Fatty pancreas increases diabetes risk, but may be reversible with weight loss
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Adults with an elevated level of pancreatic fat have higher risk for developing incident diabetes, but weight loss may be able to lower diabetes risk by reducing fat levels and increasing pancreatic volume, according to a presenter.
“Fatty pancreas is associated with insulin resistance and increased insulin secretion cross-sectionally in nondiabetic individuals and is more prevalent in type 2 diabetes,” Richard E. Pratley, MD, the Samuel E. Crockett Chair in Diabetes Research, medical director of AdventHealth Diabetes Institute and a Healio | Endocrine Today Co-editor, said during a presentation at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “I think this might be a compensatory response initially. Longitudinally, fatty pancreas is associated with a loss of insulin secretory function and diabetes, but this seems to be reversible [with weight loss].”
Prevalent diabetes is common in people with chronic and acute pancreatitis. According to multiple published studies, about one-third of adults with chronic pancreatitis have prevalent diabetes, and the lifetime risk for developing diabetes with chronic pancreatitis is as high as 75%.
For adults with acute pancreatitis, the risk for developing diabetes within 5 years is between 15% and 24% and increases to 40% after 5 years. Risk factors for diabetes with acute pancreatitis include obesity and visceral adiposity. Pratley noted there are limited data on diabetes-related risk factors and noted his institution, AdventHealth Diabetes Institute, is participating in the Type 1 Diabetes in Acute Pancreatitis Consortium to better understand how diabetes develops in people with acute pancreatitis.
Pancreatic fat and insulin secretion
Several studies have explored the mechanisms of how pancreatic fat may be linked to diabetes development. A study published in Diabetes Care in 2012 found higher pancreatic fat levels were associated with increased insulin resistance and insulin secretion in adults, but the effects varied by race. Black participants in the study had less pancreatic fat compared with Hispanic and white participants, but the group still had increased insulin secretion and insulin resistance.
“If you look at the relationship between pancreatic fat and insulin secretion, you can there’s a markedly different relationship between the Blacks, whites and Hispanics,” Pratley said. “This is telling us something about the fundamental biology.”
Several studies have analyzed how pancreatic fat affects insulin secretion. One study published in Diabetes in 2022 compared pancreas fat in 208 participants with normoglycemia, 117 with prediabetes and 43 with type 2 diabetes. The study found people with prediabetes and type 2 diabetes had more pancreas fat than those with normoglycemia. However, while pancreas fat was associated with greater insulin resistance, associations were not observed between pancreas fat and insulin secretion.
Another study conducted in Japan measured C-peptide responses in adults who underwent glucagon stimulation testing. The study found pancreatic fat was associated with greater insulin secretion. However, people with more pancreatic fat had a gradual loss of insulin secretion over time.
A study conducted with adults in Germany and Japan divided participants into groups based on whether they had high levels of liver fat, pancreatic fat, muscle fat or normal fat levels. The group with high pancreatic fat had lower insulin sensitivity and higher risk for incident diabetes than adults with normal fat levels.
Reducing pancreatic fat with weight loss
Research has shown reducing pancreas fat could have health benefits for people with type 2 diabetes. In a study where people with type 2 diabetes lost weight after eating a very low-calorie diet, the cohort had a decrease in pancreatic fat and improved insulin secretion during follow-up. Another study of adults with type 2 diabetes participating in the Diabetes Remission Clinical Trial analyzed pancreatic volume and fat changes among those who achieved diabetes remission. The remission group had increased in pancreatic volume and reductions in pancreatic fat compared with adults who did not achieve remission.
Pratley said identifying and treating fatty pancreas early is crucial in order to avoid future complications.
“If the patient is unlucky enough to develop acute pancreatitis, there is further insult with insulin secretion and diabetes may develop, without any change in insulin resistance,” Pratley said. “If you follow this spectrum down the road, you could end up with end-stage chronic pancreatitis and even pancreatic ductal adenocarcinoma. Pancreatitis is a risk factor for that.”
References:
- Al-Mrabeh A, et al. Lancet Diabetes Endocrinol. 2020;doi:10.1016/S2213-8587(20)30303-X.
- Ishibashi C, et al. J Diabetes Investig. 2020;doi:10.1111/jdi.13108.
- Skudder-Hill L, et al. Diabetes. 2022;doi:10.2337/db21-0976.
- Szczepaniak LS, et al. Diabetes Care. 2012;doi:10.2337/dc12-0701.
- Taylor R, et al. Cell Metab. 2018;doi:10.1016/j.cmet.2018.07.003.
Perspective
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The pancreas is important but is the least studied organ in type 2 diabetes. The effect of chronic fat exposure in inducing beta-cell dysfunction was demonstrated by Roger Unger, MD, back in 1994, with only beta cells from rodents genetically predisposed to obesity-induced diabetes being affected. The resulting lessons for human type 2 diabetes are profound.
There are three very different compartments of fat within the pancreas: interstitial adipose tissue, the largest but probably irrelevant to beta-cell function; inter-lobular fat depots, also distant from beta cells; and intracellular fat, likely to be directly relevant to beta-cell function. The latter is equally raised in exocrine and endocrine cells.
The recovery of first phase insulin secretion over 8 weeks of weight loss suggests a relevant, rapidly mobilizable pool of excess fat in those who clearly have fat-susceptible beta cells. Cross-sectional studies will inevitably involve mixed groups of people, some with susceptible beta cells and some unresponsive to fat, making associations artificially weak. Within all ethnic groups, pancreas fat levels in people with type 2 diabetes are higher than the relevant norm.
Excess intra-pancreatic fat appears to induce beta-cell dysfunction in the susceptible, a process reversible with weight loss.
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Pratley R. Session 8: Fatty Pancreas Disease. Presented at: World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease; Dec. 1-3, 2022; Universal City, California (hybrid meeting).
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