Urinary brush border enzymes for early diagnosis of tubular dysfunction in patients with type 2 diabetes mellitus

Background: Diabetic nephropathy is a major cause of premature morbidity and mortality in type 1 and type 2 diabetes mellitus (T2DM) and hence new markers with better sensitivities are being investigated. The study was taken up to investigate whether urinary activities of N-acetyl-β-D-glycosaminidase (NAG), alkaline phosphatase (ALP), lactate dehydrogenase LDH) and Gamma glutamyl transferase (γ-GT) can be used as screening markers of renal dysfunction in patients suffering from T2DM.Methods: One hundred and four patients with T2DM along with 30 age- and gender-matched healthy individuals were included in the study. Patients were divided into three groups based on their u-MA levels i.e. normoalbuminuric (group1), micro albuminuric (group 2) and macroalbuminuric (group 3).Results: Urinary enzymes activity was significantly higher in patients with T2DM compared to controls (p<0.05). NAG, ALP, LDH, and GGT were significantly higher in group 3 compared to group1 and group 2 (p<0.0001). NAG, ALP, LDH and GGT showed significant positive correlation with MA (p=0.0001, r=0.308; p=0.0001, r=0.369; p=0.002, r=0.304, p=0.044, r=0.202 respectively). GGT and LDH showed highest sensitivity (86.21%, 84.00% respectively) and specificity (78.57%,53.49% respectively) for diagnosing renal dysfunction in patients with normoalbuminuria.Conclusions: The study suggests that u-GGT and LDH can be useful markers for assessing renal dysfunction in T2DM patients even before microalbuminuria manifests

Association of triglycerides/high density lipoprotein cholesterol ratio with insulin resistance in polycystic ovary syndrome

Background: Insulin resistance (IR) is frequently observed in women with polycystic ovary syndrome (PCOS). Recent studies advocated that triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) can be used as a simple clinical indicator of IR. Hence, the present study was performed to investigate the use of TG/HDL-C and its association with IR in PCOS.Methods: Forty-one patients with PCOS and 40 healthy age matched women were randomly enrolled. Demographic and clinical characteristics were obtained. Insulin resistance was defined by the homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI).Results: In PCOS group, the insulin, HOMA-IR and TG/HDL-C ratio were significantly higher (p=0.001) than controls while, QUICKI was lower (p=0.001). Insulin, HOMA-IR were positively correlated with TG/HDL-C (ρ=0.303, p=0.006 and ρ=0.312, p=0.005 respectively) while, QUICKI was negatively correlated (ρ=-0.698, p=0.001). In receiver operating characteristic (ROC) analysis, area under the curve (AUC) for model based on QUICKI levels was better 0.898 (95% CI: 0.811-0.955, p=0.001) than HOMA-IR 0.636 (95% CI: 0.522-0.740, p=0.03). A cut-off value 3.23 for TG/HDL-C is proposed from the model based on QUICKI with best combination of sensitivity 83.3% and specificity 86.7%.Conclusions: Results of present study support that TG/HDL-C ratio may be a simple indicator of IR in PCOS patients which helps clinicians to identify IR in small centers, where the assays for insulin measurement are not available

High Prevalence of Associated Birth Defects in Congenital Hypothyroidism

Aim. To identify dysmorphic features and cardiac, skeletal, and urogenital anomalies in patients with congenital hypothyroidism. Patients and Methods. Seventeen children with congenital primary hypothyroidism were recruited. Cause for congenital hypothyroidism was established using ultrasound of thyroid and 99mTc radionuclide thyroid scintigraphy. Malformations were identified by clinical examination, echocardiography, X-ray of lumbar spine, and ultrasonography of abdomen. Results. Ten (59%) patients (6 males and 4 females) had congenital malformations. Two had more than one congenital malformation (both spina bifida and ostium secundum atrial septal defect). Five (29%) had cardiac malformations, of whom three had only osteum secundum atrial septal defect (ASD), one had only patent ductus arteriosus (PDA), and one patient had both ASD and PDA. Seven patients (41%) had neural tube defects in the form of spina bifida occulta. Conclusion. Our study indicates the need for routine echocardiography in all patients with congenital hypothyroidism

