Clinicopathological Study of Chronic Kidney Disease of Unknown Etiology in Odisha.

INTRODUCTION: Chronic kidney disease (CKD) is emerging as a serious health problem in Odisha, India. A new form of severe CKD affecting adults, not due to traditional risk factors like diabetes, hypertension, glomerulonephritis, has been reported in Sri Lanka, Central America, and Egypt in the last two decades. This has been named CKD of unknown origin (CKDu), and it is fatal due to late recognition and rapid disease progression. The aim of the study was to elucidate the association between different sociodemographic, and biochemical parameters with renal morphology in CKD of unknown origin patients. METHODS: A cross-sectional study was conducted on 124 consecutive patients with CKD from the period January 2018 to December 2018. Patients in the age group 18-60 years who met clinical criteria for CKD were included. Participants answered a questionnaire. After the necessary history, clinical evaluation, and blood and urine analyses, a kidney biopsy was undertaken. Kidney biopsy was feasible in 51 patients as the rest 61 patients had shrunken kidneys and 12 patients did not give consent. Patients with diabetes mellitus (DM), hypertension, glomerulonephritis, polycystic kidney disease, obstructive kidney disease or any other congenital diseases, snakebite, pregnancy, malignancy, gout, primary hyperparathyroidism, infectious diseases like human immunodeficiency virus (HIV), TB, Hepatitis B and C, malaria, syphilis, leprosy and coagulopathies were excluded. Among the 51 patients, 23 had CKDu, 25 had chronic glomerulonephritis and three biopsies were inconclusive. RESULTS: The mean age of CKDu patients was 36.78 ± 9.85 years. Males (73.9%) were predominantly affected. A family history of CKD was seen in 82.6% of CKDu cases. Hyponatremia and hypokalemia were predominant biochemical abnormalities in our CKDu cases. Binary logistic regression showed rural residence, family history of CKD, exposure to smoke from burning coal, charcoal, or biomass fuels, low socioeconomic status, and low body mass index were strongly associated with CKDu. There was an increased risk of developing CKDu in persons with a family history of CKD [p = 0.003, odds ratio (OR)- 17.58], persons exposed to smoke from burning coal, charcoal or biomass fuels (p = 0.003, OR- 32.4), and patients with low socio-economic status (p = 0.001, OR- 15.87). Interstitial fibrosis (IF), interstitial inflammation with mononuclear infiltration, tubular atrophy (TA), and global glomerulosclerosis (GS) were pertinent histopathological findings in our study. CONCLUSION: There is no strong evidence for a single cause for CKDu, and multiple environmental, occupational and social factors are probably involved. We need to design consistent and comparative multisite studies to identify etiologies of CKDu, across high-risk populations that may help elucidate the importance of region-specific vs global risk factors.

Prescribing Patterns and Response to Antihyperglycemic Agents Among Novel Clusters of Type 2 Diabetes in Asian Indians.

Aim: To assess the prescribing patterns and response to different classes of antihyperglycemic agents in novel clusters of type 2 diabetes (T2D) described in India. Materials and Methods: We attempted to replicate the earlier described clusters of T2D, in 32,867 individuals with new-onset T2D (within 2 years of diagnosis) registered between October 2013 and December 2020 at 15 diabetes clinics located across India, by means of k-means clustering utilizing 6 clinically relevant variables. Individuals who had follow-up glycated hemoglobin (HbA1c) up to 2 years were included for the drug response analysis (n = 13,247). Results: Among the 32,867 participants included in the study, 20,779 (63.2%) were males. The average age at diagnosis was 45 years and mean HbA1c at baseline was 8.9%. The same four clusters described in India earlier were replicated. Forty percent of the study participants belonged to the mild age-related diabetes cluster, followed by insulin-resistant obese diabetes (27%), severe insulin-deficient diabetes (21%), and combined insulin-resistant and insulin-deficient diabetes (12%) clusters. The most frequently used antihyperglycemic agents were sulfonylureas, metformin, and dipeptidyl peptidase-4 inhibitors apart from insulin. While there were significant differences in HbA1c reduction between drugs across clusters, these were largely driven by differences in the baseline (pretreatment) HbA1c. Conclusions: In this new cohort, we were able to reliably replicate the four subtypes of T2D earlier described in Asian Indians. Prescribing patterns show limited usage of newer antihyperglycemic agents across all clusters. Randomized clinical trials are required to establish differential drug responses between clusters.

