01-03 What is Diabetes? Metabolic Sx? Flashcards
1) Define diabetes from the perspective of the doctor and the patient 2) Know the health implications of the diagnosis of DM 1 and 2 3) Understand the basic pathophysiology and biochemistry that underlies hyperglycemia 4) Know the diagnostic criteria of Type 1, Type 2, Gestational diabetes and metabolic syndrome 5) Know the health implications of impaired glucose tolerance, impaired fasting glucose and metabolic syndrome
What is Type 1 DM?
—Definition
—Natural Hx
—Prevalence
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
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What is Type 2 DM?
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
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What is gestational DM?
—
—risks
—pathophys
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
What is impaired glucose tolerance?
—definiition
—dx
—risks
—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)
What is impaired fasting glucose?
—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
What is pre-diabetes?
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)
What are the laboratory criteria for the diagnosis of DM?
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
Draw the relation between intake, insulin, muscle, fat and liver in FASTING conditions!
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Draw the relation between intake, insulin, muscle, fat and liver in FED conditions!
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—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
Prevention of Pre-Diabetes to DM
25% reduction in study of lifestyle ∆s:
—↓ wt 5%
—↓ fat to 15g/1000kCal
—↑ exercise to > 4hrs/wk
What is metabolic syndrome?
—Dx criteria
—Prevalance
[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)
Causes of Metabolic Syndrome?
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
Lipdystrophy
—Presentation
—Assoc’d metab ∆s
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
Target A1c level in a diabetic
<7%
Target A1c level in a diabetic
<7%
Biochem of Insulin & its receptor —structure of insulin —subunits of receptor —signaling pathways —end effects
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)
Average blood glucose in pregnancy
is lower than normal in pregnancy compared w/ non-preg pts
Biochem of Insulin & its receptor
—structure of insulin
—subunits of receptor
—signaling pathways
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)
hormones released by intestines peri-meal that augment insulin
—glucagon-like peptide (GLP-1)
—gastric insulinogenic peptide (GIP)
adiponectin
hormone secreted from adipocytes that increases insulin sensitivity
What are some other hormones besides insulin that regulate nutrient metabolism?
opposing hormones: —glucagon (also from Islet of Langerhans) —GH —cortisol —epinephrine
