Medalists represent a unique group of survivors of over 50 years of type 1 diabetes (T1D) (1,2). A subgroup of Medalists, escapers, remains free of micro- and macrovascular complications. To date, there are no published studies on cardiac structure and function in these subjects.
We have undertaken a comprehensive multiparametric cardiac MRI study (3,4) to quantify myocardial structure, function, deformation, perfusion, and fibrosis in a cohort of 13 subjects with extreme-duration T1D and 14 healthy control subjects (Table 1).
Table 1.
Clinical characteristics and cardiac MRI data
| Control subjects | T1D | P | |
|---|---|---|---|
| Clinical characteristics | |||
| Age (years) | 54.6 ± 5.4 | 61.8 ± 7.6 | 0.009 |
| Diabetes duration (years) | — | 47.4 ± 5.1 | — |
| BMI (kg/m2) | 27.0 ± 3.1 | 28.1 ± 4.5 | 0.48 |
| Systolic blood pressure (mmHg) | 118 ± 11 | 128 ± 15 | 0.051 |
| Diastolic blood pressure (mmHg) | 72 ± 10 | 60 ± 14 | 0.014 |
| HbA1c (%) | 5.7 ± 0.4 | 8.3 ± 1.0 | <0.0001 |
| Total cholesterol (mmol/L) | 5.0 ± 0.74 | 4.6 ± 1.0 | 0.227 |
| LDL cholesterol (mmol/L) | 2.9 ± 0.6 | 2.1 ± 1.0 | 0.035 |
| HDL cholesterol (mmol/L) | 1.6 ± 0.4 | 2.1 ± 0.7 | 0.027 |
| Triglycerides (mmol/L) | 1.1 ± 0.5 | 0.9 ± 0.4 | 0.265 |
| eGFR (mL/kg/min) | 81 ± 9 | 72 ± 20 | 0.135 |
| Cardiac MRI | |||
| Volumetrics | |||
| Left ventricular mass index [BSA] (g/m2) | 51.1 ± 10.7 | 41.0 ± 6.4 | 0.007 |
| Left ventricular ejection fraction (%) | 61.0 ± 6.4 | 63.1 ± 6.9 | 0.425 |
| Myocardial strain | |||
| Longitudinal strain | −16.0 ± 10.8 | −18.9 ± 5.5 | 0.394 |
| Longitudinal strain rate | 0.9 ± 0.9 | 1.2 ± 0.4 | 0.243 |
| Radial strain | −34.3 ± 11.6 | −32.1 ± 17.7 | 0.707 |
| Radial strain rate | 1.3 ± 0.7 | 1.5 ± 0.5 | 0.412 |
| Circumferential strain | −22.3 ± 2.6 | −24.9 ± 5.2 | 0.109 |
| Circumferential strain rate | 2.7 ± 5.7 | 1.4 ± 0.5 | 0.29 |
| MBF | |||
| Rest (mL/min/g) | 0.75 ± 0.17 | 0.86 ± 0.24 | 0.177 |
| Stress (mL/min/g) | 2.07 ± 0.42 | 1.80 ± 0.35 | 0.094 |
| Stress/rest index | 2.81 ± 0.47 | 2.16 ± 0.66 | 0.006 |
| ECV | |||
| ECV (%) | 0.27 ± 0.05 | 0.32 ± 0.04 | 0.01 |
BSA, body surface area; eGFR, estimated glomerular filtration rate.
The T1D group had a mean duration of diabetes of 47.4 ± 5.1 years (median 48.0 years). Eight participants had a history of retinopathy and 12 were receiving statin and ACE inhibitor therapy. The mean HbA1c over the previous 16 years was 8.3 ± 1.0% (69 ± 11 mmol/mol). The T1D group had higher systolic and lower diastolic blood pressure (P = 0.05, P = 0.01), lower LDL cholesterol (P = 0.04), and higher HDL cholesterol (P = 0.03). BMI, total cholesterol, triglycerides, and estimated glomerular filtration rate did not differ between the groups.
We found no evidence of coronary artery disease or previous myocardial infarction on stress imaging and T1 mapping, respectively. Left ventricular mass index was significantly lower in the T1D group (P = 0.007), but there was no difference in left ventricular ejection fraction. Myocardial deformation as assessed by radial, circumferential, and longitudinal strain did not differ between the groups. Myocardial blood flow (MBF) at rest and during pharmacological stress did not differ between the groups; however, the MBF ratio (stress/rest), an index of coronary microvascular perfusion reserve, was significantly lower in the T1D group (P = 0.006). We did not find any correlation between myocardial perfusion reserve and markers of cardiac autonomic function. On T1 mapping, extracellular volume (ECV) was significantly higher in the T1D group than in the control group (P = 0.01).
This is the first study to describe in detail the cardiac phenotype in a Medalist cohort. Using robust, validated, and reproducible three-dimensional modeling methods for volumetric and structural analyses, we demonstrate normal systolic and diastolic cardiac function in keeping with our recent echocardiographic study (5). There were no differences in MBF, but the stress/rest index was reduced, which is suggestive of coronary microvascular dysfunction. Coronary microvascular dysfunction may partly be mediated through cardiac autonomic dysfunction, but we found no correlation between myocardial perfusion reserve and cardiac autonomic function in our cohort. Quantitative assessment of myocardial ECV, a surrogate of myocardial fibrosis, shows much promise, and we have recently validated this in humans (3). ECV was increased in our Medalist group, which is suggestive of a very early fibrosis as there was no associated left ventricular mechanical dysfunction.
Although our study had limited numbers, we believe the detailed cardiac MRI cardiac phenotyping in this unique cohort of extreme-duration patients with T1D provides considerable insight and confirms that these unique individuals are indeed protected from the long-term complications of diabetes. Clinicians responsible for the care of patients with long-duration diabetes should perform detailed cardiac assessment to aid risk stratification for cardiovascular complications.
Article Information
Funding. This study was funded by research grants from the National Health Service National Institute for Health Research (FSF-R5-OA), National Institutes of Health (R105991), and JDRF (8-2008-362).
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
Author Contributions. O.A. was the major author of the manuscript and lead investigator for the study. C.M. and M.S. designed the cardiac MRI protocols and assisted with image and data analysis. S.R. assisted with study design and funding application. R.A.M. was the principle investigator for the study. R.A.M. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
References
- 1.Sun JK, Keenan HA, Cavallerano JD, et al. Protection from retinopathy and other complications in patients with type 1 diabetes of extreme duration: the Joslin 50-Year Medalist study. Diabetes Care 2011;34:968–974 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Bain SC, Gill GV, Dyer PH, et al. Characteristics of type 1 diabetes of over 50 years duration (the Golden Years Cohort). Diabet Med 2003;20:808–811 [DOI] [PubMed] [Google Scholar]
- 3.Miller CA, Naish JH, Bishop P, et al. Comprehensive validation of cardiovascular magnetic resonance techniques for the assessment of myocardial extracellular volume. Circ Cardiovasc Imaging 2013;6:373–383 [DOI] [PubMed] [Google Scholar]
- 4.Miller CA, Naish JH, Ainslie MP, et al. Voxel-wise quantification of myocardial blood flow with cardiovascular magnetic resonance: effect of variations in methodology and validation with positron emission tomography. J Cardiovasc Magn Reson 2014;16:1–15 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Fagan A, Asghar O, Pearce K, et al. Medalists with extreme duration of type 1 diabetes exhibit only mild diastolic dysfunction and myocardial fibrosis. Diabetes Care 2015;38:e5–e6 [DOI] [PubMed] [Google Scholar]