Medalists With Extreme Duration of Type 1 Diabetes ... - Diabetes Care

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Furthermore, the medalist group was slightly older, which empha- sizes the cardiac protection they have exhibited, as age independently predicts an abnormal ...

Diabetes Care Volume 38, January 2015

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Medalists With Extreme Duration of Type 1 Diabetes Exhibit Only Mild Diastolic Dysfunction and Myocardial Fibrosis

Andrew Fagan,1 Omar Asghar,2 Keith Pearce,3 Martin Stout,3 Simon G. Ray,3 Matthias Schmitt,3 and Rayaz A. Malik 2,4

Diabetes Care 2015;38:e5–e6 | DOI: 10.2337/dc14-2100

comparable. HbA1c (P , 0.0001) and HDL (P , 0.05) were higher, and LDL (P , 0.05) was significantly lower. Medalists and control subjects had similar left ventricular end-diastolic and endsystolic diameters, ejection fraction, longitudinal strain, and torsion. However, medalists had a higher E/E’ ratio, lower E/A ratio, and higher integrated backscatter (P , 0.05) compared with control subjects. Medalists had poor glycemic control but a favorable lipid profile with a lower LDL and higher HDL, possibly explaining the lack of coronary artery disease observed on MRI and the low prevalence of cardiovascular events in this population (1). Furthermore, the medalist group was slightly older, which emphasizes the cardiac protection they have exhibited, as age independently predicts an abnormal echocardiogram in patients with type 1 diabetes (2). Furthermore, to our surprise there was no difference in longitudinal and circumferential strain, strain rate, peak apical/basal rotation, peak apical back rotation rate, and peak LV twist/untwist between medalists and control subjects. This is in contrast with previous studies showing abnormal strain, rotation, and twist in patients with type 1 diabetes (3) and systolic dysfunction in type 1

diabetic adolescents during short exercise, implying a loss of systolic reserve (4). Medalists did exhibit diastolic dysfunction, evidenced by lower E/A ratios and higher E/E’ ratios, but this was mild and has been demonstrated in patients with a much shorter duration of diabetes (5). Furthermore, there was also evidence of only mild myocardial fibrosis, despite poor glycemic control and such an extreme duration of diabetes. The sample size of this study was small; however, we believe this is a unique cardiac phenotyping study in a unique group of patients with type 1 diabetes. In summary, we demonstrate protection from systolic dysfunction and abnormalities in cardiac structure with only mild diastolic dysfunction and myocardial fibrosis in medalists. This makes the medalists a unique cohort of patients with type 1 diabetes who merit further detailed study to identify the mechanistic basis of this protection from cardiovascular disease.

Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. A.F. analyzed echocardiographic data and wrote the first draft of the manuscript. O.A. recruited the patients and edited and reviewed the manuscript. K.P. and

1

School of Medicine, Manchester University, Manchester, U.K. Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and Central Manchester National Health Services Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K. 3 North West Heart Centre, University Hospital of South Manchester, Wythenshawe Hospital, Manchester, U.K., and Institute of Cardiovascular Sciences, University of Manchester, Manchester, U.K. 4 Weill Cornell Medical College in Qatar, Doha, Qatar 2

Corresponding author: Rayaz A. Malik, [email protected] and [email protected] © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

e-LETTERS – OBSERVATIONS

Medalists are a unique subset of patients with more than 50 years of type 1 diabetes. One would expect these patients to have significant microvascular and macrovascular complications. However, the Joslin observational study showed that of their medalists, a substantial proportion remained free of proliferative diabetic retinopathy (42.6%), nephropathy (86.9%), and neuropathy (39.4%) (1). Whether this protection extends to the heart is unknown. We therefore comprehensively investigated cardiac structure and function in 14 medalists and 9 control subjects. They underwent rest and stress (vasodilator) perfusion MRI to exclude significant coronary artery disease and echocardiography to quantify cardiac structure and left ventricular systolic function, including strain, strain rate, torsion, and diastolic dimensions. Pulsedwave Doppler sequences of the mitral valve assessing passive early (E) and active atrial (A) diastolic filling as well as tissue Doppler imaging of mitral annular movement allowed an assessment of diastolic dysfunction. Myocardial fibrosis was assessed using calibrated integrated backscatter. Comparing medalists to control subjects (Table 1), BMI, blood pressure, serum cholesterol, and triglycerides were

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Diabetes Care Volume 38, January 2015

Minimal Cardiac Abnormalities in Medalists

Table 1—Clinical, demographic, and echocardiographic data in the medalist group and control subjects with significant differences Control subjects Medalists (n 5 9) (n 5 14) P Age (years)

55.3 6 6.4

62.3 6 7.1

BMI (kg/m2)

26.3 6 2.9

28.5 6 4.4

,0.05 NS

Systolic blood pressure (mmHg)

119 6 12

127 6 14

NS

Diastolic blood pressure (mmHg) HbA1c (%)

