What is a normal A1c value? What is the American Diabetes Association's goal?
normal is 4-6
goal is < 7
What is a normal blood sugar level?
Why do we need insulin?
Glucose Regulation (stimulate glucose uptake from blood, suppress gluconeogenesis and gluycolysis)
Fat storage regulation (prevent ketoacidosis
Keep eyes, kidneys, nerves form getting glucose toxic
To make sure glucose can get to other tissues (need insulin to push sugar in)
What are the s/s of metabolic syndrome? When in the clinical course of diabetes development does this happen?
LDL often normal (but small, dense, atherogenic)
waist > 40 in
This occurs as the pt is becoming insulin resistant
What does glucose toxicity in the tissues cause?
What are the glucose levels for "pre-diabetes" for 2 hour post-glucose and fasting glucose?
2 hour post glucose: 140-199
fasting glucose: 101-125
What are the fasting glucose and random glucose levels for diabetes?
fasting Glc of 126+
random Glc of 200 or greater with symptoms
What is A1c and what are the normal, pre-diabetes, and diabetes levels for diagnosis?
Hemoglobin A1c is a subfraction of hgb that is glycosylated by too much glucose - it measures the last 3 months
normal: < 5
What does A1c tell us about micro and macrovascular disease?
the higher the A1c, the higher the incidence of micro or macro vascular disease
What does incretin do?
increase gastric emptying
(doesn't work very well in T2DM)
What does glucagon do?
increases blood sugar
Which meds are GLP-1 receptor agonists? How do they work?
exenatide and liraglutide
stimulate insulin release and inhibit glucagon release
Which meds are DPP-4 inhibitors? How do they work?
sitagliptin and saxagliptin
inhibit the breakdown of GLP-1 (so keep incretin from being inactivated)
Give examples of thiazoladinediones. What is their main activity? Name some of their SEs.
Actos and Avandia (-glitazones)
they increase insulin sensitivity
peripheral edema (leading to CHF) and weight gain
If a pt is experiencing hypoglycemia, how much glucose should be given?
about 15 g (3-4 glucose tabs)
s/s of hypoglycemia
mood changes - crying
tingling around the mouth
difficulty paying attention
After having a hypoglycemic episode, when should a pt recheck their blood sugar?
15 to 20 minutes after treatment
retreat if necessary
s/s of hyperglycemia
blood glucose > 180 mg/dL
vaginal and skin infx
slow healing cuts and sores
nerve damage causing painful cold or insensitive feet, hair loss on lower extremities, ED
chronic constipation or diarrhea
What is the development/time course of Type 2 diabetes?
Insulin resistance: extra fat, liver makes more glucose, pancreas makes more insulin, BG stays normal
Pancreas cannot make extra insulin anymore: BG is high sometimes; sx like urinating more, tired, thirsty
Pancreas no longer makes normal insulin: BG is always high, worse sx, T2DM diagnosed
Physiologic difference in DM between kids and adults
insulin sensitivity is diff in kids - related to sexual maturity
ability to provide self-care
unique neurologic vulnerability to hypoglycemia
care plans must include family dynamics, developmental stages
Name 3 ways that insulin therapy can be implemented in a child with Type I diabetes
1. Split-Mixed (short acting + NPH); 70/30
2. Basal Bolus
3. Continuous Subcutaneous Insulin Pump (CSII)
Describe how Split-Mixed insulin therapy is given
2/3 given in AM, 1/3 in PM.
In AM, 1/3 is short acting and 2/3 is NPH.
In PM it is 50/50.
Not recommended post-honeymoon.
