Term
|
Definition
| a heterogeneous group of syndromes characterized by elevation of blood glucose caused by relative or absolute deficiency of insulin |
|
|
Term
| difference between type 1 and 2 diabetes in age of onset? |
|
Definition
type 1 - usually childhood or puberty
type 2 - frequently over age 35 |
|
|
Term
| difference between type 1 and 2 diabetes in nutritional status at time of onset of disease? |
|
Definition
type 1 - frequently undernourished
type 2 - obesity is usually present |
|
|
Term
| difference between type 1 and 2 diabetes in prevalence? |
|
Definition
type 1 - 10-20% of diagnosed diabetes
type 2 - 80-90% of diagnosed diabetes |
|
|
Term
| difference between type 1 and 2 diabetes in genetic predisposition? |
|
Definition
type 1 - moderate
type 2 - very strong |
|
|
Term
| difference between type 1 and 2 diabetes in defect or deficiency? |
|
Definition
type 1 - B cells destroyed eliminating production of insulin
type 2 - inability of B cells to produce appropriate quantities of insulin; insulin resistance; other unknown defects |
|
|
Term
| which type of diabetes requires insulin replacement and why? |
|
Definition
type 1
because there is a complete lack of insulin due to destruction of the B cells |
|
|
Term
| how is type 2 treated overall? |
|
Definition
1. lifestyle changes
2. drugs that influence insulin secretion and/or sensitivity
3. only in end stage - insulin therapy |
|
|
Term
| which type of diabetes is most common? |
|
Definition
|
|
Term
| which type of diabetes has a strong genetic predisposition? |
|
Definition
|
|
Term
| how does a normal individual respond to glucose infusion? |
|
Definition
| have a rapid increase of insulin in the plasma that remains elevated for 10-20 mins |
|
|
Term
| what is the response of insulin to glucose infusion in type 1 diabetes? |
|
Definition
| there is no insulin so there is no increase in plasma concentration upon infusion |
|
|
Term
| what is the response of insulin to glucose infusion in type 2 diabetes? |
|
Definition
failure of the initial response of insulin secretion
then see a blunted response later |
|
|
Term
| what measure is proportional to the average glucose concentration over previous months? |
|
Definition
| glycosylated hemoglobin - HbA1C |
|
|
Term
| what is the goal of diabetes treatment? |
|
Definition
| to maintain blood glucose concentrations as close to normal as possible to avoid long term complications |
|
|
Term
| intensive therapies in the treatment of diabetes lead to what? |
|
Definition
| 50%+ reduction in the long term complications of diabetes |
|
|
Term
| what is the structure of pro-insulin? |
|
Definition
| A, B, and intervening C chain |
|
|
Term
| what happens during the packing of pro-insulin? |
|
Definition
|
|
Term
| structure of mature insulin? |
|
Definition
| A and B chains coupled by 2 disulfide bridges |
|
|
Term
| insulin is synthesized where? |
|
Definition
|
|
Term
| insulin is released in response to what? |
|
Definition
|
|
Term
| what happens to native insulin in the presence of zinc? |
|
Definition
| it self-aggregates to form crystals |
|
|
Term
| how do insulin crystals in the presence of zinc affect release of insulin? |
|
Definition
| causes fairly slow release once it's secreted |
|
|
Term
| native insulin forms crystals in the presence of what? |
|
Definition
|
|
Term
| 3 rapidly acting insulins? |
|
Definition
1. lispro
2. aspart
3. glulisine |
|
|
Term
| how are rapidly acting insulins formulated? |
|
Definition
| with small amounts of zinc |
|
|
Term
| when are rapidly acting insulins administered? |
|
Definition
| injected 5-15 mins before each meal and even after a meal |
|
|
Term
| why are rapidly acting insulins better than insulin? |
|
Definition
less likely to form hexamer aggregates
onset and peak is quicker; duration is shorter; dissociates very rapidly |
|
|
Term
