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Summer 2024

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‘Precision Prevention' is Imperative in the Realm of Diabetes Prevention

Sathish Thirunavukkarasu MBBS, DFM, MPH, PhD1,2; Biswadeep Dhar, PhD, MEd, MS3 - the Diabetes SIG

‘Precision Prevention’ is crucial in the domain of diabetes prevention, extending the principles of precision medicine to the prevention of diseases.1 The objective of precision prevention is to identify high-risk individuals for certain diseases and providing them with interventions tailored specifically to their unique characteristics. This acknowledges the variability in disease susceptibility, and response to preventive measures among individuals, emphasizing that ‘one-size-fits-all’ approaches may not be suitable for everyone.2-4 Hence, ‘precision prevention’ works best when delivered with the right intervention, to the right individuals, and at the right time.

Prediabetes encompasses three distinct phenotypes: isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), and IFG plus IGT.5 These phenotypes differ in prevalence, risk factors, underlying pathophysiological abnormalities, and progression rates to diabetes.6-9 However, global diabetes prevention efforts often overlook these distinctions. This oversight is evident in guidelines that extend findings from landmark diabetes prevention trials, primarily conducted among individuals with IGT, to other prediabetes phenotypes.10-14

Recent evidence indicates that conventional lifestyle interventions, such as adopting to healthy eating habits, increasing moderate-intensity physical activity to 150 minutes or more per week, and aiming for a weight loss of 5-7%, do not uniformly reduce diabetes incidence across prediabetes phenotypes.2,3,15 The effectiveness varies, with the greatest reduction observed in individuals with IFG plus IGT, followed by those with i-IGT, while proving ineffective in those with i-IFG. A 2023 meta-analysis of individual-participant data from four lifestyle-based trials demonstrated that, after a median follow-up of 2.5 years, the hazard ratio for diabetes incidence was 0.51 (95% CI 0.38, 0.68) in IFG plus IGT, 0.65 (95% CI 0.44, 0.96) in i-IGT, and 0.97 (95% CI 0.66, 1.44) in i-IFG, with a significant interaction (p=0.01).15

The ineffectiveness of conventional lifestyle interventions in reducing diabetes incidence among individuals with i-IFG can be primarily attributed to their relatively lower risk of developing type 2 diabetes as compared to those with other phenotypes, as well as the specific pathophysiological abnormalities inherent to this condition.6,16 These abnormalities include severe hepatic insulin resistance and impaired early-phase insulin secretion with near-normal skeletal muscle insulin resistance.16 This contrasts with IGT, which is characterized by severe skeletal muscle insulin resistance with minimal hepatic insulin resistance and impairment of both early- and late-phase insulin secretion.16 While conventional lifestyle interventions can improve skeletal muscle insulin resistance and ß-cell function among individuals with prediabetes,17,18 their ability to mitigate hepatic insulin resistance appears to be comparatively less prominent.3

These observations underscore the importance of evaluating the efficacy of alternative lifestyle interventions tailored to the specific pathophysiological defects present in individuals with i-IFG. Approaches such as low-calorie diets and high-intensity interval training have shown to improve hepatic insulin resistance and early-phase insulin secretion in individuals with type 2 diabetes.19-22 Hence, it is plausible that these interventions may also be effective in addressing these abnormalities in i-IFG, given the shared pathophysiological features with type 2 diabetes.16 However, definitive randomized controlled trials are necessary to evaluate the efficacy of these interventions.

Overall, precision prevention holds the promise of revolutionizing preventive medicine by enabling more targeted and effective interventions that can prevent or delay the onset of type 2 diabetes in high-risk individuals.

Acknowledgement

ST was supported by the Woodruff Health Sciences Center Synergy Awards and the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) under Award Number UL1TR002378. ST was also partially supported by grant #75D30120P0742 from the Centers for Disease Control and Prevention (CDC) Atlanta.

