Cardiovascular profiling in the diabetic continuum: results from the population-based Gutenberg Health Study

Abstract

Aims: To assess the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes in the general population and to investigate the associated cardiovascular burden and clinical outcome.

Methods and results: The study sample comprised 15,010 individuals aged 35-74 years of the population-based Gutenberg Health Study. Subjects were classified into euglycaemia, prediabetes and T2DM according to clinical and metabolic (HbA1c) information. The prevalence of prediabetes was 9.5% (n = 1415) and of T2DM 8.9% (n = 1316). Prediabetes and T2DM showed a significantly increased prevalence ratio (PR) for age, obesity, active smoking, dyslipidemia, and arterial hypertension compared to euglycaemia (for all, P < 0.0001). In a robust Poisson regression analysis, prediabetes was established as an independent predictor of clinically-prevalent cardiovascular disease (PR_prediabetes 1.20, 95% CI 1.07-1.35, P = 0.002) and represented as a risk factor for asymptomatic cardiovascular organ damage independent of traditional risk factors (PR 1.04, 95% CI 1.01-1.08, P = 0.025). Prediabetes was associated with a 1.5-fold increased 10-year risk for cardiovascular disease compared to euglycaemia. In Cox regression analysis, prediabetes (HR 2.10, 95% CI 1.76-2.51, P < 0.0001) and T2DM (HR 4.28, 95% CI 3.73-4.92, P < 0.0001) indicated for an increased risk of death. After adjustment for age, sex and traditional cardiovascular risk factors, only T2DM (HR 1.89, 95% CI 1.63-2.20, P < 0.0001) remained independently associated with increased all-cause mortality.

Conclusion: Besides T2DM, also prediabetes inherits a significant cardiovascular burden, which translates into poor clinical outcome and indicates the need for new concepts regarding the prevention of cardiometabolic disorders.

Keywords: All-cause mortality; Asymptomatic organ damage; Cardiovascular disease; Disease prevention; Prediabetes; Type 2 diabetes mellitus.

Fig. 1

Study flow chart. T2DM was defined as HbA1c ≥ 6.5% or diagnosed by a physician or diabetic medication intake. Prediabetes was present if HbA1c 6.0–6.4% and no T2DM diagnosed by a physician and no diabetic medication intake. Euglycaemia was present if HbA1c < 6.0% and no T2DM diagnosed by a physician and no diabetic medication intake. Individuals without available data for glucose state and all diabetes types other than T2DM were excluded. Also, individuals of non-fasting state presenting fasting glucose > 125 mg/dl were excluded. Exclusions from the GHS cohort are given in red boxes. In total, 14,852 individuals were included. GHS Gutenberg Health Study, T2DM Type 2 diabetes mellitus

Fig. 2

Forest plot illustrating the interrelation of prediabetes and T2DM on asymptomatic organ damage as well as (sub)clinical cardiovascular disease. Graphical illustration of estimates of multiple Poisson regression analysis with asymptomatic cardiovascular organ damage as well as cardiovascular disease as dependent variables and the independent variables prediabetes and T2DM (vs. euglycaemia) adjusted for age, sex, and cardiovascular risk factors

Fig. 3

Cumulative incidence of all-cause mortality by diabetic phenotypes in Cox regression analysis. Compared to euglycaemic state, individuals with prediabetes and type 2 diabetes mellitus experienced an elevated risk for death. In the figure, the P-value of the log-rank test is provided

Fig. 4

Competing risk analyses for euglycaemia, prediabetes and T2DM with all-cause death as competing risk investigating cardiac death, cardiovascular disease, myocardial infarction, stroke, atrial fibrillation and heart failure. P value of Gray’s test is provided

Fig. 5

Competing risk analyses for euglycaemia, prediabetes and T2DM with all-cause death as competing risk investigating the combinations of cardiac death and myocardial infarction, cardiac death and stroke, cardiac death and heart failure as well as cardiac death and atrial fibrillation. P value of Gray’s test is provided