glucose regulation 1/2 DM 1

endocrine organs fx

synthesize and secrete hormones

endocrine

hormones released into bloodstream

paracrine

into adjacent tissue only

hormones

many have long half life = likely high ppb like t4 hormone

secretions triggered by

-concentrations of specific substance (glucose)

-neural stimulation (SNS & epi)

-endocrine sequences (epi → aldosterone)

regulate secretions

negative feedback mechanisms

function tests

hormone level or the affector substance level

-like glucose (indirect test of insulin fx); t4 (direct hormone level test)

endocrine dysfunctions

hyposecretion or hypersecretion (s&s will be directly related to excess or deficit of the expected hormone level)

-d/t primary endocrine disorder; signaling disorder; sequence disorder

hyposecretion

congenital defect, disease/inflammation, hypoperfusion, ageing

hypersecretion

genetic, tumours, environmental stimuli

primary energy sources

glucose, fatty acids (fats)

glucose

is readily distributed

needed for brain (cns)

extra stored as glycogen and triglycerides

-cannot store it as regular glucose for later

cns

needs constant supply of glucose (broken down: CO2 and H20)

glycogen and triglycerides

in liver and muscles and adipose cells

-fall in BG → glycogen breakdown via glycogenolysis (triggered in glucagon hormone) → for when extra glucose needed

gluconeogenesis

formation of more glucose from other sources, released prn

fatty acids

distributed via lymph to circulation

-cns and rbcs cannot use fatty acids

triglycerides

extra fatty acids stored as

-broken down into 3 fatty acids and glycerol

glycerol

glycolytic pathway into glucose

fatty acids

are not converted into glucose - cannot be used by the brain for energy

ketone metabolites

fatty acid metabolism in liver

insulin

pancreatic hormone (endocrine)

-synthesized in Beta cells (Langerhans)

insulin actions

glucose’ cellular uptake

promotes storage formation

amino acid cellular uptake; triglyceride adipose cell uptake

promotes storage formation

insulin action

-glycogen synthesis

-triglyceride synthesis

-protein synthesis

-prevents: glycogen and fat lysis (in order 1st use glucose) & protein lysis (to preserve tissue)

glucagon

synthesized in alpha cells = opposite of insulin

promotes mobilization of stores

glucagon

-glycogenolysis; gluconeogenesis (amino acid conversion into glucose); lipolysis (triglyceride breakdown)

glucagon triggered by

low plasma glucose levels (between meals; hypoglycemia) → mobilize stores and replenish blood glucose for cellular use

pancreas to release insulin

high blood glucose triggers

the beta cell in isle of langerhans

insulin released from

take up glucose from blood

blood glucose falls because cells

produces glycogen

blood glucose falls because liver

pancreas to release glucagon

low blood glucose triggers

glucagon

alpha cells secrete this (in islet of lagerhans)

down glycogen

glucagon released and liver breaks

liver breaking down glycogen

blood glucose rises due to

beta cells secrete insulin

glucose enter pancreatic beta cell via glucose transporter → metabolized via glucokinase into ATP → closes K channels (on beta cell) → depolarization → insulin secretion

insulin synthesis

stimulant is high serum glucose

50% 1st pass metabolized

insulin from pancreas enters hepatic circulation

metabolites

are renally excreted

tyrosine kinase

insulin binds to this cellular membrane receptor

kinase enzyme

tyrosine kinase activates this enzyme within cell

channels

kinase enzyme within cell stimulates these glucose transporter _____ to open to glucosse

somatostatin

is d cell produced

inhibits glucose and insulin

immediate effects of beta cell destruction

disabled transport of glucose into cells → dysfunction of glucose, fat, and protein metabolism

results from beta cell destruction

hyperglycemia, polydipsia (high solute [ ]), cellular dehydration, polyuria, glycosuria, fat for energy, ketones, metabolic acidosis

polydipsia

thirst triggered -really high solute in serum = high osmotic pressure, dictates h2o into blood

osmotic shift into filtrate

high urine production

-due to beta cell destruction

fat for energy

due to beta cell destruction

• = breakdown of triglycerides and glycerol

ketones

from hepatic metabolism of fatty acids

due to beta cell destruction

metabolic acidosis

occurs from ketones which are result of hepatic metabolism of fatty acids

-drop ph of blood less than 7.35

-lactate byproduct of aerobic metabolism also increases acidity

-also produces acetone (sweet breath)

results from beta cell destruction

ketonuria, changes in loc, acetone breath, metabolic acidosis, coma, death

acetyl CoA

from free fatty acids which leads to ketone bodies synthesis which leads to ketone bodies which produce acetone and ketonuria

