The effect of oral folic acid upon plasma homocysteine, endothelial function and oxidative stress in patients with type 1 diabetes and microalbuminuria.

AIMS: The purpose of this study was to investigate the effect of oral folic acid supplementation upon plasma homocysteine (HCY), endothelial function and oxidative stress on patients with type 1 diabetes and microalbuminuria to test the hypothesis that oral folic acid would lower plasma HCY and thereby improve endothelial function and reduce oxidant stress in this high-risk group of patients. METHODS: We measured plasma HCY, forearm blood flow, total antioxidant status and whole blood glutathione at baseline and after 2 months treatment with oral folic acid or placebo in 16 patients with type 1 diabetes and microalbuminuria. RESULTS: Plasma HCY fell by 25% in the folic acid group but there was no difference in endothelial function or markers of oxidant stress in the treatment group. CONCLUSIONS: Oral folic acid supplementation successfully lowered plasma HCY levels in patients with type 1 diabetes and microalbuminuria, however this was not associated with improvements in endothelial function or markers of oxidant stress.

Plasma homocysteine, oxidative stress and endothelial function in patients with Type 1 diabetes mellitus and microalbuminuria.

AIMS: The purpose of this study was to examine the associations between endothelial function, plasma homocysteine and oxidative stress in patients with Type 1 diabetes mellitus (DM) and microalbuminuria compared with DM patients with normoalbuminuria and non-diabetic control subjects. We wished to test the hypothesis that increased cardiovascular risk in patients with Type 1 diabetes and microalbuminuria may be in part as a result of hyperhomocysteinaemia-mediated oxidative stress leading to impaired endothelial function. METHODS: We measured forearm blood flow, total plasma homocysteine, total antioxidant status (TAOS) and whole blood glutathione in 31 DM patients, 16 with microalbuminuria and 15 with normoalbuminuria, and 15 non-diabetic control subjects. RESULTS: Plasma homocysteine levels were significantly higher in the microalbuminuric diabetic patients compared with the normoalbuminuric patients and the control subjects. TAOS was significantly lower in the micoalbuminuric and normoalbuminuric diabetic patients compared with the control subjects, although TAOS levels were similar in both groups of diabetic patients. There was no difference in forearm blood flow between the groups and no association between measured endothelial function and antioxidant defence/oxidative stress and homocysteine in each group. There was no association between plasma total homocysteine and TAOS or whole blood glutathione within the groups. CONCLUSIONS: We have found mild hyperhomocysteinaemia in microalbuminuric DM patients compared with normoalbuminuric DM patients and non-diabetic subjects and some evidence for reduced antioxidant defence in DM patients. These findings add to our understanding of the increased risk of vascular disease in patients with Type 1 diabetes.

Diabetic erectile dysfunction--an indicator of generalised endothelial function per se?

Erectile dysfunction (ED) affects up to 70% of men with diabetes. However, the pathophysiology of ED in diabetes remains uncertain with both neuronal and vascular factors cited. We examined whether ED is an indicator of generalized endothelial dysfunction. A unique group of diabetic patients free from established conventional cardiac risk factors were investigated. Forearm bloodflow responses to nitroprusside and acetylcholine on 11 diabetic men with ED and 11 potent diabetic men were measured by venous plethysmography. Patient characteristics between the impotent and potent patients were similar except for Hba1c which was higher in the group with ED (8.35% vs. 7.03%: p = 0.003). Both groups showed increases in FBF to incremental infusions of nitroprusside and acetylcholine but the area under curve (AUC) were similar in the ED and the non-ED groups (p = 0.16 and p = 0.17, respectively). We demonstrated that ED in patients with type 2 diabetes is not associated with additional generalized endothelial dysfunction.

Angiotensin II does not affect endothelial tone in Type 1 diabetes-results of a double-blind placebo controlled trial.

