Type 1 Diabetes

Question 1

Cell Types of Pancreas (4)

Answer 1

ß: 60-80% cells; secrete insulin
alpha: 20-30%; secrete glucagon
∆: secrete somatostatin, which suppresses both insulin and glucagon
PP: unknown function

Question 2

Insulin Processing

Answer 2

Preproinsulin processed to proinuslin in ER

Proinsulin processed to C-peptide and insulin in golgi

Question 3

What is significance of C-peptide?

Answer 3

Can be measured to estimate insulin production

Question 4

Requirements for Insulin Function (4)

Answer 4

Islet ßcell mass
Insulin synthesis
Glucose-dependent insulin secretion
Insulin signaling at target cells

Question 5

How many granules does a ß-cell contain? How many does it secrete each day?

Answer 5

Contains 10,000 and secretes 10^12 in a given day

Question 6

Insulin Metabolism: What are immediate effects of rise in blood glucose? More delayed effects?

Answer 6

Immediate effect of blood glucose is exocytosis of granules

If persistently high glucose, will see increased insulin synthesis in beta cells

Question 7

Insulin functions (4)

Answer 7

Trasmembrane transport of glucose/amino acids
Glycogen formation in liver/muscles
Glucose conversion to triglycerides
Nucleic acid and protein synthesis

Question 8

Special signs in T1DM

Answer 8

DKA (25-30%), coma (5%)

Question 9

How does glycosuria occur?

Answer 9

Hyperglycemia–>filtration in kidneys results in too much glucose in filtrate; it cannot all be reabsorbed so it is excreted

Question 10

Epidemiology:

Who is most likely to get Type I Diabetes?

Answer 10

Northern european ancestry
Peak ages: 5-7, onset of puberty, 1/3 above 18
Incidence higher during winter

Question 11

Risk Factors for T2DM

Answer 11

Viral infections (coxsaccie, congenital rubella, enterovirus)
Immunizations, diet, high SES, obesity, vit D deficiency

Question 12

What autoantibodies are seen in T1DM? (4)

Answer 12

Islet cell antibodies (ICA)
Insulin autoantibodies (IAA)
Antibodies to Glutamic acid decarboxylase (GAD)
ZnT8 autoantibodies (80% newly diagnosed T1DM)

Question 13

Pathogenesis:

How does chronic insulitis develop?

Answer 13

Genetic susceptibility and environmental trigger lead to development of autoantibodies
High risk MHC 
Cellular infiltrate (lymphocytes ,mø)-->Destruction of ß-cells

Question 14

What is Latent Auto-immune Diabetes of Adulthood?

Answer 14

Basically an non-obese adult that shows up with T2DM symptoms but is antibody positive

Question 15

How is LADA managed?

Answer 15

Can initially be controlled with glucose lowering pills….but eventually will become insulin dependent

Question 16

First symptoms in LADA?

Answer 16

Loss of 1st insulin response

Question 17

Treatment of Type 1 Diabetes (3)

Answer 17

Insulin replacement therapy
Education
Screening: blood glucose and complications

Question 18

Diabetics should adjust insulin doses according to _____ (3)

Answer 18

Carbohydrate intake
Exercise regimen
Blood glucose profile

Question 19

Impact of Intensive Therapy

Answer 19

Reduced retinopathy, nephropathy, neuropathy, CVD mortality and atherosclerosis

Question 20

DKA Concept

Answer 20

Body perceives state of starvation when no insulin is detected and utilizes alternate energy sources

Question 21

DKA: loss of insulin effects in liver, muscle, adipose

Answer 21

Liver: glucose output–>glucosuria–>polyuria–>dehydration

Muscle: Muscle wasting–>weight loss

Adipose: increased lipolysis–>increased ketogenesis (ß-hydroxybutyrate/acetoacetate)–>Ketoacidsois

Question 22

DKA Symptoms (big list)

Answer 22

nausea/vomiting, thirst/polyuria, weakness/anorexia, abdominal pain, visual disturbances, somnolence, tachycardia, hypotension, dehydration, kussmaul respiration (hyperventilation), fruity odor on breath, altered mental status

Question 23

DKA Treatment

Answer 23

Insulin IV (until anion gap is resolved) 
Correction of fluid/electrolyte imbalance

Question 24

What increases with increasing glycemic control?

Answer 24

Risk for hypoglycemia

Question 25

What is relative hypoglycemia?

Answer 25

Symptoms of hypoglycemia despite normal/elevated blood glucose due to patient being in a chronic hyperglycemic state