Week 7: Type 1 DM Flashcards
Type 1 DM mechanism
autoantibodies against beta cells of pancreas resulting in loss of insulin secretion
Course og Type 1 DM
over months to years, β cells are destroyed until they reach a point where a normal blood sugar can’t be maintained
Describe Islet cell autoimmunity
Type 1 DM is actually T cell mediated and not B cell mediated
People without B cell function can still have Type 1 DM
What causes Islet cell autoimmunity
Genetics but there also seems to be something else
more Type 1 DM Dxd in the winter months versus summer
more Type 1 DM further from the equator
Low prevalence zone to high prevalence zone increases chances
Cocksakie virus / enterovirus
Molecular mimicry GAD
How to screen for Islet cell autoimmunity
Historically were detected this way
Screening for the autoantibodies against β cells
4 listed
- GAD autoantibodies (Glutamic acid decarboxylase)
- Insulin autoantibodies (only on someone not on insulin yet because if exposed to injected insulin can develop antibodies)
- IA-2 autoantibodies (Insulinoma associated antigen)
- ZnT8 (Zinc Transporter 8)
GAD AKA
Glutamic acid decarboxylase
IA-2 AKA
Insulinoma associated antigen 2
ZnT8 AKA
Zinc Transporter 8
Treatment of type 1 DM
mimic the bodies tendency to use glucagon to raise fasting sugars and the insulin for when we are in the fed state
- use insulin regimen 1/2 long-acting mimics gradual gluconeogenesis
- Short-acting insulin to cover the meals in the fed state
Basal-Bolus insulin regiments
Describe the risks of insulin therapy
can be work to maintain proper dosing
Severe hypoglycemia can be life-threatening
Can switch regimens to longer-acting insulins to help prevent spikes or troughs
Severe hypoglycemia treatment
Rescue Glucagon (injection or new intranasal glucagon powder)
Acute complications of Type 1 DM
DKA
DKA AKA
Diabetic Ketoacidosis
What is DKA?
End-result of an insulin deficiency in the setting of a counterregulatory hormone surge like from pneumonia or from a trauma
DKA triad
*Classically* All 3 of these things need to be present for a Dx of DKA
- Hyperglycemia
- Ketosis
- Acidosis
Describe the Mechanism of DKA
deficiency of insulin in the setting of counterregulatory hormone surge
high glucagon, GH, cortisol, catecholamines
increases hormone-sensitive lipase activity leading to FA and glycerol mobilization
glycerol further metabolized to more glucose via gluconeogenesis adding to the already hyperglycemia
FFAs metabolized by the liver to make ketoacids (acetoacetic acid, β-hydroxybutyrate)
This happens very rapidly and the body cannot compensate especially with a deficiency of insulin or insulin signaling
DKA prevalence
New Mexico DKA prevelance
Mortality from DKA
Who is most likely to die from DKA?
Elderly
And usually not DKA itself but is the precipitating event itself
Clinical presentation of DKA
- sugars pouring out of the kidney and pulling water with it (osmotic diuresis) urinating frequently and very thirsty
- malaise, fatigue
- NV
- Abdominal pain
- Altered sensorium in severe cases (altered mental status
Physical exam of DKA
- Tachycardia
- Postural hypotension
- Kussmaul respirations (deep irregular breathing)
- Fruity breath (acetone)
- Abdominal tenderness (can look like acute surgical abdomen or acute pancreatitis)
Diagnostic criteria for DKA
- Glucose High (250 mg/dL) HHS is even higher
- pH low (less than 7.3)
- bicarb low (less than 18 mEq/L)
- Ketones + in the urine or serum
Electrolytes and hydration statues of DKA
Serum K+ can fool because often elevated and it can be caused by a transcellular shift in K+ in the setting of an acidosis (total body K+ can be deficit but appears high in serum)
Precipitating factors of DKA
- Infection
- Noncompliance
- New-onset DM
- MI
- Stroke
- Trauma
- PRegnancy
- Pancreatitis
- EtOH abuse
- Medications (that can cause hormone surge like steroids)
IV fluids
Depends on the degree of dehydration (can use pressors if necessary)
Insulin administration in DKA
don’t target normal blood sugars (target high 150-200) because want to avoid fluid shifts like cerebral edema
K+ administration for DKA
Hold off on K+ and follow it closely because insulin itself will lower K+
When K+ drops to normal range start giving K+ because total body depletion of K+
Unless K+ is low in serum then give fluids and K+ and no insulin
Assess need for HCO3-
if pH is really low
no evidence for improved outcomes
Chronic Complications of Type 1 DM
microvascular (eyes, nerves, kidneys, etc…) not unique to Type 1 DM
Diabetic Retinopathy prevalence
Diabetic Retinopathy classification
- Non-proliferative Diabetic Retinopathy
- Proliferative Diabetic Retinopathy
Macular Edema can occur in proliferative or non-proliferative Diabetic Retinopathy
Non-proliferative Diabetic Retinopathy gross histology
No new blood vessels but abnormal and have hemorrhages
hard exudate (lipids)
white areas infarcted retina (cotton wool spots)
macular edema thickening of the retina fluid has leaked out of the vessels and is accumulating in the retina
Proliferative on the bottom (abnormal blood vessels VEGF) in response to hypoperfusion of the retina (hypoxia)
Can we prevent or slow the progression of Diabetic Retinopathy
glycemic control really helps
HBA1c of < 7 came from this study
ADA screening recommendations for Diabetic Retinopathy
Adherence to screening guidelines
Lower A1Cs and improvement of microvascular complications
less than 7 = less complications
What is diabetic nephropathy histological features
KW nodules (nodular glomerular sclerosis) pathognomonic for DM
diabetic nephropathy prevalence
How to prevent diabetic nephropathy
How to screen for diabetic nephropathy
microalbumin screening annually (urine albumin to creatinine ratio)
Diabetic peripheral neuropathy prevalence
How to prevent diabetic peripheral neuropathy
diabetic peripheral neuropathy screening
feet inspection everytime
diabetic peripheral neuropathy treatment
