Relationship between imaging changes of the pancreas and islet beta-cell function

Abstract

Imaging changes in the pancreas can provide valuable information about the status of islet beta-cell function in different pancreatic diseases, such as diabetes, pancreatitis, pancreatic cancer, fatty pancreas, and insulinoma. While imaging cannot directly measure beta-cell function; it can be used as a marker of disease progression and a tool to guide therapeutic interventions. As imaging technologies continue to advance, they will likely play an increasingly important role in diagnosing, monitoring, and managing diabetes.

Core Tip: The fast-growing imaging technologies are becoming increasingly critical in the diagnosis, monitoring, and management of diabetes, other pancreas diseases, and metabolic disorders. Imaging tests of the pancreas may develop as a tool to help predict potential or existing islet beta-cell dysfunction.

INTRODUCTION

Pancreatic beta-cell function refers to the ability to synthesise, store, and secrete insulin to maintain normal blood glucose levels. The mechanism of islet beta-cell dysfunction is complex and involves environmental and genetic factors[1,2]. Some pancreatic diseases can cause beta-cell dysfunction, which can be observed using ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET).

PANCREATIC DISEASES

Diabetes

Beta-cell dysfunction is the central component in the progression of type 1 and type 2 diabetes. The measurement for the early evaluation of beta-cell mass and function has become an urgent need. Glucagon-like peptide-1-based imaging probes, manganese-based probes, and zinc-based probes are the most promising beta-cell imaging methods[3-5]. Therefore, beta-cell mass changes in the same patient can be monitored using the imaging results from multiple time points. Evaluation of transplanted islets’ survival and accurate detection of insulinomas may become possible[6]. Diabetes in children may be predicted by pancreas MRI outcomes, including reduced pancreatic parenchymal volume, which has been correlated with an increased incidence of diabetes [odds ratio (OR) = 1.16, P = 0.03] and T1 relaxation time. This indicates abnormal glucose with an area under the curve of 0.78 [95% confidence interval (CI): 0.55-1], 91% specificity, and 73% sensitivity[7]. New methods of ultrasound imaging to detect pancreatitis and beta-cell dysfunction have been tested in the laboratory and may help in the early diagnosis of type 1 diabetes[8,9].

Pancreatitis

Acute and chronic pancreatitis impair beta-cell function and are associated with diabetes. Patients with acute pancreatitis were found to have endocrine dysfunction after undergoing an oral glucose tolerance test, presenting a 43% (95%CI: 30%-56%) overall prevalence of newly diagnosed prediabetes or diabetes[10]. CT and MRI help in the diagnosis by identifying features such as swelling of the pancreas, inflammatory fat stranding, and peripancreatic fluid collections[11]. In chronic pancreatitis, pancreatic parenchymal destruction measured by CT and MRI, such as reduced pancreas volume[12], calcifications, atrophy, or ductal dilatation, was strongly correlated with impaired islet mass and 1-year diabetes outcomes, including 1-year insulin use (P = 0.07), islet graft failure (P = 0.003), haemoglobin A1c (P = 0.0004), fasting glucose (P = 0.027), and fasting C-peptide level (P = 0.008)[13]. Endoscopic US (EUS) is a useful tool to evaluate pancreatic inflammation and fibrosis in patients with chronic pancreatitis. EUS shear wave measurement can predict beta-cell dysfunction with a sensitivity of 75% and specificity of 64% in chronic pancreatitis[14]. Another study used EUS combined with the software “Image J” to measure the surface area fraction of the designated elastic blue region among the pancreatic head, pancreatic body, and pancreatic tail, which was defined as the endolymphatic sac tumor-blue score, and the endolymphatic sac tumor-blue score was significantly associated with Homeostasis Model Assessment-β in patients with early chronic pancreatitis[15]. In autoimmune pancreatitis, pathological examination of pancreatic tissues showed that islet cells were almost intact but surrounded by fibrosis. The glucagon tolerance test showed reductions in the C-peptide response (beta-cell response) and the arginine tolerance test showed reductions in the glucagon response (alpha-cell response)[16]. Transabdominal US, magnetic resonance cholangiopancreatography, and endoscopic retrograde cholangiopancreatography showed global or focal gland enlargement (39/47, 83%), main pancreatic duct irregularity (30/47, 64%), and common bile duct stricture (26/47, 55%) in paediatric patients with autoimmune pancreatitis, followed by an insulin-dependent diabetes incidence of 11% (3/27)[17].

