DIABETES CARE, VOLUME 23, NUMBER 3, MARCH 2000 305 A cute hypoglycemia induces cognitive dysfunction as a consequence of neu- roglycopenia. Cognitive functions that deteriorate include simple and choice reaction times, speed of arithmetic calcula- tion, verbal fluency, color identification, trail making and digit symbol test perfo r- mance, digit span, and other short -t erm memo ry indices (1). Mood states are also a ffected by mild hypoglycemia, which causes a reduction in levels of energet ic a rousal and an increase in tense arousal (2). Acute hypoglycemia can pro v o k e lo nger- term effects, even after norm o- glycemia has been res t o red. In nondiabetic and diabetic subjects, the symptomatic and neuroendocrine responses to acute hypo- glycemia are diminished after antecedent (episodic) hypoglycemia that has occurred within the previous 72 h (3–7). Indeed, the catecholamine response to hypoglycemia may take between 6 days and 4 weeks to ret urn to a normal magnitude (8). The effects of acute mild hypoglycemia on cog- nitive functions appear to be less pro l o nged, in that cognitive function recovers within 1 h of the restoration of normoglycemia (9–13). The long-term effects of acute hypoglycemia on other mental states such as mood and general well-being have received less atten- tion. Mood changes during acute hypogly- cemia persist for at least 30 min after restoration of normoglycemia (2), wherea s relatively brief nocturnal hypoglycemia is not associated with any cognitive impair- ment the following morning (14,15) but is associated with greater levels of fatigue in response to exercise the next day (15). S evere hypoglycemia, which is defined as an episode requiring external assistance for reco very, causes pronounced neuro gly- copenia that results in a profound degree of cognitive dysfunction and (rarely) can cause permanent neurological impairment (16–18). Fort una t ely, most patients appear to make a complete and rapid reco very after normoglycemia is res t o red, although anecdotal observation suggests that some patients have cognitive impairment for m o re protracted periods. Exposure to repeated episodes of severe hypoglycemia may possibly result in persistent cognitive im p a irment in some patients (19–23), although this has been disputed (24,25). No previous studies have examined the timing of reco very of cognitive function and mood after a single episode of severe hypo- glycemia. Delayed rec o very of cognitive functions after severe hypoglycemia could have potentially important effects on perfo r- mance of activities such as work or driving. The purpose of the present study was to examine the temporal changes in mood states and cognitive functions after a single spontaneous episode of severe hypoglycemia in people with insulin-treated diabetes. F rom the Department of Diabetes (M.W.J.S., F.M.E.E., B.M.F .), Royal Infirma ry of Edinburgh; and the Depart- ment of Psychology (I.J.D.), University of Edinburgh, Edinburgh, Scotland, U.K. Ad d ress correspondence and reprint requests to Brian M. Frier, FRCPE, Department of Diabetes, Royal I nfirma ry of Edinburgh, Lauriston Place, Edinburgh EH3 9YW, Scotland, U.K. Received for publication 3 May 1999 and accepted in revised form 2 December 1999. Abbreviatio ns : ANO VA, analysis of variance; BD, Block Design; BDS, Backward Digit Span; CFSA, Cog- nitive Function Self-Appraisal Scale; DS, Digit Symbol; FDS, Forwa rd Digit Span; FM, Figural Memory; HAD, Hospital Anxiety and Depression Scale; hypo subjects, subjects with insulin-treated diabetes who had expe- rienced a spontaneous episode of severe hypoglycemia during the preceding year; IQ, intelligence quotient; I T, Inspection Time; LM, Logical Memory; NART, National Adult Reading Test; PAS AT, Paced Auditory Ser- ial Addition Task; RT, Reaction Time; TMB, Trail-Making Test B; UW IST, University of Wales Institute of Sci- ence and Technology; VCD, Visual Change Detection; WAIS-R, Wechsler Adult Intelligence Scale-Revised. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Re c o v e ry of Cognitive Function and Mood After Severe Hypoglycemia in Adults With Insulin-Treated Diabetes O R I G I N A L A R T I C L E O BJE C TI V E — Acute hypoglycemia in humans impairs cognitive functions and alters mood states. The time requ ired for cognitive functions and moods to retu rn to normal after an acute episode of severe hypoglycemia is unknown. RESEARCH DESIGN AND M ETHODS — Cognitive functions and moods were stud- ied prospectively in 20 subjects with insulin-treated diabetes who had recently experienced a spontaneous episode of severe hypoglycemia (“hypo” subjects) and 20 matched control sub- jects with insulin-treated diabetes who had not experienced severe hypoglycemia during the preceding year. The hypo subjects had a history of a greater number of episodes of severe hypo- glycemia ( P = 0.000). Cognitive function tests and mood scales were administered at 1.5, 9, and 30 days after the severe hypoglycemia and at similar intervals for the control subjects. RE SU LTS — For most of the cognitive tests, no evidence of a “hangover” effect of the acute hypoglycemia on cognitive function was observed ( P 0.05). A trend was noted for levels of hedonic tone (P = 0.082) and energetic arousal (P = 0.053) to improve with time in the hypo subjects but not in the control subjects. However, the hypo subjects had chronically elevated levels of depression ( P = 0.011) and anxiety ( P = 0.049) and persistently perf ormed more poorly in several cognitive tests, such as the Digit Symbol Test ( P = 0.009) and the Stroop Task ( P = 0.007). C O N C L U SI O N S — These results suggest that, in general, recovery from any acute cogni- tive decrement after severe hypoglycemia was complete by 1.5 days. The cognitive decremen ts and altered mood states noted in the hypo subjects may be persistent and may be a consequence of previous exposure to recu rrent episodes of severe hypoglycemia. Diabetes Care 2 3 :3 0 5–312, 2000 MARK W.J. STRACHAN, MRCP IAN J. DEARY , PHD FIONA M.E. EWING, MRCP BRIAN M. FRIER, FRCPE Epidemiology/Health Services/Psychosocial Research