Explaining the high rate of progression from prediabetes to type 2 diabetes in China

We read with interest the report on the China Diabetes Prevention Program (CDPP) by Lihui Zhang and colleagues,1Zhang L Zhang Y Shen S et al.Safety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing progression to diabetes in a Chinese population with impaired glucose regulation: a multicentre, open-label, randomised controlled trial.Lancet Diabetes Endocrinol. 2023; 11: 567-577Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar a 2-year open-label randomised controlled trial of metformin plus lifestyle intervention versus lifestyle intervention alone in individuals with impaired glucose regulation in China. Impaired glucose regulation was defined as impaired fasting glycaemia or impaired glucose tolerance, or both. In this study, the risk of new-onset type 2 diabetes was reduced by 17% in the metformin plus lifestyle intervention group versus the lifestyle intervention alone group. Despite this encouraging result, we are concerned by the high incidence of diabetes in both groups (metformin plus lifestyle intervention: 17·27 per 100 person-years; lifestyle intervention alone: 19·83 per 100 person-years) over a median follow-up of 2·4 years. This incidence exceeded that in the control group in the Da Qing study (15·7 per 100 person-years),2Pan 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: 537-544Crossref PubMed Scopus (3430) Google Scholar the US Diabetes Prevention Program (11·0 per 100 person-years),3Knowler WC Barrett-Connor E Fowler SE et al.Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med. 2002; 346: 393-403Crossref PubMed Scopus (15190) Google Scholar or the Finnish Diabetes Prevention Study (7·8 cases per 100 person-years).4Tuomilehto J Lindström 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: 1343-1350Crossref PubMed Scopus (8593) Google Scholar The authors attributed this higher diabetes incidence to a higher baseline BMI in the CDPP cohort compared with the Da Qing cohort (26·3 kg/m2 vs 25·8 kg/m2), although, in our opinion, this difference of less than 1 kg is unlikely to be a main factor. The mean age in the CDPP cohort was higher, although the incidence of diabetes in those younger than 45 years (18·86 per 100 person-years in the lifestyle intervention group) also exceeded the incidence in the Da Qing cohort. Other possibilities include the differences in the definition of diabetes outcome. The Da Qing study defined diabetes based on values in two oral glucose tolerance tests repeated within 7–14 days2Pan 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: 537-544Crossref PubMed Scopus (3430) Google Scholar using a higher fasting plasma glucose threshold of 7·8 mmol/L. It would be interesting to clarify the proportions of those who progressed to diabetes as defined by fasting plasma glucose versus 2-h glucose criteria, and whether these were assessed by repeated glucose measurements, in each group. Additionally, all participants were recruited from hospital clinic settings. Apart from hypertension, prevalence of coexisting conditions, such as dyslipidaemia, obstructive sleep apnoea, or non-alcoholic fatty liver disease, might also contribute to the high conversion rate compared with the community-recruited Da Qing cohort. The intensity and content of the dietary component of lifestyle intervention also differed substantially from previous trials. It is noteworthy that, unlike in previous trials that emphasised overall calorie reduction and balanced meals,3Knowler WC Barrett-Connor E Fowler SE et al.Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med. 2002; 346: 393-403Crossref PubMed Scopus (15190) Google Scholar in the CDPP, participants were instructed to reduce carbohydrate intake (by 50 g per meal if BMI >25 kg/m2), which might be compensated for by increasing fat and protein intake. Data on daily calorie and macronutrient intake would be informative. Similar to previous studies,3Knowler WC Barrett-Connor E Fowler SE et al.Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med. 2002; 346: 393-403Crossref PubMed Scopus (15190) Google Scholar, 5Ramachandran 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: 289-297Crossref PubMed Scopus (1392) Google Scholar in the CDPP study1Zhang L Zhang Y Shen S et al.Safety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing progression to diabetes in a Chinese population with impaired glucose regulation: a multicentre, open-label, randomised controlled trial.Lancet Diabetes Endocrinol. 2023; 11: 567-577Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar participants with obesity and young age benefited most from metformin plus lifestyle intervention. However, 126 (15·2%) of 831 participants in the metformin plus lifestyle intervention group experienced gastrointestinal side-effects and 21 (2·5%) participants in this group discontinued treatment due to adverse events, calling for strategies to improve metformin tolerability in Chinese people with impaired glucose regulation. In summary, Zhang and colleagues1Zhang L Zhang Y Shen S et al.Safety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing progression to diabetes in a Chinese population with impaired glucose regulation: a multicentre, open-label, randomised controlled trial.Lancet Diabetes Endocrinol. 2023; 11: 567-577Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar highlight the urgent need to control the accelerating diabetes epidemic in China and implement effective interventions beyond lifestyle intervention and metformin. EC and JC have received institutional research support from Merck KGaA. JC has received speakers' fees from Merck KGaA. All other authors declare no competing interests. Safety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing progression to diabetes in a Chinese population with impaired glucose regulation: a multicentre, open-label, randomised controlled trialMetformin plus lifestyle intervention further reduced the risk of developing diabetes than lifestyle intervention alone in Chinese people with impaired glucose regulation, showing additional benefits of combined intervention in preventing progression to diabetes without new safety concerns. Full-Text PDF Explaining the high rate of progression from prediabetes to type 2 diabetes in China – Authors' replyIn our recent Article,1 we reported that metformin plus lifestyle intervention was more effective than the lifestyle intervention alone in preventing progression to diabetes in participants with impaired glucose regulation. Our study1 confirmed the high rate of progression from prediabetes to type 2 diabetes reported in the Da Qing diabetes prevention study.2 Although we realise the urgency of implementing powerful diabetes prevention in China, we are pleased that our findings have attracted attention; first from the author of the Comment, Clifford J Bailey,3 and now from Elaine Chow and colleagues in a Correspondence. Full-Text PDF