Rising tide: The global surge of type 2 diabetes in children and adolescents demands action now.

Childhood-onset obesity has emerged as a major public healthcare challenge across the globe, fueled by an obesogenic environment and influenced by both genetic and epigenetic predispositions. This has led to an exponential rise in the incidence of type 2 diabetes mellitus in children and adolescents. The looming wave of diabetes-related complications in early adulthood is anticipated to strain the healthcare budgets in most countries. Unless there is a collective global effort to curb the devastation caused by the situation, the impact is poised to be pro-found. A multifaceted research effort, governmental legislation, and effective social action are crucial in attaining this goal. This article delves into the current epidemiological landscape, explores evidence concerning potential risks and consequences, delves into the pathobiology of childhood obesity, and discusses the latest evidence-based management strategies for diabesity.

Acute worsening of microvascular complications of diabetes mellitus during rapid glycemic control: The pathobiology and therapeutic implications.

While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus (DM) is a well-known precursor to complications such as diabetic retinopathy, neuropathy (including autonomic neuropathy), and nephropathy, a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin. Although, acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications, rarely other problems such as albuminuria, diabetic kidney disease, Charcot's neuroarthropathy, gastroparesis, and urinary bladder dysfunction are also encountered. The World Journal of Diabetes recently published a rare case of all these complications, occurring in a young type 1 diabetic female intensely managed during pregnancy, as a case report by Huret et al. It is essential to have a comprehensive understanding of the pathobiology, prevalence, predisposing factors, and management strategies for acute onset, or worsening of microvascular complications when rapid glycemic control is achieved, which serves to alleviate patient morbidity, enhance disease management compliance, and possibly to avoid medico-legal issues around this rare clinical problem. This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.

Non-pharmacological interventions for diabetic peripheral neuropathy: Are we winning the battle?

Despite the advent of relatively reliable modalities of diagnosing diabetic peripheral neuropathy (DPN), such as nerve conduction studies, there is still a knowledge gap about the pathophysiology, and thus limited available interventions for symptom control and curtailing disease progression. The pharmacologic aspect of management is mainly centred on pain control, however, there are several important aspects of DPN such as loss of vibration sense, pressure sense, and proprioception which are associated with risks to lower limb health, which pharmacotherapy does not address. Furthermore, published evidence suggests non-pharmacologic interventions such as glycaemic control through dietary modification and exercise need to be combined with other measures such as psychotherapy, to reach a desired, however modest effect. Acupuncture is emerging as an important treatment modality for several chronic medical conditions including neuropathic and other pain syndromes. In their study published in the World Journal of Diabetes on the potential of acupuncture to reduce DPN symptoms and enhance nerve conduction parameters, Hoerder et al have been able to demonstrate that acupuncture improves sensory function and that this effect is likely sustained two months after treatment cessation. Although previous studies also support these findings, larger multi-center randomized control trials including a sham-controlled arm accounting for a placebo effect are required. Overall, given the satisfactory safety profile and the positive results found in these studies, it is likely that acupuncture may become an important aspect of the repertoire of effective DPN management.

Metabolic-associated fatty liver disease and sarcopenia: A double whammy.

The prevalence of metabolic-associated fatty liver disease (MAFLD) has increased substantially in recent years because of the global obesity pandemic. MAFLD, now recognized as the number one cause of chronic liver disease in the world, not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease, type 2 diabetes mellitus, obstructive sleep apnoea, lipid disorders and sarcopenia. Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies. Sarcopenia can be either part of the disease process that results in MAFLD (e.g., obesity or adiposity) or a consequence of MAFLD, especially in the advanced stages such as fibrosis and cirrhosis. Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors. Therefore, it is crucial to thoroughly understand how we deal with these diseases, especially when they coexist. We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.

Simultaneous pancreas-kidney transplantation for end-stage renal failure in type 1 diabetes mellitus: Current perspectives.

