The GenoDiabMar Registry: A Collaborative Research Platform of Type 2 Diabetes Patients

Abstract

The GenoDiabMar registry is a prospective study that aims to provide data on demographic, biochemical, and clinical changes in type 2 diabetic (T2D) patients attending real medical outpatient consultations. This registry is also used to find new biomarkers related to the micro- and macrovascular complications of T2D, with a particular focus on diabetic nephropathy. With this purpose, longitudinal serum and urine samples, DNA banking, and data on 227 metabolomics profiles, 77 immunoglobulin G glycomics traits, and other emerging biomarkers were recorded in this cohort. In this study, we show a detailed longitudinal description of the clinical and analytical parameters of this registry, with a special focus on the progress of renal function and cardiovascular events. The main objective is to analyze whether there are differential risk factors for renal function deterioration between sexes, as well as to analyze cardiovascular events and mortality in this population. In total, 650 patients with a median age of 69 (14) with different grades of chronic kidney disease—G1–G2 (eGFR > 90–60 mL/min/1.73 m2) 50.3%, G3 (eGFR; 59–30 mL/min/1.73 m2) 31.4%, G4 (eGFR; 29–15 mL/min/1.73 m2) 10.8%, and G5 (eGFR < 15 mL/min/1.73 m2) 7.5%—were followed up for 4.7 (0.65) years. Regardless of albuminuria, women lost 0.93 (0.40–1.46) fewer glomerular filtration units per year than men. A total of 17% of the participants experienced rapid deterioration of renal function, 75.2% of whom were men, with differential risk factors between sexes—severe macroalbuminuria > 300 mg/g for men OR [IQ] 2.40 [1.29:4.44] and concomitant peripheral vascular disease 3.32 [1.10:9.57] for women. Overall mortality of 23% was detected (38% of which was due to cardiovascular etiology). We showed that kidney function declined faster in men, with different risk factors compared to women. Patients with T2D and kidney involvement have very high mortality and an important cardiovascular burden. This cohort is proposed as a great tool for scientific collaboration for studies, whether they are focused on T2D, or whether they are interested in comparing differential markers between diabetic and non-diabetic populations.

IgG N‐glycans are associated with prevalent and incident complications of type 2 diabetes

“…The GenoDiabMar study is a type 2 diabetes adult registry recruited between 2012 and 2015 from the healthcare area Litoral-Mar of Barcelona, Spain. 17,18 Patients older than 45 years with a medical history of type 2 diabetes for more than 10 years and treated with anti-diabetic drugs were included (n = 640 for the current study).…”

“…Definitions for vascular complications have been described in detail for DiaGene, Geno-DiabMar and DCS cohorts. 15,16,18 In short, retinopathy for all studies was scored by an ophthalmologist based on fundus photography, and for the current study was defined as present or absent, where present includes all gradations and stages of diabetic retinopathy. Nephropathy was defined as microalbuminuria [albumin/creatinine-ratio (ACR) ≥2.5 mg/mmol for men or ≥3.5 mg/mmol for women] present at two of three consecutive measurements or when high micro-albuminuria or macro-albuminuria was present at one measurement (ACR ≥ 12.5 mg/ mmol for men or ≥17.5 mg/mmol for women).…”

“…Nephropathy was defined as microalbuminuria [albumin/creatinine-ratio (ACR) ≥2.5 mg/mmol for men or ≥3.5 mg/mmol for women] present at two of three consecutive measurements or when high micro-albuminuria or macro-albuminuria was present at one measurement (ACR ≥ 12.5 mg/ mmol for men or ≥17.5 mg/mmol for women). 15,16,18 Cardiovascular disease derived from medical records and questionnaires was defined as myocardial infarction, percutaneous coronary intervention/coronary artery bypass graft (PCI/CABG), cerebrovascular accident, transient ischaemic attack, and peripheral arterial disease (PAD). Ischaemic brain disease (IBD) comprised both cerebrovascular incidents and transient ischaemic attacks combined.…”

“…Complete data on the separate associations for the components of the macrovascular endpoint are shown in supplementary Table S4. Note: Details on the cohorts including definitions and biochemical measurements have been described elsewhere (15,16,18). For complications, numbers of participants are shown, and percentages are presented as n-case divided by n-total.…”

Serum Lipocalin-2 Levels Are Increased and Independently Associated With Early-Stage Renal Damage and Carotid Atherosclerotic Plaque in Patients With T2DM

“…In addition, diabetes mellitus was considered as the leading cause of chronic kidney disease and caused approximately 1.5 million deaths in 2016 ( 3 ). Moreover, previous clinical studies demonstrated that the cardiovascular mortality rate of patients with diabetic nephropathy (DN) was significantly higher than that of patients without DN ( 4 , 5 ); thereby, DN may be related to macrovascular lesions and promote AS to a certain extent.…”