Tumor metabolism in pheochromocytomas: clinical and therapeutic implications.

Pheochromocytomas and paragangliomas (PPGLs) have emerged as one of the most common endocrine tumors. It epitomizes fascinating crossroads of genetic, metabolic, and endocrine oncology, providing a canvas to explore the molecular intricacies of tumor biology. Predominantly rooted in the aberration of metabolic pathways, particularly the Krebs cycle and related enzymatic functionalities, PPGLs manifest an intriguing metabolic profile, highlighting elevated levels of oncometabolites like succinate and fumarate, and furthering cellular malignancy and genomic instability. This comprehensive review aims to delineate the multifaceted aspects of tumor metabolism in PPGLs, encapsulating genetic factors, oncometabolites, and potential therapeutic avenues, thereby providing a cohesive understanding of metabolic disturbances and their ramifications in tumorigenesis and disease progression. Initial investigations into PPGLs metabolomics unveiled a stark correlation between specific genetic mutations, notably in the succinate dehydrogenase complex (SDHx) genes, and the accumulation of oncometabolites, establishing a pivotal role in epigenetic alterations and hypoxia-inducible pathways. By scrutinizing voluminous metabolic studies and exploiting technologies, novel insights into the metabolic and genetic aspects of PPGLs are perpetually being gathered elucidating complex interactions and molecular machinations. Additionally, the exploration of therapeutic strategies targeting metabolic abnormalities has burgeoned harboring potential for innovative and efficacious treatment modalities. This review encapsulates the profound metabolic complexities of PPGLs, aiming to foster an enriched understanding and pave the way for future investigations and therapeutic innovations in managing these metabolically unique tumors.

Continuous glucose monitoring metrics in pregnancy with type 1 diabetes mellitus.

Managing diabetes during pregnancy is challenging, given the significant risk it poses for both maternal and foetal health outcomes. While traditional methods involve capillary self-monitoring of blood glucose level monitoring and periodic HbA1c tests, the advent of continuous glucose monitoring (CGM) systems has revolutionized the approach. These devices offer a safe and reliable means of tracking glucose levels in real-time, benefiting both women with diabetes during pregnancy and the healthcare providers. Moreover, CGM systems have shown a low rate of side effects and high feasibility when used in pregnancies complicated by diabetes, especially when paired with continuous subcutaneous insulin infusion pump as hybrid closed loop device. Such a combined approach has been demonstrated to improve overall blood sugar control, lessen the occurrence of preeclampsia and neonatal hypoglycaemia, and minimize the duration of neonatal intensive care unit stays. This paper aims to offer a comprehensive evaluation of CGM metrics specifically tailored for pregnancies impacted by type 1 diabetes mellitus.

Management of monogenic diabetes in pregnancy: A narrative review.

Pregnancy in women with monogenic diabetes is potentially complex, with significant implications for both maternal and fetal health. Among these, maturity-onset diabetes of the young (MODY) stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice. Each subtype of MODY requires a distinct approach tailored to the pregnancy, diverging from management strategies in non-pregnant individuals. Glucokinase MODY (GCK-MODY) typically does not require treatment outside of pregnancy, but special considerations arise when a woman with GCK-MODY becomes pregnant. The glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing fetus. During pregnancy, the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha (HNF1A)-MODY and HNF4A-MODY depends on the mother's specific circumstances and the available expertise. Management of other rarer MODY subtypes is individualized, with decisions made on a case-by-case basis. Therefore, a collaborative approach involving expert diabetes and obstetric teams is crucial for the comprehensive management of MODY pregnancies.

Is Type 2 Diabetes Mellitus a Behavioural Disorder? An Evidence Review for Type 2 Diabetes Mellitus Prevention and Remission through Lifestyle Modification.

The prevalence of type 2 diabetes mellitus (T2DM) is steadily rising worldwide due to an increasingly sedentary lifestyle combined with unhealthy food habits. Currently, the burden of diabetes on healthcare systems is unprecedented and rising daily. Several observational studies and randomized controlled trials provide clinical evidence that T2DM remission is possible by adopting dietary interventions and a strict exercise training protocol. Notably, these studies provide ample evidence for remission in patients with T2DM or for prevention in those with risk factors for the disease through various non-pharmacological behavioural interventions. In this article, we present two clinical cases of individuals who showed remission from T2DM/prediabetes via behavioural changes, especially through the adoption of a low-energy diet and exercise. We also discuss the recent advances in T2DM and obesity research, focusing on nutritional interventions and exercise and their benefits for weight loss, improved metabolic profile, enhanced glycaemic control and remission of diabetes.

Management of diabesity: Current concepts.

