DM Basics

Question 1

What is the normal fasting plasma glucose? Normal glucose 2 hrs post-prandial?

Answer 1

70-100

< 140 2 hrs post-prandial

Question 2

How is insulin synthesized and released from beta cells?

Answer 2

• Made by beta cells - center of acini so most sensitive to changes in blood; closest to arterioles
• Pre-proinsulin transcribed in nucleus –> RER –> pro-insulin –> insulin and C peptide in secretory granules
• Glucose taken into beta cell thru GLUT2 (insulin indep)–> gluc-6-phos by glucokinase –> glycolytic path and TCA cycle –> ATP production –> cell depolarization –> closes ATP-sensitive K+ channels –> open voltage-gated Ca channels –> Ca enters and binds secretory granules –> released

Question 3

How does insulin act on peripheral cells?

Answer 3

• Insulin-receptor - extracellular and intracellular domains
• Binding of extracellular domain –> tyrosine phosphorylase of intracellular domain phosphorylates itself and other proteins including insulin receptor substrates (11 IRSs) –> PI3 –> Protein kinase B and atypical protein kinase C
• Ultimately leads to migration of GLUT4 transporter to surface so glucose can be taken into cell

Question 4

DM v. Glucose Intolerance Diagnoses

Answer 4

• DM: fasting glucose > 125 and 2 Hr post-meal > 200
• Glucose Intolerance: fasting glucose 100-125 (impaired fasting) OR 2 hr post-meal b/n 140-200 (impaired glucose tolerance)
  • *Same risk but 2 diff terms based on labs

Question 5

4 Methods of Diagnosing DM

Answer 5

• 1- Random plasma glucose > 200 (if classic symptoms - polyuria, polydipsia, wt loss)
• 2- Fasting Plasma Glucose > 126 on 2 sep occasions
• 3- 2 hr plasma glucose > 200 w/ oral glucose tolerance test on 2 sep occasions
• 4- Hemoglobin A1C > 6.5%

Question 6

Type 1 v Type 2 Characteristics

Answer 6

Type 1 DM

• Thin
• Young age of onset
• Acute onset
• Islet cell antibodies
• HLA related (HLA-DR3, DR4, DQ alpha and DQ beta)
• Prone to ketosis
• No insulin secretion
• No insulin resistance
• Oral agents NOT helpful

Type 2 DM

• Obese
• Older age of onset
• Insidious/ progressive onset
• No islet cell antibodies
• Not HLA related
• Not prone to ketosis
• Insulin secretion still present
• Insulin resistance
• Respond to oral agents

Question 7

Classic DM Symtpoms

Answer 7

• Polyuria, nocturia, polydipsia
  
  • Glucose plasma exceeds renal threshold for reabsorption (180-200) so osmotic effect –> inc urine –> compensatory dehydration
• Frequent yeast infections - presence of high concentrations of glucose in the urine and in vaginal secretions leads to overgrowth of yeast organisms
• Polyphagia - excess appetite (glucose not getting into cells)

Question 8

HbA1C

Answer 8

• Most reliable method of assessing glycemic control
• Formed by the non-enzymatic linkage between glucose and the amino group of the terminal valine of hemoglobin A (non-enzymatic glycosylation)
• Degree of glycosylation is directly proportional to both the duration and level of exposure of the hemoglobin molecule to glucose in the plasma
• Since RBC’s live for approx 100-120 days, the amount of glycosylated hemoglobin, or HbA1c, in the blood is a reliable indicator of the degree of hyperglycemia present for the preceding 3 mo
• Normal = <6%
• DM goal is usually <7%

Question 9

MODY

Answer 9

• maturity onset diabetes of youth (genetic defects in insulin sec –> mild hyperglycemia); young, lean, familial
• Type 1, 3-6 transcription factor problems
• Type 2- glucokinase defect

Question 10

What 2 factors must be present to develop type 2 DM?

Answer 10

must have both insulin resistance AND abnormal beta cell function

Question 11

Examples of Beta Cell Abnormalities

Answer 11

• Impaired glucose and meal-stimulated insulin secretion
• Gradual decline / loss of first phase insulin response to glucose (pre-formed insulin release - acute spike w/ meal)
• Inc ratio pro-insulin:insulin
• Alterations in pulsatile insulin secretion
• Defective glucose recognition by beta cells
• Failure to suppress glucagon after meal

Question 12

GLP1

Answer 12

• (glucagon like peptide 1)
• released from jejunem when senses meal (ORAL) –> bind beta cells –> activate adenylyl cyclase –> cAMP –> amplified Ca-mediated secretion of insulin from beta cells
• “Incretin effect” - beta cell response is greater w/ oral glucose than IV