Comparison of Fetomaternal Outcomes in Patients With Gestational Diabetes Mellitus Treated With Insulin Versus Acarbose: Results of a Prospective, Open Label, Controlled Study.

Objective To evaluate fetomaternal outcomes in patients with gestational diabetes mellitus (GDM) treated with insulin versus acarbose. Material and methods In this prospective, open label, controlled study, GDM patients treated with insulin or acarbose were observed till six weeks after delivery. Maternal outcomes, fetal outcomes and glycemic control were compared between two groups.  Results Fifty patients in each group (insulin group-mean age 28.52 years; acarbose group-mean age 26.26 years; p=0.020) were included. There was no difference in body mass index (p=0.157), family history of diabetes (p=0.648), history of GDM (p=0.50) or mean gestational age at diagnosis (p=0.245) between the two groups. There was no significant difference in the incidence of recurrent infections (p=0.64), pre-eclampsia (p=0.64) or premature rupture of membranes (p=0.40) between the two groups. Mean duration of gestational weeks at the time of delivery in the insulin and acarbose group was 36.93 and 38.36 weeks respectively (p=0.002). There was no difference in the modes of delivery, mean post-operative random blood glucose (p=0.96), fasting blood glucose level at day seven (p=0.15) and after six weeks (p=0.83) between the insulin and acarbose groups. There was no difference in reduction in the postprandial blood glucose level at day seven (p=0.48) and after six weeks (p=0.23). There was no significant difference in the mean birth weight of babies born to mothers treated with the two drugs (p=0.21). There was no difference in the incidence of neonatal complications between the two groups. Conclusion Acarbose can be an effective and well tolerated option for treatment of gestational diabetes mellitus.

Hematological, Biochemical and Renal Changes in Patients of Multiple Myeloma Treated with Bortezomib Based Triple Drug Chemotherapy.

INTRODUCTION: Multiple myeloma (MM) is a neoplastic clonal plasma cell disorder. Approximately 30% of newly diagnosed MM present with baseline renal dysfunction adversely affecting prognosis and survival. But its outcome has improved with the advent of novel agents. METHODS: We undertook this clinicopathological study to assess the profile of renal involvement, evaluate hematological response, renal reversibility and renal response of 34 newly diagnosed cases of MM with renal impairment receiving 4-6 cycles of Bortezomib, Thalidomide and Dexamethasone (BTD). RESULTS: Bone pain (67.64%) and pallor (88.23%) were the most common clinical symptom and sign respectively. Mean serum creatinine before and after treatment was 3.5 mg/dl and 1.59 mg/dl respectively. After treatment 15 cases achieved renal reversibility, 8 patients had improved renal function and 3 patients became dialysis independent. The median time to renal reversal was 22weeks (2-28 weeks) and overall myeloma response rate was 78.78%. All patients showed renal response. The median time to renal response was 2.4weeks. We found 38.23% pure cast nephropathy, 14.7% myeloma immunoglobulin deposition disease (MIDD), 5.88% amylodosis apart from other lesions. CONCLUSION: BTD is safe, effective in reversing renal impairment and improves survival in newly diagnosed cases of MM with renal impairment.

Clinical characteristics, types and complications of diabetics with young age at the onset (14-25 years).

AIMS: To determine the distribution, clinical features and complications of the different types of diabetes in young age. METHODS: The records of children and adolescents with age at the onset of DM (14-25 years) between January 2017 and August 2018, were reviewed. Clinical and laboratory characteristics of the patients at diagnosis and type of diabetes were recorded. RESULTS: Out of 80 patients (48 males, 32 females), 53 had type 1 DM (66.2%) and 27 had type 2 DM (33.8%). Mean age at the onset of diabetes was 19.75 ±â€¯4.01 years for type 1 DM and 21.37 ±â€¯3.08 years for type 2 DM. Family history of DM was more common in type 2 DM (62.9% of parents, p = 0.000389). Mean BMI in type 2 DM (25.03 ±â€¯5.88 kg/m2) was higher than in type 1 DM (p = 0.009). Osmotic symptoms were more common in type 1 DM (73.06%, p = 0.00151). CONCLUSION: Osmotic symptoms and ketosis were more common in young age type 1 DM. Family history of DM was more common in parents of type 2 DM.

