Pathophysiology of Type 2

Question 1

Major clinical features of T2D

Answer 1

• Central (abdominal) obesity
• glucose intolerance
• hypertension
• atherosclerosis
• polycystic ovary syndrome (PCOS)

Question 2

Criteria categories used to define diabetes

Answer 2

• Fasting Plasma Glucose, FPG (mg/dL)
• Oral Glucose Tolerance Test, OGGT (mg/dL)
• HBA1c
• Total blood sugar

Question 3

Fasting Plasma Glucose, FPG (mg/dL): Normal, Prediabetes, Diabetes

Answer 3

• N = <100
• PDM = 101-125
• DM = ≥ 126

Question 4

Oral Glucose Tolerance Test, OGGT (mg/dL): Normal, Prediabetes, Diabetes

Answer 4

• N = <140
• PDM = 140-199
• DM = ≥ 200

Question 5

HBA1c: Normal, Prediabetes, Diabetes

Answer 5

• N = < 5.7%
• PDM = 5.7-6.4%
• DM = ≥ 6.5%

Question 6

Total blood sugar: Normal, Prediabetes, Diabetes

Answer 6

• N = < 5 g
• PDM = 5-6g
• DM = >7g

Question 7

Definition of gestational diabetes

Answer 7

• glucose intolerance develops during pregnancy (usually in the 2nd or 3rd trimester)
• Glucose tolerance usually returns to normal after delivery, but 30-40% of women with GDM develop overt diabetes within 10 years.
• Need two plasma glucose values to exceed the normal range (specific values are debated)

Question 8

Key factors in pathophysiology of T2D

Answer 8

• insulin resistance
• beta cell dysfxn
• Patients with type 2 diabetes or impaired glucose tolerance have both decreased β-cell function and decreased insulin sensitivity (i.e. insulin resistance).
• Must have decreased insulin secretion (genetic predisposition to β-cell dysfunction) and insulin resistance (lifestyle, high fat diet, obesity, genetic, aging) to develop Type-2 diabetes.

Question 9

Interventions to prevent T2D in high risk pt.s

Answer 9

• Yearly screening for diabetes
• Weight maintenance or loss
• Diet affects glucose production and glucose absorption
• Metformin
• Full CVD risk profiles and intervention
• Diet and exercise is optimal treatment for diabetes

Question 10

Impact of diet and exercise on T2D risk

Answer 10

• 30 mins. of exercise 5 days a week (150 hours/week) + loss of 3 - 5% of body mass ==>
• 60% reduction in risk

Question 11

Role of genetics in T2D

Answer 11

• Increased risk
  
  • Familial aggregation
  • African American, Hispanic, Pima Indians of Arizona, Pacific Islander
  • Twins
• Type 2 diabetes is…
  
  • Polygenic
  • No association with HLA

Question 12

Pre-diabetes definition

Answer 12

• patients with impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG)
• Criteria:
  
  • HbA1c 5.7-6.4% OR
  • fasting plasma glucose of 100-125 mg/dL OR
  • a 2 hr OGTT plasma glucose value >140 and <200 mg/dL

Question 13

Definition of insulin resistance

Answer 13

Insulin resistance is defined as inadequate biological effects of insulin to stimulate glucose uptake in the skeletal muscle glucose and to suppress endogenous glucose production by the liver.

Question 14

Pathophysiology of DKA

Answer 14

• DKA = severe insulin deficiency ==>
  
  • extreme hyperglycemia (usually glucose >300mg/dL)
  • anion gap metabolic acidosis (usually pH <7.3)
  • increase in blood ketones (usually >5 mM)
• *Need to have relative lack of insulin + increased counterregulatory hormones*

Question 15

Presentation of DKA

Answer 15

• Presentation of hyperglycemic includes polyuria, polydypsia, weight loss, weakness
• Rapid onset hours after precipitating event: abdominal pain, nausea, vomiting
• Abdominal pain correlates with severity of acidosis

Question 16

Goals in tx of DKA

Answer 16

• Unless you stop the Ketone body production you will go right back into DKA
  
  • liver makes ketone bodies is because the brain can use these for energy too.
• Need to change counterregulatory hormone otherwise will not fix the problem → replace insulin, deplete glucagon.
• Find the underlying problem.

Question 17

Pathophysiology of hypoglycemia unawareness

Answer 17

• Need to treat hypertension, hyperlipidemia, hyperglycemia to fix atherosclerosis.
• Currently only 25% of patients receiving appropriate treatment for hypercholesterolemia → most on the wrong drug or noncompliant.
• Need to aim for less than 140/90 SBP at least. UKPDS says 120-130/80. Consider a decrease in Na+ instead of another drug
• ↑ of PAI-1 causes procoagulable state; decreases fibrinolysis.