| how are rapidly acting insulins administered? |
|
Definition
pen injectors
subcutaneous infusions |
|
|
Term
| effectiveness of rapidly acting insulins in decreasing postprandial hyperglycemia? |
|
Definition
| more effective than regular insulin |
|
|
Term
| side effects of rapidly acting insulins? |
|
Definition
| less likely to cause nocturnal hypoglycemia |
|
|
Term
| why are rapidly acting insulins less likely to cause nocturnal hypoglycemia? |
|
Definition
| because they are so short acting |
|
|
Term
| how is insulin for treating diabetes synthesized? |
|
Definition
| by recombinant DNA technology |
|
|
Term
| how does the release and duration of regular insulin compare to rapidly acting insulins? |
|
Definition
slower release
longer duration |
|
|
Term
| when is regular insulin administered? |
|
Definition
| injected 15-30 mins before each meal |
|
|
Term
| properties of regular insulin? |
|
Definition
short acting
rapid onset, peak in 1-2 hours, duration 6-8 hours |
|
|
Term
| what are the 2 intermediate acting insulins? |
|
Definition
|
|
Term
| NPH insulin is complexed with what? |
|
Definition
|
|
Term
| properties of NPH insulin? |
|
Definition
longer onset, longer time to peak
duration = 10-16 hours |
|
|
Term
| how does lente insulin differ from NPH? |
|
Definition
| similar properties but complexed with more zinc |
|
|
Term
|
Definition
1. ultralente
2. glargine |
|
|
Term
|
Definition
| large zinc insulin crystals |
|
|
Term
|
Definition
several hours
don't reach a peak because dissociates so slowly |
|
|
Term
|
Definition
| long duration of up to a day |
|
|
Term
| glargine is soluble at what pH? |
|
Definition
|
|
Term
| what happens to glargine at a pH of 7.4? |
|
Definition
it forms a micro-precipitate in the extracellular space
delays absorption from subcutaneous site and leads to a longer duration of action |
|
|
Term
| why does glargine have a long duration of action? |
|
Definition
| it forms a micro-precipitate at physiologic pH (7.4) and delays absorption from the subcutaneous injection site |
|
|
Term
| what is the goal of insulin therapy? |
|
Definition
| achieve HbA1C of less than 6% of total Hb |
|
|
Term
| what is involved in intense therapy for type 1 diabetes? |
|
Definition
1. inject with ultra-short acting insulin before meals
2. longer acting insulin at night |
|
|
Term
| intense therapy for type 1 diabetes achieves what? |
|
Definition
HbA1C of 7% or even less
mean blood glucose of 150 mg/dl |
|
|
Term
| what is involved in standard therapy for type 2 diabetes in end stages? |
|
Definition
1. 2 injections per day of 2 intermediate acting insulins
2. longer acting insulin at night |
|
|
Term
| what does standard therapy for type 2 diabetes in end stages achieve? |
|
Definition
HbA1C of 8-9%
mean blood glucose of 225 mg/dl |
|
|
Term
| what is normal blood glucose? |
|
Definition
|
|
Term
| the insulin receptor has how many subunits? |
|
Definition
|
|
Term
| the insulin receptor has what type of intrinsic activity? |
|
Definition
|
|
Term
| how does insulin exert its effect on a target cell? |
|
Definition
insulin binds receptor --> receptor autophosphorylates --> phosphorylates downstream targets -->
IRS 1-4 --> mediates PI3 kinase
also MAP kinase |
|
|
Term
| what are the 2 downstream targets of the insulin receptor in the cell and what are their effects? |
|
Definition
1. PI3 kinase - metabolic effects of insulin; protein and glycogen synthesis
2. MAP kinase - mitogenesis |
|
|
Term
| what intracellular response mediates the uptake of glucose and the metabolic effects of insulin on the cell? |
|
Definition
| IRS proteins 1-4 and their activation of PI3 kinase |
|
|
Term
| what is responsible for the intracellular mitogenic response of insulin binding to its receptor? |
|
Definition
|
|
Term
| activation of what ultimately increases glucose transport in a cell? |
|
Definition
|
|
Term
| insulin is a _____ hormone |
