Stress Hyperglycemia: A Problem that Cannot be Ignored

Stress hyperglycemia is a strong neuroendocrine reaction in thehypothalamic pituitary adrenal cortex under severe infection, trauma, burns,hemorrhage, surgery and other harmful stimulated, resulting in increasedsecretion of counter-regulatory hormones. These hormones promotedthe production of sugar and cause glucose metabolism disorders withcytokines and insulin resistance. In this condition, the production of sugarexceeds the utilization of sugar by the tissues, which eventually leads to anincrease in blood glucose levels in plasma. In the intensive care unit, stresshyperglycemia is very common and can occur in patients with or withoutdiabetes. The incidence is as high as 96%, and it is an independent factorin the death of critically ill patients. Hyperglycemia not only prolongsthe hospitalization time, mechanical ventilation time and increased theincidence of serious infections in critically ill patients, but can also leadto the occurrence of type 2 diabetes. Therefore, it is very important tolearn the pathological mechanism of stress hyperglycemia, the harm ofhyperglycemia and blood sugar management.

Progesterone Receptor Antagonists – A Novel Treatment for Severe Hyponatremia from the Endocrine Paraneoplastic Syndrome

Hyponatremia related to ectopic secretion of cancer cells of argininevasopressin (AVP) or atrial natriuretic peptide (ANP) is most commonlycaused by small cell lung cancer. The ideal treatment would be one thatnot only corrects the hyponatremia, especially if it is life threatening, butat the same time causes regression of the cancer, and thus improves bothquality and length of life. As one is waiting for chemotherapy, surgery,or radiotherapy to decrease the cancer burden, tolvaptan has been usedto correct the hyponatremia to improve symptoms or prevent death.Mifepristone, a progesterone receptor modulator/antagonist has been usedto treat various cancers. The oral 200mg tablet was given to an 80-year-oldwoman who developed sudden extensive lung cancer with a serum sodiumof 118 mmol/L. She refused chemotherapy but agreed to take mifepristone.The hyponatremia was completely corrected (145 mmol/L) within onemonth of treatment. She was in complete remission for 5 years and diednot from lung cancer, but an acute myocardial infarction. Mifepristonemay serve the purpose to not only quickly correct hyponatremia when itis related to an endocrine paraneoplastic syndrome, but also to provideimproved quality and length of life.

An Update on Management of Nonalcoholic Fatty Liver Disease & Nonalcoholic Steatohepapititis is the Time Ripe for Achieving Resolution of NAFLD & NASH Soon

We earlier reviewed how obesity has assumed an endemic/pandemicproportions that has resulted in escalating incidence and prevalence ofassociated escalating worldwide incidence of Metabolic Syndrome (MetS)with non alcoholic fatty liver disease (NAFLD), that is correlated withenhanced morbidity. Later we tried to detail how probiotics, L-Carnitine(LC), Nicotinamide Ribose (NR) Combination, along with Apical SodiumDependent Bile Acids Transporter (ASBT) or Volixibat and Silybin,Vitamin D, Allyl Isothiocyanate (AITC), might aid in treating andunderstand the etiopathogenesis of NAFLD. The prevalence of NAFLDall over the world is approximately 25%, with that of non alcoholicsteatohepapititis (NASH), varying from 1.5%=6.45%. Particularly NASH,specifically the ones associated with fibrosis possess a greater chance ofgeneration of side effects that include progression to cirrhosis as well asliver-associated mortality. Despite an improvement was observed withvitamin E, Pioglitazone. liraglutide in histological appearance in liverrandomized controlled clinical trials (RCT), at present no drugs existsthat have received FDI approval for NASH. The aim of this review wasto update the newer drugs getting evaluated, undergoing phase 2-3 trials.Currently there are Obeticholic acid, elafibranor, cenicriviroc, resmetriom,in addition to aramchol, that are the five agents that are getting analysedin big, histology dependent phase 3 trials. Hopefully within another 2-4years, newer, efficacious drugs will be available for the therapy of NASH.Besides that a lot of phase 2 trials are continuing for different drugs.Further depending on outcomes of phase 2-3 trials, combination treatmentsare getting evaluated. For future therapeutic approaches would be madeup of variations in NASH phenotypes, besides personalized approachesbased on various NASH phenotypes in addition to response of every singlepatient. Further recently there were reports of utilization of curcumin withnonselective beta blocker for regression from cirrhosis (reviewed by us).Hopefully once there are approved therapies for NAFLD/NASH, we canwork in that direction.

