DRUG UTILIZATION PATTERN OF ANTIDIABETIC DRUGS AMONG DIABETIC OUTPATIENTS IN A TERTIARY CARE HOSPITAL

 Objective: The aim was to evaluate the drug utilization pattern of anti-diabetic drugs in diabetic outpatients and monitor the adverse drug reactions(ADRs) associated with anti-diabetic therapy.Methods: A prospective observational study was carried out in adult diabetic patients visiting the outpatient Departments of General Medicine andEndocrinology of a tertiary care hospital. Demographic data, drug utilization pattern and ADRs due to anti-diabetic drugs were summarized.Results: In the present study, 99 (50.3%) of the 197 diabetic patients were males. Majority of patients were in the age group of 51-60 years (39.6%) andmost of the patients (36.5%) had a diabetic history of <5 years. Metformin was the most commonly prescribed drug (68%), followed by sulfonylureaclass of drugs (49.7%). Nearly, 42% patients were using insulin preparations with 30.4% using biphasic isophane human insulin. Majority of thepatients (58.4%) were on multidrug therapy with two drug therapies being received by nearly 40%. Metformin was the most commonly prescribeddrug in monotherapy (18.8%) and glimepiride + metformin was the most common two drug therapy (13.2%). Co-morbid condition was found in 172patients (87.3%) with hypertension (68.5%) being the most common co-morbid condition. 17 ADRs were observed with hypoglycemia being the mostcommon ADR reported.Conclusions: Metformin was the most commonly used drug. The prescribing trend also appears to be moving towards combination therapyparticularly two drug therapies.Keywords: Drug utilization, Anti-diabetic drug, Adverse drug reaction

A RAS-CaMKKβ-AMPKα2 pathway promotes senescence by licensing post-translational activation of C/EBPβ through a novel 3′UTR mechanism

International audienceOncogene-induced senescence (OIS) is an intrinsic tumor suppression mechanism that requires the p53 and RB pathways and post-translational activation of C/EBPβ through the RAS-ERK cascade. We previously reported that in transformed/proliferating cells, C/EBPβ activation is inhibited by G/U-rich elements (GREs) in its 3'UTR. This mechanism, termed "3'UTR regulation of protein activity" (UPA), maintains C/EBPβ in a low-activity state in tumor cells and thus facilitates senescence bypass. Here we show that C/EBPβ UPA is overridden by AMPK signaling. AMPK activators decrease cytoplasmic levels of the GRE binding protein HuR, which is a key UPA component. Reduced cytoplasmic HuR disrupts 3'UTR-mediated trafficking of Cebpb transcripts to the peripheral cytoplasm-a fundamental feature of UPA-thereby stimulating C/EBPβ activation and growth arrest. In primary cells, oncogenic RAS triggers a Ca++-CaMKKβ-AMPKα2-HuR pathway, independent of AMPKα1, that is essential for C/EBPβ activation and OIS. This axis is disrupted in cancer cells through down-regulation of AMPKα2 and CaMKKβ. Thus, CaMKKβ-AMPKα2 signaling constitutes a key tumor suppressor pathway that activates a novel UPA-cancelling mechanism to unmask the cytostatic and pro-senescence functions of C/EBPβ