Microbiological evaluation of resection margins of the infected diabetic foot ulcer.

AIM: To evaluate the impact of surgical debridement on the microbiology of resection margins of an infected diabetic foot ulcer and to compare the use of marginal sampling as a guide for antimicrobial therapy. METHODS: Forty consecutive participants were studied. Tissue samples from infected diabetic foot ulcers were obtained at first contact by podiatrists. After surgical debridement to macroscopically healthy tissue, multiple samples were obtained from the margins of the residuum and also from excised non-viable tissue. Debridement was done by a single surgeon. Bacterial species were classified according to pathogenic potential a priori into Red Group-Definite pathogen causing infection, Yellow Group-Likely to be causing infection if present in more than one specimen and Green Group -Commensals, not causing infection. RESULTS: There was a relative reduction of 49% (p = 0.002) in bacteria in the most pathogenic (red) group, and 59% (p = 0.002) in the yellow group in podiatry samples compared with resection specimen. Positive cultures from margins of the residuum were observed in 75% of cases. There was a relative reduction of 67% (p = 0.0001) in bacteria in the red and 48% (p = 0.06) in the yellow group in marginal samples from the residuum compared with podiatry samples. CONCLUSIONS: After surgical debridement to healthy tissue, positive cultures from marginal tissue samples provided vital information on the presence of pathogenic bacteria. This allowed antibiotics to be individualised post-surgical debridement.

Assessment of normal reference values for thyroid uptake of technetium-99m pertechnetate in a single centre UK population.

OBJECTIVE: This study aims to explore the normal reference values for thyroid uptake of technetium-99m (Tc) pertechnetate in a UK population. PATIENTS AND METHODS: A retrospective review of 60 euthyroid patients who underwent thyroid imaging with Tc pertechnetate between January 2012 to April 2014 as part of dual-tracer subtraction parathyroid scintigraphy. Tc pertechnetate thyroid uptake values were determined for each patient. Medical records and biochemical thyroid function tests were reviewed to ensure that all patients were not on medication that could affect thyroid function and they were both clinically and biochemically euthyroid 6 months before and following the scan. RESULTS: Median and interquartile uptake range of Tc pertechnetate in euthyroid patients were 0.9 and 0.5-1.4%, respectively. The normal reference range in the study population was 0.2-2.0%. Thyroid uptake inversely correlated with age in females (r=-0.40, P=0.04), males (r=-0.50, P=0.04), and whole group (r=-0.40, P=0.002). CONCLUSION: The calculated normal reference range in this study was found to be less than that used in our own and many other UK institutions. The results demonstrate the importance of periodic evaluation of normal uptake values and provide support for prospective studies defining the normal reference range to be performed.

Altered volume, morphology and composition of the pancreas in type 2 diabetes.

OBJECTIVE: Although impairment in pancreatic insulin secretion is known to precede the clinical diagnosis of type 2 diabetes by up to a decade, fasting blood glucose concentration only rises abnormally once the impairment reaches a critical threshold. Despite its centrality to the pathogenesis of type 2 diabetes, the pancreas is the least studied organ due to its inaccessible anatomical position. Previous ultrasound and CT studies have suggested a possible decrease in pancreatic volume in type 2 diabetes. However, ultrasound techniques are relatively insensitive while CT uses ionizing radiation, making these modalities unsuitable for precise, longitudinal studies designed to explore the underlying mechanisms of type 2 diabetes. Hence there is a need to develop a non-invasive, safe and precise method to quantitate pancreas volume. METHODS: We developed and applied magnetic resonance imaging at 3.0T to obtain balanced turbo field echo (BTFE) structural images of the pancreas, together with 3-point Dixon images to quantify pancreatic triglyceride content. Pancreas volume, morphology and triglyceride content was quantified in a group of 41 subjects with well-controlled type 2 diabetes (HbA1c ≤ 7.6%) taking only metformin (duration of T2DM 5.7 ± 0.7 years), and a control group of 14 normal glucose tolerance subjects matched for age, weight and sex. RESULTS: The mean pancreatic volume was found to be 33% less in type 2 diabetes than in normal glucose tolerant subjects (55.5 ± 2.8 vs. 82.6 ± 4.8 cm3; p < 0.0001). Pancreas volume was positively correlated with HOMA-ß in the type 2 diabetes subjects (r = 0.31; p = 0.03) and controls (r = 0.46; p = 0.05) considered separately; and in the whole population studied (r = 0.37; p = 0.003). In type 2 diabetes, the pancreas was typically involuted with a serrated border. Pancreatic triglyceride content was 23% greater (5.4 ± 0.3 vs. 4.4 ± 0.4%; p = 0.02) in the type 2 diabetes group. CONCLUSION: This study describes for the first time gross abnormalities of the pancreas in early type 2 diabetes and quantifies the decrease in pancreas size, the irregular morphology and increase in fat content.