Role of adipokines, oxidative stress, and endotoxins in the pathogenesis of non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus

Background: Type 2 diabetes mellitus (T2DM) is associated with chronic inflammation and oxidative stress, implicated in the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Present study aimed to assess the role of adipokines, oxidative stress, and endotoxins in the pathogenesis of NAFLD in T2DM.Methods: Present cross-sectional observational study included healthy controls (n=50; group 1); T2DM patients without NAFLD (n=50; group 2), T2DM patients with NAFLD (n=50; group 3). Study subjects were age and gender matched.Results: Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high sensitive C-reactive protein (hs-CRP), endotoxin, malondialdehyde (MDA) were significantly elevated and adiponectin, ferric reducing ability of plasma (FRAP), and glutathione (GSH) were significantly lower (p<0.001) in T2DM patients with NAFLD when compared to T2DM patients without NAFLD and controls. Endotoxin showed significant positive correlation with TNF-α (r=0.304; p<0.001), hs-CRP (r=0.193; p=0.018), and MDA (r=0.420; p<0.001), and significant negative correlation with adiponectin (r=-0.406; p<0.001). TNF-α and IL-6 showed significant positive correlation with MDA (r=0.526; p<0.001, r=0.229; p=0.005) and significant negative correlation with adiponectin (r=-0.396; p<0.001, r=-0.318; p<0.001), FRAP (r=-0.418; p<00.001, r=-0.170; p=0.038), and GSH (r=-0.353; p<0.001, r=-0.301; p<0.001).Conclusions: Authors observed elevated endotoxin, oxidative stress, inflammation and lower adiponectin levels in T2DM subjects compared to controls. These changes were more pronounced in T2DM with NAFLD when compared to T2DM without NAFLD.  Lower adiponectin levels were found to be a better predictor of NALFD in T2DM and is associated with oxidative stress and systemic inflammation

Regional earth system modelling framework for CORDEX-SA: an integrated model assessment for Indian summer monsoon rainfall

An effort is made to implement a regional earth system model (RESM); ROM, over CORDEX-South Asia (SA). The added value of RESM is assessed for mean precipitation, its variability (intraseasonal to interannual), extremes, and associated processes. In this regard, ROM’s fields are compared with the respective fields of its standalone version (REMO), the models belonging coupled model intercomparison project (CMIP5 and CMIP6), and regional climate models of CORDEX-CORE simulations. RESM shows substantial improvement for most of the Indian monsoon’s aspects; however, the magnitude of the value addition varies spatiotemporally and also with different aspects.. The improved representation of intraseasonal variability (active-break spell’s duration and intensity) and Interannual variability attributed to improved mean seasonal precipitation. Additionally, correct representation of sea surface temperature, Indian Ocean Dipole, and its underlying dynamics also contribute to improving the mean precipitation. The notable improvement is seen especially over the south-eastern regions of the Bay of Bengal (BoB) and South-Central India, where increasing (decreasing) low-pressure systems over Central India (BoB) are noticed as a consequence of air-sea coupling, leading to enhanced (reduced) precipitation over Central India (BoB), reducing dry (wet) bias found in REMO and the other models. Despite substantial improvements, RESM has a systematic wet bias in the mean precipitation associated with a warm bias over the western coast of the Arabian Sea. An overestimation of very high extreme precipitation due to the enhanced contribution of low-pressure systems indicates the model’s limitations, suggesting the need for further tuning of the RESM

High-density lipoprotein cholesterol: How High

The high-density lipoprotein cholesterol (HDL-C) is considered anti-atherogenic good cholesterol. It is involved in reverse transport of lipids. Epidemiological studies have found inverse relationship of HDL-C and coronary heart disease (CHD) risk. When grouped according to HDL-C, subjects having HDL-C more than 60 mg/dL had lesser risk of CHD than those having HDL-C of 40-60 mg/dL, who in turn had lesser risk than those who had HDL-C less than 40 mg/dL. No upper limit for beneficial effect of HDL-C on CHD risk has been identified. The goals of treating patients with low HDL-C have not been firmly established. Though many drugs are known to improve HDL-C concentration, statins are proven to improve CHD risk and mortality. Cholesteryl ester transfer protein (CETP) is involved in metabolism of HDL-C and its inhibitors are actively being screened for clinical utility. However, final answer is still awaited on CETP-inhibitors

