Emerging Roles of Dipeptidyl Peptidase-4 Inhibitors in Delaying the Progression of Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) results from the immune cell-mediated destruction of functional pancreatic ß-cells. In the presymptomatic period, T1DM is characterized by the presence of two or more autoantibodies against the islet cells in patients without glycemic decompensation. Therapeutic strategies that can modify the autoimmune process could slow the progression of T1DM. Dipeptidyl peptidase-4 (DPP-4) or CD26, a multifunctional serine protease with a dual function (regulatory protease and binding protein), can modulate inflammation and immune cell-mediated ß-cell destruction. CD26 is involved in T-cell co-stimulation, migration, memory development, thymic maturation, and emigration patterns. DPP-4 degrades the peptide hormones GLP-1 and GIP. In addition to regulating glucose metabolism, DPP-4 exerts anti-apoptotic, regenerative, and proliferative effects to promote ß-cell mass expansion. GLP-1 receptor signaling may regulate murine lymphocyte proliferation and maintenance of peripheral regulatory T-cells. In patients with T1DM, the serum DPP-4 activity is upregulated. Several studies have suggested that the upregulated DPP-4 activity is correlated with T1DM pathophysiology. DPP-4, which is preferentially expressed on the Th1 surface, can promote the polarization of Th1 immunity, a prerequisite for T1DM development. CD26 inhibition can suppress T-cell proliferation and Th1 cytokine production and stimulate tumor growth factor beta-1 (TGF-ß1) secretion, which plays an important role in the regulation of autoimmunity in T1DM. Studies on humans or animal models of T1DM have suggested that DPP-4 inhibitors can improve ß-cell function and attenuate autoimmunity in addition to decreasing insulin dependence. This review summarizes the emerging roles of DPP-4 inhibitors in potentially delaying the progression of T1DM.

Glycated Hemoglobin in the Diagnosis of Diabetes Mellitus in a Semi-Urban Brazilian Population.

The study evaluated glycated hemoglobin (HbA1c) as a diagnostic tool for diabetes and pre-diabetes in the Brazilian population. Further, the homeostasis model assessment of insulin resistance (HOMA-IR) was also examined against HbA1c values to identify the most suitable cut-off points for HOMA-IR to predict the risk of diabetes. A cross-sectional study was conducted among 714 randomly selected subjects. HbA1c, fasting, and 2 h plasma glucose values were measured. Insulin resistance estimates were calculated with HOMA-IR. The receiver operating characteristic curve assessed HbA1c performance. The adjusted prevalence rate of diabetes mellitus was 14.7%, and pre-diabetes 14.2%. The optimal HbA1c cut-off value was ≥6.8% for the diagnosis of diabetes, and ≥6.0% for pre-diabetes. The area under the curve using HbA1c was 0.85 (95% CI: 0.80-0.90) for detecting diabetes and 0.61 (95% CI: 0.55-0.67) for pre-diabetes. The optimal HOMA-IR cut-off value was 2.06 for HbA1c at 6.8%. The HbA1c cut-off value of ≥6.8% may be suitable for diagnosing diabetes in the Brazilian population. Our results do not support the use of HbA1c to diagnose pre-diabetes. A HOMA-IR cut-off point of 2.06 was a sensitive marker to assess the risk of diabetes.

Risk Factors Associated With New-Onset Diabetes After Liver Transplant: A Case Control Study.

BACKGROUND: New-onset diabetes after transplant is a severe complication that can present in liver transplant recipients, negatively impacting quality of life and graft survival. It also contributes to increased risk of infection, cardiovascular disease, and rejection, which are the main causes of death among liver transplant recipients. The aim of the present study was to assess the risk factors associated with new-onset diabetes after transplant. METHOD: This was a case control study based on the data from 146 liver transplant patients at a reference hospital. The data from the charts were collected using a 2-part form: Part I (sociodemographic variables) and Part II (clinical variables). RESULTS: Multiple analysis showed that pre-existing systemic arterial hypertension (odds ratio [OR], 2.65; 95% CI, 1.12-6.28) and the use of sodium mycophenolate associated with tacrolimus (OR, 2.68; 95% CI, 1.02-7.06) increased the risk of new-onset diabetes after transplant. On comparing the anthropometric variables, lipid panel, and blood glucose levels of liver transplant patients with and without diabetes, higher glycemic levels were found in the group with diabetes (P < .001). CONCLUSION: Pre-existing systemic arterial hypertension and the associated use of sodium mycophenolate and tacrolimus increased the risk of new-onset diabetes after transplant.