Type 1 diabetes mellitus (T1DM) is one of the important causes of chronic kidney disease (CKD) and end-stage renal failure (ESRF). Even with the best available treatment options, management of T1DM poses significant challenges for cli nicians across the world, especially when associated with CKD and ESRF. Substantial increases in morbidity and mortality along with marked rise in treatment costs and marked reduction of quality of life are the usual consequences of onset of CKD and progression to ESRF in patients with T1DM. Simultaneous pancreas-kidney transplant (SPK) is an attractive and promising treatment option for patients with advanced CKD/ESRF and T1DM for potential cure of these diseases and possibly several complications. However, limited availability of the organs for transplantation, the need for long-term immunosuppression to prevent rejection, peri- and post-operative complications of SPK, lack of resources and the expertise for the procedure in many centers, and the cost implications related to the surgery and postoperative care of these patients are major issues faced by clinicians across the globe. This clinical update review compiles the latest evidence and current recommendations of SPK for patients with T1DM and advanced CKD/ESRF to enable clinicians to care for these diseases.

The role of artificial intelligence technology in the care of diabetic foot ulcers: the past, the present, and the future.

Foot ulcers are common complications of diabetes mellitus and substantially increase the morbidity and mortality due to this disease. Wound care by regular monitoring of the progress of healing with clinical review of the ulcers, dressing changes, appropriate antibiotic therapy for infection and proper offloading of the ulcer are the cornerstones of the management of foot ulcers. Assessing the progress of foot ulcers can be a challenge for the clinician and patient due to logistic issues such as regular attendance in the clinic. Foot clinics are often busy and because of manpower issues, ulcer reviews can be delayed with detrimental effects on the healing as a result of a lack of appropriate and timely changes in management. Wound photographs have been historically useful to assess the progress of diabetic foot ulcers over the past few decades. Mobile phones with digital cameras have recently revolutionized the capture of foot ulcer images. Patients can send ulcer photographs to diabetes care professionals electronically for remote monitoring, largely avoiding the logistics of patient transport to clinics with a reduction on clinic pressures. Artificial intelligence-based technologies have been developed in recent years to improve this remote monitoring of diabetic foot ulcers with the use of mobile apps. This is expected to make a huge impact on diabetic foot ulcer care with further research and development of more accurate and scientific technologies in future. This clinical update review aims to compile evidence on this hot topic to empower clinicians with the latest developments in the field.

Catecholamine-induced cardiomyopathy: an endocrinologist's perspective.

Although many endocrine diseases can be associated with acquired cardiomyopathy and heart failure, conditions except hypothyroidism, hyperthyroidism, phaeochromocytoma-paraganglioma (PPGL), and primary hyperaldosteronism are rare. PPGL is a rare catecholamine-secreting neuroendocrine tumour arising from the adrenal gland in 80-85% or extra-adrenal chromaffin cells of the autonomic neural ganglia in the remainder. The annual incidence of PPGL is 3-8 cases per million per year in the general population. Catecholamine-induced cardiomyopathy (CICMP) has got a prevalence of 8-11% among patients with PPGL. Hypertension, either sustained or episodic, is present in the vast majority (95%) of PPGL patients. However, among patients with CICMP, hypertension is present only in 65% of cases and the classical triad of paroxysmal headache, sweating, and palpitation is present only in 4%. Based on the cardiac remodelling in response to endogenous catecholamine excess, PPGL patients might present with one of the three CICMPs, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), or Takotsubo cardiomyopathy (TCM). Regardless of the subtypes, all CICMPs have many features in common - a dramatic clinical presentation, reversible cardiomyopathy, similar repolarisation electrocardiography changes, mild-moderate cardiac biomarker elevation, and normal coronary arteries on coronary angiography. CICMP should be suspected in patients with non-ischaemic, non-valvular forms of cardiomyopathy, even in those without definite features of catecholamine excess. PPGL associated TCM should be suspected in all acute coronary syndrome (ACS) patients exhibiting pronounced blood pressure variability with no culprit lesions on coronary angiography. This article will provide a review of the various CICMPs, their pathophysiology, clinical features, and the management options.

