Systematic review and meta-analysis of vildagliptin for treatment of type 2 diabetes.

This systematic review and meta-analysis provides an update on the efficacy and safety of vildagliptin for treatment of type 2 diabetes mellitus (T2DM). We searched MEDLINE, COCHRANE, EMBASE and the drug manufacturer's website for randomised controlled trials of vildagliptin in patients with T2DM. Sixty-nine studies (28,006 patients) were included in the meta-analysis. Compared with placebo vildagliptin reduced HbA1c (weighted mean difference WMD -0.69 %; 95 % CI -0.83 to -0.56 %; I (2) = 82 %), and it was as effective as other antidiabetic agents (WMD -0.01 %; 95 % CI -0.16 to 0.14 %; I (2) = 93 %), without increasing the risk for hypoglycemia (OR 0.83; 95 % CI 0.59 to 1.16; I (2) = 0 % vs. placebo, and OR 0.19; 95 % CI 0.15 to 0.24; I (2) = 78 % versus active comparators). However, it was associated with an increase in the incidence of arthralgia compared with other comparators (OR 1.23; 95 % CI 1.02 to 1.48; I (2) = 0 %). On the contrary, vildagliptin did not increase the incidence of pancreatitis (OR 0.97; 95 % CI 0.37 to 2.53; I (2) = 0 %), serious adverse events (OR 0.98; 95 % CI 0.88 to 1.09; I (2) = 0 %) or death (OR 1.10, 95 % CI 0.75 to 1.61; I (2) = 0 %). Finally, odds ratio (OR) for heart failure, and overall cardiovascular and cerebrovascular events was 0.77 (95 % CI 0.46 to 1.30; I (2) = 0 %) and 0.91 (95 % CI 0.73 to 1.14; I (2) = 0 %), respectively. Vildagliptin is an effective and safe therapeutic option for patients with T2DM, both as monotherapy and as add-on treatment.

Debilitating chronic diarrhea caused by generalized gastrointestinal cytomegalovirus infection in an immunocompetent adult.

Gastrointestinal cytomegalovirus (CMV) infection is a common opportunistic infection in immunocompromised patients, especially patients with acquired immunodeficiency syndrome and transplant recipients. In contrast, CMV infection of the gastrointestinal tract is rare in immunocompetent individuals. We report a case of severe, protracted, and debilitating diarrhea caused by generalized CMV infection of the gastrointestinal tract in an elderly woman with no apparent immunosuppression. An extensive diagnostic investigation demonstrated CMV-associated disease affecting both the upper and lower gastrointestinal tracts (esophagus, small intestine, and colon). Such extensive simultaneous involvement of the alimentary tract in an immunocompetent patient is rare and presents a diagnostic and therapeutic challenge. The diagnosis was based on a combination of endoscopic, histopathological, serological, and polymerase chain reaction analysis findings and our patient was successfully treated with intravenous ganciclovir. Our case demonstrates that gastrointestinal CMV infection should be considered in the differential diagnosis of severe chronic diarrhea in immunocompetent patients and that antiviral treatment may be justified in this setting.

Tissue and swab culture in diabetic foot infections: neuropathic versus neuroischemic ulcers.

We evaluated the diagnostic performance of swabs versus tissue cultures in 28 diabetic patients with neuropathic (group A) and 22 diabetic patients with neuroischemic foot ulcer (group B) and the differences in bacterial isolates between the 2 groups. In group A, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of swab cultures for the diagnosis of infection were 100%, 40%, 88.5%, and 100%, respectively. In group B, the corresponding values were 100%, 22.2%, 65%, and 100%. In group A, sensitivity, specificity, PPV, and NPV of swab cultures for the identification of pathogens were 100%, 14.3%, 53.8%, and 100%, respectively. In group B, the corresponding values were 100%, 18.2%, 55%, and 100%. In each group, Staphylococcus aureus and Pseudomonas aeruginosa were the most common isolates. The number of isolates was significantly higher on swab versus tissue cultures only in group A (P = .033). No differences were observed between groups in number of isolates and colony forming units. In conclusion, swab cultures are highly sensitive but less specific and have an excellent NPV both in diabetic patients with neuropathic and in those with neuroischemic foot ulcer. There are no differences between the groups in microbial load.

Anatomic variations of the right hepatic duct: results and surgical implications from a cadaveric study.

