Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Acta Diabetologica
Published in: Acta Diabetologica 1/2008

01-03-2008 | Original Article

Effect of pioglitazone on heart function and N-terminal pro-brain natriuretic peptide levels of patients with type 2 diabetes

Authors: Christos Sambanis, Konstantinos Tziomalos, Evangelia Kountana, Nikitas Kakavas, Ioanna Zografou, Aikaterini Balaska, Georgios Koulas, Asterios Karagiannis, Chrysanthos Zamboulis

Published in: Acta Diabetologica | Issue 1/2008

Login to get access

Abstract

We assessed the effect of the addition of pioglitazone on metabolic control and heart function of patients with type 2 diabetes already receiving sulfonylurea plus metformin. Forty-four patients were given 30 mg of pioglitazone for 3 months. Physical examination, laboratory tests including N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiography, were performed at baseline and at study completion. Target HbA1c levels were achieved by 44.2% of the patients. Pioglitazone ameliorated lipid profile and lowered liver enzymes and C-reactive protein. Significant increases in NT-proBNP by 39% (P < 0.005) were noticed, but echocardiographic parameters were not altered, even in high-risk subgroups (patients older than 60 years, with diabetes for more than 10 years, with hypertension, with elevated baseline NT-proBNP levels, with left ventricular hypertrophy). In patients with a greater than 60% increase in NT-proBNP levels, a significant increase in left ventricular ejection fraction (P < 0.05) and in fractional shortening (P < 0.05) was found. None of the patients developed edema or signs or symptoms of heart failure. Triple oral combination antidiabetic treatment is an effective therapeutic strategy and weight gain does not abrogate its beneficial actions. Pioglitazone does not affect heart function and even though it increases NT-proBNP, this appears to represent a reaction to volume overload.
Footnotes
Literature
1.
Gerich JE (2003) Contributions of insulin-resistance and insulin-secretory defects to the pathogenesis of type 2 diabetes mellitus. Mayo Clin Proc 78:447–456PubMedCrossRef
2.
Haffner SM, D’Agostino R Jr, Mykkanen L et al (1999) Insulin sensitivity in subjects with type 2 diabetes. Relationship to cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study. Diabetes Care 22:562–568PubMedCrossRef
3.
Morrish NJ, Wang S-L, Stevens LK, Fuller JH, Keen H, the WHO Multinational Study Group (2001) Mortality and causes of death in the WHO multinational study of vascular disease in diabetes. Diabetologia 44(Suppl 2):S14–S21PubMedCrossRef
4.
Miyazaki Y, Mahankali A, Matsuda M et al (2001) Improved glycemic control and enhanced insulin sensitivity in type 2 diabetic subjects treated with pioglitazone. Diabetes Care 24:710–719PubMedCrossRef
5.
Nesto RW, Bell D, Bonow RO et al (2004) Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Diabetes Care 27:256–263PubMedCrossRef
6.
Tang WHW, Francis GS, Hoogwerf BH, Young JB (2003) Fluid retention after initiation of thiazolidinedione therapy in diabetic patients with established chronic heart failure. J Am Coll Cardiol 41:1394–1398PubMedCrossRef
7.
Turner RC, Cull CA, Frighi V, Holman RR (1999) Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 281:2005–2012PubMedCrossRef
8.
Dailey GE, Noor MA, Park J-S, Bruce S, Fiedorek FT (2004) Glycemic control with glyburide/metformin tablets in combination with rosiglitazone in patients with type 2 diabetes: a randomized, double-blind trial. Am J Med 116:223–229PubMedCrossRef
9.
Strowig SM, Aviles-Santa ML, Raskin P (2004) Improved glycemic control without weight gain using triple therapy in type 2 diabetes. Diabetes Care 27:1577–1583PubMedCrossRef
10.
Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502PubMed
11.
Dobiasova M, Frohlich J (2001) The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in ApoB-lipoprotein-depleted plasma (FER (HDL). Clin Biochem 34:583–588PubMedCrossRef
12.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRef
13.
Katz A, Nambi SS, Mather K et al (2000) Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85:2402–2410PubMedCrossRef
14.
Cowie MR, Jourdain P, Maisel A et al (2003) Clinical applications of B-type natriuretic peptide (BNP) testing. Eur Heart J 24:1710–1718PubMedCrossRef
15.
