Lifestyle-based precision medicine for reducing diabetes incidence in people with prediabetes

Abstract

Randomized controlled trials (RCTs) have shown that lifestyle interventions focused on improving physical activity and diet quality and weight loss are highly effective in reducing diabetes incidence in people with prediabetes [ [1] Uusitupa M. Khan T.A. Viguiliouk E. Kahleova H. Rivellese A.A. Hermansen K. et al. Prevention of type 2 diabetes by lifestyle changes: a systematic review and meta-analysis. Nutrients. 2019; 11: 2611 Crossref PubMed Scopus (81) Google Scholar ]. The intervention targets in these RCTs mainly were achieving at least 5% weight loss, ≥150 min of moderate-intense physical activity, and <30% of daily calorie intake from fat (called as “conventional intervention” hereafter) [ [1] Uusitupa M. Khan T.A. Viguiliouk E. Kahleova H. Rivellese A.A. Hermansen K. et al. Prevention of type 2 diabetes by lifestyle changes: a systematic review and meta-analysis. Nutrients. 2019; 11: 2611 Crossref PubMed Scopus (81) Google Scholar ]. However, such interventions are not efficacious for everyone with prediabetes, resulting in a significant proportion of people developing diabetes over time [ [2] Gong Q. Zhang P. Wang J. Ma J. An Y. Chen Y. et al. Morbidity and mortality after lifestyle intervention for people with impaired glucose tolerance: 30-year results of the Da Qing Diabetes Prevention Outcome Study. Lancet Diabetes Endocrinol. 2019; 7: 452-461 Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar ]. For example, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are two prediabetes phenotypes with different progression rates to diabetes (lower in IFG) and pathophysiology. While IGT is characterized by progressive β-cell dysfunction and severe peripheral insulin resistance, stationary β-cell dysfunction and markedly reduced hepatic insulin sensitivity are seen in IFG [ [3] Campbell M.D. Sathish T. Zimmet P.Z. Thankappan K.R. Oldenburg B. Owens D.R. et al. Benefit of lifestyle-based T2DM prevention is influenced by prediabetes phenotype. Nat. Rev. Endocrinol. 2020; 16: 395-400 Crossref PubMed Scopus (26) Google Scholar ]. Subgroup analyses of some RCTs suggest that the efficacious conventional lifestyle intervention in those with IGT (with or without IFG) may not be effective in people with IFG in the absence of IGT [ [3] Campbell M.D. Sathish T. Zimmet P.Z. Thankappan K.R. Oldenburg B. Owens D.R. et al. Benefit of lifestyle-based T2DM prevention is influenced by prediabetes phenotype. Nat. Rev. Endocrinol. 2020; 16: 395-400 Crossref PubMed Scopus (26) Google Scholar , [4] Sathish T. Tapp R.J. Shaw J.E. Do lifestyle interventions reduce diabetes incidence in people with isolated impaired fasting glucose. Diabetes Obes. Metab. 2021; 23: 2827-2828 Crossref PubMed Scopus (1) Google Scholar ]. This may be because of the difference in diabetes risk between these two phenotypes and that the conventional lifestyle intervention primarily targets the pathophysiology of IGT rather than that of IFG [ [3] Campbell M.D. Sathish T. Zimmet P.Z. Thankappan K.R. Oldenburg B. Owens D.R. et al. Benefit of lifestyle-based T2DM prevention is influenced by prediabetes phenotype. Nat. Rev. Endocrinol. 2020; 16: 395-400 Crossref PubMed Scopus (26) Google Scholar , [4] Sathish T. Tapp R.J. Shaw J.E. Do lifestyle interventions reduce diabetes incidence in people with isolated impaired fasting glucose. Diabetes Obes. Metab. 2021; 23: 2827-2828 Crossref PubMed Scopus (1) Google Scholar ].