From the Guidelines
Yes, humans generally produce fewer incretins as they age. Incretin hormones, primarily glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released from the intestines after eating and help regulate blood glucose by stimulating insulin secretion. With advancing age, the body's ability to secrete these hormones diminishes, which contributes to the increased prevalence of glucose intolerance and type 2 diabetes in older adults. This age-related decline in incretin function appears to result from changes in gut physiology, reduced sensitivity of pancreatic beta cells to incretin signals, and alterations in the enteroendocrine cells that produce these hormones, as discussed in the context of GLP-1 receptor agonists 1.
The decreased incretin effect may explain why older individuals often have higher postprandial glucose levels even without diagnosed diabetes. Key factors influencing this decline include:
- Changes in gut physiology
- Reduced sensitivity of pancreatic beta cells to incretin signals
- Alterations in the enteroendocrine cells that produce these hormones
This natural decline in incretin production is one reason why incretin-based therapies like GLP-1 receptor agonists (such as semaglutide, dulaglutide, or liraglutide) and DPP-4 inhibitors (like sitagliptin or linagliptin) are often effective treatment options for older adults with type 2 diabetes, as they can compensate for the body's reduced natural incretin response. While physical activity can improve insulin sensitivity and overall health in older adults 1, the primary concern regarding incretin production remains its decline with age.
From the Research
Incretin Production and Aging
- The provided studies do not directly address the relationship between aging and incretin production 2, 3, 4, 5, 6.
- However, they discuss the role of incretins, such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), in glucose homeostasis and their potential as therapeutic agents for type 2 diabetes.
- The studies focus on the physiological functions of incretins, their degradation, and strategies to enhance their activity, but do not explore how their production changes with age.
Incretin Function and Diabetes
- The incretin effect is attenuated in type 2 diabetes, and strategies to leverage the beneficial effects of GLP-1, such as GLP-1 receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors, have been developed 3, 4, 5, 6.
- GLP-1 has been shown to improve glycemic control, promote weight loss, and have other beneficial effects on glucose homeostasis and pancreatic function 3, 4, 5, 6.
- However, the relationship between aging and incretin production remains unclear, and further research is needed to determine if there is a decline in incretin production with age.