Latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy.

AIM: To assess if latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy. METHODS: Participants with LADA (n=31), Type 2 diabetes (n=31) and healthy control participants without diabetes (n=31) underwent a detailed assessment of neurologic deficits, quantitative sensory testing, electrophysiology, skin biopsy and corneal confocal microscopy. RESULTS: The groups were matched for age (healthy control without diabetes: 53.5±9.1 vs. Type 2 diabetes: 58.0±6.5 vs. LADA: 53.2±11.6 years), duration of diabetes (Type 2 diabetes: 10.0±8.3 vs. LADA: 11.0±9.1 years) and blood pressure. However, BMI (P=0.01) and triglycerides (P=0.0008) were lower and HbA1c (P=0.0005), total cholesterol (P=0.01) and HDL (P=0.002) were higher in participants with LADA compared with Type 2 diabetes. Peroneal motor nerve conduction velocity (P=0.04) and sural sensory nerve conduction velocity (P=0.008) were lower in participants with latent autoimmune diabetes in adults compared with Type 2 diabetes. Intra-epidermal nerve fibre density (P=0.008), corneal nerve fibre density (P=0.003) and corneal nerve branch density (P=0.006) were significantly lower in participants with LADA compared with Type 2 diabetes. There were no significant differences in the other neuropathy parameters. CONCLUSIONS: Despite comparable age and duration of diabetes, participants with LADA demonstrate more severe neuropathy and particularly small fibre neuropathy, compared with participants with Type 2 diabetes.

Cardiovascular, obstetric and neonatal outcomes in women with previous fontan repair.

OBJECTIVES: To determine cardiovascular, obstetric and neonatal outcomes of pregnancies in women who have a Fontan circulation. METHODS: A retrospective case note review of all women with a Fontan circulation who attended the joint obstetric cardiac antenatal clinic at St Mary's Hospital, Manchester (UK) between 2004 and 2016 was performed. RESULTS: In total, there were 19 pregnancies in 9 women with a history of Fontan repair. 23 women with univentricular physiology attended in this time period. 10 pregnancies (53%) resulted in live births; 1 in a stillbirth at 31 weeks gestation and 8 in miscarriage. Cardiovascular complications occurred in 2 pregnancies (11%). There were no thrombotic events, arrhythmias, myocardial infarction, or endocarditis in the antenatal or postnatal period. Obstetric complications included miscarriage (26% first trimester, 16% second trimester), along with premature delivery (24-36+6) (80%) and fetal growth restriction (70%). The majority of women were delivered by caesarean section (60%). CONCLUSIONS: Women who become pregnant following a Fontan repair carry an increased risk of cardiovascular complications. Fetal and neonatal complication rates are high and emphasize the importance of thorough, multidisciplinary, pre-conceptual assessment and counseling to allow patients to make informed decisions regarding future pregnancy.

NerveCheck: An inexpensive quantitative sensory testing device for patients with diabetic neuropathy.

AIMS: Sensory neuropathy is central to the development of painful neuropathy, and foot ulceration in patients with diabetes. Currently, available QST devices take considerable time to perform and are expensive. NerveCheck is the first inexpensive ($500), portable QST device to perform both vibration and thermal testing and hence evaluate diabetic peripheral neuropathy (DPN). This study was undertaken to establish the reproducibility and diagnostic validity of NerveCheck for detecting neuropathy. METHODS: 130 subjects (28 with DPN, 46 without DPN and 56 control subjects) underwent QST assessment with NerveCheck; vibration perception and thermal testing. DPN was defined according to the Toronto criteria. RESULTS: NerveCheck's intra correlation coefficient for vibration, cold and warm sensation testing was 0.79 (95% LOA: -4.20 to 6.60), 0.86 (95% LOA: -1.38 to 2.72) and 0.71 (95% LOA: -2.36 to 3.83), respectively. The diagnostic accuracy (AUC) for vibration, cold and warm sensation testing was 86% (SE: 0.038, 95% CI 0.79-0.94), 79% (SE: 0.058, 95% CI 0.68-0.91) and 72% (SE: 0.058, 95% CI 0.60-0.83), respectively. CONCLUSIONS: This study shows that NerveCheck has good reproducibility and comparable diagnostic accuracy to established QST equipment for the diagnosis of DPN.

Individuals with impaired glucose tolerance demonstrate normal cardiac sympathetic innervation using I-123 mIBG scintigraphy.