Effect of vildagliptin on hepatic steatosis.

CONTEXT: Although dipeptidyl-peptidase-4 inhibitors exert their major action via an incretin mechanism, a favorable effect of vildagliptin on lipid metabolism remains unexplained. OBJECTIVE: The objective was to examine hepatic triglyceride levels and insulin sensitivity on vildagliptin. DESIGN: This was a 6-month, randomized, double-blind, placebo-controlled trial. SETTING: This was an outpatient study at a university clinical research center. PATIENTS: Individuals with type 2 diabetes (n = 44) and glycated hemoglobin ≤ 7.6% on stable metformin therapy were included. INTERVENTION: Intervention was vildagliptin 50 mg twice a day or placebo over 6 months. MAIN OUTCOME MEASURES: Main outcome measures were hepatic triglyceride levels and insulin sensitivity. RESULTS: Mean fasting liver triglyceride content decreased by 27% with vildagliptin, from 7.3 ± 1.0% (baseline) to 5.3 ± 0.9% (endpoint). There was no change in the placebo group. The between-group difference in change from baseline was significant (P = .013). Mean fasting plasma glucose concentration decreased over the study period with vildagliptin vs placebo by -1.0 mmol/L (P = .018), and there was a positive correlation between these decrements and liver triglyceride in the vildagliptin group at 3 months (r = 0.47; P = .02) and 6 months (r = 0.44; P = .03). Plasma alanine aminotransferase fell from 27.2 ± 2.8 to 20.3 ± 1.4 IU/L in the vildagliptin group (P = .0007), and there was a correlation between the decrements in alanine aminotransferase and liver triglyceride (r = 0.83; P < .0001). Insulin sensitivity during the euglycemic clamp was similar in each group at baseline (3.24 ± 0.30 vs 3.19 ± 0.38 mg/kg/min) and did not change (adjusted mean change of 0.26 ± 0.22 vs 0.32 ± 0.22 mg/kg/min; P = .86). Mean body weight decreased by 1.6 ± 0.5 vs 0.4 ± 0.5 kg in the vildagliptin and placebo groups, respectively (P = .08). CONCLUSIONS: This study demonstrates that the dipeptidyl-peptidase-4 inhibitor vildagliptin brings about a clinically significant decrease in hepatic triglyceride levels during 6 months of therapy unrelated to change in body weight. There was no change in peripheral insulin sensitivity.

Diurnal variation in skeletal muscle and liver glycogen in humans with normal health and Type 2 diabetes.

In health, food carbohydrate is stored as glycogen in muscle and liver, preventing a deleterious rise in osmotically active plasma glucose after eating. Glycogen concentrations increase sequentially after each meal to peak in the evening, and fall to fasting levels thereafter. Skeletal muscle accounts for the larger part of this diurnal buffering capacity with liver also contributing. The effectiveness of this diurnal mechanism has not been previously studied in Type 2 diabetes. We have quantified the changes in muscle and liver glycogen concentration with 13C magnetic resonance spectroscopy at 3.0 T before and after three meals consumed at 4 h intervals. We studied 40 (25 males; 15 females) well-controlled Type 2 diabetes subjects on metformin only (HbA1c (glycated haemoglobin) 6.4±0.07% or 47±0.8 mmol/mol) and 14 (8 males; 6 females) glucose-tolerant controls matched for age, weight and body mass index (BMI). Muscle glycogen concentration increased by 17% after day-long eating in the control group (68.1±4.8 to 79.7±4.2 mmol/l; P=0.006), and this change inversely correlated with homoeostatic model assessment of insulin resistance [HOMA-IR] (r=-0.56; P=0.02). There was no change in muscle glycogen in the Type 2 diabetes group after day-long eating (68.3±2.6 to 67.1±2.0 mmol/mol; P=0.62). Liver glycogen rose similarly in normal control (325.9±25.0 to 388.1±30.3 mmol/l; P=0.005) and Type 2 diabetes groups (296.1±16.0 to 350.5±6.7 mmol/l; P<0.0001). In early Type 2 diabetes, the major physiological mechanism for skeletal muscle postprandial glycogen storage is completely inactive. This is directly related to insulin resistance, although liver glycogen storage is normal.

Roth spots in pernicious anaemia.

Roth spots are white-centred retinal haemorrhages, previously thought to be pathognomonic for subacute bacterial endocarditis. A number of other conditions can be associated with Roth spots. In this case, the authors describe the association of Roth spots and pernicious anaemia. This association has been rarely described in the medical literature. Correct diagnosis and treatment with intramuscular vitamin B(12) injections resulted in complete resolution of the anaemia and Roth spots. The authors hope to alert clinicians to think of various differentials of Roth spots, and initiate prompt investigation and management.