Konstantinos Papatheodorou

Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta-analysis.

To assess the efficacy and safety of the novel sodium‐glucose cotransporter 2 (SGLT2) inhibitor empagliflozin compared with placebo or other antidiabetic agents in patients with type 2 diabetes.

Peripheral Neuropathy is Associated With Increased Serum Levels of Uric Acid in Type 2 Diabetes Mellitus

We assessed serum uric acid (SUA) levels in patients with type 2 diabetes mellitus (T2DM) with or without peripheral neuropathy (diagnosed by the Neuropathy Disability score [NDS]). We enrolled 64 patients with T2DM with peripheral neuropathy (group A: 31 men, mean age 63.0 ± 2.8 years) and 66 age-, gender-, renal function- and T2DM duration-matched patients without neuropathy (group B: 32 men, mean age 62.4 ± 3.1 years). Serum uric acid was significantly higher in group A (P < .001). There was a significant correlation between SUA and NDS in both groups (group A: rs = .93, P < .001; group B: r s = .95, P < .001). C-reactive protein (CRP) was also significantly higher in group A (P < .001) and correlated significantly with SUA in both groups (group A: rs = .93, P < .001; group B: rs = .87, P < .001). Serum uric acid is increased in patients with T2DM with neuropathy versus those without. Whether SUA is involved in the pathogenesis of T2DM peripheral neuropathy remains to be established.

A prospective study on the use of the indicator test Neuropad® for the early diagnosis of peripheral neuropathy in type 2 diabetes.

AIM The aim of this prospective study was to evaluate the contribution of the indicator test for sudomotor function Neuropad® to the early diagnosis of peripheral neuropathy in patients with type 2 diabetes mellitus. Included were 109 type 2 diabetic patients (55 men, mean age 56.15 ± 6.14 years), whose initial clinical examination (Neuropathy Disability Score, NDS) was negative for neuropathy. Patients were first examined between January and June 2004 and re-examined 5 years later by the NDS and Neuropad ®. Initially, 70 patients (64.22%) had normal and 39 (35.78%) patients had abnormal Neuropad® (groups A and B, respectively). NDS was significantly higher in group B on both examinations (p < 0.001). On the second examination, 2 patients (2.86%) in group A and 10 patients (25.64%) in group B had developed neuropathy (p = 0.001). Neuropad® had 83.33% sensitivity and 68.04% specificity for neuropathy. There was a modest but significant agreement (kappa = 0.259, p < 0.001) between Neuropad® and NDS for neuropathy. CONCLUSIONS Among type 2 diabetic patients with normal NDS, development of neuropathy is significantly more frequent in those with abnormal Neuropad®. These results suggest a potential utility of Neuropad® for the earlier diagnosis of neuropathy in type 2 diabetes.

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.

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 °C versus 32.12 ± 1.06 °C, p < .001; left foot, group A versus group B, 30.65 ± 1.06 °C versus 32.19 ± 1.10 °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.

Foot Temperature in Type 2 Diabetic Patients with or without Peripheral Neuropathy

UNLABELLED The aim of this study was to evaluate foot temperature in type 2 diabetic patients with vs. without peripheral neuropathy. The study included 30 patients (group A: 16 men, mean age 63.23+/-7.02 years) with peripheral neuropathy and 30 patients (group B: 17 men, mean age 62.37+/-6.73 years) without peripheral neuropathy. Neuropathy was diagnosed by the Diabetic Neuropathy Index (DNI). Foot temperature was measured with a handheld infrared thermometer (KM 814, Kane-May, UK) on the mid-dorsal aspect of the foot (dorsal temperature) and on the plantar aspect of the foot at the level of the first metatarsal head (plantar temperature). Dorsal temperature was significantly higher in group A than in group B (right foot 32.89+/-1.02 degrees C vs. 31.2+/-1.07 degrees C, p<0.001). The same significant difference was observed for the plantar temperature (32.2+/-0.94 degrees C vs. 30.7+/-1.07 degrees C, p<0.001). In both groups, a significant positive correlation was observed between dorsal and plantar temperature (group A: r (s)=0.913, p<0.001; group B: r (s)=0.956, p<0.001). Finally, in group A, DNI score showed a significant positive correlation with dorsal temperature (r (s)=0.856, p<0.001), as well as plantar temperature (r (s)=0.859, p<0.001). CONCLUSIONS Foot temperature is significantly higher in type 2 diabetic patients with neuropathy as compared to those without neuropathy. In patients with neuropathy, a significant positive correlation is observed between foot temperature and clinical severity of neuropathy.

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.

The Fatty Acid Amide Hydrolase (FAAH) Pro129Thr Polymorphism is not Associated with Severe Obesity in Greek Subjects

Fatty amid acid hydrolase (FAAH) has been implicated at both protein and gene level with obesity. An association between Pro129Thr variant of the FAAH gene and obesity has been described, but various studies have yielded conflicting results. Our aim was to determine whether this polymorphism is related to severe obesity and whether it confers a risk for variability of quantitative metabolic traits in a cohort of Greek obese subjects. Two groups of severely obese subjects (BMI > 40 kg/m (2)) were studied: a group of 158 metabolically healthy and a group of 145 obese subjects with metabolic syndrome, which were compared to a control group consisting of 121 lean individuals. We did not find any association between the Pro129Thr polymorphism with severe obesity in both subgroups of obese subjects, between these two subgroups (p= 0.11) or on basic anthropometric characteristics in the three groups. Statistically significant differences were found for glucose and HDL in metabolically healthy subjects and HDL in the control group. The borderline significant p-values were not significant after correction for multiple testing. We were unable to find robust evidence of an association of the Pro129Thr variant with severe obesity, and any related quantitative traits among the obese Greek subjects examined.

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.

Glycaemic Control is Correlated with Well-Being Index (WHO-5) in Subjects with Type 2 Diabetes

UNLABELLED The aim of this study was to examine the potential correlation of WHO-5 well-being index with glycaemic control and chronic complications in subjects with type 2 diabetes. The study included 156 subjects (73 men, mean age 64.05+/-9.11 years, mean diabetes duration 12.22+/-5.61 years). Well-being was assessed by the WHO-5 score via a validated questionnaire comprising 5 questions (Q1-Q5). HbA (1c) showed a significant negative correlation with overall WHO-5 score (r (s)=-0.248, p=0.002) and individual Q1-Q4 scores (r (s)=-0.262, p=0.001; r (s)=-0.248, p=0.002; r (s)=-0.207, p=0.009 and r (s)=-0.169, p=0.035 respectively). Subjects with adequate glycaemic control (HbA (1c) < 7%, n=67) had a significantly higher WHO-5 score in comparison to those with inadequate glycaemic control (HbA (1c) >or= 7%, n=89) (mean+/-SD: 19.69+/-5.47 vs. mean+/-SD: 17.11+/-6.38, p=0.011). Finally, WHO-5 score was significantly (p=0.013) lower in subjects with neuropathic pain than in those without neuropathic pain. CONCLUSIONS In type 2 diabetic subjects, glycaemic control shows a significant correlation with well-being, while neuropathic pain is associated with lower well-being score.