(Reuters Health)—In a case series report, researchers describe rapid symptom improvement in three patients with polymyalgia rheumatica (PMR) when high glucose levels were brought down.
After glucose was controlled, patients experienced improvement in both symptoms and laboratory measures of PMR without glucocorticoid administration or an increase in glucocorticoid dosage, according to the report in the Annals of Internal Medicine.1
“These findings were unexpected and are remarkable,” write the authors, led by Dr. Ken Yoshida of The Jikei University School of Medicine, Tokyo. “We believe that coincidental improvement is an unlikely explanation for these cases.”
PMR is a chronic inflammatory condition affecting elderly persons, the authors note in their report, and is characterized by severe pain and stiffness, mostly in the shoulders, upper arms, and pelvic girdle.
The researchers had no explanation for why controlling glucose levels may improve symptoms, but suggested that more research is in order.
“Treating PMR with glucocorticoid therapy is problematic,” the authors write. “Most patients require at least one to two years of treatment, and too many patients develop adverse effects, such as diabetes mellitus, osteoporosis and hypertension. Therefore, we propose that a randomized controlled trial be considered to determine whether improved glycemic control, perhaps with meglitinide, may allow patients with type 2 diabetes and PMR to avoid glucocorticoid treatment.”
The first case described by the researchers was a 68-year-old man with bilateral shoulder pain and morning stiffness. The patient, who fulfilled the 2012 EULAR/ACR provisional criteria for PMR had been taking NSAIDs for six weeks and had been receiving metformin to treat type 2 diabetes for five years. His labs showed: C-reactive protein (CRP) level, 62.9 mg/L (normal; <1.4 mg/L); hemoglobin mA1c (HbA1c) concentration, 7.9%; and fasting plasma glucose level, 8.88 mmol/L (160 mg/dL).
Before prescribing glucocorticoids, the researchers opted to first address his elevated glucose level by changing some of his antidiabetic medications and adding repaglinide, which improved his glycemic control. His PMR symptoms and laboratory findings improved considerably after just one week on the new regime and the biceps tenosynovitis initially detected on ultrasonography gradually resolved during the following year.
The second case involved a 72-year-old woman with bilateral shoulder pain, morning stiffness, bilateral hip pain and restricted hip mobility. She had been prescribed prednisolone, which did improve her symptoms, but when the dosage was tapered, the symptoms returned. When the researchers first saw her, she had a CRP level of 42.7 mg/L; an HbA1c concentration of 11.7%; and a postprandial glucose level of 18.6 mmol/L (335 mg/dL).
Instead of increasing the woman’s prednisolone dosage, the researchers started the woman on repaglinide therapy that was later switched to mitiglinide to improve her glycemic control. During the next two weeks, her symptoms improved.
The third case involved a 73-year-old man with bilateral shoulder and upper-arm pain, morning stiffness, and bilateral hip pain. The man, who fulfilled the criteria for PMR, had been using NSAIDs for five months without benefit. At that point, his labs showed a CRP level of 28 mg/L, and an HbA1c concentration of 6.7%. The researchers treated him with mitiglinide and pioglitazone. His glycemic control improved during the next two weeks, as did his symptoms and laboratory findings.
Dr. Yoshida did not respond to a request for comments.
While PMR is the second most common inflammatory autoimmune condition that affects the elderly, it’s possible that one or two of the three patients might have something else, says Ashina Makol, MD, an assistant professor in the division of rheumatology at the Mayo Clinic, Rochester, Minn. There are other disorders that could produce the same symptoms, she added.
Two of the three patients are in their 70s, which is the age at which the condition usually appears, Dr. Makol says. However, the most telling sign that a patient’s symptoms are caused by PMR is a response to steroids and two of the patients described in the paper never got steroids.
And while the authors say that the patients fulfill the 2012 EULAR/ACR provisional criteria for PMR, those criteria were not developed as a diagnostic aid, but rather to assure that there would be homogenous groups of patients in clinical trials, Dr. Makol says.
Dr. Makol would like to see long-term follow-up on the three patients and would welcome a clinical trial, but, she says, “I don’t know whether it would be feasible to do. Would one arm of the study not receive any treatment?”
Sidebar: The Rheumatologist asked Eric Matteson, MD, professor emeritus of rheumatology, Mayo Clinic, Rochester, Minn, to comment on this case series.
“So far, no studies have demonstrated an increased risk of developing PMR in patients who have diabetes, nor are there any studies that consistently demonstrate a risk of developing diabetes in patients with PMR,” Dr. Matteson says. “I think if there were a true link, we would have uncovered it. As Dr. Makol points out, the preliminary classification criteria for PMR are for not intended for diagnosis and require competing conditions be ruled out. Here, we cannot be certain about underlying disease in the non-glucocorticoid exposed patients, and the glucocorticoid exposed patient apparently was already diagnosed and under treatment for PMR.
“It has been known for some time that some diabetes drugs, including repaglinide, may have anti-inflammatory properties in nondiabetic animals, but doses required for clinical efficacy belie a practical application. Before considering a clinical trial of diabetes management in patients presenting with the polymyalgic syndrome, which may risk harm from poorly managed disease, a more definitive epidemiologic study should be considered. In my opinion, there isn’t evidence of an important pathogenetic link between PMR and diabetes,” he says.
Reference
- Yoshida K, Sakamoto N, Kurosaka D. Improvement in polymyalgia rheumatica associated with improved control of diabetes mellitus: A case series. Ann Intern Med. 2020 Sep 15. doi: 10.7326/L20-0196. Online ahead of print.
