https://orcid.org/0000-0002-0967-797X
We want to thank the authors for their letter discussing multiple etiologies explaining the association between sarcoidosis and diabetes mellitus in conjunction with our meta-analysis [Citation1].
In our study, we acknowledged that diabetes mellitus (DM) type was not reported in most studies (Supplementary Table 2). Therefore, studying the association between DM type and sarcoidosis was out of the scope in our meta-analysis. However, we recommend further investigation of this association by future large-scale studies.
To our knowledge, most sarcoidosis patients are diagnosed within the range of 20–50 years of age [Citation2]. However, in the study of Papadopoulos et al., sarcoidosis diagnosis was established between 23–38 years of age in the two cases of insulin-dependent DM -which commonly developed in childhood or adolescence- reducing the potential of sarcoidosis preceding DM. This variation of the onset of diagnosis of the two diseases rules out the possibility of sarcoidosis driving pancreatic autoimmunity in those patients [Citation3,Citation4].
Sarcoidosis is a multisystem inflammatory disease with unknown etiology and complex pathogenicity [Citation5]. Many studies aimed to prove the association of sarcoidosis with autoimmune diseases [Citation6–8]. Moreover, in the case-control study of Wu et al., the prevalence of type 1 diabetes was higher in controls (2/4948 patients) than in sarcoidosis patients (0/1237 patients) [Citation8]. In addition, markers of many autoimmune diseases were presented in approximately 10% of sarcoidosis patients without the diagnosis of autoimmune diseases [Citation7]. The immune regulation cascade derived from the immune-suppressive treatment of sarcoidosis decreases the possibility of developing autoimmune-DM [Citation5].
The lungs and the lymph nodes are the most common site of sarcoidosis involvement, with a prevalence of 90% and 75% of all sarcoidosis cases [Citation5]. Pancreatic sarcoidosis affects about 1–3% of sarcoidosis patients and mainly remain asymptomatic [Citation9]. Symptomatic presentation of pancreatic involvement mostly mimics tumor-like manifestations such as weight loss, obstructive jaundice, and abdominal pain resulting from the compression on the pancreatic duct and the surrounding organs [Citation9–11]. To a lesser extent, pancreatitis presentation may occur [Citation12]. In addition, hyperglycemia was reported in a previously diabetic patients with pancreatic sarcoid involvement after a 7-day course of prednisone treatment. This suggests that diabetes affection is more linked to the treatment itself than the autoimmune pancreatitis cascade [Citation9]. Moreover, sarcoidosis patients that received glucocorticoid treatment had more risk for developing DM (HR = 2.85 (95%CI: 0.76–10.75)) when compared to patients who did not receive glucocorticoid treatment [Citation13].
The International Diabetes Federation report published in 2017 indicated that the prevalence of DM is the highest in North America compared to other continents. However, the prevalence of undiagnosed DM is the lowest in North America. Perse, the highest prevalence of DM in sarcoidosis patients in North America is linked to another hypothesis other than the prevalence of DM in North America [Citation14].
In our meta-analysis of 19 studies, only three papers reported the obesity rate in sarcoidosis patients, 26.7% in Germany, 15.7% in Italy, and 3.3% in Poland. Therefore, we could not conduct meta-regression to assess the effects of obesity on the prevalence of DM in sarcoidosis patients due to the low number of included studies that reported obesity rates. Therefore, more studies are needed to investigate the difference in the rates of DM in all continents regarding the genetic, environmental, other comorbid association, and socioeconomic differences.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
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References
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