Triglyceride-Fasting Glucose Index and Homeostatic Model Assessment for Insulin Resistance as Predictors of Type 2 Diabetes Mellitus in South Indians With Normal Body Mass Index.

INTRODUCTION:  Early detection of type 2 diabetes mellitus (T2DM) is imperative to prevent the complications associated with the disease. Current guidelines for diagnosis rely on the assessment of serum glucose (fasting and post-prandial) and glycosylated hemoglobin (HbA1c) levels. Insulin resistance, a phenomenon associated with T2DM, has been observed before the changes in these metrics. The homeostatic model assessment for insulin resistance (HOMA-IR) has been widely used to assess the degree of insulin resistance. The triglyceride-fasting glucose (TyG) index is a newer marker of insulin resistance that merits further study.  Aim: The study aimed to assess the validity of the TyG index and HOMA-IR as markers for the development of T2DM in non-obese individuals.  Materials and methods: One hundred eight non-obese patients without T2DM were included in this prospective cohort study and followed up for eight years. Anthropometric and biochemical parameters, including fasting glucose levels, HbA1c, fasting serum insulin, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG), were measured at enrolment and eight years follow-up, and HOMA-IR and TyG index were calculated.  Results: Twenty participants out of 108 (18.5%) developed T2DM over eight years. On performing the area under the curve (AUC)-receiver operating characteristic curve analysis, TyG of >8.61 and HOMA-IR of >1.5 had the highest validity (ability) to predict new-onset T2DM in the study population (TyG: AUC: 0.612 (95% CI: 0.514-0.705); HOMA-IR: AUC: 0.529 (95% CI: 0.431-0.626)); however, this was not statistically significant.  Conclusion: At an eight-year follow-up, TyG and HOMA-IR were unreliable predictors of the development of T2DM in non-obese individuals.

The prevalence of pneumothorax in human immunodeficiency virus patients. A single center study.

OBJECTIVES: To assess the prevalence, risk factors, and associated complications of pneumothorax that are present in patients with human immunodeficiency virus (HIV) at our institution and to provide an updated local study addressing the association between pneumothorax and HIV. METHODS: This retrospective cohort study examined 161 patients who were admitted with a diagnosis of HIV from June 2017 to May 2022. They were divided into 2 groups depending on the presence of pneumothorax during their stay. Multiple variables were studied, including age, gender, tuberculosis infection, pneumocystis jiroveci pneumonia (PJP)infection, bacterial pneumonia, and pneumothorax type and treatment course. RESULTS: There were 11 patients diagnosed with pneumothorax (prevalence rate: 6.8%). Bacterial lung infection was found in 9 (81.8%) of these patients, while fungal infection was found in 6 (54.5%) (p<0.001, 0.010). The MTB was found in 3 (27.3%) patients (p=0.728), while none were infected with PJP. Intercostal tube insertion was attempted in 9 (81.8%) patients, the mean duration of tube stay was 39.3±30.7 days, and the mortality rate was 72.7% (p=0.007). CONCLUSION: Pneumothorax in patients with HIV is a manifestation of the progression of the disease and its poor outcome. It has a complicated treatment course and a high mortality rate.

Closed Catheter Drainage for Klebsiella pneumoniae Empyema Necessitans.

Empyema necessitans is a rare complication of pneumonia, which can be seen more frequently with tuberculosis (TB). In this case report, we include a 47-year-old female with empyema necessitans; closed drainage has been sought as a sole treatment based on the clinical presentation and radiological findings of an empyema necessitans. Scarce evidence with regard to adult empyema necessitans with Klebsiella was found in the literature where adult cases were managed exclusively using combination of intravenous (IV) antibiotic and closed drainage, reporting such case can help guiding management for similar presentation.

Tip-Variant Focal Segmental Glomerulosclerosis in a Patient With Primary Hypothyroidism: A Case Report.

Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome (NS) and one of the leading causes of end-stage kidney disease. Endocrinological abnormalities due to the urinary loss of hormone-binding proteins, such as transient hypothyroidism, are well documented in FSGS. Secondary FSGS can arise due to viral infections, drugs, and pre-existing glomerular diseases. Few reports have highlighted the occurrence of FSGS in the background of hypothyroidism. We present a case of a young male with primary hypothyroidism who developed the tip variant of FSGS. A combination of oral corticosteroids and angiotensin-converting enzyme (ACE) inhibitors was successful in causing remission of the FSGS with no relapse.

Granular cell tumor of the bronchus: A case report.

