Friedreich’s ataxia diabetes risk tied to lower muscle health, inactivity
More research needed to see if muscle, fat interventions could delay diabetes
Reduced muscle heath, physical inactivity, and more belly fat lowered sensitivity to insulin, a risk factor for diabetes, among adults with Friedreich’s ataxia (FA) who didn’t have diabetes, a small study finds.
Further studies are needed to determine if muscle- or fat-focused interventions could delay FA-related diabetes, the researchers noted. The study, “Insulin Sensitivity and Insulin Secretion in Adults With Friedreich’s Ataxia: The Role of Skeletal Muscle,” was published in the Journal of Clinical Endocrinology & Metabolism.
In FA, inherited genetic mutations result in a deficiency in the protein frataxin, impairing the function of mitochondria, the cell’s energy production centers.
Because of their high energy demands, nerves and muscles are particularly vulnerable to mitochondrial dysfunction, which leads to the hallmark FA symptoms such as problems with coordination and balance (ataxia), muscle weakness, heart complications, and neurological issues.
People with FA can also develop diabetes, wherein the levels of blood sugar, mainly glucose, become abnormally high over long time. The mechanisms underlying FA-related diabetes remain unclear, but the loss of frataxin appears to disrupt the production or response to insulin, a hormone that regulates blood sugar levels.
Scientists have investigated a link between the health of skeletal muscles, that is, those attached to the bones that facilitate movement, and insulin sensitivity and production in adults with FA without diabetes.
Assessing risk of diabetes in FA
Study participants included 11 adults with FA (four women) with moderate physical impairment, who were a median age of 27. A group of 24 healthy people matched by age and sex were included as controls. Both groups had similar body mass index values, a measure of body fat content.
Glucose and insulin levels were assessed during fasting and after eating, as was body composition, self-reported physical activity, and insulin sensitivity, or how well cells respond to insulin. The mitochondrial capacity in muscles was measured using CrCEST MRI, an imaging technique that measures free creatine, a metabolite needed for mitochondrial function. A higher mitochondrial capacity indicates healthier muscles.
Those with FA without diabetes had significantly higher mean fasting glucose levels than controls (5 vs. 4.6 mmol/L). After eating, glucose concentrations were similar between the two groups. While fasting insulin levels were higher in FA patients, they appeared to rise more quickly and decline more slowly after eating. The FA participants also had lower insulin sensitivity than controls.
After adjusting for age and sex, a diagnosis of FA was significantly associated with lower insulin sensitivity. This association remained significant after adjusting for mitochondrial capacity (CrCEST MRI) and body composition, as assessed by visceral (belly) fat and lean mass, the difference between total body weight and body fat weight.
According to the researchers, “any process that disrupts skeletal muscle metabolism could contribute to lower skeletal muscle insulin sensitivity.”
More visceral fat was independently associated with insulin insensitivity, regardless of a FA diagnosis. Similarly, a lower mitochondrial capacity and less physical activity were linked with insulin insensitivity, but both associations weakened when FA status was included in the calculation.
Because the impact of FA disease status on mitochondrial capacity diminished after accounting for differences in physical activity, the researchers suggested “inactivity may explain some of the effects of [FA].”
Despite having similar blood glucose levels after eating, insulin secretion was significantly higher in FA patients than healthy controls, even after adjusting for body composition and muscle health.
“Higher insulin secretion appears compensatory and, when inadequate, could herald [diabetes],” the researchers suggested.
Those with FA also had more suppressed glucose production after meals. Adults with FA and controls had similar fasting levels of lactate, a molecule produced by the body when it breaks down sugar for energy. In contrast, late post-meal lactate levels were higher in FA.
“We found that lower skeletal muscle mitochondrial … capacity and less physical activity contribute to lower skeletal muscle insulin sensitivity in adults with [FA] without overt [diabetes],” the scientists wrote.
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