Diabetes Mellitus Patho

GLUT 1

blood brain barrier,
pancreatic beta cells
insulin independent

GLUT 2

liver
insulin independent

GLUT 3

neurons, pancreatic beta cells
insulin independent

GLUT 4

insulin dependent
activated glucose transporters translocate to cell membrane, facilitate glucose diffusion into cell
muscle and adipose cells

alpha cells

glucagon
mobilizes glycogen from liver
suppresses insulin secretion
maintain blood glucose between meals

beta cells

insulin & amylin
promotes glucose utilization

delta cells

somatostatin
regulates alpha/beta

GIP

glucose-dependent insulinotropic polypeptide
insulin secretion
B cell proliferation, inhibits apoptosis

GLP-1

glucagon-like peptide 1
delays gastric emptying
increases satiety
inhibits glucagon
all GIP functions

satiety

feeling of fullness

hormonal regulation

protein & fat metabolism are regulated by anabolic effects of insulin
synthesized in pancreas by B cells of islets of langerhans
blood sugar inc, insulin released

anabolic hormones

promote glucose usage, protein synthesis, formation & storage of lipids
facilitate transport of K+ PO42-, Mg2+ into cells
inhibits production of glucose by liver

first-phase insulin release

glucose-sensitive receptors in mouth
oral intake triggers PNS to stim beta cells to release insulin

explain path of insulin receptor

protein kinase receptor that triggers an enzyme cascade within cell
translocation of sequestered GLUT4 transporters to cell surface
GLUT 4 is passive, transports glucose down its concentration gradient

what are dotted lines an indication of?

indirect pathways of activation

fed state

glucose is suppled to the bloodstream from GI tract
ingested from food
pancreas releases insulin into bloodstream
glucose send to muscle tissue and adipose tissue and liver and neural tissue

glycogenesis

production of glycogen in the muscle and the liver

glycolysis

glucose may be oxidized for the energy needs of the cell

fasting state

nothing leaves GI tract
glucose enters bloodstream from liver
glucose enters neural tissue and muscle tissue
glucagon leaves pancreas
FFA (free fatty acid) leaves muscle and adipose tissue

glycogenolysis

glucose supplied to the bloodstream from glycogen stores in the muscles and liver

gluconeogensis

manufactured from substrates like amino acids in liver

counterregulatory hormones

glucagon
epi/norepi
growth hormonth
cortisol
oppose effects of insulin
move glucose out of storage into blood
decrease cellular uptake of glucose
glycogen broken down with glycogen makes glucose

neural regulation

neural influences from symp and parasymp are directly involved with carbohydrate metabolism and glucose utilization

first-phase insulin release

glucose-sensitive receptors in mouth
oral intake triggers PNS to stim beta cells to release insulin

exercise

complex effects on glucose metabolism
decrease in production of insulin and increase in secretion of glucagon and catecholamines lead to elevated blood glucose levels
exercising muscle has increased insulin sensitivity, which facilitates glucose uptake, lowers glucose levels and decreases insulin resistance

stress

hormones increase blood glucose levels and oppose insulin effects
cortisol, growth hormone, norepi

which hormones precipitate stress hyperglycemia?

catecholamines, glucocorticoids, glucagon

normoglycemia

normal insulin production and glucose metabolism facilitates a normal fasting glucose range

what is the normal fasting glucose range?

70-99 mg/dL

pre diabetes fasting plasma glucose level

100-125 mg/dL

pre diabetes 2-hour plasma glucose testing (OGTT) level

140-199 mg/dL (IGT)

pre diabetes HbA1C level

5.7-6.4%

diabetes fasting plasma glucose level

126+ mg/dL

diabetes 2-hour plasma glucose level

200+ mg/dL during OGTT

clinical manifestations of diabetes

polyphagia (increased appetite)
polydipsia (increased thirst)
polyuria (increased urination)

diabetes HbA1C level

6.5%+

prediabetes

impaired glucose tolerance and fasting glucose
intermediated stages between normal glucose metabolism and onset of diabetes

diabetes mellitus

multisystem disease related to glucose intolerance
abnormal insulin production
impaired insulin utilization

type I diabetes

B cell destruction
type 1a immune-mediated is autoimmune
type 1b is not autoimmune
can occur at any age but peaks at ages of 2, 4 to 6, 10-14 yrs (mostly in young)

idiopathic

something happening for a reason we don't understand

onset of type 1

rapid
insulin destruction
present to ED with ketoacidosis

classical manifestations of type 1

polyuria, polydipsia, polyphagia, weight loss
increased frequency of infections

diabetic ketoacidosis

liver breakdown of stored glycogen does produce fatty acids
ketoacids released into blood
risk of dehydration
common in type 1
increased lipolysis, conversion to ketone bodies (excessive = meta acid)
4-10 hrs of onset