The Association of Non Viral Liver Diseases from NAFLD to NASH to HCC with the Pandemic of Obesity, Type 2 Diabetes, or Diabesity & Metabolic Syndrome Etiopathogenetic Correlation along with Utilization for Diagnostic & Therapeutic Purposes-A Systematic Review

Earlier we have been reviewing the etiopathogenesis (EP) of obesity, type2 Diabetes mellitus (T2DM), Metabolic Syndrome (MetS), Non Alcoholic Fatty Acid Liver Disease (NAFLD) non alcoholic steatohepapititis (NASH), along with its propagation to Hepatocellular carcinoma (HCC) in addition to their therapies exhaustively. T2DM continues to be a major health issue with reaching epidemic to pandemic proportions. Liver disease includes a spectrum of liver injury varying from isolated steatosis known as Non Alcoholic Fatty Acid Liver Disease (NAFLD) to HCC. Clinically it has been observed that the coexistence of NAFLD as well as T2DM is prevalent. T2DM aids in the biological events that results in escalation of robustness of NAFLD that constitutes the primary etiology of chronic liver diseases. In the past 2 decades the incidence of nonviral NAFLD/NASH, obtained HCC has been escalating at a fast pace. In view of no appropriate agents for therapy of NAFLD/NASH, a thiazolidenedione group of drug pioglitazone used for T2DM therapy is utilized occasionally.Thus here we conducted a systematic review utilizing search engine pubmed, google scholar; web of science; embase; Cochrane review libraryutilizingtheMeSHterms like T2DM; MetS; NAFLD; NASH; HCC;WAT; BAT; VisceralAT; Obesity; BMI; Adipocytokines; adiponectin;leptin; resistin; visfatin; irisin; Hepatokines; angiopoietin like protein 2; hepatosscin; retinol binding protein 4; treatment like pioglitazone;liraglutide; elafibranor CVC (cerviciroc); obeticholic acid; aramchol;selonosertib; simtuzumab; Oxidative stress(OS); insulin resistance (IR) from 1980’s to 2021 till date. We found a total of 1050 articles out of which we selected 236 articles for this review. No meta-analysis was done. Hence diagnosis avoidance in addition to treatment of the generation as well as propagation of NAFLD/NASH are significant areas needing tackling. Thus here we have summarized the EP of NAFLD/NASH, as well as NAFLD/NASH, obtained HCC along with the present advantageous therapies under trial,for NAFLD/NASH. Moreover how adipocyte obtained adipokines along with liver obtained hepatokines might work as both diagnostic in addition to therapeutic targets from NAFLD to HCC.

Urinary C-peptide Creatinine Ratio and Its Correlation with Parameters of Metabolic Syndrome

To assess the correlation between urinary C peptide creatinine ratio with serum C peptide, serum insulin and its correlation with clinical and biochemical parameters of metabolic syndrome. A total of 100 subjects more than 18 years of age with metabolic syndrome according to ATP III criteria with 100 controls were included in a prospective observational study for a period of 1.5 years. Individual parameters of metabolic syndrome was higher in females with hypertriglyceridemia was most common and hyperglycaemia least common parameter of metabolic syndrome. Fasting urinary C peptide creatinine ratio and Stimulated urinary C peptide correlate significantly with fasting serum C peptide (p<0.01),stimulated serum C peptide (p<0.01), serum fasting insulin (p<0.01) and HOMA IR (p<0.01). A fasting urinary C peptide creatinine ratio of more than 1.8 nmol/mmol, stimulated urinary C peptide creatinine ratio more than 2.8 nmol/mmol and HOMA IR >2.7 can be used as a parameter to distinguish individual with and without metabolic syndrome. Urinary C peptide creatinine ratio correlate with serum C peptide and parameters of metabolic syndrome and can be used as a non-invasive simple tool to assess insulin resistance and also to distinguish patients with and without metabolic syndrome.

Post-surgery Quality of Life in Patients with Acromegaly Using SF36 Quality of Life Questionnaire-prospective Study

Introduction: Acromegaly is chronic progressive disease with multisystem involvement characterised by an excess secretion of growth hormone and increased circulating insulin like growth factor 1 concentration.Aims and Objectives: To assess surgical outcome of acromegaly patients at tertiary care institute using SF 36 quality of life questionnaire. SF-36 scores comprise 3 components: the physical component summary (PCS), the mental component summary (MCS) and role-social component summary (RCS).30 acromegaly patients admitted in Guwahati medical college were enrolled in study and followed up post operatively for surgical remission. All participants completed the SF-36 preoperatively, 1 year and 2 years postoperatively.Material and Method: Out of 30 patients 6 patients had surgical remission post operatively on the basis of postoperative glucose suppressed GH Level done after 12 weeks. Preoperatively subscale scores (physical functioning, role physical, general health) which were below the set standards for the normal population show significant postoperative improvements along with mental health (MH) scores. Similarly, PCS, MCS and RCS scores changed significantly after surgery. We also compared the QOL of 6 patients whose peak GH level was < 0.4 µg/L during postoperative oral glucose tolerance testing with those patients whose nadir GH level was ≥ 0.4 µg/L. There was significant difference between partial and complete remission group in subscale score role physical, social function and mental health. Similarly, PCS and RCS score significantly different in partial and complete remission group than MCS score.Conclusions: QOL is considerably reduced in patients with acromegaly compared to general population which improves significantly after surgical treatment. Patients achieving the new remission criteria had significant improvement in physical and social components than those who did not.