BACKGROUND: Impaired glucose tolerance (IGT) is associated with an increased risk of type 2 diabetes (T2DM) and cardiovascular disease. Some but not all studies have reported cardiac autonomic dysfunction in subjects with IGT and there is only one direct study of cardiac innervation in subjects with IGT. The purpose of this study was to assess global and regional cardiac sympathetic innervation and cardiac autonomic function in individuals with IGT. METHODS AND RESULTS: We undertook (123)I-mIBG scintigraphy and cardiac autonomic function in 15 subjects with IGT and 15 age and sex-matched healthy controls. Early heart to mediastinum ratio (HMR) (1.71 ± 0.17 vs 1.67 ± 0.13, P = .49), late HMR (1.73 ± 0.18 vs 1.73 ± 0.16, P = .97) and washout rate (WR) (18.6 ± 4.2 vs 19.1 ± 7.6%, P = .84), did not differ between subjects with IGT and control subjects. More detailed regional analysis revealed reduced tracer uptake at the apex, base and inferior wall in all subjects and the anterior wall in a minority of subjects. There were no differences in total score (56.6 ± 4.0 vs 53.3 ± 8.4, P = .193), modified score (48.5 ± 3.3 vs 46.2 ± 6.0, P = .215), anterior wall score (10.2 ± 1.3 vs 10.1 ± 1.6, P = .898), inferior wall score (8.9 ± 1.9 vs 7.7 ± 2.6, P = .163), basal score (18.7 ± 1.9 vs 18.2 ± 3.3, P = .636) and tests of cardiac autonomic function between the groups. CONCLUSION: Global and regional measures of MIBG uptake and washout as well as cardiac autonomic function did not differ between subjects with IGT and healthy controls.

The diagnostic accuracy of Neuropad for assessing large and small fibre diabetic neuropathy.

AIMS: Neuropad is a simple visual indicator test, with moderate diagnostic performance for diabetic peripheral neuropathy. As it assesses sweating, which is a measure of cholinergic small nerve fibre function, we compared its diagnostic performance against established measures of both large and, more specifically, small fibre damage in patients with diabetes. METHODS: One hundred and twenty-seven participants (89 without diabetic peripheral neuropathy and 38 with) aged 57 ± 9.7 years underwent assessment with Neuropad, large nerve fibre assessments: Neuropathy Disability Score, vibration perception threshold, peroneal motor nerve conduction velocity; small nerve fibre assessments: neuropathy symptoms (Diabetic Neuropathy Symptoms score) corneal nerve fibre length and warm perception threshold. RESULTS: Neuropad has a high sensitivity but moderate specificity against large fibre neuropathy assessments: Neuropathy Disability Score (> 2) 70% and 50%, vibration perception threshold (> 14 V) 83% and 53%, and peroneal motor nerve conduction velocity (< 42 m/s) 81% and 54%, respectively. However, the diagnostic accuracy of Neuropad was significantly improved against corneal nerve fibre length (< 14 mm/mm2) with a sensitivity and specificity of 83% and 80%, respectively. Furthermore, the area under the curve for corneal nerve fibre length (85%) was significantly greater than with the Neuropathy Disability Score (66%, P = 0.01) and peroneal motor nerve conduction velocity (70%, P = 0.03). For neuropathic symptoms, sensitivity was 78% and specificity was 60%. CONCLUSIONS: The data show the improved diagnostic performance of Neuropad against corneal nerve fibre length. This study underlines the importance of Neuropad as a practical diagnostic test for small fibre neuropathy in patients with diabetes.

Diabetes, Obesity and Atrial Fibrillation: Epidemiology, Mechanisms and Interventions.

Body mass index (BMI) is a powerful predictor of death, type 2 diabetes (T2DM) and cardiovascular (CV) morbidity and mortality. Over the last few decades, we have witnessed a global rise in adult obesity of epidemic proportions. Similarly, there has been a parallel increase in the incidence of atrial fibrillation (AF), itself a significant cause of cardiovascular morbidity and mortality. This may be partly attributable to advances in the treatment of coronary heart disease (CHD) and heart failure (HF) improving life expectancy, however, epidemiological studies have demonstrated an independent association between obesity, diabetes and AF, suggesting possible common pathophysiological mechanisms and risk factors. Indeed, cardiac remodeling, haemodynamic alterations, autonomic dysfunction, and diastolic dysfunction have been reported in obese and diabetic cohorts. Moreover, diabetic cardiomyopathy is characterized by an adverse structural and functional cardiac phenotype, which may predispose to the development of AF. In this review, we discuss the pathophysiological and mechanistic relationships between obesity, diabetes and AF, and some of the challenges posed in the management of this high-risk group of individuals.

Obesity, diabetes and atrial fibrillation; epidemiology, mechanisms and interventions.

The last few decades have witnessed a global rise in adult obesity of epidemic proportions. The potential impact of this is emphasized when one considers that body mass index (BMI) is a powerful predictor of death, type 2 diabetes (T2DM) and cardiovascular (CV) morbidity and mortality [1, 2]. Similarly we have witnessed a parallel rise in the incidence of atrial fibrillation (AF), the commonest sustained cardiac arrhythmia, which is also a significant cause of cardiovascular morbidity and mortality. Part of this increase is attributable to advances in the treatment of coronary heart disease (CHD) and heart failure (HF) improving life expectancy and consequently the prevalence of AF. However, epidemiological studies have demonstrated an independent association between obesity and AF, possibly reflecting common pathophysiology and risk factors for both conditions. Indeed, weight gain and obesity are associated with structural and functional changes of the cardiovascular system including left atrial and ventricular remodeling, haemodynamic alterations, autonomic dysfunction, and diastolic dysfunction. Moreover, diabetic cardiomyopathy is characterized by an adverse structural and functional cardiac phenotype which may predispose to the development of AF [3]. In this review, we discuss the pathophysiological and mechanistic relationships between obesity, diabetes and AF, and the challenges posed in the management of this high-risk group of individuals.