energy substitutes

lipolysis and proteolysis

lipolysis

fatty acid breakdown

liver metabolism fatty acids (fatty acid oxidation) = ketones and ketonuria

proteolysis

weight loss and muscle wasting (smooth muscle too which can have severe s/e)

altered cell fx due to reduced glucose uptake consequences

insulin resistance (due to lowered fx of cells)

altered cellular repair

endothelial dysfunction and decreased angiogenesis

organ injury

endothelial dysfunction causes

increased oxidative stress → inflammatory consequences = risk of clotting

organ injury from reduced glucose uptake

retinopathy, neuropathy, nephropathy, CV

DM dx

fasting glucose >7mmol/L (normal <6)

type 1a dm

genetic predisposition + triggering event (infection, trauma) → immune rxn to beta cell antigens = autoimmune

type 1b dm

idiopathic (familial), rare

dm

total detruction of beta cells: IDDM (insulin dependent)

when is iddm dx

usually pre 30yrs of age (toddler and teens) - rapid growth and hormonal changes

iddm tx

insulin

-if no tx: diabetic ketoacidosis = death

basal insulin level

5-15 IU/mL 

-always present ongoing secretion

-cruise control

peak level insulin

60-90 IU/mL

booster at meals to match glucose content

normal levels

4-8mmol/L

tx w/ insulin goal

restore normal glucose patterns

mimic basal & peak endogenous levels

minimize risk of hypoglycemia

4 basic insulin categories

rapid acting (10-15 min onset)

long acting (up to 24hrs cruise control always present)

short acting (regular) peak and duration slightly longer

intermediate acting (NHP) slightly higher peak

SC insulin

injections, portable pen injectors, insulin pumps (basal and bolus delivery)

IV insulin

utilized in critically ill patients

drug admin rights

dose double checked by 2 rns

check dose carefully (units)

injection sites

upper outer arms

abdomen

buttocks

upper outer thighs

need to rotate sites

rapid acting insulin

onset 10-15 mins

peak 1-2 hr

duration 3-5 hrs

-ideal for meal time bolus, pt can eat right away, insulin for insulin pumps

-dose per carb contnent

check bg 1-2hr post

rapid acting insulin drugs

Humalog (lispro)

Novorapid (Aspart)

Apidra (Glulisine)

Fiasp (Aspart) faster onset of 4min

rapid acting insulin in pumps

meal time boluses

per carb content

check bg pre meal and 1-2 hr post

basal insulin requirements in pumps

always slowly given over 24 hrs

or given once to twice in hospital

check bedtime bg, if lowers too much overnight risk for hypoglycaemia = adjust basal insulin dose

endocrinology appts

long acting insulin

onset 90 min

plateaus for up to 24hrs (depends on how often you give it)

ideal for: background admin 1-2x daily consistency is important - never IV

adjust dose according to bedtime bg level

long acting insulin drugs

Levemir (Detemir)

Lantus (Glargine)

Tresiba (Degludec) ultra long acting

short acting insulin (regular)

onset 30 mins

peak 2-3 hrs

duration 6.5 hrs (dose dependent)

ideal for: meals (30-45 min pre meal) 

issues with hypoglycemia and balancing dose w intake, ensure pt eats

short acting insulin iv

used if ketoacidosis, new dx, stabilizing pt in hospital

short acting insulin drugs

Novolin ge Toronto

Humulin R

Entuzity (KwikPen) 5x more [ ]

intermediate acting insulin

onset 1-3 hrs

peak 5-8hrs hypoglycemia at peak, why not as popular

duration up to 18hrs (dose dependent)

ideal for: background replacement, admin 1-2x daily if pt on steroids

never iv

monitor night for hypoglycemia

intermediate acting insulin drugs

Humulin N

Novolin ge NHP

intensive insulin tx req

estimated daily insulin reqd: 0.55 U x Pt. wt (kg)

-doesnt factor in BMR, activity/stress, food, starting point only

-approx 40% of estimate = basal

other 60% = boluses

bolus insulin dosage based on

BG pre meal

carb content/meal

basal insulin dosage based on

estimate, bedtime bg level

am admin preferred, avoids nighttime hypoglycemia

similar amt each day, as long as bedtime bg is normal

given even if pt is npo

if pt on insulin pump, the basal dose is continuously delivered (fast acting insulin)

BBIT

basal (long acting) in am

bolus (short/rapid) @ meals

insulin correction (short/rapid) if necessary (based on bg post meal)

titrate doses to achieve glucose levels 4-8 (monitor bg through day)

bg checks recommended

pre meal, post meal (1-2 hr for new dx), at bedtime

4x day minimum

8x for newly dx pts