Serum chromogranin A level continuously rises with the progression of type 1 diabetes, and indicates the presence of both enterochromaffin‐like cell hyperplasia and autoimmune gastritis

Abstract

Aims/Introduction: The relationship of chromogranin A (CgA) levels above the normal range with various outcomes, such as glycated hemoglobin levels, enterochromaffin-like cell hyperplasia and autoimmune gastritis, was investigated in type 1 diabetes patients with special regard to the progression of comorbidities. Materials and Methods: A cohort study on 153 type 1 diabetes patients was carried out with a prospective branch on clinical and laboratory data, and a retrospective branch on histological data obtained by gastroscopy. Results: Patients with CgA levels above the upper limit of the normal range (n = 28) had significantly higher glycated hemoglobin levels (P = 0.0160) than those with CgA in the normal range (n = 125). The correlation between CgA and glycated hemoglobin was significant (P < 0.0001), but weak (R = +0.32). A slight, but steady elevation (P = 0.0410) in CgA level was observed to co-vary with the duration of type 1 diabetes. Enterochromaffin-like cell hyperplasia and autoimmune gastritis was significantly more frequent (P = 0.0087 for both) in the high CgA group. Detailed analyses on gastric tissue samples confirmed a progression of enterochromaffin-like cell hyperplasia (P = 0.0192) accompanied by CgA elevation (P = 0.0316). Conclusions: The early detection and follow up of the later progression of enterochromaffin-like cell hyperplasia and autoimmune gastritis into gastric neuroendocrine tumors, which have~100-fold greater incidence in type 1 diabetes patients, can be achieved by assessment of CgA levels. Therefore, the use of CgA could be considered as a novel auxiliary biomarker in the care of these type 1 diabetes complications.

Lower serum chromogranin B level is associated with type 1 diabetes and with type 2 diabetes patients with intensive conservative insulin treatment

“…Serum CgA level was significantly higher ( p = 0.0348) in type 1 diabetes patients than that of healthy controls (Table 1 ), in accordance with our previous reports [ 8 ]. Type 1 diabetes patients had significantly lower serum CgB level ( p = 0.0241) than the corresponding age- and sex matched control subjects (Fig.…”

“…Analysis on CgA was performed only on data where no CgA influencing factor was present [3,4,7]. Laboratory and anamnestic data of study subjects are summarized in Tables 1 and 2. Serum CgA level was significantly higher (p = 0.0348) in type 1 diabetes patients than that of healthy controls (Table 1), in accordance with our previous reports [8]. Type 1 diabetes patients had significantly lower serum CgB level (p = 0.0241) than the corresponding age-and sex matched control subjects (Fig.…”

“…Interestingly, CgA and CgB levels did not correlate with each other and changed in different directions in type 1 diabetes mellitus. The serum CgA level increases with the progression of type 1 diabetes, and it is associated with the development of enterochromaffin-like cell hyperplasia and autoimmune gastritis [ 8 ], from which neuroendocrine tumors can arise [ 17 , 18 ]. In contrast, serum CgB level was lower in the patients with type 1 diabetes than those in healthy controls.…”

“…Chromogranins are associated with the carbohydrate metabolism: CgA is known to play a significant role in the development and pathogenesis [ 5 – 7 ] of type 1 diabetes and it is associated with some type 1 diabetes complications, which could develop into neuroendocrine tumors [ 8 ]. Animal and cellular models have shown that CgB is mostly related to the physiological insulin secretion [ 9 – 11 ], however, human clinical study investigating the connection between CgB and diabetes has not been conducted yet.…”

The Emerging Roles of Chromogranins and Derived Polypeptides in Atherosclerosis, Diabetes, and Coronary Heart Disease

“…The other part of the name (chromo-) relates to the fact that chromaffin granules were the first discovered to contain granin proteins [ 7 ]. CgA is known to play a significant role in the pathogenesis and development of type 1 diabetes, and is associated with its complications [ 8 , 9 , 10 ]. A CgA-derived peptide, pancreatin, is expressed in the pancreatic islet [ 11 ], and has a strong inhibitory action on insulin secretion from the islet β-cells [ 12 ].…”