University of California Davis
University of Cincinnati Medical Center
University of Massachusetts Medical School
University of Michigan Medical School
Vanderbilt University School of Medicine
Protocols & Methods
Reagents & Resources
Tissues & Samples
Conditions of Use
Data Usage Policy
Energy Expenditure Analysis
CalR: Indirect Calorimetry Analysis
Guidelines & Policies
Iatrogenic Hyperinsulinemia, Not Hyperglycemia, Drives Insulin Resistance in
Type 1 Diabetes as Revealed by Comparison to GCK-MODY (MODY2).
Gregory JM, Smith TJ, Slaughter JC, Mason HR, Hughey CC, Smith MS, Kandasamy B,
Greeley SAW, Philipson LH, Naylor RN, Letourneau LR, Abumrad NN, Cherrington AD,
Submitted Externally on 6/24/2019
Volume : Pages
Although insulin resistance consistently occurs with type 1 diabetes, its
predominant driver is uncertain. We therefore determined the relative
contributions of hyperglycemia and iatrogenic hyperinsulinemia to insulin
resistance using hyperinsulinemic-euglycemic clamps in three participant groups
(n=10/group) with differing insulinemia and glycemia: healthy controls
(euinsulinemia, euglycemia), glucokinase maturity-onset of the young (GCK-MODY;
euinsulinemia, hyperglycemia), and type 1 diabetes (hyperinsulinemia,
hyperglycemia matching GCK-MODY). We assessed the contribution of hyperglycemia
by comparing insulin sensitivity in control and GCK-MODY and the contribution of
hyperinsulinemia by comparing GCK-MODY and type 1 diabetes. HbA1c was normal in
controls and similarly elevated for type 1 diabetes and GCK-MODY. Basal insulin
levels in control and GCK-MODY were nearly equal but were 2.5-fold higher in
type 1 diabetes. Low-dose insulin infusion suppressed endogenous glucose
production similarly in all groups and suppressed nonesterified fatty acids
similarly between control and GCK-MODY, but to a lesser extent for type 1
diabetes. High-dose insulin infusion stimulated glucose disposal similarly in
control and GCK-MODY, but was 29% and 22% less effective in type 1 diabetes,
respectively. Multivariable linear regression showed insulinemia-but not
glycemia-was significantly associated with muscle insulin sensitivity. These
data suggest iatrogenic hyperinsulinemia predominates in driving insulin
resistance in type 1 diabetes. Clinicaltrials.gov:NCT02971202.
Back to Top
There was a problem with the page:
Safari Browser Detected...
We strive to make the MMPC site compatable with as many browsers as possible, but some of our third party tools don't work with the Safari browser.
In order to explore this site we highly recommend using the most recent versions of the following browsers:
Please acknowledge all posters, manuscripts or scientific materials that were generated in part or whole using funds from the MMPC using the following text:
Financial support for this work was provided by the NIDDK Mouse Metabolic Phenotyping Centers (National MMPC, RRID:SCR_008997,
) under the MICROMouse Program, grants DK076169.
Citation text and image have been copied to your clipboard. You may now paste them into your document. Thank you!
Warranty disclaimer and copyright notice
THE NATIONAL MMPC MAKES NO REPRESENTATION ABOUT THE SUITABILITY OR ACCURACY OF THE SOFTWARE OR DATA FOR ANY PURPOSE, AND MAKES NO WARRANTIES, EITHER EXPRESS OR IMPLIED, INCLUDING MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR THAT THE USE OF THE SOFTWARE OR DATA WILL NOT INFRINGE ANY THIRD PARTY PATENTS, COPYRIGHTS, TRADEMARKS, OR OTHER RIGHTS. THE SOFTWARE AND DATA ARE PROVIDED "AS IS".
The Mouse Metabolic Phenotyping Centers (MMPC) is an NIDDK funded consortium and adheres to the
NIH Data Sharing Policy
MMPC clients make their data freely available whereby MMPC users may freely build upon, enhance and reuse those data for any purpose without restriction. Scholarly citation norms must be followed for content reuse. Please acknowledge the MMPC using the following text: 'The MMPC data used in this manuscript was supported by the NIDDK National Mouse Metabolic Phenotyping Centers (National MMPC, RRID:SCR_008997,
)'. To cite specific MMPC centers, please use the appropriate RRID available from the MMPC website (
Please note that the acknowledgment text includes a Research Resource Identifier (RRID) for the MMPC CU and Centers. Reproducibility is one of the corner stones of effective, open and transparent biomedical published research. However, too often, resources (e.g. model organisms, antibodies, and tools) are not reported with adequate detail to ensure others can replicate or expand upon the published results. The Research Resource Identification Initiative (#RII) seeks to change these limitations in reporting by the use of unique Research Resource Identifiers (RRIDs). This initiative is designed to encourage authors to provide identification of the types of resources used in their research by adding a globally unique accession number to the resources described in the their manuscripts. These identifiers, called RRIDs, will allow authors to cite the resources that they use in their manuscripts. RRIDs allow for easy tracking of all papers that have used the same resource making it easy to access how the same resources works in other scenarios.
It is expected that MMPC users follow scholarly citation norms, giving credit to fellow scholars when accessing/using protocols and data, including data derived by MMPC (such as summary data) and any plots, tables or screenshots depicting those data.
It is possible for invalid or incomplete results to be presented on the MMPC web site due to software bugs, data problems, or artifacts of human error. Data sets are not necessarily static; we reserve the right to post corrections and updates as needed.
Data contributors and data users may not use MMPC in any unlawful manner, or in any manner that could impair MMPC services, security or functionality. Automated usage (webcrawlers and similar) must observe each page's "meta robots" html tags and space requests by ≥ 2 seconds. We reserve the right to block any IP associated with what we consider to be excessive or abusive usage patterns, and/or to take any action we deem necessary.
The MMPC is a National Institutes of Health-sponsored resource that provides experimental testing services to scientists studying diabetes, obesity, diabetic complications, and other metabolic diseases in mice.
Interested in receiving MMPC News?
2017 National MMPC. All Rights Reserved.