1. An increase in capillary blood flow and pressure has been implicated in the pathogenesis of diabetic microangiopathy. Abnormal vascular reactivity of the resistance vasculature may play a contributory role by permitting alterations in regional haemodynamics. 2. We have studied the contractile behavior of isolated resistance arteries from normotensive patients with insulin-dependent diabetes mellitus and non-diabetic matched control subjects. Contractile responses to potassium (123 mmol/l), noradrenaline (10(-8) to 3 x 10(-5) mol/l) and angiotensin II (10(-11) to 3 x 10(-8) mol/l) were recorded. Relaxation studies were performed in maximally contracted vessels using acetylcholine (10(-8) to 10(-5) mol/l) and bradykinin (10(-9) to 10(-6) mol/l) (endothelium-dependent) and sodium nitroprusside (10(-9) to 10(-5) mol/l) (endothelium-independent). 3. The maximal contractile responses to potassium (P < 0.05), noradrenaline (P < 0.01) and angiotensin II (P < 0.01) were depressed in diabetic patients. Relaxation to acetylcholine was impaired (P < 0.05), but was normal with bradykinin and sodium nitroprusside. 4. These results suggest that there may be a defect in the endothelial cell acetylcholine receptor excitation-coupling in diabetes mellitus rather than a decreased ability to synthesize and release endothelium-derived relaxing factor. Impaired contraction and endothelium-dependent relaxation of resistance arteries in diabetic patients may contribute to the development of diabetic microangiopathy by causing an increase in tissue blood flow, a rise in capillary pressure and, as a result, an increase in vascular permeability.

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Summary Lipoatrophy and lipohypertrophy were the most frequently reported local complications of conventional insulin therapy. Early reports following the introduction of highly purified insulins suggested a reduction in the frequency of lipohypertrophy and lipoatrophy. Since highly purified insulins have been in common usage for 10 years, the present frequency of these complications was assessed in a study of 281 insulin treated diabetics. Lipohypertrophy was recorded in 76 (27.1%) patients including 3 with associated lipoatrophy. Lipoatrophy was found in 7 (2.5%) cases (3 porcine and 4 bovine insulin treated), 4 of which had only ever used highly purified insulins. Despite the introduction of highly purified insulins, lipohypertrophy and lipoatrophy remain prevalent in insulin treated patients. This common complication may be limited by routinely inspecting injection sites.

The relative risk of death by calendar date of diagnosis was investigated in a population-based incident cohort of 845 (463 males:382 females) IDDM diagnosed in Leicestershire before the age of 17 years between 1940 and 1989. The mortality status of 844 (99.9%) patients was determined as of the 31 December 1991, representing 14,346 person-years of risk. Trends in relative risk of death were investigated using Cox proportional hazards modelling for within cohort comparisons and age/sex and calendar time adjusted standardized mortality ratios (SMR) using generalized linear modelling for external comparisons. Median age at diagnosis was 10 years (range 3 months to 16 years); median duration of diabetes 15 years (range 1-51 years). Forty-four patients had died (5.2%; median age at death 31 years, range 11-51 years). A further four patients died at presentation (within 24 h) from ketoacidosis and are excluded from all analyses. Calendar date of diagnosis was found to be an important predictor of mortality. Adjusting for attained age there was evidence of a decline in relative risk of death with calendar date of diagnosis of 3.4% (95% CI, 0.005-6.9%) per annum, equivalent to a 32% fall per decade (95% CI, 5-51%), or 84% (95% CI, 21-97) from 1940 to 1989. The data are consistent with a large fall in mortality between the 1940s and 1950s representing over 50% of the total reduction in mortality between 1940 and 1991. Neither sex nor age at diagnosis were significant predictors of mortality. Over the study period 1940-89 the SMR (male and female combined) fell from 981 (541-1556) to 238 (60-953) relative to the general population. This population-based study shows that the prognosis for Type 1 (insulin-dependent) diabetes mellitus has improved markedly over the period 1940-1991.

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The treatment of impotence in diabetic men with vacuum tumescence therapy was studied in a specialist clinic. Of 54 diabetic men referred with impotence, seven declined treatment, three chose self-injection with papaverine, and 44 chose vacuum therapy. Patients underwent autonomic function testing (heart rate response to respiration), measurement of penile blood flow (duplex Doppler scanning), and estimation of serum prolactin and testosterone levels. After 2 months, 33 men (75%) were able to have satisfactory intercourse using vacuum therapy. Three others could produce a satisfactory erection with vacuum therapy but their partners found it unacceptable. Eight men (18%) were unable to have satisfactory intercourse; six of these were later treated by self-injection. The median frequency of use of vacuum therapy was 5.5 (1-26) times a month. Outcome was independent of penile blood flow, autonomic function or endocrine status. Impotent diabetic men should be given counselling and offered a choice of the available treatments. Vacuum tumescence therapy is an effective and simple treatment which requires little investigation.

This study investigated the relationship between the development of diabetic retinopathy and pubertal status at onset of diabetes in 521 Type 1 diabetic patients diagnosed between 1950 and 1985. Pubertal status was based on age at onset (girls > or = 11 years and boys > or = 12 years). Retinopathy (all forms) developed in 112 patients (21.5%; 65 background and 47 proliferative retinopathy). For subjects diagnosed in either the prepubertal or postpubertal period, a similar proportion survived without developing retinopathy for any given duration of diabetes (chi 2 = 0.3822, p = 0.54). However, if only the postpubertal duration of diabetes is considered, then the proportion of patients surviving without retinopathy was significantly less for those diagnosed in the prepubertal period (chi 2 = 14.2, p = 0.002). This study suggests that the prepubertal duration of diabetes is an important phase and that the years prior to puberty do contribute to the risk of developing microvascular injury.