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

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2015

Open Access 01-12-2015 | Original investigation

Diastolic dysfunction in the diabetic continuum: association with insulin resistance, metabolic syndrome and type 2 diabetes

Authors: Ricardo Fontes-Carvalho, Ricardo Ladeiras-Lopes, Paulo Bettencourt, Adelino Leite-Moreira, Ana Azevedo

Published in: Cardiovascular Diabetology | Issue 1/2015

Login to get access

Abstract

Background

Diabetes increases the risk of heart failure but the underlying mechanisms leading to diabetic cardiomyopathy are poorly understood. Left ventricle diastolic dysfunction (LVDD) is one of the earliest cardiac changes in these patients. We aimed to evaluate the association between LVDD with insulin resistance, metabolic syndrome (MS) and diabetes, across the diabetic continuum.

Methods

Within a population-based study (EPIPorto), a total of 1063 individuals aged ≥45 years (38% male, 61.2 ± 9.6 years) were evaluated. Diastolic function was assessed by echocardiography, using tissue Doppler analysis (E’ velocity and E/E’ ratio) according to the latest consensus guidelines. Insulin resistance was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score.

Results

The HOMA-IR score correlated to E’ velocity (ρ = −0.20;p < 0.0001) and E/E’ ratio (ρ = 0.20; p < 0.0001). There was a progressive worsening in E’ velocity (p for trend < 0.001) and in E/E’ ratio across HOMA-IR quartiles (p for trend <0.001). Individuals in the highest HOMA-IR quartile were more likely to have LVDD, even after adjustment for age, sex, blood pressure and body mass index (adjusted OR: 1.82; 95% CI: 1.09-3.03). From individuals with no MS, to patients with MS and no diabetes, to patients with diabetes, there was a progressive decrease in E’ velocity (11.2 ± 3.3 vs 9.7 ± 3.1 vs 9.2 ± 2.8 cm/s; p < 0.0001), higher E/E’ (6.9 ± 2.3 vs 7.8 ± 2.7 vs 9.0 ± 3.6; p < 0.0001) and more diastolic dysfunction (adjusted OR: 1.62; 95% CI: 1.12-2.36 and 1.78; 95% CI: 1.09-2.91, respectively).

