Vascular disease and diabetes: is hypoglycaemia an aggravating factor?

Abstract

Acute hypoglycaemia provokes profound physiological changes affecting the cardiovascular system and several haematological parameters, principally as a consequence of sympatho-adrenal activation and counter-regulatory hormonal secretion. Many of these responses have an important role in protecting the brain from neuroglycopenia, through altering regional blood flow and promoting metabolic changes that will restore blood glucose to normal. In healthy young adults the cardiovascular effects are transient and have no obvious detrimental consequences. However, some of the effected changes are potentially pathophysiological and in people with diabetes who have developed endothelial dysfunction, they may have an adverse impact on a vasculature that is already damaged. The acute haemodynamic and haematological changes may increase the risk of localized tissue ischaemia, and major vascular events can certainly be precipitated by acute hypoglycaemia. These include myocardial and cerebral ischaemia and occasionally infarction. Established diabetic retinopathy often deteriorates after strict glycaemic control is instituted, the latter being associated with a threefold increase in frequency of severe hypoglycaemia, and enhanced exposure to mild hypoglycaemia. The possible mechanisms underlying these hypoglycaemia-induced effects include haemorrheological changes, white cell activation, vasoconstriction, and the release of inflammatory mediators and cytokines. The concept that acute hypoglycaemia could aggravate vascular complications associated with diabetes is discussed in relation to evolving comprehension of the pathogenesis of atherosclerosis and blood vessel disease.

Relationship of glycated haemoglobin and reported hypoglycaemia to cardiovascular outcomes in patients with type 2 diabetes and recent acute coronary syndrome events: The EXAMINE trial

“…This and other evidence prompted concern among the diabetes community that hypoglycaemia might lead to an increase in cardiovascular events, both fatal and non‐fatal. Three lines of evidence are among the support for the postulation that hypoglycaemia may contribute to cardiac events: (1) experimental hypoglycaemia causes sympathoadrenal activation and prolonged low‐grade inflammation and impairs endothelial function3; (2) spontaneous hypoglycaemia, particularly at night, has been associated with an increased risk of cardiac arrhythmia4; and (3) hypoglycaemia and low levels of glycated haemoglobin (HbA1c) are linked to an increased risk of death in patients with diabetes, hospitalized for myocardial infarction (MI) 5. In the present analysis, we have evaluated the relationships of glycaemic control and reported hypoglycaemia with the risk of major adverse cardiovascular events (MACE; cardiovascular death, non‐fatal MI, non‐fatal stroke), using data from the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) study.…”

Glycemic Control and Hypoglycemia

“…In addition, acute hypoglycemia may temporarily affect the cardiovascular system; however, in those with endothelial dysfunction, these changes can trigger major cardiovascular events, including myocardial and cerebral ischemia (55). Hypoglycemia also induces distinct modifications in cardiac repolarization (decreases in the height and width of the T-wave and/or lengthened corrected QT interval), which may heighten susceptibility to cardiac arrhythmias (56,57).…”

The impact of metabolic control and QTc prolongation on all-cause mortality in patients with type 2 diabetes and foot ulcers

“…The importance of hypoglycaemia has frequently been discussed as a plausible factor or mediator of this increased mortality, although no study has been able to show causality [10][11][12]. Hypoglycaemia alters several risk factors for mortality, including vasoconstriction and cytokine responses, and increases the likelihood of lethal arrhythmias [13][14][15][16][17].…”