Brian M Frier

Symptoms of hypoglycaemia in people with diabetes

The symptoms of hypoglycaemia are fundamental to the early detection and treatment of this side‐effect of insulin and oral hypoglycaemic therapy in people with diabetes. The physiology of normal responses to hypoglycaemia is described and the importance of symptoms of hypoglycaemia is discussed in relation to the treatment of diabetes. The symptoms of hypoglycaemia are described in detail. The classification of symptoms is considered and the usefulness of autonomic and neuroglycopenic symptoms for detecting hypoglycaemia is discussed. The many external and internal factors involved in the perception of symptoms are reviewed, and symptoms of hypoglycaemia experienced by people with Type 2 diabetes are addressed. Age‐specific differences in the symptoms of hypoglycaemia have been identified, and are important for clinical and research practice, particularly with respect to the development of acquired hypoglycaemia syndromes in people with Type 1 diabetes that can result in impaired awareness of hypoglycaemia. In addition, the routine assessment of hypoglycaemia symptoms in the diabetic clinic is emphasized as an important part of the regular review of people with diabetes who are treated with insulin.

Perceived symptoms of hypoglycaemia in elderly type 2 diabetic patients treated with insulin.

Elderly insulin‐treated diabetic patients have a high risk of severe hypoglycaemia, yet their hypoglycaemic symptom profile has attracted little research. In this study, the frequency and intensity of symptoms of hypoglycaemia were recorded using a validated questionnaire in 132 insulin‐treated diabetic patients, aged 70 years or more. Principal components analysis (PCA) was used to discover the factorial structure of the symptoms. Lightheadedness and unsteadiness were prominent symptoms in the elderly patients. PCA suggested three separate groups of symptoms: (1) those related specifically to impairment of co‐ordination and articulation; (2) more general neuroglycopenic symptoms, and (3) autonomic symptoms. The frequency and classification of hypoglycaemic symptoms in this elderly population is different from those seen in younger diabetic patients treated with insulin. Neurological symptoms of hypoglycaemia were more commonly reported and may be misinterpreted as features of cerebrovascular disease. Health professionals and carers involved in the treatment and education of diabetic patients should be aware of the age‐specific differences in hypoglycaemic symptoms.

Child and parental mental ability and glycaemic control in children with Type 1 diabetes

SUMMARY

Psychosocial factors and diabetes‐related outcomes following diagnosis of Type 1 diabetes in adults: The Edinburgh Prospective Diabetes Study

Aimsu2003 To examine prospectively the relationships between psychosocial variables and diabetes‐related outcomes in adults with newly diagnosed Type 1 diabetes.

Drug-induced hypoglycaemia in type 2 diabetes.

Introduction: Hypoglycaemia is a side effect caused by some therapies for type 2 diabetes, which can cause physical, social and psychological harm. Hypoglycaemia also prevents attainment of treatment goals and satisfactory glycaemic control. Areas covered: The risk of hypoglycaemia associated with commonly prescribed therapies, including metformin, sulphonylureas, dipeptidyl peptidase-4 enzyme (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists and thiazolidinediones, is reviewed in this paper (insulin-induced hypoglycaemia is not included). Other medications that are frequently co-prescribed in type 2 diabetes are also discussed, including anti-hypertensive drugs, antibiotics and fibrates, along with various important patient-related risk factors. Expert opinion: Hypoglycaemia is a common and potentially dangerous side effect of some medications used for type 2 diabetes. The risk of hypoglycaemia should always be considered when selecting and implementing a therapy, with a focus on the individual. Future research into new therapies should measure the frequency of hypoglycaemia prospectively and accurately. Hypoglycaemia has been shown to be a potentially life-threatening metabolic stress; therefore therapies that effectively manage diabetes without the risk of hypoglycaemia are likely to be favoured in the future.

Addison's disease in type 1 diabetes presenting with recurrent hypoglycaemia

Primary adrenal insufficiency (Addisons disease) often develops insidiously. Although a rare disorder, it is more common in type 1 diabetes mellitus. A 19 year old male with type 1 diabetes and autoimmune hypothyroidism experienced recurrent severe hypoglycaemia over several months, despite a reduction in insulin dose, culminating in an adrenal crisis. Recurrent severe hypoglycaemia resolved after identification and treatment of the adrenocortical insufficiency. In type 1 diabetes, undiagnosed Addisons disease can influence glycaemic control and induce severe hypoglycaemia.

Insulin analogues and other developments in insulin therapy for diabetes

Diabetes mellitus is a common chronic disorder, which is increasing in prevalence on a global scale. Insulin replacement therapy is required for all people with Type 1 diabetes and for many with Type 2 diabetes, to correct the metabolic abnormalities of these disorders. However, the pharmacokinetics and glucodynamics of available insulins have numerous limitations. Problems include delayed absorption from subcutaneous absorption sites (soluble [regular] insulin), and wide variability of absorption characteristics (insulin isophane suspension [NPH] and insulin lente) that is influenced by the adequacy of resuspension, and by a variable and insufficient duration of action, which usually requires intermediate-acting insulins to be administered twice-daily. All insulin preparations are associated with the common side effect of hypoglycaemia, and encourage weight gain.

