Skip to main content
  • More from ADA
    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care in Diabetes
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • ADA Scientific Sessions Abstracts
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • ADA Scientific Sessions Abstracts
    • Diabetes COVID-19 Article Collection
    • Diabetes Symposium 2020
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Submit Cover Art
    • ADA Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care in Diabetes
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • My Cart

Search

  • Advanced search
Diabetes
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • ADA Scientific Sessions Abstracts
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • ADA Scientific Sessions Abstracts
    • Diabetes COVID-19 Article Collection
    • Diabetes Symposium 2020
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Submit Cover Art
    • ADA Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Obesity Studies

Mechanism by Which Caloric Restriction Improves Insulin Sensitivity in Sedentary Obese Adults

  1. Matthew L. Johnson1,
  2. Klaus Distelmaier1,
  3. Ian R. Lanza1,
  4. Brian A. Irving1,
  5. Matthew M. Robinson1,
  6. Adam R. Konopka1,
  7. Gerald I. Shulman2 and
  8. K. Sreekumaran Nair1⇑
  1. 1Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, MN
  2. 2Howard Hughes Medical Institute and the Departments of Medicine and Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT
  1. Corresponding author: K. Sreekumaran Nair, nair{at}mayo.edu.
Diabetes 2016 Jan; 65(1): 74-84. https://doi.org/10.2337/db15-0675
PreviousNext
  • Article
  • Figures & Tables
  • Suppl Material
  • Info & Metrics
  • PDF
Loading

Article Figures & Tables

Figures

  • Tables
  • Figure 1
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 1

    Experimental design. Before and after 16 weeks of CR or CON, two outpatient visits and one inpatient visit were scheduled. One outpatient visit consisted of nuclear magnetic resonance (NMR) imaging, and the second outpatient visit was for measurements of REE, DEXA scan, and a VO2peak test on a bicycle ergometer. An inpatient visit at baseline and after 16 weeks of the intervention was conducted after 5 days of a weight-maintaining diet provided by the CRU metabolic kitchen. The inpatient visit consisted of a two-stage (low- and high-dose insulin) hyperinsulinemic-euglycemic pancreatic clamp over 6 h, followed by a skeletal muscle biopsy. Blood samples were obtained every 10 min to adjust the GIR to maintain euglycemia at ∼90 mg/dL. After the clamp and biopsy were completed, standardized meals were provided to keep participants’ weight stable. The following morning in the postabsorptive state, a second fasted skeletal muscle biopsy was performed. *Blood draw.

  • Figure 2
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 2

    Insulin sensitivity. The GIR required to maintain euglycemia in 10-min intervals during the 6-h insulin infusion in CR (A) and CON (B) and corresponding glucose concentrations. C and D: The AUC and glucose Rd during the last hour of the insulin clamp for CR and CON. E: EGP measured in the basal fasting state. F: EGP percentage suppression from overnight fasted to low-dose insulin. Means ± SEM are given, and a two-way (group, time) repeated-measures ANOVA was used to compare outcomes across groups. Precise P values are given for the ANOVA. When a significant interaction was found, a Sidak post hoc test was performed. ****P < 0.0001.

  • Figure 3
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 3

    Mitochondrial function. Mitochondrial oxygen consumption rates (JO2) were measured with carbohydrate-based mitochondrial substrates for CR (A) and CON (B) and then normalized for mitochondrial protein (C and D). E: In vivo oxidative capacity measured by magnetic resonance spectroscopy before and after the 16-week period. F: Mitochondrial coupling was assessed from the respiratory control ratio (RCR). G: mtH2O2 emissions were evaluated in isolated mitochondria under state 2 conditions. Means ± SEM are given, and a two-way (group, time) repeated-measures ANOVA was used to compare outcomes across groups.

