Predictors of insulin resistance in first year of therapy

Mark Mascolini for

Studying 120 people during their first 48 weeks of antiretroviral therapy, clinicians from Malaga and Seville turned up two baseline predictors of insulin resistance – HCV infection and treatment with indinavir – and two associated factors that evolved during antiretroviral therapy – higher weight and a diagnosis of lipodystrophy [1].

These clinicians tracked 120 people at two HIV clinics who started their first antiretrovirals between June 2002 through June 2003 and stayed with the same regimen for 48 weeks. Everyone had 95% or better antiretroviral adherence, no one had diabetes, and no one took other drugs that could tip a person’s glucose-insulin balance.

Ninety-one cohort members (76%) were men, 69 (66%) smoked, 43 (36%) had HCV infection, and 16 (21%) had a family history of diabetes. Before these people started antiretrovirals their CD4 count averaged 222 cells/mm3 (interquartile range 64 to 313 cells/mm3) and their viral load averaged 5.39 log (about 245,500) copies/mL.

After 48 weeks of therapy, 81% had an undetectable viral load, while the average CD4 count climbed 182 cells/mm3. Most metabolic variables measured strayed significantly in the wrong direction in these 48 weeks. Average total cholesterol climbed from 154 to 191 mg/dL, and menacing low-density lipoprotein cholesterol from 93 to 114 mg/dL (P = 0.0001 for both changes).

The group’s average glucose rose from 90 to 95 mg/dL (P = 0.0001) and insulin from 7.24 to 10.15 microUI/mL (P = 0.002). Average body mass index edged up from 23.1 to a still-normal 24.5 kg/m2. After 48 weeks of antiretroviral therapy, 15 people (13%) had insulin resistance, defined as a HOMA score above 3.8.

Multivariate analysis settled on four factors that independently raised the risk of insulin resistance (Table 1). These researchers did not explain how they defined lipodystrophy, one of the two 48-week variables linked to insulin resistance.

Table 1: Predictors of insulin resistance in multivariate analysis (n=120)

Predictive factors Beta Coef. 95% CI p-value
HCV+ (%) 4.6 (1.002-21.8) 0.049
Indinavir 8.3 (1.7-40.6) 0.008
Higher BMI (kg/m2) 0.83 (0.72-0.95) 0.008
Lipodystrophy 5.0 (1.17-29.9) 0.031

Higher triglycerides correlated with insulin resistance in the univariate analysis, but smoking, family history of diabetes, and baseline glucose did not. People who ended up with insulin resistance had a higher pretreatment insulin reading in the univariate analysis (9.2 versus 6.8 microUI/mL in people who stayed free of insulin resistance, P = 0.01). Insulin resistance developed in none of 19 people who took a nevirapine-based regimen.



Palacios R, Merchante N, Macias J, et al. Prospective study of glucose metabolism in antiretroviral naive HIV-infected patients: incidence of insulin resistance at 48 weeks of HAART. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy. December 16-29, 2005. Washington, DC. Abstract H-344.

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