Pathophysi of Diabetes

Question 1

criteria for diagnosis of diabetes (ADA)

Answer 1

A1C ≥ 6.5%
Fasting plasma glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L)
2 hour plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during OGTT (oral glucose tolerance test)
a random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) with symptoms of diabetes

Question 2

other names of T1DM

Answer 2

Insulin Dependent Diabetes Mellitus (IDDM)
Juvenile Onset Diabetes Mellitus (JODM)

Question 3

prevalence of T1DM

Answer 3

10% of diabetic population

Question 4

cause of T1DM

Answer 4

autoimmune response targeting pancreatic beta cells (may be triggered by viruses, chemicals, etc in genetically predisposed individuals)

Question 5

typical treatment of T1DM

Answer 5

dependency on exogenous insulin

Question 6

characterization of T1DM

Answer 6

no functional insulin-secretion
near complete loss of pancreatic beta cells
glucose interolance

Question 7

common complication of T1DM

Answer 7

tendency towards ketoacidosis

Question 8

mean age of onset T1DM

Answer 8

12

Question 9

is family history often a factor in T1DM?

Answer 9

family history often negative

Question 10

ICA

Answer 10

islet cell cytoplasmic antibodies

Question 11

IAA

Answer 11

insulin autoantibodies

Question 12

presence of ICA or IAA

Answer 12

means the immune system has initiated a response against the pancreatic beta cells

Question 13

after initiation of autoimmune response, what happens to BCM?

Answer 13

gradual loss of BCM

Question 14

what happens to FBG after initiation of autoimmune response?

Answer 14

FBG levels remain normal until about 70% of BCM is lost

Question 15

C-peptide

Answer 15

a product of endogenous insulin that is a marker for insulin secretion in the presence of exogenous insulin

Question 16

stage 1 of autoimmune response

Answer 16

normal glucose-stimulated insulin release
normal FBG
ICA-positive
IAA-positive

Question 17

stage 2 of autoimmune response

Answer 17

progressive loss of glucose-stimulated insulin release
normal FBG
abnormal OGTT

Question 18

stage 3 of autoimmune response

Answer 18

overt diabetes
high FBG
C-peptide present

Question 19

autoantibodies associated with T1DM

Answer 19

islet antigen 2 (IA-2)
phogrin (IA-2B)
Zinc transporter (ZnT-8)
Glutamic acid decarboxylase (GAD65)
Voltage-gated Ca++ (Cav 1.3)
Vesicle-associated membrane protein-2 (VAMP-2)
antibodies against one or more B-cell proteins signals an increased risk for developing diabetes

Question 20

IA-2 accuracy

Answer 20

57% sensitivity –> 57% of non-diabetics who have it will develop type 1 diabetes
99% selectivity –> 99% of type 1 diabetics have Abs

Question 21

prevalence of non obese T2DM

Answer 21

10%

Question 22

prevalence of T2DM

Answer 22

80%

Question 23

age of onset of non-obese T2DM

Answer 23

often under 25

Question 24

age of onset of obese T2DM

Answer 24

usually over 30

Question 25

another name of T2DM

Answer 25

Non-insulin dependent diabetes mellitus (NIDDM) Maturity onset diabetes of the young (MODY) Adult onset DM

Question 26

is family history often a factor in T2DM?

Answer 26

yes

Question 27

insulin secretion in response to glucose challenge (non-obese)

Answer 27

low

Question 28

insulin secretion in response to glucose challenge (obese)

Answer 28

low for body mass

Question 29

cause of non-obese T2DM

Answer 29

mutations in specific proteins

Question 30

cause of obese T2DM

Answer 30

insulin resistance decreased BCM

Question 31

consequence of lack of insulin

Answer 31

hyperglycemia glucosuria hyperlipidemia uninhibited glucagon

Question 32

source hyperglycemia due to lack of insulin

Answer 32

1. decreased glucose uptake in cells where glucose uptake is insulin-dependent 2. decreased glycogen synthesis (process in the liver where glucose is stored for later release into the blood stream) 3. increased conversion of amino acids to glucose (in the absence of insulin there is nothing to inhibit gluconeogenesis)

Question 33

source of glycosuria due to lack of insulin

Answer 33

high glucose concentration in renal filtrate, overwhelming of glucose transporters in the kidneys, glucose spills into the urine

Question 34

source of hyperlipidemia due to lack of insulin

Answer 34

increased fatty acid mobilization from fat cells (lipids are broken down to fatty acids and distributed through the body to use for fuel instead of carbs) increased fatty acid oxidation (ketoacidosis)

Question 35

ketoacidosis

Answer 35

high rate of B-oxidation and accumulation of their byproduct, ketone bodies leads to a large amount of acid in the body

Question 36

source of uninhibited glucagon due to lack of insulin

Answer 36

increased glucagon levels in the presence of increased blood glucose levels, this process is usually inhibited by insulin

Question 37

complications of hyperglycemia (CV)

Answer 37

micro and macro angiopathies leads to compromised blood flow to parts of the body

Question 38

complications of hyperglycemia (NS)

Answer 38

neuropathy

Question 39

cause of neuropathy

Answer 39

high BG level increase utilization of polyol pathway water accumulation in neurons/reduced protection from oxidative damage

Question 40

complications of hyperglycemia (eye)

Answer 40

cataracts retinal micro aneurysms hemorrhage

Question 41

complications of hyperglycemia (infections)

Answer 41

increases susceptibility to infections

Question 42

goal of insulin therapy historically

Answer 42

reduce acute symptoms (polyuria, dehydration, ketoacidosis)

Question 43

current goals of insulin therapy

Answer 43

keep an average blood glucose level below 150 mg/dL prevent/delay onset of complications A1C ≤ 6 (ideal) or <7 (goal)

Question 44

risk of insulin therapy with aggressive goals

Answer 44

increased risk of hypoglycemia

Question 45

why is glucose so toxic?

Answer 45

oxidation products of glucose react irreversibly with proteins --> forms advanced glycation end products (AGEs) --> loss of normal protein function and acceleration of aging process Theorized to account for many long-term complications of diabetes

Question 46

RAGE

Answer 46

receptors for advanced glycation end products when peptides containing CML (glyoxal) and CEL (methylglyoxal) bind, inflammation is promoted

Question 47

polyol (aldose reductase) pathway

Answer 47

glucose --> sorbitol --> fructose

Question 48

effect of increased glucose in polyol pathway

Answer 48

increased accumulation of sorbitol --> increases the osmolality of the cell --> swelling and damage

Question 49

increased glucose in hexosamine pathway

Answer 49

increased formation of energized glucosamine-6-P (UDP-GIcNAc) which can diminish function of proteins/genes

Question 50

increased glucose in protein kinase C pathway

Answer 50

leads to excess of various signaling