Affiliations

  1. Department of Family and Preventive Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
  2. Emory Global Diabetes Research Center, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA
  3. Department of Human Ecology, University of Maryland, Eastern Shore, Princess Anne, MD, 21853, USA

References

  1. Gillman MW, Hammond RA. Precision Treatment and Precision Prevention: Integrating "Below and Above the Skin". JAMA Pediatr 2016; 170(1): 9-10.
  2. Campbell MD, Sathish T, Zimmet PZ, et al. Benefit of lifestyle-based T2DM prevention is influenced by prediabetes phenotype. Nat Rev Endocrinol 2020; 16(7): 395-400.
  3. Chakkalakal RJ, Galaviz KI, Sathish T, Shah MK, Narayan KMV. Test and Treat for Prediabetes: A Review of the Health Effects of Prediabetes and the Role of Screening and Prevention. Annu Rev Public Health 2023: doi: 10.1146/annurev-publhealth-060222-23417.
  4. Thirunavukkarasu S. “One-size-doesn't-fit-all” approach to diabetes prevention through lifestyle interventions. Diabetes Epidemiology and Management 2024; 14: 100199.
  5. American Diabetes Association. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47(Suppl 1): S20-S42.
  6. Richter B, Hemmingsen B, Metzendorf MI, Takwoingi Y. Development of type 2 diabetes mellitus in people with intermediate hyperglycaemia. Cochrane Database Syst Rev 2018; 10(10): Cd012661.
  7. Thirunavukkarasu S. Comment on Rooney et al. Global Prevalence of Prediabetes. Diabetes Care 2023;46:1388–1394. Diabetes Care 2023; 46(12): e219. doi: 10.2337/dc23-1539.
  8. Yip WCY, Sequeira IR, Plank LD, Poppitt SD. Prevalence of Pre-Diabetes across Ethnicities: A Review of Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT) for Classification of Dysglycaemia. Nutrients 2017; 9(11): 1273.
  9. Rooney MR, Fang M, Ogurtsova K, et al. Global Prevalence of Prediabetes. Diabetes Care 2023; 46(7): 1388-94.
  10. American Diabetes Association. 3. Prevention or Delay of Diabetes and Associated Comorbidities: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47(Suppl 1): S43-S51.
  11. Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2020; 41(2): 255-323.
  12. National Institute for Health and Care Excellence. Type 2 diabetes: prevention in people at high risk. https://www.nice.org.uk/guidance/ph38 (accessed 28 Feb 2024).
  13. Olujide OP, Olujide ME, Leonardi-Bee J, Chattopadhyay K. Content and quality of clinical practice guidelines for the management of type 2 diabetes in India: A systematic review. Endocrinol Diabetes Metab 2023; 6(2): e405.
  14. Makkar BM, Kumar K, Saboo B, Agarwal S, Group. OboRC. RSSDI Clinical Practice Recommendations for the Management of Type 2 Diabetes Mellitus 2022. Int J Diabetes Dev Ctries 2022; 42(Suppl 1): 1-143.
  15. Sathish T, Khunti K, Narayan KMV, et al. Effect of Conventional Lifestyle Interventions on Type 2 Diabetes Incidence by Glucose-Defined Prediabetes Phenotype: An Individual Participant Data Meta-analysis of Randomized Controlled Trials. Diabetes Care 2023; 46(11): 1903-7.
  16. Abdul-Ghani MA, Tripathy D, DeFronzo RA. Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes Care 2006; 29(5): 1130-9.
  17. Uusitupa M, Lindi V, Louheranta A, Salopuro T, Lindström J, Tuomilehto J. Long-term improvement in insulin sensitivity by changing lifestyles of people with impaired glucose tolerance: 4-year results from the Finnish Diabetes Prevention Study. Diabetes 2003; 52(10): 2532-8.
  18. Snehalatha C, Mary S, Selvam S, et al. Changes in insulin secretion and insulin sensitivity in relation to the glycemic outcomes in subjects with impaired glucose tolerance in the Indian Diabetes Prevention Programme-1 (IDPP-1). Diabetes Care 2009; 32(10): 1796-801.
  19. Taylor R, Al-Mrabeh A, Zhyzhneuskaya S, et al. Remission of Human Type 2 Diabetes Requires Decrease in Liver and Pancreas Fat Content but Is Dependent upon Capacity for β Cell Recovery. Cell Metab 2018; 28(4): 547-56.e3.
  20. Petersen KF, Dufour S, Befroy D, Lehrke M, Hendler RE, Shulman GI. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 2005; 54(3): 603-8.
  21. Kim JY. Optimal Diet Strategies for Weight Loss and Weight Loss Maintenance. J Obes Metab Syndr 2021; 30(1): 20-31.
  22. Thirunavukkarasu S, Taylor R, Khunti K, et al. Low-calorie diets for people with isolated impaired fasting glucose. Commun Med (Lond) 2024; 4(1): 35.