Saroglitazar for the treatment of hypertriglyceridemia in patients with type 2 diabetes: current evidence

Aravind Sosale,1 Banshi Saboo,2 Bhavana Sosale11Diacon Hospital, Bangalore, 2Dia Care (Diabetes Care and Hormone Clinic), Ahmedabad, IndiaAbstract: Diabetes mellitus (DM) is one of the most dreaded metabolic disorders in the world today. It is the leading cause of morbidity and mortality, and plays a cardinal role in quality of life and health economics. DM is associated with a high prevalence of microvascular and macrovascular complications. DM is a very important cardiovascular (CV) risk factor. Cardiovascular disease (CVD) has been implicated as the prime cause of mortality and morbidity in patients with DM. Hence, treatment of DM goes beyond glycemic control, and demands a multidisciplinary approach that comprehensively targets risk factors inherent in CV events. Lipid abnormalities are undoubtedly common in patients with DM, and they contribute to an increased risk of CVD. A high-risk lipid profile, termed atherogenic dyslipidemia of diabetes (ADD), is known to occur in patients with DM. The use of lipid-lowering agents, a quintessential part of the multifactorial risk factor approach, is a crucial intervention to minimize diabetes-related complications. In this article, we discuss the role of peroxisome proliferator activator receptor (PPAR) alpha/gamma (α/γ) agonist, saroglitazar, in the management of ADD. While statins are irrefutably the first line of drugs for dyslipidemia management in patients with residual CV risk while on a statin, PPAR α/γ agonists have been found to be of substantial benefit. Data from the PRESS I–VI clinical trials testify to the fact that saroglitazar and fibrates have similar efficacy in reducing triglycerides and improving high-density lipoprotein. The ancillary benefit of improved glycemic control, without the weight gain of PPAR γ agonists, is an added advantage. Reduction in ADD, improved glycemic control, efficacy at par with fibrates, and an acceptable safety profile form the grounds on which this group of PPAR α/γ agonists, with their novel mechanism, holds a promising future in the management of diabetic dyslipidemia.Keywords: diabetes mellitus, dyslipidemia, cardiovascular disease, atherosclerosis, PPAR α/γ agonist

The role of nateglinide and repaglinide, derivatives of meglitinide, in the treatment of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases worldwide, presenting a great challenge to the public health systems due to high morbidity and mortality, because of frequent micro-/macro-vascular complications. Many treatment options are now available, with different efficacy as well as mechanisms of action to improve deranged glucose metabolism. We review some of the available data on derivatives of meglitinide, namely nateglinide and repaglinide. These two compounds increase insulin secretion by a mechanism similar to the one of sulfonylureas, but with a shorter half-life. Nateglinide and repaglinide, derivatives of meglitinides, have characteristic pharmacodynamic and pharmacokinetic properties that, together with their proposed mechanism of action, make them useful for type 2 diabetes mellitus, especially when used in combination therapy

Cell rigidity and shape override CD47's "sell"-signaling in phagocytosis by hyperactivating myosin-II

A macrophage engulfs another cell or foreign particle in an adhesive process that often activates myosin-II, unless the macrophage also engages “marker of self” CD47 that inhibits myosin. For many cell types, adhesion-induced activation of myosin-II is maximized by adhesion to a rigid rather than a flexible substrate. Here we demonstrate that rigidity of a phagocytosed cell also hyperactivates myosin-II, which locally overwhelms self-signaling at a phagocytic synapse. Cell stiffness is one among many factors including shape that changes in erythropoiesis, in senescence and in diseases ranging from inherited anemias and malaria to cancer. Controlled stiffening of normal human red blood cells (RBCs) in different shapes does not compromise CD47’s interaction with the macrophage self-recognition receptor signal regulatory protein alpha (SIRPA). Uptake of antibody-opsonized RBCs is always fastest with rigid RBC discocytes, which also show that maximal active myosin-II at the synapse can dominate self-signaling by CD47. Rigid but rounded RBC stomatocytes signal self better than rigid RBC discocytes, highlighting the effects of shape on CD47 inhibition. Physical properties of phagocytic targets thus regulate self signaling, as is relevant to erythropoiesis, to clearance of rigid RBCs after blood storage, clearance of rigid pathological cells such as thalassemic or sickle cells, and even to interactions of soft/stiff cancer cells with macrophages

Chronic complications in newly diagnosed patients with Type 2 diabetes mellitus in India

Background: Prevalence of diabetes is on an increase in India, currently there is limited nation-wide data regarding the prevalence of chronic complications in diabetic patients at diagnosis. This information will help health-care professionals approach management more aggressively to prevent complications. Objective: To determine the prevalence of chronic complications in newly-diagnosed Type 2 diabetic (T2D) patients in India. Design and Methods: This was a cross-sectional survey of T2D patients, diagnosed within 3 months of their first visit to the centers doing the survey. Each patient was screened for diabetic complications, hypertension, dyslipidemia, and body mass index. Family history was recorded. Standard protocols were used to make the diagnosis of retinopathy, neuropathy and nephropathy. Data analysis was carried out using the standard statistical techniques. Results: Of the total 4,600 (males 67%, females 33%) newly diagnosed patients with T2D, majority were from the age group 41-50 years (40%). 13.15% of newly detected India T2D had neuropathy 6.1% had retinopathy and 1.06% had nephropathy. Risk factors of macro vascular complication such as hypertension, obesity, and dyslipidemia were observed in 23.3%, 26%, and 27% of patients respectively. Ischemic heart disease was noticed in 6%. Conclusion: High prevalence of micro vascular complications was present at diagnosis along with association of CV cardiovascular risk factors among Indian T2D. In view of this, screening must be instituted for all diabetics for complications at the time of diagnosis itself

Time-in-range and frequency of continuous glucose monitoring: Recommendations for South Asia

Background and aim: The prevalence of diabetes is on its rise and South Asia bears a huge burden. Several factors such as heterogeneity in genetics, socio-economic factors, diet, and sedentary behavior contribute to the heightened risk of developing diabetes, its rapid progression, and the development of complications in this region. Even though there have been considerable advances in glucose monitoring technologies, diabetes treatments and therapeutics, glycemic control in South Asia remains suboptimal. The successful implementation of treatment interventions and metrics for the attainment of glycemic goals depends on appropriate guidelines that accord with the characteristics of the diabetes population. Method: The data were collected from studies published for more than the last ten years in the electronic databases PubMed and Google Scholar on the various challenges in the assessment and achievement of recommended TIR targets in the SA population using the keywords: Blood glucose, TIR, TAR, TBR, HbA1c, hypoglycemia, CGM, Gestational diabetes mellitus (GDM), and diabetes. Results: The objective of this recommendation is to discuss the limitations in considering the IC-TIR Expert panel recommendations targets and to propose some modifications in the lower limit of TIR in older/high-risk population, upper limit of TAR, and flexibility in the percentage of time spent in TAR for pregnant women (GDM, T2DM) for the South Asian population. Conclusion: The review sheds insights into some of the major concerns in implementing the IC-TIR recommendations in South Asian population where the prevalence of diabetes and its complications are significantly higher and modifications to the existing guidelines for use in routine clinical practice