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Diabetic Man With Sclerosing Mesenteritis Experiences Glycemic Control With Steroids

— Case authors report an unexpected paradoxical effect

MedpageToday
An MRI image of sclerosing mesenteritis

A 57-year-old man presents for admission to hospital in Warsaw, Poland; he has very poorly controlled type 2 diabetes and chronically elevated blood pressure. He has been referred in order to gain better metabolic control of both these conditions. He also has benign prostatic hyperplasia and hyperlipidemia, and is a smoker with a 35-pack-year smoking history.

On admission, he reports suffering relentless pain on the left side of his abdomen, which worsens with activity and when he presses on the area. He adds that he has been very thirsty, and is urinating more often than usual. He has lost 35 lbs in the past 3 months. His current weight is 205 lbs (BMI 26.6).

Based on his self-monitoring, he notes that he has elevated blood pressure and blood glucose levels (16.65-26.6 mmol/L). A physical examination confirms abdominal pain on palpation, but reveals no pathological signs in the abdomen.

The patient's medication history shows that he has been receiving metformin 3 × 1,000 mg, and multiple daily injections of human regular insulin before main meals plus neutral protamine hagedorn insulin at bedtime (intermediate-acting insulin), for a total mean daily dose of 51 IU.

Blood tests reveal a high glycated hemoglobin level (12%) and leukocytosis (13.57×103/μl), but normal levels of other inflammatory markers, such as C-reactive protein and erythrocyte sedimentation rate.

An ultrasound of the patient's abdomen shows small renal cysts in the left kidney.

Clinicians start the patient on a continuous intravenous infusion of insulin. However, his poor glycemic control persists. On his third day in hospital, they replace intravenous insulin infusion with multiple daily injections of insulin.

Based on the patient's persistent hyperglycemia and abdominal pain, they perform a CT scan, which shows an atypical region of increased attenuation in mesenteric adipose tissue. The scan also shows renal cysts in both kidneys, but clinicians determine that these are not causing the patient's abdominal pain. The patient undergoes a colonoscopy and gastroscopy, which do not show any abnormalities.

Clinicians request an MRI of the abdomen; the contrast-enhanced T1 GRE fat-saturated image shows a well-demarcated mass-like lesion in the mesentery, with evidence of a capsule and spared fat around traversing vessels, which is strongly suggestive of sclerosing mesenteritis. Based on the CT and MRI findings, clinicians diagnose the patient with sclerosing mesenteritis.

Due to the patient's constant abdominal pain, they start him on 40-mg prednisone daily. This reduces his abdominal pain and improves glycemic control, as indicated by a lower insulin requirement (total mean daily dose of insulin of 32 IU).

After 2 months of receiving glucocorticoid therapy, the patient reports that his stomach pain is significantly decreased. A follow-up MRI shows that abnormalities in the mesentery are significantly reduced. The patient's glycated hemoglobin level is decreased to 8.8%. Clinicians begin to gradually lower the daily dose of prednisone to 5 mg per day.

One year later, another MRI reveals that the lesions in the mesentery have continued to decrease in size. The patient's mean glucose levels are within the range of 5 to 8.33 mmol/L, periodically reaching about 10 mmol/L.

Discussion

Clinicians presenting this believe it is the first to report the paradoxical effect of glucocorticoid therapy on metabolic control in diabetes aggravated by sclerosing mesenteritis.

While this case was accidentally diagnosed, authors note that a series of observational studies have suggested a link between sclerosing mesenteritis and diabetes. Nevertheless, the condition is generally difficult to diagnose due to its vague .

A 2017 of 192 cases of sclerosing mesenteritis revealed the symptomatology to be abdominal pain in 78.1% of patients, fever in 26.0%, weight loss in 22.9%, diarrhea in 19.3%, vomiting in 18.2%, anorexia in 13.5%, constipation in 10.9%, bloating in 9.4%, malaise in 5.7%, nausea in 5.7%, pain with eating in 4.7%, and fatigue in 2.1%.

Diabetes has been proposed as a "possible causative and/or associated factor" of sclerosing mesenteritis, authors note; the reported prevalence of diabetes in patients with sclerosing mesenteritis ranges from 8.7% to 21.5%, suggesting that insulin resistance may develop in these patients due to inflammation of mesenteric fatty tissue.

They explain that this may occur "when dying adipocytes cause inflow of macrophages to adipose tissue and synthesis of proinflammatory cytokines (IL-1, IL-6, TNFα), finally leading to increase of insulin resistance via activation of intracellular pathways such as NFκB and JNK."

Because inflammation associated with sclerosing mesenteritis is particularly severe and chronic, case authors suggest that these patients may be at increased risk of developing insulin resistance and diabetes. This inflammatory process was likely central to the metabolic decompensation that occurred in their patient, resulting in high blood glucose levels and an increased insulin requirement.

Because the etiology of inflammatory sclerosing mesenteritis is not known, it is generally treated with immunosuppressive agents, including glucocorticoids. The group notes that glucocorticoids are known not only to exacerbate diabetes-related hyperglycemia, but also to induce diabetes. They describe the various mechanisms behind the medication's diabetogenic effect, which include a "counter-regulatory effect in relation to insulin, increase of insulin resistance and hepatic gluconeogenesis, and glycogenolysis." In addition, glucocorticoids reduce beta cells' insulin secretion, activate pancreatic alpha cells, and diminish the effects of incretin.

The extent of the effect of glucocorticoid treatment depends on the dose, the active ingredient used in the formulation of the drug, and the method of administration, they observe. Use of oral glucocorticoids has been reported to be associated with an increased risk of developing diabetes of up to 2%, and an OR for new-onset diabetes of , case authors note.

reported that a cumulative oral dose equivalent to ≥2.5-g hydrocortisone was associated with an adjusted OR of diabetes of 1.25 (1.01-1.54), with 7.6% of patients exposed to a median equivalent dose of 9.9 g (interquartile range 4.7-22.0).

Given the patient's dose of glucocorticoids and inflammation of his mesentery, clinicians had predicted the potential development of significant hyperglycemia, and instead observed an unexpected and previously unreported improvement in metabolic control during treatment with glucocorticoids.

"The effect of reduction of inflammation with glucocorticoids was stronger than the hyperglycemic effect of this treatment," the authors note.

"However, because of the importance of inflammation in the development of insulin resistance, it is questioned whether type 2 diabetes mellitus can be treated as an autoimmune disease," they write.

They observe that glucocorticoids may inhibit development of insulin resistance via their capacity to prevent with target genes, and thus to inhibit the transcription of DNA; the similarity to the inflammatory process of the adipose tissue in sclerosing mesenteritis suggests that steroids can have analogous action in this disease.

Conclusions

Case authors conclude that sclerosing mesenteritis should be included in the differential diagnosis of abdominal pain in diabetes patients, and considered when seeking a cause of metabolic decompensation in patients with diabetes. While glucocorticoid treatment generally results in a significant increase in blood glucose levels, it can paradoxically lead to better glycemic control in patients with sclerosing mesenteritis.

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    Kate Kneisel is a freelance medical journalist based in Belleville, Ontario.

Disclosures

Case authors reported no conflicts of interest.

Primary Source

American Journal of Case Reports

Mrozikiewicz-Rakowska B, et al "The use of glucocorticoids for better control of diabetes mellitus: the paradox of sclerosing mesenteritis (the rare could become common)" Am J Case Rep 2021; DOI: 10.12659/AJCR.930453.