  • Figure 4
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 4

    A: Skeletal muscle TXNIP expression was evaluated using quantitative PCR and normalized to β-2-microglobulin (B2M) in muscle biopsy samples after the insulin clamp. B: The ΔTXNIP mRNA was correlated using a Pearson correlation to the ΔAUC for the 6-h insulin clamp for all participants. C: Skeletal muscle protein content was evaluated using Western blot and normalized to vinculin. D: The ΔTXNIP protein was correlated using a Pearson correlation to the ΔAUC for the 6-h insulin clamp for all participants. ΔGINF, change in GIR. Means ± SEM are given, and a two-way (group, time) repeated-measures ANOVA was used to compare outcomes across groups. When a significant interaction was found, a Sidak post hoc test was performed. **P < 0.01.

Tables

  • Figures
  • Table 1

    Characteristics of the subjects

    CharacteristicCRControlP
    Baseline (N = 11)Post (N = 11)Baseline (N = 9)Post (N = 9)GroupTimeInteraction
    Age, year55.3 ± 1.852.7 ± 1.6———
    Height, cm169.6 ± 2.4177.8 ± 3.9
    Weight, kg101.8 ± 4.991.3 ± 4.6****109 ± 7.4110.3 ± 7.70.1401<0.001<0.001
    Weight % change−10.1 ± 1.2+0.8 ± 0.6———
    BMI, kg/m235.2 ± 1.331.8 ± 1.1****34.4 ± 1.434.6 ± 1.50.6103<0.001<0.001
    Glucose, mg/dL106.6 ± 2.5102.3 ± 2.2105.0 ± 3.3105.3 ± 4.10.87160.11610.0767
    Insulin, μIU/mL12.7 ± 1.86.7 ± 0.9****11.3 ± 2.511.2 ± 2.30.5616<0.002<0.002
    FFA, mmol/L0.38 ± 0.040.45 ± 0.050.38 ± 0.060.39 ± 0.030.56200.18760.3880
    β-Hydroxybutyrate, mmol/L0.23 ± 0.010.28 ± 0.01***0.24 ± 0.010.25 ± 0.010.38260.00120.0387
    Body fat, %45.9 ± 1.642.4 ± 1.5****43.9 ± 2.044.3 ± 1.80.9918<0.001<0.001
    Lean mass, kg52.5 ± 3.250.3 ± 2.9**59.5 ± 5.359.1 ± 5.00.18540.00340.0347
    Fat mass, kg39.6 ± 4.636.8 ± 2.2****45.9 ± 3.246.2 ± 3.20.1246<0.001<0.001
    Visceral fat, cm214.6 ± 2.211.4 ± 1.3*12.1 ± 1.613.9 ± 1.90.98910.41320.0081
    Subcutaneous fat, cm245.1 ± 2.636.9 ± 2.6****43.2 ± 3.944.2 ± 4.10.57220.00780.0015
    REE, kcal/day1,668 ± 931,615 ± 921,865 ± 1281,867 ± 1090.13560.49250.4745
    VO2peak, L/min1.9 ± 0.12.2 ± 0.2———
    • Measurements were made before randomization (baseline) and again after 16 weeks of CR or CON in the fasting state. Means ± SEM are given, and a two-way (group, time) repeated-measures ANOVA was used to compare outcomes across groups. Precise P values are given for the ANOVA. When a significant interaction was found, a Sidak post hoc test was performed.

    • *P < 0.05;

    • **P < 0.01;

    • ***P < 0.001;

    • ****P < 0.0001.

  • Table 2

    Metabolic flexibility

    Caloric restrictionControlP
    BaselinePostBaselinePostGroupTimeInteraction
    RER
     Basal0.864 ± 0.0060.827 ± 0.015*0.833 ± 0.0050.850 ± 0.0120.75130.27560.0095
     Clamp0.917 ± 0.0130.933 ± 0.0220.918 ± 0.020.921 ± 0.0220.65370.71040.9356
     Δ0.053 ± 0.0160.106 ± 0.025*0.084 ± 0.0190.071 ± 0.0280.95970.11940.0147
    CHO oxidation (μmol ⋅ kgFFM−1 ⋅ min−1)
     Basal16.8 ± 1.313.9 ± 2.213.3 ± 0.815.1 ± 1.30.51650.70660.0704
     Clamp21.9 ± 1.522.3 ± 2.822.1 ± 2.522.2 ± 2.60.98490.86530.9051
    Nonoxidative glucose disposal (μmol ⋅ kgFFM−1 ⋅ min−1)
     Basal0.1 ± 1.40.9 ± 2.24.9 ± 4.42.5 ± 2.50.29490.78940.5297
     Clamp15.3 ± 6.331.5 ± 4.9**28.2 ± 5.928.9 ± 6.00.51410.00970.0157
    Lipid oxidation (μmol ⋅ kgFFM−1 ⋅ min−1)
     Basal1.2 ± 0.11.5 ± 0.1*1.5 ± 0.11.4 ± 0.10.47430.35870.0083
     Clamp0.8 ± 0.20.7 ± 0.20.7 ± 0.10.7 ± 0.20.79560.48450.6494
    • Measurements were made before randomization (baseline) and again after 16 weeks of CR or CON. Means ± SEM are given, and a two-way (group, time) repeated-measures ANOVA was used to compare outcomes across groups. Precise P values are given for the ANOVA. When a significant interaction was found, a Sidak post hoc test was performed.

