Understanding the role of hyperglycemia and the molecular mechanism associated with diabetic neuropathy and possible therapeutic strategies.

Diabetic neuropathy is a neuro-degenerative disorder that encompasses numerous factors that impact peripheral nerves in the context of diabetes mellitus (DM). Diabetic peripheral neuropathy (DPN) is very prevalent and impacts 50% of diabetic patients. DPN is a length-dependent peripheral nerve lesion that primarily causes distal sensory loss, discomfort, and foot ulceration that may lead to amputation. The pathophysiology is yet to be fully understood, but current literature on the pathophysiology of DPN revolves around understanding various signaling cascades involving the polyol, hexosamine, protein-kinase C, AGE, oxidative stress, and poly (ADP ribose) polymerase pathways. The results of research have suggested that hyperglycemia target Schwann cells and in severe cases, demyelination resulting in central and peripheral sensitization is evident in diabetic patients. Various diagnostic approaches are available, but detection at an early stage remains a challenge. Traditional analgesics and opioids that can be used "as required" have not been the mainstay of treatment thus far. Instead, anticonvulsants and antidepressants that must be taken routinely over time have been the most common treatments. For now, prolonging life and preserving the quality of life are the ultimate goals of diabetes treatment. Furthermore, the rising prevalence of DPN has substantial consequences for occupational therapy because such therapy is necessary for supporting wellness, warding off other chronic-diseases, and avoiding the development of a disability; this is accomplished by engaging in fulfilling activities like yoga, meditation, and physical exercise. Therefore, occupational therapy, along with palliative therapy, may prove to be crucial in halting the onset of neuropathic-symptoms and in lessening those symptoms once they have occurred.

Phosphodiesterase 4 D (PDE4D) gene polymorphisms and risk of ischemic stroke: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Studies on the relationship between Phosphodiesterase 4 D (PDE4D) gene polymorphism with the risk of ischemic stroke (IS) have shown discordant results. The present meta-analysis was aimed to clarify the relationship between PDE4D gene polymorphism with the risk of IS by estimating pooled analysis of published epidemiological studies. METHODS: A comprehensive literature search for all the published articles was performed in various electronic databases, including PubMed, EMbase, Cochrane Library, Trip Database, Worldwide Science, CINAHL, and Google Scholar up to 22nd December 2021. Pooled Odds ratios (ORs) with 95% Confidence Intervals (CIs) under dominant, recessive, and allelic models were calculated. Subgroup analysis based on ethnicity (Caucasian vs. Asian) was performed to examine the reliability of these findings. Sensitivity analysis was also performed to detect the heterogeneity between studies. Finally, Begg's funnel plot was used to assess the potential for publication bias. RESULTS: In our meta-analysis, we identified a total of 47 case-control studies with 20,644 ischemic stroke (IS) cases and 23,201 control subjects, including 17 studies of Caucasian descent and 30 studies of Asian descent. Our findings suggest that there was a significant relationship between SNP45 gene polymorphism and risk of IS (Recessive model: OR = 2.06, 95% CI 1.31-3.23), SNP83 overall (allelic model: OR = 1.22, 95% CI 1.04-1.42), Asian (allelic model: OR = 1.20, 95% CI 1.05-1.37), and SNP89 Asian (Dominant model: OR = 1.43, 95% CI 1.29-1.59, recessive model: OR = 1.42, 95% CI 1.28-1.58) respectively. However, no significant relationship was found between SNP32, SNP41, SNP26, SNP56, and SNP87 gene polymorphisms and risk of IS. CONCLUSION: Findings of this meta-analysis conclude that SNP45, SNP83, and SNP89 polymorphism could be capable of increasing stroke susceptibility in Asians but not in the Caucasian population. Genotyping of SNP 45, 83, 89 polymorphisms may be used as a predictor for the occurrence of IS.

Association of modifiable risk factors with ischaemic stroke subtypes in Asian versus Caucasian populations: A systematic review and meta-analysis.