A study of the PfNT3 in Plasmodium falciparum

Previous genetic studies demonstrated that survival and proliferation of Plasmodium falciparum parasites is dependent on salvage of essential purines from the host. Plasmodium falciparum, the causative agent of the most lethal form of human malaria lacks the enzymes required for de novo synthesis of purines. Analysis of the hypothetical nucleoside/nucleobase transporter protein, the gene product of PfNT3 (PF14_0662) gene in P. falciparum parasites was carried out by localisation, in view of a novel chemotherapeutic target. Immunoblotting, immunofluorescent and immunoelectron microscopic localization of PfNT3 was demonstrated using polyclonal antiserum in in vitro cultured Plasmodium falciparum parasites, propagated in human red blood cells. PfNT3 protein, the translated product of PfNT3 gene was detected in intraerythrocytic ring, trophozoite, and schizont stages. PfNT3 was localized primarily to the PPM (Parasite Plasma Membrane). The endogenous PfNT3 putative nucleoside transporter with the predominant location to the parasite plasma membrane may serve not only as routes for targeting of purine analogs/cytotoxic agents into the intracellular parasite but may also serve as drug targets. Being genome encoded the vital transporter protein can be prevented from expression by silencing of the gene, validating it to be a novel drug target.

Prevalence of inflammatory markers (high-sensitivity C-reactive protein, nuclear factor-κB, and adiponectin) in Indian patients with type 2 diabetes mellitus with and without macrovascular complications.

BACKGROUND: Atherosclerosis is more prevalent in subjects with diabetes mellitus. Recent evidence suggests that diabetic atherosclerosis is not simply a disease of hyperlipidemia, but is also an inflammatory disorder. Our aim was to study the prevalence of inflammatory markers such as high-sensitivity C-reactive protein (hsCRP), adiponectin, and nuclear factor-κB (NF-κB) expression, in peripheral blood mononuclear cells in Indian patients with type 2 diabetes mellitus (T2DM) with and without macrovascular disease (MVD). METHODS: A total of 29 consecutive cases of T2DM with proven MVD (group A), 28 matched cases without MVD (group B), and 14 healthy controls (group C) were evaluated for the clinical parameters fasting blood glucose (FBG), 2-h postprandial blood glucose (PPBG), glycosylated hemoglobin (HbA1c), lipid profile, and the above-mentioned inflammatory markers. RESULTS: Diabetic subjects with T2DM had higher hsCRP and NF-κB expression and lower values of adiponectin compared to healthy controls. Group A had significantly higher serum hsCRP than group B (P=0.0001) despite comparable values of BMI, FBG, 2-h PPBG, HbA1c, and lipid parameters. Group A had significantly higher serum hsCRP and NF-κB expression and significantly lower levels of adiponectin than group C (P=0.0001, 0.007, and 0.02, respectively). In Group A, serum adiponectin negatively correlated with NF-κB expression. In Group B, adiponectin values correlated negatively with both FBG and 2-h PPBG. CONCLUSIONS: Indian subjects with T2DM with or without MVD had higher hsCRP and lower adiponectin values as compared to healthy controls, whereas hsCRP was significantly higher in those with MVD, suggesting that our patients with T2DM were in a proinflammatory state.

Beta-cell function and insulin resistance in pregnancy and their relation to fetal development.

