Type 2 diabetes mellitus (T2DM) is the most common form of diabetes, and is rising in incidence with widespread prevalence. Multiple gene variants are associated with glucose homeostasis, complex T2DM pathogenesis, and its complications. Exploring more effective therapeutic strategies for patients with diabetes is crucial. Pharmacogenomics has made precision medicine possible by allowing for individualized drug therapy based on a patient’s genetic and genomic information. T2DM is treated with various classes of oral hypoglycemic agents, such as biguanides, sulfonylureas, thiazolidinediones, meglitinides, DPP4 inhibitors, SGLT2 inhibitors, α-glucosidase inhibitors, and GLP1 analogues, which exhibit various pharmacogenetic variants. Although genomic interventions in monogenic diabetes have been implemented in clinical practice, they are still in the early stages for complex polygenic disorders, such as T2DM. Precision DM medicine has the potential to be effective in personalized therapy for those suffering from various forms of DM, such as T2DM. With recent developments in genetic techniques, the application of candidate-gene studies, large-scale genotyping investigations, genome-wide association studies, and “multiomics” studies has begun to produce results that may lead to changes in clinical practice. Enhanced knowledge of the genetic architecture of T2DM presents a bigger translational potential. This review summarizes the genetics and pathophysiology of T2DM, candidate-gene approaches, genome-wide association studies, personalized medicine, clinical relevance of pharmacogenetic variants associated with oral hypoglycemic agents, and paths toward personalized diabetology.

Background: Diabetic foot ulcers (DFU) are a major complication of diabetes mellitus (DM). Nutrient deficiencies are among the major risk factors in DFU development and healing. In this context, we aimed to investigate the possible association between micronutrient status and risk of DFU.Methods: A systematic review (Prospero registration: CRD42021259817) of articles, published in PubMed, Web of Science, Scopus, CINAHL Complete, and Embase, that measured the status of micronutrients in DFU patients was performed.Results: Thirty-seven studies were considered, of which thirty were included for meta-analysis. These studies reported levels of 11 micronutrients: vitamins B9, B12, C, D, E, calcium, magnesium, iron, selenium, copper, and zinc. DFU, compared to healthy controls (HC) had significantly lower vitamin D (MD: -10.82 14 ng/ml, 95% CI: -20.47, -1.16), magnesium (MD: -0.45 mg/dL, 95% CI: -0.78, -0.12) and selenium (MD: -0.33 µmol/L, 95% CI: -0.34, -0.32) levels. DFU, compared to DM patients without DFU, had significantly lower vitamin D (MD: -5.41 ng/ml, 95% CI: -8.06, -2.76), and magnesium (MD: -0.20 mg/dL, 95% CI: -0.25, -0.15) levels. The overall analysis showed lower levels of vitamin D [15.55ng/ml (95% CI:13.44, 17.65)], vitamin C [4.99µmol/L (95% CI:3.16, 6.83)], magnesium [1.53mg/dL (95% CI:1.28, 1.78)] and selenium [0.54µmol/L (95% CI:0.45, 0.64)].Conclusion: This review provides evidence that micronutrient levels significantly differ in DFU patients, suggesting an association between micronutrient status and risk of DFU. Therefore, routine monitoring and supplementations are warranted in DFU patients. We suggest that personalized nutrition therapy may be considered in the DFU management guidelines.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=259817, identifier CRD42021259817.

Purpose: There has been an increase in the incidence of signet ring cell cancer (SRCC) of the stomach and gastro-esophageal junction (GEJ). The multistage carcinogenesis involving genetic and epigenetic aberrations may have a major role in the increasing incidence of SRCC. Although there are numerous studies on the prognostic value of SRCC, they are markedly inconsistent in their results, making it impossible to draw any meaningful conclusions. We aimed to examine the available evidences on molecular alterations and stage-stratified treatment approaches in SRCC of the stomach and GEJ. Methods: A systematic search was carried out in PubMed. Studies available in English related to SRCC of stomach and gastro-esophageal junction were identified and evaluated. Results: This study reviewed the current evidence and provided an insight into the molecular alterations, stage-stratified treatment approaches, and future challenges in the management of SRCC of the stomach and GEJ. Specific therapeutic strategies and personalized multimodal treatment have been recommended based on the tumor characteristics of SRCC. Conclusion: Multistage carcinogenesis involving genetic and epigenetic aberrations in SRCC is interlinked with stage-dependent prognosis. Specific therapeutic strategy and personalized multimodal treatment should be followed based on the tumor characteristics of SRCC. Endoscopic resection, radical surgery, and perioperative chemotherapy should be offered in carefully selected patients based on stage and prognostic stratification. Future studies in genetic and molecular analysis, histopathological classification, and options of multimodality treatment will improve the prognosis and oncological outcomes in SRCC of gastric and GEJ.

This systematic review evaluates the gut microbiota (GM) status in tuberculosis (TB) patients compared to healthy volunteers due to the disease or its treatment.We conducted a systematic review of ...

Infections are becoming more difficult to treat, at least partly on account of microbes that produce biofilms. Reports suggest that decreased levels of antimicrobial peptides like cathelicidin, ele...

Antiepileptic drugs (AEDs) are known to interfere with homocysteine metabolism. Hyperhomocysteinemia may be a risk factor associated in the long-term treatment with AEDs. Both genetic and non-genetic factors are responsible for hyperhomocysteinemia. MTHFR C677T polymorphism leads to the reduction in enzyme activity and subsequent elevation of plasma homocysteine. This study aimed to investigate the role of MTHFR C677T polymorphism in epileptic patients receiving AEDs as monotherapy (phenytoin, carbamazepine, and sodium valproate) and showing toxicity and non-toxicity, and the impact of AEDs on hyperhomocysteinemia in North Indian population. Blood samples for this case-control study were collected from the outpatient department and wards of the Department of Neurosciences at the All India Institute of Medical Sciences, New Delhi, India, between July 2008 and May 2010. In this study, 200 epileptic patients and 100 normal controls were assessed for total homocysteine (tHcy), vitamin B12, and folate levels using enhanced chemiluminescence enzyme immunoassay method (ImmuliteR, 1000 systems, DPC, United States); genotyping of MTHFR C677T was done using polymerase chain reaction-restriction fragment length polymorphism method. The results showed a significant increase in tHcy levels in epileptic patients with toxicity and non-toxicity than in normal controls (P < .005). The allelic and genotypic distributions were found to be statistically significant in toxicity and non-toxicity groups (P < .05). The result confirmed that hyperhomocysteinemia is common in adults receiving AED treatment for epilepsy with toxicity and non-toxicity groups. This increase in tHcy is mainly related to low folate and vita.min B12 levels, which are the main determinants for tHcy.