Diabetes Mellitus Flashcards
Type I DM pathophys
type 1A - immune mediated
type 1B - idiopathic (no apparent cause)
beta cell destruction causes levels of insulin to drop, until 80-90% gone and intake of food causes no response from pancreas
immune mediated T1Dm
vigorous autoimmune response to infectious or toxic insult
circulating Abs to islet cells tag and destroy them
Type I DM epidemiology
occurs MC in juveniles with greatest peak of early adolescence (13-14)
highest rates are in Scandinavian descent
type I DM affects about 1/400-600, more common in males, HLA subtypes
pathophysiology of Type II DM
state of hyperglycemia and hyperinsulinemia
deficient B cell response to hyperglycemia and tissue insensitivity to endogenous insulin
mechanisms are further aggravated by resultant hyperglycemia
deficient B cell response to hyperglycemia
- at first, B-cell hyperplasia and increased insulin production
- overdriving of pancreas will compensate for some time
- progressive amyloid deposition leads to B cell insufficiency and failure
how does T2DM cause vascular disease
hyperinsulinemia, hyperglycemia, and increased free fatty acid production causes endothelial cell dysfunction, inflammation (which causes increased insulin resistance)
when should you consider testing diabetes patients for autoantibodies
2 of following:
age of onset <50 y/o
acute symptoms
BMI <25
personal family history of autoimmune disease
LADA
adult onset of T1DM
no rapid decline of beta cells like in normal T1DM
may find high GAD Abs
MODY
T2DM in young patients
no antibodies
symptoms of T1DM
- weight loss/polyphagia (first due to loss of water weight, then depletion of H2O)
- Polyuria (increased urination)
- Polydipsia (thirst)
- Blurred Vision
- Postural Hypotension
- Paresthesias
diagnostic testing for type I DM
C Peptide levels (low C Peptide levels - T1DM)
Autoantibody tests (specific to insulin, GAD, Zinc transporter)
Autoabs to beta cells
C Peptide Function
produced by pancreas when proinsulin is cleaved to insulin
lasts 3-4x longer in serum than insulin
T1DM have LOW
T2DM have HIGH
T1DM screening in children
annual screening for children of T1DM before 10, then once again in adolescence
treatment of T1DM
multispecialty team
dietician to control diet, exercise
life long insulin therapy (7.5% HgbA1c goal)
T2DM risk factors
- obesity (central)
- ethnicity
- life style choices
- genetics
symptoms of T2DM
typically asymptomatic (4-7 yrs before diagnosis)
recurrent/chronic vaginal candidiasis OB complications balantitis UTI acanthus nigrans unintentional weight loss
lab analysis of T2DM
fasting plasma glycose
finger stick (not diagnostic)
glycated HgB
T2DM treatment
diet
very rare if they stick to it
limit hyperglycemia, lower LDL, lower hypertriglyceridemia
increase fiber intake and artificial sweeteners
initial DM treatment
A1c > 7 but < 9%
metformin + lifestyle modification
initial DM treatment
A1c > 9%
dual drug therapy + insulin
initial DM treatment
A1c > 10%
insulin immediately
commonly used drugs
metformin sulfonylureas GLP-1 agonists DDP-4 inhibitors SGLT-2 insulin
Metformin (Glucogphage)
works by
decreasing hepatic production of glucose and increasing muscle uptake of glucose from serum
advantages of Metformin (Glucophage)
absence of CI
reduces A1C by 1.5-2%
modest weight reduction or stabilization
monotherapy- doesn’t cause hypoglycemia
disadvantages of Metformin
GI side effects
metabolized in kidney (avoided in CKD)
use with caution in those with IV contrast, hypotension, lactic acidosis)
sulfonylureas
stimulating pancreatic beta cells to secrete more insulin
regardless of blood glucose - hypoglycemia
effectiveness decreases over time, causes weight gain, increase mortality
incretin therapy
hormones released from gut with meal to promote insulin secretion
proliferation and growth of beta cells and prevent apoptosis
GLP-agonists and DDP-4 inhibitors
GLP-1 analogs
MOA
glucose dependent insulin release
reduce glucagon secretion
slow gastric emptying
may also stimulate beta cell recovery
disadvantages of GLP-1 analogs
administration is Sub Q
can cause hypoglycemia and pancreatitis
can be used in CKD up to stage 3B
DPP-IV
inhibits breakdown of endogenous GLP-1
weight neutral and less effective than GLP-1 RA bc rely on body to work normally
lower A1c by 0.5-0.7%
DPP-IV negatives
associated with pancreatitis
increase in URI’s
SGLT2-Inhibitors
Inhibits transporter that is responsible for reabsorbing glucose from proximal renal tubule
decrease the renal glucose threshold and increasing urinary glucose excretion
lower A1c by 0.5-1%
benefits and negatives of SGLT-2 inhibitors
weight neutral and may predispose patient to weight loss
increased risk of genitourinary infection and some bone loss
must be dose adjusted in mild CKD (GFR <45)
risk of hypoglycemia
thiazolidinoediones
lower blood glucose concentration by increasing glucose uptake in muscle and fatty tissues
decrease hepatic glucose production
do not cause hypoglycemia in mono therapy
lower A1c by 0.5-1%
weight gain and fluid retention
risks of thiazolidinediones
contraindicated in patients with NYHA class III or IV heart failure
can be associated with bladder cancer
higher risk of fracture
types of insulin
rapid acting
regular insulin
NPH
long acting insulin
ultra long acting insulin
rapid acting insulin
absorbed more quickly than regular insulin
regular insulin
same insulin your pancreas produces
when are rapid acting and regular insulin typically used