Describe how BB insulin is given
rapid acting + long acting (glargine or detemir)
at least 4 injections/day
Pre-meal rapid acting dose is based on current BG, anticipated carb intake, atnicipated level of physical activity
Inject with meals and snacks
Can dose post-prandially in toddlers because it's hard to know how much/what they're going to eat
Describe CSII insulin dosing
continuous subcutaneous insulin pump
requires carb counting
must test 4-6 x/day and bolus
adult supervision and support needed
most often in pre-teens and adolescents
Describe the dosing when implementing insulin therapy in a child with Type 1 DM
0.5 - 1 units/kg/day or less during honeymoon
usually 1 unit/kg/day
during puberty up to 1.5 units/kg/day because of increased insulin resistance, growth hormone, and sex hormones
What is the honeymoon phase in Type I diabetes?
the phase where the disease has been diagnosed and insulin therapy has been started, but not all the beta-cells have been destroyed yet
Plasma BG and A1c goals for T1DM by age group
< 6 years: before meals 100-180; bedtime/overnight 110-200; A1c < 8..5 and > 7.5; rationale is that they are high risk and vulnerable to hypoglycemia
6-12 years: before meals 90-180; bedtime/overnight 100-180; A1c < 8 ; rationale is their risks of hypoglycemia and relatively low risk of complications before puberty
13-19 years: before meals 90-130; bedtime/overnight 90-150; A1c <7.5; rationale is their risk of hypoglycemia and developmental and psych issues
What ethnicity is at highest risk for Type2DM?
native american > asian > black > hispanic > white
What are the ADAs screening recommendations for Type 2 DM?
begin @ puberty or 10 year old, whichever is less
when BMI is >/= 85th percentile plus two of the following: family hx in 1st or 2nd degree relative, non-white race, signs of insulin resistance (acanthosis nigricans, PCOS, HTN, incr lipids)
Goals of treatment for T2DM in kids
physical and psychological well-being (prevent ketosis, hyperglycemia, infx)
glycemic control - euglycemia or A1c < 7%
prevention of micro and macro vascular disease complications
In treating T2DM, what must be used with severe hyperglycemia or ketosis?
Algorithm for treatment of pediatric T2DM
after diagnosis of T2DM
if mild hyperglycemia (FBG < 150; 2h OGTT < 300) do diet and exercise for 3-6 mo then if FBG is < 100 and A1c < 6% consider success, if not then go to metformin x 3-6 mo. If metformin unsuccessful add another agent like sulfonylurea, TZD, glitinide, alpha-glucosidase inhibitor
if severe hyperglycemis (FBG > 150; 2h OGTT > 300) if the BG is > 350 or diabetic ketoacidosis give insulin until stable. if not then do metformin for 3-6 mo. if unsuccessful add another agent (listed above)
How do biguanides work? Name one.
improve insulin sensitivity
decrease intestinal absorption of glucose
How do secretagogues work? Name some.
stimulate insulin secretion from pancreatic beta-cells
Sulfonylureas - glyburide, glipizide, glimipiride
Meglitinides - repaglinide, nateglinide
How do DPP-4 inhibitors work? name some.
inhibit GLP-1 and GIP from inactivating incretin
increase insulin secr from pancreas
decrease secretion of glucagon
Which diabetes med classes are PPAR modulators?
Alpha Glucosidase inhibitors
MOA of thiazolidinediones and name some
increase insulin sensitivity by modulating PPAR-gamma
decrease glucose output
MOA of alpha glucosidase inhibitors and name some
slow the conversion of polysaccharides into glucose
inhibit carb absorption in intestine
Which diabetes med classes work on the pancreas?
they increase insulin secretion
Which diabetes med classes work on the liver?
they decrease gluconeogenesis
Which diabetes med classes work on the GIT?
alpha glucosidase inhibitors
they decrease glucose absorption
Which diabetes med classes work on muscle and fat?
they increase glucose uptake
What is metformin's place in diabetes therapy?
it is first line - especially in obesity and hyperlipidemia
Treatment algorithm from ADA for diabetes
Lifestyle + metformin
then add either basal insulin or sulfonylurea
if sulfonylurea was added first, can add the basal insulin next
then add intensive insulin
What diabetes meds should not be used in pts with renal impairment?
