Dr Nichol Schultz – University of Minnesota – My Horse University
29 January 2013
No change in definition of EMS phenotype:
Obesity (BCS 7 or more)/regional adiposity (crest, shoulder, tailhead, sheath/udder)
Predisposition to subclinical or clinical laminitis.
Not all fat horses have EMS and not all EMS horses are fat.
Normal glucose function: high blood glucose causes pancreas to produce insulin which instructs fat and muscle cells to uptake glucose to achieve normal blood glucose levels.
With insulin resistance: cells become resistant to insulin's instruction to take up glucose, pancreas secretes more insulin to achieve normal blood glucose levels, leading to high blood insulin levels - high blood insulin levels can induce laminitis.
Unlike humans, horses with EMS typically maintain blood glucose levels within the normal reference range and do not develop type 2 diabetes.
Horses with EMS may also have elevated triglycerides and leptin. Impaired response to leptin results in over-eating, obesity and insulin resistance.
Why is it that several horses can be on the same pasture, eating the same diet, but only one of them develops laminitis? Likely genetic predisposition for EMS – EMS seen more in "easy keeper" breeds that need less nutrition than other horses to maintain bodyweight.
Thrifty genotype proposed where metabolic efficiency is an adaptive survival strategy for a harsh nutrient sparse environment – which in a domestic environment with rich pastures, grain feeds and low exercise can lead to weight gain and laminitis.
Uni of Minnesota research to identify any underlying genetic susceptibility to EMS looked at environmental risk factors for EMS and variation in DNA of horses with/without EMS.
Data collected from over 600 horses, paired 1 normal and 1 suspected of having EMS from same farm, data collected included neck circumference to height ratio, Body Condition Score, fasted blood samples for glucose, insulin, triglycerides, leptin, optional Oral Sugar Test, diet analysis, exercise information.
5 breeds targeted (Morgan, welsh pony, TWH, QH, Arab) either for increased incidence of EMS or highly represented in USA.
26% obese, 25% had history of laminitis (but non-representative population as 50% suspected of having EMS).
No difference in gender of horses getting laminitis.
Average reported age of laminitis onset – 10 years.
Most horses experienced their most recent laminitis episode in June – late spring and early summer had most cases – ties in with abundant pasture –but there were laminitis cases reported in every month.
Neck circumference to height ratio was greater in horses with history of laminitis, but large variation between breeds limiting usefulness without breed specific cut offs.
Fasting insulin levels higher in horses with a history of laminitis, however large amount of overlap among insulin levels from horses with and without a history of laminitis (but lack of history of laminitis doesn't preclude EMS), fasting insulin levels much more variable among horses with a history of laminitis. May be that horses with a history of laminitis are more suseptible to variation in insulin levels than horses without a history of laminitis given the presence of certain conditions e.g, obesity, dietary factors, level of exercise, genetics or combination of factors.
Proposed genetic influence – both genes and environment likely to affect risk for EMS. Say:
Group A – no gene for EMS and poor nutrition = low insulin
Group B – no gene for EMS and overfed = higher insulin
Group C – genetic risk factor for EMS, variable nutrition = variable level of insulin from low to high – if fed low NSC diet insulin can be low, if fed high NSC diet insulin can be high.
Overlap of blood test measurements between affected and unaffected (but obese) individuals makes it difficult to establish a cut off point that correctly classifies individuals as positive or negative for EMS - better diagnostic tests needed.
Identifying which genes are involved and how these genes function could improve diagnostics and direct preventative and management strategies.
Uni of Minnesota are looking at genetic variants associated with EMS traits using genome wide association analysis (GWAS) in ~ 300 morgan horses. Looked at insulin, OST, triglycerides, laminitis, scanned entire genome and at each marker perform statistical tests to identify if marker associated with EMS trait.
EMS is a complex trait - just because a horse has a mutation in a gene that makes them susceptible to EMS, doesn’t mean they will develop EMS - may depend on certain environmental factors being present, or multiple genes being involved.
Gene-Gene interactions: e.g.
Horse with several risk genes - very high insulin
Horse with 1 risk gene - high insulin
Horse with 0 risk genes - normal insulin
Gene-Environment Interactions: e.g.
Horse with 2 risk genes - lush pasture & no work - very high insulin
Horse with 2 risk genes - normal pasture & some work - high insulin
Horse with 2 risk genes - hard work - normal insulin
Work in progress:
Examining relationship between EMS traits and genetic variation.
Examining relationship of EMS traits and genetic variation under different environmental conditions.
Develop a diagnostic test to identify at risk horses for EMS, enabling management changes or therapeutic intervention to be put in place prior to development of laminitis.
Improve preventative and therapeutic management of EMS associated laminitis.
Leptin – strongly correlated with obesity status.
Grazing muzzles good way to limit grass, encourage weight loss.
Some breeds more susceptible than others – believe there is a genetic variant – draughts don’t usually get EMS.
Excessive water consumption associated with PPID (rather than EMS).
Sheath swelling – usually reduces with weight loss.
Testing – start with fasting insulin, then Oral Glucose/Sugar Test if normal or perhaps to catch earlier stages.
Testing T3 & T4 – EMS horses have normal thyroid, so testing T3/T4 not diagnostic of EMS.
Best treatment – weight loss, restrict pasture access, keep feet properly trimmed, return to exercise when able, improve insulin sensitivity.
Supplements – limited scientific studies but none found beneficial.
Thyroid hormone supplementation can be used short term to encourage weight loss.
Evidence of laminitis – hoof rings, x-rays best.
Bacteria involved in obesity? Still a lot to learn!
No longer collecting samples for genetics study at Uni of MN.