The global prevalence of obesity is increasing rapidly with an exponential rise in incidence of type 2 diabetes mellitus in recent years. 'Diabesity', the term coined to show the strong interlink between obesity and diabetes, is the direct cons-equence of the obesity pandemic, and poses significant challenges in the management of the disease. Without addressing the clinical and mechanistic complications of obesity such as metabolic-associated fatty liver disease and obstructive sleep apnoea, a rational management algorithm for diabesity cannot be developed. Several classes of anti-diabetic medications including insulins, sulphonylureas, thiazolidinediones and meglitinides are associated with the risk of weight gain and may potentially worsen diabesity. Therefore, appropriate selection of antidiabetic drug regimen is crucial in the medical management of diabesity. The role of non-pharmacological measures such as dietary adjustments, exercise interventions and bariatric procedures should also be emphasised. Unfortunately, the importance of appropriate and optimal management of diabesity is often overlooked by medical professionals when achieving adequate glycemic control which results in inappropriate management of the disease and its complications. This review provides a narrative clinical update on the evidence behind the management of diabesity.

Individualized diabetes care: Lessons from the real-world experience.

Diabetes care is often difficult without a proper collaboration between the patient and the care provider as the disease is mostly self-managed by patients through adjustments in their lifestyles, and medication doses to optimise glycaemic control. Most clinical guidelines on the management of diabetes mellitus (DM) provide only broad principles on diabetes care, and the blind follow-up of such principles without a proper review and consideration of patient characteristics often results in inadequate glycaemic control and diabetes complications consequently. Therefore, a proper understanding of the pathobiology, clinical situation, and comorbidities of the individual case is of paramount importance to tailoring the most appropriate management strategy in real-world diabetes care. With the aid of five unique cases of DM [(1) Medically managed type 2 diabetes mellitus (T2DM) with severe obesity; (2) Management of T2DM with unreliable glycated haemoglobin (HbA1c); (3) Obesity in a patient with type 1 diabetes mellitus (T1DM); and (4) Late diagnosis and subsequent management of monogenic diabetes and 5. Sudden worsening of well-controlled T2DM)] we elaborate on the importance of individualised diabetes care and the practicalities in these situations. The review also provides an evidence update on the management of different forms of DM to guide physicians in optimising the care of their patients in day-to-day clinical practice.

Diabetes and cognitive function: An evidence-based current perspective.

Several epidemiological studies have clearly identified diabetes mellitus (DM) as a major risk factor for cognitive dysfunction, and it is going to be a major public health issue in the coming years because of the alarming rise in diabetes prevalence across the world. Brain and neural tissues predominantly depend on glucose as energy substrate and hence, any alterations in carbohydrate meta-bolism can directly impact on cerebral functional output including cognition, executive capacity, and memory. DM affects neuronal function and mental capacity in several ways, some of which include hypoperfusion of the brain tissues from cerebrovascular disease, diabetes-related alterations of glucose transporters causing abnormalities in neuronal glucose uptake and metabolism, local hyper- and hypometabolism of brain areas from insulin resistance, and recurrent hypoglycemic episodes inherent to pharmacotherapy of diabetes resulting in neuronal damage. Cognitive decline can further worsen diabetes care as DM is a disease largely self-managed by patients. Therefore, it is crucial to understand the pathobiology of cognitive dysfunction in relation to DM and its management for optimal long-term care plan for patients. A thorough appraisal of normal metabolic characteristics of the brain, how alterations in neural metabolism affects cognition, the diagnostic algorithm for patients with diabetes and dementia, and the management and prognosis of patients when they have this dangerous combination of illnesses is imperative in this context. This evidence-based narrative with the back-up of latest clinical trial reviews elaborates the current understanding on diabetes and cognitive function to empower physicians to manage their patients in day-to-day clinical practice.

Bone health in ambulatory male patients with chronic obstructive airway disease - A case control study from India.

Objective: Chronic obstructive airway disease (COPD) is characterized by airflow limitation due to airway and/or alveolar abnormalities with significant extra-pulmonary manifestations. Bone health impairment is an extra-pulmonary complication of COPD which is less well studied in India. Moreover, it can contribute to significant morbidity and mortality. Hence, we aim to estimate the prevalence of osteoporosis and metabolic parameters of adverse bone health in patients with COPD. Methods: In this case control study, male subjects aged 40-70 years with COPD attending the respiratory outpatient clinic in a tertiary care hospital were recruited over a period of 2 years and the control population were derived from the historical cohort who were apparently healthy with no obvious diseases. Metabolic parameters of bone health measured from fasting blood samples were calcium, albumin, alkaline phosphatase, phosphorous, parathormone, creatinine, 25-hydroxy vitamin D, and testosterone. Bone mineral density (BMD) was estimated using DXA scan and the World Health Organization (WHO) criteria was used to categorize into osteoporosis, osteopenia, and normal BMD based on the T-score at femoral neck, lumbar spine and distal forearm. Pulmonary function tests and 6 minute walk test were performed if they had not been done in the previous 3 months. The associations of COPD with osteoporosis were analyzed using linear regression analysis and effect size are presented as beta with 95% confidence interval. Results: Of the 67 participants with COPD enrolled in the study, osteoporosis was present in 61% (41/67) and osteopenia in an additional 33% (22/67) of the cases, which was higher when compared to the control population (osteoporosis 20% [50/252] and osteopenia 58% [146/252]). In regression modeling, there was a trend toward adverse bone health with advanced age, low body mass index, low forced expiratory volume in 1 second and testosterone deficiency in COPD. Conclusion: Individuals with COPD have a substantially higher prevalence of osteoporosis and osteopenia, up to almost twice that of the general population, with a significant number demonstrating at least one parameter of adverse metabolic bone health on assessment. Hence, bone health assessment should be a part of comprehensive COPD care to prevent adverse consequences due to poor bone health.