no metformin if SCr is >/= 1.4 in women or 1.5 in males
No sulfonylureas in severe renal or hepatic impairment (no glyburide if CrCl < 50; no glipizide if CrCl < 10)
renal dose adjustment needed with Dpp-4 inhibitors
no alpha-glucosidase inhibitors if SCr > 2
Which diabetes meds have severe GI SEs?
metformin (go away in a few weeks)
alpha glucosidase inhibitors (CI's in IBD)
What must be adjusted if a pt is taking a secretagogue and a DPP-4 inhibitor?
the secretagogue dose should be decreased by 50%
Which oral diabetes meds are CI'd in class III-IV CHF? Which is CI'd with decreased perfusion?
What effect on weight do the various oral diabetes meds have?
sulfonylureas and TZDs cause gain
metformin causes loss (or is weight neutral)
if pt has metabolic syndrome or non-alcoholic fatty liver disease, use TZDs
Which oral diabetes meds are CI'd in T1DM?
How are the oral diabetes meds dosed?
Metformin is 500 mg bid-tid
Sulfonylureas 1.25 -10 mg qd -bid
TZDs 2-45 mg qd-bid
alpha glucosidase inhibitors 25-100 mg qd, then bid, then tid
What values need to be monitored with which oral diabetes meds?
FBG and A1c with all
PPBG with alpha-glucosidase inhibitors
Renal fxn with metformin, sulfonylureas, DPP-4 inhibitors
LFTs with TZDs and alpha glucosidase inhibitors
Which oral diabetes med do you need to take a multivitamin with and why?
metformin because it causes malabsorption of B12 and folic acid
Can sulfonylureas be used in patients with sulfa allergies?
What other meds need to be monitored if taken with nateglinide? Why?
phenytoin, furosemide, metformin
because of plasma protein binding
What is the MOA of insulin?
stimulate entry of glucose into cells
promotes storage of glucose as glycogen in muscle and liver cells
What meds are also known as incretin mimetics? What is their MOA?
GLP-1 agonists (exenatide, liraglutide)
stimulate glucose dependent insulin secretion
inhibit glucagon release
slow rate of gastric emptying and increase satiety
What is the MOA of pramlintide?
It is an amylin agonist
it decreases PPBG and glucagon secretion
it increases satiety
What is the different onset, peak, and duration of action of the various forms of non-oral diabetes therapies (insulin)?
TG < 150 (high TG often indicates uncontrolled DM)
What is the DOC for dyslipidemia in diabetes pts?
In a diabetes pt when should statin therapy be started regardless of the pt's LDL?
if they have overt CVD
if they are over age 40 and have one or more CV risk factor or under 40 with multiple risk factors
risk factors are HTN, family hx of CVD, smoking, dyslipidemia, albuminuria
When do we use antiplatelet treatment in diabetes pts?
primary prevention - to prevent 1st CV event
secondary prevention - to decrease morbidity and mortality in pts with previous CV event
secondary is more effective b/c there's higher risk of a 2nd event than a 1st
When is ASA indicated for prevention of thrombus formation in diabetes pts?
for anyone with personal hx of CVD or
if their 10 year framingham risk is > 10%
this usually includes med > 50 and women > 60 with one or more of these - HTN, fam hx of CVD, smoking, dyslipidemia, albuminuria
not recommended for pts < 21 y.o.
can add clopidogrel for the 1st 12 mo post event, or if pt is ASA intolerant
What are the BP goals for a pregnant diabetes pt?
If CVD is established in a diabetes pt, what meds should the pt be on?
Post MI - beta blockers for 2 years
metformin is ok if stable CHF and normal renal fxn
What are the immunization recommendations for diabetes pts?
influenza for all pts over 6 months of age
pneumococcal one time once a pt is older than 2 y.o. , then revaccination at age > 64 years (if they were less than 65 when they got the original vaccination and it has been at least 5 years since the original vacc.)
