Hypoglycemia in Diabetes

Abstract

Iatrogenic hypoglycemia causes recurrent morbidity in most people with type 1 diabetes and many with type 2 diabetes, and it is sometimes fatal. The barrier of hypoglycemia generally precludes maintenance of euglycemia over a lifetime of diabetes and thus precludes full realization of euglycemia's long-term benefits. While the clinical presentation is often characteristic, particularly for the experienced individual with diabetes, the neurogenic and neuroglycopenic symptoms of hypoglycemia are nonspecific and relatively insensitive; therefore, many episodes are not recognized. Hypoglycemia can result from exogenous or endogenous insulin excess alone. However, iatrogenic hypoglycemia is typically the result of the interplay of absolute or relative insulin excess and compromised glucose counterregulation in type 1 and advanced type 2 diabetes. Decrements in insulin, increments in glucagon, and, absent the latter, increments in epinephrine stand high in the hierarchy of redundant glucose counterregulatory factors that normally prevent or rapidly correct hypoglycemia. In insulin-deficient diabetes (exogenous) insulin levels do not decrease as glucose levels fall, and the combination of deficient glucagon and epinephrine responses causes defective glucose counterregulation. Reduced sympathoadrenal responses cause hypoglycemia unawareness. The concept of hypoglycemia-associated autonomic failure in diabetes posits that recent antecedent hypoglycemia causes both defective glucose counterregulation and hypoglycemia unawareness. By shifting glycemic thresholds for the sympathoadrenal (including epinephrine) and the resulting neurogenic responses to lower plasma glucose concentrations, antecedent hypoglycemia leads to a vicious cycle of recurrent hypoglycemia and further impairment of glucose counterregulation. Thus, short-term avoidance of hypoglycemia reverses hypoglycemia unawareness in most affected patients. The clinical approach to minimizing hypoglycemia while improving glycemic control includes 1) addressing the issue, 2) applying the principles of aggressive glycemic therapy, including flexible and individualized drug regimens, and 3) considering the risk factors for iatrogenic hypoglycemia. The latter include factors that result in absolute or relative insulin excess: drug dose, timing, and type; patterns of food ingestion and exercise; interactions with alcohol and other drugs; and altered sensitivity to or clearance of insulin. They also include factors that are clinical surrogates of compromised glucose counterregulation: endogenous insulin deficiency; history of severe hypoglycemia, hypoglycemia unawareness, or both; and aggressive glycemic therapy per se, as evidenced by lower HbA 1c levels, lower glycemic goals, or both. In a patient with hypoglycemia unawareness (which implies recurrent hypoglycemia) a 2-to 3-week period of scrupulous avoidance of hypoglycemia is advisable. Pending the prevention and cure of diabetes or the development of methods that provide glucose-regulated insulin replacement or secre...

Central nervous system: a conductor orchestrating metabolic regulations harmed by both hyperglycaemia and hypoglycaemia

“…The concept of hypoglycemia-associated autonomic failure in DM posits that recent antecedent hypoglycaemia causes both defective glucose counterregulation and hypoglycaemia unawareness [28,29]. By shifting glycaemic thresholds for the sympathoadrenal (including epinephrine) and the resulting neurogenic responses to lower plasma glucose concentrations, antecedent hypoglycaemia leads to a vicious cycle of recurrent hypoglycaemia and further impairment of glucose counterregulation.…”

“…Hypoglycaemia is a frequent side-effect of treatment with insulin and sulfonylureas for people with DM, threatening potentially serious morbidity and preventing optimal glycaemic control [28,30]. Indeed, fear of hypoglycaemia and development of syndromes such as impaired awareness and counterregulatory deficiency provide additional hazards for intensification of treatment.…”

“…Children may be more prone to acute metabolic insults, and there is evidence of developmental disadvantage associated with hypoglycaemic events [45]. Recurrent hypoglycaemia is well established to diminish counter-regulatory responses to further hypoglycaemia, as already mentioned [28,29]. However, despite significant patient concern, the impact of recurrent hypoglycaemia on cognitive and neural function remains controversial.…”

Real-time continuous glucose monitoring (CGM) integrated into the treatment of type 1 diabetes: Consensus of experts from SFD, EVADIAC and SFE

“…In the ENTRED 2007 study [10], only 26% of adult patients with type 1 diabetes reached an HbA 1c below 7% and 38% remained above 8%. The incidence of hypoglycaemia is common in patients with less than 7% HbA 1c [11] and increases with the duration of diabetes [12]. Frequent hypoglycaemias are associated with a decreased threshold of perception of hypoglycaemia, which increases the risk of severe hypoglycaemia and can reduce adherence to treatment [13].…”

Approach to assessing the economic impact of insulin‐related hypoglycaemia using the novel Local Impact of Hypoglycaemia Tool

“…In severe cases, hypoglycaemia can cause seizure, loss of consciousness, coma and even death 3. Insulin therapy is the antidiabetic treatment that is most associated with hypoglycaemia.…”