Pancreatic fat in type 2 diabetes: Causal or coincidental?

Table 1 Nomenclature of pancreatic fat accumulation

Name	Definition
Pancreatic steatosis or fatty pancreas or pancreatic lipomatosis	General terminology for accumulation of pancreatic fat
Lipomatous pseudohypertrophy	An extreme form of pancreatic fat accumulation with uniform or focal enlargement of the pancreas and replacement of exocrine system by adipose tissue which is unrelated to obesity
Fatty replacement	Replacement with adipocytes following death of pancreatic acinar cells
Fatty infiltration	Obesity-related infiltration of the pancreas with adipocytes
NAFPD	Pancreatic fat accumulation along with obesity and metabolic syndrome
Non-alcoholic fatty steatopancreatitis	Pancreatitis resulting from accumulation of pancreatic fat

NAFPD: Non-alcoholic fatty pancreas disease.

Table 2 Studies showing association or lack of association between pancreatic fat and type 2 diabetes

S.No.	Title	Inference/key observation	Ref.
Studies showing association of pancreatic fat with T2D
1	Pancreatic fat infiltration, β-cell function and insulin resistance: A study of the young patients with obesity	Elevated blood glucose levels and reduced beta cell function (HOMA-β and IGI) were reduced in subjects with HPF	Wen et al[65], 2022
2	Association of pancreatic fat content with type II diabetes mellitus	Elevated fat content in the pancreatic tail region may identify patients at risk for T2D	Nadarajah et al[64], 2020
3	Pancreatic steatosis associates with impaired insulin secretion in genetically predisposed individuals	Pancreatic fat leads to impairment of beta-cell function in subjects at genetic risk for diabetes	Wagner et al[66], 2020
4	Longitudinal association of fatty pancreas with the incidence of type-2 diabetes in lean individuals: a 6-year computed tomography-based cohort study	Lean subjects with fatty pancreas can lead to development of T2D	Yamazaki et al[67], 2020
5	Association of pancreatic steatosis with chronic pancreatitis, obesity, and type 2 diabetes mellitus	T2D is associated with higher pancreatic fat along with visceral and subcutaneous adiposity	Tirkes et al[62], 2019
6	Pancreatic fat content is associated with β-cell function and insulin resistance in Chinese type 2 diabetes subjects	Male subjects with T2D, demonstrated positive association between pancreatic fat content and insulin resistance	Lu et al[63], 2019
7	The effect of fatty pancreas on serum glucose parameters in patients with non-alcoholic steatohepatitis	NASH patients with high pancreatic fat had impairment in glucose metabolism	Uygun et al[39], 2015
8	Pancreatic fat and β-cell function in overweight/obese children with non-alcoholic fatty liver disease	Association of higher pancreatic fat content in subjects with prediabetes as compared to non-diabetic NAFLD obese children	Pacifico et al[61], 2015
9	The association between non-alcoholic fatty pancreas disease and diabetes	NAFLD and fatty pancreas were linked to diabetes, irrespective of age, gender, obesity, or other cardiometabolic risk factors	Ou et al[37], 2013
10	Pancreatic fat content and β-cell function in men with and without type 2 diabetes	Inverse correlation of pancreatic fat content with insulinogenic index and beta-cell glucose sensitivity in all the study subjects	Tushuizen et al[15], 2007
Studies showing lack of association of pancreatic fat with T2D
1	Lack of independent association between fatty pancreas and incidence of type 2 diabetes: 5-year Japanese cohort study	No independent association between T2D and pancreatic fat was observed upon correction for possible confounders such as BMI and hepatic attenuation	Yamazaki et al[68], 2016
2	Pancreatic adipose tissue infiltration, parenchymal steatosis and beta cell function in humans	Pancreatic fat was related to age, but not to blood glucose levels. No association between pancreatic fat and insulin secretion or beta cell activity in T2D subjects was observed	Begovatz et al[71], 2015
3	Ethnic differences in pancreatic fat accumulation and its relationship with other fat depots and inflammatory markers	No correlation between pancreatic fat and beta cell function was observed, during intravenous glucose tolerance tests in obese normoglycemic adolescents	Lê et al[69], 2011
4	Ectopic fat storage in the pancreas, liver, and abdominal fat depots: impact on β-cell function in individuals with impaired glucose metabolism	Pancreatic fat was increased in individuals with impaired glucose tolerance, without any direct relation with β-cell function	van der Zijl et al[70], 2011
5	Clinical implications of fatty pancreas: correlations between fatty pancreas and metabolic syndrome	Association between pancreatic fat and insulin resistance was mediated by visceral adiposity	Lee et al[38], 2009
6	Pancreas volumes in humans from birth to age one hundred taking into account sex, obesity, and presence of type-2 diabetes	Pancreatic fat levels increases with aging and obesity; however, it remained unchanged in subjects with T2D	Saisho et al[16], 2007

HPF: High pancreatic fat; HOMA-β: Homeostasis model assessment of β-cell function; NASH: Non-alcoholic steatohepatitis; NAFLD: Non-alcoholic fatty liver disease; T2D: Type 2 diabetes; IGI: insulinogenic index.