INTRODUCTION AND IMPORTANCE: Pulmonary granular cell tumor (GCT) is a very rare neoplasm that originates from Schwann cells. CASE PRESENTATION: Our case report describes a symptomatic benign pulmonary GCT found during follow-up CT imaging and was eventually excised with a good outcome. CLINICAL DISCUSSION: GCT are mostly benign tumors. Pulmonary GCTs mostly occur in the endobronchial region and can be symptomatic or discovered incidentally. CONCLUSION: Treatment options for pulmonary GCT are either conservative treatment or surgical resection depending on the size of the tumor and the presence of tracheal wall invasion.

Association and gene-gene interaction analyses for polymorphic variants in CTLA-4 and FOXP3 genes: role in susceptibility to autoimmune thyroid disease.

PURPOSE: Polymorphic variants of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and forkhead box protein P3 (FOXP3) genes are implicated in dysregulated immune homeostasis and autoimmune disorders. We analyzed the association between CTLA-4 rs231775 and FOXP3 rs3761548, rs3761549 polymorphisms and predisposition to autoimmune thyroid disease (AITD), inclusive of Hashimoto's thyroiditis (HT) and Graves' disease (GD) in South-Indian population. METHODS: A total of 355 AITD subjects (comprising 275 HT and 80 GD) and 285 randomly selected age- and sex-matched control subjects were genotyped for the aforementioned polymorphisms by PCR-RFLP method. RESULTS: The rs231775 "G" allele was preponderant in HT and GD subjects when compared with controls and exerted a dominant influence on the susceptibility to HT (p = 0.009) and GD (p = 0.02), respectively. There was no allelic association of rs3761548 and rs3761549 polymorphisms with AITD susceptibility, albeit a significant difference in genotype distribution with respect to rs3761549. Haplotype analysis revealed an increased frequency of rs3761548 "C"-rs3761549 "T" in HT and GD subjects, thereby associating it with disease predisposition (p = 0.03). Epistatic interaction analysis by multifactor dimensionality reduction approach revealed redundancy between CTLA-4 and FOXP3 genes in influencing the susceptibility to AITD. CONCLUSIONS: The genetic variation in CTLA-4 gene with reference to rs231775 polymorphism contributes to an increased predisposition to HT and GD. Also, in conjunction with FOXP3 gene variants it seems to influence the susceptibility to HT and GD respectively. The significance of these findings in combination with antithyroid antibody screening could plausibly contribute towards meticulous case-finding for effective treatment of HT and GD.

Unusual Malposition of a Chest Tube, Intrathoracic but Extrapleural.

Chest tube malpositioning is reported to be the most common complication associated with tube thoracostomy. Intraparenchymal and intrafissural malpositions are the most commonly reported tube sites. We present a case about a 21-year-old patient with cystic fibrosis who was admitted due to bronchiectasis exacerbation and developed a right-sided pneumothorax for which a chest tube was inserted. Partial initial improvement in the pneumothorax was noted on the chest radiograph, after which the chest tube stopped functioning and the pneumothorax remained for 19 days. Chest computed tomography was done and revealed a malpositioned chest tube in the right side located inside the thoracic cavity but outside the pleural cavity (intrathoracic, extrapleural). The removed chest tube was patent with no obstructing materials in its lumen. A new thoracostomy tube was inserted and complete resolution of the pneumothorax followed.

Biomarkers of Prostatic Cancer: An Attempt to Categorize Patients into Prostatic Carcinoma, Benign Prostatic Hyperplasia, or Prostatitis Based on Serum Prostate Specific Antigen, Prostatic Acid Phosphatase, Calcium, and Phosphorus.

Prostatitis, BPH, and P.Ca are the most frequent pathologies of the prostate gland that are responsible for morbidity in men. Raised levels of PSA are seen in different pathological conditions involving the prostate. PAP levels are altered in inflammatory or infectious or abnormal growth of the prostate tissue. Serum calcium and phosphorus levels were also found to be altered in prostate cancer and BPH. The present study was carried out to study the levels of PSA, PAP, calcium, and phosphorus in serum of patients with Prostatitis, BPH, or P.Ca and also to evaluate the relationship between them. Males in the age group of 50-85 years with LUTS disease symptoms and with PSA levels more than 4 ng/mL were included. A total of 114 patients were analyzed including 30 controls. Prostatitis in 35.7% of cases, BPH in 35.7% of the cases, and P.Ca in 28.57% of the cases were observed. Thus, the nonmalignant cases constitute a majority. PSA, a marker specific for prostatic conditions, was significantly high in all the diseases compared to controls. A rise in serum PSA and PAP indicates prostatitis or, in combination with these two tests, decreased serum calcium shows advanced disease.