Medically minimising the impact of hypoglycaemia in type 2 diabetes: a review

Introduction: Some therapies for type 2 diabetes (T2DM) are limited by hypoglycaemia, and this underestimated side effect carries an associated morbidity and financial burden. Large trials that have examined strict glycaemic control and cardiovascular outcomes in T2DM have highlighted the potential harm of exposure to hypoglycaemia in people with coronary heart disease. Areas covered: The responses to, and the morbidity associated with, hypoglycaemia in T2DM are discussed with identification of people most at risk of severe hypoglycaemia. The evidence base for non-pharmacological strategies and the risks of hypoglycaemia associated with various treatment modalities are examined. This review provides the clinician with a rational approach to the selection of different anti-diabetes drugs to minimize the risk of hypoglycaemia. Expert opinion: When managing T2DM, insulin and insulin secretagogues should be used judiciously and glycaemic targets individualized to avoid hypoglycaemia. Incretin mimetics present a lower risk of hypoglycaemia with similar efficacy as traditional agents in treating hyperglycaemia. The potential relationship between hypoglycaemia and precipitation of acute cardiovascular events is a highly topical area of research and may help determine what glycaemic targets are appropriate in people with T2DM.

Hypoglycaemic symptoms reported by children with Type 1 diabetes mellitus and by their parents

To compare the hypoglycaemic symptoms reported by children with Type 1 diabetes and signs observed by and symptoms reported to their parents, 101 pairs, consisting of a child with diabetes and one of their parents, were asked to report the frequency with which they experienced, or witnessed, each of 31 symptoms during hypoglycaemia. The hypoglycaemic symptoms reported by the children and the reported symptoms and signs observed by their parents were classified, using multivariate statistical analyses, and compared. Close agreement was observed between the children and their respective parents’ scores for frequencies of most symptoms/signs, as demonstrated by Spearman’s rank correlations (median τs = 0.25, p < 0.02). Principal Components Analysis of the symptoms/signs observed by the parents showed three factors: autonomic, neuroglycopenic, and behavioural disturbance. Analysis of the symptoms experienced by the children also identified three factors: behavioural disturbance, malaise and a third factor consisting of a combination of autonomic and neuroglycopenic symptoms. The parents could differentiate three separate groups of reported hypoglycaemic symptoms and signs (autonomic, neuroglycopenic, and behavioural disturbance) in their children. The children reported a similar group of behavioural symptoms but did not discriminate between autonomic and neuroglycopenic symptoms. These findings have important implications for the education of parents and children with Type 1 diabetes regarding the symptoms and signs of hypoglycaemia.

Dementia and Hypoglycemic Episodes in Patients With Type 2 Diabetes Mellitus

To the Editor: Dr Whitmer and colleagues reported a relationship between severe hypoglycemia and incident dementia in a large cohort of older people with type 2 diabetes. Although severe hypoglycemia may cause permanent cognitive impairment, the results of this study should be viewed with caution. It seems unlikely that a single episode of severe neuroglycopenia could increase the risk of dementia by 50%. Premorbid cognitive ability was assessed solely by educational attainment. Intellectually able people with diabetes may compensate for declining cognition and be less susceptible to the development of hypoglycemia. Vascular dementia is more common in people with lower cognitive ability and may confound a putative association with hypoglycemia. Cerebrovascular disease may both cause dementia and enhance the risk of hypoglycemia. Although the results were adjusted for the most overt diagnoses of stroke, which have a prevalence in the general population of 2% to 3%, no adjustment was made for subclinical cerebrovascular disease, which has a prevalence of around 18%. Other important confounding variables that were not excluded were a history of alcoholism, epilepsy, psychiatric illness, and head injury. Because the analysis did not adjust for many confounding factors, it was more likely to predict an association between hypoglycemia and dementia. Most severe hypoglycemia is treated in the community, and while 30% of people with insulin-treated type 2 diabetes require emergency assistance, very few are treated in the hospital. By contrast, hospital inpatient hypoglycemia has many causes, with renal insufficiency, malnutrition, sepsis, and liver disease being prominent factors often occurring in seriously ill people. In the study by Whitmer et al, episodes of severe hypoglycemia were identified retrospectively from coded entries in electronic hospital databases, which are frequently inaccurate. This may account for the surprising finding that 7.7% of those treated in the hospital for severe hypoglycemia had diet-controlled diabetes. Accurate measurement of the incidence of severe hypoglycemia in a diabetic population requires prospective recording; during this longitudinal study, most (unrecorded) hypoglycemic events in this cohort of patients would have occurred in thecommunity.Relianceonretrospective recordsofhospitaltreated hypoglycemia may have introduced selection bias, identifying people least able to self-manage diabetes and therefore most prone to severe hypoglycemia. Furthermore, the potential effects of changes in treatment modalities and of other comorbidities (such as hypertension) during the period of assessment have not been evaluated. Alex J. Graveling, MBChB, MRCP Brian M. Frier, BSc, MD, FRCP brian.frier@luht.scot.nhs.uk Department of Diabetes Royal Infirmary of Edinburgh Edinburgh, United Kingdom