AIMS: Previously, we have demonstrated that patients with normoalbuminuric Type 1 diabetes are characterized by impaired nitric oxide bioavailability compensated for by increased vasodilatory prostanoid-mediated vasodilation. Experimental evidence suggests vascular responses to endogenous angiotensin II involve the nitric oxide and prostaglandin pathways. We examined whether selective blockade of angiotensin II influences endothelial tone with particular reference to the nitric oxide/prostaglandin pathways in patients with Type 1 diabetes free from vascular complications. METHODS: At baseline, we studied changes in forearm blood flow in response to brachial arterial infusions of acetylcholine, l-NMMA, a combination of l-NMMA and the cyclo-oxygenase inhibitor indomethacin and nitroprusside in 30 patients with normoalbuminuric Type 1 diabetes [21 male, 9 female; age 38.5 +/- 1.9 years (mean +/- sem)]. Patients were randomized to 2 weeks' treatment with placebo or the selective angiotensin II receptor blocking agent irbesartan, 300 mg, prior to forearm vasoactive responses being re-examined. RESULTS: The forearm responses to nitroprusside and acetylcholine were unchanged by both placebo (P = 0.23 and P = 0.36, respectively) and irbesartan (P = 0.41 and P = 0.36). Similarily, dose-response curves to acetylcholine in the presense of l-NMMA alone (P = 0.42) and a combination of l-NMMA and indomethacin (P = 0.44) were not altered by angiotensin II blockade. CONCLUSION: This study demonstrated that physiological blockade of endogenous angiotensin II in Type 1 diabetes does not augment agonist-evoked vasodilation or the contribution of nitric oxides and prostanoids to endothelial tone.

Di-George syndrome presenting with hypocalcaemia in adulthood: two case reports and a review.

This report describes two cases of Di-George syndrome presenting with hypoparathyroidism in adulthood. The first patient presented with profound hypocalcaemia that resulted in a generalised seizure. Routine investigations revealed hypoparathyroidism. The clue to her underlying condition was the postnatal death of her young child. This case shows that Di-George syndrome can present in adulthood with hypocalcaemia in the absence of other classic features of this condition. This has enormous implications for future family planning and may also have important health implications. The second patient, diagnosed on routine blood testing, had previously suffered with a congenital heart condition, but the syndrome was not revealed until she was of postmenopausal age. These two patients show that Di-George syndrome can present in adulthood with hypocalcaemia. This is an important observation because the condition has profound implications for health and family planning.

The contribution of nitric oxide and vasodilatory prostanoids to bradykinin-mediated vasodilation in Type 1 diabetes.

AIMS: To investigate the effect of bradykinin on endothelial tone in normoalbuminuric Type 1 diabetic patients and specifically whether any changes are mediated through nitric oxide or prostaglandins. METHODS: Forearm blood flow was measured using venous occlusion plethysmography at baseline and after brachial artery infusions of incremental doses of bradykinin (50, 100 and 200 ng/min) in 15 patients with Type 1 diabetes and 13 non-diabetic controls. Forearm blood flow at baseline and following bradykinin was then re-examined after local infusion of L-NMMA, a nitric oxide synthase inhibitor, and L-NMMA with indomethacin, a cyclo-oxygenase inhibitor. RESULTS: Baseline blood flow in the diabetic and control groups were similar (4.46 +/- 1.11 vs. 3.41 +/- 1.23 ml/min/100 ml, respectively; P = 0.07). After infusion of L-NMMA and L-NMMA with indomethacin, there was a similar reduction in blood flow responses to bradykinin in both groups. There was no significant difference between the diabetic patients and control subjects in the percentage reduction in forearm blood flow following L-NMMA (16.55 vs. 18.12%, respectively, P = 0.94) and L-NMMA with indomethacin (47.1 vs. 37.3%, respectively, P = 0.14). CONCLUSIONS: This study demonstrates that bradykinin-stimulated vasodilation is mediated by both nitric oxide and prostaglandin release from the endothelium in patients with Type 1 diabetes and normoalbuminuria, and in healthy control subjects. We have also shown that the relative contributions of nitric oxide and prostaglandin to bradykinin-mediated vasodilation are similar in these diabetic patients compared with non-diabetic subjects.

