Endocrine Flashcards
When endogenous ACTH samples were collected 5 minutes apart, and the mean of these taken, did this provide a more accurate diagnosis of PPID?
Paired measurement of ACTH concentration offers no advantage over a single measurement. In addition to there being no statistical difference, the use of paired measurements would not have influenced clinical decision making in the population of horses investigated.
10.1111/jvim.12489
In humans, measurement of free cortisol may more accurately reflect systemic cortisol activity. How is cortisol handled in the equine?
90% of cortisol is bound to cortisol binding globulin or albumin. The free cortisol is the biologically active form, bc of its ability to bind to steroid receptors to mediate cortisol’s systemic effects.
10.1111/jvim.13839
What effects did sex, age, body condition and season have on free cortisol measurements in the healthy horse?
There was a significantly increased free cortisol concentration in healthy overweight/obese control horses.
Season significantly impacted total cortisol and insulin concentrations, but not free cortisol measurements, in our healthy horses.
10.1111/jvim.13839
How did total and free cortisol measurements between healthy adult horses and horses with endocrine diseases differ? Was total or free cortisol measurements significantly associated with insulin concentration in horses?
FCF is increased in horses with endocrine disease and associated with hyperinsulinemia, with a significant, almost 2‐fold increase in FCF, but not total cortisol observed in animals with PPID as compared to healthy age‐matched horses. Free cortisol fraction was also similarly and significantly increased in horses and ponies with endocrine disease (PPID or EMS) and concurrent ID characterized by hyperinsulinemia, and FCF and insulin were significantly and positively correlated in these hyperinsulinemic animals as anticipated and as described in people.
10.1111/jvim.13839
List four different tests for insulin dysregulation in horses and briefly describe them.
Oral sugar test - administration of light corn syrup; blood drawn before and 60 and 90 minutes after; insulin n = <45uU/mL at 60 minutes and < 60 uU/mL at 90 minutes; abn = > 60 uU/mL at any time
Basal serum insulin concentration - fasting insulin concentration should be < 20 uU/mL
Combined glucose-insulin test - blood samples before and post dextrose and insulin admin; insulin resistance = BG > baseline for 45 minutes or longer; insulin > 20 uU/mL at baseline abn or > 100 uU/mL at 45 min
Frequently sampled insulin-modified intravenous glucose tolerance test - dextrose given, then insulin 20 minutes later; blood draw to measure glucose and insulin frequently
10.1111/jvim.13934
For the oral sugar test, how long, if at all, should a horse be fasted, prior?
3 hours at minimum.
10.1111/jvim.14529
In a model of a dynamic feeding system, what effects occurred on body weight and insulin sensitivity?
Body condition score was decreased, cresty neck score was decreased and body fat score was decreased. The increase in exercise did not show an improvement in insulin sensitivity.
10.1111/jvim.14577
What is octreotide?
Octreotide is a somatostatin analog. Somatostatin is produced by the delta cells of the pancreas, and is responsible for inhibiting release of glucagon, insulin and pancreatic polypeptide. Glucose, amino acids and glucagon-like peptide-1 are responsible for stimulation of somatostatin release.
Octreotide may have the ability to be used as a diagnostic in insulin resistance. A study showed that after administration, octreotide was able to decrease plasma insulin concentrations, followed by an increase in glucose concentration.
10.1111/jvim.14718
What is metabolomics?
Metabolomics is the study of small-molecule metabolites that are involved in cellular metabolism. Eg. nucleotides, AA, FA, carbohydrates, etc.
Elevations in the serum of certain metabolites can indicate a disturbance in the metabolic process in the tissues. In humans it has been elucidated that metabolites related to insulin resistance, glucose intolerance, obesity and DM II are changed.
10.1111/jvim.15095
How are metabolites being evaluated in horses?
A study was done in Welsh ponies, (healthy and insulin-dysregulated, obese or nonobese, hx of laminitis or no history of laminitis), to evaluate metabolite levels and differences between the two groups.
Study found that metabolomic profiling is a relevant approach for further defining metabolic alterations because of insulin dysregulation and obesity in horses. Examination of the serum metabolome of this Welsh Pony cohort demonstrated significant differences in metabolites primarily derived from the lipid and amino acid pathways when comparing ponies grouped by each EMS phenotype (insulin response, obesity status, and laminitis history).
10.1111/jvim.15095
What is the role of insulin?
Insulin is released in response to an elevation of glucose in the peripheral blood stream. Insulin regulates lipid and carbohydrate metabolism, but increasing glucose uptake from the blood by skeletal muscles, adipose tissue and liver.
Glucose is stored as glycogen and triglycerides. Low levels of insulin then increases hepatic glucose secretion by promoting gluconeogenesis and glycogenolysis.
10.1111/jvim.15138
What is a proposed mechanism of insulin dysregulation?
Insulin resistance can occur with failure of tissues to respond to exogenous and endogenous sources of insulin, resulting in uncontrolled hyperglycemia.
This can be caused by decreased availability of insulin receptors as a result of cellular hypoxia and oxidative stress, causing activation of inflammation pathways and inhibition of post-receptor insulin signaling pathways.
10.1111/jvim.15138
How has systemic inflammation been assoc. with insulin dysregulation in horses?
Lipopolysaccharide (LPS) infusion has been shown to result in peripheral tissue insulin resistance, and acute gastrointestinal disease results in hyperglycemia, also suggesting peripheral tissue insulin resistance.
10.1111/jvim.15138
What was the result of a study looking at assoc. between hyperinsulinemia and hyperglycemia, with outcome, in horses with SIRS?
There was an assoc. of hyperinsulinemia and favorable outcome and assoc. of hyperglycemia and poor outcome. This suggests an appropriate pancreatic response to SIRS-assoc hyperglycemia is assoc with survival.
This indicates that severe hyperglycemia, in the face of an inadequate insulin response, is associated with non‐survival and reflects a possible state of relative hypoinsulinemia or inappropriate lack of insulin secretion. In addition, although serum insulin concentration was significantly higher in survivors, it was rarely above reference range (20 µIU/mL) suggesting that, rather than excessive insulin secretion in survivors, decreased insulin secretion was observed in nonsurvivors. Taken together, these data suggest that, in horses, SIRS‐associated hyperglycemia is caused by peripheral tissue insulin resistance and by pancreatic dysfunction resulting in decreased insulin secretion.
Clinicopathologic evidence of insulin dysregulation, reflected by hyperinsulinemia and peripheral tissue insulin resistance, may not be associated with poor prognosis in the context of SIRS. In such cases, hyperinsulinemia might indicate a better prognosis, because it implies an intact endocrine pancreas capable of responding to SIRS‐associated hyperglycemia.
10.1111/jvim.15138
What is the insulin/glucose ratio used to estimate? How was the ratio affected in horses with SIRS?
This ratio is used to estimate pancreatic insulin secretion in response to a glycemic challenge.
In this study, the insulin/glucose ratio was lower in nonsurvivors. Although the use of proxies, such as this ratio, has not been fully validated in horses, this difference between survivors and nonsurvivors confirms that the degree of pancreatic dysfunction in nonsurvivors was worse than in survivors.
10.1111/jvim.15138
