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

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • New and Noteworthy
    • Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Special Collections
    • Recent ADA Position Statements
  • Info
    • About the Journal
    • Meet the Editors
    • Reprints & Permissions
    • Journal Policies
    • For Authors
    • For Reviewers
    • For Advertisers
  • Subscriptions
    • Manage Online Access
    • Individual Subscriptions
    • Institutional Subscriptions
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Diabetes Discovery
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • Peer Review
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • Standards of Medical Care
    • Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in

Search

  • Advanced search
Diabetes Care
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • New and Noteworthy
    • Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Special Collections
    • Recent ADA Position Statements
  • Info
    • About the Journal
    • Meet the Editors
    • Reprints & Permissions
    • Journal Policies
    • For Authors
    • For Reviewers
    • For Advertisers
  • Subscriptions
    • Manage Online Access
    • Individual Subscriptions
    • Institutional Subscriptions
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Diabetes Discovery
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • Peer Review
Original Research

The Second-Meal Phenomenon in Type 2 Diabetes

  1. Ana Jovanovic, MD,
  2. Jean Gerrard, SRN and
  3. Roy Taylor, MD
  1. From the Diabetes Research Group and Newcastle Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, U.K.
  1. Corresponding author: Roy Taylor, roy.taylor{at}ncl.ac.uk.
Diabetes Care 2009 Jul; 32(7): 1199-1201. https://doi.org/10.2337/dc08-2196
PreviousNext
  • Article
  • Figures & Tables
  • Info & Metrics
  • PDF
Loading

Abstract

OBJECTIVE In health, the rise in glucose after lunch is less if breakfast is eaten. We evaluated the second-meal effect in type 2 diabetes.

RESEARCH DESIGN AND METHODS Metabolic changes after lunch in eight obese type 2 diabetic subjects were compared on 3 days: breakfast eaten, no breakfast, and no breakfast but intravenous arginine 1 h before lunch.

RESULTS Despite comparable insulin levels, the rise in plasma glucose after lunch was considerably less if breakfast had been eaten (0.68 ± 1.49 vs. 12.32 ± 1.73 vs. 7.88 ± 1.03 mmol · h−1 · l−1; P < 0.0001). Arginine administration almost halved the lunch rise in plasma glucose (12.32 ± 1.73 vs. 7.88 ± 1.03 mmol · h−1 · l−1). The plasma free fatty acid concentration at lunchtime directly related to plasma glucose rise after lunch (r = 0.67, P = 0.0005).

CONCLUSIONS The second-meal effect is preserved in type 2 diabetes. Premeal administration of a nonglucose insulin secretagogue results in halving the postprandial glucose rise and has therapeutic potential.

The effect of a prior meal in decreasing the rise in blood glucose after a subsequent meal was first recognized almost a century ago (1). It has repeatedly been confirmed in healthy subjects, but tests with intravenous or oral glucose suggested that the second-meal effect does not occur in type 2 diabetes (2–4). We observed incidentally that a second meal in subjects with type 2 diabetes brought about a 70% lesser rise in blood glucose (5).

This study was designed to determine whether the second-meal phenomenon is present in type 2 diabetes and, if so, whether this can artificially be induced as a possible therapeutic approach.

RESEARCH DESIGN AND METHODS

Eight subjects with type 2 diabetes were recruited (aged 56.1 ± 2.8 years, BMI 36.0 ± 2.5 kg/m2, A1C 6.7 ± 0.2%, diabetes duration 8.1 ± 0.5 years, diet and/or metformin treatment). Ethics committee permission was obtained.

Study methods

The metabolic response to a standard lunch was studied on 3 separate days in random order with 2–4 weeks between studies. On day A, the subjects had a standard breakfast followed by the standard lunch. On day B, breakfast was omitted. On day C, breakfast was omitted and arginine was infused 1 h before lunch. The details of metabolic testing, arginine administration, and hormone and metabolites assays were as previously described (5,6).

Meal composition

The standard breakfast consisted of 50 g muesli, 100 g milk, two slices of toast (56 g), 20 g marmalade, 20 g margarine, and 200 ml orange juice (106 g carbohydrate, 18 g fat, 15 g protein, 646 kcal). The standard lunch comprised a cheese sandwich, 200 ml orange juice, 170 g yogurt, and 150 g jelly (103 g carbohydrate, 30 g fat, 44 g protein, 858 kcal).

