184/185. Diabetes

Question 1

ROS generation results in DNA strand breaks with activation of __

__ activation results in inactivation of GAPDH
- furthers ROS production by mitochondria and shunting of glucose and glycolytic intermediates into pathways mediating diabetic complications (polyol, PKC, AGE, glucosamine)

Answer 1

PARP (ADP ribose polymerase)

Question 2

Not absolutely dependent upon exogenous insulin

Not prone to ketoacidosis

Often obese

Historically was typically diagnosed after the age of 40 yo
- recognized with increasing frequency in children d/t childhood obesity

Strong family history

Answer 2

Type 2 DM

Question 3

__ will decrease w/ time as islet cells are destroyed due to lack of antigen

Answer 3

Islet cell antibodies

Question 4

Vast majority of genes associated with Type 2 DM affect __ function
- as opposed to insulin resistance

Leads to glucotoxicity, lipotoxicity, ER stress, mitochondrial dysfunction, oxidative stress, islet inflammation, increase islet amyloid polypeptides

Answer 4

Beta-cell

Question 5

Microvascular complication of diabetes that is the leading cause of adult renal failure

Answer 5

Nephropathy

Question 6

Autoantibodies to the zinc transporter which transports zinc into insulin granules (expressed in beta cells)

Present in 60-80% at diagnosis of type 1 DM

Answer 6

ZnT8 autoantibodies

Question 7

What is the key electrolyte to focus on when treating diabetic ketoacidosis?

Will need to add __ supplements to fluid when it enters normal range

Answer 7

K+

Question 8

Hyperglycemia-induced complication

Increased intracellular glucose results in increase __ formation and protein glycation

• __s damage target cells by 3 mechanisms:
  1. function of __-modified proteins may be altered
  2. components of the ECM modified by __s may interact abnormally with other matrix components and/or integrins
  3. plasma proteins modified by __ precursors are able to bind to a receptor for __s which results in the generation of ROS

There is an increase of their receptors

Answer 8

AGE

Question 9

Patients with Type 1 diabetes who are treated with insulin are at a higher risk of __ than type 2 diabetics

Answer 9

Hypoglycemia

Question 10

Acute effect of insulin deficiency:

1. In absence of insulin proteolysis and breakdown of __ occur
2. __ output increases secondary to glucogenolysis and gluconeogenesis
3. __ are metabolized into ketoacids which decreases plasma pH
4. __ occurs secondary increased hepatic glucose and decreased peripheral uptake of glucose
5. Hyperglycemia causes __ with resulting dehydration and loss of electrolytes in urine

Answer 10

1. TGs
2. Hepatic
3. Free fatty acids
4. Hyperglycemia
5. Glucosuria

Question 11

Complex metabolic disorder
- multiple factors contribute

Defined as decreased ability of insulin to lower circulating glucose concentrations

• impaired stimulation of glucose utilization by muscle and fat
• impaired suppression of glucose production by liver

Answer 11

Insulin resistance

Question 12

Fasting plasma glucose more than 100 but less than 125

Answer 12

Impaired fasting glucose

Question 13

3 most common microvascular complications to worry about in diabetic patients

Answer 13

Retinopathy
Nephropathy
Neuropathy

Question 14

The combination product of hemoglobin A and glucose (glycation)

Reflects the average levels of glucose in the blood for the previous several months and therefore indicates the degree of diabetic control

Answer 14

HgbA1c

Question 15

Leading cause of death among pts with diabetes

Answer 15

Ischemic heart disease

Question 16

Symptoms of type 1 diabetes?

Due to glucose spilling into urine and water following

Due to not incorporating calories into tissues

Answer 16

Polyuria (95%)
Weight loss (60%)
Fatigue (50%)

Question 17

Diabetes is a chronic metabolic disorder that impacts the metabolism of what 3 types of energy sources?

Answer 17

Carbohydrates
Protein
Fat

Question 18

What kind of immune cells are thought to be causative of Type 1 DM?

Answer 18

T-cells

Question 19

What are the peak ages for Type 1 DM diagnosis?

Answer 19

10-14yo

Question 20

Hyperglycemia-induced complication

High glucose flux through constitutive glucose transporters on the surface of endothelial cells increases intracellular glucose levels and results in the generation of __ by mitochondria

Answer 20

ROS

Question 21

Autoantibodies that are present in 40-50% at diagnosis

Presence of this with ICA are highly predictive of diabetes

Answer 21

IAA (Insulin autoantibodies)

Question 22

2 hour plasma glucose more than 140 but less than 200

Answer 22

Impaired glucose tolerance

Question 23

Microvascular complication of diabetes that is the leading cause of nontraumatic amputations in adults

