No abstract

Abnormalities of microvascular function may be important in the pathogenesis of diabetic microangiopathy. As such changes are already present at diagnosis in patients with Type 2 (non-insulin-dependent) diabetes mellitus, subjects at risk of developing the disease, who had elevated fasting plasma glucose concentrations below the diabetic range, were studied. The maximal microvascular hyperaemic response to local heating was determined in the feet of 11 subjects with fasting hyperglycaemia and 11 age- and sex-matched control subjects. There was reduced maximal hyperaemia in the subjects with fasting hyperglycaemia (1.01 [0.71-1.57]V, median and range), when compared to control subjects (1.41 [1.32-2.13]V, p < 0.001). It is unlikely that this limited vasodilation is a result of the mild degree of hyperglycaemia observed in the subjects included in this study. Further studies are therefore required to address the possible mechanisms of limited microvascular reactivity in subjects at risk of developing Type 2 diabetes.

The annual rate at which patients defaulted from follow up at the Wolverhampton diabetic clinic between 1971 and 1981 was 4-1% overall and 3 5% in white patients. In 1982 a study was started to discover what happened to white patients, born after 1919, who defaulted from the hospital clinic. There were 162 defaulters, of whom 19 had died. Of the remaining 143 patients, 19 were attending another hospital diabetic clinic, 22 had moved out of the area, and 28 refused to participate in the study. Seventy four agreed to participate: 39 were treated with diet, 15 with oral hypoglycaemic agents, and 20 with insulin. They were matched for sex, age, treatment, and duration of diabetes with patients attending the clinic.Non-insulin dependent defaulters were significantly more overweight at diagnosis (40% v 25%; p<0 05) and remained more obese. They developed significantly higher diastolic blood pressure (94 v 86 mm Hg; p<002) and higher haemoglobin A, (HbA,) concentrations (11.7% v 8-4%; p<001). They had significantly more neuropathy at reassessment (15 v 6 out of 54; p<005) and a greater incidence of new retinopathy (p<002), which correlated with their higher diastolic blood pressures (p<0-01) and HbA, concentration (p<0.02). In defaulters who were treated with insulin only the prevalence of neuropathy was significantly different from that in controls (p<005).Defaulters received minimal medical supervision and suffered greater morbidity than regular attenders at the clinic. Introduction Diabetic care in this district comprises a hospital run by consultants and 23 general practice diabetic clinics run independently (mini clinics). Patients who attended either clinic between 1971 and 1981 had a punchcard giving basic information and treatment, as previously described.' Information on attenders is continually updated.In a survey of punchcards carried out in 1982 1117 people attended the hospital clinic and 1061 the mini clinic practices. The overall annual rate of defaulting from the hospital clinic was 4 1% with annual rates of Il% for patients receiving diet alone, 6% for those treated with oral hypoglycaemics, and 4% and 1% for those treated with insulin once or twice a day, respectively. Defaulting from mini clinics is much less of a problem and is not reviewed here.

We found that the quality of life of patients treated and under follow up for non-functioning pituitary tumours was similar to that of patients treated by mastoid surgery and under similar follow up. The pituitary patients deficient in two hormones and thus most likely to be GH deficient were also similar to the controls. These results suggest that adding GH replacement in this patient group may not be routinely indicated for improvement in quality of life and needs careful assessment. Patients who had received radiotherapy were more depressed and anxious than controls. Further investigation into the psychological and psychomotor effects of radiotherapy in this group of patients is required.

A high proportion of the female patients who are members of maturity onset diabetes of the young (MODY) pedigrees, and whose diabetes mellitus is due to a glucokinase mutation, originally presented with gestational diabetes. To establish whether glucokinase mutations could be a common cause of gestational diabetes, we studied 50 subjects who presented with gestational diabetes and on follow-up had hyperglycaemia (5.5-10.0 mmol/l). Screening for glucokinase mutations using single-stranded conformational polymorphism (SSCP) analysis detected a missense mutation at position 299 (Gly299-->Arg) in three subjects. As two pedigrees in the Oxford area had the same glucokinase mutation, we suspected the role of a founder-effect, and carried out pedigree extension, haplotype construction (using microsatellite markers GCK1 and GCK2) and mutation screening of at-risk subjects from the same geographical area. One of the gestational diabetic subjects was found to be related to one of the previous pedigrees via her paternal grandmother. Subjects with the mutation were found to have the Z + 4/2 (GCK1/ GCK2) haplotype, suggesting that the observed high prevalence of the Gly299-->Arg glucokinase mutation in the Oxford region was due to a founder-effect. Since glucokinase mutations predominantly induce subclinical hyperglycaemia, it is likely that in the locality of other pedigrees there will be undiagnosed subjects with the same glucokinase mutation, which remains undetected unless pregnancy occurs.