Recurrent severe hyperandrogenism during pregnancy: a case report.

This report describes the case of a 28 year old woman with virilisation occurring in two successive pregnancies. Recurrent maternal virilisation is rare (seven previous reports) and this case is unique in its severity. Differential diagnoses include ovarian disease and fetal aromatase deficiency. New techniques to exclude a fetal cause were used in this case. This patient presented during the third trimester of her first pregnancy with rapid onset of hirsuitism, increased musculature, and deepening voice. A blood hormone profile revealed significant hyperandrogenism (testosterone, 72.4 nmol/litre; normal range, 0.5-3.0). She delivered a normal boy and maternal androgen concentrations returned rapidly to normal (testosterone, 0.8 nmol/litre). She presented two years later, during her second pregnancy, with similar symptoms and biochemistry (testosterone, 47.5 nmol/litre). Again, she delivered a healthy normal boy and androgens returned immediately to normal (serum testosterone, 2.0 nmol/litre). Ultrasonography revealed no evidence of ovarian (or adrenal) masses in either pregnancy. Umbilical cord venous blood sampling and placental assays revealed no evidence of fetal aromatase deficiency. Recurrent hyperandrogenism during pregnancy is rare. Ovarian luteoma rarely recurs and hyperreactio luteinalis does not lead to such pronounced androgen concentrations. Therefore, this patient has a unique ovarian condition that could be harmful to offspring and mother.

Cardiovascular risk in women with polycystic ovarian syndrome (PCOS).

AIMS: Studies have suggested that polycystic ovary syndrome (PCOS) is associated with increased cardiovascular risk. The aim of this study was to examine cardiovascular risk profiles in women with PCOS compared with healthy age and weight matched control subjects using novel biochemical and biophysical markers. METHODS: After ethics committee approval, 11 women with PCOS and 12 controls were recruited (mean age, 32; SD, 6.5 years; mean body mass index (BMI), 33.1; SD, 5.9 kg/m2). Serum was analysed for lipid and lipoprotein profile (total and high density lipoprotein cholesterol, triglycerides, apolipoprotein B-100, apolipoprotein A1, lipoprotein (a)), and sialic acid, fibrinogen, homocysteine, and C reactive protein (CRP) concentrations. Endothelial function was also assessed by a standard venous occlusion plethysmography technique to measure reactive hyperaemic forearm blood flow (RH), and expressed as per cent increase from baseline. RESULTS: There were no significant differences in glucose, lipid, or lipoprotein concentrations between the two groups. Furthermore, sialic acid (PCOS: mean, 70.5; SD, 149 mg/litre; controls: mean, 71.3; SD, 112 mg/litre), fibrinogen (PCOS: mean, 3.1; SD, 1.0 g/litre; controls: mean, 3.3; SD, 0.7 g/litre), CRP (PCOS: mean, 4.6; SD, 4.2 mg/litre; controls: mean, 5.41 SD, 5.5 mg/litre), and RH (PCOS: mean, 158.7; SD, 135.5%; controls: mean, 200.1; SD, 114.2%) were similar. CONCLUSIONS: There were no differences in surrogate markers of the processes linked to enhanced cardiovascular risk between patients with PCOS and weight matched controls.

Reduced forearm reactive hyperaemia in normoalbuminuric subjects with Type 1 diabetes and retinopathy.

