S. Rubtchinsky

TL;DR: Interventions that delay or prevent the onset of type 2 diabetes in overweight/obese subjects with dysglycemia who are at risk for diabetes do not reduce the development of diabetic retinopathy for up to 20 years.

TL;DR: A well-phenotyped, densely genotyped, multi-ancestry resource to study gene–drug interactions, uncover novel variation associated with response to common glucose-lowering medications and provide insight into mechanisms of action of type 2 diabetes-related variation is presented.

TL;DR: The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) 3rd expert report highlights up-to-date Cancer Prevention Recommendations that may reduce burdens of many chronic diseases, including diabetes as mentioned in this paper .

Abstract: BACKGROUND In the US Diabetes Prevention Program (DPP), a 3-year randomised clinical trial in 3234 adults with prediabetes, type 2 diabetes incidence was reduced by 58% with intensive lifestyle intervention (ILS) and by 31% with metformin, compared with placebo. We sought to assess the long-term effects and potential heterogeneity of treatment effects over approximately 21 years of follow-up. METHODS The DPP trial was continued with protocol modifications as the DPP Outcomes Study (DPPOS). In the DPPOS, placebo was discontinued, metformin (850 mg twice a day as tolerated) was continued after unmasking, and group-based booster intervention classes were offered to the ILS group twice a year; additionally, all participants were offered group-based lifestyle intervention four times a year. The prespecified primary outcome during DPP and DPPOS was diabetes incidence defined by American Diabetes Association criteria. The DPPOS protocol specified continued diabetes incidence as an outcome; Feb 23, 2020, was chosen as the closing date for the present analysis, as a date prior to the COVID-19 pandemic, which caused major disruptions in clinic visits and complicated longitudinal data analyses. We assessed long-term persistence of intervention effects on diabetes incidence, and heterogeneity of effects in subgroups defined by baseline diabetes risk factors. Follow-up is reported for the combined study from July 31, 1996, to Feb 23, 2020, and analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, NCT00004992 (DPP) and NCT00038727 (DPPOS); follow-up is ongoing but the trial is closed to enrolment except for previous DPP participants. FINDINGS 3195 participants originally enrolled in the DPP were included in the present analyses. This population comprised 2171 (67·9%) female participants and 1024 (32·1%) male participants, with a mean baseline age of 50·6 years (SD 10·7). Individual follow-up times ranged from 0·2 to 23·2 years (median 8·0 years [IQR 3·0 to 18·0]); remaining numbers at risk decreased sharply after 21 years because of administrative censoring and thus follow-up was considered to represent a 21-year period. During follow-up, compared with placebo, diabetes incidence rate was reduced in the original ILS group (hazard ratio [HR] 0·76 [95% CI 0·68 to 0·85], rate difference [RD] -1·59 cases [95% CI -2·25 to -0·93] per 100 person-years) and in the original metformin group (HR 0·83 [0·74 to 0·93], RD -1·17 [-1·85 to -0·49]), with corresponding increases in median diabetes-free survival of 3·5 years and 2·5 years, and mean diabetes-free survival of 2·0 years (95% CI 1·2 to 2·8) and 1·2 years (0·4 to 2·0), respectively. The diabetes cumulative incidence curves separated early, especially in the first 3 years, with lower incidence rates in the metformin and ILS groups than in the placebo group. The metformin and ILS curves progressively converged with longer follow-up. The overall treatment effects appeared to result from large early effects during the DPP. Absolute intervention effects, measured as RDs versus placebo, were greater with ILS in participants with higher values for baseline fasting glucose, HbA1c, and multivariable clinical and physiological risk indices, and with metformin in younger participants. INTERPRETATION The large initial intervention effects seen in the DPP trial were followed by sustained reductions in cumulative diabetes incidence for 21 years. Intervention effects were heterogeneous according to some baseline variables. These findings could guide precision interventions to help address the current type 2 diabetes epidemic. FUNDING US National Institute of Diabetes and Digestive and Kidney Diseases and other agencies. TRANSLATION For the Spanish translation of the abstract see Supplementary Materials section.