Diabetes linked to altered long-term inflammatory response in mesh implantation

There is a link between diabetes and altered long-term inflammatory response in complicated mesh implantation, according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

Approximately 87% of type 2 diabetes cases are diagnosed in women aged at least 45 years, indicating a significant prevalence in this population. Older women also experience higher rates of pelvic floor disorders such as pelvic organ prolapse and stress urinary incontinence.

In one study, urinary incontinence was reported at least weekly in 21% of participating women.² Urge incontinence was reported by 42% of these patients, with associated factors including White race, diabetes treated with insulin, depressive symptoms, oral estrogen use, and decreased physical performance.

Pelvic floor disorders are often repaired using polypropylene urogynecologic meshes.¹ Of US patients who annually receive urogynecologic meshes, approximately 14% present with diabetes. Data has indicated an increased risk of mesh-related complications has been reported in this population, but data about the mechanism underlying this risk is lacking.

Investigators conducted a study to determine the association between diabetes and aberrations in the host inflammatory response to mesh.Participants included women receiving vaginal mesh removal because of exposure or pain at Magee-Womens Hospital from February 2012 to August 2020.¹

Women with acute infection, prior mesh revisit operations, and a history of chronic pelvic pain, irritable bowl, endometriosis, interstitial cystitis, fibromyalgia, or vulvodynia were excluded from the analysis.

Participant characteristics included body mass index (BMI), race, age, parity, gravidity, smoking status, menopausal status, comorbidities, menopausal hormonal therapy, and mesh variables. Medical records and a recorded blood glucose (BG)-lowering agent during the visit were used to determine diabetes.

Investigators collected random BG and hemoglobin A1c (HbA1c) measurements from before and after mesh removal. Diabetes with a median BG level of 200 mg/dL or more was considered poorly managed.¹

TRIzol reagent (Invitrogen, Carlsbad, CA) was used to isolate total RNA. Geometric means of the experimental group (E) to the control group (C) indicated increases in the gene expression of fold, while a negative E/C ratio indicated decreases in gene expression.

An 11.6% increase in BMI was reported in women with diabetes vs those without diabetes. However, no other significant differences in demographic and clinical characteristics were observed. Similar mesh-associated characteristics were also reported between groups.¹

HbA1c control at 5.7% and BG at 95 mg/dL was reported before mesh implantation in patients with diabetes. These numbers were similar to those in patients without diabetes. HbA1c over 8% was reported in 23% of cases before mesh removal and 36% after mesh removal. Rates of poorly controlled BG were 25% and 50%, respectively.

Suboptimal longitudinal glucose management was found, with loose glucose control reported in 24% of patients and poor glucose control in 35%. In comparison, normal and consistent BG and HbA1c levels were reported in the group without diabetes.¹

Of the 32 cytokines/chemokines and 7 growth factors associated with inflammatory response, most did not have differentially expressed genes. Exceptions included C-C motif chemokine ligand 13 (Ccl13), C-C motif chemokine ligand 24 (Ccl24), and interleukin 1 alpha (Il1a).

In the diabetes vs nondiabetic groups, Ccl13 and Ccl24 expressions were upregulated by 1.5-fold and 1.8-fold, respectively, while Il1a expression was downregulated by 2.2-fold. This indicated patients with diabetes had a dysregulated inflammatory response to mesh.

These results indicated an association between diabetes and altered long-term inflammatory response in complicated mesh implantation. Investigators recommended further mechanistic studies to determine the role of suboptimal glycemic control after mesh implantation in this immune dysregulation.¹

Reference

1. Liang R, Shaker ER, Zhao M, et al. Dysregulated inflammatory response to urogynecologic meshes in women with diabetes and its implications. Am J Obstet Gynecol. 2024;231:115.e1-11. doi:10.1016/j.ajog.2024.02.282
2. Jackson RA, Vittinghoff E, Kanaya AM, et al. Urinary incontinence in elderly women: findings from the Health, Aging, and Body Composition Study. Obstet Gynecol. 2004;104(2):301-7. doi:10.1097/01.AOG.0000133482.20685.d1