Statistical analysis

Data are presented as means ± SE. One-way ANOVA and linear correlation were performed using MINITAB (State College, PA).

RESULTS

Glucose

The rise in plasma glucose after lunch was greatest on the day without breakfast and almost 40% lower on the arginine day (0.68 ± 1.49 vs. 12.32 ± 1.73 vs. 7.88 ± 1.03 mmol · h−1 · l−1; P < 0.0001) (Fig. 1A).

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

A: Incremental change in plasma glucose after lunch. *P < 0.0001 area under the curve (AUC; 4-8 h). B: Strong positive correlation between lunchtime plasma FFAs and the increase in plasma glucose concentration after lunch (r = 0.67, P = 0.0005) in type 2 diabetes.

On day A, breakfast increased plasma glucose from 7.6 ± 0.4 to 13.3 ± 1.0 mmol/l at 2 h and 8.4 ± 0.7 mmol/l at 4 h. On day B (no breakfast), plasma glucose fell from 8.0 ± 0.4 to 6.5 ± 0.3 mmol/l by 4 h. Two hours after the test, lunch plasma glucose was 8.6 ± 0.6 mmol/l on day A compared with 10.9 ± 0.8 mmol/l on day B.

On day C, fasting plasma glucose fell from 7.6 ± 0.6 mmol/l to 6.6 ± 0.6 mmol/l at 3 h just before the arginine infusion and was 7.1 ± 0.7 mmol/l at 4 h.

Serum insulin and C-peptide

Fasting serum insulin was similar on each of the days (127 ± 23, 140 ± 48, and 115 ± 27 pmol/l for days A, B, and C, respectively; P = 0.87). The post-lunch serum insulin concentrations were comparable on days A, B, and C (1,918 ± 45 vs. 2,040 ± 75 vs. 1,472 ± 40 pmol · h−1 · l−1, respectively; P = 0.76). On day A, serum insulin peaked at 954 ± 237 pmol/l 2 h after breakfast. On day C, insulin concentrations increased sharply after 30 min of the arginine infusion (418 ± 177 pmol/l) but returned to the baseline (157 ± 37 pmol/l) before lunch.

Insulin–to–C-peptide ratios were similar after the test lunch on all three experimental days (144 ± 23, 185 ± 47, and 168 ± 31 pmol/nmol, respectively; P = 0.73 at 2 h after lunch).

Glucagon and catecholamines

Fasting glucagon levels were similar on each of the three experimental days (87 ± 11, 83 ± 9, and 83 ± 7 pg/ml, respectively). On day C, the arginine infusion induced a threefold increase in glucagon concentrations after 30 min to a short-lived peak of 263 ± 28 pg/ml.

Pre-lunch and 30-min post-lunch adrenaline levels were similar on each day (0.32 ± 0.06, 0.36 ± 0.04, and 0.37 ± 0.04 nmol/l; P = 0.77; and 0.34 ± 0.04, 0.41 ± 0.06, and 0.39 ± 0.04 nmol/l, respectively; P = 0.67).

Plasma free fatty acids

Fasting plasma free fatty acids (FFAs) were similar on the three study days (0.64 ± 0.07, 0.65 ± 0.9, and 0.67 ± 0.7 mmol/l, respectively; P = 0.96). After breakfast on day A, plasma FFA levels were suppressed within 2 h to 0.18 ± 0.04 mmol/l. On day B, plasma FFAs were 0.65 ± 0.4 mmol/l before and 0.27 ± 0.04 mmol/l 2 h after lunch. On day C, plasma FFAs were suppressed by the arginine infusion (0.35 ± 0.04 mmol/l) and the lunch (0.18 ± 0.03 mmol/l 2 h after lunch). The concentration of plasma FFAs was strongly related to the area under the curve of the plasma glucose concentration after lunch (r = 0.67, P = 0.0005) (Fig. 1B).

CONCLUSIONS

In obese type 2 diabetic subjects, the rise in plasma glucose was 95% less after lunch when the lunch had been preceded by breakfast, confirming the occurrence of the second-meal effect in type 2 diabetes. The effect on plasma glucose was similar or slightly greater than that in healthy subjects (73% decrease in post-lunch hyperglycemia) (7). Substrate oxidation rates were unchanged across experimental days (data not shown). The plasma FFA concentration before lunch correlated positively with the post-lunch rise in plasma glucose after lunch. The post-lunch insulin profiles were similar on all test days.