Management of metabolic-associated fatty liver disease: The diabetology perspective.

The metabolic syndrome as a consequence of the obesity pandemic resulted in a substantial increase in the prevalence of metabolic-associated fatty live disease (MAFLD) and type 2 diabetes mellitus (T2DM). Because of the similarity in pathobiology shared between T2DM and MAFLD, both disorders coexist in many patients and may potentiate the disease-related outcomes with rapid progression and increased complications of the individual diseases. In fact, awareness about this coexistence and the risk of complications are often overlooked by both hepatologists and diabetologists. Management of these individual disorders in a patient should be addressed wholistically using an appropriate multidisciplinary team approach involving both the specialists and, when necessary, liaising with dieticians and surgeons. This comprehensive review is to compile the current evidence from a diabetologist's perspective on MAFLD and T2DM and to suggest optimal management strategies.

Clinical implications of COVID-19 in patients with metabolic-associated fatty liver disease.

People across the world are affected by the "coronavirus disease 2019 (COVID-19)", brought on by the "SARS-CoV type-2 coronavirus". Due to its high incidence in individuals with diabetes, metabolic syndrome, and metabolic-associated fatty liver disease (MAFLD), COVID-19 has gained much attention. The metabolic syndrome's hepatic manifestation, MAFLD, carries a significant risk of type-2-diabetes. The link between the above two conditions has also drawn increasing consideration since MAFLD is intricately linked to the obesity epidemic. Independent of the metabolic syndrome, MAFLD may impact the severity of the viral infections, including COVID-19 or may even be a risk factor. An important question is whether the present COVID-19 pandemic has been fueled by the obesity and MAFLD epidemics. Many liver markers are seen elevated in COVID-19. MAFLD patients with associated comorbid conditions like obesity, cardiovascular disease, renal disease, malignancy, hypertension, and old age are prone to develop severe disease. There is an urgent need for more studies to determine the link between the two conditions and whether it might account for racial differences in the mortality and morbidity rates linked to COVID-19. The role of innate and adaptive immunity alterations in MAFLD patients may influence the severity of COVID-19. This review investigates the implications of COVID-19 on liver injury and disease severity and vice-versa. We also addressed the severity of COVID-19 in patients with prior MAFLD and its potential implications and therapeutic administration in the clinical setting.

Bedside lung ultrasonography: comparison with chest radiography (BLUR), a diagnostic study in a developing country.

BACKGROUND: This study determines the diagnostic utility of lung ultrasonography (LUS) in a medical ward in a developing country. In a low resource country like India, we hope that use of lung ultrasound in primary and secondary hospitals will assist in earlier and better bedside diagnosis. METHODS: This prospective diagnostic study was done to test the diagnostic accuracy of LUS against a composite reference standard, which included clinical history and examination, basic laboratory investigations, imaging and the diagnosis at discharge. We evaluated 321 consecutive patients, admitted in our medical wards with an LUS within 24 hours of the chest radiograph being done. FINDINGS: Between August 2016 and August 2017, we enrolled 321 patients. The sensitivity and specificity of the LUS for all pathologies were found to be 82.5% (76.50 to 87.20) and 78.2% (69.09 to 85.26) respectively. A subgroup analysis including the patients in whom CT was part of the composite reference standard showed sensitivity and specificity of 87.9% and 92.9% for all lung pathologies. It was found that there was superior sensitivity and specificity of LUS compared with chest radiograph in a subgroup analysis of pulmonary oedema and acute respiratory distress syndrome (ARDS). INTERPRETATION: We found that the LUS was better than chest radiograph and as good as CT in most pathologies, especially pulmonary oedema and ARDS. We believe that training in the basics of bedside LUS must be part of the medical curriculum and a low-cost ultrasound machine must be made available in medical wards, so that clinical diagnosis can be supplemented with this tool. In a low resource setting like India, where access to chest radiograph and CT may be difficult particularly in a rural setup, expertise in LUS would be helpful in easy bedside diagnosis and saving cost on a CT scan.

COVID-19 vaccine-associated subacute thyroiditis: an unusual suspect for de Quervain's thyroiditis.

Subacute thyroiditis following vaccination is an uncommon presentation of thyrotoxicosis. As the world undertakes its largest immunisation campaign to date in an attempt to protect the population from COVID-19 infections, an increasing number of rare post vaccine side effects are being observed. We report a case of a middle-aged woman who presented with painful thyroid swelling following the second dose of the COVID-19 mRNA vaccine BNT162b2 (Pfizer-BioNTech) with clinical, biochemical and imaging features consistent with destructive thyrotoxicosis. Symptomatic management only was required for the self-limiting episode. Thyroiditis typically has a mild and self-limiting course and thus this observation should not deter people from vaccination, as COVID-19 infection has a far greater morbidity and mortality risk than thyroiditis.