Latent Autoimmune Diabetes in Adults: A Case Report.

Latent autoimmune diabetes in adults (LADA) is a slow progressive autoimmune destruction of pancreatic beta cells. This condition tends to manifest during adulthood, often around 35 years of age. While LADA can initially be managed by oral medications, eventually the patient will require insulin. We report a case of a 34-year-old woman who was initially treated for type 2 diabetes mellitus but was later diagnosed with LADA.

Diabetes Care During Hajj.

Diabetes mellitus affects over 463 million individuals worldwide. Religious activities such as the Hajj pilgrimage have a major impact on patients with diabetes mellitus, including increasing the risk of hyperglycaemia and hypoglycaemia. This increased risk is due to dietary changes and intense physical activity during pilgrimage while being on antidiabetic medications. Approximately 20% of the pilgrims with underlying illnesses who visit Mecca are diabetic, and complications, such as diabetic ketoacidosis, nonketotic hyperosmolar state, and fatigue/unconsciousness due to hypoglycaemia, have been observed among these patients. Diabetic patients are also at a high risk for foot complications and infections. To avoid any aggravation of the diabetes, a complete biochemical evaluation of the patient must be conducted before Hajj, and the patients must be provided contextualized educational guidance to avert these potential health challenges. This counselling should include the importance of carrying with them at all time their relevant medical history, summaries of the current treatment regimen and emergency snacks. In addition, to reduce the risk of hypoglycaemia, the dosage of insulin should be reduced in selected patients by 20% and that of sulfonylurea should be reduced as needed. Basal insulin and glucagon-like peptide 1 receptor agonists are associated with fewer complications and can be preferentially prescribed. Those patients with type 1 diabetes can continue with the use of insulin pump with suitable education prior to Hajj. For the prevention of foot problems, the use of padded socks and well-fitting shoes is recommended along with an insistence on not walking barefoot. After Hajj, the patient must be followed up, and necessary investigations must be made along with readjustment of insulin dosage in those patients for whom it was reduced. Until the pandemic situation abates, all diabetic patients should avoid making the Hajj journey.

Treatment options in people with COVID19: Selecting the best armamentarium against the novel virus.

Novel coronavirus disease (COVID-19) infection is a global pandemic, of high infectivity, variable mortality, with currently no established treatment. This review summarizes different molecules which are being evaluated for COVID19 treatment. PubMed and Medline, search for articles published to March 2020 was done using terms "COVID19" OR "corona-virus 2019" OR "2019-nCoV" or "severe acute respiratory syndrome coronavirus" AND "treatment". As of today, we have >350 RCTs happening with different agents. COVID19 treatment agents can be broadly classified into immuno-modulators (prevent hyperimmune-activation and cytokine storm) and anti-viral therapies (prevent virus entry, replication or viricidal). Hydroxychloroquine/chloroquine, Interferon-l, glucocorticoids, interleukin antagonists, Ulinastatin, intravenous immunoglobulins, plasmapheresis are main immunomodulators showing initial positive outcomes. Umifenovir. Lopinavir/Ritonavir, Ribavirin, remdesivir and Ravipiravir are some of the major antiviral agents showing initial encouraging results. It may be concluded that the most successful regimen is going to be multi-drug therapy, a combination of immunomodulatory agent with anti-viral agent.

Utility of Precision Medicine in the Management of Diabetes: Expert Opinion from an International Panel.

AIM: The primary objective of this review is to develop a practice-based expert group opinion on the role of precision medicine with a specific focus on sulfonylureas (SUs) in diabetes management. BACKGROUND: The clinical etiology, presentation and complications of diabetes vary from one patient to another, making the management of the disease challenging. The pre-eminent feature of diabetes mellitus (DM) are chronically elevated blood glucose concentrations; however, in clinical practice, the exclusion of autoimmunity, pregnancy, pancreatic disease or injury and rare genetic forms of diabetes is crucial. Within this framework, precision medicine provides unique insights into the risk factors and natural history of DM. Precision medicine goes beyond genomics and encompasses patient-centered care, molecular technologies and data sharing. Precision medicine has evolved in the field of diabetology. It has helped improve the efficacy of SUs, a class of drugs, which have been effectively used in the management of diabetes mellitus for decades, and it has enabled the expansion of SUs use in diabetes patients with genetic mutations. REVIEW RESULTS: After due discussions, the expert group analyzed studies that focused on the use of SUs in diabetes patients with genomic variations and rare mutations. The expert group opined that SUs are important glucose-lowering drugs and that precision medicine helps in improving the efficacy of SUs by matching them to those patients who will benefit most. CONCLUSION: Precision medicine opens new vistas for the effective use of SUs in unexpected patient populations, such as those with genetic mutations.

BE-SMART (Basal Early Strategies to Maximize HbA1c Reduction with Oral Therapy): Expert Opinion.

The past three decades have seen a quadruple rise in the number of people affected by diabetes mellitus worldwide, with the disease being the ninth major cause of mortality. Type 2 diabetes mellitus (T2DM) often remains undiagnosed for several years due to its asymptomatic nature during the initial stages. In India, 70% of diagnosed diabetes cases remain uncontrolled. Current guidelines endorse the initiation of insulin early in the course of the disease, specifically in patients with HbA1c > 10%, as the use of oral agents alone is unlikely to achieve glycemic targets. Early insulin initiation and optimization of glycemic control using insulin titration algorithms and patient empowerment can facilitate the effective management of uncontrolled diabetes. Early glucose control has sustained benefits in people with diabetes. However, insulin initiation, dose adjustment, and the need to repeatedly assess blood glucose levels are often perplexing for both physicians and patients, and there are misconceptions and concerns regarding its use. Hence, an early transition to insulin and ideal intensification of treatment may aid in delaying the onset of diabetes complications. This opinion statement was formulated by an expert panel on the basis of existing guidelines, clinical experience, and economic and cultural contexts. The statement stresses the timely and appropriate use of basal insulin in T2DM. It focuses on the seven vital Ts-treatment initiation, timing of administration, transportation and storage, technique of administration, targets for titration, tablets, and tools for monitoring.Funding: Sanofi.

The Lipo- Phenotypic Screening Tool for Familial Hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is a common disorder of lipid metabolism. However, it is rarely diagnosed in time, leading to a high burden of preventable cardiovascular (CV) morbidity. The authors describe a lipophenotypic screening tool, which can be used by clinicians to screen for FH. This simple construct is based on history, physical examination, lipid profile and non-invasive cardioimaging. Structured as a bidirectional three column rubric, this tool should be able to improve clinical skills and teaching related to FH.

Expert Opinion: Patient Selection for Premixed Insulin Formulations in Diabetes Care.

Premixed insulins are an important tool for glycemic control in persons with diabetes. Equally important in diabetes care is the selection of the most appropriate insulin regimen for a particular individual at a specific time. Currently, the choice of insulin regimens for initiation or intensification of therapy is a subjective decision. In this article, we share insights, which will help in rational and objective selection of premixed formulations for initiation and intensification of insulin therapy. The glycemic status and its variations in a person help to identify the most appropriate insulin regimen and formulation for him or her. The evolution of objective glucometric indices has enabled better glycemic monitoring of individuals with diabetes. Management of diabetes has evolved from a 'glucocentric' approach to a 'patient-centered' approach; patient characteristics, needs, and preferences should be evaluated when considering premixed insulin for treatment of diabetes.Funding: Novo Nordisk, India.

Correction to: Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart (IDegAsp).

Unfortunately, the fifth author name was incorrectly published in the original publication. The correct name should read as 'Ozgur Demir'.

Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart (IDegAsp).

