The Role of the Kidneys and Liver in the Elimination of Glucagon

University Hospital, Gentofte, Copenhagen48 enrolled

Overview

The study aims to evaluate the kinetics and effect of glucagon in patients with chronic kidney disease and liver cirrhosis and matched healthy subjects, respectively.

In the present project the investigators wish to identify whether the effect, elimination and degradation of glucagon differ between healthy control subjects and patients with Chronic Kidney Disease (CKD) and liver cirrhosis, respectively. By performing glucagon infusions on healthy control subjects and matched subjects with either limited renal and hepatic function, the contribution of both organs to the metabolic clearance rate (MCR) of glucagon can be tested. A primed infusion of stable isotopic labelled tracers will allow the researchers to investigate the effects of the glucagon infusion on the glucose, lipid and amino acid metabolism. The quantification of the MCR of glucagon will be accompanied by a range of pharmacodynamic measures in order to substantiate whether a potentially altered glucagon MCR inflicts pharmacodynamic changes of glucagon, which could contribute to the pathophysiology of CKD and liver cirrhosis.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Chronic Kidney Diseases Liver Cirrhosis Hyperglucagonemia

Interventions

Glucagon infusionBIOLOGICAL

One hour glucagon-clamp followed by one hour of blood sampling

Primed tracer infusionBIOLOGICAL

Infusion of primed isotopically labelled glucose, amino acids and lipids. From 2 hours prior to glucagon infusion and throughout the test day,

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: The CKD group * Men/women between 18 and 75 years of age * CKD stage 4 or 5 * Normal liver function (alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), albumin and coagulation factor II, VII and X (INR) within normal range, * Informed consent The cirrhosis group * Men/women between 18 and 75 years of age * Verified diagnosis of cirrhosis - Child-Pugh Score of 5-12 * Normal kidney function (estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73m2 and absence of proteinuria) * Informed consent The control group * Men/women between 18 and 75 years of age * Normal kidney function (estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73m2 and absence of proteinuria)(plasma creatinine ≤105 micromol/L (µM) for men and ≤90 µM for women) * Normal liver function (alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), albumin and coagulation factor II, VII and X (INR) within normal range * Informed consent Exclusion Criteria: All groups * Diagnosis of diabetes and/or HbA1c ≥43 mmol/mol and/or fasting plasma glucose ≥6 mmol/l. * Previous kidney transplantation with remaining kidney graft * Present treatment with oral glucocorticoids * Polycystic kidney disease * Pregnancy or breastfeeding * Inflammatory bowel disease * Surgical procedure within the last 3 months * Haemoglobin \< 6 mmol/l (women) or \< 7 mmol/l (men) * First-degree relatives with diabetes * Any condition that the investigators feel would interfere with trial participation

Locations (1)

Center for Clinical Metabolic Research, Department of Medicine, Gentofte Hospital

Hellerup, Copenhagen, Denmark

Outcomes

Primary Outcomes

Metabolic clearance rate of glucagon

Glucagon plasma concentration steady state glucagon concentrations

Time frame: t = 50 minutes