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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Blood glucose response after oral lactulose intake in type 2 diabetic individuals
Thomas R Pieber, Eva Svehlikova, Ines Mursic, Tamara Esterl, Manfred Wargenau, Tina Sartorius, Lioba Pauly, Susann Schwejda-Guettes, Annalena Neumann, Valentin Faerber, John Friedrich Stover, Barbara Gaigg, Angelika Kuchinka-Koch
Thomas R Pieber, Eva Svehlikova, Ines Mursic, Tamara Esterl, Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz 8036, Austria
Manfred Wargenau, Department of Statistic, M.A.R.C.O. GmbH & Co. KG, Institute for Clinical Research and Statistics, Düsseldorf 40211, Germany
Tina Sartorius, Department of Nutritional CRO, BioTeSys GmbH, Esslingen 73728, Germany
Lioba Pauly, Susann Schwejda-Guettes, Department of Medical & Clinical Affairs, Market Access & Education Business Unit Enteral Nutrition, Bad Homburg 61352, Germany
Annalena Neumann, Valentin Faerber, Department of Medical, Clinical & Regulatory Affairs, Business Unit Parenteral Nutrition, Keto-Analogues and Standard I.V. Fluids, Fresenius Kabi Deutschland GmbH, Bad Homburg 61352, Germany
John Friedrich Stover, Department of Consultancy, Stover-Solutions, Zurich 8006, Switzerland
Barbara Gaigg, Angelika Kuchinka-Koch, Market Unit Lactulose, Fresenius Kabi Austria GmbH, Linz 4020, Austria
Author contributions: Pieber TR, Svehlikova E, Mursic I, and Esterl T performed the study, data collection and interpretation; Stover JF, Pauly L, Schwejda-Guettes S, Kuchinka-Koch A, and Gaigg B designed and supervised the study; Wargenau M planned and performed the statistical analysis of the data and interpreted the results; Sartorius T, Neumann A, and Faerber V wrote the manuscript; all authors reviewed, edited, and approved the manuscript for submission.
Supported by Fresenius Kabi Deutschland GmbH, Germany.
Institutional review board statement: This study protocol was reviewed and approved by the Independent Ethics Committee of the Medical University of Graz, Austria.
Clinical trial registration statement: This study was registered in the European Union Drug Regulating Authorities Clinical Trials Database, No. 2018-002359-14.
Informed consent statement: All study participants provided written informed consent prior to enrollment.
Conflict-of-interest statement: The study was sponsored by Fresenius Kabi Deutschland GmbH, Germany. The sponsor’s representatives contributed to the study design and the selection of outcome measures before study start but had no role in study execution or data collection, or data analyses. All other authors declare no potential conflicts of interest related to this paper.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to that statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Valentin Faerber, PhD, Director, Department of Medical, Clinical & Regulatory Affairs, Business Unit Parenteral Nutrition, Keto-Analogues and Standard I. V. Fluids, Fresenius Kabi Deutschland GmbH, Else-Kroener-Straße 1, Bad Homburg 61352, Germany. valentin.faerber@fresenius-kabi.com
Received: December 3, 2020
Peer-review started: December 3, 2020
First decision: March 14, 2021
Revised: April 7, 2021
Accepted: April 22, 2021
Article in press: April 22, 2021
Published online: June 15, 2021
ARTICLE HIGHLIGHTS
Research background
Lactulose is approved for the symptomatic treatment of constipation, a gastrointestinal (GI) complication common in individuals with diabetes. Lactulose products contain carbohydrate impurities that occur during the lactulose manufacturing process. These impurities may affect the blood glucose levels of individuals with type 2 diabetes mellitus (T2DM) using lactulose for the treatment of mild constipation.
Research motivation
Currently, there is no information on whether lactulose in marketed formulations (crystals and liquid) has an impact on the blood glucose profile in mildly constipated, non-insulin-dependent subjects with T2DM.
Research objectives
The main objective was to assess possible changes in blood glucose levels after oral intake of lactulose in mildly constipated, non-insulin-dependent subjects with T2DM in an outpatient setting.
Research methods
The study was performed as a prospective, double-blind, randomized, controlled, single-center trial with a four-period crossover and incomplete block design in a total of 24 mildly constipated non-insulin-dependent subjects with T2DM. Capillary blood glucose concentrations were assessed over a period of 180 min after a single oral dose of 20 g or 30 g lactulose (crystal and liquid formulation). Water and 30 g glucose served as a negative and positive control, respectively.
Research results
Lactulose when administered at the recommended maintenance dose of 20 g and at a higher dose of 30 g (crystal or liquid formulation) had no impact on blood glucose baseline-corrected area under the curve of blood glucose concentrations over the complete assessment period [AUCbaseline_c (0-180 min)]. The early, small, self-limited increase in maximal blood glucose increase of 0.63 mmol/L (maximum blood glucose concentration, P = 0.0059 vs water) compared to water is not clinically relevant. As expected for subjects with T2DM, the dose of 30 g glucose (positive control) resulted in a pronounced increase in blood glucose concentration. No differences in blood glucose response were observed between the different lactulose formulations. Lactulose increased the number of bowel movements and was generally well tolerated with only mild to moderate GI symptoms due to the laxative action of lactulose.
Research conclusions
As expressed by the AUCbaseline_c (0-180 min) carbohydrate impurities in oral lactulose products administered at the recommended doses of 20 g/d and 30 g/d do not have to be considered for the blood glucose management of mildly constipated, non-insulin-dependent individuals with T2DM taking lactulose as a laxative.
Research perspectives
Future research could focus on the impact of oral lactulose supplementation at different doses over a longer period of time on blood glucose profile and gut microbiota.
