Can duplex arterial ultrasonography reduce unnecessary angiography?

OBJECTIVE: To assess the value of arterial duplex ultrasound, which assesses the location and severity of arterial disease, in determining whether invasive vascular intervention is required.METHOD: A total of 166 consecutive diabetic patients presenting at a multidisciplinary foot clinic with severe peripheral vascular disease, with or without a foot ulcer, were included in this prospective study. The choice of vascular intervention was based on the results of a duplex ultrasound examination. Subjects were followed up for two years, and their clinical management, vascular assessments and interventions given, and patient outcomes were recorded in a specially designed protocol.RESULTS: Based on findings of the duplex ultrasound, it was recommended that 55 patients (33%) should undergo angioplasty (percutaneous transluminal angioplasty [PTA] and/or subintimal recanalisation), 64 patients (39%) diagnostic angiography and 47 patients (28%) medical treatment only, thereby avoiding unnecessary angiography and its potential complications. Diagnostic angiography was recommended when the duplex ultrasound results were inconclusive. Fifty-two of the 55 patients recommended angiography with simultaneous angioplasty had an angiography; of these, 42 (81%) then had an angioplasty. Fifty-seven of the 64 patients with inconclusive results had an angiography. Of these, 23 (40%) subsequently had angioplasty, only 10 (18%) had reconstructive surgery and 24 (42%) had a diagnostic angiography only.CONCLUSION: Arterial duplex ultrasound may assist evaluations of the need for and type of invasive vascular intervention in patients with an ischaemic diabetic foot. It can thus help avoid diagnostic angiographies that do not result in vascular intervention. However, such decision-making remains at the discretion of the vascular surgeon and radiologist

First-degree relatives of type 2 diabetic patients have reduced expression of genes involved in fatty acid metabolism in skeletal muscle

Context: First-degree relatives of patients with type 2 diabetes (FH+) have beens hown to have decreased energy expenditure and decreased expression of mitochondrial genes in skeletal muscle. In previous studies, it has been difficult to distinguish whether mitochondrial dysfunction and differential regulation of genes are primary (genetic) or due to reduced physical activity, obesity, or other correlated factors. Objective: The aim of this study was to investigate whether mitochondrial dysfunction is a primary defect or results from an altered metabolic state. Design: We compared gene expression in skeletal muscle from 24 male subjects with FH and 26 without FH matched for age, glucose tolerance, VO (peak oxygen uptake), and body mass index using microarrays. Additionally, type fiber composition, mitochondrial DNA content, and citrate synthase activity were measured. The results were followed up in an additional cohort with measurements of in vivo metabolism. Results: FH+vs. FH- subjects showed reduced expression of mitochondrial genes (P = 2.75 × 10), particularly genes involved in fatty acid metabolism (P = 4.08 × 10), despite similar mitochondrial DNA content. Strikingly, a 70% reduced expression of the monoamine oxidase A (MAOA) gene was found in FH+ vs. FH- individuals (P = 0.0009). Down-regulation of the genes involved in fat metabolism was associated with decreased in vivo fat oxidation and increased glucose oxidation examined in an additional cohort of elderly men. Conclusions: These results suggest that genetically altered fatty acid metabolism predisposes to type 2 diabetes and propose a role for catecholamine-metabolizing enzymes like MAOA in the regulation of energy metabolism

Less pronounced response to exercise in healthy relatives to type 2 diabetic subjects compared with controls

Healthy first-degree relatives with heredity of type 2 diabetes (FH+) are known to have metabolic inflexibility compared with subjects without heredity for diabetes (FH-). In this study, we aimed to test the hypothesis that FH+ individuals have an impaired response to exercise compared with FH-. Sixteen FH+ and 19 FH- insulin-sensitive men similar in age, peak oxygen consumption ((V) over dot(O2 peak)), and body mass index completed an exercise intervention with heart rate monitored during exercise for 7 mo. Before and after the exercise intervention, the participants underwent a physical examination and tests for glucose tolerance and exercise capacity, and muscle biopsies were taken for expression analysis. The participants attended, on average, 39 training sessions during the intervention and spent 18.8 MJ on exercise. (V) over dot(O2 peak)/kg increased by 14%, and the participants lost 1.2 kg of weight and 3 cm waist circumference. Given that the FH- group expended 61% more energy during the intervention, we used regression analysis to analyze the response in the FH+ and FH- groups separately. Exercise volume had a significant effect on (V) over dot(O2 peak), weight, and waist circumference in the FH- group, but not in the FH+ group. After exercise, expression of genes involved in metabolism, oxidative phosphorylation, and cellular respiration increased more in the FH- compared with the FH+ group. This suggests that healthy, insulin-sensitive FH+ and FH- participants with similar age, (V) over dot(O2 peak), and body mass index may respond differently to an exercise intervention. The FH+ background might limit muscle adaptation to exercise, which may contribute to the increased susceptibility to type 2 diabetes in FH+ individuals

Impact of exercise training on DNA methylation in skeletal muscle from first degree relatives of patients with type 2 diabetes

Several studies have investigated the relationship between genetic variation and DNA methylation with respect to type 2 diabetes, but it is unknown if DNA methylation is a mediator in the disease pathway or if it is altered in response to disease state. This study uses genotypic information as a causal anchor to help decipher the likely role of DNA methylation measured in peripheral blood in the etiology of type 2 diabetes. Illumina HumanMethylation450 BeadChip data were generated on 1,018 young individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. In stage 1, 118 unique associations between published type 2 diabetes single nucleotide polymorphisms (SNPs) and genome-wide methylation (methylation quantitative trait loci [mQTLs]) were identified. In stage 2, a further 226 mQTLs were identified between 202 additional independent non-type 2 diabetes SNPs and CpGs identified in stage 1. Where possible, associations were replicated in independent cohorts of similar age. We discovered that around half of known type 2 diabetes SNPs are associated with variation in DNA methylation and postulated that methylation could either be on a causal pathway to future disease or could be a noncausal biomarker. For one locus (KCNQ1), we were able to provide further evidence that methylation is likely to be on the causal pathway to disease in later life