Exam 2 Metabolism Part 1 - Diabetes

Question 1

T1DM cause

Answer 1

Autoimmune destructions of ß-cells manifesting when 80-90% destruction with metabolic disease and insulin deficiency

Question 2

T1DM genetics

Answer 2

10-20% FHx +
Risk: HLA DR3 and DR4
Protection: HLA DR2, DQA1, DQB1
Insulin gene: increased # tandem repeats increases thymus exposure and decreases risk

Question 3

T1DM environment

Answer 3

Infant diet: decreased breastfeeding -> increased risk
Accelerator hyp: increased obesity leads to increased oxidative stress on ß-cells
Hygiene hyp: decreased immune exposure leads to overactive immune system

Question 4

Autoimmune associations (and dx test)

Answer 4

Autoimmune thyroid dz: 15-20% (TSH)
Celiac dz: 5-10% (TTG)
Addison’s dz: 1-1.5% (21-OH)

Question 5

Diabetes presetnation

Answer 5

Polyuria
Polydipsia
Weight loss/fatigue
Blurry vision
DKA - more with T1DM, acute onset (10% mortality)

Question 6

Diagnostic tests

Answer 6

Fasting glucose, OGTT, HbA1C
Autoantibodies in T1DM
Decreased C-peptide in T1DM

Question 7

T1DM Islet cell autoantibodies

Answer 7

mIAA (to insulin)
IA-2
GAD65 (GAA)
ZnT8
(last three in granule)
Presence of two or more = 100% progression

Question 8

Type of damage in T1DM

Answer 8

T-cell mediated (CD4 and CD8)

Lobular (not uniform) ß-cell destruction

Question 9

3 parts of insulin deficiency pathophys

Answer 9

Decreased GLUT4
Increased glucose production via glycogen and gluconeo
Increased hormone sensitive lipase (FFA and ketones)

Question 10

Consequences of diabetes

Answer 10

Macrovascular (CAD - main cause of death, 80%)
Microvascular:
1. Retinopathy
2. Nephropathy - microalbuminemia (elevated urine alb/cr ratio)
3. Neuropathy
Diabetic Foot Disease: combination of macro and micro
Pyschosocial: depression and anxiety

Question 11

Consequences of prediabetes

Answer 11

Macrovascular risk

No microvascular risk

Question 12

LADA

Answer 12

30-70 yr old
6 months of non-insulin requiring diabetes
Presence of autoantibodies

Question 13

T2DM causes

Answer 13

Insulin resistance with eventual ß-cell destruction (decreased production)

Question 14

T2DM associations

Answer 14

obesity
lipid abnormalities
PCOS
non-alcoholic fatty liver disease

Question 15

T1DM prevention

Answer 15

Primary: genetically at risk, diet/lifestyle
Secondary: antibody positive, oral insulin when IAA>80
Tertiary: early in clinical dz, preserve ß cells, intensive insulin

Question 16

Signs: prandial glucose vs. fasting glucose

Answer 16

Prandial glucose rises fist

Fasting glucose levels rise later

Question 17

Signs: insulin resistance and ß-cell function

Answer 17

Insulin resistance rises while at risk “pre-diabetes”, plateaus after onset
ß cells begin to fail with onset of diabetes (approx 50% fxn is gone at clinical diagnosis)

Question 18

Main determinant of fasting blood glucose in T2DM

Answer 18

Hepatic glucose output (important to control with treatment)

Due to increased hepatic insulin insensitivity (should decrease output with insulin)

Question 19

Normal vs diabetic meal response

Answer 19

Normal: increase insulin, decrease glucagon
Diabetes: insulin stays low, glucagon remains high

Question 20

Incretin effect

Answer 20

Greater increase in C-peptide (insulin) with oral compared to IV glucose
Due to effect of GLP-1

Question 21

MODY

Answer 21

Inherited DM - autosomal dominant
Mutation in glucokinase gene, defect in glucose sensor, less insulin secretion
Treat with sulfonureas or insulin

Question 22

Diagnostic labs in DKA

Answer 22

Blood sugar >200/300 and ketones >5
Acidosis <7.3
Apparent hyponatremia (need to correct 2 Na/100 glucose)
Apparent hyperkalemia (H/K shift to correct acidosis)

Question 23

Adrenergic hypoglycemia symptoms

Answer 23

Sweating
Tremor
Tachycardia
Anxiety
Hunger

Question 24

Neuro hypoglycemia symptoms

Answer 24

Dizzy
HA
Confusion
Convulsions
LoC

Question 25

Hypoglycemia with and without diabetes

Answer 25

With: more common in T1DM
Without: Whipple’s triad (hypoglycemia, symptoms, relieved with glucose)

Question 26

Macrovascular disease

Answer 26

CVD most common, 80% cause of mortality in DM
Hyperglycemia leads to endothelial dysfxn
Hyperinsulinemia leads to vessel damage
T2DM -> HTN (not T1DM unless renal impairment)
Procoag state
Statins and BP control

Question 27

Hypoglycemic unawareness

Answer 27

Tolerance of adrenergic symptoms so abrupt onset of neuro symptoms
Tx: avoid all hypoglycemia for 3 weeks

Question 28

Microvascular disease: retinopathy

Answer 28

Pericyte and capillary drop out
BM thickening
Intravascular leakage -> exudate
Hypoxic stress -> VEGF, neovascularization
Treatment: intervene and prevent with annual exam, tight control, and photocoagulation
Steroids for macular edema

Question 29

Microvascular disease: nephropathy

Answer 29

Monitor for with microalubuminemia (Alb/Cr ratio)
Increased osm -> hyperfiltration:
1. Intrarenal HTN
2. BM thickening
3. Mesangial proliferation
4. Glomerular obliteration
Tx: ACEI/ARB, metabolic control, protein restriction?

Question 30

Microvascular disease: neuropathy

Answer 30

1. mononeuritis multiplex (vessel infarct, ptosis)
2. distal symmetric polyneuropathy (most common)
3. autonomic neuropathy (unawareness)
4. Amyotrophy