Purpose. Thorough understanding of biliary anatomy is required when performing surgical interventions in the hepatobiliary system. This study describes the anatomical variations of right bile ducts in terms of branching and drainage patterns, and determines their frequency. Methods. We studied 73 samples of cadaveric material, focusing on the relationship of the right anterior and posterior segmental branches, the way they form the right hepatic duct, and the main variations of their drainage pattern. Results. The anatomy of the right hepatic duct was typical in 65.75% of samples. Ectopic drainage of the right anterior duct into the common hepatic duct was found in 15.07% and triple confluence in 9.59%. Ectopic drainage of the right posterior duct into the common hepatic duct was discovered in 2.74% and ectopic drainage of the right posterior duct into the left hepatic duct in 4.11%. Ectopic drainage of the right anterior duct into the left hepatic ductal system and ectopic drainage of the right posterior duct into the cystic duct was found in 1.37%. Conclusion. The branching pattern of the right hepatic duct was atypical in 34.25% of cases. Thus, knowledge of the anatomical variations of the extrahepatic bile ducts is important in many surgical cases.

Uncoupling protein-2 45-base pair insertion/deletion polymorphism: is there an association with severe obesity and weight loss in morbidly obese subjects?

BACKGROUND: Uncoupling proteins are attractive candidate genes for obesity and type 2 diabetes mellitus. Our aim was to investigate the potential association of the uncoupling protein-2 (UCP2) 45-bp insertion/deletion (ins/del) polymorphism with obesity, as well as the potential effect of this polymorphism on weight loss variability in severely obese subjects. METHODS: A total of 158 severely obese subjects (94 without and 64 with metabolic syndrome) and 91 age and sex-matched lean controls were recruited. A subgroup of 124 obese patients participated in a 3-month weight loss program. Anthropometric and metabolic variables were measured. Participants were genotyped for the UCP2 ins/del polymorphism. RESULTS: Allelic frequency differed neither between obese subjects and controls (P=0.56), nor between obese subjects with versus without metabolic syndrome (P=0.58). At 3 months, metabolically healthy subjects carrying the insertion allele had significantly greater reduction in body mass index (P=0.029) and fat-free mass (P=0.013) and a borderline significant improvement in the homeostatic model assessment index (P=0.048). CONCLUSION: There is no association of the UCP2 ins/del polymorphism with morbid obesity in our population, but this genotype appears to be linked with a favorable response to dietary changes in metabolically healthy obese subjects.

Serotonin receptor 2A -1438G/A promoter polymorphism in relation to obesity and response to sibutramine.

AIMS: Serotonin has been related to appetite and body weight control. The aim of this study was to investigate a possible association of the -1438 /A promoter polymorphism of the serotonin 2A receptor (5HT2AR) gene with obesity-related variables and response to sibutramine. PATIENTS/METHODS: We examined the potential impact of this polymorphism on obesity and related metabolic traits in a cohort of 234 overweight/obese and 103 lean Greek subjects. Additionally, we examined whether the 5HT2AR 1438A/G polymorphism influences weight reduction and change in body composition among 106 out of these subjects, who were treated with 15 g sibutramine. Genotyping was carried out by polymerase chain reaction and restriction enzyme analysis. RESULTS: Body mass index, fat mass, and waist circumference were not significantly different across the 5HT2AR 1438A/G genotype groups in overweight/obese women. Polymorphic G allele was associated with higher triglyceride and insulin levels but not with other biochemical and metabolic parameters. Distribution of genotypes and alleles was not different between responders and nonresponders (weight loss >5 or <5 g). CONCLUSIONS: Based on these results, it seems unlikely that the 5HT2AR 1438 /A polymorphism has a major impact on obesity and related traits or the response to sibutramine in Greek overweight/obese subjects.

Accuracy of the Neuropad test for the diagnosis of distal symmetric polyneuropathy in type 2 diabetes.

OBJECTIVE: To estimate the accuracy of Neuropad for the diagnosis and staging of distal symmetric polyneuropathy (DPN) across different stages of neuropathy, using multiple-level likelihood ratios (LRs) to interpret the time necessary to complete the color change of the test. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional, cohort-type diagnostic accuracy study in 251 consecutive adult type 2 diabetic patients with no peripheral arterial disease or other potential causes of neuropathy, who were recruited between January 2005 and December 2008 from the diabetes outpatient clinics in Alexandroupolis Hospital, Greece. Patients were tested for DPN by means of the neuropathy disability score (NDS) and Neuropad. Multiple-level LRs for time to complete color change were calculated across different stages of neuropathy. RESULTS: The areas under the curve for the diagnosis of any (NDS of ≥3), at least moderate (NDS of ≥6), or severe (NDS of ≥9) DPN were 0.91, 0.96, and 0.97, respectively. The calculation of multiple-level LRs showed that time to complete color change <360 s suggested the absence of neuropathy. Values between 360 and 1,000 s were indicative of mild neuropathy. Finally, values between 1,000 and 1,200 or >1,200 s were strongly suggestive of moderate or severe DPN, respectively. CONCLUSIONS: Neuropad could be used as a triage test for the diagnosis and staging of DPN in patients with type 2 diabetes, prompting referral to specialized care setting.