AIM: To determine whether the forearm vasodilatory response to reactive hyperaemia (RH) is reduced in normoalbuminuric subjects with Type 1 diabetes mellitus and retinopathy compared with subjects with no retinopathy. METHODS: Forearm RH, an indicator of endothelial function, was measured, using strain-gauge plethysmography, in 39 normoalbuminuric subjects (22 with retinopathy) with long-standing Type 1 diabetes mellitus. RESULTS: were evaluated in relation to conventional risk factors for atherosclerosis, and C-reactive protein (CRP), which we have recently determined to be an independent correlate of forearm RH. RESULTS: Forearm RH was decreased in subjects with retinopathy compared with those with no retinopathy (219 +/- 182 vs. 473 +/- 355, P < 0.01). Both retinopathy and CRP proved to be independent and negative predictors, and explain 27% of the variance, in forearm RH. CONCLUSION: Retinopathy in subjects with Type 1 diabetes mellitus may reflect a generalized process of endothelial dysfunction, even in the absence of microalbuminuria.

Effects of cyclo-oxygenase inhibition on vasodilatory response to acetylcholine in patients with type 1 diabetes and nondiabetic subjects.

OBJECTIVE: Studies examining vasodilatory responses to acetylcholine (ACh) and its derivatives have been conflicting. Enhanced activation of the cyclo-oxygenase pathway and increased availability of vasodilatory prostanoids may occur in type 1 diabetes, and this may compensate for the observed reduction in nitric oxide (NO) activity We examined the role of cyclo-oxygenase inhibition on vasodilatory responses in 12 healthy normotensive type 1 diabetic adults and 12 nondiabetic control subjects of similar age, sex, and BMI. RESEARCH DESIGN AND METHODS: Forearm blood flow was measured using a venous occlusion plethysmography technique at baseline and after brachial artery infusions of ACh (7.5, 15, and 30 microg/min). Forearm blood flow at baseline and after ACh was then reexamined after local intra-arterial infusion of indomethacin (0.3 mg/100 ml forearm volume), a cyclo-oxygenase inhibitor. RESULTS: Baseline blood flow in the diabetic and control groups were similar (2.65 +/- 0.26 vs. 2.59 +/- 0.20 ml/min per 100 ml, respectively; P = 0.4). After indomethacin infusion, the vasodilatory responses to all doses of ACh were reduced in both the diabetic (by 25.30 +/- 4.90%) and control group (by 11.23 +/- 5.45%). However, the reduction in blood flow response to ACh after indomethacin was greater in diabetic patients compared with control subjects (P = 0.03). CONCLUSIONS: Our findings suggest that vasodilatory, prostanoids are important in determining endothelial response to ACh in diabetic and nondiabetic subjects. Increased prostaglandin-mediated vasodilation may compensate for attenuated responses to NO previously reported in diabetic subjects. These findings may partly explain the conflicting reports of endothelial dysfunction in patients with type 1 diabetes.

Oral treatment with an antioxidant (raxofelast) reduces oxidative stress and improves endothelial function in men with type II diabetes.

AIMS/HYPOTHESIS: To determine whether raxofelast, a new water soluble antioxidant decreases oxidative stress and improves endothelial function in men with Type II (non-insulin dependent) diabetes mellitus. METHODS: We treated ten normotensive, normocholesterolaemic men with Type II diabetes and as controls ten healthy men matched with them for age with raxofelast (600 mg twice daily) for 1 week. Plasma 8-epi-PGF(2a), a non-enzymic oxidation product of arachidonic acid was measured by gas chromatography/mass spectrometry as an index of oxidative stress. Forearm vasodilator responses to brachial artery infusion of acetylcholine (7.5, 15 and 30 microg min(-1)) and of the nitric oxide donor nitroprusside (1, 3 and 10 microg min(-1)) were measured by strain gauge plethysmography. RESULTS: Plasma concentrations of 8-epi-PGF(2a), were greater in diabetic than in control men (0.99 +/- 0.20 vs 0.18 +/- 0.01 nmol 1(-1), means +/- SEM, p < 0.001) and fell after raxofelast (from 0.99 +/- 0.20 to 0.47 +/- 0.07 nmol 1(-1), p < 0.05) in diabetic men but not in control men. Blood flow responses to acetylcholine were lower (p < 0.05) in diabetic than in control men (7.4 +/- 1.0 vs 12.9 +/- 2.3 ml min(-1) x 100 ml(-1) for the highest dose). In diabetic men, but not in control men, raxofelast increased (p < 0.05) blood flow responses to acetylcholine (from 7.4 +/- 1.0 m x min(-1) x 100 ml(-1) to 11.3 +/- 2.3 ml x min(-1) x 100 ml(-1) at highest dose). Blood flow responses to nitroprusside were similar in control and diabetic men and in both groups were similar before and after raxofelast. CONCLUSION/INTERPRETATION: Oral treatment with raxofelast for 1 week reduces oxidative stress and improves endothelial function in men with Type II diabetes.

