In a major prospective analysis of more than 370,000 UK adults, researchers have found that elevated insulin resistance (IR)-related indices—especially those combining triglyceride-glucose levels with waist measurements—are strongly associated with the development and progression of cardiometabolic multimorbidity (CMM), defined as the coexistence of two or more major cardiometabolic diseases such as type 2 diabetes (T2D), coronary heart disease (CHD), and stroke. The results were published in Cardiovascular Diabetology.

Using data from the UK Biobank and a median follow-up of nearly 14 years, the study examined five IR-related indices, including the triglyceride-glucose (TyG) index and composite metrics involving body mass index (BMI), waist circumference (WC), and waist-height ratio (WHtR). During the follow-up, 1.3% of the 374,274 initially healthy participants developed CMM.
The results showed that each 1-standard deviation increase in IR indices was linked to significantly increased CMM risk. The TyG-WC (HR: 1.54) and TyG-WHtR (HR: 1.52) indices were the strongest predictors compared to other markers like TyG-BMI (HR 1.42) and the TG/HDL-C ratio (HR 1.19). 

IR indices influenced both CMM incidence and disease progression. Individuals had a higher likelihood of transitioning from being disease-free to developing T2D first. Among those with CHD, the risk of progressing to full CMM was markedly higher in those with higher IR markers.

Liver function, renal function, and inflammatory markers were found as mediators in nearly one-third of the associations between IR indices and CMM.