Evaluation of a new foam to increase skin hydration of the foot in type 2 diabetes: a pilot study.

The aim of the present study was to evaluate the efficacy of a new product (Neuropad repair foam(®)) in promoting skin hydration of the foot in type 2 diabetes. Included in this study were 20 type 2 diabetic patients (10 men, mean age 61·40 ± 2·44 years). Patients applied Neuropad repair foam(®) on the plantar aspect of the right foot twice daily. No agent was applied on the left foot. Patients were examined at baseline, after 7 treatment days and after 14 treatment days. Evaluation of skin dryness was performed by means of the Multi Skin test Corneometer MC 900. In the right foot, skin capacitance was 26·55 ± 4·14 arbitrary units (a.u.) at baseline, 28·90 ± 4·53 a.u. after 7 days of treatment and 32·05 ± 4·54 a.u. after 14 days of treatment. There was a significant increase in skin capacitance from baseline to 7 days of treatment (P < 0·001), from baseline to 14 treatment days (P < 0·001), as well as from 7 to 14 days of treatment (P < 0·001). The same significant (P < 0·001) increases were observed both in men and in women. No changes were noted in the left foot. At baseline, there was no difference in skin capacitance between right and left foot (P = 0·186). However, skin capacitance was significantly higher on the right versus left foot, both after 7 days (P < 0·001) and after 14 days of treatment (P < 0·001). In conclusion, results with the new foam appear encouraging in ameliorating skin dryness in the diabetic foot and further investigation is warranted.

Association between foot temperature and sudomotor dysfunction in type 2 diabetes.

BACKGROUND AND AIMS: Increased foot skin temperature has been described as a feature of diabetic neuropathy. The aim of this present study was to investigate the association between foot temperature and sudomotor dysfunction in type 2 diabetes mellitus. PATIENTS AND METHODS: This study included 51 patients (group A: 25 men, mean age 61.14 +/- 6.11 years) without sudomotor dysfunction and 52 patients (group B: 25 men, mean age 59.54 +/- 6.18 years) with sudomotor dysfunction. Sudomotor dysfunction was defined as time until complete Neuropad color change from blue to pink exceeding 600 s in at least one foot. Time until complete color change of the test was also recorded. Foot skin temperature was measured with a handheld infrared thermometer on the plantar aspect of the foot at the level of the first metatarsal head. RESULTS: On both feet, temperature was significantly higher in group B than in group A (right foot, group A versus group B, 30.62 +/- 1.13 degrees C versus 32.12 +/- 1.06 degrees C, p < .001; left foot, group A versus group B, 30.65 +/- 1.06 degrees C versus 32.19 +/- 1.10 degrees C, p < .001). There was a significant positive correlation between time to complete Neuropad color change and foot skin temperature (right foot, r = 0.742, p < .001; left foot, r = 0.758, p < .001), which was confirmed in both groups. CONCLUSIONS: Patients with sudomotor dysfunction have significantly higher foot temperature than those without sudomotor dysfunction. Foot temperature is positively correlated with severity of sudomotor dysfunction, as evaluated by the time to complete Neuropad color change.

Sensitivity and specificity of a new indicator test (Neuropad) for the diagnosis of peripheral neuropathy in type 2 diabetes patients: a comparison with clinical examination and nerve conduction study.

OBJECTIVE: The objective of this study was to evaluate the sensitivity and specificity of a new indicator test (Neuropad) for the diagnosis of peripheral neuropathy in type 2 diabetes patients as compared with clinical examination and nerve conduction study (NCS). PATIENTS AND METHODS: This study included 120 type 2 diabetes patients (58 men) with a mean age of 67.3 +/- 5.9 years and a mean diabetes duration of 13.1 +/- 3.2 years. Diabetic neuropathy was diagnosed through the Neuropathy Disability Score. An NCS was performed on radial, ulnar, sural, and common and deep peroneal nerves. Patients were also examined with the new indicator test. The "time to complete color change of the test" from blue to pink was recorded. The test was considered abnormal in patients who exhibited a time to complete color change of the test exceeding 600 s in at least one foot. RESULTS: Neuropathy was diagnosed by clinical examination in 83 (69.2%) patients. The sensitivity of the indicator test for clinical neuropathy was 95.2%, and its specificity was 67.6%. The sensitivity of NCS for clinical neuropathy was 94%, and its specificity was 62.1%. The sensitivity of the indicator test for abnormal NCS was 97.8%, and its specificity was 96.4%. CONCLUSIONS: The new indicator test has a very high sensitivity not only for the diagnosis of clinical neuropathy but also for the diagnosis of neurophysiological neuropathy. Specificity is moderately high for the diagnosis of clinical neuropathy, while it is particularly high for the diagnosis of neurophysiological neuropathy. The indicator test has a validity comparable to that of NCS for the diagnosis of diabetic neuropathy. Finally, the time to complete color change of the test is associated with the severity of nerve conduction impairment.

