The roles of genetics and glycaemic control in the development of LVH and Heart Failure in Type 2 Diabetes

Cardiovascular disease is the leading cause of morbidity and mortality in diabetes. Not everyone with diabetes develops either LVH or HF, proposed factors influencing this include glycaemic control and genetic factors. No studies to date have looked at the genetics of LVH and HF specifically in T2DM.This thesis investigates the importance of glycaemic control and genetic factors in HF and LVH in T2DM. Data from patients with T2DM in the Go-DARTS study were used to identify individuals with HF, non-HF controls, individuals with LVH and non-LVH controls. Weighted mean HbA1C was calculated for each of them. Logistic regression analysis and proportional hazard regression analysis were performed to investigate whether glycaemic control was independently related to LVH and HF. Genetic typing for published loci associated with glycaemic control was performed and included in the proportional hazard regression analysis. Genotyping for published SNPs associated with LVH was also performed and included survival analysis looking at LVH. Proportional hazard regression analysis showed weighted mean HbA1C >=8% was associated with LVH (HbA1C >=8 to 9% HR 1.25, CI 1.04-1.50, HbA1C >=9 to 10% HR 1.64, CI 1.29-2.09, HbA1C>=10% HR 1.80, CI 1.32-2.44, all p-values <0.05) and also demonstrated weighted mean HbA1C <6% was associated with LVH in T2DM (HR 1.95, CI 1.57-2.43, p-value <0.05). Two out of 9 published SNPs were associated with LVH in our cohort with T2DM: rs17132261 and rs2292462 (p-value <0.05).Proportional hazard regression analysis showed HbA1C >=8% was associated with HF development and HbA1C<6% was also associated with HF development in T2DM (HbA1C<6% HR 2.2, CI 1.7-2.9, >=8 to 9% HR 1.6, CI 1.2-2.0, >=9 to 10% HR 2.5, CI 1.8-3.4 and weighted mean HbA1C>=10% HR 4.82, CI 3.6-7.0, all p-values <0.05). Conditional logistic regression analysis also showed 3 SNPs previously associated with fasting glucose were associated with HF development here (rs560887, rs7944584 and rs10885122).19These results suggest glycaemic variation and genetic factors are important factors in HF and LVH in T2DM.

Name dc:type.qualificationname

Doctor of Medicine

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

University of Dundee

Year dc:date.issued

2015

Author dc:creator

• Parry, Helen

Advisors dc:contributor.advisor

• Lang, Chim
• Palmer, Colin

Language dc:language

eng

Identifier

oai:discovery.dundee.ac.uk:studenttheses/b7000b88-606c-4675-afe7-b720e33d7952

OAI identifier oai:identifier

oai:discovery.dundee.ac.uk:studenttheses/b7000b88-606c-4675-afe7-b720e33d7952