DKA lab values

serum glucose level more than 300mg/dL
serum pH less than 7.30 (6.8-7.3)
urine ketones moderate to high
Na,K: low, normal, high
Hct, Hb, protein, WBC count, Cr, BUN, serum osmolarity: high

clinical manifestations of DKA

Kussmal respirations
acetone breath
ketonuria
ketonemia
metabolic acid
low serum bicarb with anion gap
tachycardia, hypotension, high blood sugar

DKA needs (treatment)

hydration
insulin
electrolyte replacement

skeletal muscle effects of insulin

insulin increases amino acid uptake and protein synthesis

skeletal muscle effects of lack of insulin

without insulin, protein catabolism with release of amino acids into blood, decrease insulin synthesis

adipose tissue effects of insulin

insulin increases fatty acid uptake

adipose tissue effects of lack of insulin

lipolysis with release of fatty acids into blood

liver effects of insulin

insulin inhabits gluconeogenesis (opposes action of glucagon)
increases glycolysis

liver effects of lack of insulin

increased gluconeogenesis using amino acids released from muscle, glucose into blood, hyperglycemia

impaired glyoclysis leads to incomplete metabolism of free fatty acids released from adipose tissue, release of ketoacids into blood (diabetic ketoacidosis)

type 2

resistance to insulin on peripheral tissues
mostly in older adults
overweight patients (sedentary lifestyle, genetics, diet)
family history
increased prevalence in native americans, african, hispanic & asian people
inc in females
insulin dysfunction (not enough), decreased production

insulin resistance

body tissues don't respond to insulin
decrease in receptor sites, action of glucose transporters
results in hyperglycemia
beta cells hypertrophy, fatigue from overproduction (atrophy at end)
amylin around beta cells

onset of type 2

gradual
person may go years under detected

hyperosmolar hyperglycemic nonketotic syndrome

hyperglycemia of over 600 mg/dL
increased serum osmolality
high glucose level
dehydration
common in type 2 bc endogenous insulin suppresses ketone formation, prevents ketoacid

HHS lab values

glucose: more than 600
urine ketones: none
pH: normal
Na,K: low, normal, high
Hct, Hb... high

clinical manifestations of type 2

fatigue, recurrent infections, prolonged wound healing, polyuria, polydipsia

metabolic syndrome

excess abdominal adipose tissue, insulin resistance, hypertension, hyperglycemia, dyslipidemia
increases risk of cardiovascular disease
age, family history, NA, AA, hispanic

metabolic syndrome AHHL

A: abdominal obesity
men: 40+ inch
women: 35+ inch

H: hyperglycemia
fasting BS of greater than 99

H: hypertension
taking meds for high BP

L: lipids
triglycerides over 150 mg/dL
HDL less than 40 for men, less than 35 for women

other specific types of diabetes

genetic beta cell defects
exocrine pancreas disease
drug induced

gestational diabetes

disorder of glucose intolerance during pregnancy
24-28 weeks
resolves after delivery
can evolve into type 2 with further pregnancies
high infant birth rate and neonatal hypoglycemia

neonatal hypoglycemia

baby secretes insulin on their own too soon, could drop glucose levels

type 1 DM differs from type 2 in that type 1 is

usually associated in middle/late adult
associated with insulin resistance
most common form
from an absolute deficiency of insulin

from an absolute deficiency of insulin

what BMI indicates a screening for diabetes?

