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. The algorithm was informed by age, anthropometry, and metabolic milieu (glucose, insulin, C-peptide, and free fatty acid (FFA) levels during the oral glucose tolerance test OGTT). For cluster profiling, we additionally used indexes of metabolism mechanisms (e.g., tissue-specific insulin resistance, insulin clearance, and insulin secretion), non-alcoholic fatty liver disease (NAFLD), and glomerular filtration rate (GFR). We found prominent heterogeneity within two optimal clusters, mainly representing normometabolism (Cluster-I) or insulin resistance and NAFLD (Cluster-II), at higher granularity. This was illustrated by sub-clusters showing similar NAFLD prevalence but differentiated by glycemia, FFA, and GFR (Cluster-II). Sub-clusters with similar glycemia and FFA showed dissimilar insulin clearance and secretion (Cluster-I). This work reveals that T2D heterogeneity can be captured by a thorough metabolic milieu and mechanisms profiling-metabolic footprint. It is expected that deeper phenotyping and increased pathophysiology knowledge will allow to identify subject's multidimensional profile, predict their progression, and treat them towards precision medicine.publishersversionpublishe

Methodology used in studies reporting chronic kidney disease prevalence: a systematic literature review

Background Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods. Methods For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers. Results We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m2 in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval. Conclusions The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study result