Fatty Pancreatic Disease Among DMtype2 Obese & Non-obese People and the Role of Microbiome-Metabolomics
Vol. 28, Issue 2 (June 2023)
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Reda Elbadawy, MD
Banha University Hospital
Egypt
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Fatty pancreas emerged as serious component related to Metabolic Syndrome Mets. Also, potentially leading to DM type 2, chronic pancreatitis with pancreatic insufficiency, and lastly pancreatic cancer. Fatty pancreas or nonalcoholic fatty pancreatic disease (NAFPD) is an excessive fat infiltration of the pancreas due to obesity in the absence of significant alcohol intake. The potential systemic and local consequences of excessive fat accumulation in the pancreas have not been well established.
Although non-alcoholic fatty pancreas (NAFP) was reported early in the 1930s, our knowledge about this disease is still in its infancy and perceived as a relatively new condition. NAFP is defined as pancreatic fat deposition in the absence of significant alcohol intake.1, 2 It was considered a benign incidental finding, and therefore its clinical consequences were ignored. The prevalence of NAFP ranges from 16–35% and is increasingly associated with obesity, IR, deterioration of beta-cell function and metabolic syndrome which might lead to the development of diabetes and pancreatitis.1 Therefore, its early detection may help to diagnose prediabetic patients to reduce the rising morbidity and mortality due to diabetes mellitus.
High energy intake in human (obesity) may lead to excessive fat which could be accumulated in visceral organs that are unusual for adipose tissue storage, the so-called ectopic fat.3
Fatty pancreas or non-alcoholic fatty pancreatic disease (NAFPD) is an excessive fat infiltration of the pancreas in the absence of significant alcohol intake.4 Fatty pancreas is a common ultrasound finding which has increased echogenicity when compared to the normal pancreas which contain fat up to 6% of its tissue.5
On the contrary to the nonalcoholic fatty liver disease (NAFLD), the potential systematic and local consequences of excessive fat accumulation in the pancreas have not been well established. Fatty infiltration in the pancreas has been shown to correlate with the metabolic risk factors and may represent a meaningful manifestation of metabolic syndrome. Epidemiology study also suggests that obesity is a risk factor for pancreatic cancer.6 Based on a study, fatty infiltration in the pancreas may increase the risk of pancreatic ductal adenocarcinoma beyond the effect of obesity alone.7 It is usually an incidental finding during transabdominal ultrasound examination and its clinical significance is still poorly understood.
Prevalence of NAFPD has been reported in Asia as well as in Western countries. In Taiwan, Wang et al. reported that 16% of Chinese population had fatty pancreas.8 In USA, Sepe et al. reported as high as 27.8% of the patients who underwent EUS evaluation had NAFPD.3 In Indonesia, which represents the biggest Southeast Asian country, the prevalence of NAFPD in the medical check-up population was 35%. Egyptian studies had explored NAFPD and its relation to obesity or DM and the conclusions were that fatty pancreas was triple that of fatty liver and present in non-obese non-diabetics too.10 Pancreatic fat content may play a role in several local pathological processes such as pancreatic cancer or subtypes of pancreatitis. In addition, available data suggest that decreased pancreatic volume and increased pancreatic fat content are more frequently observed in subjects suffering from impaired glucose metabolism and pancreatic fat content was reported to correlate with insulin secretion in subjects at increased risk for metabolic diseases. Larger studies covering greater numbers of participants report rather inconsistent results on a direct association of pancreatic fat content and impaired glucose metabolism.
Endoscopic ultrasound (EUS) examination is the most sensitive tool for examining the pancreas in the era of modern imaging development; however, the availability, cost, and training are still debatable, especially in most developing countries.7 The new paradigm of NAFPD, risk factors, its clinical impact on pancreatic cancer development and screening modalities for early detection are considered by use of EUS. Other modalities like CT and MRI can also be used but are expensive and not available at all centers.
Patients with type 2 DM have a two-fold increase in the risk of pancreatic cancer.8 Therefore, T2DM patients with NAFPD should be considered for pancreatic cancer screening and surveillance. However, previous studies provided inconsistent results regarding the association of NAFPD with age, sex, hypertension, hypertriglyceridemia, and NAFLD. Gut microbiome in patients with diabetes secondary to chronic pancreatitis (called Type 3c DM) is different from those with Type 1 and Type 2 diabetes in a cross-sectional preliminary study that included eight patients with Type 1, 10 with Type 2, 17 with Type 3c diabetes and nine healthy controls.9
Fatty pancreas was diagnosed even in non-obese non-diabetic subjects in an Egyptian pilot study and it was three times that of NAFLD too.10
Currently, no Microbiome/metabolomics studies have been done in Egypt examining fatty pancreas DM/non-DM, and also using obese/non obese as simple noninvasive biomarker for diagnosis and therapy too. As such, a cross sectional study will be conducted to determination the prevalence of NAFPD among obese and non-obese people with and without DM type 2. Evaluation of associated risk factors will be explored. This helps to handle and treat NAFPD and reduce the progress of the disease to DM, chronic pancreatitis with its complications like cancer pancreas. Also evaluation of microbiome profile /metabolomics as a simple noninvasive biomarker in diagnosis , therapy for NAFPD to prevent the development of DM and its complications. For this study, enrollment and randomization of patients will be from Banha University Hospital. There will be two cohorts, Group 1: obese and non-obese with diabetes and Group 2: obese and non-obese without diabetes included, as well as additional randomly selected patients with no history of chronic pancreatic diseases, DM type 2 or drugs induced pancreatic disorders. All patients will be evaluated clinically with laboratory testing and abdominal ultrasound for grading of fatty liver and pancreas echogenicity. We anticipate that the results of our study will provide a better understanding of prevalence of NAFPD among different study populations, explore metabolomics and other risk factors for disease progression.
References:
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