Novel Approaches to Restore Pancreatic Beta-Cell Mass and Function.

Beta-cell dysfunction and beta-cell death are critical events in the development of type 2 diabetes mellitus (T2DM). Therefore, the goals of modern T2DM management have shifted from merely restoring normoglycemia to maintaining or regenerating beta-cell mass and function. In this review we summarize current and novel approaches to achieve these goals, ranging from lifestyle interventions to N-methyl-D-aspartate receptor (NMDAR) antagonism, and discuss the mechanisms underlying their effects on beta-cell physiology and glycemic control. Notably, timely intervention seems critical, but not always strictly required, to maximize the effect of any approach on beta-cell recovery and disease progression. Conventional antidiabetic medications are not disease-modifying in the sense that the disease does not progress or reoccur while on treatment or thereafter. More invasive approaches, such as bariatric surgery, are highly effective in restoring normoglycemia, but are reserved for a rather small proportion of obese individuals and sometimes associated with serious adverse events. Finally, we recapitulate the broad range of effects mediated by peripheral NMDARs and discuss recent evidence on the potential of NMDAR antagonists to be developed as a novel class of antidiabetic drugs. In the future, a more refined assessment of disease risk or disease subtype might enable more targeted therapies to prevent or treat diabetes.

The effect of short-term intensive insulin therapy in newly-diagnosed Type-2 diabetic patients.

OBJECTIVES: We aimed to determine the effect of short-term intensive insulin therapy (SIIT) on long-term glycemic control in newly-diagnosed Type-2 diabetes mellitus (nT2DM) patients. METHODS: In this retrospectively study conducted at Sakarya University Medical Faculty Training and Research Hospital Outpatient Clinic between 2016 and 2019, 65 nT2DM patients were enrolled soon after their SIIT was initiated and were followed for at least a year. Intensive insulin treatment was discontinued after three or 12 months in a total of 65 (23-73-year-old) patients who had been newly diagnosed with T2DM. Intensive insulin therapy was discontinued when glycemic control and the target Glycated Hemoglobin (HbA1c) level had been attained, after which oral anti-diabetic drug (OAD), long-term insulin, and diet therapies were pursued. RESULTS: There was a significant decrease in mean HbA1c from 11.25±1.96% to 6.67±1.07%. Fasting plasma glucose (FPG) was found to be an independent predictor of whether intensive insulin therapy could be discontinued after three months in a model that included FPG, HbA1c, and body mass index measured at baseline. Patients with FPG>13.8 mmol/L were 7.6 times more likely to require intensive insulin therapy beyond three months. There were significant decreases in HbA1c and low-density lipoprotein-cholesterol concentration, but no change in C-peptide between baseline and 3 months of therapy. CONCLUSION: These results demonstrate that in nT2DM patients, intensive insulin therapy could be effective on long-term glycemic control and high FPG prior to three months of SIIT may predict poor long-term glycemic control.