Diabetic heart disease:A clinical update

Diabetes mellitus(DM) significantly increases the risk of heart disease,and DMrelated 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.

Gastroenteropancreatic neuroendocrine neoplasms:A clinical snapshot

Our understanding about the epidemiological aspects,pathogenesis,molecular diagnosis,and targeted therapies of neuroendocrine neoplasms(NENs)have drastically advanced in the past decade.Gastroenteropancreatic(GEP)NENs originate from the enteroendocrine cells of the embryonic gut which share common endocrine and neural differentiation factors.Most NENs are welldifferentiated,and slow growing.Specific neuroendocrine biomarkers that are used in the diagnosis of functional NENs include insulin,glucagon,vasoactive intestinal polypeptide,gastrin,somatostatin,adrenocorticotropin,growth hormone releasing hormone,parathyroid hormone-related peptide,serotonin,histamine,and 5-hydroxy indole acetic acid(5-HIAA).Biomarkers such as pancreatic polypeptide,human chorionic gonadotrophin subunits,neurotensin,ghrelin,and calcitonin are used in the diagnosis of non-functional NENs.5-HIAA levels correlate with tumour burden,prognosis and development of carcinoid heart disease and mesenteric fibrosis,however several diseases,medications and edible products can falsely elevate the 5-HIAA levels.Organ-specific transcription factors are useful in the differential diagnosis of metastasis from an unknown primary of well-differentiated NENs.Emerging novel biomarkers include circulating tumour cells,circulating tumour DNA,circulating micro-RNAs,and neuroendocrine neoplasms test(NETest)(simultaneous measurement of 51 neuroendocrine-specific marker genes in the peripheral blood).NETest has high sensitivity(85%-98%)and specificity(93%-97%)for the detection of gastrointestinal NENs,and is useful for monitoring treatment response,recurrence,and prognosis.In terms of management,surgery,radiofrequency ablation,symptom control with medications,chemotherapy and molecular targeted therapies are all considered as options.Surgery is the mainstay of treatment,but depends on factors including age of the individual,location,stage,grade,functional status,and the heredity of the tumour(sporadic vs inherited).Medical management is helpful to alleviate the symptoms,manage inoperable lesions,suppress postoperative tumour growth,and manage recurrences.Several molecular-targeted therapies are considered second line to somatostatin analogues.This review is a clinical update on the pathophysiological aspects,diagnostic algorithm,and management of GEP NENs.