|
Definition
|
|
Term
| 2 things insulin promotes? |
|
Definition
1. glucose storage in the liver as glycogen and in adipocytes as triglycerides of fatty acids
2. amino acid storage in muscle as protein |
|
|
Term
| 2 things that insulin inhibits? |
|
Definition
1. gluconeogenesis
2. glycogenolysis
both promote glycogen storage |
|
|
Term
| what is the main complication of insulin therapy? |
|
Definition
|
|
Term
| 3 complications of insulin therapy? |
|
Definition
1. hypoglycemia
2. subcutaneous fat hypertrophy
3. immune insulin resistance |
|
|
Term
| hypoglycemia as a complication of insulin therapy is associated with what symptoms? |
|
Definition
1. tachycardia
2. sweating
3. confusion
4. coma |
|
|
Term
| how is hypoglycemia as a complication of insulin therapy treated? |
|
Definition
glucose if conscious
glucagon if unconscious |
|
|
Term
|
Definition
| subcutaneous fat hypertrophy at the site of insulin injection |
|
|
Term
| cause of lipohypertrophy as a complication of insulin therapy? |
|
Definition
| due to the lipgenic effects of insulin |
|
|
Term
| solution for lipohypertrophy as a complication of insulin therapy? |
|
Definition
| rotate sites of injection |
|
|
Term
| why is immune insulin resistance not as big of a problem now with insulin therapy? |
|
Definition
insulin used to come from cow or pig pancreas
now it's purified from E. coli or humans
much less likely to make Abs to |
|
|
Term
| factors that influence the efficacy of insulin therapy (7) |
|
Definition
1. insulin sensitivity
2. endogenous insulin
3. absorption site
4. skin perfusion
5. insulin Abs
6. caloric intake
7. GI function |
|
|
Term
| from what location is insulin more rapidly absorbed? |
|
Definition
| abdomen rather than a limb |
|
|
Term
| what can increase skin perfusion and therefore absorption rate of insulin? |
|
Definition
|
|
Term
| most diabetics have what type? |
|
Definition
|
|
Term
| pancreas function in type 2 diabetes? |
|
Definition
|
|
Term
| insulin levels in type 2 diabetes? |
|
Definition
| variable - insufficient to maintain glucose homeostasis |
|
|
Term
| type 2 diabetes is often accompanied by what along with decreased insulin levels? |
|
Definition
target organ insulin resistance
either receptor-mediated or occurring after insulin binds to the receptor (downstream targets) |
|
|
Term
| initial treatments of type 2 diabetes? |
|
Definition
| weight reduction, exercise, and dietary modification |
|
|
Term
| effect of initial treatments for type 2 diabetes? |
|
Definition
| can decrease insulin resistance and correct hyperglycemia |
|
|
Term
| what is necessary to maintain normal glucose levels later in the course of type 2 diabetics? |
|
Definition
|
|
Term
| what are the 5 different treatment agents used for type 2 diabetes? |
|
Definition
1. second generation sulfonylureas
2. metformin
3. thiazolidinediones (glitazones)
4. GLP-1 agonists
5. DPP-4 inhibitors |
|
|
Term
| what is a drug that works like sulfonylureas but has a different chemical makeup? |
|
Definition
|
|
Term
| how do sulfonylureas and replaglinide cause insulin release in the presence of glucose? |
|
Definition
| glucose enters the beta cell --> ATP is generated from glucose metabolism --> ATP closes K channel --> cell membrane depolarizes --> open voltage gated Ca channels --> Ca causes exocystosis of insulin |
|
|
Term
| what is the effect of sulfonylureas and replaglinide on insulin secretion from the beta cell? |
|
Definition
| cause insulin release due to increased Ca in the cell |
|
|
Term
| where do sulfonylureas and replaglinide work in the beta cell? |
|
Definition
| block the K channel that maintains membrane potential --> leads to depolarization of the membrane and an increase in Ca |
|
|
Term
|
Definition
1. glipizide
2. glyburide
3. glimepiride |
|
|
Term
| mechanism of action of sulfonylureas and replaglinide? |
|
