DM Flashcards
Defintion: a group of common ____ disorders and share the ___ of ____ that affects multiple ___ _____
metabolic disorders
phenotype
hyperglycemia
organ systems
Types of diabetes are caused by ___ and ___
genetics and environmental factors
Factors that can contribute to hyperglycemia are: (3)
- reduced insulin secretion
- decrease glucose utilisation
- increased glucose production
What are some consequences of diabetes?
- adlult blindness
- amputation
- end stage renal disaes (ESRD)
- CV disease
- burden on helath care system and those affected
Broad categories of DM
type 1 and type 2
some other categories of diabetes
MODY
Gestational DM
Which diabetes do we need insulin to survive and which is it just to control glucose levels with?
type 1 - survive
type 2 - control
Where are the three diagnostic measuring tools and what does each one stand for?
FPG - fasting blood glucose
OGTT - oral glucose tolerance test
HbA1c - average glucose levels over past 1 -2 months
The diagnostic range for normal glucose homeostasis - values?
FPG < 5.6 mmol/L
OGTT < 7.9 mmol/L
HbA1c < 5.7 %
The diagnostic range for impaired glucose homeostasis - values?
FPG 6.1-6.9 mmol/L
OGTT 7.8 -11 mmol/L
HbA1c 5.7-6.4%
The diagnostic range for DM - -values?
FPG > 7.00
OGTT > 11
HbA1c >= 6.5
What lab values are recommended to use for screening purposes?
FPG
HbA1c
what are some screening recommendations?
aboe 45 screen every 3 years or if BMI is over 25
- can be asptomatic and unaware
- can have for a decade without knowning
- if we find pre-diabetes values we can maybe prevent DM
- early tx can alter course of DM
Talk about glucose hometostias. like when we have too much glucose vs when we have low levels
too much - message send to pancreas and brain - B isletes cells produced (insulin produced) - fat and msucle take in glucose form the blood
Too little - message sent to brain and pancrease - glucagon relase by al[ha cells, liver relases glucose into blood
Role of incretins? what stimulates them?
incretins are used for hormonal regulation
they are stimulated by the ingestion of food in the gut
The kinds of incretins are:
1. glucose-dependent insulinotropic polypeptide (GIP)
2. Glucose 0like peptide 1 (GLP-1)
They:
- stimulate insulin production and inhibit glucagon
- promote proliferation of beta cells and inhibit apoptosis
- GLP-1 delays gastric emptying and increases satiety
what delays gastric emptying and increases satiety
GLP-1
If we have low arterial glucose comment on what happens along the brain pathway (already covered pancreas pathway)
- stimulate pituitary hormone, growth factor, ACTH Adrenal cortex and then cortisol levels
- increases sympathoadrenal outflow so adrenal medullae produce more ephedrine and sympathetic postganglionic neurons increase norepinephrine and acetylcholine
Epinphrine - stimulates liver whihc causes increase glucose and arterila glucose
norepehinre and acetycholine cause ingestion and less glucose clearance whihc causes increase in arterial glucose
Hypoglycemia activates what 3 responses in Dm and in Dm people?
What are the results of these?
pro-inflammatory, pro-coagulant, pro -atherothrombotic
Results:
1. increase platelet aggregation
2. increase intravascular aggreagtion
3. decreased arterial vasodilation mechanisms
Where is insulin produced?
in the pancreas by beta cells of the islets of langerhans
What are some other pancreatic cells and their functions?
alpha - glucagon production
delta - produce somatostatin
F - produce pancreatic polypeptide
Synthese and insulin production
2 insulin chain with high molecular weight are synthesise and called preproinsulin
after this is sequestered in the lumen of the endoplasmic reticulum they are cleaved by porteases into insulin and C-peptide in the scretory glands of beta- cells
Insulin scretion
glucose enters the beta cell via GLUT
via glucokinase, ATD is generated
ATP then blocks the ATP-sensitive K+ channel meaning that K is effluxed out of the cell.
The cell is then depolarized and ca enter via a calcium voltage-dependent channel.
This stimulates insulin exocytosis from the cell
Insulin receptor and action
Insulin attaches to receptor and tyrosine kinase intrinsic activity is stimulated
the receptor autophsophoryaltes
Actiavting PI-3 kinase
then GLUT4 translocates from inside of cell to cell surface
Glucose is taken up by sketal muscle or fat
What are the effects of insulin on the body sepcifically on carbohydartes,
carbohydrates (muscle, adipose tissue and liver) :
- increase in glucose uptake, oxidation, storage
- increase in glycogon synthesis
- decrease in gluconeogenesis
- decrease in glycogenolysis
What are the effects of insulin on the body sepcifically on AA and proetins
AA and proetins (muslcle):
- increase in aa uptake and protein synthese
- decrease in aa release
What are the effects of insulin on the body sepcifically on lipids
Lipids (adipose tissue and liver):
- increase in triglyceride synthesis
- decrease in free fatty acid and glycerol
- decrease in oxidation of FFa to ketoacids (liver)
what kind of activty does inuslin produce in the body?
