September/October 2016 

Can the ratio of triglycerides to good cholesterol help predict diabetes?

Researchers in Italy have analysed health-related information collected from HIV-positive people between 1997 and 2013, focusing on new cases of type 2 diabetes. They found that rates of diabetes in HIV-positive people were not significantly different from those in HIV-negative people in northern Italy. However, they did find that a ratio of two fatty substances in the blood—triglycerides and good cholesterol (HDL-C)—was statistically linked to an increased risk for developing type 2 diabetes. Participants who had extensive liver injury (scarring of the liver) due to chronic viral hepatitis were also at increased risk for diabetes. Due to issues with the study’s design its findings should be treated as interesting and preliminary until they can be confirmed.

Study details

Researchers with the ICONA foundation have been collecting health-related information from HIV-positive people for the past two decades. The latest analysis of this data focused on 3,546 participants, as researchers sought to help healthcare professionals find ways to predict which of their patients would be at high risk for developing type 2 diabetes.

Here is the average profile of participants upon entering the study:

  • 74% men, 26% women
  • age – 38 years
  • duration of HIV infection – one and a half years
  • CD4+ count – 286 cells/mm3
  • HIV viral load – 63,000 copies/mL
  • ratio of triglycerides to HDL – 2.8

Researchers also used an indirect but useful assessment of liver injury called FIB-4. This is a score calculated using figures derived from a person’s age, the levels of liver enzymes ALT and AST, and platelets in the blood. FIB-4 values greater than 3.25 suggest extensive scarring of the liver. This problem can occur as a result of chronic infection with hepatitis B or C viruses.


Over the course of the study, 80 participants developed type 2 diabetes (herein after simply referred to as diabetes).

According to the researchers, analysis of a ratio of triglycerides to HDL that was high (greater than 4.5) was associated with a heightened risk for developing diabetes. Other factors associated with an increased risk for diabetes in this study were as follows:

  • older age
  • body mass index (BMI, a relative assessment of fatness) greater than 30
  • use of the combination of two older anti-HIV drugs, d4T (stavudine, Zerit) and 3TC (lamivudine)
  • use of the anti-HIV drugs atazanavir (Reyataz) and ritonavir
  • FIB-4 scores greater than 3.25

Bear in mind

This study, which looked back upon previously collected data, is retrospective in design. While relatively inexpensive, such studies can sometimes arrive at inadvertently biased conclusions. However, it is likely that most of the findings from the present analysis are probably correct in their conclusions. Retrospective analyses are a first step in exploring an idea and their results can be used to seek funding for a study of a more robust statistical design. Indeed, the present study’s main finding about using the ratio of triglycerides to HDL to help predict diabetes risk is interesting but requires confirmation in a study of a more robust statistical design.

The finding of an association between an increased risk for diabetes and the use of d4T and 3TC is probably due to the presence of d4T in a regimen. The drug 3TC is generally safe and in well-designed studies has not been associated with an increased risk for diabetes. On the other hand, d4T is an older drug that is seldom used in high-income countries today because it has many toxicities. Also, some studies have found an association between exposure to d4T and an increased risk of diabetes.

The link between the use of atazanavir (in combination with ritonavir) and an increased risk for diabetes is puzzling. There is no evidence from previous studies that atazanavir causes diabetes. Furthermore, compared to earlier protease inhibitors, atazanavir was found to be generally neutral when it comes to changes in cholesterol and blood sugar. It is possible that because atazanavir does not generally have an unfavourable impact on cholesterol and blood sugar levels, it may have been preferentially prescribed to patients who were already at elevated risk for diabetes, hence the apparent association found in this study.


HIV and cardiovascular disease – CATIE fact sheet

—Sean R. Hosein


  1. Squillace N, Lorenzini P, Lapadula G, et al. Triglyceride/HDL ratio and its impact on the risk of diabetes mellitus development during ART. Journal of Antimicrobial Chemotherapy. 2016 Sep;71(9):2663-9.
  2. Noor MA, Flint OP, Maa JF, et al. Effects of atazanavir/ritonavir and lopinavir/ritonavir on glucose uptake and insulin sensitivity: demonstrable differences in vitro and clinically. AIDS. 2006 Sep 11;20(14):1813-21.
  3. Karamchand S, Leisegang R, Schomaker M, et al. Risk factors for incident diabetes in a cohort taking first-line nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy. Medicine. 2016 Mar;95(9):e2844.
  4. Riyaten P, Salvadori N, Traisathit P, et al. New-onset diabetes and antiretroviral treatments in HIV-infected adults in Thailand. Journal of Acquired Immune Deficiency Syndromes. 2015 Aug 1;69(4):453-9.
  5. Tien PC, Schneider MF, Cole SR, et al. Antiretroviral therapy exposure and insulin resistance in the Women's Interagency HIV Study. Journal of Acquired Immune Deficiency Syndromes. 2008 Dec 1;49(4):369-76.