BACKGROUND: Insulin resistance in pregnancy is consequent to the physiological adaptation necessary to provide glucose to the growing fetus. Disturbance in the maternal metabolism can induce structural and functional adaptations during fetal development. METHODS: Pregnant women with duration of conception between 24 and 28 weeks were assessed for insulin resistance (IR) and beta-cell function by using homeostatic model assessment IR (HOMA-IR) and homeostatic model assessment of beta-cell function (HOMA-B) models, respectively. One hundred pregnant women and 42 age-matched controls were taken for the study. Fourteen pregnant women were diagnosed as gestational diabetes mellitus (GDM) as per World Health Organization (WHO) criteria. RESULTS: Pregnant women with normal glucose tolerance (NGT) did not reveal significant IR as compared to controls but the HOMA-B was higher (268.91 +/- 197.16 vs 188.6 +/- 88.83, P < 0.01), suggesting excessive beta-cell function to maintain glucose homeostasis. The subset of pregnant women who presented with GDM had significantly higher HOMA-IR values (6.59 +/- 2.93 vs. 1.77 +/- 1.49, P < 0.001) and similar HOMA-B values as compared to pregnant women with NGT. Pregnant women with severe IR manifested as GDM, even without any previous history of dysglycemia. CONCLUSIONS: With regard to fetal outcome, HOMA-IR is an independent predictor in pregnant women with NGT (biparietal diameter r(2) = 0.204, P < 0.01; weight r(2) = 0.097, P < 0.01), whereas beta-cell function (HOMA-B) is a strong independent predictor of fetal outcome in pregnant GDM (biparietal diameter r(2) = 0.58, P < 0.05; FL r(2) = 0.71, P < 0.01 AC r(2) = 0.79, P < 0.001; weight r(2) = 0.57, P < 0.01).

Insulin resistance and beta cell function as prognostic indicator in multi-organ dysfunction syndrome.

Insulin resistance (IR) is a major factor in the pathogenesis of sepsis. Critically ill patients with multi-organ dysfunction syndrome (MODS), diagnosed as per modified Acute Physiology and Chronic Health Evaluation II (modified APACHE II) score criteria and admitted to the medical ward in our hospital, were assessed for IR and beta cell function by using the homeostasis model assessment A (HOMA-A) and HOMA-B models, respectively. Of 80 consecutive patients, 60 were followed up to day 7; 16 patients died and 4 did not agree to follow up. The mean value of IR in all the 80 patients studied on the day 1 of hospitalization was 6.67 +/- 10.65. The initial high values of serum insulin and IR were significantly reduced (p < 0.05) as these patients recovered from their critical illness. Of those who died, the first day mean insulin levels were high (13.80 +/- 14.72 micro/ml as well as IR 5.14 +/- 6.76 values), but they had statistically low beta cell function (46.45 +/- 433.64%) as compared to those who recovered (227.60 +/- 430.36%; p < 0.05). This suggests that, beta cell overexhaustion occurs in critically ill patients, because it was required to overcome the prevailing state of IR and has more bearing in patients having less than 4 organ failures. beta cell failure ensued from the onset in those who were more moribund and had more than four organs failing or those who died. IR and beta cell function are reliable indicators of the state of severity of critical illness, and they corroborated with mortality in patients with MODS.

Autoimmunity, insulin resistance and Beta cell function in subjects with low body weight type 2 diabetes mellitus.

In developing countries like India, the majority of Type 2 diabetics are non-obese, and many are "lean" with a body mass index (BMI) below 18.5. This type is referred to as "Low Body Weight Type 2 DM" (LB Type 2 DM). LB Type 2 DM are confused with Type 1 DM or late autoimmune diabetes in adults (LADA) due to their high blood glucose levels and early insulin-requiring state. We assessed pancreatic islet cell autoimmunity by using both glutamic acid decarboxylase 65 antibody (GADA) and anti-IA(2) antibody estimation in 23 patients with LB Type 2 DM and 10 age-matched normal weight (NW) Type 2 DM. Fasting blood glucose (FBG) and 2 hr postchallenge blood glucose (PGBG2) were significantly higher in LB (p < 0.05), while mean values of fasting insulin (24.47 +/- 73.15 muIU/mL vs. 13.4 +/- 16.54 muIU/mL, p > 0.7) and fasting C-peptide (180.81 +/- 357.08 pM/mL vs. 279.83 +/- 281.38 pM/mL, p > 0.5) in LB and NW respectively were not statistically different. All 23 LB and 10 NW subjects were GADA negative while IA(2) positivity was found in 1/23 and 1/10 cases, respectively. LB Type 2 DM revealed good beta cell function with homeostasis model assessment beta cells (HOMAB) values of 57.41 +/- 153.18 as compared to 44.74 +/- 56.24 (p > -0.2) in NW Type 2 DM. Insulin resistance as assessed by homeostasis model assessment insulin resistant (HOMA IR) was 13.50 +/- 42.83 and 5.68 +/- 6.90 (p > 0.6) in LB and NW Type 2 DM, respectively, suggesting that LB Type 2 DM are a phenotypic variant of Type 2 DM.