Effect of angiotensin-converting enzyme insertion/deletion genotype on collagen type I synthesis and degradation in patients with atrial fibrillation and arterial hypertension.

OBJECTIVE: The present study was undertaken to assess the impact of the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphisms on circulating markers of collagen type I synthesis and degradation, and also to study the effect of therapy with ACE inhibitors on these markers in hypertensive patients with atrial fibrillation (AF). RESEARCH DESIGN AND METHODS: ACE I/D genotypes were assessed in 158 hypertensive patients (71 +/- 9 years; 72 male) with AF and 174 patients with arterial hypertension in sinus rhythm (SR) (71 +/- 9 years; 88 male). Serum concentrations of amino-terminal propeptide of pro-collagen type I (PINP) and of carboxy-terminal telopeptide of collagen type I (CITP), indices of collagen type I synthesis and degradation, respectively, were measured. RESULTS: Of the 332 study participants, 74 (22.3%) were I/I, 158 (47.6%) were I/D and 100 (30.1%) were D/D carriers. Genetic variation in ACE significantly influenced serum CITP levels in AF patients (p = 0.011). CITP levels were lower in D allele carriers (DD and ID) compared with I/I carriers. There was no difference in PINP levels between the different ACE genotype groups (p = 0.302). Patients treated with ACE inhibitors had higher CITP levels compared with those not treated (p = 0.036). CONCLUSIONS: This study suggests that the presence of the D allele in hypertensive patients with AF is associated with attenuation of type-I collagen degradation, and that therapy with ACE inhibitors increases degradation of collagen type I. The data indicate a subgroup of patients with AF and arterial hypertension who may benefit to a greater extent from therapy with ACE inhibitors, thus, providing a basis for pharmacogenetics.

The new indicator test (Neuropad): a valuable diagnostic tool for small-fiber impairment in patients with type 2 diabetes.

PURPOSE: The purpose of this study was to evaluate the new indicator test for sudomotor function (Neuropad) in the diagnosis of small-fiber impairment in patients with type 2 diabetes. METHODS: This study included 123 patients with type 2 diabetes (59 men; mean age, 64.3 +/- 8.6 years; mean diabetes duration, 12 +/- 6.1 years). Sudomotor dysfunction was assessed by means of the new indicator test. Neuropathy was diagnosed by the Neuropathy Disability Score and small-fiber impairment by temperature perception (Tiptherm device) and pain perception (Neurotip). RESULTS: The frequency of sudomotor dysfunction was significantly (P = .001) higher in patients with neuropathy (95%) than in those without neuropathy (30.2%). Sensitivity of the indicator test for neuropathy was 95%, and specificity was 69.8%. Frequency of neuropathy was significantly (P = .018) higher with the indicator test (74.8%) than with conventional clinical examination (65.4%). Sudomotor dysfunction was significantly (P = .001) more frequent in patients with small-fiber impairment (99%) than in those without small-fiber impairment (21.7%). Sensitivity for small-fiber impairment was 99%, and specificity was 78.3%. There was no difference (P = .999) in the frequency of small-fiberimpairment as diagnosed with the indicator test (80.5%) and with clinical examination (81.3%). CONCLUSIONS: The indicator test has a very high sensitivity and specificity for small-fiber impairment in patients with type 2 diabetes.

Thyroxine replacement dose in patients with Hashimoto disease: a potential role for interleukin-6.

