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A 47-year-old man presented with severe clinical hypoglycaemia. He had long-standing insulin-dependent diabetes with previously good glycaemic control. Intense headaches and vomiting initiated hospitalization. A brain computed tomography (CT) scan was normal, and a lumbar puncture showed elevated cerebrospinal fluid (CSF) protein [0.67 g/L; normal range (NR) 0.15-0.45 g/L], suggesting resolving viral meningitis. Routine thyroid function tests were abnormal (free thyroxine 10.6 pmol/L, NR 9-22.5 pmol/L; thyroid-stimulating hormone 0.16 mU/L, NR 0.35-5 mU/L). In the absence of evident thyroid therapy, the laboratory policy required an urgent cortisol assay to be added; this was very abnormal (42 nmol/L), suggesting hypopituitarism. Later analysis showed that concentrations of gonadotrophins and adrenocorticotrophin were low. An urgent pituitary magnetic resonance imaging scan revealed an unsuspected pituitary tumour with recent haemorrhage (pituitary apoplexy). The patient was given intravenous hydrocortisone and then stabilized on oral hydrocortisone, thyroxine and mesterolone. He made a full recovery and the hypoglycaemia resolved. The normal brain CT scan was falsely reassuring and the CSF protein was not due to viral meningitis but to haemorrhage into the pituitary tumour. If laboratory policy had not required the urgent cortisol assay be added, the diagnosis of hypopituitarism would have been delayed or even missed altogether. This could have led to the death of the patient.

Diabetic ketoacidosis (DKA) and poor glycaemic control in young adults with Type 1 diabetes may be associated with street drug use. There are few studies in the UK looking at the prevalence of drug use in young adults with diabetes.One hundred and fifty-eight young adults, aged sixteen to thirty years, with Type 1 diabetes attending an urban diabetes clinic were sent an anonymous confidential postal questionnaire to determine the prevalence of street drug use.We received 85 completed responses. Twenty-nine percent of respondents admitted to using street drugs. Of those, 68 percent habitually took street drugs more than once a month. Seventy-two percent of users were unaware of the adverse effects on diabetes.Self-reported street drug usage in young adults with Type 1 diabetes is common and may contribute to poor glycaemic control and serious complications of diabetes.

A 27-year-old man, who had type 1 diabetes, presented with agitation, confusion, vomiting and faecal incontinence. There was an abscess on his right upper arm at an insulin injection site (temperature 38.5°C, pulse 140 per minute, and blood pressure 125/85 mmHg). Investigations included neutrophil count 13.6 ×109/litre, glucose 26 mmol/litre, pH 7.4, free thyroxine (T4)>77 pmol/litre (normal range (NR) 9–22.7), thyroid-stimulating hormone (TSH) After 24 hours there was a marked clinical improvement with resolution of his agitation and confusion and his pulse rate was normal (T4 22 pmol/litre, TSH

Seventy-seven per cent of 235 newly diagnosed and untreated patients with diabetes mellitus were polysymptomatic at their first visit to hospital. The larger the number of typical symptoms, the greater was the duration of the longest lasting one (p less than 0.001). Symptom duration was positively correlated with pre-treatment fasting plasma glucose (p less than 0.05), but this was more strongly linked to the number of symptoms (p less than 0.001). In those patients diagnosed because of symptoms typical of diabetes mellitus, mean fasting glucose was higher than when symptoms were elicited retrospectively in patients in whom glycosuria had been found unexpectedly. Weight loss at diagnosis (from 'highest remembered') was positively correlated with fasting plasma glucose (p less than 0.001). One hundred and thirty-two patients had fundal colour photography 7 or 8 years after diagnosis. The mean pre-diagnosis duration of symptoms was 2 +/- S.D.17 months in 80 without retinopathy compared to 8 +/- 6 months for 52 with retinopathy (p less than 0.001). The severity of retinopathy was also positively associated with symptom duration, as was failure to attend for these ocular reviews. Prolonged symptoms pre-diagnosis were associated with increased risk of death during the first 5 years post-diagnosis among those with a normal electrocardiogram (ECG) initially (p less than 0.003), but was unrelated to ECG abnormality then or during the next 5 years. These findings accord with (but offer no proof of) the inherently plausible expectation that both morbidity and mortality would be lessened by earlier diagnosis of non-insulin-dependent diabetes mellitus.

Facial and sublingual temperatures were measured in 61 diabetics undergoing intravenous glucose tolerance tests. Within 2 minutes of starting glucose injection, 58 patients felt warm in the face and trunk, 56 showed a rise in cheek temperature and 23 had visible facial reddening. The most important determinant of cheek temperature rise was initial cheek temperature. Cheek temperature rise was a unimodally distributed variable and was significantly larger in patients with fasting plasma glucose greater than or equal to 6.1 mmol/l than in those with lower glucose (despite similar initial cheek temperatures). Initial cheek temperature correlated with ambient temperature in men with fasting glucose greater than or equal to 6.1 mmol/l but not in those with fasting glucose less than or equal to 6.0 mmol/l nor in women. Initial tongue temperature was also related to ambient temperature in men but not in women and fell following the glucose injection. Although the glucose flush differs from the the chlorpropamide-alcohol flush in its unimodal distribution and relatively small temperature rise, some of the factors which influence reaction could well be considered with benefit in analysis of the chlorpropamide-alcohol flush, in particular the initial cheek (and ambient) temperatures, sex and fasting plasma glucose concentration.