Association Analysis of Polymorphisms in Genes Related to Oxidative Stress in South Indian Type 2 Diabetic Patients with Retinopathy.

BACKGROUND: Diabetic Retinopathy (DR) is one of the most common microvascular complications of type 2 diabetes mellitus (T2DM) and is polygenic with a multitude of genes contributing to disease susceptibility. The present study aimed at exploring the association between DR and seven polymorphisms in oxidative stress-related genes, i.e. ACE, eNOS, p22phox subunit of NAD(P)H oxidase, PARP-1 and XRCC1 in South Indian T2DM subjects. MATERIALS AND METHODS: The study included 149 T2DM subjects with DR (diagnosed through funduscopic examination) and 162 T2DM patients with no evidence of DR. The selected polymorphisms were genotyped by polymerase chain reaction (PCR) and Taqman allele discrimination assay. RESULTS: There was no significant difference in the genotype and allele distribution of ACE ins/del, eNOS-786T>C, 894G>T, 4a4b and p22phox 242C>T polymorphisms between T2DM groups with and without DR. Contrastingly, there appeared to be a significant association of PARP-1 Val762Ala and XRCC1 Arg399Gln polymorphisms with DR, wherein 762Ala allele seemed to confer significant protection against DR (p = 0.01; OR = 0.51 [0.3-0.86]), while the presence of 399Gln allele was associated with an enhanced risk for DR (p = 0.02; OR = 1.52 [1.07-2.15]). Multiple logistic regression analysis revealed a significant and independent association of Val762Ala and Arg399Gln polymorphisms and other putative risk factors with DR in T2DM individuals. CONCLUSIONS: The polymorphisms in the DNA repair genes PARP-1 and XRCC1 tended to associate significantly with DR. While Val762Ala polymorphism was associated with reduced susceptibility to DR, the Arg399Gln polymorphism contributed an elevated to risk for DR in South-Indian T2DM individuals.

Polymorphisms in oxidative stress pathway genes and risk of diabetic nephropathy in South Indian type 2 diabetic patients.

AIM: Diabetic nephropathy (DN), a common microvascular complication of type 2 diabetes mellitus (T2DM) is polygenic, with a vast array of genes contributing to disease susceptibility. Accordingly, we explored the association between DN and six polymorphisms in oxidative stress related genes, namely eNOS, p22phox subunit of NAD(P)H oxidase, PARP-1 and XRCC1 in South Indian T2DM subjects. METHODS: The study included 155 T2DM subjects with DN and 162 T2DM patients with no evidence of DN. The selected polymorphisms were genotyped by polymerase chain reaction and Taqman allele discrimination assay. RESULTS: No significant difference was observed in the genotype and allele distribution of eNOS -786T > C, intron 4a4b, p22phox 242C > T and XRCC1 Arg399Gln polymorphisms between T2DM groups with and without DN. Contrastingly, there appeared to be a significant association of eNOS 894G > T and PARP-1 Val762Ala polymorphisms with DN wherein, the presence of 894T allele was associated with an enhanced risk for DN [P = 0.005; OR = 1.78 (1.17-2.7)], while the 762Ala allele seemed to confer significant protection against DN [P = 0.02; OR = 0.59 (0.37-0.92)]. Multiple logistic regression analysis revealed a significant and independent association of eNOS 894G > T, PARP-1 Val762Ala polymorphisms and hypertension with DN in T2DM individuals. CONCLUSIONS: eNOS 894G > T and PARP-1 Val762Ala polymorphisms appeared to associate significantly with DN, with the former contributing to an enhanced risk and the latter to a reduced susceptibility to DN in South Indian T2DM individuals.

Association of FOXP3 (rs3761548) promoter polymorphism with nondermatomal vitiligo: A study from India.