Comparison of vasodilator effects of substance P in human forearm vessels of normoalbuminuric Type 1 diabetic and non-diabetic subjects.

AIMS: To compare the vasodilatory responses to substance P in human forearm vessels in Type 1 normoalbuminuric diabetic and non-diabetic subjects. METHODS: Forearm blood flow (FBF) was measured using a plethysmography technique in 12 normoalbuminuric Type 1 diabetic subjects (six males, six females) (HbA(1c) 8.2 +/- 0.3% (mean +/- SEM)) and 12 non-diabetic healthy control subjects in response to the infusion of the vasodilators substance P (SP), acetylcholine (ACh) and nitroprusside. RESULTS: There was no significant difference in baseline FBF between the two groups (2.80 +/- 0.29 ml/min per 100 ml forearm tissue (diabetic group) vs. 2.85 +/- 0.37 ml/min per 100 ml (non-diabetic group), P = 0.45). Infusion of SP was associated with an incremental increase in FBF in the diabetic (0.6, 2 and 6 ng/min - 6.08 +/- 1.07, 7.82 +/- 1.08 and 9.48 +/- 1.14 ml/min per 100 ml, respectively) and the non-diabetic group (0.6, 2 and 6 ng/min - 5.41 +/- 0.80, 6.93 +/- 0.96 and 9.25 +/- 1.11 ml/min per 100 ml, respectively). Similarly, an incremental rise in FBF was observed during infusion of ACh (diabetic group: 7.5, 15 and 30 microg/min - 7.14 +/- 1.22, 8.91 +/- 1.40 and 11.67 +/- 1.93 ml/min per 100 ml, respectively; non-diabetic group: 7.5, 15 and 30 microg/min - 5.87 +/- 0.81, 7.49 +/- 0.96 and 10.74 +/- 1.29 ml/min per 100 ml, respectively). When FBF was expressed as percentage change from baseline, there was no significant difference in vasodilatory responses between the two groups for SP (0.6 ng/min, P = 0.21; 2 ng/min, P = 0.19; 6 ng/min, P = 0.19) or ACh (7.5 microg/min, P = 0.20; 15 microg/min, P = 0.20; 30 microg/min, P = 0.35). CONCLUSIONS: This study suggests that endothelium-dependent vasodilatory responses to SP (and ACh) are not impaired in Type 1 diabetic subjects with normal urinary albumin excretion.

Endothelial dysfunction in Type 2 diabetic subjects with and without microalbuminuria.