Presents in a stocking-glove distribution

Can lead to diabetic ulcers

Answer 23

Neuropathy

Question 24

Hyperglycemia-induced complication

Activation of ___

• intracellular hyperglycemia results in increased DAG synthesis with subsequent activation of __
• increased __ activity has a variety of effects in endothelial and other cell types

Increase __ leads to increase collagen, fibronectin, decrease fibrinolysis, and increased ROS

Answer 24

Protein Kinase C

Question 25

What kind of obesity has a major impact on underlying insulin sensitivity

Answer 25

Central obesity

Question 26

Aspect of lifestyle changes for Type 2 DM pts: - decrease fat content and total calories - decreased saturated fat - decrease salt for hypertension - healthy diet - weight reduction in obese patients Used along with moderate-intensity exercise and smoking cessation

Answer 26

Nutrition therapy

Question 27

Type 1 diabetes is associated with certain __ types In particular, DR3 and/or DR4 Some of these genes are unique to Type 1 DM and some also associated with other autoimmune disorders

Answer 27

HLA

Question 28

Occurs due to autoimmune destruction of beta cells in pancreatic islets Insulitis can be seen on histology during the development of this disease

Answer 28

Type 1 diabetes

Question 29

Highly associated with insulin resistance

Answer 29

Obesity

Question 30

What is the mechanism for hyperkalemia occurring diabetic ketoacidosis?

Answer 30

Increased H+/K+ transporter therapy moving H+ into cells and K+ into ECF

Question 31

Accounts for 5-10% of diabetes worldwide Insulinopenic - dependent on exogenous insulin for life - ketosis prone under basal conditions

Answer 31

Type 1 diabetes

Question 32

Absence of __ phase insulin release is common in type 2 DM This causes hyperglycemia to ensue

Answer 32

first

Question 33

Antibodies that are present in 70-80% at diagnosis of type 1 DM Persist longer than ICA

Answer 33

GADA (glutamic acid decarboxylase autoantibodies)

Question 34

Fasting plasma glucose < 100 2 hour plasma glucose < 140

Answer 34

Normal

Question 35

Fasting plasma glucose more than 125 and 2 hour plasma glucose more than 200

Answer 35

Diabetes

Question 36

HLA locus demonstrates strong associated with type 1 DM There is a significant effect of insulin and __ genes as well

Answer 36

PTPN22

Question 37

Markers of autoimmunity useful for predicting disease and diagnosing disease when presentation is not classic for type 1 DM

Answer 37

Islet cell antibodies

Question 38

Antibodies to the transmembrane protein tyrosine phosphatase Present in about 60% of individuals at diagnosis

Answer 38

IA2A (Insulinoma associated 2 autoantibodies)

Question 39

Hyperglycemia with a secondary decrease in plasma pH due to increased production of ketoacids is referred to as

Answer 39

Diabetic ketoacidosis

Question 40

Adipose tissue inflammation is due to __ which interfere with insulin signaling - along with lipid metabolites

Answer 40

Cytokines

Question 41

Islet cell antibodies present years to months before onset of clinical type 1 DM Those with __ or more autoantibodies are at highest risk for progressing to type 1 diabetes

Answer 41

2

Question 42

Obesity => - skeletal muscle: increased FFA uptake, increased extramyocellular adipose, macrophage activation/recruitment, ER stress - Adipose: Adipocyte hypertrophy, macrophage recruitment, macrophage polarity switch, increased cytokine production, increased lipolysis, ER stress - Liver: increased lipid content, steatosis, kupffer cell activation/recruitment, increased cytokine production, ER stress Thus, obesity leads to insulin resistance and __

Answer 42

Inflammation

Question 43

People with type 2 DM don't increase insulin secretion in response to hyperglycemia due to decrease __ - central obesity has a major impact Decreased beta-cell compensation for the insulin resistance

Answer 43

Insulin sensitivity

Question 44

Detected by incubating patient serum with pancreatic sections 75-80% of caucasian children are positive for this antibody at the time of type 1 DM diagnsosis

Answer 44

ICA (islet cell autoantibodies)

Question 45

Hyperglycemia-induced complication Increased flux of glucose and other sugars through the polyol pathway - hyperglycemia is associated with increased intracellular glucose in insulin-unresponsive tissues which results in the conversion of glucose to the polyol __ by aldose reductase - this reaction consumes NADPH which is required for regenerating reduced glutathione - as reduced glutathione is depleted oxidative stress is induced or exacerbated

Answer 45

Sorbitol

Question 46

Diabetic ketoacidosis treatment includes 2 separate treatments

Answer 46

1. IV insulin therapy | 2. IV saline (.9 first then alternating .9 and .45 after fluids are restored)

Question 47

Microvascular complication of diabetes that is the leading cause of adult blindness

Answer 47

Retinopathy

Question 48

__ is exacerbated by obesity, sedentary lifestyle, age, and some medications (steroids)

Answer 48

Insulin resistance