Computer assisted learning is an effective way of teaching endocrinology.

OBJECTIVES: Computers are a part of everyday life and offer an exciting way of learning. The aim of our study was to determine the effectiveness of teaching undergraduate endocrinology using a Computer Assisted Learning (CAL) programme. DESIGN AND SUBJECTS: One hundred and eighty-five first year clinical medical students were randomly assigned either to attend a series of conventional lectures (n = 77) or to have the same material available through a CAL programme. MEASUREMENTS: A multiple choice question examination was performed before and after the course. Lecture attendance and individual usage of the computer system were recorded. Students were asked to fill in an evaluation form at the end of the study. RESULTS: There was no significant difference in the first examination scores between the groups. Both groups improved their scores after the course. Students spent longer performing CAL than attending lectures. Those who scored lowest in the first examination spent the most time on the CAL course. Those who spent the most time on the CAL course showed the largest improvement in examination score. Thirty-six out of the 42 students, who completed an evaluation of the CAL programme, rated it better than the standard lectures. CONCLUSIONS: Computer assisted learning is an effective way of increasing knowledge in teaching undergraduate endocrinology. The course was easy to run and was valued more highly than conventional lectures. The module is now running routinely in the year 3 clinical firms at St Thomas' and has resulted in an increase in knowledge in the end of firm assessment.

Changes in regional brain (18)F-fluorodeoxyglucose uptake at hypoglycemia in type 1 diabetic men associated with hypoglycemia unawareness and counter-regulatory failure.

We examined the effects of acute moderate hypoglycemia and the condition of hypoglycemia unawareness on regional brain uptake of the labeled glucose analog [(18)F]fluorodeoxyglucose (FDG) using positron emission tomography (PET). FDG-PET was performed in diabetic patients with (n = 6) and without (n = 7) hypoglycemia awareness. Each patient was studied at plasma glucose levels of 5 and 2.6 mmol/l, applied by glucose clamp techniques, in random order. Hypoglycemia-unaware patients were asymptomatic during hypoglycemia, with marked attenuation of their epinephrine responses (mean [+/- SD] peak of 0.77 +/- 0.39 vs. 7.52 +/- 2.9 nmol/l; P < 0.0003) and a reduced global brain FDG uptake ([mean +/- SE] 2.592 +/- 0.188 vs. 2.018 +/- 0.174 at euglycemia; P = 0.027). Using statistical parametric mapping (SPM) to analyze images of FDG uptake, we identified a subthalamic brain region that exhibited significantly different behavior between the aware and unaware groups. In the aware group, there was little change in the normalized FDG uptake in this region in response to hypoglycemia ([mean +/- SE] 0.654 +/- 0.016 to 0.636 +/- 0.013; NS); however, in the unaware group, the uptake in this region fell from 0.715 +/- 0.015 to 0.623 +/- 0.012 (P = 0.001). Our data were consistent with the human hypoglycemia sensor being anatomically located in this brain region, and demonstrated for the first time a change in its metabolic function associated with the failure to trigger a counter-regulatory response.

Reduced counterregulation during hypoglycemia with raised circulating nonglucose lipid substrates: evidence for regional differences in metabolic capacity in the human brain?

