Pancreas PART I

Question 1

What is Diabetes Mellitus?

Answer 1

It is a group of metabolic disorders sharing the common feature of hyperglycemia

Question 2

What is Hyper­glycemia in diabetes caused by?

Answer 2

• defects in insulin secretion
• abnormal insulin function
• or, most commonly, both

Question 3

Chronic hyperglycemia and associated metabolic dysregulation might cause what?

Answer 3

secondary damage in multiple organ systems, especially the kidneys, eyes, nerves and blood vessels

Question 4

What does Insulin in normal subjects do?

Answer 4

1. It decreases liver glucose production by decreasing both glycogenolysis and gluconeogenesis
2. It increases glucose uptake by skeletal muscle and adipose tissue by translocating glucose transporters

Question 5

What is the Response to Hypoglycemia in Normal Subjects?

Answer 5

• Counter-regulatory hormones
• Relation between insulin and glucagon
• Behavioral defenses

Question 6

What is the Response to Hypoglycemia in Diabetes?

Answer 6

• Impairment of behavioral and counter-regulatory responses
• Hypoglycemia-associated autonomic failure (HAAF)
• Nocturnal hypoglycemia
• Exercise

Question 7

What is HAAF?

Answer 7

Hypoglycemia-Associated Autonomic Failure (HAAF), clinical syndromes of defective glucose counter-regulation and hypoglycemia unawareness

Question 8

What is the mechanism of HAAF?

Answer 8

reducing the sympathoadrenal response to subsequent hypoglycemia due to changes in hypothalamic functions and increase in cortisol

Question 9

What is glucose utilization?

Answer 9

Insulin stimulates glucose uptake by skeletal muscle and fat by GLUT-4

Question 10

What is the Clinical Pearl (Measuring Glycemic Control) for?

Answer 10

Clinical test to estimate blood glucose control

A1C assay

Question 11

What are the Diabetes Mellitus Broad Classification?

Answer 11

Type 1 diabetes (autoimmune disease)

Type 2 diabetes (combination of peripheral resistance to insulin action)

Question 12

What are the short and long term training effects of Muscle Metabolism In Nondiabetics?

Answer 12

short term effects- Glucose cannot be transferred out of muscle to prevent hypoglycemia
long term effects- GLUT4 promotes glucose uptake  increase in insulin sensitivity

Question 13

What are the Short-term effects in type 1 and 2 diabetes?

Answer 13

-T1DM
well-controlled diabetics–> decrease in blood glucose

poorly controlled diabetics–> increases ketogenesis

-T2DM: improves insulin sensitivity as it does in nondiabetics

Question 14

What are the Long-term effects in type 1 and 2 diabetes?

Answer 14

• T1DM: less evidence

- T2DM: increased activity of mitochondria, increased insulin sensitivity and muscle capillary recruitment

Question 15

What is Type 1 Diabetes Mellitus?

Answer 15

An autoimmune disease-> islet destruction by endogenous β-cell antigens

Question 16

What is the Immunological Response in Type 1 DM?

Answer 16

• the antigen binds to MHC class II-> autoimmune injury to the pancreatic beta cells
• costimulatory pathways that further increase T cell activation

Question 17

What are the risk of type 1 diabetes?

Answer 17

the measurement of islet autoantibodies

the presence of two or more of these islet autoantibodies

Question 18

What’s the time Course of Type 1 Diabetes Mellitus for Immune markers?

Answer 18

• first appear at the time of the environmental triggering events
• Clinically evident type 1 diabetes does not occur until there has been a much greater loss of functioning beta cell mass

Question 19

What’s the time Course of Type 1 Diabetes Mellitus for Genetic markers?

Answer 19

present from birth

Question 20

What is Type 2 Diabetes Mellitus?

Answer 20

Complex disease that involves an interplay of genetic and environmental factors and a pro-inflammatory state. there is NO evidence of an autoimmune basis

Question 21

What is of metabolic syndrome?

Answer 21

co-occurrence of metabolic risk factors for both type 2 diabetes and CVD

Question 22

What are the Metabolic Defects in Type 2 Diabetes?

Answer 22

• Insulin resistance
• Inadequate insulin secretion
• Impaired insulin processing

Question 23

What is Insulin Resistance?

Answer 23

Broadly defined as a subnormal biological response to normal insulin

Question 24

What are the Major Organs Affected by Insulin Resistance?

Answer 24

Liver, skeletal muscle and adipose tissue

Question 25

What are the Consequences of Insulin resistance?

Answer 25

• Failure to inhibit gluconeogenesis –> high fasting blood glucose levels
• Failure of glucose uptake and glycogen synthesis–> high post-prandial blood glucose level
• Failure to inhibit lipoprotein lipase–> FFAs–>amplify the state of insulin resistance

Question 26

What activates pro-inflammatory mediators?

Answer 26

Hyperglycemia and dyslipidemia collectively

Question 27

What is often linked to insulin resistance?

Answer 27

Central obesity 
(abdominal fat)

Question 28

What are The Clinical Presentation of Diabetes?

Answer 28

• Asymptomatic

- polyuria, polydipsia, nocturia, blurred vision, and, infrequently, weight loss

Question 29

What are the Chronic Complications of Diabetes?

Answer 29

morbidity associated with longstanding diabetes of either type is due to damage induced in: diabetic macrovascular disease,
diabetic microvascular disease

Question 30

The effects of microvascular disease are most profound in what?

Answer 30

Retina-> diabetic retinopathy
Kidneys->diabetic nephropathy
Peripheral nerves-> diabetic neuropathy

Question 31

Macrovascular disease causes accelerated atherosclerosis in diabetics, what are some effects?

Answer 31

• increased risk of myocardial infarction
• stroke
• lower extremity ischemia

Question 32

What are the Clinical significance of AGEs in diabetes?

Answer 32

• major cause of morbidity in patients with type 1 and type 2 diabetes.
• chronic hyperglycemia is the primary cause
• two basic changes within the retinal vessels