Discrepancies in the clinical and radiological profiles of COVID-19: A case-based discussion and review of literature.

The current gold standard for the diagnosis of coronavirus disease-19 (COVID-19) is a positive reverse transcriptase polymerase chain reaction (RT-PCR) test, on the background of clinical suspicion. However, RT-PCR has its limitations; this includes issues of low sensitivity, sampling errors and appropriate timing of specimen collection. As pulmonary involvement is the most common manifestation of severe COVID-19, early and appropriate lung imaging is important to aid diagnosis. However, gross discrepancies can occur between the clinical and imaging findings in patients with COVID-19, which can mislead clinicians in their decision making. Although chest X-ray (CXR) has a low sensitivity for the diagnosis of COVID-19 associated lung disease, especially in the earlier stages, a positive CXR increases the pre-test probability of COVID-19. CXR scoring systems have shown to be useful, such as the COVID-19 opacification rating score which helps to predict the need of tracheal intubation. Furthermore, artificial intelligence-based algorithms have also shown promise in differentiating COVID-19 pneumonia on CXR from other lung diseases. Although costlier than CXR, unenhanced computed tomographic (CT) chest scans have a higher sensitivity, but lesser specificity compared to RT-PCR for the diagnosis of COVID-19 pneumonia. A semi-quantitative CT scoring system has been shown to predict short-term mortality. The routine use of CT pulmonary angiography as a first-line imaging modality in patients with suspected COVID-19 is not justifiable due to the risk of contrast nephropathy. Scoring systems similar to those pioneered in CXR and CT can be used to effectively plan and manage hospital resources such as ventilators. Lung ultrasound is useful in the assessment of critically ill COVID-19 patients in the hands of an experienced operator. Moreover, it is a convenient tool to monitor disease progression, as it is cheap, non-invasive, easily accessible and easy to sterilise. Newer lung imaging modalities such as magnetic resonance imaging (MRI) for safe imaging among children, adolescents and pregnant women are rapidly evolving. Imaging modalities are also essential for evaluating the extra-pulmonary manifestations of COVID-19: these include cranial imaging with CT or MRI; cardiac imaging with ultrasonography (US), CT and MRI; and abdominal imaging with US or CT. This review critically analyses the utility of each imaging modality to empower clinicians to use them appropriately in the management of patients with COVID-19 infection.

Diabetic heart disease: A clinical update.

Diabetes mellitus (DM) significantly increases the risk of heart disease, and DM-related healthcare expenditure is predominantly for the management of cardiovascular complications. Diabetic heart disease is a conglomeration of coronary artery disease (CAD), cardiac autonomic neuropathy (CAN), and diabetic cardiomyopathy (DCM). The Framingham study clearly showed a 2 to 4-fold excess risk of CAD in patients with DM. Pathogenic mechanisms, clinical presentation, and management options for DM-associated CAD are somewhat different from CAD among nondiabetics. Higher prevalence at a lower age and more aggressive disease in DM-associated CAD make diabetic individuals more vulnerable to premature death. Although common among diabetic individuals, CAN and DCM are often under-recognised and undiagnosed cardiac complications. Structural and functional alterations in the myocardial innervation related to uncontrolled diabetes result in damage to cardiac autonomic nerves, causing CAN. Similarly, damage to the cardiomyocytes from complex pathophysiological processes of uncontrolled DM results in DCM, a form of cardiomyopathy diagnosed in the absence of other causes for structural heart disease. Though optimal management of DM from early stages of the disease can reduce the risk of diabetic heart disease, it is often impractical in the real world due to many reasons. Therefore, it is imperative for every clinician involved in diabetes care to have a good understanding of the pathophysiology, clinical picture, diagnostic methods, and management of diabetes-related cardiac illness, to reduce morbidity and mortality among patients. This clinical review is to empower the global scientific fraternity with up-to-date knowledge on diabetic heart disease.

