Man’s case shows how SMA muscle loss may lead to diabetes
Ketoacidosis is first sign of diabetes in 27-year-old patient
A man with type 3 spinal muscular atrophy (SMA) and no history of diabetes developed diabetic ketoacidosis, a severe diabetes complication, which researchers said may be linked to metabolic changes.
SMA can cause major loss of muscle, which plays a key role in processing sugars and fats. Muscle loss may disrupt metabolism and raise the risk of diabetes or similar conditions, especially in adults with SMA. “The possibility of metabolic abnormalities in patients with SMA should be considered among patients who live well into adulthood,” the researchers wrote.
The study, “Ketosis-prone Diabetes as a Presentation of New-onset Diabetes in a Patient With Spinal Muscular Atrophy Type III,” was published in the journal JCEM Case Reports.
SMA is caused in most cases by mutations in the SMN1 gene, which carries the instructions for making a protein called SMN. Without enough SMN, the nerve cells that control movement lose their protection, become damaged, and eventually die. As these cells are lost, muscles weaken and shrink, leading to the hallmark symptoms of SMA.
As muscles degenerate, they may lose their ability to absorb glucose, a sugar that is a primary fuel source for cells to produce energy. They may also respond more poorly to insulin, a hormone that helps muscles and other tissues absorb glucose. With these changes in metabolism, body fat (adipose tissue) may accumulate and release lipids, a class of molecules including fats. “Therefore, patients with muscular atrophies are more prone to diabetes from insulin resistance and increased adipose tissue,” the researchers wrote.
Patient’s journey highlights metabolic disease risk
In diabetic ketoacidosis, cells can’t use glucose effectively, so they begin to break down fat. As ketones, byproducts of the fat breakdown process, accumulate in the blood, they make the blood more acidic. If unaddressed, this may lead to life-threatening complications.
The case study focused on a 27-year-old man in Thailand who was diagnosed at age 17 with type 3 SMA, a milder form of SMA in which symptoms typically appear between 18 months and the end of adolescence. Over time, muscle weakness can develop, and without treatment, people with type 3 SMA may lose the ability to walk.
The man’s “motor capabilities deteriorated slightly during adolescence but he could walk independently with limited physical activity,” the researchers wrote. Although he hadn’t shown signs of diabetes, he had a family history of the disease. He was also producing unusually large amounts of urine each day, a sign that high blood sugar is making the body flush out excess sugar through urine.
The researchers noted abnormal distribution of fat through the man’s body, with fat loss in his upper arms. His thigh muscles showed more atrophy than his calf muscles, and he had moderate weakness in all four limbs. In the three months before he sought care for diabetes, he had lost 12 kg (about 26 lbs), resulting in a weight of 61 kg (about 134 lbs).
Diagnostic testing revealed high blood acidity consistent with ketoacidosis, as well as high cholesterol. The man had low muscle mass but excess body fat.
Clinicians began administering fluids into the vein and started the man on insulin infusions. Within eight hours, he reported feeling better and his ketoacidosis had resolved.
He continued on insulin, and blood tests a week later showed reduced markers of insulin production. Genetic analysis showed a relatively low genetic risk of developing diabetes.
After a month on insulin, the man was able to safely discontinue its use. Since then, he has been taking metformin and thiazolidinedione, two medications for type 2 diabetes.
“At the last follow-up (5 months after [diabetic ketoacidosis]), the patient’s diabetes has been well-controlled … and his weight increased to 70 kg [about 154 lbs],” the researchers wrote.
The case highlights a potential risk of metabolic disease in adults with SMA, as progressive muscle atrophy could increase the possibility of these diseases developing over time. Animal studies have also demonstrated hormonal imbalances in SMA, which could further increase risk of ketoacidosis.
Clinical vigilance may help care teams quickly respond to metabolic complications, according to the researchers. “The possibility of glucose and lipid abnormalities should be considered and diabetes and lipid screening should be monitored periodically to determine the appropriate and timely interventions if required,” they wrote.
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