BACKGROUND: Ischaemic stroke (IS) is associated with various modifiable risk factors but the association of these risk factors based on TOAST classification, which characterises IS into five subtypes: large artery atherosclerosis (LAA), small vessel occlusion (SVO), cardioembolic disease (CE), other determined aetiology (ODE) and undetermined aetiology (UDE), is unknown. We aimed to summarise the published evidence for the association of modifiable risk factors with IS subtypes based on TOAST classification, specifically focussing on the Asian versus Caucasian population. METHOD: A comprehensive search for all the published articles was performed in electronic databases including PubMed, EMBASE, Cochrane Library, and Google Scholar from 01st January 1950 to 10th April 2022 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratio (OR) with 95% confidence interval (CIs) along with random-effect models was used to calculate summary estimates. RESULTS: In our meta-analysis, 32 studies with a total of 23,404 IS (14,364 in Asian vs. 9040 in Caucasian population), 7121 LAA (5219 in Asian vs. 1902 in Caucasian), 5532 SVO (3604 in Asian vs. 1928 in Caucasian), 3498 CE (1634 in Asian vs. 1864 in Caucasian), 1131 ODE (546 in Asian vs. 585 in Caucasian) and 4519 UDE (2076 in Asian vs. 2443 in Caucasian) were included. Our findings suggest a significant association between LAA and hypertension (OR = 1.07, 95% CI = 1.02-1.12), smoking (OR = 1.11, 95% CI = 1.04-1.17), dyslipidemia (OR = 1.13, 95% CI = 1.06-1.21), diabetes mellitus (OR = 1.18, 95% CI = 1.11-1.25) and atrial fibrillation (OR = 0.55, 95% CI = 0.40-0.75). Significantly strong association of hypertension, smoking, dyslipidemia, diabetes mellitus and atrial fibrillation was observed with SVO and CE stroke subtypes. Subgroup analysis based on ethnicity revealed a significant association for dyslipidemia, diabetes mellitus and atrial fibrillation in LAA for both Asians and Caucasians. Hypertension was significantly associated with SVO and ODE subtypes in both Asians and Caucasians; however, only Asian population showed significant association of hypertension in LAA and CE subtypes. The other risk factors did not show any statistical difference between the ethnic groups for the different stroke subtypes. The majority of the risk factors depicted positive association with LAA and SVO, negative with CE and neutral with ODE and UDE. CONCLUSION: Our findings suggest strong association of smoking, dyslipidemia and diabetes mellitus with LAA and SVO subtypes in the Caucasian population. However, only diabetes mellitus showed significant association with both LAA and SVO subtypes in Asian population as well. Thus, a majority of the traditional modifiable risk factors had a positive association in LAA and SVO, while a negative protective association was observed in CE subtype, among both the Asian and the Caucasian subgroups.

Lipoprotein (a) level as a risk factor for stroke and its subtype: A systematic review and meta-analysis.

The role of lipoprotein-A [Lp (a)] as a risk factor for stroke is less well documented than for coronary heart disease. Hence, we conducted a systematic review and meta-analysis for the published observational studies in order to investigate the association of Lp (a) levels with the risk of stroke and its subtypes. In our meta-analysis, 41 studies involving 7874 ischemic stroke (IS) patients and 32,138 controls; 13 studies for the IS subtypes based on TOAST classification and 7 studies with 871 Intracerebral hemorrhage (ICH) cases and 2865 control subjects were included. A significant association between increased levels of Lp (a) and risk of IS as compared to control subjects was observed (standardized mean difference (SMD) 0.76; 95% confidence interval (CIs) 0.53-0.99). Lp (a) levels were also found to be significantly associated with the risk of large artery atherosclerosis (LAA) subtype of IS (SMD 0.68; 95% CI 0.01-1.34) as well as significantly associated with the risk of ICH (SMD 0.65; 95% CI 0.13-1.17) as compared to controls. Increased Lp (a) levels could be considered as a predictive marker for identifying individuals who are at risk of developing IS, LAA and ICH.