Journal of General Internal Medicine

, Volume 28, Issue 12, pp 1629–1636 | Cite as

Early Response to Preventive Strategies in the Diabetes Prevention Program

  • Nisa M. Maruthur
  • Yong Ma
  • Linda M. Delahanty
  • Julie A. Nelson
  • Vanita Aroda
  • Neil H. White
  • David Marrero
  • Frederick L. Brancati
  • Jeanne M. Clark
  • for the Diabetes Prevention Program Research Group
Original Research

ABSTRACT

BACKGROUND

Recommendations for diabetes prevention in patients with prediabetes include lifestyle modification and metformin. However, the significance of early weight loss and glucose measurements when monitoring response to these proven interventions is unknown.

OBJECTIVE

To quantify the relationship between early measures of weight and glucose and subsequent diabetes in patients undergoing diabetes prevention interventions.

DESIGN

Analysis of results from a randomized controlled trial in 27 academic medical centers in the United States.

PARTICIPANTS/INTERVENTIONS

3,041 adults with hyperglycemia randomized to lifestyle (n = 1,018), metformin (n = 1,036), or placebo (n = 987) with complete follow-up in The Diabetes Prevention Program.

MAIN MEASURES

Independent variables were weight loss at 6 and 12 months; fasting glucose (FG) at 6 months; hemoglobin A1c (HbA1c) at 6 months; and post-load glucose at 12 months. The main outcome was time to diabetes diagnosis.

KEY RESULTS

After 6 months, 604 participants developed diabetes in the lifestyle (n = 140), metformin (n = 206), and placebo (n = 258) arms over 2.7 years. In the lifestyle arm, 6-month weight loss predicted decreased diabetes risk in a graded fashion: adjusted HR (95 % CI) 0.65 (0.35–1.22), 0.62 (0.33–1.18), 0.46 (0.24–0.87), 0.34 (0.18–0.64), and 0.15 (0.07–0.30) for 0–<3 %, 3–<5 %, 5–<7 %, 7–<10 %, and ≥10 % weight loss, respectively (reference: weight gain). Attainment of optimal 6-month FG and HbA1c and 12-month post-load glucose predicted >60 % lower diabetes risk across arms. We found a significant interaction between 6-month weight loss and FG in the lifestyle arm (P = 0.038).

CONCLUSION

Weight and glucose at 6 and 12 months strongly predict lower subsequent diabetes risk with a lifestyle intervention; lower FG predicts lower risk even with substantial weight loss. Early reduction in glycemia is a stronger predictor of future diabetes risk than weight loss for metformin. We offer the first evidence to guide clinicians in making interval management decisions for high-risk patients undertaking measures to prevent diabetes.

KEY WORDS

diabetes prevention diabetes risk type 2 diabetes 

Supplementary material

11606_2013_2548_MOESM1_ESM.doc (59 kb)
ESM 1(DOC 59 kb)
11606_2013_2548_MOESM2_ESM.doc (67 kb)
Appendix Table 1Distribution of Baseline Characteristics Based on Inclusion in Study Sample (DOC 67 kb)

REFERENCES

  1. 1.
    Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393–403.CrossRefGoogle Scholar
  2. 2.
    Knowler WC, Fowler SE, Hamman RF, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374(9702):1677–86. Epub 2009/11/03.PubMedCrossRefGoogle Scholar
  3. 3.
    Hamman RF, Wing RR, Edelstein SL, et al. Effect of weight loss with lifestyle intervention on risk of diabetes. Diabetes Care. 2006;29(9):2102–7. Epub 2006/08/29.PubMedCrossRefGoogle Scholar
  4. 4.
    Lachin JM, Christophi CA, Edelstein SL, et al. Factors associated with diabetes onset during metformin versus placebo therapy in the Diabetes Prevention Program. Diabetes. 2007;56(4):1153–9. Epub 2007/03/31.PubMedCrossRefGoogle Scholar
  5. 5.
    Standards of medical care in diabetes—2012. Diabetes Care. 2012;35(Suppl 1):S11–63. Epub 2012/01/04.Google Scholar
  6. 6.
    The Diabetes Prevention Program. Design and methods for a clinical trial in the prevention of type 2 diabetes. Diabetes Care. 1999;22(4):623–34. Epub 1999/04/06.CrossRefGoogle Scholar
  7. 7.
    American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care. 2011;34(Supplement 1):S11–61.CrossRefGoogle Scholar
  8. 8.
    Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 1997;20(7):1183–97. Epub 1997/07/01.Google Scholar
  9. 9.
    Lin D, Wei L. The robust inference for the cox proportional hazards model. J Am Stat Assoc. 1989;1074–78.Google Scholar
  10. 10.
    Wing RR, Hamman RF, Bray GA, et al. Achieving weight and activity goals among Diabetes Prevention Program lifestyle participants. Obes Res. 2004;12(9):1426–34. Epub 2004/10/16.PubMedCrossRefGoogle Scholar
  11. 11.
    Svetkey LP, Stevens VJ, Brantley PJ, et al. Comparison of strategies for sustaining weight loss: the weight loss maintenance randomized controlled trial. JAMA. 2008;299(10):1139–48.PubMedCrossRefGoogle Scholar
  12. 12.
    Sarwer DB, von Sydow Green A, Vetter ML, Wadden TA. Behavior therapy for obesity: where are we now? Curr Opin Endocrinol Diabetes Obes. 2009;16(5):347–52. Epub 2009/07/23.PubMedCrossRefGoogle Scholar
  13. 13.
    Perreault L, Kahn SE, Christophi CA, Knowler WC, Hamman RF. Regression from pre-diabetes to normal glucose regulation in the Diabetes Prevention Program. Diabetes Care. 2009;32(9):1583–8. Epub 2009/07/10.PubMedCrossRefGoogle Scholar
  14. 14.
    Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344(18):1343–50.PubMedCrossRefGoogle Scholar
  15. 15.
    Pan XR, Li GW, Hu YH, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. 1997;20(Journal Article):537–44.PubMedCrossRefGoogle Scholar
  16. 16.
    Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V. The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia. 2006;49(2):289–97. Epub 2006/01/05.PubMedCrossRefGoogle Scholar

Copyright information

© Society of General Internal Medicine 2013

Authors and Affiliations

  • Nisa M. Maruthur
    • 1
    • 2
  • Yong Ma
    • 3
  • Linda M. Delahanty
    • 4
  • Julie A. Nelson
    • 5
  • Vanita Aroda
    • 6
  • Neil H. White
    • 7
  • David Marrero
    • 8
    • 9
  • Frederick L. Brancati
    • 1
    • 2
    • 10
  • Jeanne M. Clark
    • 1
    • 2
    • 10
  • for the Diabetes Prevention Program Research Group
  1. 1.The Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Welch Center for Prevention, Epidemiology, and Clinical ResearchBaltimoreUSA
  3. 3.George Washington UniversityRockvilleUSA
  4. 4.Massachusetts General Hospital Diabetes Research Center and Harvard Medical SchoolBostonUSA
  5. 5.Southwest American Indian Center-Arizona, NIDDKPhoenixUSA
  6. 6.Department of MedicineUniversity of CaliforniaSan DiegoUSA
  7. 7.Washington University School of MedicineSt. LouisUSA
  8. 8.Regenstrief Institute for Health CareIndianapolisUSA
  9. 9.Diabetes Translational Research CenterIndiana University School of MedicineIndianapolisUSA
  10. 10.The Johns Hopkins University Bloomberg School of Public HealthBaltimoreUSA

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