Prefinal exam OSCE

Case : A 77 yr old female with uncontrolled diabetes mellitus 

OSCE questions:

 1) Steroid induced diabetes mellitus

Steroid-induced diabetes mellitus is defined as an abnormal increase in blood glucose associated with the use of glucocorticoids in a patient with or without a prior history of diabetes mellitus. 

The criteria for diagnosing diabetes by the American Diabetes Association  is 

 8 h fasting blood glucose ≥ 7.0 mmol/L (126 mg/dL), 

2 h post 75 g oral glucose tolerance test (OGTT) ≥ 11.1 mmol/L (200 mg/dL), 

HbA1c ≥ 6.5% or in patients with symptoms of hyperglycemic, a random plasma glucose of ≥ 11.1 mmol/L (200 mg/dL).

The effect of glucocorticoids on glucose metabolism is likely the result of impairment of multiple pathways including beta cell dysfunction (sensitivity to glucose and ability to release insulin) and insulin resistance in other tissue.

RISK FACTORS: 

Proposed risk factors for steroid-induced diabetes beyond cumulative dose and longer duration of steroid course include:

older age, family history, high body mass index and impaired glucose tolerance . 

The association with family history of diabetes is not well defined. 

 compared the demographics and clinical characteristics of patients with new onset SIDM with those with type 2 diabetes with and without steroid treatment. Those individuals who developed new onset SIDM had significantly less family history of diabetes when compared with individuals with type 2 diabetes mellitus and glucocorticoid treatment.

PATHOGENESIS 

Molecular basis of glucocorticoid action on glucose regulation

The insulin-mediated pathways of glycogen synthesis and protein degradation and synthesis are directly influenced by glucocorticoids . Skeletal muscle is responsible for the majority of insulin-mediated glucose uptake. Insulin recruits GLUT4 glucose transporters to the cell surface enabling glucose uptake into cell. Glucocorticoids impair insulin-mediated glucose uptake by directly interfering with components of the insulin signalling cascade, such as glycogen synthase kinase-3, glycogen synthase and GLUT4 translocation. 

An increase in protein degradation and decrease in protein synthesis is due to glucocorticoid inhibition of post-insulin receptor .

2) What is the mechanism of action of insulin at cellular level?

Insulin acts on a glycoprotein- tyrosine kinase receptors on the cell membrane and it binds to the alpha subunit which leads to phosphorylation of beta subunit.

This leads to transport of GLUT RECEPTORS on to the cell membrane which in-turn transports glucose into the target cell( adipocyte and muscle cell)

Learning points:

Tidal percussion in diaphragm palsy.

Clincical differentiation between type 1 and type diabetes mellitus.

Differences between osteoarthritis and rheumatoid arthritis. 

Treatment options for portal hypertension.