Risk factors for cardiac autonomic neuropathy in type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Cardiac autonomic neuropathy (CAN) is associated with increased morbidity and mortality in type 1 diabetes. Apart from glycaemic control, risk factors for CAN have not been extensively studied. METHODS: As part of the EURODIAB Prospective Complications Study, CAN--defined as either a loss of heart rate variability or postural hypotension on standing--was assessed at baseline and follow-up (7.3+/-0.6 years from baseline) in patients with type 1 diabetes. RESULTS: Follow-up measurements were available for 956 participants without CAN at baseline (age at baseline 31.3+/-8.9 years, duration of diabetes 13.5+/-8.3 years). During follow-up, 163 (17%) subjects developed CAN, yielding an incidence of 23.4 per 1,000 person-years. Blood pressure, weight, the presence of cardiovascular disease, albuminuria, distal symmetrical polyneuropathy (DSP) and retinopathy at baseline were associated with the incidence of CAN after adjustment for sex, duration of diabetes and HbA(1)c. In a multivariate regression model, baseline factors associated with an increased risk of developing CAN were age [odds ratio (OR)=1.3 per decade, 95% CI 1.1-1.7], HbA(1)c (OR=1.2 per percentage point, 95% CI 1.1-1.4), systolic blood pressure (OR=1.1 per 10 mmHg, 95% CI 1.0-1.3), feeling faint on standing (OR=2.0, 95% CI 1.2-3.2), DSP (OR=1.9, 95% CI 1.2-3.0) and retinopathy (OR=1.7, 95% CI 1.1-2.6). CONCLUSION/INTERPRETATION: This study confirms the importance of exposure to hyperglycaemia as a risk factor for CAN. A small set of variables, including HbA(1)c, hypertension, DSP and retinopathy, predict the risk of CAN. Clinical trials are needed to address the impact of intensive antihypertensive treatment on CAN in type 1 diabetes.

Increased sural nerve epineurial blood flow in human subjects with painful diabetic neuropathy.

AIMS/HYPOTHESIS: The pathogenesis of painful diabetic neuropathy remains unknown. As a consequence we still do not have any effective, rational treatments and a greater understanding of the mechanisms is urgently required. Previous studies have shown no consistent morphological differences in the nerves of patients with and without painful neuropathy. The aim of this study was to compare epineurial haemodynamics in patients with chronic painful and painless neuropathy. METHODS: The techniques of microlightguide spectrophotometry and fluorescein angiography were used to measure epineurial intravascular oxygen saturation and blood flow respectively. Eleven patients with painful and eight with painless neuropathy were studied, with the groups matched carefully in terms of severity of neuropathy and diabetes control. RESULTS: Intravascular oxygen saturation was higher in the painful neuropathy group compared to those without pain (median 73.8% vs 67.7%, respectively; p=0.021). Fluorescein rise time was also faster in those with painful symptoms (median 18.3 s vs 53.6 s; p=0.046) indicating higher epineurial blood flow in these subjects. CONCLUSION/INTERPRETATION: These results indicate that there are distinct differences in haemodynamics within the epineurium of the sural nerve in subjects with painful and painless neuropathy. Haemodynamic factors could therefore have an important role in the pathogenesis of neuropathic pain and might offer further insight into potential treatments for this distressing condition.

Clinical experience of amiodarone-induced thyrotoxicosis over a 3-year period: role of colour-flow Doppler sonography.

OBJECTIVE: Current thinking is that amiodarone-induced thyrotoxicosis (AIT) might be either iodine-induced thyrotoxicosis in latent hyperthyroidism (Type 1) or destructive thyroiditis (Type 2), and also that colour-flow Doppler sonography (CFDS) of the thyroid and serum interleukin 6 (IL-6) are tools that can classify AIT and direct treatment. To assess the validity of this thinking, our objective was to determine whether CFDS and IL-6 identified AIT subgroups with distinct features. DESIGN: Retrospective case-note audit of all patients presenting with AIT to the Endocrine Department of a UK teaching hospital over a 3-year period. To assess proportions of Type 1 vs. Type 2 AIT and to compare and contrast their clinical features. PATIENTS: 37 patients were identified with AIT (mean age 65, range 20-86 years). In 30 patients in whom AIT persisted, 25 underwent CFDS. RESULTS: In 25 patients who underwent CFDS, 10 (40%) were classified as Type 1, 10 (40%) as Type 2 and 5 (20%) as indeterminate type. In the patients classified by CFDS in whom AIT persisted, 40% of Type 1 patients were male vs. 90% of Type 2 patients. Also, free T4 tended to be lower in patients presenting with Type 1 AIT (52.1 +/- 7.5 pmol/l) compared to Type 2 (74.8 +/- 8.1 pmol/l, P = 0.08), free T3 was lower (8.8 +/- 0.9 vs. 15.6 +/- 3.0 pmol/l, P = 0.03) and the cumulative amiodarone dose was lower (66 +/- 20 vs. 186 +/- 28 g, P = 0.002). We used less prednisolone to achieve euthyroidism in patients with Type 1 AIT whereas carbimazole doses were not different and the time to euthyroidism was the same in both groups (81 +/- 21 vs. 88 +/- 13 days). IL-6 was raised in two patients with Type 1 and in one patient with Type 2 AIT. CONCLUSIONS: CFDS could characterize two distinct subtypes in patients with AIT. Conversely, IL-6 seemed to be an unhelpful test in this context.