Impact of prediabetes and type 2 diabetes mellitus on cardiac function in the general population
Authors: Schmitt V , Billaudelle A M , Schulz A , Keller K , Hahad O , Troebs S O , Koeck T , Michal M , Schuster A K , Toenges G , Lackner K J , Prochaska J H , Munzel T , Wild P S 
Published: October 2022

Abstract

Introduction
Prediabetes and type 2 diabetes mellitus (T2DM) are risk factors for heart failure (HF). The association of prediabetes and T2DM to different forms of functional left ventricular impairment and their impact on clinical outcome in the general population needs to be further investigated. In this context, little is known about the prevalences of prediabetes and different HF subtypes in the general population, especially in Europe.

Purpose
To investigate the prevalence and clinical impact of prediabetes and type 2 diabetes mellitus (T2DM) on functional cardiac disorder (FCD).

Methods
The participants of the Gutenberg Health Study sample (15,010 subjects, 35–74 years) were stratified in individuals with euglycaemia, prediabetes and T2DM based on clinical information and HbA1c level. FCD included asymptomatic systolic and diastolic dysfunction, symptomatic systolic and diastolic heart failure, asymptomatic diastolic dysfunction and preserved left ventricular ejection fraction (EF), asymptomatic diastolic dysfunction and reduced EF, asymptomatic preserved diastole and reduced EF, symptomatic heart failure with preserved EF (HFpEF) and symptomatic heart failure with reduced EF HFrEF). Using structured follow-up clinical outcome was assessed.

Results
Overall, 14,870 individuals were included in the present analysis. Among them, 9,426 individuals were categorized in the euglycaemia group, 4,128 participants had prediabetes and in 1,316 individuals T2DM was present. Prevalence of FCD increased from euglycaemia (19.6%) over prediabetes (33.3%) to T2DM (46.8%, p&lt;0.0001). Prevalence of symptomatic HF was increased in patients with T2DM (euglycaemia 2.8%, prediabetes 5.9%, T2DM 11.9%). T2DM was associated with reduced EF (β −0.63, 95% CI −0.99 to −0.26, P=0.00088) and elevated E/E' (β 0.08, 95% CI 0.06 to 0.10, P&lt;0.0001), whereas prediabetes was associated to elevated E/E' (β 0.02, 95% CI 0.01 to 0.03, P=0.0029). Prediabetes and T2DM revealed increased prevalences of FCD (13%, 18%), asymptomatic diastolic dysfunction with preserved EF (prediabetes: 14%, T2DM: 11%), symptomatic heart failure (prediabetes: 46%, T2DM: 70%) and HFpEF (prediabetes: 49%, T2DM: 82%). With prediabetes and T2DM all-cause mortality was elevated in presence and absence of FCD, only T2DM was also a risk factor for cardiovascular mortality with and without FCD. Within a 5-years follow-up, T2DM was an independent risk factor for the development of FCD, asymptomatic diastolic dysfunction with reduced ejection fraction, symptomatic heart failure and HFrEF. Prediabetes was not an independent risk factor for FCD.

Conclusions
In the general population, a high prevalence of asymptomatic FCD is present. Coexisting FCD and prediabetes as well as T2DM result in increased mortality elucidating the need for early detection and prevention of DM development, especially with regard to numerous asymptomatic people concerned. T2DM, but not prediabetes, is a risk factor for incident FCD.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): The Gutenberg Health Study is supported by the government of Rheinland-Pfalz (`Stiftung Rheinland-Pfalz für Innovation'), the research programmes `Wissen schafft Zukunft' and the Centre forTranslational Vascular Biology (CTVB) of the Johannes Gutenberg-University of Mainz, Germany, and its contract with Boehringer Ingelheim and Philips Medical Systems including an unrestricted grant forthe Gutenberg Health Study. P.S.W. and J.H.P. are funded by the Federal Ministry of Education and Research (BMBF 01EO1503). P.S.W. and T.M. are principal investigators of the German Center for Cardiovascular Research (DZHK). P.S.W. is principal investigator of the DIASyM research core (BMBF 161L0217A).