Insulin resistance Flashcards
What constitutes insuline resistance?
• No insulin dose clearly defines insulin resistance
• Most dogs and cats controlled on ≤1 IU/kg q12h
• Consider insulin resistance if…
- hyperglycaemia despite insulin dose >1.5 IU/kg q12h
- excessive dose of insulin required to maintain BG
<17mmol/L
- erratic control of hyperglycaemia with frequent dose
adjustment
- fructosamine >500μmol/L, up to 700μmol/L if severe
What problems with insulin therapy should be considered?
- Storage/handling/injection technique
- Diet/Exercise
- Insulin underdosing
- Stress hyperglycaemia
- Somogyi response?
- Short duration of insulin effect
- Prolonged duration of insulin effect
- Impaired insulin absorption
- Anti-insulin antibodies
Outline anti insulin antibodies
• Lente insulin: 10-14h in most dogs; 8-10h in most cats
• Significant increase in remission rates using long-acting insulin such as glargine or detemir in cats (up to 90%) vs lente insulin (~30%)
• AIA identified in 40-65% of dogs receiving pork/beef or beef source insulin – variable effect on glycaemia
• Species of origin is not a consideration in choosing insulin for cats
Diagnose by showing a nadir >4 less than 8 hours and a hyperglycaemia over 14 within 10 hours of injection
Either change to a longer acting insulin or do 8 hourly dosing
Outline HAC as a cause of resistance
- Glucocorticoids antagonise the actions of insulin in both hepatic and peripheral cells
- Iatrogenic? Stop glucocorticoid therapy
- Naturally occurring – most common concurrent disease in diabetic dogs - Chicken or the egg? Suspected HAC occurs first and unmasks subclinical diabetes
- Physical findings consistent with HAC often not evident when DM diagnosed
- Early indicators – ALP >500 IU/L; USG <1.020
- ~80% of cats with HAC have DM
Outline dioestrus induced DM resistance
• Direct effect of progesterone or indirect effect of GH
production from the mammary tissues
• GH is produced in feline mammary tissue however
it does not enter the systemic circulation
• Consider in newly diagnosed or poorly controlled intact female dogs with DM
• Treatment – OVH
• Outcome – resolution vs long-term DM (dependent
on the degree of β cell destruction)
Outline acromegaly/ hypersomatotropism as a cause of resistance
• Hypersomatotropism – excess GH production from pars distalis of the pituitary gland (hyperplasia or adenoma most common)
• Catabolic effects (insulin antagonism) DM
• Anabolic effects (in part mediated by IGF-1) -acromegaly
• Marcoadenoma may cause CNS signs
• Diagnosis – insulin resistant DM, IGF-1 >1000ng/mL (measure after 6-8wk of therapy), documented
pituitary mass
• Treatment – radiotherapy versus hypophysectomy versus insulin therapy
• Likely underdiagnosed - prevalence 17-25% of DM cats
• GH-secreting pituitary adenoma rare in dogs – 5 reported cases in the literature
Outline hyperthyroidism as a cause of insulin resistance
• Documented cause of insulin resistance in cats – rare comorbidity
• Hyperthyroidism glucose intolerance and insulin
hypersecretion
• Treat medically – methimazole/carbimazole;
consider reduction in exogenous insulin dose
• Glucose intolerance and insulin hypersecretion
deteriorate in some cats following treatment
Outline hypothyroidism as a cause of insulin resistance
• Mechanisms of carbohydrate intolerance controversial
- post-receptor defect in insulin-mediated glucose transport and metabolism
• Obesity, hyperlipidaemia
• [Fructosamine] increased due to reduced protein turnover
• BEWARE euthyroid sick syndrome – measure TSH +/- fT4
• Hypothyroidism can cause similar physical changes to acromegaly, due, at least in part, to increased
GH and IGF-1
• Treatment – levothyroixine (0.02-0.04mg/kg/day)
50-60% reduction of insulin requirement
How do concurrent illnesses cause insulin resistance?
• Increases secretion of counter-regulatory hormones
• Hyperglucocagonaemia documented in diabetic people with insulin resistance 2° to bacterial infection, CKD, metabolic acidosis
• Increased risk of infection in diabetic patients
- UTI in approximately 13% of cats
- periodontal disease
Outline chronic pancreatitis as a cause of insulin resistance?
- Probably under diagnosed
- Histological evidence in approximately 35% of dogs and 50% of cats at necropsy
- Release of diabetogenic hormones may exacerbate β cell depletion
- Fluctuating insulin requirements
- Supportive therapy
- EPI? – measure serum TLI
Outline CKD as a cause of insulin resistance
• Relatively common in diabetic cats – aged patients +
increasing evidence of diabetic nephropathy (histologically consistent lesions reported)
• Abnormal renal function may be 2° to DM or independent problem
• Can lead to prolonged duration of insulin effect or insulin resistance
Outline hyperlipidaemia as a cause of insulin resistance
diagnosis requires 16-24h fast. Usually the
result of poor diabetic control or presence of concurrent disease causing lipid dysregulation e.g. hypoT4, HAC, idiopathic hyperlipidaemia (miniature schnauzers)
Outline the effect of obesity on insulin resistance
The effects of obesity and glucose toxicity on insulin resistance are reversible and insulin sensitivity improves with correction of obesity and hyperglycaemia
What are the most common neoplasias to cause insulin resistance
pheochromocytoma, glucogonoma, mast cell
tumour, lymphoma
How do you address insulin resistance
- Rule out problems with insulin dosing first
- Dogs – severe obesity, diabetogenic drugs, HAC, dioestrus, chronic pancreatitis, CKD, infection (oral or urinary tract), hyperlipidaemia, anti-insulin antibodies
- Cats – severe obesity, CKD, chronic pancreatitis, stomatitis/periodontal dz, HAC, hypersomatotropism
- If the cause of insulin resistance cannot be identified, mild insulin resistance can often be overcome by increasing the insulin dose