Conclusions

HOMA-IR score and metabolic syndrome were independently associated with LVDD. Changes in diastolic function are already present before the onset of diabetes, being mainly associated with the state of insulin resistance.
Literature
1.
Redfield MM, Jacobsen SJ, Burnett Jr JC, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003;289:194–202.PubMedCrossRef
2.
Kane GC, Karon BL, Mahoney DW, Redfield MM, Roger VL, Burnett Jr JC, et al. Progression of left ventricular diastolic dysfunction and risk of heart failure. JAMA. 2011;306:856–63.PubMedCentralPubMedCrossRef
3.
Mogelvang R, Sogaard P, Pedersen SA, Olsen NT, Marott JL, Schnohr P, et al. Cardiac dysfunction assessed by echocardiographic tissue Doppler imaging is an independent predictor of mortality in the general population. Circulation. 2009;119:2679–85.PubMedCrossRef
4.
Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Jr., Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, et al.: 2013 ACCF/AHA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013.
5.
Russo C, Jin Z, Homma S, Rundek T, Elkind MS, Sacco RL, et al. Effect of obesity and overweight on left ventricular diastolic function: a community-based study in an elderly cohort. J Am Coll Cardiol. 2011;57:1368–74.PubMedCentralPubMedCrossRef
6.
Canepa M, Strait JB, Abramov D, Milaneschi Y, AlGhatrif M, Moni M, et al. Contribution of central adiposity to left ventricular diastolic function (from the Baltimore Longitudinal Study of Aging). Am J Cardiol. 2012;109:1171–8.PubMedCentralPubMedCrossRef
7.
Canepa M, Strait JB, Milaneschi Y, Alghatrif M, Ramachandran R, Makrogiannis S, et al. The relationship between visceral adiposity and left ventricular diastolic function: Results from the Baltimore Longitudinal Study of Aging. Nutr Metab Cardiovasc Dis. 2013;23:1263–70.PubMedCrossRef
8.
Ingelsson E, Sundstrom J, Arnlov J, Zethelius B, Lind L. Insulin resistance and risk of congestive heart failure. JAMA. 2005;294:334–41.PubMedCrossRef
9.
Horwich TB, Fonarow GC. Glucose, obesity, metabolic syndrome, and diabetes relevance to incidence of heart failure. J Am Coll Cardiol. 2010;55:283–93.PubMedCentralPubMedCrossRef
10.
Zabalgoitia M, Ismaeil MF, Anderson L, Maklady FA. Prevalence of diastolic dysfunction in normotensive, asymptomatic patients with well-controlled type 2 diabetes mellitus. Am J Cardiol. 2001;87:320–3.PubMedCrossRef
11.
12.
Stahrenberg R, Edelmann F, Mende M, Kockskamper A, Dungen HD, Scherer M, et al. Association of glucose metabolism with diastolic function along the diabetic continuum. Diabetologia. 2010;53:1331–40.PubMedCentralPubMedCrossRef
13.
Bajraktari G, Koltai MS, Ademaj F, Rexhepaj N, Qirko S, Ndrepepa G, et al. Relationship between insulin resistance and left ventricular diastolic dysfunction in patients with impaired glucose tolerance and type 2 diabetes. Int J Cardiol. 2006;110:206–11.PubMedCrossRef
14.
Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010;56:1113–32.PubMedCrossRef
15.
DelasFuentes L, Brown AL, Mathews SJ, Waggoner AD, Soto PF, Gropler RJ, et al. Metabolic syndrome is associated with abnormal left ventricular diastolic function independent of left ventricular mass. Eur Heart J. 2007;28:553–9.
16.
Azevedo A, Bettencourt P, Almeida PB, Santos AC, Abreu-Lima C, Hense HW, et al. Increasing number of components of the metabolic syndrome and cardiac structural and functional abnormalities–cross-sectional study of the general population. BMC Cardiovasc Disord. 2007;7:17.PubMedCentralPubMedCrossRef
17.
Seo JM, Park TH, Lee DY, Cho YR, Baek HK, Park JS, et al. Subclinical Myocardial Dysfunction in Metabolic Syndrome Patients without Hypertension. J Cardiovasc Ultrasound. 2011;19:134–9.PubMedCentralPubMedCrossRef
18.
Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112:2735–52.PubMedCrossRef
19.
Cortez-Dias N, Martins S, Belo A, Fiuza M. Comparison of definitions of metabolic syndrome in relation to risk for coronary artery disease and stroke. Rev Port Cardiol. 2011;30:139–69.PubMed
