Sex Differences in the Global Prevalence of Nonsuicidal Self-Injury in Adolescents: A Meta-Analysis.

Importance: Nonsuicidal self-injury (NSSI) is a strong predictor of suicide attempts. The prevalence of NSSI has been increasing among female adolescents in North America and Europe, but less is known about trends in other geographical regions. Objective: To examine sex differences in the prevalence of NSSI among adolescents within and between geographical regions. Data Sources: MEDLINE and PsycINFO were searched using the keywords adolescents, self-injury, sex factors, and synonyms for articles published in English between January 1, 2000, and May 10, 2022. Study Selection: Studies were included if they presented original data (any study design), included adolescents aged 10 to 19 years, reported results stratified by sex, and explicitly defined self-injury as behaviors occurring without suicidal intent. Data Extraction and Synthesis: This meta-analysis was registered with PROSPERO and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Articles were assessed for quality by 2 independent coders (F.M. and J.A.). A random-effects model was used to calculate prevalence. Data were analyzed from July 2022 to April 2023. Main Outcomes and Measures: The prevalence of NSSI in male and female adolescents within and between regions was the main outcome. Odds ratios (OR) with 95% CIs were calculated for community samples. Results: Eight hundred and two studies were screened, and 38 were included (266 491 participants). Across 17 countries, the pooled prevalence of NSSI was 17.7% (female:male OR, 1.60; 95% CI, 1.29-1.98). NSSI was twice as prevalent among female adolescents compared with male adolescents in North America (OR, 2.49; 95% CI, 2.16-2.86) and Europe (OR, 2.08; 95% CI, 1.69-2.58), but not in Asia (OR, 1.00; 95% CI, 0.71-1.41). Conclusions and Relevance: In this meta-analysis of sex differences in global prevalence of NSSI, the female predominance of NSSI observed among adolescents in North America and Europe aligned with rising rates of suicide in these populations. The comparable prevalence of NSSI among male and female adolescents in Asia also aligned with the lower male-to-female suicide ratio compared with other countries. More research is needed to characterize regional (and potentially cultural) sex differences among adolescents with NSSI to prevent and treat the behavior and to understand the possible interplay with corresponding regional trends in suicide.

Antidiabetic effects of cis-9, trans-11-conjugated linoleic acid may be mediated via anti-inflammatory effects in white adipose tissue.

Adipose tissue may be the source of insulin desensitizing proinflammatory molecules that predispose to insulin resistance. This study investigated whether dietary fatty acids could attenuate the proinflammatory insulin-resistant state in obese adipose tissue. The potential antidiabetic effect of cis-9, trans-11-conjugated linoleic acid (c9,t11-CLA) was determined, focusing on the molecular markers of insulin sensitivity and inflammation in adipose tissue of ob/ob C57BL-6 mice. Feeding a c9,t11-CLA-enriched diet reduced fasting glucose (P < 0.05), insulin (P < 0.05), and triacylglycerol concentrations (P < 0.01) and increased adipose tissue plasma membrane GLUT4 (P < 0.05) and insulin receptor (P < 0.05) expression compared with the control linoleic acid-enriched diet. Interestingly, after the c9,t11-CLA diet, adipose tissue macrophage infiltration was less, with marked downregulation of several inflammatory markers in adipose tissue, including reduced tumor necrosis factor-alpha and CD68 mRNA (P < 0.05), nuclear factor-kappaB (NF-kappaB) p65 expression (P < 0.01), NF-kappaB DNA binding (P < 0.01), and NF-kappaB p65, p50, c-Rel, p52, and RelB transcriptional activity (P < 0.01). To define whether these observations were direct effects of the nutrient intervention, complimentary cell culture studies showed that c9,t11-CLA inhibited tumor necrosis factor-alpha-induced downregulation of insulin receptor substrate 1 and GLUT4 mRNA expression and promoted insulin-stimulated glucose transport in 3T3-L1 adipocytes compared with linoleic acid. This study suggests that altering fatty acid composition may attenuate the proinflammatory state in adipose tissue that predisposes to obesity-induced insulin resistance.

Conjugated linoleic acid supplementation reduces peripheral blood mononuclear cell interleukin-2 production in healthy middle-aged males.

