Insulin:Glucagon Bipolar Axis in Obesity With a Glimpse Into Its Association With Insulin Resistance in Different Glucose Tolerance States.

BACKGROUND: Dysregulation of insulin and glucagon secretion alters the normal insulin:glucagon ratio (IGR) in type 2 diabetes mellitus, obesity, and metabolic syndrome. This study explores the scope of construing the role of these two diametrically opposing hormones on the glucose level not just in obesity but in different glucose tolerance states by looking at the hormone levels and at the insulin glucagon bipolar axis itself. MATERIALS AND METHODS: This is an analytical cross-sectional study of 60 healthy adults consisting of an equal number of adults who are lean and adults who are obese. It was conducted at North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), located in Shillong City, Meghalaya, India. Fasting glucose, insulin, glucagon, and lipids were estimated. Postprandial estimation of glucose was done two hours after oral administration of 75 grams of glucose solution. RESULT: The study demonstrated a state of hyperinsulinemia and hyperglucagonemia prevailing in obesity and all sub-categories of the group of persons who are obese. The study showed a higher fasting IGR in the group consisting of adults who were obese (with a mean of 4.11) when compared with the group of adults who are lean (with a mean of 2.24). Fasting IGR was seen to increase with increasing levels of insulin resistance and increasing impairment in glucose tolerance. IGR showed a positive correlation with the homeostatic model assessment for insulin resistance (HOMA-IR) in the impaired fasting glucose (IFG) category and strongly in the impaired glucose tolerance (IGT) category. CONCLUSION: Hyperglucagonemia in the group of adult persons who are obese indicates a decreased sensitivity of alpha cells to insulin failing insulin to adequately suppress the secretion of glucagon. The study also demonstrated a positive correlation between IGR and HOMA-IR in obesity and all glucose tolerance states of the group of adults who are obese. It is telltale that the sturdier the insulin resistance, the higher the IGR.

Exploring the Role of Serum Hydrogen Sulphide (H2S) Levels in Manic Depressive Psychosis in Terms of Its Association, Diagnostic Ability, and Severity Prediction: Findings From a Tertiary Care Center in North Bengal.

INTRODUCTION: Manic depressive psychosis (MDP) or bipolar disorder, a prevalent psychiatric condition globally and in the Indian population, has been attributed to various pathological mechanisms. Hydrogen sulphide (H2S), a member of the gasotransmitter family, may be linked to the development of bipolar disorder because it plays a crucial role in maintaining proper neuronal function in terms of excitability, plasticity, and homeostatic functions. There is very little data regarding the role of the gasotransmitter H2S in MDP in terms of its association, diagnostic ability, and severity prediction, which led us to conduct this study among MDP patients in the Sub-Himalayan region of West Bengal. METHODS: This was an observational case-control study performed in the Department of Biochemistry, North Bengal Medical College and Hospital, Siliguri, West Bengal, India, from January 2022 to December 2022. Fifty diagnosed MDP patients and 50 healthy age- and sex-matched control subjects satisfying the inclusion and exclusion criteria were studied. The H2S level in the blood was assayed using the standardised spectrophotometric methylene blue method. The severity of depression was assessed by Hamilton Depression Rating Scale (HAM-D) scoring. RESULTS: Of the 50 MDP patients, 45 (90%) were in the depressive phase, and five (10%) were in the manic phase. Of the 45 depressive patients, eight (17.8%) had mild depression, 12 (26.7%) had moderate depression, 19 (42.2%) had severe depression, and six (13.3%) had very severe depression. The mean H2S level in MDP patients (41.98±18.88 µmol/l) was significantly (P<0.05) lower than that in control subjects (99.20± 15.20 µmol/l). It was also observed that the mean H2S level in MDP patients decreased with the duration of the disease but was not statistically significant. The mean H2S levels in the different depression severity groups were found to be significantly different (P<0.001). Receiver operating characteristic (ROC) curve analysis revealed that a cut-off value of H2S <78.5 µmol/l was associated with MDP, with a sensitivity of 96% and a specificity of 88%, and a cut-off value of H2S < 53 µmol/l predicted the severity of depression with a sensitivity of 89.3% and a specificity of 76.5%. CONCLUSION: The significant association of the gasotransmitter H2S in MDP patients and its role as a diagnostic and severity predictive marker can help us to employ proper measures for better management of MDP and improving quality of life.

Idiopathic post prandial glucose lowering, a whistle blower for subclinical hypothyroidism and insulin resistance. A cross-sectional study in Tertiary Care Centre of northeast India.

