Prediabetes blunts DPP4 genetic control of postprandial glycaemia and insulin secretion.

Aims/hypothesis: Imbalances in glucose metabolism are hallmarks of clinically silent prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) representing dysmetabolism trajectories leading to type 2 diabetes. CD26/dipeptidyl peptidase 4 (DPP4) is a clinically proven molecular target of diabetes-controlling drugs but the DPP4 gene control of dysglycaemia is not proven.

Methods: We dissected the genetic control of post-OGTT and insulin release responses by the DPP4 gene in a Portuguese population-based cohort of mainly European ancestry that comprised individuals with normoglycaemia and prediabetes, and in mouse experimental models of Dpp4 deficiency and hyperenergetic diet.

Loss of postprandial insulin clearance control by Insulin-degrading enzyme drives dysmetabolism traits.

Systemic insulin availability is determined by a balance between beta-cell secretion capacity and insulin clearance (IC). Insulin-degrading enzyme (IDE) is involved in the intracellular mechanisms underlying IC. The liver is a major player in IC control yet the role of hepatic IDE in glucose and lipid homeostasis remains unexplored.

Metabolic Footprint, towards Understanding Type 2 Diabetes beyond Glycemia.

Type 2 diabetes (T2D) heterogeneity is a major determinant of complications risk and treatment response. Using cluster analysis, we aimed to stratify glycemia within metabolic multidimensionality and extract pathophysiological insights out of metabolic profiling. We performed a cluster analysis to stratify 974 subjects (PREVADIAB2 cohort) with normoglycemia, prediabetes, or non-treated diabetes.

Immunoglobulin M gene association with autoantibody reactivity and type 1 diabetes.

Several lines of evidence show that autoimmune responses evolving in type 1 diabetes (T1D) patients include the generation of multi-reactive autoantibody (AutoAb) repertoires, but their role in T1D pathogenesis remains elusive. We tested the hypothesis that variants at the immunoglobulin heavy chain (IGH) locus are genetic determinants of AutoAbs against pancreatic antigens and contribute to T1D susceptibility. With this aim, two independent study designs were used: a case-control study and a family-based cohort comprising a total of 240 T1D patients, 172 first-degree relatives (mother and/or father), and 130 unrelated healthy controls living in Portugal.

First Incidence and Progression Study for Diabetic Retinopathy in Portugal, the RETINODIAB Study: Evaluation of the Screening Program for Lisbon Region.

Purpose: To estimate the 5-year incidence and progression of diabetic retinopathy (DR) among persons with type 2 diabetes mellitus (DM).

Design: Population-based, prospective, cohort study.

Participants: The RETINODIAB (Study Group for Diabetic Retinopathy Screening) program was implemented in the Lisbon and Tagus Valley area between July 2009 and December 2014.

Prevalence of chronic kidney disease and associated risk factors, and risk of end-stage renal disease: data from the PREVADIAB study.

Background/aims: Chronic kidney disease (CKD) is a growing public health problem. However, data on risk factors and prevalence of CKD exist only in a small number of countries. Portugal has the highest incidence of end-stage renal disease (ESRD) among European countries, but there are huge disparities among countries.