Aims/hypothesis: People with type 2 diabetes are heterogeneous in their disease trajectory, with some progressing more quickly to insulin initiation than others. Although classical biomarkers such as age, HbA_1c and diabetes duration are associated with glycaemic progression, it is unclear how well such variables predict insulin initiation or requirement and whether newly identified markers have added predictive value. Methods: In two prospective cohort studies as part of IMI-RHAPSODY, we investigated whether clinical variables and three types of molecular markers (metabolites, lipids, proteins) can predict time to insulin requirement using different machine learning approaches (lasso, ridge, GRridge, random forest). Clinical variables included age, sex, HbA_1c, HDL-cholesterol and C-peptide. Models were run with unpenalised clinical variables (i.e. always included in the model without weights) or penalised clinical variables, or without clinical variables. Model development was performed in one cohort and the model was applied in a second cohort. Model performance was evaluated using Harrel’s C statistic. Results: Of the 585 individuals from the Hoorn Diabetes Care System (DCS) cohort, 69 required insulin during follow-up (1.0–11.4 years); of the 571 individuals in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) cohort, 175 required insulin during follow-up (0.3–11.8 years). Overall, the clinical variables and proteins were selected in the different models most often, followed by the metabolites. The most frequently selected clinical variables were HbA_1c (18 of the 36 models, 50%), age (15 models, 41.2%) and C-peptide (15 models, 41.2%). Base models (age, sex, BMI, HbA_1c) including only clinical variables performed moderately in both the DCS discovery cohort (C statistic 0.71 [95% CI 0.64, 0.79]) and the GoDARTS replication cohort (C 0.71 [95% CI 0.69, 0.75]). A more extensive model including HDL-cholesterol and C-peptide performed better in both cohorts (DCS, C 0.74 [95% CI 0.67, 0.81]; GoDARTS, C 0.73 [95% CI 0.69, 0.77]). Two proteins, lactadherin and proto-oncogene tyrosine-protein kinase receptor, were most consistently selected and slightly improved model performance. Conclusions/interpretation: Using machine learning approaches, we show that insulin requirement risk can be modestly well predicted by predominantly clinical variables. Inclusion of molecular markers improves the prognostic performance beyond that of clinical variables by up to 5%. Such prognostic models could be useful for identifying people with diabetes at high risk of progressing quickly to treatment intensification. Data availability: Summary statistics of lipidomic, proteomic and metabolomic data are available from a Shiny dashboard at https://rhapdata-app.vital-it.ch. Graphical Abstract: (Figure presented.).

Background The COVID-19 pandemic led to mental health fallout in the US; yet research about mental health and COVID-19 primarily rely on samples that may overlook variance in regional mental health. Indeed, between-city comparisons of mental health decline in the US may provide further insight into how the pandemic is disproportionately affecting at-risk groups. Purpose This study leverages social media and COVID-19-city infection data to measure the longitudinal (January 22- July 31, 2020) mental health effects of the COVID-19 pandemic in 20 metropolitan areas. Methods We used longitudinal VADER sentiment analysis of Twitter timelines (January-July 2020) for cohorts in 20 metropolitan areas to examine mood changes over time. We then conducted simple and multivariate Ordinary Least Squares (OLS) regressions to examine the relationship between COVID-19 infection city data, population, population density, and city demographics on sentiment across those 20 cities. Results Longitudinal sentiment tracking showed mood declines over time. The univariate OLS regression highlighted a negative linear relationship between COVID-19 city data and online sentiment (β = -.017). Residing in predominantly white cities had a protective effect against COVID-19 driven negative mood (β = .0629, p < .001). Discussion Our results reveal that metropolitan areas with larger communities of color experienced a greater subjective well-being decline than predominantly white cities, which we attribute to clinical and socioeconomic correlates that place communities of color at greater risk of COVID-19. Conclusion The COVID-19 pandemic is a driver of declining US mood in 20 metropolitan cities. Other factors, including social unrest and local demographics, may compound and exacerbate mental health outlook in racially diverse cities.

Individuals with depression are prone to maladaptive patterns of thinking, known as cognitive distortions, whereby they think about themselves, the world, and the future in overly negative and inaccurate ways. These distortions are associated with marked changes in an individual’s mood, behavior, and language. We hypothesize that societies can undergo similar changes in their collective psychology that are reflected in historical records of language use. Here, we investigate the prevalence of textual markers of cognitive distortions in over 14 million books for the past 125 y and observe a surge of their prevalence since the 1980s, to levels exceeding those of the Great Depression and both World Wars. This pattern does not seem to be driven by changes in word meaning, publishing and writing standards, or the Google Books sample. Our results suggest a recent societal shift toward language associated with cognitive distortions and internalizing disorders.