Hypoglycaemia in diabetes

Abstract

Why is hypoglycaemia important?The achievement and maintenance of blood glucose concentrations as near normal as possible are major targets of modern diabetes care. 1,2 Unfortunately, this increases the frequency of hypoglycaemia, so people with diabetes are all too familiar with insulin acting at the wrong time or intensity. 3 Hypoglycaemia, the most common acute complication of type 1 diabetes, usually develops rapidly. Its effects range from mild symptoms to brain damage or death. 4 Alarmingly, severe hypoglycaemia may occur with no perceived symptoms. In elderly people, it can mimic stroke. A young person with type 1 diabetes presenting with a seizure has a hypoglycaemia-induced convulsion unless proven otherwise.Hypoglycaemia is important because it limits therapeutic efforts to attain normoglycaemia and protect against long-term complications. It embarrasses, frightens and injures people with diabetes so that fear of hypoglycaemia can dominate their own and their families' lives. How common is hypoglycaemia?Major hypoglycaemia was experienced by 27% of patients with intensively treated type 1 diabetes in the Diabetes Control and Complications Trial (DCCT) but by only 2% of those in the UK Prospective Diabetes Study (UKPDS) of type 2 diabetes despite broadly similar levels of glycaemic control. 1,5 Thus, the rates of severe hypoglycaemia in type 2 diabetes are substantially lower than those seen in type 1 diabetes (of the order of 10% lower). 6 When it does occur, however, severe hypoglycaemia may have more serious consequences than in type 1 diabetes because older people have more comorbidities (Table 1). In the UKPDS study over the first 10 years, major hypoglycaemia rates varied with treatment modality: 2• diet treated patients: 0.5% • chlorpropamide: 0.4% • glibenclamide: 0.6% • insulin: 2.3%. Hypoglycaemia-associated autonomic failureThe pursuit of normoglycaemia in diabetes is bedevilled because 'hypoglycaemia begets hypoglycaemia' . 8 Indeed, the single most significant risk factor for severe hypoglycaemia is previous severe hypoglycaemia. In insulin deficient diabetes, (exogenous) insulin-levels do not decrease as glucose levels fall so the integrity of counter-regulatory hormonal responses assumes greater significance. The glucagon response to hypoglycaemia is blunted with increasing duration of type 1 diabetes so the catecholamine response becomes the critical defence mechanism. The epinephrine response is itself progressively blunted by antecedent hypoglycaemia, as is awareness of hypoglycaemia. The coexistence of deficient glucagon and epinephrine responses constitutes a major breach in counter-regulatory defence. The combination of defective glucose counter-regulation and impaired awareness of hypoglycaemia due to antecedent hypoglycaemia is termed hypoglycaemia associated autonomic-failure (HAAF) (Fig 1) Prediction and preventionThe symptoms of hypoglycaemia are idiosyncratic, non-specific and variable, even within an individual. The most important aspect of prevention is for patients to have...

Pharmacological Properties and Functional Role of Kslow Current in Mouse Pancreatic β-Cells

“…There is currently much interest in the islet field in investigating novel targets for drugs that might increase insulin secretion in a glucose-dependent manner ( MacLeod, 2004 ). Our work suggests that inhibition of K slow could be useful clinically, as K slow appears to help control Ca 2+ influx into the β-cell when glucose is elevated and that its inhibitors significantly enhance insulin secretion.…”

“…The similar potentiating effects of these two structurally unrelated K slow blockers suggest that targeting this channel may represent a new pharmacological approach for increasing insulin release from the pancreas without also producing hypoglycemia (MacLeod, 2004). Thus, blockers of K slow such as AZ and UCL 1684 could work in a similar manner to the K ATP channelblocking sulfonylureas, as both drug types block a resting K ϩ conductance, resulting in cell membrane depolarization, increased Ca 2ϩ uptake, and increased insulin exocytosis (Ferner and Neil, 1988;Aguilar-Bryan et al, 1995;Philipson and Steiner, 1995).…”

Experience of hypoglycaemia and strategies used for its management by community-dwelling adults with diabetes mellitus: a systematic review

“…While people with diabetes (regardless of type) may experience hypoglycaemia of varying levels of severity at some point in their lives, people with type 1 diabetes mellitus are reported to be more susceptible to hypoglycaemia and can experience as many as two episodes in a week 17–19 . Conversely, the incidence of hypoglycaemia is reported to be significantly less for people with type 2 diabetes mellitus in the initial stages of their disease 20,21 . However, as type 2 diabetes mellitus progresses, the beta cells of the pancreatic islets responsible for the production and secretion of insulin decrease, leading to an increased need for exogenous insulin 6 .…”