Processed Radio Frequency towards Pancreas Enhancing the Deadly Diabetes Worldwide

Diabetes is a chronic and debilitating disease, which is associated with a range of complications putting tremendous burden on medical, economic and socio-technological infrastructure globally. Yet the higher authorities of health services are facing the excruciating cumulative reasons of diabetes as a very imperative worldwide issue in the 21st century. The study aims to relook at the misapplication of the processed radio frequency that frailties in the pancreas within and around the personal body boundary area. The administered sensor data were obtained at laboratory experiments from the selected specimens on dogs and cats in light and dark environments. The study shows the frequent urine flow speed varies with sudden infection due to treated wireless sensor networks in active open eyes. The overweight and obese persons are increasingly affected in diabetes with comprehensive urinary pressure due to continuous staying at dark environment. The findings replicate the increasing tide of diabetes globally. The study also represents the difficulties of physicians to provide adequate diabetic management according to their expectancy due to insecure personal area network control unit.Dynamic sensor network is indispensable for healthcare but such network is at risk to health security due to digitalized poisoning within GPS positions. The study recommends the anti-radiation integrated system policy with user’s security alternative approach to inspire dealing with National Health Policy and Sustainable Development Goals 2030.

Effect of Metformin on Lactate Metabolism in Normal Hepatocytes under High Glucose Stress in Vitro

Objective To study the effect of metformin on lactate metabolism in hepatocytes in vitro under high glucose stress. In vitro LO2 cells, liver cells were randomly divided into blank control group, 25 tendency/L glucose solution, 27 tendency/L glucose solution,29 tendency/L glucose solution, 31 tendency/L glucose solution, 33 tendency/L glucose solution,35 tendency/L glucose solution treatment group, the optimal concentration of 31 tendency after L, use 30 tendency for L metformin solution, and then divided into blank control group, the optimal concentration of glucose solution, normal liver cells + metformin solution normal liver cells. The optimal concentration of glucose solution normal liver cells + metformin solution respectively in the 12 h, 24 h,48 h on cell count plate to calculate the number of liver cells, and using lactic acid determination kit the optimal concentration of glucose solution + normal liver cells and normal liver cells + the optimal concentration of glucose solution + metformin solution respectively in the 12 h, 24 h, 48 h of cell cultures of lactic acid value. There was no significant change in the lactic acid concentration but significant increase in the number of surviving hepatocytes in the highglycemic control group compared with that in the high-glycemic control group without metformin. Metformin has no significant effect on lactic acid metabolism of hepatocytes under high glucose stress in vitro, and has a protective effect on hepatocytes under high glucose stress. Based on this,it is preliminarily believed that metformin is not the direct factor leading to diabetic lactic acidosis.

Metformin and Lactic Acidosis in Diabetic Patients

Metformin is the basic drug in the clinical treatment of Diabetes, often used in the treatment of Type 2 Diabetes Mellitus (T2DM).Its effect has been fully verified in the clinical treatment of T2DM. However, in the treatment of T2DM with metformin, there is still a certain probability of related lactic acidosis, and the fatality rate is high. Therefore, is the use of metformin drug treatment a direct risk factor for lactic acidosis in diabetic patients? This paper will review the hypoglycemic mechanism of metformin and related studies on lactic acidosis, so as to further explore the relationship between metformin and lactic acidosis in diabetic patients, and provide help and reference for metformin drugs in the clinical treatment of T2DM.

Covid-19 Mutations and the Effect of Different Vaccines on Immune Memory

We traced the coronavirus classification and evolution, analyzed the Covid-19 composition and its distinguishing characteristics when compared to SARS-CoV and MERS-CoV. Despite their close kinship, SARS-CoV and Covid-19 display significant structural differences,including 380 amino acid substitutions, and variable homology between certain open reading frames that are bound to diversify the pathogenesis and virulence of the two viral compounds. A single amino acid substitution such as replacing Aspartate (D) with Glycine (G) composes the D614G mutation that is around 20% more infectious than its predecessor 614D. The B117 variant, that exhibits a 70% transmissibility rate, harbours 23 mutants,each reflecting one amino acid exchange. We examined several globally spreading mutations, 501.V2, B1351, P1, and others, with respect to the specific amino acid conversions involved. Unlike previous versions of coronavirus, where random mutations eventually precipitate extinction, the multiplicity of over 300,000 mutations appears to have rendered Covid-19 more contagious, facilitating its ability to evade detection, thus challenging the effectiveness of a large variety of emerging vaccines. Vaccination enhances immune memory and intelligence to combat or obstruct viral entry by generating antibodies that will prohibit the cellular binding and fusion with the Spike protein, restricting the virus from releasing its contents into the cell. Developing antibodies during the innate response,appears to be the most compelling solution in light of the hypothesis that Covid-19 inhibits the production of Interferon type I, compromising adaptive efficiency to recognize the virus, possibly provoking a cytokine storm that injures vital organs. With respect to that perspective, the potential safety and effectiveness of different vaccines are evaluated and compared,including the Spike protein mRNA version, the Adenovirus DNA, Spike protein subunits, the deactivated virus genres, or, finally, the live attenuated coronavirus that appears to demonstrate the greatest effectiveness, yet,encompass a relatively higher risk.