Differential sex and ethnic cardiac remodelling in a prospectively recruited multi-ethnic cohort of 530 asymptomatic people with type 2 diabetes.

Presenting Author(s)

• 

  Alice C. Cowley, MB

  Clinical Research Fellow
  University of Leicester
  Leicester, England, United Kingdom

Primary Author(s)

• 

  Alice C. Cowley, MB

  Clinical Research Fellow
  University of Leicester
  Leicester, England, United Kingdom

Co-Author(s)

• AD

  Abhishek Dattani, MBBS

  Clinical Research Fellow
  University of Leicester
  Leicester, United Kingdom
• JY

  Jian L. Yeo, MD

  Clinical Research Fellow
  University of Leicester, United Kingdom
• KP

  Kelly Parke

  Research radiographer
  University Hospitals of Leicester
  Leicester, United Kingdom
• AM

  Anna-Marie Marsh, PhD

  Senior Chief Cardiac Physiologist
  The University of Leicester
  Leicester, England, United Kingdom
• MS

  Manjit Sian

  Cardiac physiologist
  University Hospitals of Leicester
  Leicester, United Kingdom
• JW

  Joanne Wormleighton, DCR(R)

  Lead research radiographer
  University Hospitals Leicester
  Leicester, England, United Kingdom
• JA

  Jayanath Arnold, PhD

  Associate Professor
  University of Leicester, England, United Kingdom
• 

  Anvesha Singh, PhD

  Associate Professor
  University of Leicester
  Leicester, England, United Kingdom
• GG

  Gaurav Gulsin, PhD

  Clinical Lecturer
  University of Leicester
  Leicester, United Kingdom
• EB

  Emer M. Brady, PhD, BSc

  Post doctoral research fellow
  University of Leicester
  Leicester, England, United Kingdom
• GM

  Gerry P. McCann, MD

  Professor
  University of Leicester
  Leicester, England, United Kingdom

Background: The importance of sex and ethnic stratification in epidemiology is increasingly recognised, particularly in cardiometabolic disease where differences in pathophysiology and outcomes are often underexplored. The aim of this work was to identify sex and ethnic specific differences in cardiac remodelling in T2D using cardiac magnetic resonance (CMR) imaging.

Methods: Middle-aged adults with T2D and no history or symptoms of cardiac disease were prospectively recruited at a single centre (NCT03132129) and compared to a cohort of healthy controls (HC) recruited to the same study and HC from UK biobank. All participants underwent long and short axis cine imaging by CMR and participants recruited locally underwent contrast enhanced imaging including pre/post contrast T1 maps using a modified inversion recovery Look-Locker technique and adenosine stress/rest perfusion, using a dual-sequence T1-weighted saturation recovery gradient echo sequence, with fully automated blood flow quantification played on pixel-wise perfusion maps. The relative percentage difference between T2D and HC by sex and ethnicity for key CMR parameters of subclinical cardiac dysfunction were calculated and multivariable linear regression employed to determine if observed differences were independent of age, ethnicity/sex, body mass index and systolic blood pressure. Interaction terms for sex and ethnicity (White European [WE] vs. South Asian [SA]) by diabetes status were then explored for key cardiac remodelling parameters.

Results: 530 T2D (321 male/209 female) were compared to 317 HC (195male/122 females) Table 1. Both males and females with T2D had higher LV mass-to-volume ratio, lower global longitudinal strain (GLS) but higher global circumferential strain (GCS) relative to HC. GCS was increased more significantly in diabetic females (beta 1.28, p 0.001). For ethnicity, mass:volume ratio was disproportionately higher (beta 0.13, p < 0.001) and GLS was disproportionately reduced (beta -1.26, p 0.001) in SA with T2D compared to WE with T2D, independent of age, sex, BMI and systolic blood pressure. Both male and female T2D participants had significantly higher extracellular volume and lower myocardial perfusion reserve (Figure 1) without significant sex or ethnic interactions by diabetes status.

Conclusion: The pattern and magnitude of subclinical cardiac dysfunction evident in asymptomatic T2D is similar between the sexes, apart from GCS which is increased more in females. SA with T2D had disproportionately greater mass:volume and reduced GLS compared to their WE counterparts and may partly explain increased cardiovascular risk in SA with T2D.

Baseline characteristics of female/male people with type 2 diabetes and healthy controls

Baseline characteristics	Females		Males
	Type 2 diabetes (n=209)	Healthy volunteer (n=122)	Type 2 diabetes (n=321)	Healthy volunteer (n=195)
Age, years	62 (7)	59 (8)	64 (7)	58 (8)
White ethnicity	141 (67%)	65 (53%)	217 (68%)	105 (54%)
Hypertensive	111 (53%)	7 (6%)	202 (63%)	11 (6%)
Diabetes duration, years	10 (5-15)	-	10 (5-15)	-
Body mass index, kg/m2	29.7 (26.5-34.6)	23.7 (22.2-25.8)	29.2 (26.0-32.7)	25.7 (23.6-27.7)
Systolic BP, mmHg	138 (17)	125 (19)	136 (16)	130 (15)
Heart rate, BPM	78 (12)	67 (9)	74 (13)	65 (9)
HbA1c, %	7.10 (6.60-7.80)	-	7.10 (6.50-7.85)	-
LV mass:volume, g/mL	0.89 (0.13)	0.69 (0.13)	0.92 (0.15)	0.75 (0.15)
GCS, %	20.9 (2.4)	17.6 (3.2)	19.0 (2.5)	16.9 (2.6)
GLS, %	17.0 (2.2)	20.5 (2.7)	15.9 (2.3)	19.3 (3.0)
ECV, %	28 (3)	27 (2)	27 (3)	25 (2)
MPR	2.7 (0.8)	3.0 (0.7)	2.8 (0.8)	3.2 (0.9)
BP, blood pressure, BPM, beats per minute; ECV, extracellular volume; GCS, global circumferential strain; GLS, global longitudinal strain; HbA1c, glycosylated haemoglobin; MPR, myocardial perfusion reserve

Subclinical cardiac dysfunction with relative percentage differences in males and females with type 2 diabetes compared to their healthy counterparts
Subclinical cardiac dysfunction with relative percentage differences in White Europeans and South Asians with type 2 diabetes compared to their healthy counterparts