The aim of this study was to characterise the microbiome of new and recurrent diabetic foot ulcers using 16S amplicon sequencing (16S AS), allowing the identification of a wider range of bacterial species that may be important in the development of chronicity in these debilitating wounds. Twenty patients not receiving antibiotics for the past three months were selected, with swabs taken from each individual for culture and 16S AS. DNA was isolated using a combination of bead beating and kit extraction. Samples were sequenced on the Illumina Hiseq 2500 platform. Conventional laboratory culture showed positive growth from only 55 % of the patients, whereas 16S AS was positive for 75 % of the patients (41 unique genera, representing 82 different operational taxonomic units (OTU’s). S. aureus was isolated in 72 % of culture-positive samples, whereas the most commonly detected bacteria in all ulcers were Peptoniphilus spp., Anaerococcus spp. and Corynebacterium spp., with the addition of Staphylococcus spp. in new ulcers. The majority of OTU’s residing in both new and recurrent ulcers (over 67 %) were identified as facultative or strict anaerobic Gram-positive organisms. Principal component analysis (PCA) showed no difference in clustering between the two groups (new and recurrent ulcers). The abundance of anaerobic bacteria has important implications for treatment as it suggests that the microbiome of each ulcer “starts afresh” and that, although diverse, are not distinctly different from one another with respect to new or recurrent ulcers. Therefore, when considering antibiotic therapy the duration of current ulceration may be a more important consideration than a history of healed ulcer.
OBJECTIVE To quantify the relationship of residual C-peptide secretion to glycemic outcomes and microvascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS C-peptide was measured in an untimed blood sample in the Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) cohort of 6,076 people with type 1 diabetes monitored for an average of 5.2 years. RESULTS In regression models adjusted for age at onset and duration, effect sizes for C-peptide ≥200 vs. <5 pmol/L were as follows: insulin dose at baseline, 9% lower (P = 2 × 10−17); HbA1c during follow-up, 4.9 mmol/mol lower (P = 3 × 10−13); hazard ratio for hospital admission for diabetic ketoacidosis during follow-up, 0.44 (P = 0.0001); odds ratio for incident retinopathy, 0.51 (P = 0.0003). Effects on the risk of serious hypoglycemic episodes were detectable at lower levels of C-peptide, and the form of the relationship was continuous down to the limit of detection (3 pmol/L). In regression models contrasting C-peptide 30 to <200 pmol/L with <5 pmol/L, the odds ratio for self-report of at least one serious hypoglycemic episode in the last year was 0.56 (P = 6 × 10−8), and the hazard ratio for hospital admission for hypoglycemia during follow-up was 0.52 (P = 0.03). CONCLUSIONS These results in a large representative cohort suggest that even minimal residual C-peptide secretion could have clinical benefit in type 1 diabetes, in contrast to a follow-up study of the Diabetes Control and Complications Trial (DCCT) intensively treated cohort where an effect on hypoglycemia was seen only at C-peptide levels ≥130 pmol/L. This has obvious implications for the design and evaluation of trials of interventions to preserve or restore pancreatic islet function in type 1 diabetes.
1 October 2012 in American Journal of Clinical Oncology
Prostate cancer is the most frequently diagnosed malignancy among UK men and accounts for 12% of male deaths. Androgen deprivation therapy (ADT) is commonly used as part of the treatment for prostate cancer. It is effective at suppressing prostate-specific antigen, stabilizing disease, alleviating symptoms in advanced disease, and potentially prolonging survival. However ADT, presumably at least in part owing to low testosterone levels is associated with insulin resistance, the development of metabolic syndrome plus increased overall and cardiovascular disease mortality. We have reviewed the relationship between prostate cancer, ADT, metabolic syndrome, type 2 diabetes, and cardiovascular disease. We have not reviewed other potential medical problems such as osteoporosis. We suggest that there should be a baseline assessment of patients' risk for cardiovascular disease before starting ADT. Consideration should be given to starting appropriate therapies including lifestyle advice, antihypertensive and lipid-lowering agents, insulin sensitizer, plus possibly aspirin. Having started ADT, the patients should have a regular (possibly annual) assessment of their cardiovascular risk factors.
27 August 2016 in Journal of Diabetes Investigation
Aims/Introduction: Gestational diabetes mellitus (GDM) is defined as ‘carbohydrate intolerance of varying degrees of severity with onset or first recognition during pregnancy,’ and is associated with increased fetal and maternal risks. The aims of the present study were to investigate the prevalence of GDM in Scotland over 32 years (1981–2012), and using the data from 2012, to assess how GDM related to maternal body mass index, maternal age, parity, smoking, Scottish Index of Multiple Deprivation, infant gender and macrosomia status.Materials and Methods: GDM prevalence along with anthropometric, obstetric and demographic data were collected on a total of 1,891,097 women with a delivery episode between 1 January 1981 and 31 December 2012 using data extracted from the Scottish Morbidity Record 02. Univariate and multivariate logistic regression analysis was undertaken to investigate their association with GDM.Results: A ninefold increase in GDM prevalence was observed from 1981 to 2012 (P < 0.001). GDM prevalence in 2012 was 1.9%. Maternal body mass index, age, parity status, Scottish index of multiple deprivation and fetal macrosomia were positively associated with GDM. Reported smoking status at booking was inversely associated with GDM. Multivariable analysis showed that fetal macrosomia was not associated with GDM status.Conclusions: The present study confirmed that the reporting of GDM is low in Scotland, and that GDM is associated with maternal body mass index, maternal age, multiparity and social deprivation. GDM was negatively associated with smoking and requires further investigation. The lack of association between GDM and macrosomia (following multivariate analysis) might reflect the screening processes undertaken in Scotland.
OBJECTIVE To assess the contemporaneous prevalence of diabetic peripheral neuropathy (DPN) in people with type 1 diabetes (T1D) in Scotland and study its cross-sectional association with risk factors and other diabetic complications. RESEARCH DESIGN AND METHODS We analyzed data from a large representative sample of adults with T1D (N = 5,558). We assessed the presence of symptomatic neuropathy using the dichotomized (≥4) Michigan Neuropathy Screening Instrument Patient Questionnaire score. Logistic regression models were used to investigate associations between DPN and risk factors, as well as with other complications. RESULTS The burden of DPN is substantial with 13% prevalence overall. Adjusting for attained age, diabetes duration, and sex, the odds of DPN increased mainly with waist-to-hip ratio, lipids, poor glycemic control (odds ratio 1.51 [95% CI 1.21–1.89] for levels of 75 vs. 53 mmol/mol), ever versus never smoking (1.67 [1.37–2.03]), and worse renal function (1.96 [1.03–3.74] for estimated glomerular filtration rate levels <30 vs. ≥90 mL/min/1.73 m2). The odds significantly decreased with higher HDL cholesterol (0.77 [0.66–0.89] per mmol/L). Living in more deprived areas was associated with DPN (2.17 [1.78–2.65]) for more versus less deprived areas adjusted for other risk factors. Finally, individuals with prevalent DPN were much more likely than others to have other diabetes complications. CONCLUSIONS Diabetic neuropathy remains substantial, particularly affecting those in the most socioeconomically deprived groups. Those with clinically manifest neuropathy also have a higher burden of other complications and elevated levels of modifiable risk factors. These data suggest that there is considerable scope to reduce neuropathy rates and narrow the socioeconomic differential by better risk factor control.