Efficacy and Cardiovascular Safety of Meglitinides.

Meglitinides are a group of oral hypoglycemic medications currently approved for the treatment of type 2 diabetes mellitus (T2DM). Two meglitinide molecules, Repaglinide and Nateglinide, are presently in use. Repaglinide is preferred because of its superior glycemic efficacy. They have modest efficacy with a mean decrement of glycosylated haemoglobin (HbA1c) ranging between -0.2 to -1.50% with individual therapy. Additional HbA1c reduction can occur with combination therapy with other oral hypoglycemics. This class of drugs is effective in controlling postprandial hyperglycemia with minimal risk of hypoglycemia. It is also useful in patients with variable meal timings, especially in the elderly, and in patients with renal failure. There are a dearth of long-term studies on meglitinides to assess cardiovascular outcomes or mortality in T2DM, although the Nateglinide and Valsartan in Impaired Glucose ToleranceOutcomes Research (NAVIGATOR) study showed no difference between Nateglinide and placebo with regard to the core composite cardiovascular outcomes. Based on a PubMed literature search using key words: 'meglitinides', 'repaglinide', 'nateglinide', 'HbA1c', 'glycated haemoglobin', 'cardiovascular safety', 'cardiovascular events', 'cardiovascular outcome trials', 'type 2 diabetes mellitus' and heart failure, and combining the search terms using Boolean operators 'AND', 'OR' and 'NOT' as needed we compiled current evidence for use of these oral hypoglycemic agents in clinical use. This article is an attempt to review the efficacy and cardiovascular (CV) safety of Meglitinides to help clinicians to use this class of oral hypoglycaemic agents prudently.

Efficacy and Cardiovascular Safety of Thiazolidinediones.

Type 2 diabetes mellitus (T2DM) is characterized by a progressive beta cell dysfunction in the setting of peripheral insulin resistance. Insulin resistance in subjects with type 2 diabetes and metabolic syndrome is primarily caused by an ectopic fat accumulation in the liver and skeletal muscle. Insulin sensitizers are particularly important in the management of T2DM. Though thiazolidinediones (TZDs) are principally insulin sensitizers, they possess an ability to preserve pancreatic ß-cell function and thereby exhibit durable glycemic control. Cardiovascular outcome trials (CVOTs) have shown that Glucagon-like-peptide 1 receptor agonists (GLP-1 RAs) and sodium glucose transporter-2 inhibitors (SGLT2i) have proven cardiovascular safety. In this era of CVOTs, drugs with proven cardiovascular (CV) safety are often preferred in patients with preexisting cardiovascular disease or at risk of cardiovascular disease. In this review, we will describe the three available drugs belonging to the TZD family, with special emphasis on their efficacy and CV safety.

Efficacy and Cardiovascular Safety of SGLT2 Inhibitors.

Patients with diabetes continued to exhibit a high risk for cardiovascular and renal events despite achieving satisfactory glycemic, blood pressure and lipid targets. Studies evaluating new diabetes medications focused on cardiovascular events, largely overlooking heart failure (HF). The latter has recently been recognised as a major cause of morbidity and mortality in patients with diabetes mellitus. There had been an unmet need for drugs with cardiovascular (including HF) and renal protection, with an expectation that an ideal diabetic drug should improve these endpoints. Moreover, an ideal drug should have weight reducing benefits. Recently published outcome trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) can reduce cardiovascular and renal events, together with statistically significant weight reduction. As a result, many recently published international guidelines have recommended SGLT2 inhibitors and GLP-1RAs in patients with diabetes and pre-existing cardiovascular disease (CVD). In this review, we will critically analyse the efficacy and cardiovascular (CV) safety of SGLT2 inhibitors, based on the available literature to help position them in the clinical decision process.