Definition
block K channel
causes depolarization of the membrane and increase insulin secretion |
|
|
Term
| what is the main side effect of sulfonylureas and replaglinide? |
|
Definition
|
|
Term
| metabolism of sulfonylureas is by? |
|
Definition
|
|
Term
| sulfonylureas are excreted in what? |
|
Definition
|
|
Term
| what can lead to increased side effects with sulfonylureas and why? |
|
Definition
any impairment of hepatic or renal function
have increased plasma levels of drug --> more likely to have hypoglycemia |
|
|
Term
| other side effects of sulfonylureas? |
|
Definition
nausea
generalized hypersensitivity reactions
pruritis
alcohol-induced flush
anemia |
|
|
Term
| which sulfonylurea causes the least hypoglycemia? |
|
Definition
|
|
Term
| is metformin a euglycemic or hypoglycemic agent? |
|
Definition
|
|
Term
| why is metformin euglycemic? |
|
Definition
| it inhibits hepatic gluconeogenesis |
|
|
Term
|
Definition
| alone or in combo with sulfonylureas |
|
|
Term
|
Definition
| AMP-activated protein kinase |
|
|
Term
| side effects of metformin? |
|
Definition
1. anorexia, vomiting, diarrhea - 20%
2. lactic acidosis
3. much less likely to cause hypoglycemia |
|
|
Term
| side effects of metformin are what type? |
|
Definition
| predominantly GI and so bad that patients can't take the drug |
|
|
Term
| who is at risk for lactic acidosis as a side effect of metformin? |
|
Definition
| alcoholics or anyone at risk for overproduction of lactic acid |
|
|
Term
| what kind of drug is acarbose? |
|
Definition
| alpha-glucosidase inhibitors |
|
|
Term
| what is alpha glucosidase? |
|
Definition
| an enzyme in the intestine that breaks down complex sugars |
|
|
Term
| mechanism of action of acarbose? |
|
Definition
| inhibits alpha-glucosidase --> inhibits the absorption of starch and complex sugar |
|
|
Term
|
Definition
before meals
postprandial rise in glucose is blunted |
|
|
Term
| side effects of acarbose? |
|
Definition
1. flatulence
2. cramping
3. diarrhea |
|
|
Term
| what are the 2 glitazones? |
|
Definition
1. rosiglitazone
2. pioglitazone |
|
|
Term
| mechanism of action of glitazones? |
|
Definition
activate PPAR gamma which activates insulin-responsive genes affecting CHO and lipid metabolism
bypass insulin receptor |
|
|
Term
| what has to be monitored with glitazone use? and why? |
|
Definition
liver function
because the original glitazone (troglitazone) was taken off the market because of liver damage |
|
|
Term
|
Definition
1. liraglutide
2. exenatide |
|
|
Term
| what type of drugs are the GLP-1 agonists? |
|
Definition
peptides
have to be given in pens once or twice a day or subcutaneously |
|
|
Term
|
Definition
cytokines released by the intestine during meals
degraded by dipeptidyl peptidase 4 (DPP-4) enzyme |
|
|
Term
| GLP-1 agonists increase what? |
|
Definition
|
|
Term
| effect of incretins in the body? |
|
Definition
1. increase insulin secretion
2. decrease glucagon |
|
|
Term
| side effects of GLP-1 agonists? |
|
Definition
1. hypoglycemia especially if with sulfonylurea
2. nausea
3. diarrhea |
|
|
Term
|
Definition
1. saxagliptin
2. sitapliptin |
|
|
Term
| effect of DPP-4 inhibitors? |
|
Definition
|
|
Term
| how are DPP-4 inhibitors effective? |
|
Definition
in mono- or combined therapy
orally active |
|
|
Term
| mechanism of DPP-4 inhibitors? |
|
Definition
|
|
Term
Treatment of type 1 and type 2 diabetes can be quite different. All of the following are true regarding treatment of diabetes EXCEPT:
a. With continued therapy, sulfonylureas such as glyburide can lose their efficacy in some patients
b. Glyburide is sometimes used in combination therapy with metformin to treat type 2 diabetes
c. Repaglinide stimulates insulin release from the beta cells of the pancreas
d. Metformin is useful in treating type 1 diabetes |
|
Definition
| d. Metformin is useful in treating type 1 diabetes |
|
|
