Martina Guthoff1,2,3, Robert Wagner1,2,3, Dorothea Vosseler1, Andreas Peter1,2,3, Silvio Nadalin4, Hans-Ulrich Häring1,2,3, Andreas Fritsche1,2,3, Nils Heyne1,2,3. 1. Department of Endocrinology and Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany. 2. Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany. 3. German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany. 4. Department of General, Visceral and Transplant Surgery, University of Tübingen, Tübingen, Germany.
Abstract
Background: Renal function is known to affect glucose metabolism. The aim of this study was to assess glucose metabolism in end-stage renal disease (ESRD) patients and in matched controls with normal renal function and to delineate its underlying pathophysiology. Methods: ESRD patients without diabetes mellitus on the active kidney transplant waiting list of a large European university hospital were metabolically phenotyped by an oral glucose tolerance test (OGTT) and by calculating insulin sensitivity and secretion indices. Matched controls with normal renal function were derived from the TUEF (Tuebingen Family) study cohort, which includes healthy non-diabetic individuals with an increased risk of developing type 2 diabetes. Matches were made for (i) gender, age and body mass index (BMI) (cohort 1) and for (ii) gender, age, BMI, fasting plasma glucose (FPG) and 2-h glucose in OGTT (cohort 2). Results: A total of 107 patients (90 on haemodialysis and 17 on peritoneal dialysis) and two cohorts, each comprising 107 matched controls, were investigated. ESRD patients had significantly lower FPG. Additional matching for OGTT glucose concentrations revealed significantly lower insulin sensitivity in ESRD patients than in controls. This finding was abrogated after adjustment for triglyceride levels. Insulin secretion, however, was significantly higher in ESRD patients. Insulin kinetics during OGTT as well as C-peptide levels demonstrate higher insulin secretion to be a compensation for lower insulin sensitivity and not to result from impaired insulin clearance. Conclusion: Our study is the first to provide metabolic phenotyping in patients with ESRD and to compare them with matched controls with normal renal function. Glucose metabolism differs substantially between cohorts, with insulin resistance and a compensatory increase in insulin secretion in ESRD patients.
Background: Renal function is known to affect glucose metabolism. The aim of this study was to assess glucose metabolism in end-stage renal disease (ESRD) patients and in matched controls with normal renal function and to delineate its underlying pathophysiology. Methods:ESRDpatients without diabetes mellitus on the active kidney transplant waiting list of a large European university hospital were metabolically phenotyped by an oral glucose tolerance test (OGTT) and by calculating insulin sensitivity and secretion indices. Matched controls with normal renal function were derived from the TUEF (Tuebingen Family) study cohort, which includes healthy non-diabetic individuals with an increased risk of developing type 2 diabetes. Matches were made for (i) gender, age and body mass index (BMI) (cohort 1) and for (ii) gender, age, BMI, fasting plasma glucose (FPG) and 2-h glucose in OGTT (cohort 2). Results: A total of 107 patients (90 on haemodialysis and 17 on peritoneal dialysis) and two cohorts, each comprising 107 matched controls, were investigated. ESRDpatients had significantly lower FPG. Additional matching for OGTT glucose concentrations revealed significantly lower insulin sensitivity in ESRDpatients than in controls. This finding was abrogated after adjustment for triglyceride levels. Insulin secretion, however, was significantly higher in ESRDpatients. Insulin kinetics during OGTT as well as C-peptide levels demonstrate higher insulin secretion to be a compensation for lower insulin sensitivity and not to result from impaired insulin clearance. Conclusion: Our study is the first to provide metabolic phenotyping in patients with ESRD and to compare them with matched controls with normal renal function. Glucose metabolism differs substantially between cohorts, with insulin resistance and a compensatory increase in insulin secretion in ESRDpatients.
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