Teichholz LE, Kreulen T, Herman MV, Gorlin R (1976) Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence of absence of asynergy. Am J Cardiol 37:7–11PubMedCrossRef
16.
Devereux RB, Alonso DR, Lutas EM et al (1986) Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 57:450–458PubMedCrossRef
17.
Guidelines Committee (2003) European Society of Hypertension-European Society of Cardiology guidelines for management of arterial hypertension. J Hypertens 21:1011–1053CrossRef
18.
Ganau A, Devereux RB, Roman MJ et al (1992) Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension. J Am Coll Cardiol 19:1550–1558PubMedCrossRef
19.
American Diabetes Association (2006) Standards of medical care in diabetes-2006. Diabetes Care 29(Suppl 1):S4–S42
20.
Chiquette E, Ramirez G, Defronzo R (2004) A meta-analysis comparing the effect of thiazolidinediones on cardiovascular risk factors. Arch Intern Med 164:2097–2104PubMedCrossRef
21.
Nagasaka S, Aiso Y, Yoshizawa K, Ishibashi S (2004) Comparison of pioglitazone and metformin efficacy using homeostasis model assessment. Diabet Med 21:136–141PubMedCrossRef
22.
Fonseca V, Rosenstock J, Patwardhan R, Salzman A (2000) Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial. JAMA 283:1695–1702PubMedCrossRef
23.
Einhorn D, Rendell M, Rosenzweig J, Egan JW, Mathisen AL, Schneider RL (2000) Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-controlled study: the Pioglitazone 027 Study Group. Clin Ther 22:1395–1409PubMedCrossRef
24.
Bailey CJ (2005) Treating insulin resistance in type 2 diabetes with metformin and thiazolidinediones. Diabetes Obes Metab 7:675–691PubMedCrossRef
25.
Dormandy JA, Charbonnel B, Eckland DJA et al, on behalf of the PROactive investigators (2005) Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 366:1279–1289PubMedCrossRef
26.
Hanefeld M, Brunetti P, Schernthaner GH, Matthews DR, Charbonnel BH; QUARTET Study Group (2004). One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes. Diabetes Care 27:141–147PubMedCrossRef
27.
Charbonnel B, Schernthaner G, Brunetti PH et al (2005) Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes. Diabetologia 48:1093–1104PubMedCrossRef
28.
Krauss RM (2004) Lipids and lipoproteins in patients with type 2 diabetes. Diabetes Care 27:1496–1504PubMedCrossRef
29.
Assmann G, Schulte H (1998) The prospective cardiovascular Münster (PROCAM) study: prevalence of hyperlipidemia in persons with hypertension and/or diabetes mellitus and the relationship to coronary heart disease. Am Heart J 116:1713–1724CrossRef
30.
Freed MI, Ratner R, Marcovina SM et al Rosiglitazone Study 108 investigators (2002) Effects of rosiglitazone alone and in combination with atorvastatin on the metabolic abnormalities in type 2 diabetes mellitus. Am J Cardiol 90:947–952PubMedCrossRef
31.
Lewin AJ, Kipnes MS, Meneghini LF et al Simvastatin/Thiazolidinedione Study Group (2004) Effects of simvastatin on the lipid profile and attainment of low-density lipoprotein cholesterol goals when added to thiazolidinedione therapy in patients with type 2 diabetes mellitus: a multicenter, randomized, double-blind, placebo-controlled trial. Clin Ther 26:379–389PubMedCrossRef
32.
Belcher G, Schernthaner G (2005) Changes in liver tests during 1-year treatment of patients with Type 2 diabetes with pioglitazone, metformin or gliclazide. Diabet Med 22:973–979PubMedCrossRef
33.
Enomoto N, Takei Y, Hirose M et al (2003) Prevention of ethanol-induced liver injury in rats by an agonist of peroxisome proliferator-activated receptor-gamma, pioglitazone. J Pharmacol Exp Ther 306:846–854PubMedCrossRef
34.
Soinio M, Marniemi J, Laakso M, Lehto S, Ronnemaa T (2006) High-sensitivity C-reactive protein and coronary heart disease mortality in patients with type 2 diabetes: a 7-year follow-up study. Diabetes Care 29:329–333PubMedCrossRef
35.
Pfutzner A, Marx N, Lubben G et al (2005) Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control: results from the Pioneer study. J Am Coll Cardiol 45:1925–1931PubMedCrossRef
36.
Miyazaki Y, Mahankali A, Matsuda M et al (2002) Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 87:2784–2791PubMedCrossRef
37.
Sowers JR (1998) Obesity and cardiovascular disease. Clin Chem 44:1821–1825PubMed
38.
