Association of serum NF-κB levels with peripheral neuropathy in type 2 diabetes mellitus patients: a pilot study.

OBJECTIVES: Hyperglycaemia-induced inflammation plays a vital role in the development of diabetic peripheral neuropathy (DPN). Recent evidences had reported the involvement of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) in diabetic experimental models. So, this pilot study aimed to evaluate serum NF-κB levels in DPN patients. METHODS: We recruited 50 T2DM patients, of which 25 were T2DM with neuropathy and 25 were T2DM without neuropathy. In all the participants peripheral neuropathy was diagnosed based on Total neuropathy score (TNS). Serum NF-κB levels were measured by ELISA. RESULTS: We observed that the serum NF-κB levels were higher in DPN patients in comparison to T2DM patients without neuropathy. On spearman correlation, a positive correlation was found between serum NF-κB levels and TNS in the DPN group (r=0.741, p<0.001). The regression model shows the TNS to be an independent determinant of serum NF-κB levels after adjustment for potential confounders like age, duration of diabetes, and HbA1C (B=81.34; p<0.001). CONCLUSIONS: NF-κB activation plays a key role in promoting inflammation which is associated with the progression of DPN. In this respect, the study of NF-κB levels in serum may be an additional diagnostic marker for DPN.

Impaired Cardiovagal Activity as a Link Between Hyperglycemia and Arterial Stiffness in Adults With Type 2 Diabetes Mellitus Among an Eastern Indian Population: A Cross-sectional Study.

OBJECTIVES: Cardiac autonomic neuropathy (CAN) is one of the most common yet overlooked complications of type 2 diabetes mellitus (T2DM). Individuals with T2DM with CAN have a 5-fold higher rate of cardiovascular morbidity and mortality. The presence of CAN in T2DM could potentially lead to arterial stiffness. However, only sparse data are available suggesting any association between autonomic dysfunction and arterial stiffness in T2DM. METHODS: We recruited 80 people with T2DM and 74 healthy controls for our study. Heart rate variability (HRV) testing was performed to assess autonomic function. Assessment of arterial stiffness was done by measuring the brachial pulse wave velocity (baPWV) and augmentation index (AI). RESULTS: The time-domain parameters were significantly decreased (p<0.001) and frequency-domain parameters, such as total power and high-frequency band expressed as a normalized unit, were found to be significantly reduced in people with T2DM (p<0.001). Both baPWV and AI were significantly higher in people with T2DM compared with healthy controls (p<0.001). We observed a moderate correlation between standard deviation of normal to normal interval (SDNN) and baPWV (r=-0.437, p=0.002) and AI (r=-0.403, p=0.002). A multiple linear regression model showed an association between SDNN and arterial stiffness parameters, such as baPWV and AI, which were statistically significant (p<0.05) in a fully adjusted model that included the conventional risk factors for atherosclerosis. CONCLUSIONS: Impaired cardiovagal activity is an independent risk factor for the development of arterial stiffness. Incorporation of HRV testing into the diabetes management protocol would have potential benefits for identifying individuals at high risk of developing cardiovascular events. Hence, preventive measures can be taken as early as possible to improve patient outcomes.

Impact of Cardiac Autonomic Dysfunction on Cognitive Event-Related Potential in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study.

Introduction: Type 2 diabetes mellitus (T2DM) is a chronic metabolic condition that is responsible for various long-term complications. Cognitive impairment is one of the most common complications, but the underlying mechanisms are still undetermined. The autonomic imbalance is a major cause for CVS morbidity in T2DM which could also potentially affect cognition. But there is sparse data available in the literature to prove the association between autonomic dysfunction and cognitive impairment. Methodology: We recruited 40 T2DM patients and 40 healthy controls. The assessment of cognitive functions was done by cognitive P300 event-related potential (ERP) and MoCA. Heart rate variability (HRV) was done to assess autonomic function. Results: The P300 ERP latency in Fz, Cz and Pz sites was significantly prolonged in T2DM patients (P < 0.001). We found moderate correlation is present between P300 latency and total power (r = -0.466, P < 0.01) and LFnu (r = -0.423, P < 0.01) in T2DM patients. The total power and HbA1C show independent association with P300 latency after adjustment for confounding factors like age and duration of diabetes (P < 0.05). Conclusion: As the incidence of Alzheimer's disease is rising among T2DM patients increasing their dependency, making necessary lifestyle measures at earliest to improve autonomic balance may prevent or delay the onset of cognitive decline and alleviate its consequences and improve the quality of life in T2DM patients.