Efficacy and Cardiovascular Safety of Insulins.

Insulin is a lifesaving drug for patients with type 1 diabetes mellitus. Many type 2 diabetes mellitus patients will eventually require insulin. The rapid-acting and long-acting insulin analogues (RAIAs and LAIAs) have a pharmacological profile that closely mimics normal human physiology when compared to Neutral Protamine Hagedorn (NPH) insulin and regular human insulin, respectively. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) were found to have a proven cardiovascular safety. They are preferred over insulin in many recent guidelines. Fixed-ratio combinations of GLP-1RAs and insulin are also recommended when either of these molecules fail to achieve glycaemic control. Despite decades of experience in using insulin, there is a debate among the scientific community over the safety of exogenous insulin, especially regarding their cardiovascular safety and the risk of cancer. There is also an ongoing debate regarding the safety, even though two long-acting insulin analogues (glargine and degludec) have proven their cardiovascular non-inferiority. Drugs with proven safety are often preferred in patients with pre-existing cardiovascular disease or at high risk of cardiovascular disease. In this review we will critically analyse efficacy and safety issues related to insulin molecules to help in clinical decision making.

A Review of the Efficacy and Cardiovascular Safety of Amylin Analogues.

A large proportion of persons with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) do not reach the glycosylated haemoglobin (HbA1c) target of < 7% (53 mmol/- mol), with an increasing proportion of them being overweight or obese. In both T1DM and T2DM, there is accelerated gastric emptying and postprandial hyperglucagonemia. Furthermore, insulin therapy itself is associated with risk of hypoglycemia and weight-gain both of which are barriers to achieving good control. Medications which can achieve significant HbA1c and weight reduction associated with an ability to delay gastric emptying and suppress the glucagon secretion with minimal/ no hypoglycemia are of particular interest as an adjuvant to insulin. A synthetic amylin analogue, pramlintide is a drug with above mentioned properties. Other medications with similar properties are glucagon-like peptide-1 receptor agonists (GLP-1 RAs). In this article, we will review the efficacy of pramlintide when given with insulin in improving HbA1c, weight, and cognition with- /without GLP-1 RAs as well as its cardiovascular (CV) safety.

Efficacy and Cardiovascular Safety of Sulfonylureas.

There is a universal agreement that when lifestyle modifications are inadequate to control the hyperglycemia, metformin should be considered the first line of pharmacological therapy. However, when metformin monotherapy fails, there is no consensus as to which drug should be added. Many new classes of drugs that are currently available including DPP-4 inhibitors, GLP-1 agonists and SGLT-2 inhibitors have undergone cardiovascular outcome trials which had been made mandatory by the regulatory authority and thereby established their cardiovascular safety or at least neutrality. Though sulfonylureas are one of the widely prescribed drugs both in developed and developing countries and have proven their efficacy for glycemic control and prevention of microvascular complications, there is considerable uncertainty about its cardiovascular safety which has been going on for nearly five decades. In this review, we will critically analyze the efficacy and cardiovascular safety of sulphonylureas, based on the latest available literature to clarify their role in our day-to-day clinical practice.

Myasthenia gravis presenting as bilateral pseudointernuclear ophthalmoplegia in a patient with an incidental prolactinoma.

Myasthenia gravis (MG) is a rare and potentially dangerous autoimmune condition, which affects the acetylcholine receptors at the neuromuscular junction of skeletal muscle. MG's diverse symptomatology may readily masquerade as other neurological conditions, posing a diagnostic challenge to clinicians. We describe a 24-year old man who presented to the emergency department with a new onset internuclear ophthalmoplegia. After a series of investigations, we eventually arrived at a diagnosis of MG with pseudointernuclear ophthalmoplegia with an incidentally detected prolactinoma. We explore the literature regarding the pathophysiology of pseudointernuclear ophthalmoplegia, the link between prolactin and autoimmunity and the association between prolactinoma and MG.