Hyperglycaemia and cognitive function--acute and chronic effects and work.

Diabetes is characterized by hyperglycaemia that, prior to the introduction of insulin, was seen as ‘a disease, so often hopeless’ [1]. Hyperglycaemia produces characteristic signs of polydipsia, polyuria and thirst in Type 1 diabetes and other symptoms such as confusion, stupor and coma if insulin is not introduced. A series of studies has shown that improved control of diabetes reduces the risk of microvascular complications in Type 1 [Diabetes Control and Complications Trial (DCCT) Study] [2] and Type 2 [UK Prospective Diabetes Study (UKPDS)] diabetes [3]. Thus, modern guidelines on management highlight the need to achieve a target glycated haemoglobin (HbA1C) of 53 mmol/mol [4] that is equivalent to 7.0% in the previously used notation [5]. Since the introduction of insulin, concerns have existed about iatrogenic hypoglycaemia. It engenders fear and is a barrier to achieving good control of blood sugar that is known to reduce the risk of complications in diabetes [6]. Episodes of severe hypoglycaemia impact on the ability of a person with diabetes to hold a driving licence in many countries including the UK [7], USA [8] and Canada [9]. A loss of awareness of hypoglycaemia is seen as a safety issue in the revised Driving Vehicle and Licensing Agency guidance on diabetes and driving that has been introduced as a result of a European Union directive [7]. Hypoglycaemia also restricts opportunities for employment [10]. Thus, there is an emphasis on hypoglycaemia in information on driving and employment. Hyperglycaemia has not received the same consideration in terms of safety and employment issues. A paper from Australia highlights the impact of hypoglycaemia on cognitive function in diabetic subjects who developed the condition in childhood [11]; 106 young adults with mean age of 20.5 years 12 years after the diagnosis of diabetes were compared to a control group (75 subjects) with no significant difference in IQ at baseline 12 years previously. These Type 1 diabetic subjects had significantly lower verbal IQ (VIQ) and full-scale IQ (FSIQ) scores than the control group. Hypoglycaemia predicted lower VIQ and early disease onset predicted lower performance IQ and FSIQ. Others have also noted an effect of severe hypoglycaemia in children on later cognitive function [12]. However, in the paper from Australia, when the participants with blood glucose levels >15 mmol/l at the time of testing (n = 34) were removed from the analysis, the group differences on VIQ and FSIQ became trends only (P < 0.06 and P < 0.07, respectively) [11]. This suggests there is an acute effect of hyperglycaemia on cognitive function. Others have confirmed that hyperglycaemia (blood glucose > 15 mmol/l) was associated with slowing of cognitive performance tests in Type 1 and Type 2 diabetic subjects, with an effect that was highly individualized and that impacted on ∼50% of subjects studied [13]. The acute effects have also been confirmed in Type 2 diabetic subjects by other authors [14]. Recent papers have indicated that there are long-term cognitive changes that are associated with hyperglycaemia. These deal with people with diabetes diagnosed at different stages of life and with Type 1 and Type 2 diabetes. An 18-year follow-up of the participants in the DCCT evaluated the participants using the same cognitive test battery as used at baseline in the DCCT. The group had a mean age of 45.7 years and a mean duration of diabetes of 24.5 years. Multivariate modelling identified five variables that predicted decline in psychomotor efficiency over the follow-up period: age, education, renal complication, proliferative diabetic retinopathy, and HbA1C. Long-term metabolic control and microvascular complications suggest hyperglycaemia as a cause of the cognitive decline. Test scores were unrelated to number of events of severe hypoglycaemia (defined as any event leading to seizure of coma) in this follow-up cohort [15]. This finding confirmed the results of an earlier study in a smaller group of adults with Type 1 diabetes with a mean duration of 31.5 years [16]. A second paper examined people with Type 2 diabetes aged 60–75 years in a population-based cohort with varying duration of diabetes from ≤3 years to ≥22 years. After age and sex adjustment, a significant relationship was observed with increasing severity of diabetic retinopathy (as measured by binocular digital retinal photography) for most cognitive measures. There was also a relationship between severity of diabetic retinopathy and mean HbA1C [17]. The papers showing an acute effect of hyperglycaemia [11,13,14] suggest that cognitive function can be affected when the blood glucose falls outside the range 4–15 mmol/l. Occupational physicians should be aware that hyperglycaemia as well as hypoglycaemia may impact on work performance. Individual factors, job factors and organizational factors need to be considered when making the assessment. Thus, when a person with diabetes EditorialS