Pathophys of T1/2D

Question 1

Diabetes mellitus definition

Answer 1

Chronic incurable disease characterized by elevated blood glucose resulting from defective insulin production and/or action
Hyperglycemia is definitive diagnosis

Question 2

4 main symptoms of diabetes

Answer 2

Thirst
Hunger
Urination
Weight loss

Question 3

T1D

Answer 3

“Juvenile diabetes” but can occur in adulthood
Due to autoimmune destruction of beta cells
Involves both genes and environment

Question 4

Evidence for T1D being an autoimmune disease

Answer 4

T cell infiltration of the islet (recognize beta cell autoantigens)
Islet cell antibodies (more markers of autoimmunity than active in beta cell attack)
Strong genetic associated with certain HLA loci
Associated with other autoimmune diseases (ex: celiac)

Question 5

Is type 1 or 2 diabetes more associated with genetics?

Answer 5

Type 2!

Concordance in twins 90% compared to 50% in T1D

Question 6

Treatment of T1D

Answer 6

Insulin!
Islet transplantation (stem cell derived beta cell replacement)

Question 7

Prevention for T1D

Answer 7

Immunosuppression
Peptide therapy (ex: insulin)
New immunosuppressive therapies

Question 8

T2D

Answer 8

“Adult onset” but now seen in children
Associated with defects in insulin action (increased resistance) and insulin secretion
Associated with sedentary lifestyle and Western diet

Question 9

Can we prevent T2D

Answer 9

Yes
Metformin and lifestyle factors can cause a risk reduction
Slows the rate that you develop diabetes

Question 10

Insulin resistance in T2D

Answer 10

Associated with obesity, particularly intra-abdominal obesity
Commonly seen in metabolic syndrome
Involved genetic and/or acquired post-receptor defects in insulin action
Associated with inflammation in adipose tissue

Question 11

3 characteristics of insulin secretion in T2D

Answer 11

Impaired glucose-induced insulin secretion
Impaired proinsulin processing
A progressive decline in insulin secretion as the disease progresses

Question 12

3 reasons for the loss of insulin secretion in T2D

Answer 12

Glucotoxicity and lipotoxicity
Pro-inflammatory cytokines (from islet macrophages)
Islet amyloid deposits (toxic deposits)

Question 13

Metabolic syndrome

Answer 13

Insulin resistance is commonly seen in metabolic syndrome

Central obesity, hyperlipidemia, hyperinsulinemia, hypertension, diabetes

Question 14

Gluco and lipotoxicity

Answer 14

Prolonged exposure to high glucose and FFAs is toxic to beta cells

Question 15

Mature Onset Diabetes of the Young (MODY)

Answer 15

Monogenic form of diabetes
Associated with genes that regulate beta cell mass or function
Ex: MODY2: glucokinase mutation (impaired insulin secretion)

Question 16

Neonatal diabetes mellitus

Answer 16

Monogenic form of diabetes
Rare: born with diabetes
Previously diagnosed as early onset T1D
Ex: mutations in sulfonylurea receptor (can just be treated with sulfonylureas, not insulin)

Question 17

Gestational DM

Answer 17

Diabetes appears during pregnancy and disappears following birth
Pregnant women become insulin resistant, insulin secretion increases
Carries risk for the infant (increases size, difficult birth)
Many women develop T2D later (pregnancy may unmask genetic defects that reappear in older age)

Question 18

How is the immune system involved in T1D?

Answer 18

CD4 and CD8 T cells
They recognize beta cell autoantigens
Antibodies present are more the markers of autoimmunity, not what is actually causing the destruction

Question 19

IGT

Answer 19

Impaired glucose tolerance (prediabetes)
Normal fasting glucose levels, but abnormal OGTT
Treated with diet and exercise