We have investigated the potential for the human brain to use lipid fuels during acute hypoglycemia. Nine healthy male subjects underwent hyperinsulinemic (1.5 mU/kg x min) stepped hypoglycemic clamps on two occasions, infusing Intralipid (20%) and heparin (0.1 U/kg x min) on one occasion only (ILH), with an identical study without infusion of ILH acting as a control. Five subjects also underwent euglycemic clamping with Intralipid/heparin infusion. During hypoglycemia, ILH raised circulating levels of nonesterified fatty acids, glycerol, and beta-hydroxybutyrate, although the latter did not rise until after the onset of counterregulation. With ILH, epinephrine responses [area under the curve (AUC), 127.9 +/- 31.7 vs. 175.1 +/- 27.4 nmol/L x 180 min; P = 0.03] and GH responses (AUC, 260 +/- 91 vs. 1009 +/- 150, P < 0.01) were reduced and delayed (glucose thresholds, 2.8 +/- 0.04 vs. 3.0 +/- 0.1 mmol/L; P = 0.04), with a trend toward reduced cortisol responses. Similarly, hypoglycemic symptom scores were diminished during ILH (AUC, 647 +/- 162 vs. 1222 +/- 874; P = 0.03). However, there was no significant effect on the deterioration in four-choice reaction time, one measure of cognitive deterioration [glucose thresholds, 2.6 +/- 0.1 vs. 2.7 +/- 0.1 mmol/L, ILH vs. control (P = 0.75); AUC, 1420 +/- 710 vs. 2250 +/- 1080 ms/min (P = 0.59)]. During euglycemic clamping with Intralipid/heparin infusion studies, there was no rise in hormones, four-choice reaction time, or symptoms other than hunger and tiredness. Both nonesterified fatty acids and glycerol can penetrate the mammalian brain and be metabolized. Raised levels were able to reduce neurohumoral responses to hypoglycemia, but could not protect cognitive function. This suggests that regional differences exist in human brain metabolism between glucose-sensing and cognitive areas of brain, which may be important in the understanding of the mechanisms of glucose sensing and in the genesis of hypoglycemia unawareness in insulin-dependent diabetes.

Regional differences in cerebral blood flow and glucose utilization in diabetic man: the effect of insulin.

To determine the effect of insulin on regional cerebral blood flow (rCBF) and glucose metabolism (CMRglu), we performed quantitative dynamic PET scanning of labeled water (H215O) and deoxyglucose (18FDG) using two protocols in 10 diabetic men. In protocol A, to test reproducibility of the technique, insulin was infused at 1.5 mU.kg-1.min-1 twice (n = 5). In protocol B, low (0.3 mU.kg-1.min-1) and high (3 mU.kg-1.min-1) dose insulin was given on separate occasions (n = 5). Euglycemia (5 mmol/L) was maintained by glucose infusion. In protocol A, CMRglu was 6% higher during the first infusion, and catecholamines were also increased, indicating stress. Blood flow was not different. Changing free insulin levels from 20.5 +/- 4.8 to 191 +/- 44.5 mU/L (P < 0.001, low versus high dose, protocol B) did not alter total or regional CMRglu (whole brain 36.6 +/- 4.0 versus 32.8 +/- 6.2 mumol.100 g-1.min-1, P = 0.32) or CBF (41.7 +/- 5.1 and 45.6 +/- 9.7 mL.100 g-1.min-1, P = 0.4) or rCBF. In cerebellum, CMRglu was lower than in cortex and the ratio between rate constants for glucose uptake and phosphorylation (K1 and k3) was reversed. There are regional differences in cerebral metabolic capacity that may explain why cerebral cortex is more sensitive to hypoglycemia than cerebellum. Brain glucose metabolism is not sensitive to insulin concentration within the physiologic range. This suggests that intracerebral insulin receptors have a different role from those in the periphery.

NIGHTINGALE MM system--the work in progress.

A multimedia computer based system for the self-learning of Nursing Informatics has been designed as a part of NIGHTINGALE project. A video thread has been designed as a central structure and "a real life anchor" for the abstract concepts related to the Electronic Patient Record. The hypermedia structure of the application has been maintained through the mapping of illustrated IT entries to specific points in the video sequences.

