Hypertriglyceridemia is a Dose-dependent Risk Factor for Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

Luca Havelda^1,2Eszter Ágnes Szalai^1,3Mahmoud Obeidat¹Dalma Dobszai^1,4Dániel Sándor Veres^1,5Tamás Kói¹Emese Sipter^1,6Szilárd Váncsa^1,2Péter Jenő Hegyi^1,2Maria Bucur¹Anita Molnár¹Klára Lara Vámossy^1,2Péter Hegyi^1,2,7,8Andrea Szentesi^1,7*

• ¹Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
• ²Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
• ³Department of Restorative Dentistry and Endodontics, Semmelweis University, Budapest, Hungary
• ⁴Institute for Translational Medicine, Medical School, University of Pécs,, Pécs, Hungary
• ⁵Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary
• ⁶Department of Internal Medicine and Haematology, Semmelweis University, Budapest, Hungary
• ⁷Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
• ⁸Translational Pancreatology Research Group, Interdisciplinary Centre of Excellence for Research Development and Innovation, University of Szeged, Szeged, Hungary

Introduction The prevalence of type 2 diabetes (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 also has a high prevalence. We aimed to investigate the dose-dependent effect of HTG on the development of T2DM. Methods We carried out a systematic search in three databases (MEDLINE, Embase, and CENTRAL) on November 9, 2023. We investigated adult population with different triglyceride levels (exposure). The outcome of interest was the development of T2DM. Pooled hazard (HR), odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI) 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). Results We 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 the development of T2DM. Those who had their TG levels between 1.7-2.3 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 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]). Conclusion HTG 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.