Association of peripheral neuropathy with skeletal muscle mass and function in type two diabetes mellitus patients: A cross-sectional study.

BACKGROUND & OBJECTIVE: Diabetic peripheral neuropathy (DPN) is considered to be a risk factor for development of sarcopenia. Therefore, our study aimed to detect the association between peripheral neuropathy with skeletal muscle mass and function in type two diabetes mellitus (T2DM) patients. METHODS: A total of 176 participants, ≥45 years were included in the study. Out of 176, 60 were healthy volunteers, 60 had T2DM without neuropathy, 56 had T2DM with neuropathy. In all the participants peripheral nerve function was assessed by nerve conduction studies (Common peroneal and Sural nerve) and sarcopenia parameters were evaluated according to the Asian Working Group for Sarcopenia (AWGS) criteria. RESULTS: The present study suggested that diabetic peripheral neuropathy (DPN) was associated with decline in muscle mass, which was found only in men. Our study showed a positive correlation between appendicular skeletal muscle index (ASMI) and common peroneal nerve amplitude and sural nerve amplitude with r=0.527, p<0.05; r=0.847, p<0.001 respectively. Furthermore, in multiple linear regression analyses, we found a positive relationship between ASMI and sural nerve amplitude after adjustment for confounders like age, duration of diabetes, and HbA1C (B=0.739; p<0.001). CONCLUSION: As DPN patients are more prone to developing sarcopenia, and periodic assessment of skeletal muscle mass and function is warranted to initiate early lifestyle interventions in these patients, which will improve their quality of life.

The Burden of Peripheral Neuropathy in Nondiabetic Chronic Kidney Disease and the Role of Ghrelin Isoforms in its Development.

Introduction: Peripheral neuropathy is one of the most common complications in chronic kidney disease (CKD). The neuroprotective role of ghrelin is being explored recently. Here we aim to determine the burden of neuropathy in nondiabetic CKD and to find the association of peripheral nerve function with plasma ghrelin levels in these patients. Methods: This was a cross-sectional study conducted in nondiabetic CKD patients on conservative management to determine the magnitude of neuropathy. The association of ghrelin isoforms with nerve functions was assessed between three groups, namely CKD with neuropathy, CKD without neuropathy, and healthy volunteers, with 20 participants in each group. Results: The proportion of neuropathy in nondiabetic CKD was 78% (n = 78), of which 51% (n = 40) were asymptomatic. Des acyl ghrelin (DAG) and total ghrelin (TG) levels were 1545.5 ± 487.4 and 1567.4 ± 485.3 pg/mL, respectively, in CKD patients with neuropathy and were found to be elevated compared to those without neuropathy, who had 1000.4 ± 264.2 and 1019.7 ± 264.3 pg/mL of DAG and TG, respectively (P < 0.001). Assessment of correlation between nerve conduction parameters and DAG levels showed positive correlation between DAG levels and common peroneal latency (r = 0.69; P < 0.01), median sensory latency (r = 0.45; P < 0.05), and sural latency (r = 0.51; P < 0.05). We found negative correlation between median velocity (r =-0.56; P < 0.05), common peroneal velocity (r = -0.64; P < 0.01), median sensory velocity (r =-0.49; P < 0.05), and sural velocity (r = -0.54; P < 0.05). There was no statistically significant difference in acyl ghrelin levels among the groups. Conclusion: The prevalence of peripheral neuropathy in CKD is significantly higher with almost half of them being asymptomatic. Impaired renal clearance in CKD leads to the accumulation of DAG, which subsequently inhibits the neuroprotective functions of AG leading to neuropathy in CKD.