Clinical approaches to treat impaired awareness of hypoglycaemia

Abstract

Impaired awareness of hypoglycaemia (IAH) affects between 25% and 30% of all people with type 1 diabetes (T1D) and markedly increases risk of severe hypoglycaemia. This greatly feared complication of T1D impairs quality of life and has a recognised morbidity. People with T1D have an increased propensity to hypoglycaemia as a result of fundamental physiological defects in their ability to respond appropriately to a fall in blood glucose levels. With repeated exposure to low glucose, many then develop a condition referred to as IAH, where there is a reduced ability to perceive the onset of hypoglycaemia and take appropriate corrective action. The management of individuals with IAH relies initially on its identification in the clinic through a detailed exploration of the frequency of hypoglycaemia and an assessment of the individual’s ability to recognise these episodes. In this review article, we will address the clinical strategies that may help in the management of the patient with IAH once identified, who may or may not also suffer from problematic hypoglycaemia. The initial focus is on how to identify such patients and then on the variety of approaches involving educational programmes and technological approaches that may be taken to minimise hypoglycaemia risk. No single approach can be advocated for all patients, and it is the role of the health care professional to identify the clinical strategy that best enables their patient to achieve this goal.

Hypoglycaemia: Still the main drawback of insulin 100 years on: “From man to mouse”

“…Despite vast improvements in insulin formulation, education, treatment plans and technology, the incidence of hypoglycaemia has remained constant. These categories are addressed in depth in a comprehensive review by Farrell and McCrimmon 22 . Notable advancements have been accomplished in insulin preparations and technology.…”

“…Since the original animal‐derived insulins, there has been much research into the formulation of long‐ and short‐acting insulin and finally to analogue insulins. These are scientifically engineered preparations that improve the overall action of therapeutic insulin 22 . Technological advancements include the generation of insulin pumps and closed‐loop systems, acting as an artificial pancreas, in addition to widely available continuous‐glucose‐monitoring (CGM) equipment, 22 removing the requirement for finger‐pricking.…”

“…In summary, those with IAH take longer to experience symptoms meaning they face more severe hypoglycaemic events and have reduced hormonal capacity to overrule hypoglycaemia. Technological advancements include the generation of insulin pumps and closed-loop systems, acting as an artificial pancreas, in addition to widely available continuousglucose-monitoring (CGM) equipment, 22 removing the requirement for finger-pricking.…”

Altered Caffeine Metabolism Is Associated With Recurrent Hypoglycemia in Type 2 Diabetes Mellitus: A UPLC–MS-Based Untargeted Metabolomics Study

“…IAH is characterized by lower glycemia thresholds of counter-regulatory responses (8), markedly increasing the risk of severe hypoglycemia up to sixfold (9). Thus far, the clinical approaches to IAH treatment are limited to patient education, frequent glucose monitoring, and appropriate adjustment of the therapy target (10). The underlying mechanism remains unclear, but includes alternatives of fuel transport and/or storage (11,12), neuronal modulators (13,14), changes in the transduction of the energy signal into neuronal firing rates (15), may involve multiple steps in the integrative networks that control glucose homeostasis (8).…”

Protective and risk factors of recurrent severe hypoglycemia in adults with type 1 diabetes: A cross-sectional analysis of baseline data from the PR-IAH study

“…This condition is considered lethal and is the cause of death in 4-10% of children and adolescents with T1D [3]. Repeated exposure to glucose levels below 3 mmol/l can blunt physiological warning signs, leading to impaired awareness of hypoglycemia (IAH), which increases the risk of SH by three-to six-folds [4][5][6]. In particular, recurrent SH (RSH) deteriorates cognitive dysfunction characterized by severe memory and cognitive processing speed impairment in adults with diabetes [7,8].…”