Diagnosis, Classification, and Pathophysiology of Diabetes Flashcards
List the Ominous Octet
- Impaired insulin secretion—Islet b-cells
- Increased glucagon secretion—Islet a-cells
- GI tract/decreased incretin effect
- Increased lipolysis
- Increased glucose reabsorption (kidney)
- Decreased glucose uptake (muscle)
- Neurotransmitter dysfunction
- Increased hepatic glucose production
B-cell function and dysfunction
Secretes insulin and amylin
Dysfunction reduces quality and quantity
Amylin function
Inhibits food intake
Delays gastric emptying
Inhibits glucagon secretion, decreasing blood glucose levels
Leading to the reduction of body weight
A-cell function
Glucagon secretion - signals liver to make more sugar (gluconeogenesis) to prevent blood glucose from dropping too low
Role of muscle in managing blood glucose levels
Insulin signals muscles to store glucose
Insulin resistance
Insulin sends signal to muscle to uptake glucose, but the muscle has a reduced amount of glucose transporters to take it in
GI tract function in diabetes
Food normally moves through the small intestines in 90 minutes
In T2DM, it takes 30 minutes, increasing postprandial glucose spikes.
It takes about 20 minutes for the brain to recognize that it’s full. People with T2DM feel hungry quicker due to speed of GI tract and decreased incretin (GIP and GLP-1) effect
What are the two major incretins?
GIP — gastric inhibitory polypeptide, glucose-dependent insolinotropic polypeptide
GLP-1 — glucagon like peptide-1
Kidney function in diabetes
Kidney raises renal threshold to hold onto sugar that isn’t being absorbed into the muscle
BG > 180 overloads kidneys and causes glucose to be secreted into urine
Normal renal threshold is about 180 mg/dl
A1c of 6.5% — about 205 mg/dc
A1c of 9% — about 260 mg/dc
Increased Lipolysis function in diabetes
High insulin levels cause excess visceral fat (belly fat or bad fat). This leads to increased fat breakdown (lipolysis).
Bad fat is metabolically active fat that increases cytokines, interleukins, tumor necrosis factor, and decreases adiponectin (insulin resistance sensitizer) when broken down. This causes inflammation and damage to the tissues within the body.
Natural History of T2DM
It takes about 9-12 years to be diagnosed with T2DM if not monitored. Diagnosis happens after a complication arises (wound won’t heal, blurry eye sight, MI, etc.)
Postprandial BG increases first while fasting BG stays normal. Postprandial BG directly related to macrovascular complications.
Fasting BG increase with time due to b-cell decreased function.
We tend to look at fasting for diagnosis, so diagnosis can be missed early on.
80-85% b-cell function lost by time of diagnosis.
What contributes to b-cell dysfunction?
Insulin resistant organs
-Liver (increased lipids exposure can lead to b-cell dysfunction)
-Muscle
-Adipose tissue (increased lipids exposure can lead to b-cell dysfunction)
Other Organs
-Brain
-Colon
-Immune System
Hyperglucagonemia
B-cells outnumber a-cells in healthy subjects
A-cell mass is not altered in T2DM
As T2DM progresses, the ratio of alpha to beta cells increases
Glucagonoma leads to diabetes-like symptoms and other severe symptoms, including: high blood sugar. excessive thirst and hunger due to high blood sugar
Gut Mictobiome role in T2DM
Effects immune system (can prevent infections)
Antibiotics may increase risk of diabetes
-killing good bacteria allows bad bacteria to dominate and can alter nutrient absorption and metabolism
Pre/probiotics may address this mediator of hypoglycemia
ADA Diabetes Diagnosis Criteria
FPG >= 126 mg/dl
2 hr PPG (75 g OGTT) >= 200 mg/dl
Random >= 200 mg/dl
A1c >= 6.5%
A1c measurement interference and alterations
Pathophysiology of T1D
T1D Endotypes
ADA Staging of T1D
Differences between Type 1 and Type 1.5 Diabetes
Who should be screened for immune-mediated diabetes?
What are the three groups of diabetes in pregnancy?
Gestational Diabetes Diagnosis Criteria — one-step
Gestational Diabetes Diagnosis Criteria — two-step
Differences between Overt Diabetes and GDM
Monogenic Diabetes
(Slide with Fasting and A1c ranges, no mutations listed)
How to diagnose monogenic diabetes?
MODY
Type 3c Diabetes
Why is Type 3c diabetes frequently misclassified?
B-cell Centric Model
