Determinants of glucose metabolism and the role of NPY in the progression of insulin resistance in chronic migraine

Abstract

Background Chronic migraine has a well-documented association with increased insulin resistance and metabolic syndrome. The hypothalamus may play a role in the progression of insulin resistance in chronic migraine through the regulation of orexigenic peptides such as neuropeptide Y. Insulin resistance may lead to increased risk of future type 2 diabetes mellitus in patients with chronic migraine, which is more likely to occur if other pathogenetic defects of type 2 diabetes mellitus, such as impaired pancreatic β-cell functions and defects in intestinal glucagon-like peptide-1 secretion after meals. We studied the relationship of fasting neuropeptide Y with insulin resistance, β-cell function, and glucagon-like peptide-1 secretion in non-obese female chronic migraine patients. We also aimed to investigate glucose-stimulated insulin and glucagon-like peptide-1 secretions as early pathogenetic mechanisms responsible for the development of carbohydrate intolerance. Methods In this cross-sectional controlled study, 83 non-obese female migraine patients of reproductive age categorized as having episodic migraine or chronic migraine were included. The control group consisted of 36 healthy females. We studied glucose-stimulated insulin and glucagon-like peptide-1 secretion during a 75 g oral glucose tolerance test. We investigated the relationship of neuropeptide Y levels with insulin resistance and β-cell insulin secretion functions. Results Fasting glucose levels were significantly higher in migraine patients. Plasma glucose and insulin levels during the oral glucose tolerance test were otherwise similar in chronic migraine, episodic migraine and controls. Patients with chronic migraine were more insulin resistant than episodic migraine or controls ( p = 0.048). Glucagon-like peptide-1 levels both at fasting and two hours after glucose intake were similar in chronic migraine, episodic migraine, and controls. Neuropeptide Y levels were higher in migraineurs. In chronic migraine, neuropeptide Y was positively correlated with fasting glucagon-like peptide-1 levels (r = 0.57, p = 0.04), but there was no correlation with insulin resistance (r = 0.49, p = 0.09) or β-cell function (r = 0.50, p = 0.07). Discussion Non-obese premenopausal female patients with chronic migraine have higher insulin resistance, but normal β-cell function is to compensate for the increased insulin demand during fasting and after glucose intake. Increased fasting neuropeptide Y levels in migraine may be a factor leading to increased insulin resistance by specific alterations in energy intake and activation of the sympathoadrenal system.

Serotonin and Neuropeptides in Blood From Episodic and Chronic Migraine and Cluster Headache Patients in Case‐Control and Case‐Crossover Settings: A Systematic Review and Meta‐Analysis

“…This might also be the case for plasma and serum, for example, we observed a significant increase in the NPY serum level but a significant decrease in the NPY plasma level in migraine patients compared with CTRL (Table 3). 38,88,89 Complete metabolomic profiling of primary headache patients and use of the serum metabolome database might reveal useful knowledge in the discussion of unique subgroup profiles, for example, defined by multiple strata 90 . In the future, investigation of plasma, serum, and whole blood in the same study might aid in the understanding of differential signaling molecule profiles in primary headache patients.…”

The metabolic face of migraine — from pathophysiology to treatment

“…Multiple studies have provided evidence for an associa tion between migraine and insulin resistance (reviewed elsewhere 84 ), although this association was not seen at all in one study 85 and only in women with migraine in another 86 . One study has shown that β cell function, and therefore insulin production, is normal in patients with migraine but that the degree of insulin resistance correlates with disease severity 87 .…”

Insulin Resistance is Associated with Central Pain in Patients with Fibromyalgia

“…Evolving work in rheumatology and chronic pain has recognized IR in many pain conditions, including migraine, neuropathic pain, and multiple other conditions leading to chronic pain (9)(10)(11)(12)(13). Also, IR is associated with dementia in patients with Parkinson's disease and cognitive impairment with fibromyalgia (FM) (14,15).…”