Research paperIndices of insulin resistance and glucotoxicity are not associated with bipolar disorder or major depressive disorder, but are differently associated with inflammatory, oxidative and nitrosative biomarkers

- Mood disorders are not associated with changes in insulin resistance or glucotoxicity.
- Insulin resistance (IR) is positively associated with protein oxidation.
- IR is negatively associated with haptoglobin levels and nitric oxide (NO) production.
- β cell function is inversely associated with haptoglobin levels and NO production.
- Inflammation and nitro-oxidative stress modulate IR and β cell function.

BackgroundInsulin resistance (IR) is a key factor in diabetes mellitus, metabolic syndrome (MetS) and obesity and may occur in mood disorders and tobacco use disorder (TUD), where disturbances of immune-inflammatory, oxidative and nitrosative stress (IO&NS) pathways are important shared pathophysiological pathways.MethodsThis study aimed to a) examine IR and β-cell function as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity and β cell function (HOMA-B) and glucotoxicity (conceptualized as increased glucose levels versus lowered HOMA-B values) in 74 participants with major depressive disorder (MDD) and bipolar disorder, with and or without MetS and TUD, versus 46 healthy controls, and b) whether IR is associated with IO&NS biomarkers, including nitric oxide metabolites (NOx), lipid hydroperoxides (LOOH), plasma advanced oxidation protein products (AOPP), C-reactive protein (CRP), haptoglobin (Hp) and uric acid.ResultsMood disorders are not associated with changes in IR or glucotoxicity, although the number of mood episodes may increase IR. 47.8% of the variance in HOMA-IR is explained by AOPP and body mass index (BMI, both positively) and NOx, Hp and TUD (all inversely). 43.2% of the variance in HOMA-B is explained by NOx, Hp and age (all inversely associated) and higher BMI and sex. The glucotoxic index is strongly associated with NOx, Hp and BMI (positively), male gender and lower education.LimitationsThis is a cross-sectional study and therefore we cannot draw firm conclusions on causal associations.ConclusionsActivated IO&NS pathways (especially increased Hp and NOx) increase glucotoxicity and exert very complex effects modulating IR. Mood disorders are not associated with increased IR.