BACKGROUND AND AIMS: There has been a lot of confusion in management of apparently healthy individuals whose post prandial plasma glucose levels were lower than fasting levels. It has been observed that many clinicians do send for repeat tests to rule out analytical error since there is common knowledge that post prandial glucose should be higher than fasting glucose level. Blood glucose level is regulated by a fully integrated mechanism with complex interplay of hormones and enzymes on metabolic pathways. Increase or decrease of thyroid hormones can break this equilibrium leading to alterations of carbohydrate metabolism. The objective for this study was to look for subclinical hypothyroidism (SCH) and insulin resistance (IR) in Idiopathic Post prandial glucose lowering and the correlation between thyroid stimulating hormone (TSH) with IR in them. METHODS: A cross-sectional study with subgroup analysis, 34 cases and 34 controls. Cases comprises of otherwise healthy individuals whose post prandial glucose is lower than fasting glucose and controls as those healthy individual whose post prandial glucose is higher than fasting. Thyroid hormones and insulin were measured in fasting serum samples. Homeostasis model assessment for IR was calculated as per formula. RESULTS: Among the 34 cases with idiopathic post prandial glucose lowering, 76% (n = 26) had subclinical hypothyroidism and 61% (n = 21) had insulin resistance. A positive correlation (r = 0.55) was observed between Thyroid-Stimulating hormone (TSH) and Index of insulin resistance and homeostatic model assessment (HOMA-IR) and was statistically significant with P < 0.1. CONCLUSIONS: The study highlights the importance of evaluating glycoregulatory hormones like thyroid hormones and insulin in cases with idiopathic post prandial glucose lowering for early diagnosis and prevention of overt clinical diseases like Hypothyroidism and Diabetes Mellitus.

Study of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency and Genotype Polymorphism of G6PD B and G6PD (A+/A-) in Patients Treated for Plasmodium vivax Malaria in a Tertiary Care Hospital in North East India.

Introduction Glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency is the most common enzymopathy in humans, and its distribution has been historically described to be closely associated with that of malaria. North East India provides optimal conditions for transmission of malaria and bears a considerable burden of Plasmodium vivax (P. vivax) malaria. Primaquine, a mainstay in the treatment of vivax malaria, may trigger episodes of acute hemolysis in patients with G6PD deficiency. The present study sought to delineate the frequency and genotypes of G6PD deficiency among patients suffering from vivax malaria infections.  Methods Blood specimens from 80 individuals diagnosed with vivax malaria underwent enzyme assay for G6PD deficiency. Samples with deficient phenotype underwent isolation of DNA using a genomic DNA isolation kit (Qiagen India Pvt. Ltd., New Delhi, India). The genomic DNA underwent amplification, serial denaturation, annealing, extension, final extension followed by digestion with restriction endonucleases Nla III and Fok I. The digested products were subjected to horizontal agarose electrophoresis for the separation of digested fragments. Samples without nucleotide 376 adenine→guanine (A→G) mutation were classified as G6PD B. Those with the mutation were further classified into G6PD A(+) and G6PD A(-) based on the presence of Nla III site. Results Twenty-seven out of 80 individuals (33.75%) with P. vivax malaria were found to have G6PD deficiency, of which a majority (n=24) had G6PD B genotype. Three individuals had Asparagine→Aspartic Acid mutation at position 376 (A→G), of which G6PD A(+) and G6PD A(-) were present in two and one cases, respectively. Conclusion G6PD deficiency was noted in about a third of patients with vivax malaria. Since primaquine therapy is contraindicated in this group of patients, there is a rationale for looking into screening patients with vivax malaria from the region prior to primaquine therapy. Further large scale studies may substantiate this and help in better genotypic and geographic characterization of G6PD deficiency in the region.

No association of 25-hydroxyvitamin D and parathormone levels with glucose homeostasis in type 2 diabetes - a study from Shillong, Meghalaya.

Background: Although inadequate vitamin D and altered parathyroid hormone (PTH) are implicated in deranged glucose metabolism and risk of future diabetes, their role in regulating glucose homeostasis in established cases of diabetes is unclear. We aimed to (i) evaluate vitamin D status, and (ii) determine if vitamin D and PTH were associated with parameters of glucose homeostasis in type 2 diabetes (T2D) patients from Meghalaya, India. Methods: We determined 25-hydroxyvitamin D (25-OH-D) and PTH concentrations in 251 T2D patients (not on insulin), and examined their associations with the following parameters of glucose homeostasis: fasting blood sugar (FBS), post-prandial blood sugar (PPBS), glycated hemoglobin (HbA1c), fasting insulin (FI), homeostasis model assessments of insulin resistance (HOMA-IR) and ß-cell function (HOMA-ß). Results: None of the patients had adequate vitamin D (mean 25-OH-D = 19.3 ng/mL); 47.8% patients were deficient (25-OH-D < 20 ng/mL), while 52.2% were insufficient (25-OH-D < 30 ng/mL) vitamin D. Significant (P < 0.05) univariate associations were observed between: 25-OH-D and FI (r = 0.14); 25-OH-D and HOMA-ß (r = 0.13); PTH and FI (r = -0.18), and PTH and HOMA-ß (r = -0.11). However these associations disappeared after controlling for potential confounders. The 25-OH-D and PTH levels were not associated with any of the tested parameters of glucose homeostasis. Conclusion: There was widespread prevalence of vitamin D deficiency/insufficiency in our sample T2D patients. However, neither vitamin D nor PTH appeared to play a major role in influencing glucose homeostasis in this present selection of T2D cases.

