01-03 What is Diabetes? Metabolic Sx?

Question 1

What is Type 1 DM?
—Definition
—Natural Hx
—Prevalence

Answer 1

DEFINITION
—Low or absent levels of endogenous insulin and dependence on injected insulin to prevent ketoacidsis and sustain life

NATURAL Hx
—insulin prod stops usu before teen
—subsequent glucose ↑

PREVALENCE
— < 0.20% general pop
—Rare in Asians
—B/c of severity it does not go undiagnosed for long

[IMAGE]

Question 2

What is Type 2 DM?

Answer 2

DEFINITION
—Insulin resistance and abnormal insulin secretion combined. Not prone to ketoacidosis under normal circumstances but may require insulin therapy for glucose control.
—Likely an underlying inherited problem of metabolism brought to light by western diet
—Much greater genetic linkage than DM 1 though no single mutation

NATURAL Hx
—insulin prod ↑s to make up for ↑ing resistance for several years
—eventually can’t resistance overcomes and glucose begins to rise
—later insulin prod fails

PREVALENCE
—8-9% of general pop
—B/c less severe than DM1, may go un-dx
[IMAGE]

Question 3

What is gestational DM?
—
—risks
—pathophys

Answer 3

DEFINITION
—↑ plasma [glucose] during pregnancy that resolves post-partum

↑ RISK OF:
—DM2 post-partum ~25%
—eclampsia (b/o salt retention)
—large infant

PATHOPHYS
—”due to exaggeration of insulin resistance, and, to a lesser degree, a failure to secrete enough insulin”
—sex hormones ↑ insulin resistance
—placenta makes human placenta lactogen which also ↑ insulin resistance; some ♀ just make more

Question 4

What is impaired glucose tolerance?
—definiition
—dx
—risks

Answer 4

—a “Pre-Diabetes” state- not a dz itself per se
—tolerance test: 140 < [glucose] < 200
RISKS
—damages macrovasc (vs. none in IFG) but NOT microvasc (as w/ DM)
—25% advance to DM; ↑ risk of progression w/ certain meds (e.g. steroids s/p asthma attack may cause polydipsia, polyuria and blurred vision)

Question 5

What is impaired fasting glucose?

Answer 5

—a “Pre-Diabetes” state
—Fasting glucose >100 but <140
—same ~25% risk of DM in 5 years as IGT but WITHOUT the macrovascular complications of IGT

Question 6

What is pre-diabetes?

Answer 6

Not technically a disease state in need of treatment but a “state” suggesting increased risk of developing DM 2 later on
—Either “impaired fasting glucose” (less severe/earlier) or “impaired glucose tolerance” (more severe/later)

Question 7

What are the laboratory criteria for the diagnosis of DM?

Answer 7

1) DM sx (polydipsia/polyuria and/or unexplained wt loss) + random gluc >200mg/dL
2) 2 Fasting measurements >125
3) glucose of 200 s/p 75g glucose bolus*
* using std reagent + at least 2 days carb rich diet before

Question 8

Draw the relation between intake, insulin, muscle, fat and liver in FASTING conditions!

Answer 8

[IMAGE q9]

Question 9

Draw the relation between intake, insulin, muscle, fat and liver in FED conditions!

Answer 9

[IMAGE q10]
—recognize that DM is not just about sugar; it is a d/o of nutrient metabolism which includes lipids, proteins, amino acids, etc.
—glucose is just the easiest to measure

Question 10

Prevention of Pre-Diabetes to DM

Answer 10

25% reduction in study of lifestyle ∆s:
—‪↓‬ wt 5%
—‪↓‬ fat to 15g/1000kCal
—↑ exercise to > 4hrs/wk

Question 11

What is metabolic syndrome?
—Dx criteria
—Prevalance

Answer 11

[Nat'l Chol Ed Pgm Criteria]
ANY THREE OF THESE FIVE
1) ↑ waist circum (♂: > 40"; ♀: > 35")
2) ↑ trigs (> 150 mg/dL)
3) ‪↓‬ HDL (♂:  < 40mg/dL; ♀: < 50)
4) Hypertension (> 130/85)
5) Impaired fasting gluc (>100mg/dL)

PREVALENCE
—↑ w/ age
—34% of U.S. residents > 20 y/o
—80% of DM2 pts! (DM1 pts have same prev as gen pop)

Question 12

Causes of Metabolic Syndrome?

Answer 12

DIET
OBESITY
↑ VISCERAL FAT
ADIPOCYTE DYSFUNCTION
—adiponectin
—leptin
—PAI-1: plasogen acti. inhib (↑ thrombus risk)
—Free fatty acids
—interleukins
—adipsin
HAART HIV MEDICATION
—Causes lipdystrophy

Question 13

Lipdystrophy
—Presentation
—Assoc’d metab ∆s

Answer 13

PRESENTATION
—face/arms/legs fat → central (belly/buffalo hump) and hepatic depots

ASSOC'D METAB ∆s
—insulin resistance
—hypertriglyceridemia
—hyperglycemia
—‪↓‬ fat secretion of adiponectin & leptin

Question 14

Target A1c level in a diabetic

Answer 14

<7%

Question 14

Target A1c level in a diabetic

Answer 14

<7%

Question 15

Biochem of Insulin & its receptor
—structure of insulin
—subunits of receptor
—signaling pathways
—end effects

Answer 15

INSULIN STRUCTURE
—two peptide chains w/ disulfide linkages

RECEPTOR STRUCTURE
—α-subunit: extracellular, binds insulin
—β-subunit: intracellular, begins signal cascade

SIGNAL PATH
—β-subunit is tyrosine kinsase that signal thru:
—1. insulin receptor substrates (IRS-1&2)
—2. phosphoinositides (IP3)
ACTIVATES: glucose storage (e.g. glycogen synthase & pyruvate kinase), fat storage and a.a./prot storage enzymes
INACTIVATES: gluconeogenic enzymes (e.g. G-6-phosphotase); lipolytic enzymes; catabolic proteases
TRANSLOCATES: GLUT-4 from vesicle to cell membrane of fat and muscles (liver does NOT need GLUT-4)

Question 15

Average blood glucose in pregnancy

Answer 15

is lower than normal in pregnancy compared w/ non-preg pts

Question 16

Biochem of Insulin & its receptor
—structure of insulin
—subunits of receptor
—signaling pathways

Answer 16

INSULIN STRUCTURE
—two peptide chains w/ disulfide linkages

RECEPTOR STRUCTURE
—α-subunit: extracellular, binds insulin
—β-subunit: intracellular, begins signal cascade

SIGNAL PATH
—β-subunit is tyrosine kinsase that signal thru:
—1. insulin receptor substrates (IRS-1&2)
—2. phosphoinositides (IP3)

Question 17

hormones released by intestines peri-meal that augment insulin

Answer 17

—glucagon-like peptide (GLP-1)

—gastric insulinogenic peptide (GIP)

Question 18

adiponectin

Answer 18

hormone secreted from adipocytes that increases insulin sensitivity

Question 19

What are some other hormones besides insulin that regulate nutrient metabolism?

Answer 19

opposing hormones:
—glucagon (also from Islet of Langerhans)
—GH
—cortisol
—epinephrine