Fatty pancreas

Fatty pancreas, also known as pancreatic steatosis, pancreatic lipomatosis, lipomatous pseudohypertrophy, non-alcoholic fatty pancreatic disease, or fatty infiltration of the pancreas[18,19]. Various factors can lead to pancreatic steatosis, such as alcoholic damage, toxins, viruses, or metabolic syndromes, etc[19]. Two mechanisms lead to a fatty pancreas: Fatty replacement, in which acinar cells are irreversibly replaced by adipocytes, and fat accumulation, called non-alcoholic fatty pancreas disease[18]. Few studies on the prevalence of fatty pancreas exist; however, some estimate a 16%-35% prevalence in Asian populations[17]. On abdominal US, pancreatic echogenicity is usually compared with that of the liver, spleen, and kidneys. A hyperechogenic pancreas is present in a fatty pancreas[18]. EUS shows a clear view of the pancreas. In widely used CT, the fatty pancreas shows decreased attenuation. MRI measures intrapancreatic fat and correlates with histopathological results[18]. Different opinions exist on whether fatty infiltration of the pancreas affects beta-cell function. Beta-cell dysfunction was found to be significantly correlated with the mean CT value of the pancreas/spleen in univariate analysis (OR = 0.61, 95%CI: 0.43-0.83, P = 0.0013) and multivariate analysis (OR = 0.38, 95%CI: 0.22-0.61, P < 0.0001) for all participants[13]. Another study suggests no relationship between impaired beta-cell function and a fatty pancreas[20]. On the therapeutic level, reducing caloric intake may repair beta-cell function by reducing fat content in the pancreas[21]. For individuals with central obesity, the effects of a fatty pancreas, measured by the pancreatic fat fraction, were negatively correlated with the homeostatic model assessment of beta-cell function[22].

Pancreatic cancer

Pancreatic cancer has become one of the most fatal cancers, with a 5-year survival rate of approximately 4%[23]. In the assessment of pancreatic cancer, multidetector CT shows vessel details, PET highlights the function and metabolism of tissues at the molecular level, and EUS has a higher diagnostic sensitivity compared with multidetector CT[24]. Pancreatic cancer impairs pancreatic function and is associated with diabetes. In vitro studies have explored the mechanisms by which pancreatic cancer affects beta cells[25]. Exosomes were reported as important mediators of pathogenesis, and the effector molecule may be miR-19a[25]. Through inducing oxidative stress and beta-cell dedifferentiation, overly expressed Vanin1 aggravated the dysfunction of paraneoplastic islets[26]. Imaging tests can be used to explore the mechanisms underlying islet dysfunction and to predict diabetes. Pancreatic duct obstruction and dilation were measured on CT, using the pancreatic atrophic index and remnant pancreatic volume in pancreatic cancer[27]. Remnant pancreatic volume was significantly correlated with the C-peptide index after pancreaticoduodenectomy, thus helping to evaluate the potential risk of new-onset diabetes after pancreaticoduodenectomy[28]. Conversely, some studies have indicated that beta-cell function remains the same in healthy individuals and patients with pancreatic cancer and normal blood glucose[29].

Insulinoma

An insulinoma, a functioning neuroendocrine tumour, is derived from neuroendocrine cells or multipotent stem cells in pancreatic islets. Insulinomas secrete insulin independent of the effects of glucose stimulation[30]. Patients with an insulinoma experience glucose levels of less than 2.5 mmol/L with insulin exceeding 6 mU/mL, and the C-peptide level increasing to 200 pmol/L[31]. The beta-cell function of an insulinoma was found to increase (359.0% ± 171.5%), but the range differed widely (110.6%-678.6%)[32]. Insulinomas can be evaluated by US, CT, MRI, and somatostatin receptor scintigraphy; however, only 10%-60% were positioned accurately[31]. PET and PET/CT, using conventional [18F] dihydroxyphenylalanine or burgeoning [68Ga] DOTA-D-Phe1-Tyr3-octreotide, show higher sensitivity than traditional imaging tests[31]. Over 90% of the high-density expression of glucagon-like peptide-1 receptors on the benign insulinoma cell surface enables 68 Ga-NOTA-MAL-cys40-exendin-4 PET/CT to have a sensitivity of 97.7%[30]. Despite the increasing sensitivity and localisation capabilities of pancreatic imaging, predicting islet cell function requires further exploration.

CONCLUSION

The relationship between the declined islet beta-cell function and the imaging changes in different pancreatic diseases, such as diabetes, pancreatitis, pancreatic cancer, fatty pancreas, and insulinoma has been reported by an increasing number of studies, but larger sample sizes and more rigorous studies are still needed. As imaging technologies continue to advance, they will likely play an increasingly important role in diagnosing, monitoring, and managing diabetes and other blood glucose disorders due to pancreatic diseases.