Contemporary evaluation of cardiovascular manifestations and related outcomes in type 2 diabetes mellitus : 'cardiovascular imaging and big data'

Abstract

Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease that constitutes a significant healthcare burden due to its associated micro- and macrovascular complications. Although cardiovascular manifestations in T2DM have been explored by a variety of studies, this thesis further assesses the association of diabetic risk factors and novel biomarkers with diabetic cardiomyopathy using prospective echocardiography studies, as well as the pharmacological effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular related outcomes in T2DM. This thesis is comprised of four sections. Section I introduces an overview of diabetes, diabetic complications, study population and research methods. Section II evaluates the cardiovascular manifestations, especially diabetic cardiomyopathy in patients with T2DM using transthoracic echocardiography. There was an increase in left ventricular (LV) hypertrophy (LVH), deterioration of systolic dysfunction and diastolic dysfunction from baseline to over 1-year follow-up. Women had a higher prevalence of LVH and diastolic dysfunction at baseline and follow-up compared with men. Moreover, Women, but not men, with pre-clinical diastolic dysfunction had a higher incidence of major adverse cardiovascular events (MACE) than those with normal diastolic function. Section III investigates mechanisms associated with cardiovascular manifestations in T2DM. Chapter 4 evaluates the association of adipocyte fatty acid-binding protein (AFABP) with longitudinal changes to LV remodelling and diastolic dysfunction in T2DM. Results found sex-specific AFABP in the highest quartile at baseline was independently associated with increase in LVM and deterioration of diastolic dysfunction. Moreover, AFABP was independently associated with incident MACE in patients with T2DM. We likewise explored the association of thrombospodin-2 (TSP2), a matricellular protein promotes fibrosis and anti-angiogenesis, with longitudinal changes to LV structure and function in T2DM. Chapter 5 showed TSP2 was positively and independently associated with deterioration of diastolic dysfunction. Section IV explores the cardiovascular related outcomes in T2DM using data retrieved from territory-wide database in Hong Kong. LVH and diastolic dysfunction predict incidence of heart failure (HF), which affects 9-22% of patients with T2DM. Similarly, chronic kidney disease (CKD) is another common complication in patients with T2DM, with over 30% of patients being affected by this comorbidity. We investigated the interplay of incident CKD and/or HF and their associations with prognostics in T2DM. Results found the time from baseline to incident CKD or HF was similar, while cardiorenal syndrome occurred soon after new-onset of CKD or HF. The presence of CKD or HF was associated with 3-fold risk of mortality, and concomitant CKD and HF (regardless of which comes first) was associated with 6-7-fold of mortality compared with CKD/HF-free status. SGLT2 inhibitors have been widely used due to its cardiorenal protective effect. we compared the risk of hyperkalemia, pneumonia and sepsis between new users of SGLT2 inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors. The use of SGLT2 inhibitors was associated with a lower risk of severe hyperkalemia, hyperkalemia, new initiation of potassium binders, while it did not increase risk of hypokalemia, compared to DPP-4 inhibitors. Moreover, prescribing SGLT2 inhibitors was also independently associated with a lower risk of pneumonia, sepsis and related death, compared with DPP-4 inhibitors.