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Background: Impaired awareness of hypoglycaemia (IAH) is common in adults with Type 1 diabetes mellitus (T1DM) and is a major risk factor for severe hypoglycaemia. Little is known about its effect on employment status., Aims: To examine the effect that IAH has on the employment status or employability of people with T1DM., Methods: A randomly selected cohort of adults of employment age with T1DM completed a questionnaire detailing the history of their diabetes, their occupational history (including job and industry type) and assessing both their hypoglycaemia awareness status and whether in their view their ability to obtain or retain employment had been adversely affected by having diabetes., Results: A total of 252 patients participated, with the following characteristics: 135 males, mean HbA1c 8.5% [standard deviation (SD) 1.4], mean age 43.3 years (SD 13.2), mean duration of diabetes 21.3 years (SD 12.8) and prevalence of IAH 23.4%. The employment rate was comparable between those with preserved awareness (73%) and the IAH group (66%) (not significant). People with IAH were older (P < 0.05) and also more commonly felt that having diabetes affected their ability to work (P < 0.05)., Conclusions: This study is the first to demonstrate that those with T1DM and IAH remain as economically active as those with normal awareness of hypoglycaemia, although subjects with IAH were significantly more likely to feel that having diabetes had adversely affected their capacity for employment.

Context: Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the metabolic syndrome, but whether circulating cortisol levels predict cardiovascular end points is less clear. People with type 2 diabetes are at increased cardiovascular disease risk and thus are suitable to study associations of plasma cortisol with cardiovascular risk., Objective: We aimed to assess whether altered HPA axis activity was associated with features of the metabolic syndrome and ischemic heart disease in people with type 2 diabetes., Design and Setting: We conducted a cross-sectional cohort study in the general community, including 919 men and women aged 67.9 (4.2) yr with type 2 diabetes (the Edinburgh Type 2 Diabetes Study)., Intervention: We measured fasting morning plasma cortisol., Main Outcome Measurement: Associations between cortisol levels, features of the metabolic syndrome, obesity, and ischemic heart disease were determined., Results: Elevated plasma cortisol levels were associated with raised fasting glucose and total cholesterol levels (P < 0.001). These findings remained significant after adjustment for potential confounding factors (P < 0.001). Elevated cortisol levels were associated with prevalent ischemic heart disease (>800 vs. <600 nmol/liter; odds ratio, 1.58; P = 0.02). This association remained significant after adjustment for duration and control of diabetes and other cardiovascular risk factors (P = 0.03)., Conclusions: The previously described associations between HPA axis activation and features of the metabolic syndrome are present among people with type 2 diabetes. Elevated plasma cortisol is also associated with a greater prevalence of ischemic heart disease, independent of conventional risk factors. Understanding the role of cortisol in the pathogenesis of ischemic heart disease merits further exploration.

Introduction: The prevalence of type 2 diabetes and dementia are set to rise inexorably over the next 30-40 years. There are now substantial data to suggest that type 2 diabetes is associated with an increased risk of dementia., Sources of Data: This is a narrative review using data from individual studies and review articles known to the authors. A Medline search was also undertaken and reference lists were reviewed to identify additional relevant studies., Areas of Agreement: Type 2 diabetes is associated with an increased risk of both Alzheimer's and Vascular dementia, although the reality is that many affected individuals have mixed forms of dementia., Areas of Controversy: The mechanisms underpinning this association remain to be clearly delineated. Type 2 diabetes is a complex disorder and so it is likely that multiple different, synergistic processes may interact to promote cognitive decrements., Growing Points: Recent data suggest that glucocorticoids excess and elevated inflammatory markers may also have a role in the aetiology of diabetes-related cognitive impairment., Areas Timely for Developing Research: Large-scale, prospective epidemiological studies are now required to accurately delineate the pathogenesis of cognitive impairment in people with type 2 diabetes. These are underway and randomized trials of diabetes-specific interventions are also starting to include cognitive function as an outcome measure.

Primary adrenal insufficiency (Addison's 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 Addison's disease can influence glycaemic control and induce severe hypoglycaemia.

Contrast sensitivity testing, in common with color vision (another test of psychophysical function), demonstrates significant changes in diabetic subjects compared with nondiabetic controls, and there is some evidence for a relationship with grade of retinopathy. Changes in contrast sensitivity have been demonstrated in children and adults with diabetes of short duration, and some evidence exists for a correlation with poor glycemic control, although prospective studies are required to assess this relationship over a longer time period. Although both color vision and contrast sensitivity demonstrate similar patterns, studies that directly compare the two tests suggest that measurement of contrast sensitivity is the more sensitive and specific.

