Reconsidering the role of glycaemic control in cardiovascular disease risk in type 2 diabetes: A 21st century assessment

Abstract

It is well known that the multiple factors contributing to the pathogenesis of type 2 diabetes (T2D) confer an increased risk of developing cardiovascular disease (CVD).Although the relationship between hyperglycaemia and increased microvascular risk is well established, the relative contribution of hyperglycaemia to macrovascular events has been strongly debated, particularly owing to the failure of attempts to reduce CVD risk through normalizing glycaemia with traditional therapies in high-risk populations. The debate has been further fuelled by the relatively recent discovery of the cardioprotective properties of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Further, as guidelines now recommend individualizing glycaemic targets, highlighting the importance of achieving glycated haemoglobin (HbA1c) goals safely, the previously observed negative influences of intensive therapy on CVD risk might not present if trials were repeated using current-day treatments and individualized HbA1c goals. Emerging longitudinal data illuminate the overall effect of excess glucose, the impacts of magnitude and duration of hyperglycaemia on disease progression and risk of CVD complications, and the importance of glycaemic control at or early after diagnosis of T2D for prevention of complications. Herein, we review the role of glucose as a modifiable cardiovascular (CV) risk factor, the role of microvascular disease in predicting macrovascular risk, and the deleterious impact of therapeutic inertia on CVD risk. We reconcile new and old data to offer a current perspective, highlighting the importance of effective, early treatment in reducing latent CV risk, and the timely use of appropriate therapy individualized to each patient's needs.

Acute pharmacodynamic responses to exenatide: Drug‐induced increases in insulin secretion and glucose effectiveness

“…This suggests that genetic variants associated with glycaemic effects may also contribute to predicting the magnitude of cardiovascular risk reduction. Comparative effectiveness confirmed that GLP‐1R agonists providing the largest HbA1c lowering also provided the greatest cardioprotection 28,29 …”

“…Comparative effectiveness confirmed that GLP-1R agonists providing the largest HbA1c lowering also provided the greatest cardioprotection. 28,29 F I G U R E 3 Correlation of rate of glucose disappearance with glucose effectiveness (S g ). Rates of glucose disappearance (vertical axis) are plotted as a function of glucose effectiveness (S g ) (horizontal axis).…”

Acute pharmacodynamic responses to exenatide: Drug-induced increases in insulin secretion and glucose effectiveness

“…A similar conclusion was reached in a comparative effectiveness analysis comparing different GLP1R agonists. The drugs providing the largest HbA1c-lowering also provided the greatest cardioprotection 33,34 .…”

“…There has been discussion about challenges in estimating glucose effectiveness from data derived from intravenous glucose tolerance tests. For example, it has been suggested that higher levels of insulin secretion may lead to higher mathematical estimates of glucose effectiveness; it has been challenging to identify detailed mechanisms accounting for these higher estimates of S g 15,34 . In any case, it is theoretically possible that the exenatide-induced increase in insulin secretion may contribute to the larger mathematical estimates of S g .…”

In Kliniken wird Diabetes vielfach nicht diagnostiziert

“…Der Anteil von Menschen mit einem nicht-diagnostizierten Diabetes wird in den Krankenhausstatistiken logischerweise nicht erfasst. Da die Patienten mit einem Diabetes (unabhängig von der Diagnosestellung) vermehrt mikro-und makrovaskuläre Komplikationen haben oder entwickeln, ist die Kenntnis eines manifesten Diabetes für eine adäquate Behandlung dieser Patienten im Krankenhaus und für deren weiteres Schicksal nach der Entlassung sehr wichtig [6,7,8].…”