Audit of ethnic differences in risk factors and outcomes for diabetic patients attending St. Thomas hospital 1975-1995

Over the past twenty years a computerized record sytem `Diabeta' has been used to collect and collate clinical information on all patients attending the Diabetes Centre. In this time over 8000 patients have been registered, of these 42 percent have been grouped `caucasian' and 32 percent `afro-caribbean' by their own description. These large groups allow us to look at ethnic differences in disease pattern and outcomes, in order to better plan future diabetes health care requirement of different ethnic groups. Specific and significant differences between caucasians and afro-caribbeans are seen in many aspects of disease process and outcome. Age of onset of diabetes in European populations charateristically follows a bi-modal distribution, with peaks around the age of 10 and 60 years, this is mirrored in our own caucasian population in Lambeth. By contrast incidence of diabetes in our afro-Caribbean population is extremely low under the age of 20, but peaks at 50 years. True insulin-dependent diabetes (IDDM) is thus uncommon in afro-Caribbeans whilst non-insulin dependent diabetes (NIDDM) is somewhat more common. Patients with NIDDM have increased risks for cardio-vascular disease and peripheral vascular disease in addition to the specific diabetes-related complications, thus attention is given in the clinic to blood pressure, cholesterol, smoking habits and weight in addition to measures of glycaemic control. Risk factors differ significantly between the two groups, afro-caribbeans having higher blood pressure (despite treatment) but lower rates of smoking. Glycaemic control (percentage of HbALc) is not significantly different between the groups as a mean, but 2/3 of the worst 5 percent of glycaemic control are afro-caribbean. Despite these differences, stroke rates are similar in the two groups, cardiovascular disease higher in caucasians, and almost all specific diabetes complications higher in caucasians. The only major significant outcome that shows higher in afro-caribbeans is the onset of persistent proteinuria (heralding renal failure). Diabetes complications create a large health and financial burden on patients, knowledge of ethnic differences in relative risks of complications will allow us to better tailor the care and health-screening offered in the clinic to the individual needs of our patients. (AU)

Altered hierarchy of protective responses against severe hypoglycemia in normal aging in healthy men.

OBJECTIVE: To investigate the effect of normal aging on the protective responses against hypoglycemia, in view of the fact that type II diabetes is primarily a disease of aging, and its treatment is associated with risk of hypoglycemia with cognitive impairment. RESEARCH DESIGN AND METHODS: Plasma glucose was lowered stepwise from 5 to 2.4 mmol/l and restored by manipulation of an infusion of 20% glucose during 220-min intravenous infusion of 1.5 mU.kg-1.min-1 soluble insulin in 14 men; 7 were aged 60-70 years and the other 7 were 22-26 years. Changes in neurohumoral responses, subjective awareness, and choice reaction time were assessed. RESULTS: Hormonal responses were similar in the two groups, but symptoms began earlier in the younger men (at a plasma glucose of 3.6 +/- 0.1 vs. 3.0 +/- 0.2 mmol/l, P = 0.02) and were more intense (P = 0.03). Four-choice reaction time, a measure of psychomotor coordination, deteriorated earlier in the older men (at a plasma glucose of 3.0 +/- 0.1 vs. 2.6 +/- 0.1 mmol/l, P = 0.07) and to a greater degree. The difference between the glucose level for subjective awareness of hypoglycemia and the onset of cognitive dysfunction was lost in the older men (0.0 +/- 0.2 vs. 0.8 +/- 0.1 mmol/l, P < 0.007). CONCLUSIONS: Older men are prone to more severe cognitive impairment during hypoglycemia than younger men and are less likely to experience prior warning symptoms if blood glucose falls. This effect of normal aging may contribute to the risk of severe hypoglycemia in older diabetic patients treated with sulfonylureas and insulin.

Effect of metformin on glucose disposal and hyperinsulinaemia in a 14-year-old boy with acanthosis nigricans.

