Page 70 - Retail Pharmacy November/Decemeber 2020

Risk factors for hypoglycaemia in patients with diabetes include:3,17,18,19,20 • Longer duration of diabetes. • Older age. • Renal impairment and chronic kidney disease. • Liver disease. • Insulin use. • Sulfonylurea use. • Other antihyperglycaemic drugs when used in combination with either sulfonylurea or insulin. • Malnutrition with depletion in glycogen. • Recent history of severe hypoglycaemia. • Lower blood glucose levels (due to medications). • Hypoglycaemia-associated autonomic failure (HAAF). • Impaired awareness of hypoglycaemia (hypoglycaemia unawareness). • Pregnancy and breastfeeding. • Cognitive impairment. • Recent weight loss. • Bariatric surgery history. • Malabsorption due to primary gastrointestinal disease (eg, coeliac disease). • Primary hormonal deficiency in hormones responsible for raising blood glucose. • Lipohypertrophy (in patients who inject insulin). The following may also be considered risk factors but may be better described as acute precipitants of hypoglycaemia. Acute precipitants of hypoglycaemia can include: 3,19,20,21 • Errors in dose of antihyperglycaemic medication (eg, higher dose of insulin, incorrect insulin type administered). • Errors in or administration of antihyperglycaemic medication (eg, inadvertent administration of insulin in lipohypertrophy or muscle) • Stopping drugs that induce hyperglycaemia (eg, corticosteroids) • Carbohydrate intake variation (eg, missed meals, low carbohydrate content in meal, erratic timing of meals, while fasting, enteral feed cessation). • Exercise (particularly vigorous or of a kind one is not accustomed to) – due to glycogen depletion • Alcohol intake (can mask symptoms of hypoglycaemia and inhibit hepatic glucose output). Sulfonylureas and insulin can cause hypoglycaemia in patients with diabetes.20 Glibenclamide appears to have the highest risk, while glimepiride (due to active metabolites) and gliclazide (due to long half- life) also can cause severe hypoglycaemia.20 Other antihyperglycaemic drugs when given in combination with either insulin or a sulfonylurea can increase the risk of hypoglycaemia further, including: SGLT2 inhibitors, DPP-4 inhibitors, GLP-1 agonists, acarbose, metformin and pioglitazone.20 Clinical presentation Patients can experience varying symptoms of hypoglycaemia. It’s important that symptoms are recognised in order for patients to receive adequate treatment and correct hypoglycaemia events.3 It’s also possible for no symptoms of hypoglycaemia to be experienced. The symptoms of hypoglycaemia are classed as either neurogenic (autonomic) or neuroglycopenic. See Table 2 below for a detailed list of symptoms. Neurogenic symptoms are as a result of the counterregulatory activation of the autonomic nervous system in response to hypoglycaemia.22 The neuroglycopenic symptoms, however, are due to glucose deprivation in the central nervous system.22 Impaired awareness of hypoglycaemia Impaired awareness of hypoglycaemia (also known as hypoglycaemia unawareness) is clinically challenging as patients don’t receive prompts to adequately self-treat their episodes of hypoglycaemia.3 Patients with impaired awareness of hypoglycaemia are six times more likely to experience severe hypoglycaemia,23 and need to test their blood glucose more frequently.24 The proposed mechanism of impaired awareness of hypoglycaemia is hypoglycaemia associated autonomic failure (HAAF).25 HAAF can occur in type 1 diabetes and in advanced type 2 diabetes.26 HAAF is a cycle whereby repeated episodes of hypoglycaemia contribute to defective glucose counterregulation and an impaired awareness of hypoglycaemia, which in turn CPD ACTIVITY 69 causes further hypoglycaemia and further worsening of glucose counterregulation.27 It’s important to note that beta blockers and alcohol may also mask some of the signs and symptoms of hypoglycaemia.20 Nocturnal hypoglycaemia Nocturnal hypoglycaemia occurs at night-time during sleep. Sleep is a time of risk for the development of severe hypoglycaemia as the adrenergic response to hypoglycaemia is lower while sleeping.28 Nocturnal hypoglycaemia is common in adults and children with type 1 diabetes.29 Nocturnal self-monitoring of blood glucose or the use of continuous blood glucose monitoring systems are beneficial for patients who experience or are at risk of nocturnal hypoglycaemia.28 Exercise can increase the risk of hypoglycaemia seven to 12 hours afterwards, and one could be at risk in this timeframe, so may have an impact on nocturnal hypoglycaemia.3,28 However, this effect with exercise is variable between patients, and advice should be individually sought from their diabetes care team.3,28 Some patients will require dose reductions of medications and higher night-time blood glucose targets to avoid nocturnal hypoglycaemia.30 Impact on quality of life Hypoglycaemia can significantly affect a patient’s quality of life and functioning, including physical, mental and social function.1,31 It can also have effects on occupational activities such as travel, leisure activities, driving and employment.1,31 Hypoglycaemia can cause fear of hypoglycaemia and anxiety in patients.1 It’s proposed that this fear could potentially lead to compensatory activities by patients that hinder effective blood glucose control (such as overeating or reducing insulin doses to avoid hypoglycaemia).1,32 Table 2. Neurogenic and neuroglycopenic symptoms of hypoglycaemia9 TO PAGE 70 Neurogenic (autonomic) symptoms Neuroglycopenic symptoms Adrenergic mediated symptoms: Abnormal mentation *Shakiness *Irritability *Anxiety *Confusion *Nervousness *Difficulty speaking *Palpitations *Ataxia *Sweating *Paraesthesia *Dry mouth *Headaches *Pallor *Stupor *Pupil dilation If untreated: *Seizures, coma, and even death Cholinergic mediated symptoms: *Diaphoresis *Hunger *Paraesthesia RETAIL PHARMACY • NOV/DEC 2020