AUTHOR=Havelda Luca , Szalai Eszter Ágnes , Obeidat Mahmoud , Dobszai Dalma , Veres Dániel Sándor , Kói Tamás , Sipter Emese , Váncsa Szilárd , Hegyi Péter Jenő , Bucur Maria , Molnár Anita , Vámossy Klára Lara , Hegyi Péter , Szentesi Andrea TITLE=Hypertriglyceridemia is a dose-dependent risk factor for type 2 diabetes mellitus: a systematic review and meta-analysis JOURNAL=Frontiers in Endocrinology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1710007 DOI=10.3389/fendo.2025.1710007 ISSN=1664-2392 ABSTRACT=IntroductionThe prevalence of type 2 diabetes mellitus (T2DM) has more than doubled in the past 20 years. Most T2DM cases are preventable if risk factors are eliminated early. Hypertriglyceridemia (HTG) is also a potential but modifiable risk factor, and has a high prevalence as well. We aimed to investigate the dose-dependent effect of HTG on the development of T2DM.MethodsWe carried out a systematic search in three databases (MEDLINE, Embase, and CENTRAL) on 9 November 2023. We investigated an adult population with different triglyceride levels (exposure). The outcome of interest was the development of T2DM. Pooled hazard ratio (HR), odds ratio (OR), and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Risk of bias was assessed with the Quality In Prognosis Studies (QUIPS) tool. The protocol was registered in PROSPERO (CRD42023471288).ResultsWe identified 31,098 articles and included 101 in our meta-analysis. We found that people with HTG had more than a 1.5-fold higher risk (HR: 1.73 [1.31; 2.29]) of developing T2DM. Those who had their TG levels between 1.7 and 2.3 mmol/L had a 42% higher risk (HR: 1.42 [1.13; 1.79]), while those with TG levels above 2.3 mmol/L had an even higher risk for T2DM (HR: 1.82 [1.18; 2.87]) compared with patients with TG levels below 1.7 mmol/L. When investigating the hypertriglyceridemic waist phenotype, we found that only those with increased waist circumference had a higher risk in both sex groups among the different phenotype groups (female: HR: 2.86 [1.59; 5.14], male: HR: 3.31 [1.57; 7.27]).ConclusionHTG is a dose-dependent risk factor for T2DM. Elevated waist circumference may have an even more important role in the development of T2DM than HTG.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023471288.