BACKGROUND: The rs3761548 polymorphism (-3279 C>A) of FOXP3 gene is associated with several autoimmune disorders. OBJECTIVE: We sought to determine whether rs3761548 polymorphism is associated with nondermatomal vitiligo in Indian subjects. METHODS: Genomic DNA was isolated from blood samples of 303 patients and 305 control subjects and genotyping was done by allele-specific primers. Data analysis was carried out for the entire cohort and separately for male and female participants as FOXP3 is an X-linked marker. Statistics were performed using software. RESULTS: The genotype frequencies differed significantly from patients to control subjects (P = .002). Further analysis demonstrated female participants with CC genotype were protected (CC vs CA+AA; odds ratio 0.38, 95% confidence interval 0.238-0.615) and those with CA genotype were at higher risk to develop vitiligo (CA vs CC+AA; odds ratio 2.634, 95% confidence interval 1.604-4.325). However, no such statistical difference was observed in male participants. LIMITATIONS: Our study is, to our knowledge, the first report from India with respect to vitiligo and rs3761548; however, we lack adequate literature assistance. CONCLUSIONS: The rs3761548 of FOXP3 gene in our population may be associated with susceptibility to vitiligo because of altered expression. CC genotype appears to be protective and CA genotype seems to impart nearly 3-fold risk to develop vitiligo in women and girls.

Arg399Gln polymorphism of X-ray repair cross-complementing group 1 gene is associated with angiographically documented coronary artery disease in South Indian type 2 diabetic patients.

AIMS: DNA damage resulting from oxidative stress contributes significantly to the development and progression of atherosclerosis in type 2 diabetic (T2DM) individuals, thereby implicating polymorphisms in DNA repair genes in the modulation of DNA repair efficiency. Based on this premise, we explored the association between X-ray repair cross-complementing group 1 (XRCC1) gene Arg399Gln polymorphism, coronary artery disease (CAD), and myocardial infarction (MI) in type 2 diabetic patients. We screened 283 T2DM patients, inclusive of 160 with angiographically defined CAD, 73 with MI, 89 without MI, and 121 T2DM individuals with no evidence of CAD for XRCC1 Arg399Gln polymorphism. RESULTS: There appeared to be a significant difference in the distribution of genotype and allele frequencies of XRCC1 Arg399Gln polymorphism between T2DM groups with and without CAD (p=0.03), albeit no significant association with MI was observed (p=0.055). A further analysis revealed that the frequencies of the Arg/Gln, Gln/Gln genotypes and 399Gln allele were considerably higher in patients with triple vessel disease (TVD) as compared with those with the single and double vessel disease (p=0.03), thereby associating this polymorphism with severity of CAD in T2DM individuals. Multiple logistic regression analysis revealed a significant and independent association of XRCC1 Arg399Gln polymorphism and other putative risk factors with CAD/TVD in T2DM individuals. CONCLUSIONS: These findings reveal a significant association between XRCC1 gene Arg399Gln polymorphism, CAD/TVD, and coincident putative risk factors in T2DM individuals in the South Indian population.

Association of the genetic variants of endothelial nitric oxide synthase gene with angiographically defined coronary artery disease and myocardial infarction in South Indian patients with type 2 diabetes mellitus.

INTRODUCTION: The polymorphic variants of endothelial nitric oxide synthase (eNOS) gene have been implicated in endothelial dysfunction and are highly relevant to macroangiopathies. We investigated the relationship between eNOS gene T-786C, G894T, intron 4a/b polymorphisms and coronary artery disease (CAD) in South Indian type 2 diabetic (T2DM) individuals. METHODS: We screened 283 T2DM patients, inclusive of 160 with angiographically defined CAD, 73 with myocardial infarction (MI), 89 without MI and 121 T2DM individuals with no evidence of CAD for eNOS gene polymorphisms. RESULTS: There appeared to be a significant difference in the genotype and allele distribution of eNOS T-786C polymorphism between T2DM groups with and without CAD (p=0.004), albeit no significant association with MI was observed. The frequencies of TC and CC genotypes and -786C allele were considerably higher in patients with triple vessel disease (TVD) as compared to those without CAD (p=0.003), thereby associating this polymorphism with severity of CAD. Genotype and allele distributions of G894T and intron 4a/b polymorphisms were not significantly different between T2DM subjects with and without CAD/MI. Significant linkage disequilibrium was observed between intron 4a/b and T-786C polymorphisms. Multiple logistic regression analysis revealed a significant and independent association of eNOS T-786C polymorphism and other putative risk factors with CAD/TVD in T2DM individuals. CONCLUSIONS: These findings reveal a significant association between eNOS T-786C polymorphism, CAD/TVD and coincident putative risk factors in T2DM individuals in South Indian population.

Relationship between NADPH oxidase p22phox C242T, PARP-1 Val762Ala polymorphisms, angiographically verified coronary artery disease and myocardial infarction in South Indian patients with type 2 diabetes mellitus.