What is the #1 cause of renal failure and dialysis?
Screening for diabetic nephropathy
random spot test for albumin (albumin:SCr ratio) - once a year
SCr - get checked yearly - to estimate GFR; normal is < 30, microalbuminuria is 30-299, macroalbuminuria (aka proteinuria) is 300+
Screening for diabetic neuropathy
Sensory neuropathies - painful or loss of sensation
monofilament test - tests for loss of sensation (testing for vibration and temperature increases the sensitivity of the monofilament test)
diabetic foot exams - annually
autonomic neuropathy d/t loss of vagal stimulation
What is the DOC for diabetic nephropathy?
ACE inhibitors (they are renoprotective) - should use in all pts with microalbuminuria
ARBs are good for pts who get the ACE cough
ACE + ARB is superior to monotreatment in decreasing the progression of renal disease
What meds should be used for diabetic nephropathy?
ACEs and ARBs
Non-DHP CCBs (verapamil and diltiazem)
Do not use DHP CCBs (amlodipine)
What meds can be used for diabetic neuropathy?
these drugs are to treat painful neuropathies
TCAs (most data and most effective)
gabapentin or pregabalin - must do renal adjustments
What meds are used to treat gastroparesis in diabetes pts?
What is used to treat retinopathy in the diabetes pt?
no vitamin E
laser photocoagulation is best to prevent blindness
What are SEs of nephropathy meds used in DM?
ACEs - hyperkalemia, cough
ARBs - hyperkalemia
What are SEs of drugs used to treat diabetic neuropathy?
TCAs: decrease nerve conduction speed, anticholinergic, weight gain, QT prolongation
What is GDM? When a Type 1 pt becomes pregnant do they have GDM? Could a pt with GDM be an undiagnosed T2DM pt?
GDM is gestational diabetes mellitus. Any degree of Glc intolerance with onset or first recognition during preg.
Does not include T1DM
A pt with T2DM could be found out this way and it would be considered GDM
Women @ high risk for GDM should undergo glc testing ASAP. What 4 factors palace a woman at high risk of GDM?
2. hx of GDM
3. strong family hx of GDM
Women at average risk should undergo testing at how many weeks of gestation?
Women at low risk of GDM require no glc testing in pregnancy. What characteristics put a woman in this category?
< 25 y.o.
normal pre-preg weight
no known DM in 1st degree relatives
no hx of abnormal Glc tolerance
no hx of poor OB outcome
For the average or high risk pt who requires screening but has a normal fasting or casual plasma glucose, what are the 2 approaches for glucose tolerance testing?
1. Perform OGTT (100 g oral load and fasting 1,2, & 3 hour postprandial Glc checks)
2. 50 g GCT with 1 hr post prandial with those who fail going on to take an OGTT to confirm
name 7 obstetric and perinatal complications assoc with GDM
1. fetal macrosomia
2. post partum neonatal hypoglycemia
3. post partum neonatal jaundice
4. post partum neonatal polycythemia
5. post partum neonatal hypocalcemia
6. maternal HTN
What are the long-term risks to the mother with GDM and her child after pregnancy?
risk of obesity and DM in adolescents
increased risk of T2DM later in the mother
When MNT fails to reach maternal glycemic goals during pregnancy, insulin therapy should be started. What are these glycemic goals?
FBG </= 105
1 hour PP </= 155
2 hour PP </= 130
For a pt who had GDM in the post partum period assuming glucose levels are now normal, how often should we recheck the glycemic status? Does that differ from pts with IFG of IGT post partum? What meds should be avoided in pts with a hx of GDM to prevent development of glucose intolerance/DM?
check glycemic status at least 6 wk post delivery and q 3 years after that
women with post partum IFG and IFT should be checked annually and be on a diet and exercise regimen
avoid corticosteroids and high-dose niacin (would tip pt toward Glc intolerance)