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

Jul 16, 2017Journal of affective disorders

Insulin resistance and sugar-related damage are not linked to bipolar or major depression but relate differently to inflammation and cell stress markers

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Abstract

47.8% of the variance in insulin resistance is explained by certain biomarkers and body mass index.

Mood disorders do not appear to be linked with increased insulin resistance or glucotoxicity.
The number of mood episodes may contribute to higher insulin resistance.
Increased levels of advanced oxidation protein products and body mass index are positively associated with insulin resistance.
Nitric oxide metabolites and haptoglobin are inversely associated with insulin resistance and β-cell function.
Glucotoxicity is positively correlated with nitric oxide metabolites, haptoglobin, body mass index, male gender, and lower education.

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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.

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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

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