The concept that the second-meal phenomenon did not occur in type 2 diabetes is derived from study of repeated intravenous glucose (3), although this has a poor effect on insulin secretion (8). In contrast, a mixed meal or injection of amino acids brings about an increase in plasma insulin levels, even in type 2 diabetes (8,9).

The second-meal phenomenon is not mediated by an acute effect on insulin secretion, and FFA suppression must be considered. Increased FFA induces insulin resistance in humans (10,11). Conversely, suppression of plasma FFA by acipimox acutely improves insulin action in type 2 diabetes by increasing glucose storage as muscle glycogen and decreasing hepatic glucose production (9,12,13). An increase in FFAs leads to an inhibition of net hepatic glycogen breakdown and increases gluconeogenesis (14). We recently observed that, in normal subjects, the second-meal phenomenon was associated with increased rates of storage of lunchtime carbohydrate in muscle glycogen (7).

The present data demonstrate that under everyday conditions, postprandial glucose metabolism in type 2 diabetes is facilitated by suppression of plasma FFA concentrations after a previous meal.

Acknowledgments

This study was supported by the Wellcome Trust U.K. (Grant GR073561).

No potential conflicts of interest relevant to this article were reported.

We are grateful to the volunteers for their commitment during the study. We thank Heather Gilbert for technical assistance.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received December 20, 2008.
    • Accepted March 21, 2009.
  • Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

  • © 2009 by the American Diabetes Association.

References

  1. ↵
    1. Staub H
    : Untersuchungen uber den Zuckerstoffwechsel des Munchen. Z Clin Med 1921; 91: 44– 48
    OpenUrl
  2. ↵
    1. Grill V,
    2. Adamson U,
    3. Viklund M
    : Effects of previous intake of glucose on postprandial hyperglycemia in type 2 diabetics. Acta Med Scand 1985; 217: 41– 45
    OpenUrlPubMedWeb of Science
  3. ↵
    1. Reich A,
    2. Abraira C,
    3. Brunken R,
    4. Soneru I
    : Potentiation of glucose-stimulated insulin release by tolazamide and paradoxical absence of glucose facilitation (Staub effect) in non-insulin-dependent diabetes. Metabolism 1986; 35: 367– 370
    OpenUrlCrossRefPubMedWeb of Science
  4. ↵
    1. Ravanam A,
    2. Jeffery J,
    3. Nehlawi M,
    4. Abraira C
    : Improvement of glucose-primed intravenous glucose tolerance and correction of acute insulin decrement by glipizide in type II diabetes. Metabolism 1991; 40: 1173– 1177
    OpenUrlCrossRefPubMedWeb of Science
  5. ↵
    1. Carey PE,
    2. Halliday J,
    3. Snaar JE,
    4. Morris PG,
    5. Taylor R
    : Direct assessment of muscle glycogen storage after mixed meals in normal and type 2 diabetic subjects. Am J Physiol Endocrinol Metab 2003; 284: E688– E694
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Herman WH,
    2. Fajans SS,
    3. Smith MJ,
    4. Polonsky KS,
    5. Bell GI,
    6. Halter JB
    : Diminished insulin and glucagon secretory responses to arginine in nondiabetic subjects with a mutation in the hepatocyte nuclear factor-4α/MODY1 gene. Diabetes 1997; 46: 1749– 1754
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Jovanovic A,
    2. Leverton E,
    3. Solanky B,
    4. Snaar JEM,
    5. Morris PG,
    6. Taylor R
    : The second meal phenomenon is associated with enhanced muscle glygogen storage in humans. Clin Sci (Lond); 1 23 2009 [ Epub ahead of print]
  8. ↵
    1. Pfeifer MA,
    2. Halter JB,
    3. Porte D, Jr
    : Insulin secretion in diabetes mellitus. Am J Med 1981; 70: 579– 588
    OpenUrlCrossRefPubMedWeb of Science
  9. ↵
    1. Carey PE,
    2. Gerrard J,
    3. Cline GW,
    4. Dalla Man C,
    5. English PT,
    6. Firbank MJ,
    7. Cobelli C,
    8. Taylor R
    : Acute inhibition of lipolysis does not affect postprandial suppression of endogenous glucose production. Am J Physiol Endocrinol Metab 2005; 289: E941– E947
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Johnson AB,
    2. Argyraki M,
    3. Thow JC,
    4. Cooper BG,
    5. Fulcher G,
    6. Taylor R
    : Effect of increased free fatty acid supply on glucose metabolism and skeletal muscle glycogen synthase activity in normal man. Clin Sci (Lond) 1992; 82: 219– 226
    OpenUrlPubMed
  11. ↵
    1. Roden M,
    2. Price TB,
    3. Perseghin G,
    4. Petersen KF,
    5. Rothman DL,
    6. Cline GW,
    7. Shulman GI
    : Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest 1996; 97: 2859– 2865
    OpenUrlCrossRefPubMedWeb of Science
  12. ↵
    1. Piatti PM,
    2. Monti LD,
    3. Davis SN,
    4. Conti M,
    5. Brown MD,
    6. Pozza G,
    7. Alberti KG
    : Effects of an acute decrease in non-esterified fatty acid levels on muscle glucose utilization and forearm indirect calorimetry in lean NIDDM patients. Diabetologia 1996; 39: 103– 112
    OpenUrlPubMed
  13. ↵
    1. Vaag A,
    2. Skott P,
    3. Damsbo P,
    4. Gall MA,
    5. Richter EA,
    6. Beck-Nielsen H
    : Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1991; 88: 1282– 1290
    OpenUrlCrossRefPubMedWeb of Science
  14. ↵
    1. Stingl H,
    2. Krssak M,
    3. Krebs M,
    4. Bischof MG,
    5. Nowotny P,
    6. Furnsinn C,
    7. Shulman GI,
    8. Waldhausl W,
    9. Roden M
    : Lipid-dependent control of hepatic glycogen stores in healthy humans. Diabetologia 2001; 44: 48– 54
    OpenUrlCrossRefPubMedWeb of Science
View Abstract
PreviousNext
Back to top
Diabetes Care: 32 (7)

