Individuals with type 2 diabetes (T2D) experienced two-fold more cardiovascular disease events than matched comparisons in the general population as much as 30 years before their diagnosis of T2D, according to results from a large, contemporary, nationwide registry-based study published Nov. 25 in JACC.

Christine Gylenkerne, MD, et al., conducted a combined case-control and cohort study to investigate the occurrence of cardiovascular disease three decades before and five years after the diagnosis of T2D in individuals diagnosed with T2D in Denmark between 2010 and 2015. The study comprised 127,092 individuals with T2D and 381,023 age- and sex-matched individuals form the general population. Their median age at the index date was 62 years and 54% were men. 

T2D was defined as either first-time hospital-registered inpatient or outpatient clinic diagnosis of diabetes or first-time redemption of a glucose-lowering drug prescription issued by a primary care physician or a hospitalist. The authors note that a previous validation study of diabetes diagnoses has indicated a positive predictive value of 95% for prescription-based diagnoses and 97% for hospital-based diagnoses.

Cardiovascular disease was defined as a composite of myocardial infarction (MI) and ischemic stroke, and these events were also assessed individually. Cardiovascular disease events were ascertained from the Danish National Patient Registry according to discharge diagnoses from an inpatient hospital stay. Validation studies have previously reported a positive predictive value of >95% for discharge diagnoses of MI and >95% for ischemic stroke.

Results of the study showed that more individuals with T2D than comparisons (11.2% vs. 4.7%) had a cardiovascular disease event in the 30-year period prior to the diagnosis of T2D. In the entire period before T2D was diagnosed, the prevalence of cardiovascular disease was higher among those with T2D than comparisons, and odds ratios ranged from 2.18 in the earliest period (25-30 years before diagnosis) to 2.96 in the latest period (<5 years before diagnosis). After T2D was diagnosed, the five-year incidence of cardiovascular disease was similarly increased in T2D (hazard ratio 2.20).

The authors write that the results suggest that at least part of the increased risk for cardiovascular disease associated with T2D is attributable to cardiovascular disease risk factors associated with developing T2D vs. the T2D itself. “Furthermore, they indicate an unrealized potential for initiating cardiovascular disease prevention measures at earlier stages in individuals at risk of developing cardiovascular disease and T2D, although more research is needed to confirm this hypothesis.”

In an accompanying editorial comment, Laurence S. Sperling, MD, FACC, writes the current study provides an answer to the “ticking clock” hypothesis, showing the clock for risk for heart disease starts to tick before the onset of diabetes. “This is both a cause for concern and a window of opportunity.” He adds, “This challenging window of opportunity must be recognized because it is the gateway to solutions anchored in tackling the root causes of this problem. Developing strategies to flatten the curve of an epidemic necessitates identification of vectors and understanding of complex contributory factors.”

Clinical Topics: Vascular Medicine

Keywords: Diabetes Mellitus, Type 2, Cardiovascular Diseases, Ischemic Stroke, Myocardial Infarction, Case-Control Studies, Denmark, Registries