Type II diabetes mellitus and obesity: Common links, existing therapeutics and future developments

Type II diabetes mellitus (T2DM) and obesity are two common pathophysiological conditions of metabolic syndrome(MetS), a collection of similar metabolic dysfunctions due to sedentary lifestyle and overnutrition. Obesity arises fromimproper adipogenesis which otherwise has a crucial role in maintaining proper metabolic functions. Downstream eventsarising from obesity have been linked to T2DM. The nuclear receptor peroxisome proliferator activator gamma (PPAR-c),responsible for maintaining lipid and glucose homeostasis, is down-regulated under obesity leading to a weakened insulinsensitivity of the human body. In course of our review we will outline details of the down-regulation mechanism, provide anoverview of the current clinical therapeutics and their shortcomings. Toxicity studies on the seminal drug troglitazone,belonging to the most effective glitazone anti-diabetic category, is also discussed. This will lead to an overview aboutstructural adaptations on the existing glitazones to alleviate their side effects and toxicity. Finally, we forward a concept ofnovel therapeutics mimicking the glitazone framework, based on some design concepts and preliminary in silico studies.These could be later developed into dual acting drugs towards alleviating the deleterious effects of obesity on normalglucose metabolism, and address obesity in itself.

Non-HIV AIDS presenting with adrenal histoplasmosis and pulmonary tuberculosis: a mesmerising case report and discussion.

Non-HIV AIDS or idiopathic CD4 lymphocytopenia (ICL) is an acquired immunodeficiency syndrome resulting in CD4 lymphopenia without any evidence of HIV infection or any other apparent cause of immunosuppression. A non-diabetic patient presented with adrenal histoplasmosis and UTI leading to adrenal failure. No immediate cause of immunosuppression was found, HIV, HTLV screening were negative. A CD4 count was done and the patient was found to be having non-HIV AIDS (idiopathic CD4 lymphocytopenia). He was treated and discharged. Few months later the patient presented again with adrenal failure & pulmonary tuberculosis. Adrenal FNAC showed persisting adrenal histoplasmosis. CD4 count found to be low again, but this time it was worse than the previous scenario

Tolosa-Hunt syndrome: a rare case report with uncommon imaging findings and discussion.

A 45 year old diabetic but non hypertensive female presented with unilateral ptosis and complete external ophthalmoplegia on the left side. All the routine investigations were inconclusive. A signal void change was found in MRI study including angiogram of brain. On performing VEP (visually evoked potential), there was mild left optic pathway dysfunction (axonal and demyelinating). A probable diagnosis of Tolosa-Hunt Syndrome (THS) was made and the patient was started on steroids. She responded dramatically to the therapy and was discharged on steroids. Thus the diagnosis of THS was confirmed. On follow up after one month, both her ptosis and ophthalmoplegia had resolved completely. On subsequent follow up visits, she was free of any ophthalmological symptoms and signs.

Progressive disseminated histoplasmosis presenting like chronic parenchymal liver disease with ascites: a rare case report and discussion.

A 82 year old diabetic and hypertensive Muslim man presented with ascites along with features of portal hypertension. Though it initially seemed to be a primary case of chronic parenchymal liver disease, investigations revealed it to be a case of Progressive Disseminated Histoplasmosis (PDH) with bilateral adrenomegaly, hepatosplenomegaly and ascites. The ascites was high SAAG in nature and no evidence of malignancy or tuberculosis could be found. The patient was treated with liposomal amphotericin B and was subsequently discharged on oral itraconazole therapy. On follow-up he was found to be significantly better at 3 months.