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Updated: Sep 10, 2025
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Risk and protective factors for coronary atherosclerosis and myocardial dysfunction in individuals with long-duration
Marc Gregory Yu1,2, Hetal Shah1,2, Surya Jangolla1,2
1Dianne Nunnally Hoppes Laboratory, Research Division, Joslin Diabetes Center, Boston, MA, USA.
Insights
People with long-duration type 1 diabetes without kidney disease still face high cardiovascular disease (CVD) risks. Managing blood sugar and inflammation, particularly osteopontin, may reduce CVD in this population.
Area of Science:
- Cardiology
- Endocrinology
- Diabetology
Background:
- Cardiovascular disease (CVD) is a leading cause of mortality in individuals with long-duration type 1 diabetes, even in the absence of diabetic kidney disease (DKD).
- The Joslin 'Medalists' cohort, comprising individuals with type 1 diabetes for ≥50 years, offers a unique population to study CVD risks.
Purpose of the Study:
- To assess biomarkers associated with CVD risks in individuals with long-duration type 1 diabetes, focusing on those without DKD.
- To investigate the relationship between glycaemic control, inflammatory markers, and CVD, coronary artery calcium (CAC), and cardiac magnetic resonance (CMR) findings.
Main Methods:
- A cross-sectional study involving 1038 participants with self-reported CVD, with subsets undergoing CAC (n=142) and CMR (n=111) imaging.
- Multivariable regression analysis was used to examine associations between circulating factors (including inflammatory biomarkers and osteopontin), glycaemic markers (HbA1c, continuous glucose monitoring, advanced glycation end-products), and CVD outcomes, adjusting for DKD and other risk factors.
Main Results:
- Despite excellent cardiometabolic management, 40% of participants had CVD and a high CAC burden, irrespective of DKD status.
- In the non-DKD group, HbA1c remained associated with CVD (OR 1.40), while hypoglycaemia and glycaemic variability did not.
- Osteopontin was significantly associated with CVD (β=0.50) in the non-DKD group, highlighting its potential role.
Conclusions:
- Individuals with long-duration type 1 diabetes and without DKD, even with optimal cardiometabolic control, exhibit substantial coronary atherosclerosis.
- Strategies to improve hyperglycaemia and reduce inflammation, particularly targeting osteopontin, may be crucial for managing CVD risk in this population.
Aims/Hypothesis:
CVD remains a major cause of mortality in people with long-duration type 1 diabetes, even among those without diabetic kidney disease (DKD). We assessed biomarkers that may be associated with CVD risks among the Joslin 'Medalists', namely those with type 1 diabetes of ≥50 years.
Methods:
In this cross-sectional study, participants were evaluated for self-reported CVD (n=1038), with subsets undergoing coronary artery calcium (CAC; n=142) and cardiac magnetic resonance (CMR; n=111) imaging. Using multivariable regression analysis, multiple circulating factors such as inflammatory biomarkers and osteopontin (n=300) were analysed for associations with CVD, CAC and CMR, adjusting for DKD and other cardiometabolic and glycaemic risk factors, including HbA1c, continuous glucose monitor (n=102) metrics and advanced glycation end-products (n=200).
Results:
Only 32% of participants had DKD (eGFR <60 ml/min per 1.73 m2), but 40% had CVD. Despite having excellent cardiometabolic management (mean blood pressure of 132/64 mmHg; LDL and HDL-cholesterol of 2.10 mmol/l and 1.69 mmol/l, respectively, and a median HbA1c of 54.1 mmol/mol [7.1%]), participants exhibited a high CAC burden (median score 937), which did not differ between those with and without DKD (1136 vs 878, respectively). Among the glycaemic markers, HbA1c, but not hypoglycaemia or glycaemic variability, remained associated with CVD (OR 1.40, p<0.01) in the non-DKD group compared with the DKD group. Similarly, among the inflammatory markers, only osteopontin was associated with CVD (β=0.50, p<0.01) in the non-DKD group compared with the DKD group.
Conclusions/Interpretation:
Ageing people with long-duration type 1 diabetes and without DKD, but with excellent cardiometabolic management, still possess a high burden of coronary atherosclerosis. Improving hyperglycaemia and mitigating inflammation, especially osteopontin, are potentially important for the management of CVD in long-duration type 1 diabetes.
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