title: Energy loss via urine and faeces--a combustive analysis in diabetic rats and the impact of antidiabetic treatment on body weight.
abstract: OBJECTIVE
  Intensive glycaemic control in type 2 diabetes achieved by insulin is generally accompanied by body weight gain. This study was performed to emphasize the meaning of caloric analysis of urine and faeces for energy balance.
  
  
  METHODS
  We measured energetic loss via urine and faeces during antihyperglycaemic treatment in male obese Zucker diabetic fatty (ZDF) rats. Rats were treated for 10 days with the sodium-glucose-linked transporter-2 (SGLT2) inhibitor AVE2268, with insulin glargine, with the GLP-1 receptor agonist lixisenatide and with the combination of insulin glargine and lixisenatide. Each study was accompanied by one lean (Fa/?) and one obese (fa/fa) untreated non-diabetic and diabetic control group, respectively. Blood glucose, body weight alterations and food assimilation efficiency were monitored.
  
  
  RESULTS
  In control ZDF rats, more than 12 g/day of pure glucose was urinarily excreted. In total, the energetic loss via urine exceeded 30% from total energy uptake. Insulin glargine treatment decreased urinary energetic loss, leading to a body weight gain of approximately 3 g/day. An almost body weight-neutral antihyperglycaemic treatment could be achieved with AVE2268 and lixisenatide. While lixisenatide reduced body weight gain via reduction of energy uptake, the SGLT2 inhibitor even increased urinary glucose and thus energy excretion. Combining insulin glargine with lixisenatide attenuated the anabolic effect of insulin resulting in weight neutrality.
  
  
  CONCLUSIONS
  Our data clearly show renal contribution to the body's energy control by urinary glucose excretion (UGE) during antidiabetic treatment. The undesired retained energy could be reduced via additional UGE or via simultaneous reduction of energy uptake and/or energy retention.
authors.affiliation: R&D Diabetes Division, Translational Medicine, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany. ralf.elvert@sanofi.com
authors.forename: R
authors.initials: R
authors.lastname: Elvert
authors.forename: A
authors.initials: A
authors.lastname: Wille
authors.forename: J
authors.initials: J
authors.lastname: Wandschneider
authors.forename: U
authors.initials: U
authors.lastname: Werner
authors.forename: H
authors.initials: H
authors.lastname: Glombik
authors.forename: A W
authors.initials: AW
authors.lastname: Herling
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D005960:Glucosides / Q000494:pharmacology*; D006442:Glycated Hemoglobin / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D018027:Receptors, Glucagon / Q000819:agonists; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D015430:Weight Gain / Q000187:drug effects; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D001786:Blood Glucose; D000067757:Glucagon-Like Peptide-1 Receptor; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D010455:Peptides; D018027:Receptors, Glucagon; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C535206:AVE2268; C000593835:Glp1r protein, rat; C490300:Slc5a2 protein, rat; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor