Interleukin-6 (IL-6), tissue inhibitor of metalloproteinase-1 (TIMP-1), and most significantly serum galectin-3, were predictors of coronary heart disease (CHD) in individuals with long standing childhood onset type 1 diabetes (T1D), according to study results published in Diabetes Care. Investigators believe that these findings, along with conventional risk factors may aid in the prediction of CHD risks in these individuals.

Patients with type 1 diabetes are at high risk of premature death due to cardiovascular disease, but they also have an increased risk of acute myocardial infarction, heart failure and cerebral stroke. These patients are routinely monitored for conventional coronary heart disease risk factors, such as hemoglobin A1c (HbA1c) and the duration of diabetes duration, but still, patients with type 1 diabetes have increased risk of coronary heart disease.

Few studies have documented the long-term coronary heart disease outcomes of patients with childhood-onset type 1 diabetes. In this study investigators, led by Maryam Saeed, MD, Oslo University Hospital, Norway, sought to determine whether biomarkers associated with inflammation, fibrosis, and and myocardial injury were associated with risk of coronary heart disease in patients with childhood-onset type 1 diabetes.


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For this longitudinal, population based, nationwide study, researchers retrospectively selected patients who were aged <15 years during 1973–1982 with newly diagnosed T1D (n=1,906, all Caucasian). A random sample (n=355) of these individuals underwent a standardized clinical examination in 2002 to 2003 at their local hospital. The examination included blood and urine sampling, which investigators defined as baseline for the study analyses. Of the 355 individuals, 295 met inclusion criteria and were included in the study cohort. The participants were followed prospectively for end points from the time of examination in 2002 to 2003 until the end of 2017.

The primary outcome assessed was incident CHD event, which investigators defined as the first hospitalization with a primary or secondary diagnosis of CHD or death with CHD as the underlying cause. At baseline, the mean age was 32.7 years (range 21–44), mean diabetes duration was 24.3 years (range 19–30), and mean HbA1c was 8.2% (66 mmol/mol) (range 4.9– 13.7). Of these individuals, 19.7% had micro- or macroalbuminuria.  All patients were examined by the same doctor, and all blood samples were analyzed by the same laboratory.

Information on CHD events for all subjects was obtained by personal patient identification numbers that were linked to nationwide hospitalization data from 1994 to 2014 from the Cardiovascular Disease in Norway project and the Norwegian Patient Registry. Moreover, data on the underlying cause of death were obtained from the Norwegian Cause of Death Registry.

Out of 295 subjects, 40 (13.6%) had their first CHD event during a mean follow-up of 9.4 years (range 0.5–15.7), and a documented CHD event during a mean follow-up of 14.4 years (range 0.5–16). The mean age at first CHD event was 44 years (range 30–58). Out of 40 subjects with a CHD event, 2 of the subjects had a fatal event. IL-6 (adjusted Hazard Ration [aHR] 1.32 [95% CI 1.07–1.63]), galectin-3 (aHR 1.44 [95% CI 1.09–1.80]), and TIMP-1 (aHR 1.37 [95% CI 1.04–1.81]) were significant predictors of CHD after adjustment for conventional risk factors. Despite comparable duration of diabetes, the group who later suffered a CHD event had numerically higher proportions with retinopathy and albuminuria and higher levels of HbA1c.

Limitations of the study included the small size of the patient pool and the lack of repeated measures of biomarkers and risk factors, such as diabetic ketoacidosis and severe hypoglycemic events. The small quantity of blood sample available to researchers limited the number of markers that could be analyzed. Investigators also noted, “As our study is observational, we cannot rule out the possibility that there are unmeasured confounders.”

“If our findings are replicated, galectin-3 may represent a novel finding in multivariable risk prediction for CHD,” researchers concluded.

Disclosures

This study was funded by Stiftelsen Dam, The University of Oslo, and Oslo University Hospital. No potential conflicts of interest were reported. Please see the original study for the complete list of disclosures.

Reference

Saeed M, Tapia G, Ariansen I. et al, https://care.diabetesjournals.org/content/early/2021/01/05/dc20-1712.long. Published online January 6, 2021. Diabetes Care. Doi: 10.2337/dc20-1712