“Reduced glucose tolerance has long been recognized as a potential risk factor for PD, and there is increasing scrutiny of insulin resistance as a pathologic driver of neurodegeneration.” (Source)

That’s a simple sentence with profound implications. It’s increasingly recognized that insulin resistance or chronic hyperinsulinemia are major risk factors for cognitive impairment and Alzheimer’s disease. A neuronal energy deficit—a reduction in neurons’ ability to metabolize glucose—leads to neuronal atrophy and eventually the clinical signs & symptoms of Alzheimer’s. An emerging body of research suggests that other neurodegenerative conditions—especially Parkinson’s disease—may have similar etiology. In the case of Parkinson’s disease (PD), the cells most affected would be dopamine-secreting neurons.

A new study looking at insulin resistance (IR) in PD patients has revealed that IR among those with PD may be much higher than was previously realized. The study was small—just 154 subjects (109 males, 45 females; mean age 67.7±10.5), but it’s worth paying attention to. Despite normal fasting glucose and in many cases also normal HbA1c, over half the subjects (58.4%) had undiagnosed insulin resistance. IR was found more frequently in overweight and obese subjects (61.1% and 82.8% respectively), but even among “normal weight” subjects, 41% were found to be insulin resistant. Mean HOMA-IR in the cohort was 2.3±1.8. Some medical professionals consider HOMA-IR < 1 to indicate optimal insulin sensitivity, with a score > 1.9 indicating early insulin resistance and > 2.9 indicating significant resistance, so several of these subjects fell squarely over the threshold of insulin resistance. (In this study, IR was defined as HOMA-IR ≥ 2.0 or HbA1c ≥ 5.7.)   

It’s crucial to note that all subjects in this study were not diagnosed as having type 2 diabetes. So there was a substantial proportion of PD patients with peripheral insulin resistance even in the absence of type 2 diabetes. They’re certainly not alone: chronic hyperinsulinemia—even, or perhaps especially, in individuals with normal blood sugar—appears to be a driving factor in a host of modern, chronic, noncommunicable diseases. This cannot be emphasized enough: there is a myopic focus solely on blood glucose with regard to metabolic health, with insulin being nearly ignored. 

New theories are emerging that defective insulin signaling in the central nervous system may contribute to Parkinson’s pathology, and that type 2 diabetes and PD might have shared etiologies:

“…there is growing evidence that a process analogous to peripheral insulin resistance occurs in the brains of Parkinson's disease patients, even in those without diabetes. This raises the possibility that defective insulin signalling pathways may contribute to the development of the pathological features of Parkinson’s disease, and thereby suggests that the insulin signalling pathway may potentially be a novel target for disease modification. Given these growing links between PD and Type 2 diabetes it is perhaps not unsurprising that drugs used the treatment of T2DM are amongst the most promising treatments currently being prioritised for repositioning as possible novel treatments for PD and several clinical trials are under way.” (Athauda & Foltynie, 2016)

Again we see recognition of the fact that insulin resistance—even when blood sugar is normal and individuals are not diagnosed diabetics—may be a pathological factor in neurodegeneration.

According to the lead investigator of the study assessing the extent of IR in Parkinson’s patients, “Now that, for the first time, we understand how common insulin resistance is in non-diabetic patients with PD, we can begin to address this public health challenge. This increases the importance of finding new treatments and lifestyle interventions that can address this metabolic dysfunction with multiple implications, from diabetes to neurodegenerative disorders like PD and Alzheimer's disease.”

Indeed. If insulin resistance is a major contributor to the pathology of neurodegenerative conditions, then it stands to reason that dietary and lifestyle interventions that reduce insulin levels may be beneficial for people living with these. Promising research is already underway looking at ketogenic diets as a nutritional therapy for PD, and there may be a role for other adjunctive strategies, such as fasting and increased physical activity.   

It will be interesting to keep an eye on related research in the future. Perhaps diet and lifestyle changes can make inroads in these otherwise devastating and difficult-to-treat illnesses.

By Amy Berger, MS, CNS