Insulin degludec/aspart (IDegAsp) is the first soluble insulin co-formulation, combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In type 2 diabetes patients with oral antidiabetes agent (OAD) inadequacy, insulin initiation with IDegAsp once daily provides superior long-term glycemic control compared to insulin glargine, with similar fasting plasma glucose (FPG) and insulin doses, and numerically lower rates of overall and nocturnal hypoglycemia. Furthermore, in patients with uncontrolled type 2 diabetes previously treated with insulins, IDegAsp twice daily effectively improves glycated hemoglobin and FPG, with fewer hypoglycemic episodes versus premix insulins and basal bolus therapy. In patients with type 1 diabetes mellitus, IDegAsp once daily with two doses of IAsp is a convenient, yet effective, regimen as compared to the conventional 4-5 injection-based basal bolus therapy. IDegAsp is an appropriate and reasonable option for initiation of insulin therapy in both type 1 and type 2 diabetes.

Consensus Recommendations on Sulfonylurea and Sulfonylurea Combinations in the Management of Type 2 Diabetes Mellitus - International Task Force.

For decades, sulfonylureas (SUs) have been important drugs in the antidiabetic therapeutic armamentarium. They have been used as monotherapy as well as combination therapy. Focus on newer drugs and concerns about the risk of severe hypoglycemia and weight gain with some SUs have led to discussion on their safety and utility. It has to be borne in mind that the adverse events associated with SUs should not be ascribed to the whole class, as many modern SUs, such as glimepiride and gliclazide modified release, are associated with better safety profiles. Furthermore, individualization of treatment, using SUs in combination with other drugs, backed with careful monitoring and patient education, ensures maximum benefits with minimal side effects. The current guidelines, developed by experts from Africa, Asia, and the Middle East, promote the safe and smart use of SUs in combination with other glucose-lowering drugs.

Improving community case management of diarrhoea and pneumonia in district Badin, Pakistan through a cluster randomised study--the NIGRAAN trial protocol.

BACKGROUND: Diarrhoea and pneumonia contribute 30% of deaths in children under 5 in Pakistan. Pakistan's Lady Health Workers Programme (LHW-P) covers about 60% of the population but has had little impact in reducing morbidity and mortality related to these major childhood killers. An external evaluation of the LHW-P suggests that lack of supportive supervision of LHWs by lady health supervisors (LHSs) is a key determinant of this problem. Project NIGRAAN aims to improve knowledge and skills of LHWs and community caregivers through supervisory strategies employed by LHSs. Ultimately, community case management (CCM) of childhood pneumonia and diarrhoea will improve. METHODS/DESIGN: NIGRAAN is a cluster-randomised trial in District Badin, Pakistan. There are approximately 1100 LHWs supervised by 36 LHSs in Badin. For this study, each LHS serves as a cluster. All LHSs working permanently in Badin who regularly conduct and report field visits are eligible. Thirty-four LHSs have been allocated to either intervention or control arms in a ratio of 1:1 through computer-generated simple randomisation technique. Five LHWs from each LHSs are also randomly picked. All 34 LHSs and 170 LHWs will be actively monitored. The intervention consists of training to build LHS knowledge and skills, clinical mentorship and written feedback to LHWs. Pre- and post-intervention assessments of LHSs, LHWs and community caregivers will be conducted via focus group discussions, in-depth interviews, knowledge assessment questionnaires, skill assessment scorecards and household surveys. Primary outcome is improvement in CCM practices of childhood diarrhoea and pneumonia and will be assessed at the cluster level. DISCUSSION: NIGRAAN takes a novel approach to implementation research and explores whether training of LHSs in supervisory skills results in improving the CCM practices of childhood diarrhoea and pneumonia. No significant harm to participants is anticipated. The enablers and barriers towards improved CCM would provide recommendations to policymakers for scale up of this intervention nationally and regionally. TRIAL REGISTRATION: NIGRAAN is registered with the 'Australian New Zealand Clinical Trials Registry'. REGISTRATION NUMBER: ACTRN12613001261707.

