Key result
Idiopathic intracranial hypertension is linked to ~48% higher insulin resistance beyond obesity alone.
Why the study?
Idiopathic intracranial hypertension is associated with metabolic dysregulation, androgen excess, and increased cardiovascular morbidity, motivating evaluation of systemic and adipose-specific metabolic determinants of the phenotype.
Case-Control (n=140)
No
Absolute Event Rate: 1.97% vs 1.33%
p-value: p=0.0030
Idiopathic intracranial hypertension is characterized by systemic and adipose-specific metabolic dysregulation, including insulin and leptin resistance, in excess of what is driven by obesity alone.
Supports viewing IIH as a metabolic disorder with adipose dysfunction beyond obesity; leaves open whether targeting insulin/leptin resistance modifies outcomes.
BACKGROUNDIdiopathic intracranial hypertension (IIH) is a condition predominantly affecting obese women of reproductive age. Recent evidence suggests that IIH is a disease of metabolic dysregulation, androgen excess, and an increased risk of cardiovascular morbidity. Here we evaluate systemic and adipose specific metabolic determinants of the IIH phenotype.METHODSIn fasted, matched IIH (n = 97) and control (n = 43) patients, we assessed glucose and insulin homeostasis and leptin levels. Body composition was assessed along with an interrogation of adipose tissue function via nuclear magnetic resonance metabolomics and RNA sequencing in paired omental and subcutaneous biopsies in a case-control study.RESULTSWe demonstrate an insulin- and leptin-resistant phenotype in IIH in excess of that driven by obesity. Adiposity in IIH is preferentially centripetal and is associated with increased disease activity and insulin resistance. IIH adipocytes appear transcriptionally and metabolically primed toward depot-specific lipogenesis.CONCLUSIONThese data show that IIH is a metabolic disorder in which adipose tissue dysfunction is a feature of the disease. Managing IIH as a metabolic disease could reduce disease morbidity and improve cardiovascular outcomes.FUNDINGThis study was supported by the UK NIHR (NIHR-CS-011-028), the UK Medical Research Council (MR/K015184/1), Diabetes UK, Wellcome Trust (104612/Z/14/Z), the Sir Jules Thorn Award, and the Midlands Neuroscience Teaching and Research Fund.
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Westgate et al. (2021) conducted a case-control in Idiopathic intracranial hypertension (n=140). Idiopathic intracranial hypertension vs. Obese controls matched for BMI and sex was evaluated on HOMA2-IR (Insulin Resistance) (p=0.0030). Idiopathic intracranial hypertension is associated with an insulin- and leptin-resistant phenotype in excess of that driven by obesity, including significantly higher HOMA2-IR (1.97 vs 1.33) compared to matched controls.
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