OBJECTIVE: To investigate the potential association between serum inflammatory cytokine levels and thyroxine replacement dose in patients with Hashimoto disease. PATIENTS AND METHODS: The study included 40 patients (12 men) with a mean age of 56.52+/-6.12 years who had hypothyroidism due to Hashimoto disease. Serum interleukin-1b (IL-1b), tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels, as well as TSH, T(3) and T(4) were measured (ELISA). RESULTS: Serum IL-6 showed a significant positive correlation both with total thyroxine replacement dose (r=0.551, p=0.001) and with dose per kilogram of body weight (r=0.482, p=0.002). There was also a significant negative linear correlation between serum IL6 and T(3) (r=-0.322, p=0.043), as well as between serum IL6 and T(3)/T(4) ratio (r=-0.332, p=0.036). A further significant (r=0.419, p=0.007) positive association was demonstrated between IL6 and TNF-alpha. However, no association was found between T(3) or T(3)/T(4) ratio and TNF-alpha or IL1b. CONCLUSIONS: In patients with Hashimoto disease serum IL-6 levels are positively associated with thyroxine replacement dose and negatively associated with T(3) and T(3)/T(4) ratio. These results are possibly attributable to the inhibitory effect of IL6 on deiodination of T(3) and imply a role for IL6 in determining thyroxine replacement dose among these patients.

Vascular endothelial growth factor gene polymorphisms and idiopathic recurrent pregnancy loss.

OBJECTIVE: To investigate whether four common polymorphisms (-2578C/A, -1154G/A, -634G/C, and 936C/T) of the gene encoding for vascular endothelial growth factor (VEGF) are associated with idiopathic recurrent miscarriage. DESIGN: Prospective case-control study. SETTING: University teaching hospital. PATIENT(S): Fifty-two patients with a history of three or more unexplained consecutive pregnancy losses and 82 healthy, postmenopausal controls with at least two live births and no history of pregnancy loss. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Polymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the different VEGF alleles. RESULT(S): There was a significant difference in the -1154G/A genotype and allele frequency between women with recurrent pregnancy loss and controls. The risk of recurrent pregnancy loss was lower in the carriers of the G allele than in women carrying the A allele (odds ratio = 1.91, 95% confidence interval, 0.12-3.28). No significant association between recurrent spontaneous abortions and -2578C/A, -634G/C, and 936C/T genotypes was found. Between women with primary and secondary idiopathic recurrent miscarriage, no statistically significant differences with respect to allele frequencies were observed. CONCLUSION(S): This is the first report on VEGF gene polymorphisms in women with recurrent miscarriage, demonstrating that the -1154G/A VEGF gene polymorphism is associated with idiopathic recurrent abortions.

Vascular endothelial growth factor gene polymorphisms and pre-eclampsia.

Vascular endothelial growth factor (VEGF) plays a crucial role in physiological vasculogenesis and vascular permeability and has been implicated in the pathogenesis of pre-eclampsia. Our present study was undertaken to identify associations between three functional VEGF gene polymorphisms, linked with altered VEGF gene responsiveness, and pre-eclampsia. The study involved 42 pre-eclamptic and 73 healthy control women who were genotyped for the -2578C/A, -634G/C and 936C/T polymorphisms of the VEGF gene. No significant association between genotypic or allelic frequencies in women with pre-eclampsia relative to controls was found. A statistically significant difference was found for allelic frequencies of the 936C/T polymorphism between women with severe pre-eclampsia and controls (odds ratio: 2.70; 95% confidence interval: 1.09-6.63; P = 0.019). VEGF gene polymorphisms studied are unlikely to be major predisposing factors for pre-eclampsia. The presence of the 936T allele probably has a considerable effect on disease modification.

Behavior of Escherichia coli O157:H7 during the manufacture and ripening of feta and telemes cheeses.

Pasteurized whole ewe's and cow's milk was used in the manufacture of Feta end Telemes cheeses, respectively, according to standard procedures. In both cases, the milk had been inoculated with Escherichia coli O157:H7 at a concentration of ca. 5.1 log CFU/ml and with thermophilic or mesophilic starter cultures at a concentration of ca. 5.3 to 5.6 log CFU/ml. In the first 10 h of cheesemaking, the pathogen increased by 1.18 and 0.82 log CFU/g in Feta cheese and by 1.56 and 1.35 log CFU/ g in Telemes cheese for the trials with thermophilic and mesophilic starters, respectively. After 24 h of fermentation, a decrease in E. coli O157:H7 was observed for all trials. At that time, the pH was reduced to 4.81 to 5.10 for all trials. Fresh cheeses were salted and held at 16 degrees C for ripening until the pH was reduced to 4.60. Cheeses were then moved into storage at 4 degrees C to complete ripening. During ripening, the E. coli O157:H7 population decreased significantly (P < or = 0.001) and finally was not detectable in Feta cheese after 44 and 36 days and in Telemes cheese after 40 and 30 days for the trials with thermophilic and mesophilic starters, respectively. The estimated times required for one decimal reduction of the population of E. coli O157:H7 after the first day of processing were 9.71 and 9.26 days for Feta cheese and 9.09 and 7.69 days for Telemes cheese for the trials with thermophilic and mesophilic starters, respectively.