In the UK, licensing of taxi drivers is dealt with by local government authorities. In Scotland, before the recent reorganization of local government, taxi licensing was under the jurisdiction of District Councils, so a telephone survey was conducted of all 52 mainland Scottish District Councils to ascertain the procedures which were being employed in assessing medical fitness to drive a taxi, for which there is no national standard. Medical enquiries relevant to fitness to drive were being made by 41 (79%) of local authorities, but in 38 (73%) this was limited to a single question about health. No enquiry regarding health status was being made by 11 (21%) District Councils (all serving < 100,000 population size). Only three Scottish District Councils conducted a routine medical examination of all applicants. Thirteen of the 15 large (> 100,000 population size), and 20 of the 21 medium-sized (50,000-100,000) Scottish District Councils carried out medical examinations either when a relevant medical disorder was declared by the applicant, or when the applicant was above a defined age (which varied between local authorities). The small local authorities (population < 50,000) examined only those applicants who declared medical disorders. This survey has shown considerable variation and limitations in the approach of the previously existing Scottish District Councils to the assessment of medical fitness to drive of applicants for taxi licences. It is suggested that national standards and guidelines are required for medical fitness to drive in relation to taxi licensing.

A general impairment of cognitive performance occurs during acute insulin-induced hypoglycaemia, but little objective evidence is available for disruption of more specific cognitive processes. The effect of controlled hypoglycaemia on the early stages of visual information processing and contrast sensitivity was examined in a homogeneous group of 20 nondiabetic human subjects. Hypoglycaemia caused a significant disruption in general cognitive performance as assessed by a digit symbol task (P < 0.001) and the trail making B task (P < 0.05). Hypoglycaemia also produced a highly significant deterioration in performance on all of the visual information processing tasks, namely inspection time (IT) (P = 0.01), visual change detection (VCD) (P < 0.005) and visual movement detection (VMD) (P < 0.005). A significant deterioration in contrast sensitivity was observed during hypoglycaemia (P < 0.005). In contrast, no significant effect of hypoglycaemia was demonstrated on standard clinical measures of visual acuity or stereoscopic vision. Thus, although hypoglycaemia caused no detectable deterioration in visual acuity as measured by Snellen-type tests, a marked deterioration occurred in the speed of visual information processing and in contrast sensitivity. As many decisions are made under conditions of limited perceptual time and low visual contrast (e.g. when driving), the disruptive effect of moderate insulin-induced hypoglycaemia on visual perception will have important practical implications in diabetic humans exposed to this metabolic stress. The present results are congruent with other evidence which shows that the early stages of visual information processing are susceptible to deterioration by general cerebral insults.

Renal responses to low-dose infusion of angiotensin II (ANGII, 1.25 and 2.5 ng.kg-1 min-1) were examined in 15 patients with type 1 diabetes and in 10 control subjects after pretreatment with lithium carbonate (750 mg, 20 mmol). Mean arterial pressure rose during ANGII infusion in both groups. The renal haemodynamic response to angiotensin II was not abnormal in the diabetic patients. Absolute proximal reabsorption of sodium was increased at baseline in the diabetic group, and fell during ANGII. Fractional lithium excretion was reduced in the diabetic patients at baseline (P < 0.05), and the fall in fractional lithium excretion during ANGII was less than in the control group (P = 0.012). In the diabetic group correlations existed between glycated haemoglobin and baseline glomerular filtration rate (P < 0.05), baseline fractional lithium excretion (P = 0.03), and the fall in fractional lithium excretion during angiotensin II infusion (P = 0.013). There was no correlation between glycated haemoglobin and absolute lithium clearance. Some indices of sodium reabsorption by the proximal renal tubule in diabetic patients correlate with prevailing chronic glycaemic control, largely reflecting changes in glomerular filtration rate. Reduced fractional proximal tubular responsiveness to exogenous angiotensin II is consistent with a role for endogenous angiotensin II as one mediator of increased tubular reabsorption of sodium in type 1 diabetes, but the data does not exclude alternative mechanisms.

To examine the interaction between angiotensin II (ANGII) and dopamine in type 1 diabetes mellitus, urinary dopamine excretion was examined during ANGII infusion in 15 diabetic patients and 10 control subjects after pretreatment with lithium 750 mg and placebo. The antinatriuretic response and the urinary dopamine response to ANGII did not differ within or between the two groups on each study day. No correlation was observed between the decrements in urinary sodium excretion and urinary dopamine output during ANGII infusion in either group. The effect of insulin on urinary dopamine excretion was studied separately in seven non-diabetic subjects; sodium and potassium retention occurred during a hyperinsulinaemic euglycaemic clamp, but urinary dopamine did not change. The data suggest that the relationship between urinary sodium excretion and tubular dopamine synthesis remains normal in early type 1 diabetes mellitus both at baseline and during the antinatriuresis induced by angiotensin II. The cause of the reduction in urinary dopamine during ANGII infusion is unclear, but is probably not mediated directly by changes in proximal tubular sodium transport.

