01 Thera VI DM Intro Gong

Question 1

What is the general definition of Type 1 Diabetes?

Answer 1

Pancreas makes too little or no insulin

Question 2

What is the general definition of Type 2 Diabetes?

Answer 2

Cells do not use insulin well (insulin resistance). Ability for pancreas to make insulin decreases over time

Question 3

What is the normal Islet function for glucose regulation when there is an increase in blood glucose?

Answer 3

Increase in insulin secretion (B-cell). Decrease in Glucagon secretion (a-cell)

Question 4

What is the normal Islet function for glucose regulation when there is a decrease in blood glucose?

Answer 4

Decrease in Insulin secretion (B-cell). Increase in Glucagon secretion (a-cell)

Question 5

What are the four main organs affecting plasma glucose insulin response?

Answer 5

Intestine (glucose absorption, cause Incretin release). Pancreas (insulin and glucagon secretion. Liver (glucose production and insulin action). Adipose tissue and muscle (glucose uptake insulin action)

Question 6

What can C-peptide tell you about a patient?

Answer 6

C-peptide is the result from a cleavage creating insulin. If C-peptide is excessively high its an indication that your body is making too much insulin (usually a sign of type 2 DM (insulin resistance)). When C-peptide is too low it’s usually a sign that your body isn’t making enough insulin (type I DM)

Question 7

What are the core defects resulting in Hyperglycemia?

Answer 7

Liver with increased Hepatic Glucose Production (HGP). Muscle cells with decreased glucose uptake. Pancreas with impaired insulin secretion and excess glucagon secretion

Question 8

Besides the core contributors, what other organs can contribute to hyperglycemia?

Answer 8

GI tract with decreased Incretin effect. Increased lipolysis. Kidney with increased glucose reabsorption. Brain with neurotransmitter dysfunction. Islet a-cell with increased glucagon secretion

Question 9

What are Incretins?

Answer 9

A hormone originating in the GI tract and released during nutrient absorption (food in stomach/intestines). Incretins augment insulin secretion at physiologic concentrations. The insulinotropic effects of Incretins are glucose dependent (do not cause hypoglycemia on their own). Some Incretins also decrease glucagon secretion from the a-cells

Question 10

What is the general definition of GLP-1 and GIP?

Answer 10

Major Incretins in humans are Glucagon-Like Peptide (GLP-1) and Glucose-Dependent Insulinotropic Peptide (GIP)

Question 11

What does GLP-1 do?

Answer 11

Increase insulin secretion and suppresses glucagon secretion. Regulates rate of gastric emptying. Affects CNS, resulting in increased satiety (sensation of fullness) and reduction of food intake

Question 12

What does GIP do?

Answer 12

Increase insulin secretion

Question 13

What are GLP-1 and GIP inactivated by?

Answer 13

Dipepidyl Peptidase 4 (DPP-4)

Question 14

GLP-1 actions may extend beyond the pancreas. What other organs are affected?

Answer 14

Can increase cardio-protection and CO. Increases neuroprotection. Can actually increase B-cell proliferation and decrease B-cell apoptosis

Question 15

Why is there a higher insulin response after PO glucose vs. IV glucose?

Answer 15

Glucose taken PO activate the Incretin Effect (Type 2 DM effect)

Question 16

How does GLP-1 modulate insulin secretion?

Answer 16

GLP-1 potentiates glucose-dependent insulin secretion. GLP-1 enhances gene expression, synthesis, and release of insulin

Question 17

How does GLP-1 also affect Insulin gene expression and B-cell function?

Answer 17

Upregulates insulin gene expression. Upregulates expression of genes essential for B-cell function. Promotes B-cell neogenesis and progenitor-cell differentiation (in animal models). Inhibits apoptosis (in animal models)

Question 18

How does GLP-1 control glucagon secretion?

Answer 18

Suppresses glucagon release in glucose-dependent manner. Enhances glucagon release in response to hypoglycemia. Improves a-cell glucose sensing

Question 19

What are the major Incretins?

Answer 19

GLP-1 and GIP

Question 20

What is the major role of Glucagon?

Answer 20

Released from a-cells and have a positive effect on the liver, causing an increase in Hepatic Glucose Output (HGO). Ultimately increases glucose

Question 21

What is the major role of Insulin?

Answer 21

Secreted by B-cells. Negatively acts on the liver, decreasing HCO. Acts positively on muscle cells/liver/fat cells to promote glucose uptake

Question 22

What is the First-Phase Insulin Secretion?

Answer 22

Rapid and sharp increase. Begins 1-3 minutes after glucose rises. Returns to baseline within ~10 minutes. Derived from stored secretory granules docked on/near plasma membrane

Question 23

What is the Late-Phase Insulin Secretion?

Answer 23

Gradual, several minutes to hours. Derived from stored secretory granules and de novo insulin synthesis. Persists as long as glucose levels remain elevated

Question 24

What are the general roles of B-Cells?

Answer 24

Comprise about 70-80% of the endocrine mass of the pancreas. Located in the central portion of the islet. Produce insulin and amylin. Insulin released in response to elevated blood glucose levels

Question 25

What are the general roles of a-Cells?

