Insulin Resistance in HIV-Patients: Causes and Consequences

Abstract

Here we review how immune activation and insulin resistance contribute to the metabolic alterations observed in HIV-infected patients, and how these alterations increase the risk of developing CVD. The introduction and evolution of antiretroviral drugs over the past 25 years has completely changed the clinical prognosis of HIV-infected patients. The deaths of these individuals are now related to atherosclerotic CVDs, rather than from the viral infection itself. However, HIV infection, cART, and intestinal microbiota are associated with immune activation and insulin resistance, which can lead to the development of a variety of diseases and disorders, especially with regards to CVDs. The increase in LPS and proinflammatory cytokines circulating levels and intracellular mechanisms activate serine kinases, resulting in insulin receptor substrate-1 (IRS-1) serine phosphorylation and consequently a down regulation in insulin signaling. While lifestyle modifications and pharmaceutical interventions can be employed to treat these altered metabolic functions, the mechanisms involved in the development of these chronic complications remain largely unresolved. The elucidation and understanding of these mechanisms will give rise to new classes of drugs that will further improve the quality of life of HIV-infected patients, over the age of 50.

Insulin Resistance and Glucose Intolerance in HIV Infected Children on Antiretroviral Therapy at Lubango Pediatric Hospital - Angola

“…Most children had a fasting blood sugar of 5.6-6.9 have Insulin Resistance (p 0.027) ( Table 5). In the bivariate analysis, children who had history of diabetes in the family were significantly more likely to or it treatment [10]. The primary objective of this facility-based study was to determine the pattern of Insulin Resistance and glucose intolerance among HIV infected children on ART being followed up at lubango pediatric Hospital.…”

Immune Activation, Inflammation, and Non-AIDS Co-Morbidities in HIV-Infected Patients under Long-Term ART

“…PLWH with MetS showed higher levels of aspartate transaminase, triglycerides, and blood pressure, and lower levels of cholesterol HDL compared to patients without MetS. The immune activation caused by HIV infection and ART and the increasing levels of circulating pro-inflammatory cytokines and LPS were shown to also be the cause of insulin resistance (IR), nowadays considered a chronic inflammatory disease in PLWH, and consequently a high concentration of blood glucose and the development of hyperinsulinemia and DM [101,102,103]. Chronic immune activation and high levels of pro-inflammatory cytokines in several tissues (liver, adipose tissue, gastrointestinal tract, muscle) are also associated with lipid alterations and IR [78].…”

Good Fences Make Good Neighbors: Human Immunodeficiency Virus and Vascular Disease

“…These conditions contribute significantly to CVD risk in PWH [83, 84]. Chronic inflammation (with circulating pro-inflammatory cytokines) can predispose to insulin resistance through the phosphorylation of insulin receptor substrate-1 [85, 86]. Antiretroviral therapy is associated with lipid- abnormalities and dysregulation of glucose-processing pathways, which are independently associated with an increased risk of type 2 diabetes mellitus [85].…”

“…Chronic inflammation (with circulating pro-inflammatory cytokines) can predispose to insulin resistance through the phosphorylation of insulin receptor substrate-1 [85, 86]. Antiretroviral therapy is associated with lipid- abnormalities and dysregulation of glucose-processing pathways, which are independently associated with an increased risk of type 2 diabetes mellitus [85]. Hypertension in PWH is common and a number of potential pathogenic mechanisms have been identified, including lipodystrophy, a pro-inflammatory state associated with the secretion of cytokines and adipokines, and renal disease [87].…”