20.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.PubMedCrossRef
21.
Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification. Eur J Echocardiogr. 2006;7:79–108.PubMedCrossRef
22.
Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr. 2009;10:165–93.PubMedCrossRef
23.
Dinh W, Lankisch M, Nickl W, Scheyer D, Scheffold T, Kramer F, et al. Insulin resistance and glycemic abnormalities are associated with deterioration of left ventricular diastolic function: a cross-sectional study. Cardiovasc Diabetol. 2010;9:63.PubMedCentralPubMedCrossRef
24.
Utsunomiya H, Yamamoto H, Kunita E, Hidaka T, Kihara Y. Insulin resistance and subclinical abnormalities of global and regional left ventricular function in patients with aortic valve sclerosis. Cardiovasc Diabetol. 2014;13:86.PubMedCentralPubMedCrossRef
25.
Beltran-Sanchez H, Harhay MO, Harhay MM, McElligott S. Prevalence and trends of metabolic syndrome in the adult U.S. population, 1999–2010. J Am Coll Cardiol. 2013;62:697–703.PubMedCentralPubMedCrossRef
26.
Masugata H, Senda S, Goda F, Yoshihara Y, Yoshikawa K, Fujita N, et al. Left ventricular diastolic dysfunction as assessed by echocardiography in metabolic syndrome. Hypertens Res. 2006;29:897–903.PubMedCrossRef
27.
Ayalon N, Gopal DM, Mooney DM, Simonetti JS, Grossman JR, Dwivedi A, et al. Preclinical Left Ventricular Diastolic Dysfunction in Metabolic Syndrome. Am J Cardiol. 2014;114:838–42.PubMedCrossRef
28.
Abel ED, O'Shea KM, Ramasamy R. Insulin resistance: metabolic mechanisms and consequences in the heart. Arterioscler Thromb Vasc Biol. 2012;32:2068–76.PubMedCentralPubMedCrossRef
29.
Peterson LR, Herrero P, Schechtman KB, Racette SB, Waggoner AD, Kisrieva-Ware Z, et al. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation. 2004;109:2191–6.PubMedCrossRef
30.
Ogata T, Miyauchi T, Sakai S, Takanashi M, Irukayama-Tomobe Y, Yamaguchi I. Myocardial fibrosis and diastolic dysfunction in deoxycorticosterone acetate-salt hypertensive rats is ameliorated by the peroxisome proliferator-activated receptor-alpha activator fenofibrate, partly by suppressing inflammatory responses associated with the nuclear factor-kappa-B pathway. J Am Coll Cardiol. 2004;43:1481–8.PubMedCrossRef
31.
Anderson EA, Hoffman RP, Balon TW, Sinkey CA, Mark AL. Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. J Clin Invest. 1991;87:2246–52.PubMedCentralPubMedCrossRef
32.
Park JS, Nam JS, Cho MH, Yoo JS, Ahn CW, Jee SH, et al. Insulin resistance independently influences arterial stiffness in normoglycemic normotensive postmenopausal women. Menopause. 2010;17:779–84.PubMed
33.
MacIsaac RJ, Thomas MC, Panagiotopoulos S, Smith TJ, Hao H, Matthews DG, et al. Association between intrarenal arterial resistance and diastolic dysfunction in type 2 diabetes. Cardiovasc Diabetol. 2008;7:15.PubMedCentralPubMedCrossRef
34.
Ceriello A, Taboga C, Tonutti L, Quagliaro L, Piconi L, Bais B, et al. Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation. 2002;106:1211–8.PubMedCrossRef
35.
Kuster GM, Lancel S, Zhang J, Communal C, Trucillo MP, Lim CC, et al. Redox-mediated reciprocal regulation of SERCA and Na + −Ca2+ exchanger contributes to sarcoplasmic reticulum Ca2+ depletion in cardiac myocytes. Free Radic Biol Med. 2010;48:1182–7.PubMedCentralPubMedCrossRef
36.
Fuseya T, Furuhashi M, Yuda S, Muranaka A, Kawamukai M, Mita T, et al. Elevation of circulating fatty acid-binding protein 4 is independently associated with left ventricular diastolic dysfunction in a general population. Cardiovasc Diabetol. 2014;13:126.PubMedCentralPubMedCrossRef
37.
38.
Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114:597–605.PubMedCrossRef
39.
Lind M, Bounias I, Olsson M, Gudbjornsdottir S, Svensson AM, Rosengren A. Glycaemic control and incidence of heart failure in 20,985 patients with type 1 diabetes: an observational study. Lancet. 2011;378:140–6.PubMedCrossRef
40.