AIMS: The primary aim of this study was to determine whether microalbuminuria is associated with endothelial dysfunction in Type 1 diabetes mellitus. The secondary aim was to determine whether any reported biochemical markers of cardiovascular risk are associated with endothelial dysfunction in this group. METHODS: Measurements were made of the vasodilatory responses of the brachial artery to post-ischaemic hyperaemia and to sublingual glyceryl trinitrate (GTN) (causing endothelium-dependent and endothelium-independent dilation, respectively) using a high-resolution ultrasound technique in 18 Type 1 diabetic patients with microalbuminuria, 18 age and sex-matched normoalbuminuric Type 1 diabetic patients and 18 non-diabetic control subjects. RESULTS: There was a significant reduction in flow-mediated dilation (FMD) in microalbuminuric and normoalbuminuric diabetic patients compared with control subjects (2.4% (95% confidence interval (CI) 1.0-3.8%) and 2.3% (95% CI 0.7-3.9%) respectively vs. 6.3% (95% CI 5.1-7.5%), P<0.0001) but no difference in GTN-mediated dilation (14.7% (95% CI 10.7-18.7%) and 15.2% (95% CI 11.2-19.2%) vs. 18.7% (95% CI 16.1-21.3%), P = 0.09). There was no significant difference in FMD, however, between the microalbuminuric group and normoalbuminuric group (P=0.45). FMD was not significantly associated with urinary albumin-creatinine ratio, glycosylated haemoglobin, plasma glucose, lipid or lipoprotein concentrations in diabetic patients. There was a positive correlation between active transforming growth factor (TGF)-beta concentration, a novel biochemical marker of macrovascular disease, and FMD in diabetic patients (r=0.36, P<0.05). GTN-mediated dilation was positively associated with HDL-cholesterol concentration (r = 0.49, P = 0.002) but not with other biochemical variables (including active TGF-beta concentration). Active TGF-beta concentration was not associated with degree of microalbuminuria or other biochemical parameters. CONCLUSIONS: These data suggest that endothelial dysfunction occurs in Type 1 diabetic patients regardless of urine albumin status. Endothelial dysfunction appears therefore to predate the development of microalbuminuria as a marker for the development of coronary artery disease. It is also concluded that low plasma levels of active TGF-beta are associated with an impaired endothelial response and this may provide a useful tool for identifying Type 1 diabetic patients at a greater risk of coronary artery disease.

Exercise-induced GH secretion is enhanced by the oral ingestion of melatonin in healthy adult male subjects.

There is evidence that melatonin may play a role in modulating pituitary secretion, although the mechanisms are unclear. We examined the effects of a single dose of oral melatonin (5mg) on exercise-induced GH secretion. In a randomised, double-blind, placebo-controlled study, seven healthy male subjects undertook an initial period of graded bicycle ergometric exercise to determine maximum workload and oxygen uptake (VO(2max)). Subjects were subsequently studied on two further occasions, receiving either melatonin or placebo in random order at the onset of each study (-60min). At 0 min a period of bicycle exercise was performed for 8 min at a workload corresponding to 70% of that achieved at VO(2max). Serum GH and IGF-binding protein-1 (IGFBP-1) concentration was measured at 15-min intervals from the onset of the study until 120 min post-exercise. Blood was also sampled for the measurement of plasma glucose, insulin, non-esterified fatty acids, IGFBP-3, melatonin and vasopressin concentration. There was an exercise-induced increase in GH concentration following melatonin which was greater compared with placebo as assessed by both area under the curve (P<0.01) and peak increase in GH levels (P<0.01). The peak increase in IGFBP-1 levels post-exercise was also significantly greater following melatonin compared with placebo (P<0. 01) but did not quite reach levels of significance as measured by area under the curve (P=0.07). Since exercise-induced GH secretion is thought to be mediated predominantly through a hypothalamic pathway, it seems likely that melatonin facilitates GH secretion at a hypothalamic level.

Dynamic updating in DIAS-NIDDM and DIAS causal probabilistic networks.

Diabetes advisory system (DIAS) is a decision support system, which has been developed to provide advice on the amount of insulin injected by subjects with insulin-dependent diabetes mellitus (IDDM). DIAS employs a temporal causal probabilistic network (CPN) to implement a stochastic model of carbohydrate metabolism. The CPN network has recently been extended to provide also advice to subjects with noninsulin-dependent diabetes mellitus (NIDDM). However, due to increased complexity and size of the extended CPN the calculations became unfeasible. The CPN network was, therefore, simplified and a novel approach employed to generate conditional probability tables. The principles of dynamic CPN's were adopted and, in combination with the method of conditioning, learning, and forecasting, were implemented in a time- and memory-efficient way. An evaluation using experimental data was carried out to compare the original and revised DIAS implementations employing data collected by patients with IDDM, and to assess the a posteriori identifiability of model parameters in patients with NIDDM.

