Type I vs Type II
Which diabetes can be prevented through lifestyle modifications?
Type II
A major risk factor for type II is obesity. Weight loss can improve glucose levels.
What type of cells are destroyed in type I diabetes?
Pancreatic Beta Cells
Type I is an autoimmune disorder, causing a destruction of beta cells. The destruction is set off by an environmental trigger in a genetically susceptible person.
What is usually the first line therapy in new diagnosis of type II diabetes?
Lifestyle modifications - weight loss and exercise can improve glucose levels.
Whats the difference between a basal insulin and a bolus insulin?
Basal is long acting and can be taken once a day to keep a low steady level of insulin.
Bolus is rapid acting insulin that can be taken with meals.
Name some acute symptoms of diabetes
Polyuria, polydipsia, dehydration, hunger, weight loss, blurred vision, altered mental status
Which type can have chronic complications such as cardiac disease, renal failure, neuropathy and blindness?
BOTH!
A few pathways can lead to complications of diabetes: non-enzymatic glycation, sorbitol accumulation and atherosclerosis.
What causes decreased glucose transport into cells in type II diabetes?
Increased free fatty acids from visceral fat breakdown.
Visceral fat presents a greater risk for diabetes than subcutaneous fat because visceral fat breakdown is less inhibited by insulin, leading to more lipolysis and thus more free FAs. The FAs are used as fuel more than glucose.
What is the first line medication therapy in type II?
Metformin - it increases insulin sensitivity and can cause weight loss.
What type of diabetes is treated with insulin?
Type I is ALWAYS treated with insulin.
Type II may require insulin in the advanced stages of the disease.
Name a condition that diabetes can come secondary to
Pancreatic disease --> destruction of islet tissue
Other endocrinopathies --> excess hormones that antagonize effect of insulin
Drugs --> corticosteroids can increase insulin resistance
Which type will see amyloid deposition in pancreatic islets?
Type II
When hyperinsulinemia occurs in T2DM, amylin is produced along with insulin. This can be seen in up to 70% of patients.
What genetic component is found in 90-95% of patients with type I diabetes?
HLA-DR3 and HLA-DR4
Multiple genes may be involved
What receptor do TZDs bind to?
PPAR-gamma.
Bind to PPAR-gama, then that complex binds to RXR receptors. This complex is able to modify gene transcription.
Increase expression of genes involved in promoting lipid storage and decrease genes associated with inflammation (IL-6).
Which insulin is linked to a fatty acid chain?
Detemir
Detemir was a FA(d)
What type of hypersensitivity reaction is type I diabetes?
Type IV hypersensitivity --> T cell mediated destruction of Beta cells
Which type can have an associated complication with "fruity" smelling breath as a symptom?
Type I --> DKA, breath smells fruity from acetone odor. Insulin deficiency leads to ketone production.
How are the renal arterioles affected in diabetic kidney disease?
Afferent arteriole = ischemia
Efferent arteriole = hyperfiltration
From hyaline arteriosclerosis, often from AGEs.
Why do sulfonylureas cause insulin release from beta cells by binding to their receptors in the pancreas?
Sulfonylurea receptors are associated with ATP dependent K+ channels in beta cells - when they bind, the K+ channels will close raising the resting membrane potential. Cell will depolarize and open calcium channels allowing calcium to enter the cells and then cause insulin release.
Meglitinides have a similar mechanism but can be used in patients who have a sulfa allergy.
Which type of insulin is give in an emergent DKA or HHS situation?
IV regular insulin.
Rapid acting insulin and regular insulin have the same onset of action (immediate) when given IV. Rapid acting is only faster when given in a sub-cutaneous route.
Which scenario carries a higher risk of developing type I diabetes: your mother has type I or your father has type I?
Father = 5-6%
Mother = 2-3%
67 y/o M, BMI of 41, 20 ppd smoker comes in to the office reporting foot pain that has turned to numbness. What is the most likely etiology of his symptoms?
Peripheral neuropathy in the setting of type II diabetes.
Peripheral neuropathy is the most common complication of T2DM (50% of patients). Risk factors are chronic hyperglycemia, smoking, HTN, hyperlipidemia.
A patient known to have type I diabetes comes in with fruity smelling breath, fever, headache, and eye pain. What is the most likely diagnosis?
DKA with complication of mucormycosis --> fungal infection that thrives in high glucose, ketoacidosis conditions. Starts in the sinuses and spreads to adjacent structures.
Which class of drugs slows the absorption of glucose by inhibiting the actions of an upper GI enzyme that breaks the alpha 1,4 bonds in a glucose polymer?
Alpha-Glucosidase Inhibitors
Acarbose and Miglitol
55 y/o woman with medically managed T2DM is experiencing recurrent UTIs. What medication is she most likely taking?
An SGLT2 Inhibitor.
SGLT2 inhibitors act on the SGLT2 glucose transporter in the proximal tubule that normally reabsorbs 90% of filtered glucose. Patients will then excrete a lot more glucose in their urine to lower glucose levels in the body. Bacteria causing UTIs feed off this sugar.
What is the only diagnostic criteria for diabetes that does not need a repeat test?
Random plasma glucose > 200 mg/dL with symptoms