What is the relationship between iron overload and excess insulin production in horses?
Horses with too much insulin circulating in their blood — a condition known as hyperinsulinemia — are known to be at risk from equine Cushing’s disease and equine metabolic syndrome, a condition linked to laminitis.
Eleanor Kellon and Kathleen Gustafson, writing in the Open Veterinary Journal, noted that research in other species had revealed elevated body iron levels as both a predictor and consequence of insulin resistance.
The pair, with the Equine Cushing’s and Insulin Resistance Group in Tempe, Arizona, set out to explore the relationship between equine hyperinsulinemia and body iron levels.
The pair reviewed case histories and laboratory results from an open access database maintained by their group.
They identified 33 horses with confirmed hyperinsulinemia for which laboratory results were available for serum iron, total iron binding capacity, and ferritin (a protein that contains iron).
They found that serum ferritin exceeded the published reference range in all of the horses.
The researchers also found a trend for higher ferritin levels with advancing age.
“Since there is no avenue of excretion for excess iron, the degree of iron overload will represent iron accumulation over time and also may be more representative of the duration of hyperinsulinemia rather than hyperinsulinemia per se or degree of hyperinsulinemia.”
Additionally, the pair performed a secondary analysis of a previously reported controlled trial originally designed to test the correlation between iron status and the insulin response in horses.
They found significantly elevated ferritin levels in horses considered hyperinsulinemic by dynamic insulin testing compared to horses with a normal response.
“These results suggest the potential for iron overload in hyperinsulinemic horses, a feature documented in other species,” they said.
The findings, they said, should stimulate further study into the relationship between insulin and iron dysregulation in horses.
The researchers, discussing their findings, said considerable interplay has been described between iron metabolism and metabolic syndrome and type 2 diabetes in humans, laboratory animals and zoo animals.
“Increased body iron stores are a risk factor for insulin resistance and the development of type 2 diabetes.”
The pair noted that research in insulin-resistant, type 2 diabetic rats showed increased intestinal absorption of iron, making the iron-insulin link a self-perpetuating situation.
“Our data suggest similar interactions between hyperinsulinemia and body iron burden that could exist in the horse and are directions for future study.”
Kellon and Gustafson say many factors other than hyperinsulinemia may be associated with altered iron status.
“Serum ferritin is also an acute-phase reactant. Therefore, exercise, illness, and injury are known to increase serum ferritin levels.”
The term for the relationship between body iron stores and insulin in humans is dysmetabolic hyperferritinemia. “The influence is bidirectional, with iron burden influencing insulin levels and vice versa.
“Iron has been suggested as a therapeutic target for people with, or at risk of, hyperinsulinemia and type 2 diabetes, as well as laboratory animal models, dolphins, and other zoo species.
“If the situation is confirmed to be similar in horses, iron may be a modifiable risk factor for hyperinsulinemia.”
They say that while even severe iron overload can occur in horses without evidence of metabolic syndrome — and iron is unlikely to be an independent causal factor — the interplay uncovered in other species shows this is a factor worthy of further investigation.
“This preliminary retrospective investigation should increase awareness of the potential for iron overload in hyperinsulinemic horses and stimulate further study into the relationship between insulin and iron dysregulation.”
Possible dysmetabolic hyperferritinemia in hyperinsulinemic horses
Eleanor M. Kellon and Kathleen M. Gustafson
Open Veterinary Journal, (2019), Vol. 9(4): 287–293 DOI: http://dx.doi.org/10.4314/ovj.v9i4.2