The adrenergic control of intact PTH secretion was investigated by measuring its plasma concentration during insulin-induced hypoglycemia in normal human subjects under control conditions (n = 12) and after alpha (n = 5)- or beta (n = 6)-adrenoceptor blockade. Blood samples were taken at baseline, at the time of the acute hypoglycemic reaction, and at regular intervals for 60 min thereafter. Plasma concentrations of intact PTH, catecholamines, total calcium, magnesium, albumin, phosphate, and glucose were measured in all subjects, and plasma ionized calcium was also assayed in three subjects during acute hypoglycemia without pharmacological blockade. At the time of the acute hypoglycemic reaction, the plasma concentration of intact PTH in the control subjects fell to 60.8% of baseline values and was accompanied by a small but significant increase in plasma total calcium. Intact PTH concentrations remained suppressed after the plasma calcium concentration had returned to normal. The two groups of subjects who were exposed to adrenoceptor blockade exhibited a reduced fall in plasma intact PTH and showed no significant increase in plasma total calcium. Therefore, insulin-induced acute hypoglycemia was associated with a fall in plasma intact PTH. Adrenoceptor blockade reduced, but did not abolish, the response, suggesting that other factors are involved.

Gastric carcinoma may rarely be the cause of tumour-associated hypoglycaemia. We report the case of an elderly woman who presented in hypoglycaemic coma, and who was found subsequently to have an adenocarcinoma of the stomach. Hypoglycaemia persisted despite prednisolone, diazoxide, and a high concentration dextrose infusion. The few published cases are reviewed in which an association was established between gastric carcinoma and hypoglycaemia, and the possible aetiology of the hypoglycaemia is discussed.

The turnover of isotopically labeled squalene formed in plasma from [14C]mevalonate has been used to measure cholesterol synthesis in diabetics over a 7-h period. Five patients were studied while in poor diabetic control (mean daytime glycemia, 349 mg/dl) and at a later date once improved control was established by multiple daily insulin injections (mean glycemia, 175 mg/dl). This degree of diabetic control resulted in an increase in the fractional conversion of [14C]mevalonic acid to [14C]squalene from 55.2 +/- 1% to 67.5 +/- 4% (P less than 0.025). These data together with the area under the squalene specific activity curve yeild an estimated rate of cholesterol synthesis based on the likely assumption that mevalonate pool size did not decrease. Insulinization increased this calculated mean rate of cholesterol synthesis from 961 +/- 151 to 1206 +/- 223 mg/day (P less than 0.025). The use of squalene kinetics to evaluate changes in cholesterol synthesis deserves further study, particularly in metabolically unstable states such as diabetes in which conventional methods for measuring cholesterol synthesis are difficult to apply and to interpret.

In normal humans, arginine vasopressin and oxytocin are released acutely from the posterior pituitary gland in response to hypoglycemia, and their release may assist counterregulation. The responses of these hormones to insulin-induced hypoglycemia were measured in 16 insulin-dependent diabetic patients with no autonomic neuropathy (8 patients who had been diabetic less than 5 yr and 8 patients who had been diabetic greater than 15 yr) and in 6 normal subjects. The time of the onset of hypoglycemia and the mean blood glucose nadirs were similar in all groups, but the blood glucose recovery was delayed in the diabetic patients. In the normal subjects plasma arginine vasopressin rose from a mean basal value of 0.4 +/- 0.2 (+/- SE) pmol/L to a maximum of 1.3 +/- 0.6 pmol/L, and plasma oxytocin rose from 0.7 +/- 0.1 pmol/L to a maximum of 1.2 +/- 0.2 pmol/L 30 min after the onset of hypoglycemia. The plasma arginine vasopressin and oxytocin concentrations after hypoglycemia were significantly higher in both of the diabetic groups compared with those in the normal group. Arginine vasopressin and oxytocin rose in all control subjects after hypoglycemia. The individual hormonal profiles in the diabetic patients were variable, with an exaggerated rise of oxytocin in some diabetic patients and no rise in others. The arginine vasopressin responses were exaggerated in all of the diabetic patients. There was no correlation between the hormonal responses and the duration of diabetes. The exaggerated plasma arginine vasopressin and oxytocin responses to hypoglycemia in diabetic patients may indicate the failure of a normal inhibitory mechanism which modulates hormonal secretion or a compensatory response to impaired glucose recovery.

Convulsions may occur as a consequence of insulin-induced hypoglycaemia. We report three patients with insulin-dependent diabetes, who presented with generalized tonic-clonic seizures associated with nocturnal hypoglycaemia. None of the patients had experienced hypoglycaemia during waking hours and the convulsions were mistakenly diagnosed as idiopathic epilepsy. Recognition of the possible hypoglycaemia aetiology of these convulsions permitted appropriate alteration of the insulin regimens with no recurrence of convulsions. In one case, the seizure was associated with bilateral fractures of the neck of the humerus. Unrecognized hypoglycaemia should be considered as a possible cause of convulsions in insulin-dependent diabetic patients.