.
Zurück zum Zitat Meier JJ, Gethmann A, Gotze O et al (2006) Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans. Diabetologia 49:452–458PubMedCrossRef Meier JJ, Gethmann A, Gotze O et al (2006) Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans. Diabetologia 49:452–458PubMedCrossRef
28.
Zurück zum Zitat Juutilainen A, Lehto S, Ronnemaa T, Pyorala K, Laakso M (2005) Type 2 diabetes as a ‘coronary heart disease equivalent’: an 18-year prospective population-based study in Finnish subjects. Diabetes Care 28:2901–2907PubMedCrossRef Juutilainen A, Lehto S, Ronnemaa T, Pyorala K, Laakso M (2005) Type 2 diabetes as a ‘coronary heart disease equivalent’: an 18-year prospective population-based study in Finnish subjects. Diabetes Care 28:2901–2907PubMedCrossRef
Metadaten
Titel
Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes
verfasst von
N. Matikainen
S. Mänttäri
A. Schweizer
A. Ulvestad
D. Mills
B. E. Dunning
J. E. Foley
M.-R. Taskinen
Publikationsdatum
01.09.2006
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 9/2006
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-006-0340-2

Weitere Artikel der Ausgabe 9/2006

Diabetologia 9/2006 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.