Endo - Diabetes Type I

Front 1

Type I Diabetes
- cause?
- presentation?
- % of diabetes?

Back 1

Cause
- autoimmune
- pancreatic B-cell destruction --> complete insulin deficiency

Sx
- hyperglycemia
- glucosuria
- often ketoacidosis
***Usually presents with sx, which is good bc allows urgent tx

= 10% of diabetes

Front 2

Type II Diabetes
- cause?
- presentation?
- % of diabetes?

Back 2

Cause
- complex metabolic disturbance
- insulin resistance
- inadequate B cell insulin secretion

Presentation
- often asymptomatic (30-40% cases undiagnosed!) --> problem bc don't get tx

= 90% of diabetes (most common type)

Front 3

Intermediate Diabetes
- aka?
- what is?

Back 3

aka: "pre-diabetes"

- Impaired Glucose Tolerance (IGT)
- Impaired Fasting Glucose (IFG)

Front 4

Gestational Diabetes
- what is?
- pathogenesis?
- frequency?
- consequences?
- tx?

Back 4

- diabetes that develops during 2nd or 3rd trimester; usully subsides after delivery

Pathogenesis
- insulin resistance due to pregnancy - diabetes occurs if B-cell insulin secretion is inadequate

~6% of pregnancies

Consequences
- increased fetal morbidity and mortality
- 30-40% develop Type II Dm 5-10 years later

Tx: INSULIN ONLY!!!

Front 5

What are 3 minor causes of DM - other than type I and type II?

Back 5

1. Pancreatic Disease - e.g., hemochromatosis, pancreatitis

2. Endocrinopathies - due to excess secretion of hormones that can antagonize action of insulin on muscle and liver tissue
- Cushing's
- Acromegaly
- Pheochromocytoma
- Glucagonoma

3. Drug Therapy - corticosteroids increase insulin resistance

Front 6

What is the genetic association with Type I DM?

Back 6

- Insulin Receptor mutations are rare causes of severe peripheral resistance

- Glucokinase mutations - cause abnormal set-point for glucose-stimulated insulin release
... found in MODY - Maturity Onset Diabetes of Youth

Front 7

What are the functions of INSULIN? (by organ)

Back 7

LIVER
- decrease glucose output
- decrease gluconeogenesis
- decrease glycogenolysis

SKELETAL MUSCLE
- increase glucose uptake and metab
- increase AA uptake
- decrease protein degredation

ADIPOSE
- increase glucose uptake and metab
- decrease TG breakdown and FA release

Front 8

What is the pathophysiology behind the development of Type I DM?

Back 8

1. Initial genetic susceptibility - defect in immune recognition of B cell antigens

2. Environmental trigger/precipitating event - often VIRAL infection --> after, virus goes and sits in B cells

3. Immune attack against B cells (GAD65 Ab); Insulitis - lymphocytic inflammatory reaction ag B cells --> B cell destruction

4. When > 90% B cells are destroyed, hyperglycemia develops - often presents with ketoacidosis

Front 9

What is a great serum marker for Type I DM?

Back 9

GAD65 Ab
- released when body mounts immune attack on B cells

Front 10

Risk of developing Type I DM?
- general pop?
- first-degree relative?
- monozygotic twin?

Back 10

- general pop: 0.3-0.5%
- first-degree relative: 2-6% (more likely if father has it - suggests imprinting)
- monozygotic twin: 30-40%

Front 11

If you know you might have a genetic susceptibility, how can you prevent Type I DM?

Back 11

YOU CAN'T!
(can prevent type II - lose weight)

Front 12

What are ACUTE sx of diabetes?

Back 12

... Anabolic effect of insulin - failure to utilize calories in diet
- weight loss with good appetite
- increased food intake (polyphagia)

... Effects of diuretic effect of glucose
- polyuria, nocturia
- dehydration
- polydipsia

... symptoms of Hyperglycemia
- vaginal infections
- blurred vision
- altered mental status

Front 13

DIAGNOSIS of Diabetes

Back 13

1. Fasting Glucose - fast for 8 hour
Normal < 100 mg/dL
Pre-Diabetes = 100-125 mg/dL
DIABETES > 126 mg/dL

2. Random Glucose - no regard for meals; must do TWICE!
- Normal < 140
- DIABETES > 200 (twice)
*No pre-diabetes dx with this test
- usually when pt presents with sx

3. Oral Glucose Tolerance Test 3. (OGTT) - give 75 gm at fasting, then wait 2 hours...
- Normal < 140
- Pre-diabetes = 140-200
- DIABETES > 200 (twice)

Front 14

What are the main disadvantages of getting exogenous insulin?

Back 14

- injection required
- hypoglycemia
- weight gain

Front 15

Who needs insulin meds?

Back 15

**ALL Type I DM
- Type II with hyperglycemia despite other meds; acute injury, infection, stress; surgery
- Gestational diabetes (only option!!!)

Front 16

What are the types of insulin on the market?
- function
- names?

Back 16

RAPID-ACTING ANALOGS - give right before meal; quickly depleted
- Lispro
- Aspart
- Glulisine

SHORT-ACTING - give 30-60 min before meal; last up to 8 hours (could cause hypoglycemia)
- "Regular Insulin" = "R"

INTERMEDIATE - give BID
- "Neutral Protamine Hagedorn" = "NPH"
- no longer used much bc of high peak (surge of insulin) and weight gain

BASAL INSULIN ANALOGS - long-lasting; stim physiologic, peakless pattern
- Glargine
- Detemir, Levemir

PREMIXED - combo of rapid/short-acting with an intermediate insulin --> allows shot BID for lazy pts, but not idea bc doesn't mimic physiologic state

Front 17

How do the Basal Insulin Analogs work?

- advantages?

Back 17

Glargine - soluble at acidic pH, but forms micro-precipitate in subcutaneous tissues --> prolonged release (peakless)

Levemir - linked to FA chain, which binds to albimin; prolongs t1/2 in circulation --> lasts 14-16 hours


ADVANTAGES
- little/no peak (mirrors physiologic basal insulin)
- less hypoglycemia
- less weight gain

Front 18

What is our normal physiologic insulin secretion pattern?

Back 18

- Basal Insulin - always secreted throughout day (~1/2 of our insulin)

- Bolus Insulin - surges released after meals to break down carbs (~1/2 of our insulin)

Front 19

Insulin Pump

Back 19

***Best artificial insulin!!
- infuses constantly
- contains a rapid-acting analog
- when you eat, must tell the pump so it can inject the correct bolus
- change cath 48-72 hours

Disadvantages:
- expensive
- "attached to device"