Effect of metformin in asian Indian women with polycystic ovarian syndrome.

BACKGROUND: This study was conducted to study the therapeutic benefits of metformin and to determine the correction of insulin resistance on 25 patients of polycystic ovarian syndrome (PCOS) attending the Department of Obstetrics and Gynaecology, S.C.B. Medical College and Hospital, Cuttack, India, for varying complaints. METHODS: Twenty-five women diagnosed as having PCOS received metformin in doses of 500 mg every 8 h for 6 months. Periodical evaluation with respect to clinical improvement was done after months 3 and 6, while evaluations of changes in biochemical parameters and hormone levels were done at the end of month 6. RESULTS: Out of 23 cases (92%) women who presented with menstrual disturbances, the cycles were regularized in 21 (91%). Fourteen women complained of infertility, and five (35.7%) of them conceived within the span of treatment. In six (24%) cases with complaints of hirsutism, there was improvement in three cases (50%). Twelve (91.6%) of obese patients with PCOS had weight loss with significant changes in waist-to-hip ratio (WHR) after metformin therapy. Of the three patients with low FSH, the level became normal in two cases. Polycystic changes in ovary regressed in 12 (85.7%) cases. Of the 13 patients with elevated serum testoterone level, normalization of values was seen in 12 cases. Abnormal LH/FSH ratio and impaired glucose tolerance were normalized, and insulin resistance was significantly reduced in all the cases studied, with mean HOMA values decreasing from 3.34 to 1.82. CONCLUSIONS: This study conclusively points out the beneficial effects of metformin in cases of PCOS in Asian women, both in the adolescent and the reproductive age. This mode of treatment is successful and has an etiological rationale behind its use. The additional benefits are a relatively low cost of therapy and diminished hazards associated with surgical intervention.

Relationship of metabolic syndrome with quantum of coronary artery disease in Indian patients with chronic stable angina.

BACKGROUND: The current study was aimed to ascertain presence and severity of coronary artery lesions in patients of Type 2 diabetic mellitus (DM) with coronary artery disease (CAD), in our population, by using scoring system analysis of the coronary angiography. METHODS: 147 consecutive patients with Type 2 DM of chronic stable angina (CSA) were enrolled in the study with 147 age- and sex-matched patients of CSA who did not have diabetes to serve as control. All of them underwent coronary angiography and were evaluated by using four scores to quantify the coronary artery lesions. The scores analyzed were coronary score, extent score, severity score, and atherosclerosis score. Other major risk factors such as smoking and hypertension lipid profile were also evaluated. RESULTS: Type 2 diabetics with CAD had higher coronary score (0.91 +/- 0.63 in diabetics vs. 0.43 +/- 0.39, p < 0.001), extent score (4.91 +/- 3.1 vs. 2.3 +/- 1.8, p < 0.001), severity score (1.85 +/- 0.41 vs. 1.2 +/- 0.32, p < 0.001), and atherosclerosis score (0.52 +/- 0.31 vs. 0.21 +/- 0.26, p < 0.001) as compared to non-diabetics with CAD. Left main stem involvement, 2-vessel disease, and 3-vessel disease were also more frequent in the diabetics. These diabetes also had higher incidence of obesity, hypertension, and dyslipidemia. CONCLUSIONS: In our population, diabetics suffer from higher prevalence of diffuse and extensive coronary atherosclerosis. The grades of stenosis in coronary arteries are also higher in diabetic patients when compared with non-diabetics with CAD, as was the prevalence of other components of the metabolic syndrome.

Combination of drugs in the management of diabetes mellitus.

Combination of drugs or polypharmacy is a therapeutic procedure and this can be needed in diabetes also. To consider the basis of polypharmacy, certain knowledges regarding likely mechanism operating in diabetic patient are to be known. Drugs available in polypharmacy are well elaborated in this article. The drugs can be categorised in three headings: Obese type 2 diabetes mellitus, non-obese or standard weight diabetes and low body weight subjects. Severity of hyperglycaemia is another factor to be looked into while treating type 2 diabetic patients. Besides, certain other situations are narrated where the combination therapy can be helpful.