In a group of 149 maturity-onset type diabetic patients followed from diagnosis, 55 (37%) had retinopathy on colour photography 7 years later. Those patients with retinopathy had significantly greater glycaemia, as shown by higher fasting plasma glucose levels at diagnosis, larger mean values for fasting glucose 1, 3 and 5 years later, and higher random glucose and haemoglobin A1c at ophthalmic review (p = 0.001, 0.002, 0.007 and 0.001, respectively). Substantial retinopathy, as measured by greater than 5 microaneurysms, also correlated significantly with each index of glycaemic control.

Twelve-lead electrocardiograms (ECGs) were recorded at diagnosis from 247 initially non-insulin-requiring diabetics. The record was normal in 208 (84%) patients and abnormal in 39 (16%). The latter were older (p = 0.002), with higher blood pressures (diastolic and systolic) and greater cardiothoracic ratios (all p less than 0.02). They also had higher fasting (p less than 0.01) and post-glucose (p less than 0.04) plasma insulin concentrations per body mass index than those with normal ECGs. Five years later 17 patients had died (4 from proven and 6 from suspected cardiac cause), 5 had sustained a proven myocardial infarct and 3 a suspected cardiac event. ECGs were recorded from 138 patients both at diagnosis and 5 yr later. The record was normal on both occasions in 100 (72%), changed from normal to abnormal in 21 (15%), from abnormal to normal in 9 (7%), and was abnormal on both occasions in 8 (6%). Patients who developed ECG abnormalities were older (p = 0.011), and had greater mean fasting cholesterol during the 5 yr (p = 0.05). They also had greater fasting insulin levels per body mass index both before (mean of initial and 1-yr values, p = 0.02) and after the abnormality developed (p = 0.003) than those with persistently normal recordings. Insulin levels post-glucose were greater at 5 yr in those with cardiac abnormality but, as with the higher diastolic blood pressure and fasting glucose concentration then (both p less than 0.05), this difference was not significant initially. (ABSTRACT TRUNCATED AT 250 WORDS)

Seventy-one Type 2 (non-insulin-dependent) diabetic patients showed only a slight deterioration in mean vibration sensory threshold (measured biothesiometrically) on the feet during the 5 years from diagnosis. However, multiple linear regression analysis of the wide range of individual changes in this threshold showed as significant independent associated factors the initial sensory threshold (p less than 0.001), age, gender, and both the mean fasting blood glucose and failure to become thinner under treatment (p less than 0.05 for all). The relationship with fasting glucose was stronger if the pre-treatment value was included in calculation of the mean (p less than 0.001). Mean fasting blood glucose under treatment accounted for only a small fraction of the total variance of the deterioration of the vibration sensory threshold, but represented one-twelfth of that attributable to identified factors, and one-third of the variance ascribable to factors subject to therapy. Interim values revealed the persistent effect of hyperglycaemia over the 5 years. An increase of 1 mmol/l in mean fasting blood glucose has an equivalent effect on the sensory threshold to an extra 5 years of age.

At diagnosis of non-insulin-requiring diabetes, in 215 patients, systolic and diastolic (Korotkow 4) blood pressures, corrected for arm circumference, correlated with fasting plasma insulin concentration (r = 0.29, p less than 0.001), body mass index (BMI) (W/H2), and age (p less than 0.05 in all cases for both systolic and diastolic pressures). Women had higher pressures but were also heavier than men. Systolic pressure fell by 13 +/- SD 11%, diastolic by 8 +/- 15%, over 1 month and remained decreased over 5 yr. The fall was greater with high initial pressure (r = 0.6-0.7, p less than 0.001 all years). The correlation of initial pressure with plasma insulin remained significant even when allowing for age, surface area, BMI, and plasma concentrations of glucose, urea, creatinine, sodium and urate. Neither gender nor treatment with sulphonylureas or hypotensives influenced this relationship. During the first 5 yr after diagnosis the correlation between blood pressure and insulin weakened, particularly when allowing for the factors above (at 5 yr, systolic p = 0.025, diastolic NS).

Erythrocyte aldehyde dehydrogenase activity (EALDH) was measured in 21 diabetics on long-term chlorpropamide therapy. Median EALDH was 0.362 units, range 0.108 to 0.750 units and correlated neither with previously assessed chlorpropamide alcohol flushing nor with coincident plasma or erythrocyte chlorpropamide concentration. The hypothesis that genetic or permanently acquired reduction in EALDH correlates with CPAF status was not supported. There was no concentration-related inhibition of the enzyme by prevailing plasma or erythrocyte chlorpropamide.

Forty-three diabetic patients on maintenance chlorpropamide (100-750 mg daily) drank 0.2 ml/kg 90% ethanol after equilibration in a room controlled at 20 degrees C. Twenty-five patients had already noted marked alcohol flushing since starting chlorpropamide therapy (group A), while 13 had not observed this (group B). The remainder were teetotal or unsure of their reaction. Cheek temperature rise correlated with plasma chlorpropamide concentration (r = 0.6, p less than 0.001) in all patients and was inversely related to basal cheek temperature (r = -0.35, p less than 0.02). Plasma chlorpropamide correlated with daily chlorpropamide dose (r = 0.8, p less than 0.001) but not with basal cheek temperature. The correlation between chlorpropamide level and cheek temperature rise was strengthened on analysis of group A alone (r = 0.7, p less than 0.001) and absent in group B (r = 0.2, p greater than 0.3) who tended to have lower chlorpropamide levels and cheek temperature rise than group A.

Further progress can depend only on standardised testing to determine the response precisely, after consideration of known interacting factors (e. g. initial cheek temperature, plasma chlorpropamide concentration). Until liver biopsy to identify the alcohol dehydrogenase isoenzymes becomes harmless, further studies will perhaps reveal more about the extra-pancreatic effects of one sulphonylurea than about the aetiology of Type 2 diabetes and its complications.