Clinical applications of glycosylated haemoglobin

Glycosylated haemoglobin (HbA1c) has been in use since 1980s as the 'gold standard' for monitoring glycaemic control and as a predictor of diabetic complications. Even though several conditions, such as, haemolytic anaemia (lowers HbA1c) and aplastic anaemia (raises HbA1c) tend to confound and interfere with HbA1c measurement, in most circumstances HbA1c is a valid and reliable index of glycaemic status. Recently, HbA1c has also been recommended as a diagnostic test for diabetes mellitus by the American Diabetes Association (ADA); HbA1c offers logistical advantages over the conventional oral glucose tolerance test as it requires a non-fasting random sample. In this article the history of discovery of HbA1c, biochemical processes behind its formation, its assay techniques, various factors influencing HbA1c, importance of standardization of its assay so as to make the results reported from different laboratories much more comparable are critically reviewed. This review also provides an update on the optimal HbA1c targets, its reliability in control of diabetic complications, limitations of test results and its importance in control of diabetes patients and their complications, various cut-off values obtained in studies performed both in India and worldwide and its role as a surrogate marker of metabolic syndrome, among others

Indices of insulin resistance in paediatric obesity

Background: Paediatric obesity is associated with insulin resistance (IR), which increases risk of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). Hyperinsulinaemic-euglycaemic clamp and minimal-model analysis frequently sampled intravenous glucose tolerance test (FSIVGTT) are used to assess IR, which are invasive, complex and expensive. Objective: To assess IR using the derived indices namely, homeostasis model assessment of insulin resistance (HOMAIR), fasting glucose-to-insulin ratio (FGIR), quantitative insulin-sensitivity check index (QUICKI), in obese children. Methods: Fifty obese children (cases) and 50 apparently healthy age-and gender- matched non- obese children (controls) were studied. Obese children with body mass index (BMI; Kg/m2) greater than 95th percentile and nonobese children with BMI between 5th to 95th percentile were included in the study. Results: Obese children had higher fasting insulin levels, HOMA-IR (p<0.001), FGIR (p<0.001) and QUICKI (p<0.001) when compared to controls; fasting blood glucose levels were comparable (p=0.170). A statistically significant correlation was observed between serum insulin and BMI, between insulin and all the derived indices and between the derived indices and BMI (p<0.001). HOMA-IR had more area under the curve (0.760) followed by FGIR (0.721) when compared to QUICKI (0.240). Conclusions: Obese children were normoglycaemic with IR. HOMA-IR was found to be a stronger predictor of IR when compared to FGIR and QUICKI in obese children

Malignancy in solitary thyroid nodule: A clinicoradiopathological evaluation

Background: Thyroid nodules are common. They can be either benign or malignant. Solitary thyroid nodules (STN) have a high likelihood of being malignant. They should be characterized properly for optimum management. Materials and Methods: In this study, we have analyzed our departmental data over a period of 5 years. All the patients who presented to the outpatient department with a clinically detected STN were included in the study group. Our approach was individualized. Preoperative ultrasonography (USG) and fine-needle aspiration cytology were planned in all these patients. Hemi thyroidectomy and total thyroidectomy with and without neck dissection were performed wherever appropriate. Results: There were 162 cases of clinically detected STN. USG findings were available in 146 cases. Postoperative histopathology was reported as malignant in 58 cases. Malignant STN was more likely in males. Ultrasonographically detected solid STN were more prone for malignancy as compared to multinodular goiter (P = 0.000) Presence of micro calcification and cervical lymphadenopathy were more commonly noted in malignant thyroid swellings. Conclusion: Solitary thyroid nodules do have a high likelihood of harboring a malignancy. Solid echogenicity, micro calcification and cervical lymphadenopathy on USG were seen more frequently in malignant nodules