mealtimes to provide coverage of prandial hyperglycemia
basal insulins
give 1-2 injections daily to maintain all day control of blood sugar
NPH insulin
Insulin glargine and deter
Insulin degludec
NPH insulin
inexpensive
req. two daily injections
Insulin glargine and deter
require 1 (or 2) injections
nearly peak less
expensive
Insulin degludec
daily injections provide steady state
lasts almost 2 days in the body
how is insulin therapy given in type II patient
long acting basal bolus + rapid acting insulin to get best results
must have multiple injections
complications of insulin therapy
insulin allergy
lipodystrophy
hypoglycemic reactions
lipodystrophy
two types
complication of insulin therapy
atrophy (SC fatty tissue from immune run, loss of tissue)
Lipohypertrophy (SC of fatty tissue from repeated injection of insulin at same site)
hypoglycemic reactions
most common in older diabetics, those on insulin pimp, pts with pumps nc
more likely to forget to eat or take meds
improper management of pump
slow development of hypoglycemia symptoms
confusion, seizures
neuroglycopenic
rapid development of hypoglycemia symptoms
catecholemine reactions
Epinephrine
blunting of sympathetic system
body doesn’t have typical reactions to hypoglycemia
blunting of sympathetic system by age, beta blocker therapy, repeated hypoglycemia
increases risk of complications
goals of T2DM treatment
obtain level of glucose control for individual pt without causing fq. hypoglycemia
glycemic targets
HgB A1c 6.5%
for otherwise healthy patients with DM of short duration, w/o CVD, long line expectancy
glycemic targets
HgB A1c 7% or less
pts with longer duration DM, those with significant CVD
glycemic targets
HgB A1c 8% or Less
pts with severe comorbidities, limited life expectancy those with freq. hypoglycemia
importance of early DM control
intensity glycemic control at diagnosis have continued benefits and prevention of complications
treatment guidelines for T2DM HgB A1c
less than 7.5% @ diagnosis
lifestyle changes + metformin
alternatives to metformin
less than 7.5%
GLP-1 RA SLGT2-I DPP4 TZDs Alpha glycosides inhibitors sulfonylureas
treatment guidelines for T2DM HgB A1c
> or = to
lifestyle changes and dual therapy with metformin and another agent
if pt on monotherapy does not achieve goal A1c in 3 months
dual therapy
GLP-1 RA SGLT2 DPP4-I TZDs Basal Insulin, alpha glucosidase, sulfonylureas
if dual therapy with metformin and another agent are initiated and the patient does not achieve goal A1c in 3 months
triple therapy is indicated
what is triple therapy
metformin
another first line agent
plus:
GLP RA, SGLT2, TZD (caution), Basal insulin, DPP4, alpha glucosidade inhibitors, sulfonylureas
if triple therapy does not achieve goal of A1c in 3 months
insulin is added or intensified until goal is achieved
patient has A1c > 9%
dual therapy is immediately initiated if patient is asymptomatic
Insulin +/- other agents
surgical treatment for diabetes
pats with obesity (BMI > 30) should be considered
can be curative
lap band and roux-en-y gastric bypass
lap band
band is surgically implanted around the stomach and restricted to limit gastric size, procedure is reversible, performed laparoscopically
drawbacks of weight loss surgery
protein/calorie malnutrition
surgical complications
anastomotic leak (decreased protein and decreased healing)
somogyi effect
notctural hypoglycemia leads to a surge of counter regulatory hormones hyperglycemia by 7am
glucose drops overnight then rises so hyperglycemic by 7 AM
how do we fix somogyi
eliminate dinnertime intermediate insulin and give it back at a lower dose at bedtime
alternative give a snack at bedtime
dawn phenomenon
secretion of GH overnight or cortisol surge causes increased insulin resistance and morning hyperglycemia
health care management of diabetic (10)
PCP visit 3-6 months
exam of feet
screen for albuminuria, CAD/lipids
asses glycemic control
smoking cessation
ASA, BP control
routine cancer screenings
dental disease
vaccination
contraception and pre-preg
diabetics and surgery outcomes
hyperglycemia is significant cause of M & M B/c:
all infectious issues are worse, poor healing of
typically go for < 180
T2DM and glucose control
minor procedures or non-general anesthesia
meds up to day of surgery
on day of hold meds and resume after procedure
T2DM and glucose control
general anesthesia
have their oral and non-insulin injectable meds held on day of surgery and added back as diet is advanced
sliding scale insulin in mean time
T1DM/insulin dependent T2 and glucose control
surgery
reduced dose of usual insulin on morning of surgery
T2DM and glucose control
long surgery
performed if long/ocmplex
simultaneous insulin got with dextrose containing IV solutions to avoid starvation ketosis
gestational diabetes
pregnancy and hormones associated with it causes increased tissue resistance to insulin
screening b/t 24th and 28th week of pregnancy
increased risk of developing frank DM in 10-15 years
diabetes and pregnancy
pre pregnancy
counseling and eval of HgbA1c
asses baseline renal, ocular, and CV disease
try to get HgB A1c to 6%
first trimester and diabetes
congenital abnormalities
result from hyperglycemia during organogenesis in first 4-8 weeks
principal cause of perinatal fetal death (miscarriage)
third trimester and diabetes
fluctuations in blood glucose grow worse
regular antepartum fetal testing is indicated to see how much longer the pregnancy can go
true to deliver b/t 38-39 weeks
