Presse Med
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The pharmacotherapy of type 2 diabetes mellitus (T2DM) has markedly evolved in the last two decades. Classical antidiabetic agents (sulphonylureas, metformin, insulin) are now in competition with new glucose-lowering medications. Alpha-glucosidase inhibitors and thiazolidinediones (glitazones) were not able to replace older agents, because of insufficient efficacy and/or poor tolerability/safety. ⋯ More recently sodium-glucose cotransporter 2 inhibitors (SGLT2is or gliflozins, oral agents) also showed cardiovascular protection, especially a reduction in hospitalization for heart failure, as well as a renal protection in patients with and without T2DM, at high cardiovascular risk, with established heart failure and/or with chronic kidney disease. Thus, GLP-1RAs and SGLT2is are now considered as preferred drugs in T2DM patients with or at high risk of atherosclerotic cardiovascular disease whereas SGLT2is are more specifically recommended in patients with or at risk of heart failure and renal (albuminuric) disease. The management of T2DM is moving from a glucocentric approach to a broader strategy focusing on all risk factors, including overweight/obesity, and to an organ-disease targeted personalized approach.
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The Phoenix Epidemiology and Clinical Research Branch of the National Institute of Diabetes and Digestive and Kidney Diseases has conducted prospective studies of diabetes and its complications in the Pima Indians living in Arizona, USA for over 50 years. In this review we highlight areas in which these studies provided vital insights into the criteria used to diagnose type 2 diabetes, the pathophysiologic changes that accompany the development of type 2 diabetes, and the course and determinants of diabetes complications-focusing specifically on diabetic kidney disease. We include data from our longitudinal population-based study of diabetes and its complications, studies on the role of insulin resistance and insulin secretion in the pathophysiology of type 2 diabetes, and in-depth studies of diabetic kidney disease that include measures of glomerular function and research kidney biopsies. We also focus on the emerging health threat posed by youth-onset type 2 diabetes, which was first seen in the Pima Indians in the 1960s and is becoming an increasing issue worldwide.
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Type 2 diabetes is associated with an increased risk for end-stage renal disease and heart failure, contributing to premature death. All these 3 events are inter-related, suggesting common risk factors and/or pathophysiological pathways. The SURDIAGENE (SUrvie Rénale DIAbète et GENEtique) cohort is a single center hospital-based cohort of persons living with type 2 diabetes, recruiting participants at Poitiers university hospital, France, from 2002 to 2011 with further follow-up till 2015. ⋯ Interestingly, the incidence of renal event was lower than the incidence of all-cause death in all KDIGO stages, at variance with the data from recent renal outcome trials on SGLT2 inhibitors and finerenone. We conclude that KDIGO stages should be considered for renal but also for HFH risk classification. The analysis of the respective incidence of renal events and deaths in observational studies and RCTs deserves further evaluation in type 2 diabetes.
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Major clinical advances over the last 20 years in the area of diabetic kidney disease (DKD) have been confirmed in large seminal clinical trials. These findings add to the previously identified benefits resulting from intensive glucose and blood pressure control therapies. Furthermore, newer glucose lowering treatments such as SGLT2 inhibitors and GLP-1 agonists appear very promising and are likely to transform the management and outlook of DKD over the next decade. In addition, novel mineralocorticoid receptor antagonists and a recently reported trial with an endothelin receptor blocker also have the potential to change clinical practice.