Circulating netrin-1 levels are reduced and related to corneal nerve fiber loss in patients with diabetic neuropathy.

AIMS/INTRODUCTION: Deficiency of neurotropic factors is implicated in diabetic neuropathy (DN). Netrin-1 is a neurotropic factor, but its association with DN has not been explored. We have assessed the association between serum netrin-1 levels and early diabetic neuropathy assessed by quantifying corneal nerve fiber loss using corneal confocal microscopy. MATERIALS AND METHODS: A total of 72 participants with type 2 diabetes, without and with corneal nerve fiber loss (DN- n = 42, DN+ n = 30), and 45 healthy controls were studied. Serum netrin-1 levels were measured by enzyme-linked immunosorbent assay, and corneal nerve morphology was assessed using corneal confocal microscopy. RESULTS: Corneal nerve fiber density, branch density, fiber length and serum netrin-1 levels were significantly lower in the DN- and DN+ groups compared with controls (P < 0.001). Netrin-1 levels correlated with corneal nerve fiber length in the DN+ group (r = 0.51; P < 0.01). A receiver operating characteristic curve analysis showed that a netrin-1 cut-off value of 599.6 (pg/mL) had an area under the curve of 0.85, with a sensitivity of 76% and specificity of 74% (P < 0.001; 95% confidence interval 0.76-0.94) for differentiating patients with and without corneal nerve loss. CONCLUSIONS: Serum netrin-1 levels show a progressive decline with increasing severity of small nerve fiber damage in patients with diabetes. Netrin-1 could act as a biomarker for small nerve fiber damage in DN.

Serum Chemerin Levels Correlate With Severity of Dysglycemia in Young Adult Women With Polycystic Ovary Syndrome.

Context: A subset of polycystic ovary syndrome (PCOS) individuals also have type 2 diabetes (T2D); an unmet need to identify this subgroup exists. Objective: We looked at the potential role of serum chemerin, a proinflammatory adipokine, in identifying dysglycemic PCOS. Methods: A total of 93 PCOS and 33 healthy controls were classified, based on fasting and 2-hour plasma glucose levels (2hPGPG) and glycated hemoglobin A1c (HbA1c) (%) into normoglycemic (n = 34), dysglycemic (n = 33), and T2D (n = 26). Serum chemerin were measured by enzyme-linked immunosorbent assay. Homeostatic model 2 assessment of insulin resistance (HOMA-2IR) and homeostatic model 2 assessment of ß-cell function (HOMA-2ß) were computed using serum C-peptide. Results: Metabolic syndrome was present in 9.7% (National Cholesterol Education Program) of PCOS. Waist circumference, body fat (%), 2hPGPG, and HbA1c levels were significantly higher in T2D group. Serum triglycerides/high-density lipoprotein cholesterol (TGs/HDL-c) ratio was increased in PCOS individuals with T2D; no significant changes in total cholesterol and LDL-c levels were seen. Serum chemerin levels were significantly higher (P < .001) in the PCOS group. Total body fat (%), 2hPGPG, HbA1c, and TG/HDL-c ratio correlated positively with chemerin levels. Serum chemerin levels correlated positively with HOMA2IR and negatively with HOMA-2ß. On receiver operating characteristic curve analysis, a serum chemerin cutoff level of greater than 309.3 ng/mL differentiated PCOS individuals with dysglycemia from those without (sensitivity 85.71%, specificity 89.47%). The Cohen kappa test revealed a substantial agreement (P < .001) between chemerin cutoff and 2hPGPG levels greater than 200 mg/dL. The present study is arguably the first ever to define a serum chemerin cutoff to distinguish PCOS individuals with T2D from those without. Conclusion: Elevated serum chemerin levels reliably identify PCOS individuals with dysglycemia. Further, longitudinal studies with larger samples are required to confirm this association.

Toe brachial index and not ankle brachial index is appropriate in initial evaluation of peripheral arterial disease in type 2 diabetes.

BACKGROUND: Non-invasive clinic-based tools for assessing PAD are not without limitations. Therefore, costly tests like Doppler study, CT angiography and MR angiography are often required to make a diagnosis. Ankle brachial index (ABI), commonly used for assessment of PAD, has high false positivity rates in sclerosed, calcified arteries which render them non-compressible. Toe brachial index (TBI) can be an alternative, as digital arteries are relatively unaffected by these changes. AIM: To compare the reliability of ABI and TBI in diagnosing PAD in type 2 diabetes using CT angiography (CTA) as the reference. METHODS: 175 adults with T2D were selected. ABI &TBI were measured with an automated vascular Doppler XT 6 ports bilaterally for all subjects. For any subject, the limb with lower ABI and TBI was included for analysis. ABI < 0.9 & TBI < 0.6 were taken as evidence of PAD. CTA showing > 50% narrowing was taken as evidence of PAD. RESULTS: 24% of our study subjects had CTA confirmed PAD. ABI has low sensitivity of 35.29% (95% CI 0.21-0.52) compared to TBI being 82.35% (95% CI 0.66-0.92). The specificity however was similar. ABI < 0.9 was able to detect CTA confirmed PAD, but ABI > 0.9, including the so-called normal ABI (0.9-1.3) was unable to detect PAD. ROC showed ABI at 1.005 has sensitivity 64.71% (95% CI 0.48- 0.79) and specificity 61.7% (95% CI 0.53-0.69) and TBI at 0.6 has sensitivity 82.35% (95% CI 0.66-0.92) & specificity 92% (95% CI 0.87-0.96). Utilizing Cohen's Kappa, the reliability of ABI with respect to CTA showed fair agreement (K = 0.225, p = 0.001), whereas the reliability of TBI with respect to CTA showed substantial agreement (K = 0.759, p < 0.0001). CONCLUSION: ABI < 0.9 detects PAD reliably, but presence of PAD in patients with ABI > 9.0 including the normal of ABI (0.9-1.3) can be confirmed with TBI, which correlated strongly with CTA. TBI is also non-inferior for PAD detection, when ABI < 0.9. TBI and not ABI can be utilized for initial assessment of PAD in subjects with T2D.