In this Issue

July 2009, 32(7)
  • Table of Contents
  • About the Cover
  • Index by Author
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 Care.

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.
The Second-Meal Phenomenon in Type 2 Diabetes
(Your Name) has forwarded a page to you from Diabetes Care
(Your Name) thought you would like to see this page from the Diabetes Care web site.
Citation Tools
The Second-Meal Phenomenon in Type 2 Diabetes
Ana Jovanovic, Jean Gerrard, Roy Taylor
Diabetes Care Jul 2009, 32 (7) 1199-1201; DOI: 10.2337/dc08-2196

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

The Second-Meal Phenomenon in Type 2 Diabetes
Ana Jovanovic, Jean Gerrard, Roy Taylor
Diabetes Care Jul 2009, 32 (7) 1199-1201; DOI: 10.2337/dc08-2196
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
    • RESEARCH DESIGN AND METHODS
    • RESULTS
    • CONCLUSIONS
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Tables
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

Original Research

  • Type 2 Diabetes in Relation to the Risk of Renal Cell Carcinoma Among Men and Women in Two Large Prospective Cohort Studies
  • Hemoglobin A1c Accurately Predicts Continuous Glucose Monitoring–Derived Average Glucose in Youth and Young Adults With Cystic Fibrosis
  • A Tailored Letter Based on Electronic Health Record Data Improves Gestational Weight Gain Among Women With Gestational Diabetes: The Gestational Diabetes’ Effects on Moms (GEM) Cluster-Randomized Controlled Trial
Show more 3

Clinical Care/Education/Nutrition/Psychosocial Research

  • Improved Health-Related Quality of Life in a Phase 3 Islet Transplantation Trial in Type 1 Diabetes Complicated by Severe Hypoglycemia
  • Magnitude and Pattern of Placebo Response in Clinical Trials of Oral Antihyperglycemic Agents: Data From the U.S. Food and Drug Administration, 1999–2015
  • Efficacy and Safety of IDegLira Versus Basal-Bolus Insulin Therapy in Patients With Type 2 Diabetes Uncontrolled on Metformin and Basal Insulin: The DUAL VII Randomized Clinical Trial
Show more 3

Similar Articles

Navigate

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

 

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

© 2018 by the American Diabetes Association. Diabetes Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.