Answer 25

Comprise about 15% of the endocrine mass of the pancreas. Located in the periphery of the islet. Produce glucagon. Glucagon released in response to low blood glucose levels

Question 26

What can diabetes do to the heart?

Answer 26

A 2- to 4-fold increase in cardiovascular mortality

Question 27

What can diabetes do to the kidneys?

Answer 27

The leading cause of new cases of end stage renal disease

Question 28

What can diabetes do to the eyes?

Answer 28

The leading cause of new cases of blindness in working-aged adults

Question 29

What can diabetes do to limbs?

Answer 29

The leading cause of nontraumatic lower extremity amputations

Question 30

What are the Macrovascular complications of diabetes?

Answer 30

Angina. MI. Transient cerebral ischemia. Stroke. Intermittent claudication. Ischemic foot ulcers

Question 31

What are the Microvascular complications of diabetes?

Answer 31

Retinopathy. Nephropathy. Peripheral and autonomic neuropathy. Hyperglycemia is the most identifiable risk factor for microvascular complications in patients with diabets

Question 32

How do you differentiate the different levels of Albumin secretion?

Answer 32

Spot collection. Normal < 30. Microalbuminuria: 30-299. Macro (clinical)-albuminuria: > 300

Question 33

What is a more specific definition of Type 1 DM?

Answer 33

B-cell destruction, usually leading to absolute insulin deficiency. Immune mediated. Idiopathic. Usually found in childhood and adolescence. Low undetectable C-peptide levels

Question 34

What is a more specific definition of Type 2 DM?

Answer 34

May range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance. Adult onset. Obesity

Question 35

What are the common symptoms of Type 1 DM?

Answer 35

Three Ps: Polyuria, Polydipsia, Polyphagia. Unusual weight loss. Fatigue. Irritability

Question 36

What are the common symptoms of Type 2 DM?

Answer 36

Any type 1 symptoms. Blurred vision. Frequent infections. Poor wound healing. Tingling/numbness of hands or feet

Question 37

What are the Non-Modifiable risk factors for Type 2 DM?

Answer 37

Genetics. Ethnicity. Age

Question 38

What are the Modifiable risk factors for Type 2 DM?

Answer 38

Obesity. Physical inactivity. Diet. Elevated fasting and 2h glucose levels. Insulin resistance. Impaired insulin secretion

Question 39

What are the criteria for diagnosing DM?

Answer 39

A1C > 6.5%. FPG > 126. A 2-hour plasma glucose > 200 during an oral glucose tolerance test using 75g glucose. Symptoms of diabetes

Question 40

What is Gestational Diabetes?

Answer 40

Any degree of glucose intolerance during pregnancy. Re-evaluate patients six to twelve weeks after pregnancy and reclassify as diabetes, pre-diabetes, or normoglycemia. Most patients return to normoglycemia

Question 41

What is done to determine Gestational DM?

Answer 41

Perform fasting (8h) 75g OGTT at 24-28 weeks. Diagnosis is made using any of the following: Fasting glucose > 92, 1h > 180, 2h > 153. No need to repeat to confirm GDM

Question 42

What is Pre-Diabetes?

Answer 42

Relatively high risk for developing DM. Risk factor for DM and CVD. Associated with obesity, dyslipidemia of high TG and/or low HDL, and HTN. Need lifestyle modification increasing physical activity and producing 5-10% of body weight

Question 43

What is the only drug approved for Pre-Diabetes?

Answer 43

Metformin

Question 44

What is the relationship between Obesity and Diabetes?

Answer 44

Excess body fat is associated with increased insulin resistance in adipose tissues and skeletal muscles. Liver develops insulin resistance and increase glucose output. Peripheral tissues become resistant to glucose uptake. Pancreas compensates by producing more insulin

Question 45

Which ethnic groups seem to have the greatest prevalence of diabetes?

Answer 45

African-Americans. Native Americans/Alaska Natives

Question 46

Which income group has the highest prevalence of type 2 diabetes?

Answer 46

Low income

Question 47

What does the largest portion of costs for diabetes complications go to?

Answer 47

Macrovascular complications

Question 48

What is the relationship between Diabetes and older people?

Answer 48

Half of all patients with diabetes > 60 years. Diabetes accelerate aging process such that a person with diabetes is 10 years older physiologically than their chronological age

Question 49

What does Diabetes do to mortality?

Answer 49

Doubles the risk of death compared with that in nondiabetics of similar age. Seventh leading cause of death in the US

Question 50

What is the Incretin secretion following a mixed meal like in patients with type 2 diabetes?

Answer 50

GLP-1 was much lower than those with normal glucose tolerance. GIP wasn't that much lower

Question 51

What are the glucagon levels like in patients with type 2 diabetes?

Answer 51

Fasting plasma glucagon is higher in patients with type 2 DM. Postprandial glucagon levels are high in patients with type 2 DM

Question 52

What type of vascular damage occurs first with diabetes?

Answer 52

Macrovascular changes occur before microvascular

Question 53

What happens to the insulin supply and demand as diabetes progresses?

Answer 53

Insulin demand slowly increases while supply greatly decreases

Question 54

What what A1c does the risk of sustained retinopathy vastly increase?

Answer 54

Once A1c is above 8%