    • CHO, carbohydrate.

    • *P < 0.05;

    • **P < 0.01.

PreviousNext
Back to top
Diabetes: 65 (1)

In this Issue

January 2016, 65(1)
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by Author
  • Masthead (PDF)
Sign up to receive current issue alerts
View Selected Citations (0)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about Diabetes.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Mechanism by Which Caloric Restriction Improves Insulin Sensitivity in Sedentary Obese Adults
(Your Name) has forwarded a page to you from Diabetes
(Your Name) thought you would like to see this page from the Diabetes web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Mechanism by Which Caloric Restriction Improves Insulin Sensitivity in Sedentary Obese Adults
Matthew L. Johnson, Klaus Distelmaier, Ian R. Lanza, Brian A. Irving, Matthew M. Robinson, Adam R. Konopka, Gerald I. Shulman, K. Sreekumaran Nair
Diabetes Jan 2016, 65 (1) 74-84; DOI: 10.2337/db15-0675

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Add to Selected Citations
Share

Mechanism by Which Caloric Restriction Improves Insulin Sensitivity in Sedentary Obese Adults
Matthew L. Johnson, Klaus Distelmaier, Ian R. Lanza, Brian A. Irving, Matthew M. Robinson, Adam R. Konopka, Gerald I. Shulman, K. Sreekumaran Nair
Diabetes Jan 2016, 65 (1) 74-84; DOI: 10.2337/db15-0675
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Research Design and Methods
    • Results
    • Discussion
    • Article Information
    • Footnotes
    • References
  • Figures & Tables
  • Suppl Material
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Defective FXR-SHP Regulation in Obesity Aberrantly Increases miR-802 Expression, Promoting Insulin Resistance and Fatty Liver
  • Deficiency of Stat1 in CD11c+ Cells Alters Adipose Tissue Inflammation and Improves Metabolic Dysfunctions in Mice Fed a High-Fat Diet
  • Placental Insulin/IGF-1 Signaling, PGC-1α, and Inflammatory Pathways Are Associated With Metabolic Outcomes at 4–6 Years of Age: The ECHO Healthy Start Cohort
Show more Obesity Studies

Similar Articles

Navigate

  • Current Issue
  • Online Ahead of Print
  • Scientific Sessions Abstracts
  • Collections
  • Archives
  • Submit
  • Subscribe
  • Email Alerts
  • RSS Feeds

More Information

  • About the Journal
  • Instructions for Authors
  • Journal Policies
  • Reprints and Permissions
  • Advertising
  • Privacy Policy: ADA Journals
  • Copyright Notice/Public Access Policy
  • Contact Us

Other ADA Resources

  • Diabetes Care
  • Clinical Diabetes
  • Diabetes Spectrum
  • Scientific Sessions Abstracts
  • Standards of Medical Care in Diabetes
  • BMJ Open - Diabetes Research & Care
  • Professional Books
  • Diabetes Forecast

 

  • DiabetesJournals.org
  • Diabetes Core Update
  • ADA's DiabetesPro
  • ADA Member Directory
  • Diabetes.org

© 2021 by the American Diabetes Association. Diabetes Print ISSN: 0012-1797, Online ISSN: 1939-327X.