For decades, the conversation around multiple sclerosis has centered on nerves and immunity. New research reveals a third, unexpected player in this complex drama—and it begins with how our bodies process food.
When we think of multiple sclerosis (MS), we typically picture an autoimmune disorder where the body attacks the protective sheath around nerve fibers. When we consider insulin, we think of blood sugar regulation and diabetes. These two conditions appear to occupy entirely separate medical universes.
Yet groundbreaking research is revealing an unexpected connection that could transform how we understand, treat, and potentially prevent the progression of this neurological condition 1 5 .
The emerging story of hyperinsulinemia in MS patients represents a paradigm shift in neuroscience—one that suggests metabolic health may be intimately intertwined with brain health in ways we never imagined.
To appreciate this connection, we must first understand both players individually.
Multiple sclerosis is a chronic inflammatory disease where the immune system mistakenly attacks the protective myelin sheath covering nerve fibers in the central nervous system 4 . This damage disrupts communication between the brain and body, leading to symptoms that can include fatigue, vision problems, muscle weakness, cognitive changes, and difficulty with coordination.
The disease typically begins in young adulthood, between ages 20 and 40, and affects women more commonly than men 4 . While various disease-modifying treatments can reduce relapses and delay progression, there remains no cure.
Hyperinsulinemia refers to abnormally high levels of insulin circulating in the bloodstream 2 . This condition often develops as a compensatory mechanism when cells become resistant to insulin's effects—a state known as insulin resistance. The pancreas produces more and more insulin to overcome this resistance and maintain normal blood sugar levels.
Key Insight: What makes hyperinsulinemia particularly insidious is that blood glucose measurements may appear "normal" because glucose is being kept in check by sky-high insulin 2 . This means standard diabetes screening tests can miss the problem entirely, allowing metabolic dysfunction to fly under the radar for years.
The first clues emerged from a seminal 2015 study published in Metabolic Brain Disease that specifically examined glucose metabolism in newly diagnosed MS patients 1 . The research team designed an elegant experiment to compare insulin sensitivity between MS patients and healthy controls.
The study enrolled 19 MS patients and 19 age, sex, and body mass index-matched healthy controls. Importantly, the MS patients were newly diagnosed, untreated, and had low disability scores, suggesting their metabolic changes weren't simply consequences of advanced disease or medication side effects 1 .
All participants underwent an oral glucose tolerance test (oGTT), which involves drinking a glucose solution and having blood drawn at regular intervals to measure how the body processes the sugar load. Researchers analyzed not just glucose and insulin, but also lactate, GLP-1 (a gut hormone involved in insulin secretion), and various inflammatory markers and adipokines (signaling proteins from fat tissue) 1 .
The findings revealed something remarkable: while MS patients and healthy controls had nearly identical blood glucose levels, both fasting and after the glucose challenge, their insulin responses were dramatically different 1 .
| Metabolic Parameter | MS Patients | Healthy Controls | P-value |
|---|---|---|---|
| Fasting glucose (mmol/L) | 5.2 ± 0.3 | 5.0 ± 0.4 | 0.05 |
| Fasting insulin | Elevated | Normal | <0.01 |
| ISI (Matsuda) | 6.95 ± 3.44 | 10.60 ± 4.81 | 0.011 |
| ISI (Cederholm) | 49.9 ± 15.3 | 61.3 ± 16.3 | 0.032 |
The MS patients showed significantly increased insulin response to the oral glucose load, with insulin sensitivity indices markedly lower than healthy controls 1 . This pattern—normal glucose with elevated insulin—is the classic signature of hyperinsulinemia and early insulin resistance.
Perhaps equally important was what the researchers did not find: there were no significant differences in inflammatory markers, adipokines, or lipid parameters between the groups 1 . This suggests the hyperinsulinemia wasn't simply a byproduct of chronic inflammation or physical inactivity, pointing instead toward a more fundamental metabolic disturbance in MS.
The discovery of hyperinsulinemia in MS patients raises a crucial question: why would insulin resistance matter for a neurological condition? The answer lies in insulin's surprisingly diverse roles beyond blood sugar regulation.
"The single-minded focus on glucose has eclipsed what may be an even more important part of metabolic health: insulin," notes an article on chronic hyperinsulinemia 2 . "If you're used to thinking of insulin solely as a 'blood sugar hormone,' hang on to your hat. Insulin has many other roles, almost to the point that lowering blood sugar is one of the least impressive things it does."