anabolism effects (conservative)
Type 1 DM is the reuslt of what? whats the consquence?
autoimmunity against pancreatic beta cells
consquence: Complete or near total inuslin loss
Immunogenic Markers of T1D
Islet cell autobodies (ICA) :
GAD, insulin, IA-2/ICA-512 and ZnT-8
Present in 85% of people diagnosed with T1d
5-10% for T2D
3-4% in first degree relative
ICA combined with what helps us predict DM. and what are the predictions?
ICA with IV GTT:
- 50 % will get Dm in 5 years
- 70% t1d in 10 years
- 80% Dm in 15 years
Etiology of T1D can be ___ or ____
immune-mediated or idiopathic
What autoimmune markers or HLA association offer protective or put you are risk?
Class II MHC genes (HLA region on chromosome 6)
Haplotype: 301, 302, 201 - strong risk
Haplotype: 102, 602 = protective factors
what environmental factors can cause T1D?
- Molecular mimicry - rubella, Coxsakievirus, protein (GAD), bovine milf proteins
- Vit D defieincy
- microbiome
Age for T1D
usualy before 20
do all have evidence for islet-directed autoimmunity?
no, some but not all
Those that lack immunologic and gentic markers have what assumptions amde for them (3)?
- insulin defeiceny is due to unknonw, nonimmune mechanisms
- are prone to ketosis
- many are of afriacn american or asian heritage
humoral and cellualr abnormallities in T1D
- islate cells antibodies, avticated lymphocytes, T lymphocytes, cytokines release within the insulitis
Explain what happens when we don’t have enough insulin?
no beta cells
no insulin availble to cells
no glucose entering cells
glucose acucmulates in blood
- cells satrve (less ATP prpduction) -less energy = tired = difficulty concenrtraion
compensetory mec is activated
Compensatory Mechanisms for hyperglycemia
Catecholamines release Ne/Ep which increase glycogenolysis in liver
Cortisol released promotes gluconeogeneis
Increased ICP
- dehydration
kideney increases (GFR)
- polyuria
-glusaria
Thirst center
- polydipsia
complications of chronic hyperglycemia
HTN, CVD, ESRD, stroke
- effects are vascular or neuropathic
Vascular complications categorized as what?
Macrovascular
- leads to CVD and stroke
and microvascular
- retinophathy and nephropathy
Expand on microvascular complications
- hyperglycemia disrupts platelt function and gorwth of basment membrane
- thickening of basement membrane may improve glycemic control
- risk factors of microvascualr complications include HTn nad smoking
Some overall complications of t1D
- increased risk of infection
- rapid growth of gersm
- reduce defense agaisnt gersm
(poor skin helaing or affects to WBC that can’t get to site to bind due to altered blood suppple or due to phagocytic fucntion of cells)
Diabeteic ketoacidosis
increased lipolysis, FFA, ketoacids, ketosis, and ketoacidosis
How do we manage DKA?(4)
- insulin
- water sodium and potassium replacemnt
- bicarbonate replacemnt
- normalization of glucose level s
insulin therapies?
- BID
- Continouse sc insulin infusion (pump)
- Multple daily insulun injectiosn (MDII)
T2D gentic compont?
yes
Definiton: T2D a ___ ___ disease with strong ____ componet
polygenetic, multifactorial disease with a genetic component
Cause of T2D, contributing factors?
Fro every knonw, one unknonw
obesity contributes
Defect in ___ for T2D
defect in insulin resistacne - change in number or seniticity of insulin receptos leads to developing insulin resistacne
what is T2D characterized by?
- impaired insulin secretion
- excesscive haptic glucose production
- abnormal fat metabolism
- systemic low - grade inflammation
- overprodution and secrtaion for glucagon - therefore more glucose over production
DM and FFA, Lipotoxicity, inflammation, amylin
with obesity FFA increase
- lipotoxicity: decrease signalling in IRs pathway so less adiponectin and leptin levels
- inflammtion: PPAR(Y) by TNF
- Amrylin deposition may cause decreased insulin secretion
MODY 3 vs MODY 5
MODY 3
- respond to sulfonylureas
- mutation in HNR-1 alpha
MODY 5
-minmial repsonse to sulfonylureas so insulin required
- mutation in HNF -1 beta
T2D ketoacidosis?
no
Managment of t2d
- diet and excerise
- oral hypoglymic
- two OH
- OH and insulin
- Insulin
- insulin plus TZD