INTRODUCTION: There has been compelling evidence for the role of oxidative stress in the pathogenesis of cardiovascular complications in type 2 diabetes mellitus (T2DM). We analyzed the association of C242T and Val762Ala polymorphisms of NADPH oxidase p22phox and poly (ADP-ribose) polymerase-1 (PARP-1) genes respectively with coronary artery disease (CAD) and its severity, myocardial infarction (MI) and cardiovascular risk factors in T2DM patients. MATERIALS AND METHODS: We screened 283 T2DM patients, inclusive of 160 with angiographically defined CAD, 73 with and 89 without MI and 121 T2DM individuals with no evidence of CAD for the two gene polymorphisms. RESULTS: The 242T and 762Ala alleles were significantly more frequent in T2DM subjects without CAD than those with CAD, thereby associating them with a significant protective effect against development of CAD [p=0.002 (C242T); 0.02 (Val762Ala)]. The association was further characterized by a relatively lower frequency of 242T and 762Ala alleles in T2DM patients with multi (MVD)/triple vessel disease respectively [p=0.003 (C242T); 0.02 (Val762Ala)]. Conversely, the genotype and allele frequencies of these polymorphisms were not significantly different in T2DM+CAD patients with or without MI. Stratification of risk by putative risk factors for CAD revealed a significant interaction with these polymorphisms. Multiple logistic regression analysis revealed a significant and independent association of C242T and Val762Ala polymorphisms and other putative risk factors with CAD/MVD in T2DM individuals. CONCLUSIONS: Our observations indicate a significant relationship between p22phox C242T and PARP-1 Val762Ala polymorphisms, CAD and its severity, but not with occurrence of MI in T2DM individuals with significant coronary stenoses.

Relationship between angiotensin-converting enzyme gene insertion/deletion polymorphism, angiographically defined coronary artery disease and myocardial infarction in patients with type 2 diabetes mellitus.

INTRODUCTION: The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been implicated in the pathogenesis of cardiovascular diseases. The objective of the present study was to investigate the influence of ACE gene I/D polymorphism on the development and progression of coronary artery disease (CAD) and myocardial infarction (MI) in type 2 diabetic (T2DM) patients. MATERIALS AND METHODS: We screened 283 T2DM patients, inclusive of 160 patients with angiographically defined CAD, 73 patients with MI, 89 patients without MI and 121 T2DM individuals with no evidence of CAD for ACE gene I /D polymorphism. RESULTS: There was no significant difference in the distribution of genotypes and alleles of ACE gene I/D polymorphism between T2DM+CAD and T2DM (non-CAD) groups. However, a significant association of this polymorphism with MI in T2DM+CAD patients (p=0.024) was observed. Further analysis revealed that the frequencies of the DD and ID genotypes increased with the number of stenosed coronary vessels (p=0.026). The DD genotype and the D allele were more frequent in the subgroup of T2DM patients with multivessel CAD (p=0.01) than in individuals with single vessel stenosis. CONCLUSIONS: These findings reveal a significant relationship between ACE gene I/D polymorphism, multivessel CAD and also the occurrence of MI in T2DM individuals with significant coronary stenoses in our population.

Angiotensin converting enzyme (ACE) gene polymorphism in vitiligo: protective and predisposing effects of genotypes in disease susceptibility and progression.

Vitiligo is a depigmenting skin disorder with profound heterogenity in its aetio-pathophysiology, and is associated with inter-individual variation in progression of disease. Angiotensin converting enzyme (ACE) is a regulator of renin angiotensin system (RAS) that plays an important role in the physiology of the vasculature, blood pressure, inflammation, adipocyte distribution of various diseases. The present study was carried out in 243 vitiligo patients (132 males and 111 females), aged between 3-62 years with a mean age at onset of 21.6  ±  13.6 yrs, and in 205 healthy controls of south Indian origin. The main objectives of the present study were to evaluate the ACE I/D (insertion/deletion) polymorphism in the patient and control groups. Further, I/D genotypes were compared among the patients with and without the family history of vitiligo as well as the progression of the disease, through polymerase chain reaction (PCR) methods.

The results revealed a highly significant association of DD genotype with disease susceptibility (p < 0.01) in patients with a family history of vitiligo (p < 0.05) in terms of early age at onset. Further, the pre-dominance of ID genotype among patients revealed its association with a slow progression of the disease (p < 0.05). The present study is the first report to highlight the protective role of II genotype and the significant association of ID genotype with slow progression of the disease.