Belcher G, Lambert C, Edwards G, Urquhart R, Matthews DR (2005) Safety and tolerability of pioglitazone, metformin, and gliclazide in the treatment of type 2 diabetes. Diabetes Res Clin Pract 70:53–62PubMedCrossRef
39.
Delea TE, Edelsberg JS, Hagiwara M, Oster G, Phillips LS (2003) Use of thiazolidinediones and risk of heart failure in people with Type 2 diabetes: a retrospective cohort study. Diabetes Care 26:2983–2989PubMedCrossRef
40.
Karter AJ, Ahmed AT, Liu J, Moffet HH, Parker MM (2005) Pioglitazone initiation and subsequent hospitalization for congestive heart failure. Diabet Med 22:986–993PubMedCrossRef
41.
Masoudi FA, Inzucchi SE, Wang Y, Havranek EP, Foody JM, Krumholz HM (2005) Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study. Circulation 111:583–590PubMedCrossRef
42.
Asakawa M, Takano H, Nagai T, Uozumi H, Hasegawa H, Kubota N et al. (2002) Peroxisome proliferator-activated receptor γ plays a critical role in inhibition of cardiac hypertrophy in vitro and in vivo. Circulation 105:1240–1246PubMedCrossRef
43.
Tsuji T, Mizushige K, Noma T et al (2001) Pioglitazone improves left ventricular diastolic function and decreases collagen accumulation in prediabetic stage of a type II diabetic rat. J Cardiovasc Pharmacol 38:868–874PubMedCrossRef
44.
Ghazzi MN, Perez JE, Antonucci TK, Driscoll JH, Huang SM, Faja BW, Whitcomb RW, The Troglitazone Study Group (1997) Cardiac and glycemic benefits of troglitazone treatment in NIDDM. Diabetes 46:433–439PubMedCrossRef
45.
St. John Sutton M, Rendell M, Dandona P et al (2002) A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes. Diabetes Care 25:2058–2064PubMedCrossRef
46.
Gæde P, Hildebrandt P, Hess G, Parving HH, Pedersen O (2005) Plasma N-terminal pro-brain natriuretic peptide as a major risk marker for cardiovascular disease in patients with type 2 diabetes and microalbuminuria. Diabetologia 48:156–163PubMedCrossRef
47.
Isotani H, Kameoka K, Sasaki I, Hida H, Kakutani S, Tasaki T (2000) Plasma brain natriuretic peptide levels in normotensive type 2 diabetic patients without cardiac disease. Diabetes Care 23:859–860PubMedCrossRef
48.
El Muayed M, Lavis VR, Safi HJ, Fuentes F (2004) Use of glitazones in cardiac patients: a case for B-type natriuretic peptide monitoring? Am J Cardiol 93:600–602PubMedCrossRef
49.
Wu AH, Smith A, Wieczorek S et al (2003) Biological variation for N-terminal pro- and B-type natriuretic peptides and implications for therapeutic monitoring of patients with congestive heart failure. Am J Cardiol 92:628–631PubMedCrossRef
50.
Ogawa S, Takeuchi K, Ito S (2003) Plasma BNP levels in the treatment of type 2 diabetes with pioglitazone. J Clin Endocrinol Metab 88:3993–3996PubMedCrossRef
51.
Kahn SE, Haffner SM, Heise MA et al for the ADOPT Study Group (2006) Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 355:2427–2243PubMedCrossRef
Metadata
Title
Effect of pioglitazone on heart function and N-terminal pro-brain natriuretic peptide levels of patients with type 2 diabetes
Authors
Christos Sambanis
Konstantinos Tziomalos
Evangelia Kountana
Nikitas Kakavas
Ioanna Zografou
Aikaterini Balaska
Georgios Koulas
Asterios Karagiannis
Chrysanthos Zamboulis
Publication date
01-03-2008
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 1/2008
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-007-0014-7

Other articles of this Issue 1/2008

Acta Diabetologica 1/2008 Go to the issue

Original Article

The effect of insulin glargine and nutritional model on metabolic control, quality of life and behavior in children and adolescents with type 1 diabetes mellitus

Original Article

Lack of association between the Pro12Ala polymorphism of the PPAR-γ2 gene and type 2 diabetes mellitus in the Qatari consanguineous population

Original Article

Prevalence and associated factors of lens opacities among Chinese type 2 diabetics in Kinmen, Taiwan

Original Article

Therapeutic options for elderly diabetic subjects: open label, randomized clinical trial of insulin glargine added to oral antidiabetic drugs versus increased dosage of oral antidiabetic drugs

Original Article

Metabolic effects of time-released garlic powder tablets in type 2 diabetes mellitus: the results of double-blinded placebo-controlled study

Original Article

Metabolic syndrome in a large chemical company: prevalence in a screened worksite sample
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits