Diabetes 2 Flashcards
type 1 diabetes pathophys
Results from an autoimmune process that destroys the pancreatic islet cells leaving inadequate levels of insulin production (insulin deficiency)
type 2 diabetes pathogeneis is __
a combo of
Pathogenesis is multifactorial, a combination of genetic and environmental conditions
type 2 diabetes leads to
1. defective __ secretion from __ dysfunction leading to relative __
2. __ resistance
3. increased __ production by the liver
type 2 diabetes leads to
1. defective insulin secretion from beta-cell dysfunction leading to relative hypoinsulinemia
2. insulin resistance
3. increased glucose production by the liver
3 acute complications of diabetes
- DKA
- HHS
- Hypoglycemia
DKA is an __ complication of diabetes characterized by absolute or relative __
DKA is an acute complication of diabetes characterized by absolute or relative insulin deficiency
which type is DKA more common in
T1DM (but it happens in both)
DKA characterized by
biochemical triad
biochemical triad for DKA
- hyperglycemia
- ketonemia: positive serum or urine ketones
- anion gap metabolic acidosis
anion gap metabolic acidosis values
anion gap > 10
pH < 7.3
serum bicarbonate < 18 mEq/L
Anion Gap Calculation: Sodium-(Chloride + HCO3)
clinical presentation of DKA
- rapidly evolving (seen within 24-hour period)
- hyperglycemia
- dehydration
- acidosis
- hyperosmolarity
causes of DKA
- forgetting insulin
- acute stressors
- infection
- new onset T1DM
- drugs
- GI illness
- other: MI, CVA, pregnancy
DKA: insulin deficiency leads to __ and a perceived __ state, indirectly activating __ and __
DKA: insulin deficiency leads to hyperglycemia and a perceived fasting state, indirectly activating lipolysis and ketogenesis
DKA: counterregulatory hormones promote __, __, and __ which lead to __ and __
DKA: counterregulatory hormones promote glycogenolysis, gluconeogenesis, and lipolysis which lead to hyperglycemia and ketogenesis
DKA dehydration
Hyperglycemiainduced osmotic diuresis leads to electrolyte loss, decreased glomerular filtration and worsens hyperglycemia
DKA hormone imbalance: too much __
too little (4)
DKA hormone imbalance: too much insulin
too little glucagon, cortisol, atecholamines, growth hormone
ways to measure ketone production
- 3-beta-hydroxybutyrate in blood
- acetoacetate in urine
- acetone released in lungs (fruity breath)
hyperosmolar hyperglycemic state (HHS) is when you have low or no
ketones
HHS characterized by
severe hyperglycemia, hyperosmolarity, and dehydration in the absence of significant ketoacidosis
HHS has no (which symptom)
ketoacidosis
clinical presentation of HHS resembles __ but is __ severe and takes __ to develop
clinical presentation of HHS resembles DKA but is more severe and takes longer to develop
lab findings for HHS
Hyperglycemia: typically above 600mg/dl
Hyperosmolarity: serum osmolality > 320 mOsmol/kg
Serum pH >7.3
Absent to mildly elevated ketones
pathophys of HHS
__ deficiency
__regulation of counter-regulatory hormones
__ ketone production
dehydration
pathophys of HHS
insulin deficiency
upregulation of counter-regulatory hormones
limited ketone production
dehydration
goal of DKA/HHS treatment
- Restore intravascular volume with IVF
- Correct electrolyte abnormalities
- Correct hyperglycemia and acidosis with insulin therapy
- Identify and treat any precipitating factors
- Provide patient and family education to prevent future recurrent episodes of DKA/HHS
clinical hypoglycemia
is a plasma (or serum) glucose concentration low enough to cause symptoms and/or signs, including impairment of brain function.
lower limit of normal fasting glucose:
hypoglycemia symptoms occur at:
lower limit of normal fasting glucose: 70 mg/dL
hypoglycemia symptoms occur at: < 55 mg/dL
hypoglycemia can be caused by too much __ or __, too little __, or excessive __
hypoglycemia can be caused by too much insulin or oral anti-hyperglycemic agents, too little food, or excessive excessive PA
hypoglycemia is confirmed by __ triad
hypoglycemia is confirmed by Whipple’s triad
Whipple’s Triad
- Symptoms, signs or both consistent with hypoglycemia
- Low plasma glucose concentration
- Resolution of symptoms/signs after the plasma glucose is raised
hypoglycemia symptoms and signs
Autonomic Symptoms (adrenergic): palpitations, tremor, anxiety
Neuroglycopenic symptoms (glucose deprivation in the brain): dizziness, confusion, weakness
why is hypoglycemia so concerning?
brain can’t synthesize glucose, so it needs a continuous supply from circulation
counter-regulatory systems to prvent and rapidly correct hypoglycemia
Decrease insulin secretion
Increase glucagon secretion ->glycogen breakdown in the liver
Increase epinephrine secretion ->increases hepatic glucose production
Increase cortisol and GH secretion -> enhance hepatic glucose production, increase insulin resistance
hypoglycemia is corrected with __ grams of __
hypoglycemia is corrected with 15 grams of fast acting concentrated carbohydrate
hyperglycemia can lead to
diabetic tissue damage
mechanisms that lead to diabetic tissue damage in hyperglycemia
Activation of the polyol pathway
Glycation (AGE’s)
Protein kinase C activation
Increased hexosamine pathway
hyperglycemia increases flux through the __ pathway
hyperglycemia increases flux through the polyol pathway
hyperglycemia and polyol pathway
Glucose is normally phosphorylated by the enzyme hexokinase
Hyperglycemia saturates hexokinase → we push to polyol pathway
polyol pathway leads to reduced levels of __ and __ –> reduced __ synthesis and increased risk for __ and __
polyol pathway leads to reduced levels of NADPH and NAD+ –> reduced glutathione synthesis and increased risk for oxidative stress and damage
hyperglycemia leads to the __ complications observed in diabetes
hyperglycemia leads to the microvascular complications observed in diabetes
other factors such as __ and __ contribute to tissue damage
other factors such as genetic determinants and HTN contribute to tissue damage
microvascular vs. macrovascular complication
Microvascular complications: effect small vessels of body (main focus of today)
Macrovascular complications: large vessels of the body
chronic complications of DM
- microvascular
- macrovascular
- blindness
- kidney damage
- nerve damage
- amputation
- CVD (stroke, heart attack, loss of circulation in arms and legs)
diabetic retinopathy is when diabetes causes damage to
the capillary endothelial cells of the retina
most common DM complication
retinopathy
main cause of blindness in middle age persons in industrialized nations
diabetic retinopathy
3 classifications of diabetic retinopathy
- non-proliferative
- proliferative
- macular edema
non-proliferative diabetic reitnopathy
aka background
absence of abnormal new blood vessels
Mild Moderate Severe
proliferative diabetic retinopathy
presence of abnormal new blood vessels
Mild Moderate Severe
macular edema diabetic retinopathy
retinal thickening and edema of the macula
Can occur at any stage of diabetic retinopathy
characteristics of nonproliferative diabetic retinopathy
Exudates: cholesterol deposits in eye
Hemorrhage: bleeding in eye
Microaneurysms: can bleed into eye
characteristics of proliferative diabetic retinopathy
neurovascularization
risk factors for progression of retinopathy
Poor glycemic control
Longer duration of DM
Baseline severity
Pre-pubertal onset of Type 1 DM
Pregnancy → additional estrogen is a problem
Sudden improvement in glucose control
HTN
Smoking
Dyslipidemia
3 retinopathy treatment options
- meds
- photocoagulation (laser)
- vitrectomy
meds to treat retinopathy
Vascular endothelial growth factor inhibitors are injected into the vitreous eye.
Help stop growth of new blood vessels and decrease fluid build-up
photocoagulation to treat retinopathy
Burning the blood vessels leads to shrinkage and scar formation
Can stop or slow leakage of blood and fluid in the eye
vitrectomy for diabetic retinopathy
Tiny incisions are made in the eye to remove blood from the middle of the eye (vitreous)
diabetic neuropathy prevalence
30%
diabetic neuropathy prevalence increases with __ and disease __
diabetic neuropathy prevalence increases with age and disease duration
other factors contributing to diabetic neuropathy
smoking
poor glycemic control
clinical symptoms of diabetic neuropathy
Distal Symmetrical Polyneuropathies
Autonomic
Radiculopathies (Thoracic and Lumbar)
Micro Neuropathies
Cranial neuropathy
Limb mononeuropathy
diabetic nephropathy prevalence
T1DM 25-40%
T2 DM 5-40%
leading cause of end stage renal disease
diabetic nephropathy
risk factors fo diabetic nephropathy
Poor glycemic control
Genetic susceptibility
HTN
Smoking
Dyslipidemia
how to monitor diabetic nephropathy
urine protein to characterize degree of progression
early phase diabetic nephropathy
Hyperfiltration
↑ GFR: from afferent arteriole dilation»>efferent arteriole dilation
↑ Glomerular Pressure
Thickened GBM and mesangial expansion
microalbuminuria
Dysfunction of the Glomerular Filtration Barrier: podocyte and endothelial damage
Damage may be reversible
macroalbuminuria
Decreased GFR
↑ BP
end stage renal disease
Uremia
HD/renal transplant
how to prevent diabetic nephropathy
yearly screening for urine albumin excretion rate
lifestyle modifications
tight glucose control
hypertension control
most common diabetic neurpathy
distal symmetric polyneuropathy
distal symmetric polyneuropathy
Affects 10-50% of patients with DM
Predominantly sensory
“stocking/glove distribution” → hands and feet
Large or small fibers
small fiber sensory neuropathy
Small = Not covered in myelin
Typically send messages about illness and injury including pain, itch, and temperature discrimination
Pain
Autonomic small fibers also carry messages that control our internal organs
Assess function by testing temperature with a hot and cold test and sensation with a pinprick exam
small neuropathy means
not covered in myelin
large fiber sensory neuropathy
Large fiber sensory neuropathy
Thicker fibers covered in myelin
Loss of protective sensation
Loss of sense of position of different parts of the body (proprioception)
Poor balance
Decreased vibration sense
Decreased ankle reflex
May lead to callus, foot ulcers, Charcot foot, amputations
how to test for large fiber sensory neuropathy
tuning fork
Hit fork, touch bony part of foot
If they say sensation in foot stops vibrating before tuning fork does, they’ve lost a bit of sensation
Semmes-Weinstein monofilament
Patient closes eyes, touch them in 10 spots
Monofilament always exerts same amount of force
Failing this test is bad bc the patient can’t feel cuts or injuries on their feet (make sure they’re self checking)
autonomic neuropathy
Affects the sympathetic and parasympathetic system
Responsible for a significant proportion of the morbidity and mortality associated with DM
autnomic neuropathy involves which system
cardiovascular and GI
macrovascular complications of diabetes
CVD
skin complications
insulin lipodystrophy
acanthosis nigricans
Darkening of skin on neck
insulin lipodystrophy
areas where insulin is injected have fat loss (lipoatrophy) or fibrofatty scar tissue (lipohypertrophy) at injection sites → important because insulin won’t work well if injected into scar tissues
if insulin is injected into scarred areas,
absorption may be delayed
how to prevent diabetes macrovascular complications
strict glycemic control