72 6 11 5.85 6 0.52

61 6 14 8.29 6 1.05

NS ,0.0001

Total cholesterol (mmol/L)

5.03 6 0.74

4.56 6 1.11

NS

HDL (mmol/L)

1.56 6 0.37

2.04 6 0.72

,0.05 ,0.05

LDL (mmol/L)

2.80 6 0.62

2.11 6 0.94

Triglycerides (mmol/L)

1.12 6 0.48

0.90 6 0.39

NS

Ejection fraction (%)

50.6 6 2.6

50.6 6 1.4

NS

IVSd (mm)

9.62 6 0.29

9.91 6 0.27

,0.05

LVIDd (mm) LVPWd (mm)

38.42 6 2.74 9.72 6 0.45

38.14 6 4.60 9.74 6 0.34

NS NS

LVIDs (mm)

24.71 6 1.57

24.42 6 2.66

NS

Fractional shortening (%)

35.58 6 1.66

35.89 6 1.95

NS

EDD (mm)

57.76 6 4.7

57.80 6 2.7

NS

ESD (mm)

44.06 6 2. 70

44.07 6 1.7

NS

Mitral E velocity (cm/s)

67.23 6 11.18

82.86 6 14.74

0.02

Mitral A velocity (cm/s)

53.89 6 9.55

84.49 6 24.11

,0.001

E/A ratio

1.28 6 0.27

1.02 6 0.18

,0.01

Septal E’ (cm/s) Lateral E’ (cm/s)

7.69 6 1.30 6.99 6 1.59

7.08 6 0.96 6.72 6 1.19

NS NS

Average E’ (cm/s)

7.34 6 1.41

6.90 6 0.90

NS

E/E’ ratio

9.40 6 2.01

12.10 6 2.06

,0.01

Longitudinal strain (%)

18.63 6 3.57

19.45 6 3.27

NS

Peak longitudinal strain rate (%/s)

1.10 6 0.26

1.29 6 0.16

NS

Circumferential strain (%)

16.48 6 3.62

15.12 6 2.12

NS

Peak twist (8)

15.30 6 7.52

10.94 6 5.69

NS

2.43 6 1.93 101.04 6 35.28

3.05 6 2.77 88.96 6 24.22

NS NS NS

Peak untwist (8) Peak twist rate (8/s) Peak untwist rate (8/s)

94.26 6 55.24

93.02 6 41.77

Time to peak untwist rate (%)

112.30 6 9.60

111.15 6 7.96

NS

Peak apical rotation (8)

11.19 6 5.71

7.71 6 2.56

NS

7.09 6 2.78

6.82 6 3.14

NS

Peak apical back rotation rate (8)

73.61 6 32.24

78.16 6 27.26

NS

Time to peak apical back rotation rate (%)

118.81 6 13.77

115.53 6 12.17

NS

Septal signal (dB) LV posterior wall signal (dB)

222.13 6 2.73 220.33 6 2.73

219.50 6 2.33 219.07 6 2.09

,0.05 NS

Peak basal rotation (8)

Pericardial signal (dB)

20.31 6 0.38

20.41 6 0.35

NS

Septal cIBS (dB)

221.81 6 2.52

219.09 6 2.11

0.02

LV posterior wall cIBS (dB)

220.01 6 2.76

218.66 6 2.09

NS

Mean cIBS (dB)

220.91 6 2.22

218.88 6 1.72

,0.05

cIBS, calibrated integrated backscatter; EDD, end-diastolic dimension; ESD, end-systolic dimension; IVSd, interventricular septal thickness in end diastole; LVIDd, left ventricular internal diameter during diastole; LVPWd, left ventricular posterior wall dimension; LVIDs, left ventricular internal diameter during systole; NS, not statistically significant to 5% a-value.

M.St. acquired the echocardiographic sequences and assisted in analysis of images. S.G.R. reviewed and edited the manuscript. M.Sc. contributed to the discussion and reviewed and edited the manuscript. R.A.M. supervised the project, contributed to the data analysis, and edited the manuscript. 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 2. Wai B, Patel SK, Ord M, et al. Prevalence, predictors and evolution of echocardiographically defined cardiac abnormalities in adults with type 1 diabetes: an observational cohort study. J Diabetes Complications 2014;28:22–28 3. Piya MK, Shivu GN, Tahrani A, et al. Abnormal left ventricular torsion and cardiac autonomic dysfunction in subjects with type 1 diabetes mellitus. Metabolism 2011;60:1115–1121 4. Gusso S, Pinto TE, Baldi JC, Robinson E, Cutfield WS, Hofman PL. Diastolic function is reduced in adolescents with type 1 diabetes in response to exercise. Diabetes Care 2012;35: 2089–2094 5. Yazici D, Yavuz DG, Toprak A, Deyneli O, Akalin S. Impaired diastolic function and elevated Nt-proBNP levels in type 1 diabetic patients without overt cardiovascular disease. Acta Diabetol 2013;50:155–161

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