Covid-19 and T2D – when two pandemics meet

Posted in Covid-19, Diabetes, Obesity & Metabolism

May 13, 2020

13th May 2020, Dr Chee L Khoo

Covid-19 have exposed the numerous risks patients with type 2 diabetes (t2D) face when the two pandemics meet head on. We have seen that patients with diabetes are over-represented in patients hospitalised with Covid-19 in Wuhan. Patients with diabetes are also affected more severely if they contracted Covid-19 especially if glycaemic control is suboptimal. Many of our patients with T2D also have heart disease including coronary artery disease and heart failure and these patients are also worse off if they contract Covid-19. As most of these patients are managed in primary care by their GP, it is probably timely to revisit cardiovascular mortality in patients with T2D.

Patients with T2D have higher cardiovascular morbidity and mortality. Patients with T2D have a 54% increase risk of myocardial infarct and 72% increase in ischaemic strokes compared with patients without T2D (1). They also have a 33% increase in hospitalisation for heart failure compared with those without T2D (2). In patients with T2D without overt cardiac disease, asymptomatic left ventricular dysfunction was detectable in 68% of patients within 5 years of diagnosis (3).

Traditionally, we were taught that for every 1% reduction in HbA1c, we can reduce myocardial infarction by 14%, strokes by 12% and amputations by 43% (4). Patients with T2D loses at least 6 years of life (plus another 6 of disability free life) compared with those without T2D. If the patient also have heart disease, they lose 12 years of life. If we are able to prevent heart disease, we add 8.2 years to their life. In patients with diabetes and heart disease who are under 50 years old, the extension of life stretches out to 20 years! (5).

The advent of SGLT2 inhibitors have really change the scene over the last decade. While the SGLT2 inhibitor class is potent in reducing HbA1c and getting our patients nearer to target, international guidelines for management of hyperglycaemia in T2D has become a lot less glucocentric. While the above numbers look impressive in reducing micro and macrovascular complications, the emphasis is now on selecting the next agent after metformin by considering whether the patients is at risk of cardiovascular events. The latest AHA/EASD guidelines have an algorithm that reflects that emphasis. You will recall that we explore the DECLARE TIMI 58 trial results in November 2018.

DECLARE-TIMI 58 was a large (17,160 patients) trial of dapagliflozin in patients with T2D and either established ASCVD or multiple risk factors for ASCVD. 17,160 patients with T2D were evaluated. 10,186 of those patients did not have established CV disease which is an important point because the study replicates what we see in general practice. Patients were followed up for 4.2 years, much longer than the other SGLT2 trials (EMPA-REG and CANVAS).

But if we looked into just cardiovascular death and hospitalisation for health failure, there was a 17% reduction with dapagliflozin. Most of the benefit came from reduction in heart failure (27% reduction). Interestingly, most patients did not have a history of heart failure at baseline. There were no difference in cardiovascular deaths between the groups.

From this month, dapagliflozin (Forxiga and XigDuo) is indicated in adults with Type 2 diabetes mellitus and established cardiovascular disease or risk factors for cardiovascular disease to reduce the risk of hospitalisation for heart failure.

Management of T2D is not just management of glucose. T2D is a multi-system disease and we all know that patients with T2D most commonly die of cardiovascular related deaths. Most of the damage occurs prior to symptoms of any heart disease surfaces and this usually occurs during their care in general practice under the watchful eye of the primary care team. You can make a giant difference in reducing those numbers. Your selection of the next agent after metformin is vital in altering the trajectory of complications in patients with T2D.

References

Shah AD, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1· 9 million people. Lancet Diabetes Endocrinol. 2015;3:105 113.
Cavender MA, et al. Impact of Diabetes Mellitus on Hospitalization for Heart Failure, Cardiovascular Events, and Death Outcomes at 4 Years From the Reduction of Atherothrombosis for Continued Health (REACH) Registry. Circulation. 2015;132:923 931.
Faden G et al. The Increasing Detection of Asymptomatic Left Ventricular Dysfunction in Patients With Type 2 Diabetes Mellitus Without Overt Cardiac isease: Data From the SHORTWAVE Study. Diabetes Res Clin Pract. 2013;101(3):309-16.
Stratton IM et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405-12.
Emerging Risk Factors Collaboration. Association of Cardiometabolic Multimorbidity With Mortality JAMA. 2015;314(1):52-60.