Evaluation of thyroid function in type 2 diabetes in north-eastern part of India: A hospital-based study.

BACKGROUND: Diabetes mellitus (DM) and thyroid dysfunctions are the two most common endocrine disorders to come across in any clinical practice. Both thyroid hormones and insulin act antagonistically in metabolic pathways or cycles of cells. The aim of our study is to look for thyroid dysfunction in patients with type 2 DM and its correlation with insulin resistance (IR). METHODS: A cross-sectional study was carried out among 80 newly diagnosed type 2 diabetic patients. Thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, and insulin were measured in fasting serum sample. Homeostasis model assessment for IR was calculated as per formula. RESULTS: Among 80 diabetic patients, 20 were hypothyroid, 4 were hyperthyroid, and 56 were found to be euthyroid. IR was found to be significantly higher in hypothyroid as compared to euthyroid patients. A positive association was found between TSH and IR (r = 0.230) among hypothyroid patients though association was not significant. In hyperthyroid patients, a strong negative correlation (r = -0.94933) was found between TSH and IR, but no association was found among euthyroid patients. CONCLUSION: The inability to recognize the presence of thyroid hormone dysfunction may be one of the important causes of poor management of type 2 DM. Therefore, there is a need for routine assay of thyroid hormones in type 2 diabetic patients to improve the medical management as well as to reduce the morbidity in them.

Monoclonal gammopathy with double M-bands: An atypical presentation on serum protein electrophoresis simulating biclonal gammopathy.

Monoclonal gammopathies, such as multiple myeloma, typically exhibit high levels of a monoclonal immunoglobulin (M-protein), produced by a clone of abnormally proliferating B-lymphocytes and/or plasma cells. The M-protein can be evaluated by serum protein electrophoresis (SPEP), which yields a single discrete band (M-band), usually in the γ-globulin region. Rarely, two M-bands appear simultaneously at different positions during SPEP - a condition known as biclonal gammopathy, which is a result of clonal expansion of two different neoplastic cell lines. Here, we describe an atypical case of IgA-λ multiple myeloma, where double M-bands (one in ß- and the other in γ-globulin region) were found during SPEP simulating biclonal gammopathy, although it was monoclonal in nature. This peculiar presentation of double M-bands in monoclonal gammopathy was attributed to polymeric forms of IgA by systematic workup. Further, we discuss how true and apparent biclonality can be distinguished by inexpensive analytical techniques in resource-constrained settings.

Presence of Concurrent Derangements of Liver Function Tests in Type 2 Diabetes and Their Relationship with Glycemic Status: A Retrospective Observational Study from Meghalaya.

BACKGROUND AND OBJECTIVES: The liver plays a pivotal role in carbohydrate metabolism. Therefore, functional state of the liver in patients with diabetes is of interest. The objectives of the current study were to (i) identify co-existent biochemical derangements of liver function tests (LFTs) in type 2 diabetes and (ii) determine the association between liver function parameters and glycemic status in type 2 diabetics from Shillong, Meghalaya. MATERIALS AND METHODS: Data from 320 type 2 diabetes patients were screened retrospectively for abnormalities in LFTs. Relationship of fasting serum glucose was assessed with the following tests in the LFT panel: Total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and albumin. Correlation coefficient was computed between individual LFT and fasting glucose status. These bivariate analyses were supplemented by multivariate linear regression analyses. RESULTS: 71.25% subjects had an abnormality in at least one LFT. Elevated ALT (46.8%) and elevated ALP (48.5%) were the most common abnormality in males and females, respectively. ALP correlated positively with fasting glucose in both sexes. AST, ALT, and ALP were found to be independent determinants of glycemic status. CONCLUSION: Derangements in liver function are widely co-existent in type 2 diabetics from Shillong. Deranged liver enzymes are associated with glycemic status. Screening for liver dysfunction in diabetics and subsequent workup may lead to the identification of hepatic co-morbidities and better management.

Association of Serum Calcium Levels with Infarct Size in Acute Ischemic Stroke: Observations from Northeast India.