We report the treatment of a 14-year-old Indian boy with acanthosis nigricans and hyperinsulinaemia with metformin in an attempt to improve his skin lesions. Oral metformin was used for 6 months with assessment of insulin status during an intravenous glucose tolerance test and hyperinsulinaemic-euglycaemic clamping before and after treatment. The first-phase insulin response reduced from 19,593 to 5,410 pmol/l/min (normal 1,900-13,400), and the second-phase insulin response improved from 59,120 to 34,020 pmol/l/min (normal 2,900-18,100). During hyperinsulinaemic-euglycaemic clamping hepatic glucose production was normally suppressed prior to therapy, but peripheral glucose remained abnormally low, 152 and 138% of basal (expected 199%). The acanthosis nigricans remained unaltered but over this period puberty progressed and his body mass index increased. We conclude that, in this patient, metformin had a minimal effect on the hyperinsulinism and none on the acanthosis nigricans in the relatively short term, but further studies in more patients over longer time intervals are warranted.

Diabetes--trials, tribulations and pay-off of tight control.

In June 1993 the results of the Diabetes Control and Complications Trial (DCCT) were made public. It showed that intensive insulin therapy, designed to produce 'near-normal' blood glucose levels, resulted in a spectacular reduction in long-term risks of all microvascular complications of insulin dependent diabetes mellitus (IDDM) when compared with 'conventional' insulin therapy. On 6 April 1995 a well-attended conference, organised by Professor Stephanie A Amiel, was held at the Royal College of Physicians to discuss the issues arising from the DCCT, the practicalities of implementing change in diabetes care in the light of its results, the benefits and potential risk of such intensive therapy (tight control), the implications of the DCCT findings to patient groups not included in it and other ways of minimising the long-term complications of diabetes.

Restoration of hypoglycaemia awareness in patients with long-duration insulin-dependent diabetes.

Hypoglycaemia without warning is a dangerous complication of insulin-dependent diabetes mellitus and it limits the use of intensified insulin therapy to reduce chronic diabetic complications. To investigate the possibility of restoring awareness; symptomatic, cognitive, and hormonal responses to controlled hypoglycaemia were studied in insulin-dependent diabetic patients with long disease duration (6 with good glycaemic control and 6 with poor control) before and after hypoglycaemia avoidance. At the start of the study, all had loss of hypoglycaemia awareness. Responses to the initial challenge were small (pooled area under curve [AUC] adrenaline 5.75 [SE 0.07] nmol/L per 260 min, pooled AUC symptom score 80 [1.3]) and only started when plasma glucose was significantly lower than the 2.8 (0.1) mmol/L at which cognitive function deteriorated. After 4.1 (1.1) months' scrupulous hypoglycaemia avoidance, hormone and symptom responses to the challenge were increased (AUC adrenaline 15.9 [0.1] nmol/L per 260 min, p = 0.01; AUC symptom score 275 [7], p < 0.001), starting at plasma glucose concentrations significantly higher than that causing cognitive dysfunction. Glycosylated haemoglobin did not deteriorate significantly. We conclude that the normal hierarchy of subjective awareness before cognitive dysfunction during hypoglycaemia can be restored by avoiding hypoglycaemia. This is independent of disease duration or initial metabolic control.

Protection by lactate of cerebral function during hypoglycaemia.

Severe hypoglycaemia with brain dysfunction limits intensified therapy in patients with insulin-dependent diabetes mellitus, despite evidence that such therapy reduces the risk of chronic complications of the disease. We have investigated the effect of infusing lactate (a potential non-glucose fuel for brain metabolism) on protective, symptomatic neurohumoral responses and on brain function during hypoglycaemia in seven healthy men. Elevation of lactate (within a physiological range) substantially diminished catecholamines, growth hormone, cortisol, and symptomatic responses to hypoglycaemia and lowered the glucose level at which these responses began. Glucagon responses were unaffected. Lactate was also associated with a significant lowering of the glucose level at which brain function deteriorated, suggesting that brain function was protected during the hypoglycaemia. The defect in counter-regulation is similar to that seen in hypoglycaemia-prone diabetic patients. Initiation of the protective responses to hypoglycaemia (except glucagon) can be delayed by supporting metabolism with an alternative metabolic fuel. Cerebral cortical dysfunction of severe hypoglycaemia is also delayed. Our demonstration that higher brain function can be protected during hypoglycaemia may have therapeutic potential.