RD Lawrence Lecture 2015 Old habits are hard to break: lessons from the study of hypoglycaemia

Abstract

Despite the introduction of newer technologies and improved insulin formulations, recurrent hypoglycaemia continues to affect the lives of many people with Type 1 and Type 2 diabetes. Developing strategies or therapies designed to prevent or minimize hypoglycaemia risk is of utmost importance to help individuals safely achieve glycaemic targets. Novel, educational or behavioural approaches need to be based on a clear understanding of the mechanisms underpinning both the detection of hypoglycaemia and why repeated exposure to hypoglycaemia leads to the development of a clinical syndrome referred to as impaired awareness of hypoglycaemia. In the present review, I propose that impaired awareness of hypoglycaemia may represent a form of learning called habituation, a response that, at a cellular level, represents a biological adaptation designed to protect the organism from future exposure to that stressor. In diabetes, this survival response to low glucose is, however, overwhelmed by high systemic insulin levels resulting from exogenous insulin therapy, leading to progressively more severe hypoglycaemia. A recognition of the underlying mechanism means that the development of impaired awareness of hypoglycaemia can perhaps be better understood and explained to individuals with diabetes, and novel therapeutic approaches such as dishabituation or cognitive behavioural therapies can be considered.

Impaired hypoglycaemia awareness in type 1 diabetes: lessons from the lab

“…Likewise, recovery of CRR through hypoglycaemia avoidance [47] is in keeping with the second characteristic of habituation; namely, 'if the stimulus [hypoglycaemia] is withheld, the response [CRR] tends to recover over time (spontaneous recovery)'. In fact, studies in rodent and human models of IAH have reported findings consistent with six of the nine principles of habituation proposed by Thompson and Spencer (for review see [48]). …”

ISPAD Clinical Practice Consensus Guidelines 2018: Assessment and management of hypoglycemia in children and adolescents with diabetes

“…IAH is not an “all or none phenomenon” but reflects a continuum in which differing degrees of impaired awareness can occur and can vary over time in any one individual. IAH is proposed to be a result of intracellular and extracellular physiological adaptations to recurrent hypoglycemia that are in essence survival responses designed to protect the cell from subsequent exposure to glucose deprivation . This adaptive process is referred to as habituation .…”

“…IAH is proposed to be a result of intracellular and extracellular physiological adaptations to recurrent hypoglycemia that are in essence survival responses designed to protect the cell from subsequent exposure to glucose deprivation. 112 This adaptive process is referred to as habituation. 113 A habituated response can also be, at least temporarily, reversed by the introduction of a novel (heterotypic) stimulus (dishabituation).…”

An international survey on hypoglycemia among insulin-treated type I and type II diabetes patients: Turkey cohort of the non-interventional IO HAT study

“…Hypoglycemia is the main hurdle for achieving optimal glycemic control in patients on insulin therapy [ 3 ]. Development of strategies or therapies to control hypoglycemia is important to help individuals achieve glycemic targets [ 4 ]. Achieving optimum glycemic control following the diagnosis of T2DM is vital to improving clinical outcomes, yet many patients and clinicians are hesitant to initiate and intensify insulin therapy.…”