Screening of Gestational Diabetes and Hypertension Among Antenatal Women in Rural West India.

BACKGROUND: Hypertension and gestational diabetes are among the leading causes of maternal and perinatal mortality, especially in rural areas of developing countries with meager health facilities. With early diagnosis and timely treatment, these adverse events can be decreased. The primary aim of this study was to implement a screening program for gestational diabetes and hypertension, and to assess risk factors associated with these conditions among antenatal women in the rural area of the Gujarat province in India. METHODS: A cross-sectional study was conducted at one of the rural areas of Gujarat province in India. Following a random cluster sampling procedure, the village of Davas was selected. A multistage random sampling method was utilized, resulting in a sample of 346 antenatal women. Screening guidelines from the American Diabetes Association were followed for gestational diabetes screening. RESULTS: The majority of antenatal mothers (55.50%) were between 21-25 years of age. 242 antenatal women were multigravida, and among them, 85.96% had institutional delivery at their last pregnancy. Of the total 346 women, 17.60% were prehypertensive. The prevalence of systolic hypertension was 1.40%, diastolic hypertension was 0.90%, and gestational diabetes was 1.73%. CONCLUSION: Socioeconomically upper class, a family history of hypertension, and BMI ≥ 25 were strong risk factors for hypertension during pregnancy and gestational diabetes. Health education should be made readily available to antenatal mothers by paramedical workers regarding symptoms of hypertension and gestational diabetes mellitus for early self identification.

An efficient approach to the synthesis of highly congested 9,10-dihydrophenanthrene-2,4-dicarbonitriles and their biological evaluation as antimicrobial agents.

An efficient and novel method for the synthesis in moderate to good yield (72%-84%) of a series of 3-amino-1-substituted-9,10-dihydrophenanthrene-2,4-dicarbonitriles 1-5 via one-pot multi-component reactions of aldehydes, malononitrile, 1-tetralone and ammonium acetate has been delineated. Cyclocondensation attempts of aminocyanophenanthrene derivatives 1, 2, 4 and 5 with acetic anhydride in the presence of conc. H2SO4 failed and instead the diacetylamino derivatives 10-13 were obtained. All prepared compounds were structurally elucidated by various spectroscopic methods and X-ray crystallography. N,N-diacetylamino-derivatives of phenanthrene have shown good antimicrobial activity.

MELD era: is this time to replace the original Child-Pugh score in patients with decompensated cirrhosis of liver.

OBJECTIVE: To compare the predictive value of MELD (Model of end stage liver disease) and Child-Pugh (CP) scores in patients with decompensated cirrhosis of liver. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Medical Department, Liaquat University of Medical and Health Sciences, Jamshoro/ Hyderabad, from August 2006 to October 2007. METHODOLOGY: This study included 110 consecutive patients with decompensated cirrhosis of liver diagnosed either clinically or radiologically were followed-up during hospital stay. Studied variables included demographic data, cirrhosis related complications and investigations. Patients were classified according to original CP classification into A, B and C. MELD score was estimated from serum bilirubin, serum creatinine and INR (International normalized ratio) of the patients. Duration of hospitalization and in-hospital mortality were made as the end points of the study. T-test and Chi-square test were done for continuous and categorical data. Original CP and MELD score were compared by the ROC curve. 0.05 was kept as the level of significance. RESULTS: There were 110 patients with decompensated cirrhosis of liver. Mean age was 46.76+12.93 years. There were 72 (65%) male and 38 (35%) females patients. Hepatitis C was the most prevalent cause of cirrhosis of liver present in 60/110 (60%) cases. Ascites was present in 93/110 (83%) patients. The mean MELD scores were 2.23+0.712 (95% CI 2.09 - 2.36) and for CTP 2.52+0.586 (95%; CI 2.41-2.63). The outcome of the patients were 12 deaths (11%); 54 (49%) remained hospitalized for up to 14 days and 44 (40%) for > 14 days. The majority of deaths and prolong hospitalization were found in patients with MELD score > 15 as well as with Child-Pugh grade C. The c-statistic was 0.726 (p=0.001) for CP score, and 0.642 for MELD score (p=0.021). CONCLUSION: The MELD score was not found to be superior to CTP score for short-term prognostication of patients with cirrhosis in this study.