Aurigemma GP, Gottdiener JS, Shemanski L, Gardin J, Kitzman D. Predictive value of systolic and diastolic function for incident congestive heart failure in the elderly: the cardiovascular health study. J Am Coll Cardiol. 2001;37:1042–8.PubMedCrossRef
41.
Bella JN, Palmieri V, Roman MJ, Liu JE, Welty TK, Lee ET, et al. Mitral ratio of peak early to late diastolic filling velocity as a predictor of mortality in middle-aged and elderly adults: the Strong Heart Study. Circulation. 2002;105:1928–33.PubMedCrossRef
42.
Holland DJ, Kumbhani DJ, Ahmed SH, Marwick TH. Effects of treatment on exercise tolerance, cardiac function, and mortality in heart failure with preserved ejection fraction. A meta-analysis. J Am Coll Cardiol. 2011;57:1676–86.PubMedCrossRef
43.
Banerjee D, Biggs ML, Mercer L, Mukamal K, Kaplan R, Barzilay J, et al. Insulin resistance and risk of incident heart failure: Cardiovascular Health Study. Circ Heart Fail. 2013;6:364–70.PubMedCentralPubMedCrossRef
44.
Vardeny O, Gupta DK, Claggett B, Burke S, Shah A, Loehr L, et al. Insulin resistance and incident heart failure the ARIC study (Atherosclerosis Risk in Communities). JACC Heart Fail. 2013;1:531–6.PubMedCentralPubMedCrossRef
45.
Bibbins-Domingo K, Lin F, Vittinghoff E, Barrett-Connor E, Hulley SB, Grady D, et al. Predictors of heart failure among women with coronary disease. Circulation. 2004;110:1424–30.PubMedCrossRef
46.
Burla AK, Lobato NS, Fortes ZB, Oigman W, Neves MF. Cardiac fibrosis and vascular remodeling are attenuated by metformin in obese rats. Int J Cardiol. 2013;165:483–7.PubMedCrossRef
47.
Cittadini A, Napoli R, Monti MG, Rea D, Longobardi S, Netti PA, et al. Metformin prevents the development of chronic heart failure in the SHHF rat model. Diabetes. 2012;61:944–53.PubMedCentralPubMedCrossRef
48.
Xiao X, He Q, Lu C, Werle KD, Zhao RX, Chen J, et al. Metformin impairs the growth of liver kinase B1-intact cervical cancer cells. Gynecol Oncol. 2012;127:249–55.PubMedCentralPubMedCrossRef
49.
Zhang CX, Pan SN, Meng RS, Peng CQ, Xiong ZJ, Chen BL, et al. Metformin attenuates ventricular hypertrophy by activating the AMP-activated protein kinase-endothelial nitric oxide synthase pathway in rats. Clin Exp Pharmacol Physiol. 2011;38:55–62.PubMedCrossRef
50.
Ladeiras-Lopes R, Fontes-Carvalho R, Bettencourt N, Sampaio F, Gama V, Leite-Moreira AF. METformin in DIastolic Dysfunction of MEtabolic syndrome (MET-DIME) trial: rationale and study design: MET-DIME trial. Cardiovasc Drugs Ther. 2014;28:191–6.PubMedCrossRef
Metadata
Title
Diastolic dysfunction in the diabetic continuum: association with insulin resistance, metabolic syndrome and type 2 diabetes
Authors
Ricardo Fontes-Carvalho
Ricardo Ladeiras-Lopes
Paulo Bettencourt
Adelino Leite-Moreira
Ana Azevedo
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2015
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-014-0168-x

Other articles of this Issue 1/2015

Cardiovascular Diabetology 1/2015 Go to the issue

Original investigation

Coronary microvascular function is independently associated with left ventricular filling pressure in patients with type 2 diabetes mellitus

Original investigation

Impaired fasting glucose and left ventricular diastolic dysfunction in middle-age adults: a retrospective cross-sectional analysis of 2971 subjects

Original investigation

Sensitivity of various adiposity indices in identifying cardiometabolic diseases in Arab adults

Original investigation

Association between brachial-ankle pulse wave velocity and progression of coronary artery calcium: a prospective cohort study

Original investigation

Relationship between serum osteocalcin level and carotid intima-media thickness in a metabolically healthy Chinese population

Original investigation

The inflammation, vascular repair and injury responses to exercise in fit males with and without Type 1 diabetes: an observational study
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
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
Image Credits