Type 1 Diabetes Flashcards
When glucose stimulates insulin secretion, you get regulated secretion of insulin in the form of _____
insulin and c peptide (96%) and proinsulin/intermediates (4%)
Insulin secretory vesicles
10k granules/beta cell
Secretory granules contain insulin and ____
zinc, proinsulin, proteolytic enzymes, iapp (islet amyloid polypeptide)
Glucose is taken up by the beta cell via ___
Glut2
Rate limiting step of glucose in beta cell
glucokinase
Insulin vesicle release are dependent on the contribution of ____ form voltage gated channels.
Calcium
______ is used diagnosticlaly to determine if someone is secreting insulin
c-peptide release
Insulin release in beta cell
glucose –> glut 2–> glycolysis –>atp/adp ratio increase –> atp sensitive potassium channel –> voltage gated ca channel –> calcium –> vesicle release
Stimulators of insulin secretion
nutrient load, vagus nerve (inhibited by sympathetics, cephalic phase sight/smell of food, gut hormons (GLP1/GIP)
Inhibitors of insulin secretion
starvation/hypoglycemia, glucagon, epinephrine, growth hormone, cortisol
The major regulator of insulin secretion is ___
glucose
If secretory stimulus persists, a ___ response follows which involves active synthesis of insulin in the beta cells
second/delayed
sulfonylureas stimulate/inhibit insulin secretion
stimulate
Insulin is a ____ hormone
anabolic
Principal metabolic function of insulin
increase rate of glucose transport into select cells in body
Type 1 diabetes subtypes
1a = autoimmune, 1b = non-autoimmune
Most T1D are auto/non auto immune
autoimmune
Gestational diabetes is a precursor of ____
t2d
LADA
latent auto-immune diabetes of adulthood –> adult age at diagnosis, initially appears as nonobese t2d –> initially controlled with meal planning with or without oral pills –> low c peptide concentration and antibody psotiive
monogenic diabetes
characterized by pancreatic beta cell dysfunction –> autosomal dominant
T1D or T2D? absolute insulin deficiency
t1d
T1D or T2D? abrupt onset
t1d
T1D or T2D? life long insulin injection
t1d
T1D or T2D? propensity for development of dka
t1d
T1D or T2D? predominant under 30 yrs old
t1d
T1D or T2D? insulin resistance with relative insulin deficiency
t2d
T1D or T2D? gradual onset of hyperglycemia with decline of beta cell function
t2d –> initially silent
T1D or T2D? oral treatment
t2d
T1D or T2D? hhnk
t2d –> hyperosmolar hyperglycemic non-ketosis
T1D or T2D? dka
either
T1D or T2D? family history rare
t1d
T1D or T2D? family history common
t2d
T1D or T2D? first functional bnormality is decrease in insulin secretion
t1d
T1D or T2D? first functional abnormality is decreased insulin secretion and decreased response to insulin
t2d
T1D or T2D? insulinitis
t1d
T1D or T2D? amyloid deposition, fibrosis, beta cell mass reduction
t2d
T1D or T2D? absence of beta cells, increase in alpha and gamma cells
t1d
Dx of t2d
diabetes symptoms + glucose >200 or fasting glucose >126 or 2 hour glucose ogtt >200, a1c > 6.5
HbA1c
non enzymatic glycosylation of hemoglobin AA residues – accumulates over 2-3 lifespan of rbc’s
T/F HbA1c can be used for dx
T
highest risk ethnicity for t1d
n europe
peak ages for onset of t1d
5-7rs and onset of puberty
T/F t1d onset is more common in winter
T
Risk factor for t1d or not? viral infection
yes
Risk factor for t1d or not? immunization
yes
Risk factor for t1d or not? cows milk
yes
Risk factor for t1d or not? high socioeconomic status
yes
Risk factor for t1d or not? obesity
yes
Risk factor for t1d or not? d deficiency
yes
Risk factor for t1d or not? low birthweight
no
Ab measured during preclinical t1d
islent cell antibodies, insulin autoantibodies, antibodies to glutamic acid decarboxylase (GAD), antibodies to tyrosine phosphatase like proteins such as insulinoma associated protein (IA2)
The ____ has been identified as a candidate t1d autoantigen since 60-80% have autoantibodies to it.
ZnT8 cation efflux zinc transporter
Pathogenesis of t1d
chronic auto-immune insulitis –> high risk MHC class II genes encoding HLADQ induce presentation of peptides form islet autoantigens to CD4 and CD8 –> destruction of beta cells –> cellular infiltrate –> destruction of beta cells but not alpha or gamma cells
T/F there is often a concurrence of other auto-immunities with t1d
T
Tx of T1d
insulin replacement, education, adjust doses according to cho intake, exercise, blood glucose profile, test glucose levels, screen for complications
The ______ approach involves basal insulin to meet the insulin requirement to suppress hepatic glucose production between meals and bolus insulin to meet the insulin requirement after eating.
basal-bolus approach
Dx? Low blood pressure, high heart rate, plasma glucose 550, urine ketones +
type 1d + dka
DKA
no insulin –> starvation –>
- liver production of glucose –> glucosuria –> polyuria –> dehydration
- muscle –. increase plasma glucose and muscle wasting –> weight loss
- adipose –> increase plasma FFA –> increase plasma Beta hydroxybutyrate and acetoacetate –>acidosis
Acute problems with DKA
hyperosmolar dehydration and acidosis
DKA tx adverse events
cerebral edema, hypokalemia
Tx of DKA
insulin + fluid/electrolyte
hypoglycemia
most common in t1d from overdose of insulin
relative hypoglycemia
patients with chronically high glucose suddenly have a reduction to normal or less high glucose