BACKGROUND: Calcium is known to be major mediator in ischemic neuronal cell death. Recent studies have shown that elevated serum calcium levels at admission in patients with stroke have been associated with less severe clinical deficits and with better outcomes. AIM: The aim of this to determine the correlation between serum calcium (total, corrected, and ionized) and infarct size (IS) in patients with acute ischemic stroke. MATERIALS AND METHODS: Data were collected from 61 patients presenting with acute ischemic stroke from May 2015 to April 2016 at a tertiary care institute in Northeast India. Only patients aged ≥40 years and diagnosed as having acute ischemic cerebrovascular stroke with clinical examination and confirmed by a computed tomography scan were included in the study. Serum calcium levels (total, albumin corrected, and ionized) were collapsed into quartiles, and these quartile versions were used for calculating correlation. Pearson's correlation coefficient was used for comparing calcium levels with IS. RESULTS: Total calcium, albumin-corrected calcium, and ionized calcium had a statistically significant negative correlation with IS with r = -0.578, -0.5396, and -0.5335, respectively. Total and ionized calcium showed a significant negative correlation with IS across all four quartiles. Albumin-corrected calcium levels showed a significant negative correlation with IS only across the lowest and highest quartiles. CONCLUSION: The findings in our study suggest that serum calcium can be used as a prognostic indicator in ischemic stroke as its levels directly correlates with the IS.

Thyroid profile status of patients treated for multidrug-resistant tuberculosis in state of Meghalaya, India.

BACKGROUND: Meghalaya has high tuberculosis burden with increasing multidrug-resistant tuberculosis (MDR-TB) cases. Drug-induced hypothyroidism is one of the well-documented adverse effects in treatment of MDR-TB, the data of which are unavailable in the population residing in this part of the Indian subcontinent. AIM: This study was undertaken to assess the thyroid profile status of patients under DOTS Plus treatment and to evaluate the effects of anti-tubercular drugs on thyroid functions with respect to the pre-treatment thyroid status. METHODS: A prospective study of 114 patients who initiated treatment for MDR-TB between June 2012 and August 2013 was performed. Thyroid hormones, viz., TSH, Total T3, Total T4, Free T3 and Free T4 were estimated. RESULTS: Out of our study group of 114 MDR-TB patients, 15 dead patients and defaulters were excluded. So, out of 99 patients, till now, 76 patients have completed 6 months of DOTS Plus treatment and were re-evaluated for thyroid status. 52(68%) patients showed TSH levels more than the reference limit of 5.60 µIU/mL and 5(7%) patients had TSH >10 µIU/mL suggesting presence of sub-clinical hypothyroidism. CONCLUSION: We suggest the need for Mandatory TSH screening at baseline and then six months interval for all patients taking DOTS Plus so that no adverse effect goes under-reported and early intervention if required should be done to maintain proper adherence.

Association of secondary hyperparathyroidism with hemoglobin level in patients with chronic kidney disease.

PURPOSE: Secondary hyperparathyroidism (SHPT) is one of the less recognized reasons of anemia in chronic kidney disease (CKD). In this study, we evaluated the role of SHPT as a cause of anemia and correlation of intact parathyroid hormone (iPTH) and hemoglobin (Hb) level in hemodialysis (HD) patients. METHODS: This cross-sectional study was carried out in 63 individuals admitted in HD unit of the institute. Serum samples were collected and urea, creatinine, Hb, ferritin and iPTH levels were measured. Statistical analysis was carried out using the SPSS software (IBM, NY, USA). RESULTS: Mean ± standard deviation for serum urea, creatinine, Hb, ferritin and intact PTH were 177 ± 15.52, 15.16 ± 2.28 mg/dl, 7.03 ± 2.26 g/dl, 654.7 ± 563.4 ng/ml, 539.18 ± 493.59 pg/ml respectively. A reverse correlation was found between intact PTH and Hb level. CONCLUSIONS: A variety of postulated pathophysiological mechanisms linking SHPT and anemia in CKD are discussed. An efficient control of parathyroid hormone hypersecretion may be required to achieve a better management of anemia in HD patients.

Lipid peroxidation and antioxidant vitamins in urolithasis.

The present, study was conducted to determine the level of malondialdehyde (MDA) as an index of free radial induced lipid peroxidation and antioxidant vitamins-vitamins A, vitamin C and vitamin E in 75 confirmed cases of urolithiasis. Significantly high level of MDA (p<0.001) with significantly low levels of vitamin E (p<0.001) and vitamin A (p<0.001) with no significant decrease in vitamin C (p>0.05) were observed in the plasma of urolithiasis cases as compared to normal controls. In conclusion, it appears that a role of lipid peroxidation and oxidative function exists in the pathogenesis of urolithiasis. But, the exact mechanism how this occurs remains to be elucidated.