Social isolation, loneliness, and incident type 2 diabetes mellitus: results from two large prospective cohorts in Europe and East Asia and Mendelian randomizationResearch in context

Summary: Background: Social isolation and loneliness pose significant public health challenges globally. The objective of this study is to investigate the association between social isolation, loneliness, and the risk of type 2 diabetes mellitus (T2DM). Methods: 423,503 UK adults from the UK Biobank (UKB) and 13,800 Chinese adults from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. The exposures of interest were social isolation and loneliness. Social isolation was evaluated based on the number of household members, frequency of social activities, contact with others, and marriage status (CHARLS only). Loneliness was evaluated by the subjective feeling of loneliness and the willingness to confide in others (UKB only). The primary endpoint was incident T2DM. The two-sample Mendelian randomization (MR) analysis was based on the genome-wide association studies of UKB (n = 463,010) and the European Bioinformatics Institute (n = 655,666). Findings: The UKB cohort study documented 15,072 T2DM cases during a mean follow-up of 13.5 years, and the CHARLS cohort study recorded 1,249 T2DM cases during a mean follow-up of 5.8 years. Social isolation and loneliness showed significant associations with an elevated risk of T2DM in both UKB (social isolation [most vs least]: HR 1.17, 95% CI 1.11–1.23; loneliness [yes vs no]: HR 1.21, 95% CI 1.13–1.30) and CHARLS cohorts (social isolation [yes vs no]: HR 1.22, 95% CI 1.06–1.40; loneliness [yes vs no]: HR 1.21, 95% CI 1.07–1.36). These associations remained significant after accounting for baseline glucose status and genetic susceptibility to T2DM. Two-sample MR analyses determined that feeling lonely (OR 1.04, 95% CI 1.02–1.06) and engaging in fewer leisure/social activities (OR 1.03, 95% CI 1.02–1.05) were associated with increased T2DM risk, whereas more contact with friends or family (OR 0.99, 95% CI 0.98–0.99) was associated with reduced T2DM risk. Interpretation: Social isolation and loneliness are each associated with an elevated risk of T2DM, with MR analyses suggesting potential causal links. These associations remain significant after considering genetic susceptibility to T2DM. The findings highlight the importance of promoting initiatives to address social isolation and loneliness as part of T2DM prevention strategies. Funding: CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-008) and National Natural Science Foundation of China (No. 72103187)

Comparison of Estimated LDL Cholesterol Equations with Direct Measurement in Patients with Angiographically Confirmed Coronary Artery Disease

Background and aims: Our goals in the study were to (1) quantify the discordance in LDL-C levels between equations (the Friedewald, Sampson, and Martin/Hopkins equations) and compare them with direct LDL-C (dLDL-C); and (2) explore the proportion of misclassified patients by calculated LDL-C using these three different equations. Methods: A total of 30,349 consecutive patients with angiographically confirmed coronary artery disease (CAD) were prospectively enrolled. Concordance was defined as if the LDL-C was <1.8 mmol/L with each pairwise comparison of LDL-C equations. Estimated LDL-C that fell into the same category as dLDL-C at the following levels: <1.4, 1.4 to 1.7, 1.8 to 2.5, 2.6 to 2.9, and ≥3.0 mmol/L was considered to have been correctly categorized. Results: The concordance was 96.3% (Sampson vs. Martin/Hopkins), 95.0% (Friedewald vs. Sampson), and 91.4% (Friedewald vs. Martin/Hopkins), respectively. This proportion fell to 82.4% in those with hypertriglyceridemia (TG ≥ 1.7 mmol/L). With an accurate classification rate of 73.6%, the Martin/Hopkins equation outperformed the Sampson equation (69.5%) and the Friedewald equation (59.3%) by a wide margin. Conclusions: Comparing it to the validated Martin/Hopkins equation, the Friedewald equation produced the lowest levels of LDL-C, followed by the Sampson equation. In the classification of LDL-C, the Martin/Hopkins equation has also been shown to be more accurate. There is a significant difference between the equations and the direct measurement method, which may lead to overtreatment or undertreatment

A long noncoding RNA–microRNA expression signature predicts metastatic signature in pheochromocytomas and paragangliomas

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