Indices 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

Kamila Landucci Bonifácio, Décio Sabbatini Barbosa, Estefânia Gastaldello Moreira, Carine Coneglian de Farias, Luciana Higachi, Alissana Ester Iakmiu Camargo, Janaina Favaro Soares, Heber Odebrecht Vargas, Sandra Odebrecht Vargas Nunes, Michael Berk, Seetal Dodd, Michael Maes

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7 Citations (Scopus)


Background Insulin 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. Methods This 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. Results Mood 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. Limitations This is a cross-sectional study and therefore we cannot draw firm conclusions on causal associations. Conclusions Activated 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.

Original languageEnglish
Pages (from-to)185-194
Number of pages10
JournalJournal of Affective Disorders
Publication statusPublished - Nov 2017
Externally publishedYes


  • Bipolar disorder
  • Depression
  • Inflammation
  • Insulin resistance
  • Mania
  • Oxidative stress

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