25
AA with BMI of 23+

nurse is reviewing lab results for glycosylated hemoglobin levels in patient with diabetes. the nurse is monitoring for

hyperlipidemia
actue complications of diabetes
long-term serum glucose control
fasting glucose levels

long-term serum glucose control (3 month avg) HbA1C

acute hyperglycemia

alterations in nutrition, inactivity, inadequate use of antidiabetic medications
nausea, fatigue, bluured vision

hypoglycemia causes

insufficient food, excess exercise, excess insulin

hypoglycemia symptoms

anxious, sweaty, hungry, confused, blurred vision, shaky, irritable, cool clammy skin, agitation, weakness, paresthesia (tingling)
coma, death unlikely

hypoglycemia counterregulatory mechanisms

pallor
tremor
diaphoresis (sweating)
palpation
anxiety

chronic hyperglycemia

vascular comp (macro and micro)
neuropathic comp
skin comp
infection
comp in pregnancy

macrovascular complications

damage to large blood vessels provide circulation to brain, heart, extremities, resulting from accelerated atherosclerosis

atherosclerosis

a stage of arteriosclerosis involving fatty deposits inside the arterial walls, thus narrowing the arteries (plaque)

macrovascular coronary arteries

coronary heart disease, angina, heart attack, failure
chest pain to diff parts of body
dyspnea, diaphoresis, feeling of doom, edema, distended neck vain...

macro cerebral arteries

cerebral accident or vascular dementia
one-sided weakness or paralysis, aphasia, cognitive impairment

macro arteries in lower extremities

arterial insufficiency
thin, shiny hairless skin on calf
thick toenail
muscle wasting
gangrene
amputation
poor wound healing

peripheral vascular disease (PVD)

risk of leg amputation
neuropathy increases susceptability
fatigue or aching of leg muscles with short walking (intermittent claudication)

arterial ulcers (PVD)

intermittent claudication pain
no edema
no pulse, weak pulse
no drainage
round smooth sores
black eschar
on toes and feet

venous ulcers (PVD)

dull, achy pain
lower leg edema
pulse present
drainage
sores with irregular borders
yellow slough or ruddy skin
on ankles

retinopathy

microvascular
thickening of capillary membranes - obstruction and rupture
can lead to blindness
lack of O2

nephropathy

microvascular
thickening of capillary membranes - obstruction
protein breakdown, excessive osmotic diuresis & glomerular HTN, lead to glomerular hypoxia and sclerosis

neuropathy

microvascular
thick sclerotic blood vessels impaired supply to nerves
excessive glucose impairs myoinositol
nerves demyelinate due to impaired metabolism
can effect any part of nervous system, more in lower extremities

impaired senses for diabetes

vision/touch
subject to repeated trauma, wounds/soft tissue damage

ischemia/hypoxia for diabetes infection risk

micro and macro changes impair blood flow and O2 supply
glycoslyated hemoglobin in RBCs less efficient in gas exhange

pathogens for infection risk

rapid proliferation due to hyperglycemia

suppressed immune response for infection risk

chronic hyperglycemia impairs the innate and adaptive immune responses

a sign of early diabetic nephropathy is

microalbuminuria
allows larger things to enter, wants to hold onto protein but doesn't

the symptom of polyuria in DM is caused by

increased glucose in the urine

which s/sx can help distinguish between type 1 and 2 dm?
hyperglycemia
weight loss
polydipsia
polyuria

weight loss
the other 3 both have

nutrition for type 1

meal plan based on person's usual food intake, balanced with insulin and exercise patterns
eating disorders common in women with type 1

nutrition for type 2

emphasis on receiving glucose, lipid, blood pressure
calorie reduction
obesity is strongest risk

exercise

oldest treatment for diabetes
reduces insulin requirements, keeps weight loss in check, dec risk of heart issues
eat small carb snacks every 30 min to prevent hypoglycemia
after meals, plans should be personalized
measure BG levels before, during, after

pharmacologic agents

oral antidiabetic agents
incretin enchancers, incretins, amylins
insulin

what is the most common complication for pharmacologic agents?

hypoglycemia

insulin

required for type 1
type 2 for those who can't control BG in other ways
rapid-acting, short-acting, intermediate, long, combo (prob don't need to know the specifics) - just that there are diff types

some have a fast onset and peak quickly, others take more time to have an effect

hypoglycemia insulin therapy

admin juice if conscious
admin glucagon if un

allergic reactions insulin

admin benadryl

lipodystrophy reactions insulin

rotate injection sites
hypertrophy or atrophy causes sporadic absorption

somogyi effect insulin

type 1
need to decrease evening or night insulin dose
hypo with rebound hpyer in the morning

dawn phenomenon insulin

early in the morning, rise in BG levels
morning hyper, limit snacks