Conjugated linoleic acid (CLA) refers to geometric and positional isomers of linoleic acid. Animal studies have shown that CLA modulates the immune system and suggest that it may have a therapeutic role in inflammatory disorders. This double-blind placebo-controlled intervention trial investigated the effects of CLA supplementation on indices of immunity relating to cardiovascular disease (CVD) in a cohort of healthy middle-aged male volunteers. Subjects were randomly assigned to supplement their diet with 2.2 g 50:50 isomeric blend of cis 9, trans 11 (c9, t11)-CLA and trans 10, cis 12 (t10, c12)-CLA or placebo daily for 8 weeks. Interleukin (IL) 2, IL-10 and tumour necrosis factor (TNF) alpha were measured in the supernatant of cultured unstimulated and concanavalin A (Con A)-stimulated peripheral blood mononuclear cells (PBMC) by ELISA. Serum IL-6 and plasma CRP were measured by ELISA and plasma fibrinogen by automated clotting assay. Gene expression was investigated by real-time RT-PCR. CLA supplementation significantly reduced Con A-stimulated PBMC IL-2 secretion (37.1%; P=.02). CLA supplementation had no significant effect on transcription of IL-2. CLA supplementation had no direct significant effects on PBMC TNFalpha or IL-10 secretion. Other inflammatory markers associated with CVD, including IL-6, CRP and fibrinogen, were not affected by CLA supplementation. This study showed that CLA supplementation reduced PBMC IL-2 secretion from Con A-stimulated PBMC but lacked effect on other markers of the human inflammatory response.

Eicosapentaenoic acid and 3,10 dithia stearic acid inhibit the desaturation of trans-vaccenic acid into cis-9, trans-11-conjugated linoleic acid through different pathways in Caco-2 and T84 cells.

Stearoyl-CoA desaturase (SCD) is a key enzyme that determines the composition and metabolic fate of ingested fatty acids, in particular the conversion of trans-vaccenic acid (TVA) to conjugated linoleic acid (CLA). The present study addressed the hypothesis that intestinal TVA absorption and biotransformation into CLA can be modulated by EPA and 3,10-dithia stearic acid (DSA) via altered SCD mRNA levels and desaturation indices (cis-9, trans-11-CLA:TVA and oleic acid:stearic acid ratios) in Caco-2 and T84 cells, two well-established in vitro models of the human intestinal epithelium. The study determined the effect of acute (3 h with 0.3 mm-EPA or 0.3 mm-DSA) and acute-on-chronic (1 week with 0.03 mm-EPA or -DSA, followed by respectively, 0.3 mm-EPA or -DSA for 3 h) treatments. In both cell lines, acute EPA treatment did not alter SCD desaturation indices, whereas the acute-on-chronic treatment affected these surrogate markers of SCD activity. This was associated with reduced sterol regulatory-element binding protein-1c and SCD mRNA levels. In contrast, acute and acute-on-chronic DSA treatments significantly reduced SCD desaturation indices without affecting SCD mRNA levels in Caco-2 cells. The present study on intestinal cells shows that the conversion rate of TVA to c9, t11-CLA is affected by other fatty acids present in the diet such as EPA, confirming previous observations in hepatic and mammary cell models.

Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus.

BACKGROUND: Some animal studies have suggested that conjugated linoleic acid (CLA) supplementation may have therapeutic potential with respect to insulin sensitivity and lipid metabolism, which are important cardiovascular disease (CVD) risk factors associated with type 2 diabetes mellitus. OBJECTIVE: We investigated the effect of CLA supplementation on markers of glucose and insulin metabolism, lipoprotein metabolism, and inflammatory markers of CVD in subjects with type 2 diabetes. DESIGN: The study was a randomized, double-blind, placebo-controlled trial. Thirty-two subjects with stable, diet-controlled type 2 diabetes received CLA (3.0 g/d; 50:50 blend of cis-9,trans-11 CLA and trans-10,cis-12 CLA) or control for 8 wk. A 3-h 75-g oral-glucose-tolerance test was performed, and fasting plasma lipid concentrations and inflammatory markers were measured before and after the intervention. RESULTS: CLA supplementation significantly increased fasting glucose concentrations (6.3%; P < 0.05) and reduced insulin sensitivity as measured by homeostasis model assessment, oral glucose insulin sensitivity, and the insulin sensitivity index (composite) (P = 0.05). Total HDL-cholesterol concentrations increased by 8% (P < 0.05), which was due to a significant increase in HDL(2)-cholesterol concentrations (P < 0.05). The ratio of LDL to HDL cholesterol was significantly reduced (P < 0.01). CLA supplementation reduced fibrinogen concentrations (P < 0.01) but had no effect on the inflammatory markers of CVD (C-reactive protein and interleukin 6). CONCLUSIONS: CLA supplementation had an adverse effect on insulin and glucose metabolism. Whereas CLA had positive effects on HDL metabolism and fibrinogen, a therapeutic nutrient should not be associated with potentially adverse effects on other clinical markers of type 2 diabetes.