Diabetes Lecture

Question 1

Diabetes definition

Answer 1

group of metabolic diseases characterized by high BGL, resulting from defects of insulin secretion, action, or both

Question 2

What are 3 major health complications that DM is the #1 cause of?

Answer 2

Blindness, leg amputation, and chronic renal failure

Question 3

Acute complications of DM:

4 things

Answer 3

1. ketoacidotic coma (DKA)
2. hyperosmolar hyperglycemic non-ketoacidotic syndrome
3. lactic acidosis
4. hypoglycemia

Question 4

Chronic complications of DM:

4 things

Answer 4

1. microangiopathia (retino, nephro, neuro)
2. macroangiopathia (atherosclerosis, HTN)
3. neuropathia (sensory-motor, autonomous)
4. increased risk of infection

Question 5

Prevalence of DM in developed countries, and difference between type I and II

Answer 5

5-5.5% of population
90% are type II
5-10% type I

Question 6

What type of type II diabetes might be confused for type I?

Answer 6

LADA: Latent Autoimmune Diabetes in Adults

Up to 20% of type II diagnoses may actually be this

Question 7

What is MODY?

Answer 7

Matury Onset Diabetes of Young. Caused by genetic mutations of beta cell function that reduce insulin production. 6 types but most common if HNF1-alpha

Question 8

Monogenic mutations related to MODY:

this is a bullshit list but they seem to love bullshit on the quizzes

Answer 8

HNF1-alpha, GCK, HNF4-alpha, IPF1, HNF1-beta, NEUROD1

Question 9

What is Rabson-Mendenhall syndrome?

Answer 9

severe insulin resistance due to mutations in insulin receptor gene

Question 10

What are some drugs that affect pancreas functioning?

Answer 10

Pentamidin, nicotinic acid, glucocorticoids, thiazids, beta adrenegic agonists

Question 11

What are some genetic abnormalities related to DM type I? (i.e. sex chromosome linked diseases, etc)

Answer 11

Down syndrome, Turner syndrome, Klinefelter syndrome, Huntington’s chorea, Porphyria, Myotonic Dystrophy

Question 12

What are some endocrinopathies related to DM?

Answer 12

Acromegaly, Cushing syndrome, hyperthyreosis, pheochromocytoma

Question 13

What is the difference between the two types of DM type I?

Answer 13

Type 1a: classic autoimmune cause, covers vast majority of cases

Type 1b: rare, non-autoimmune, idiopathic cause. More common in Asian or African people. May not need insulin.

Question 14

What are the 3 classic symptoms of DM type I?

excluding DKA from untreated diabetes

Answer 14

Poluria
Polydipsia
Polyphagia (yet weight loss)

Question 15

What is the total mass of islet cells?

Answer 15

1-1.5g

Question 16

What are some HLA alleles that are correlated to more or less diabetes mellitus type I risk?

Answer 16

HLA Class I: A, B, C all increase
HLA Class II: DRB1, DQA1, DQB1 increase

But DRB10403 and DRB10406 decrease chance

Question 17

What are some non-HLA gene regions of the human genome that are associated with DM type I?

Answer 17

Insulin, CTLA4, PTPN22, IL2RA

These have overlap with other autoimmune diseases

Question 18

How is the incidence of DM influenced by geography?

Answer 18

Incidence decreases from North to South direction (at least in Europe and China)

Question 19

What are 3 ways that viruses could trigger autoimmune destruction of beta cells?

Answer 19

1. viral epitopes and antigens being similar matches
2. cytolytic infections might present the sequestred proteins
3. moleculary mimicry (coxsackie P2-C and GAD65; enterovirus VP1 and tyrosine phosphase IA-2)

Question 20

What are 4 viruses in the etiology of type 1 DM?

Answer 20

Mumps
Coxsackie A, B
Rubeola
Cytomegalovirus

Question 21

Polymorphisms in which genes are related to response to viral infections and have a link to DM type I?

Answer 21

IFIH1, MDA5, OAS1

Question 22

What are 3 toxins in the etiology of Type 1 DM?

Answer 22

Alloxan
Streptozotocin
Nitrozamin

Question 23

What type of food product that kids frequently ingest shows a relation with DM type I, and why?

Answer 23

Cow Milk: has bovine serum albumin (BSA), where a 17 AA fragment might induce immune rxn in which antibodies cross-react with human beta cell proteins.

Could be bovine insulin in the milk too.

Question 24

What is the order of pathogenesis of type I DM?

Answer 24

1. Genetic predisposition
2. Trigger (virus or toxin)
3. Insulitis
4. Autoimmune rxn
5. Beta cell destruction (via cytotoxic T cells and specific antibodies)
6. Clinical manifestations on destruction of 80-90% of beta cells

Question 25

What is the difference between early and late stage insulitis?

Answer 25

Early stage: CD8+ T cells and macrophages attack beta cells

Late stage: mature B cells have specific antibodies against beta cells

Question 26

What are 3 antibodies related to developing type I DM?

Answer 26

1. Islet cell antibody (ICA)
2. Insulin autoantibodies (IAA)
3. Glutamic acid decarboxylase antibodies (GADA)

Question 27

3 factors of the etiology of type 2 DM:

Answer 27

1. genetic predisposition
2. insulin resistance
3. decreased insulin secretion (insufficient beta cell function)

Question 28

Metabolic syndrome requires at least 3 of these 5 traits:

Answer 28

1. abdominal obesity (>102cm in males, >88 in females)
2. Raised triglycerides >1.7 mM
3. Reduced HDL cholesterol (<1 mM in male, <1.3 mM in females)
4. Raised BP >130/85
5. Insulin Resistance

Question 29

Stopping here

Answer 29

Incomplete deck