Indeed, insulin plays multiple critical roles in brain health:
When insulin resistance develops, these functions may be compromised even while blood sugar remains normal.
Since that initial 2015 study, additional research has strengthened the connection between insulin resistance and MS.
A 2023 study examined the relationship between insulin resistance and cognitive dysfunction in 74 relapsing-remitting MS patients 3 . The findings were striking: 37.8% of MS patients had insulin resistance, and 67.56% showed cognitive decline 3 . More significantly, those with insulin resistance performed worse on tests of verbal memory, spatial comprehension, and executive function 3 .
| Cognitive Test | MS Patients with IR | MS Patients without IR | Significance |
|---|---|---|---|
| California Verbal Learning Test | Lower scores | Higher scores | Significant |
| Delayed Free Recall | Lower scores | Higher scores | Significant |
| Judgment of Line Orientation | Lower scores | Higher scores | Significant |
| Controlled Oral Word Association | Lower scores | Higher scores | Significant |
Most recently, a 2024 comprehensive meta-analysis pooled data from 18 studies published between 2012 and 2022, confirming that people with MS have significantly higher levels of both insulin resistance and circulating insulin compared to those without MS 5 . The analysis found this association was even stronger in studies that included mixed types of MS (both relapsing and progressive forms) compared to those focusing solely on relapsing-remitting MS 5 .
| Analysis Type | Standardized Mean Difference | Interpretation |
|---|---|---|
| Insulin Resistance (HOMA-IR) | 0.78 | Moderate to large effect |
| Circulating Insulin | 0.72 | Moderate to large effect |
| Mixed MS Types | 1.09 | Large effect |
| RRMS Only | 0.59 | Medium effect |
Understanding this relationship requires specialized tools and methodologies. Here are key components of the researcher's toolkit in this emerging field:
| Tool/Technique | Primary Function | Application in MS Research |
|---|---|---|
| Oral Glucose Tolerance Test (oGTT) | Measures body's response to glucose load | Identifies hyperinsulinemia despite normal glucose 1 |
| Homeostatic Model Assessment (HOMA-IR) | Calculates insulin resistance from fasting levels | Quantifies insulin resistance in MS cohorts 3 |
| Enzyme-Linked Immunosorbent Assay (ELISA) | Measures specific proteins in biological samples | Detects insulin, adipokines, inflammatory markers 1 |
| Minimal Assessment of Cognitive Function in MS (MACFIMS) | Evaluates cognitive function in MS patients | Correlates insulin resistance with cognitive decline 3 |
| Magnetic Resonance Imaging (MRI) | Visualizes brain structure and lesions | Assesses MS disease burden and cerebral atrophy 4 |
The growing evidence linking hyperinsulinemia to MS opens several promising avenues:
Current findings suggest that standard glucose tests alone are insufficient to detect metabolic dysfunction in MS patients. Incorporating insulin measurements and insulin resistance assessment could provide earlier warning of metabolic issues that may influence disease progression 2 .
The recognition of hyperinsulinemia in MS suggests potential benefits from insulin-sensitizing approaches already used in metabolic medicine. These might include dietary modifications, physical activity tailored to MS limitations, and possibly insulin-sensitizing medications 2 .
Since insulin resistance appears linked to cognitive dysfunction in MS, addressing hyperinsulinemia might help preserve cognitive function—one of the most concerning aspects of MS for many patients 3 .
The discovery of hyperinsulinemia in newly diagnosed MS patients represents more than just an additional health concern for those living with the disease. It suggests that metabolic health may be fundamentally intertwined with neurological health in ways we are only beginning to comprehend.
This research invites us to see MS not solely as an isolated autoimmune condition, but as a disorder that may involve complex interactions between immunity, metabolism, and neurodegeneration. The finding that these metabolic changes appear early in the disease process, even before significant disability develops, suggests they might play a role in pathogenesis rather than simply being consequences of the disease 1 .
As research continues to unravel these connections, there is growing hope that addressing insulin resistance might open new pathways to protect neurological function and improve quality of life for people living with MS. The metabolic road in multiple sclerosis may be less traveled, but it appears increasingly likely that it could make all the difference.