Etiological patterns of stroke in young patients at a tertiary care hospital.

OBJECTIVE: To observe frequency of various causes of stroke in patients of young (15-35 years) age. METHODS: This Descriptive case series study was conducted in all Medical Units of Liaquat University Hospital (LUH) Jamshoro, Hyderabad, from August 2006 to February 2008 and included 50 patients of stroke aged 15-35 years, irrespective of sex and community. Data of these patients was collected through a pre-designed proforma by completing a comprehensive history, detailed examination and carrying out basic and relevant investigations. Patients suffering from hypoglycaemia, space occupying lesions, transient ischaemic attack or psychosis were excluded from the study. The collected data was analyzed on SPSS version 16.0. RESULTS: Out of total number of 113 acute strokes, 50 patients fulfilling inclusion criteria were selected, comprising 30 males and 20 females. Forty-three (86%) patients suffered from ischaemic strokes while seven (14%) had haemorrhagic strokes. Infective meningitis including Tuberculosis meningitis and Bacterial meningitis was the leading cause of stroke (34%). The second most common cause was cardio-embolism (20%) comprising Valvular heart diseases (14%), Cardiomyopathies (4%) and atrial myxoma (2%).Hypertension was found in 14% cases. Pregnancy related causes (including Pregnancy induced hypertension and puerperal sepsis) were 12%. Systemic lupus erythematous and nephritic syndrome was 4% each. Various causes which constitute 4% or less were grouped together as miscellaneous and they include hyperhomocysteinaemia, and hyperlipidaemias. CONCLUSIONS: Common cause of stroke detected was infective meningitis (Tuberculosis and Bacterial). Predominant cause of haemorrhagic stroke was Hypertension. Stroke in young age occurred predominantly in males. Cardio embolism, pregnancyinduced hypertension and puerperal sepsis were other major causes.

Validation of three non-invasive markers in assessing the severity of liver fibrosis in chronic hepatitis C.

OBJECTIVE: To compare various biochemical markers i.e. APRI (AST to platelet ratio index), aspartate aminotransferase (AST) alanine aminotransferase (ALT) ratio, FIB-4 (AST, platelet, AST and age) with biopsy for assessing the severity of hepatic fibrosis in patients with hepatitis C. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Medical Department, Liaquat University of Medical and Health Sciences, Jamshoro, from July 2005 to March 2007. METHODOLOGY: Consecutive hepatitis C virus RNA positive and previously untreated patients were studied. Liver biopsy with histological evaluation and AST/ALT ratio, AST to platelet ratio index and FIB-4 were assessed in all patients. Receiver operative curves were developed. RESULTS: There were 158 patients (109 males, 49 females). On histological grounds non-advanced fibrosis (F0-1) was present in 74 (46.5%) of cases, whereas 84 (53.5%) patients had advanced (F2-4) fibrosis. The area under the receiver operating characteristic curves of APRI < 0.05-1 and FIB-4 < 1.45 were 0.7 and 0.74 respectively, which means that APRI < 1 and FIB-4 < 1.45 will exclude advanced fibrosis in 70% and 74% of patients respectively. An APRI of > 1 and FIB-4 will predict advanced fibrosis in 87% and 98% of patients respectively. AST/ALT ratio was inferior to both of these biomarkers. CONCLUSION: Both APRI and FIB-4 not only exclude minimal fibrosis but can predict advanced fibrosis in the majority of the patients. The simultaneous use of several indirect markers of liver fibrosis does not improve their diagnostic accuracy.