Serum Galectin-3 and Subsequent Risk of Coronary Heart Disease in Subjects With Childhood-Onset Type 1 Diabetes: A Cohort Study

Abstract

OBJECTIVE To study whether serum galectin-3 and other biomarkers of inflammation predict coronary heart disease (CHD) in subjects with long-standing childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS A population-based nationwide cohort of 299 subjects with type 1 diabetes diagnosed in Norway at <15 years of age during 1973–1982 was examined in 2002–2003 at a mean age of 33 years (range 21–44), with mean diabetes duration of 24 years (range 19–30). Subjects were followed through 31 December 2017 for their first CHD event registered by a hospitalization or cause of death using nationwide registries. Stored serum samples were available for 296 subjects and analyzed for interleukin-6 (IL-6), IL-6 receptor, IL-18, hs-CRP, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), galectin-3, and high-sensitivity troponin T. Adjusted hazard ratios (aHRs) for CHD per SD increase in biomarker were estimated using Cox regression. RESULTS Of 295 subjects, 40 (13.6%) had a documented CHD event during a mean follow-up of 14.4 years (range 0.5–16). IL-6 (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. CONCLUSIONS Galectin-3 was significantly associated with future CHD in subjects with type 1 diabetes, and if the results are replicated in larger studies, it may aid in prediction together with conventional risk factors for CHD.

Nine-fold higher risk of acute myocardial infarction in subjects with type 1 diabetes compared to controls in Norway 1973–2017

“…Hyperglycemia induced inflammation, oxidative stress and hypercoagulability is also discussed, leading to micro- and macrovascular complications [ 41 ]. Our study is observational, but our findings in this study and in a former study may support these hypotheses [ 21 ].…”

“…The primary outcome was an incident AMI event using the International Classification of Diseases 9th revision (ICD-9) codes 410 or ICD-10 codes I21–I22 [ 21 ]. First hospitalization with a primary or secondary diagnosis of AMI or death with AMI as the underlying cause, whichever occurred first, was defined as the first event of AMI.…”

Hepatic Meteorin-like and Krüppel-like Factor 3 are Associated with Weight Loss and Liver Injury

“…Interestingly, KLF3 knockout mice did not gain weight after feeding on a high-fat diet [24]. KLF3 was also shown to inhibit beiging of white adipose tissue in mice [22] and directly repress galectin-3, a regulator of inflammation in metabolic tissues [39,40], thus protecting pancreatic beta cells against IL-1β cytotoxicity [41].…”

Emerging roles of Galectin-3 in diabetes and diabetes complications: A snapshot

“…Ozturk et al performed coronary CT scans on 158 patients with T2D and reported that Galectin-3 was positively correlated with the number of coronary arteries with atherosclerosis [ 63 ]. Saeed et al followed up a population-based nationwide cohort in Norway, and found that after the adjustment of conventional risk factors, Galectin 3 was significantly associated with the risk of future coronary heart disease (CHD) and may help to predict the occurrence of CHD in patients with T1D [ 64 ]. These findings suggest that Galectin-3 could be a predictor for coronary atherosclerosis in patients with T1D or T2D.…”