Targeting beta-cell preservation in the management of type 2 diabetes

Abstract

Type 2 diabetes (T2D) is widely considered a chronic and progressive disease without cure. As beta-cell function progressively declines over time, blood glucose rises. Current management of T2D involves incremental introduction of dietary and drug therapies to achieve normoglycaemia. However, recent studies have demonstrated remission of T2D following bariatric surgery, very low calorie diet or intensive insulin therapy, raising the possibility that the declining beta-cell function in T2D may be arrested or even reversed. The point at which such interventions are introduced in the course of T2D is key for clinical benefit. Future treatment strategies should be revised to target early betacell preservation and thus disease remission. This article reviews the pathogenesis of beta-cell dysfunction and evidence for the clinical benefit of preserving beta-cell function in T2D, and discusses the evidence for beta-cell preservation of current glucose-lowering therapies with particular reference to their effect when initiated at the time of diagnosis of T2D. Br J Diabetes 2017;17:134-144

Reducing Glucokinase Activity to Enhance Insulin Secretion: A Counterintuitive Theory to Preserve Cellular Function and Glucose Homeostasis

“…In clinical studies, beta-cell rest involves decreasing secretory stress on the beta-cells, hoping for a return of function that continues once the treatment is stopped. The period of rest is thought to allow time for replenishment of the readily releasable pool of insulin (99,111), a reduction in oxidative stress (118)(119)(120), or recovery of normal GK activity levels (41,43,121). Many clinical studies discussing beta-cell rest focus on the use of oral medications that restore euglycemia, therefore indirectly lowering the demand on the beta cell to secrete insulin while also decreasing the effects of glucotoxicity.…”

Insulin resistance and specific biomarkers in blood and urine of type 2 diabetic patients with or without nephropathy in Basrah, Iraq

“…So, obesity could be one of the etiological factors in the development of T2DM, and mostly because of loss of early phase insulin secretion in response to glucose which happens relatively earlier in the development of T2DM (Park et al, 2018). This loss is critically crucial as the early blast of insulin secretion plays a substantial role in priming target tissues of insulin, especially the liver responsible for normal glucose homeostasis after food uptake and mealtime glucose deflection take place when this process was deteriorated (Boughton et al, 2017). Obesity is considered one of the modifiable cardiovascular risk factors that is far more predominant in those people with T2DM than in the general population.…”

Early combination versus initial metformin monotherapy in the management of newly diagnosed type 2 diabetes: An East Asian perspective

“…It also suppresses glucagon from the α‐cells, leading to a lowering of fasting blood glucose. These dual effects address the key defects in people with diabetes and IGT 53,83 . In a meta‐analysis of 360 randomized clinical trials, incretin‐based therapies (DPP4‐i or GLP‐1 RA) increased HOMA‐β and fasting C‐peptide levels while reducing homeostatic model assessment of insulin resistance (HOMA‐IR) and fasting plasma glucose compared with placebo.…”

“…Among the currently available glucose‐lowering drugs, TZDs, GLP‐1 RAs, DPP4‐is and SGLT‐2is are known to have beneficial effects on β‐cell function in clinical studies 53 . TZDs can restore first‐phase insulin response and improve other markers of β‐cell function independent of the correction of glucotoxicity.…”

“…will provide further insights into the long-term durability of triple combination therapy with metformin, SGLT2-is and DPP4-is compared with conventional stepwise therapy in drug-naïve patients with T2D with HbA1c levels of 8.0%-10.5% 89. Among the currently available glucose-lowering drugs, TZDs, GLP-1 RAs, DPP4-is and SGLT-2is are known to have beneficial effects on β-cell function in clinical studies 53. TZDs can restore firstphase insulin response and improve other markers of β-cell function independent of the correction of glucotoxicity.…”