DIAS-NIDDM--a model-based decision support system for insulin dose adjustment in insulin-treated subjects with NIDDM.

A decision support system has been developed, Diabetes Insulin Advisory System for patients with non-insulin dependent diabetes mellitus (DIAS-NIDDM), assisting in the adjustment of insulin doses in insulin-treated subjects. DIAS-NIDDM uses a causal probabilistic network (CPN) model of carbohydrate metabolism to make stochastic predictions of blood glucose (BG) excursions. The CPN model is an extension of an existing model with an added component representing endogenous insulin secretion. A linear relationship between BG and insulin concentration due to BG stimulated insulin secretion is assumed. Model parameters (pancreatic sensitivity, insulin sensitivity, and time-to-peak of NPH insulin) are estimated by Bayesian probability updating from patient's specific data (food intake, insulin doses, BG measurements) recorded over a period of 4 days. The estimated parameters allow the system to be potentially used as a diagnostic tool to identify abnormalities of carbohydrate metabolism: impaired insulin secretion, insulin resistance and the severity of the impairments. DIAS-NIDDM was used to predict patient-specific BG profiles and advise on insulin doses during a pilot study in eight patients with NIDDM of whom five were treated with insulin. Compared to the administered insulin amount, daily insulin amount advised by DIAS-NIDDM was similar (within 4 U) in three patients, higher by 20% (19 U) in one patient and lower by 40% (18 U) and 50% (11 U) in two patients, respectively. The inter-day coefficient of variation of the daily insulin advice suggests that, at least according to DIAS-NIDDM criteria, day-to-day adjustment of insulin doses is necessary to maintain optimum control.

Alcohol ingestion and glycaemic control in patients with insulin-dependent diabetes mellitus.

It is widely accepted that alcohol consumption by patients with insulin-dependent (Type 1) diabetes mellitus is associated with an increased risk of hypoglycaemia. This association has been the subject of few studies, however, and there is not much evidence to support advice currently given to patients. Available information suggests that moderate alcohol consumption by healthy, fed subjects does not cause acute hyper- or hypoglycaemia although there may be a delayed risk of hypoglycaemia the morning after evening alcohol intake. Alcohol can lead to potentially hazardous hypoglycaemia in fasted individuals or in those dependent upon alcohol and has been associated with hypoglycaemic unawareness.

Assessing the impact of diabetes on female sexuality.

Sexual dysfunction in men is well recognised but the effects of diabetes on women's sexual health is less researched and understood. Few women seek help for sexual problems and yet effective treatments may be available. Some genito-urinary diseases are more common in diabetes and the community nurse should consider this as part of the patient's assessment. Women with diabetes should be given appropriate advice on pregnancy. Community nurses have a major role to play in helping women with diabetes to talk freely about their sexuality and sexual health problems.

Pneumomediastinum complicating diabetic ketoacidosis.

A 24-year-old previously healthy man presented with a 3-week history of progressively intensifying symptoms of diabetes mellitus. He had become increasingly unwell during the night preceding his admission to hospital and had developed central pleuritic chest pains with nausea; he had vomited once. On admission, he was clinically dehydrated and acidotic with Kussmaul's respiration. A diagnosis of diabetic ketoacidosis was confirmed by laboratory tests (arterial pH 7.21; bicarbonate 11.6 mmol l-1; blood glucose 40.5 mmol l-1, and heavy ketonuria). Subcutaneous emphysema was palpable in the neck tissues and a chest X-ray revealed mediastinal emphysema. There was no clinical or radiological evidence of acute or chronic pulmonary disease and a barium swallow confirmed the integrity of the oesophagus. He made an uneventful recovery from the ketoacidosis with conventional therapy. The subcutaneous emphysema and pneumomediastinum had completely resolved at review 4 weeks later.