Diabetes Flashcards
Types of DM
Type I (Juvenile onset)
- MAY be autoimmune→ Body produces antibodies that attack beta cells
- Initially→ ability of beta cells to produce insulin is impaired
-
Later→ Pancreas stops producing the hormone insulin
- Usually young, but can be 20’s or >
Types of DM
Type II
- Initially→ Insulin present BUT insulin resistance exists: cells do not recognize insulin
- Later→ Pancreas stops producing insulin
- Usually adulthood, BUT growing #’s of children w/ TIIDM
- Young as 3
- NOTE: TIIDM is REVERSIBLE!!!!!!!
Symptoms of Diabetes
- HypERglycemia, metabolic acidosis (kidneys), polydipsia/polyuria, dehydration, wt loss, INC food intake, blurred vision, Incd yeast infxs (infx’s love sugar), skin infx’s
-
Long-term issues:
- retinopathy, nephropathy, neuropathy, autonomic neuropathy, cataracts, glaucoma, CHD, peripheral vascular disease (PVD), stroke*
Criteria for Dx of Diabetes and Prediabetes
Looking @ Oral Glucose Tolerance Test (OGTT), Fasting Plasma Glucose Test (FPG) → see chart
also note A1C %
-
Prediabetes
- FBG→ >/= 100 but <126
- OGTT→ >/= 140 but <200
- A1C%→ 5.7-6.4%
-
Diabetes
- FBG→ >/= 126 (no cals for 8hrs)
- Hyperglycemia w/ plasma glucose >/= 200
- 2hr plasma glucose >/= 200 during OGTT
- A1C%→ >/= 6.5%
Correlation of A1C w/ Plasma Glucose Lvl
- A1C %→ 6 (upper lvl of normal) Plasma Glu (mg/dL)→ 126 (DM)
- A1C %→ 7 Plasma Glu (mg/dL)→ 154
see chart
What are normal glucose levels?
Depends on timing of the last meal or snack***
- Fasting NORMAL→ 70-100 mg/dL
- BELOW 70→ HypOglycemia
- ABOVE 100→ pre-diabetes
- ABOVE 126→ diabetes and hypERglycemia*
Normal Glucose Lvls
Preprandial (fasting or before meals) vs Post-prandial (after meal)
- Preprandial→ 70-100 mg/dL for overnight and before meals
- Post-prandial→ <140 mg/dL
Glycemic Goals NON-Pregnant Adults
- Reasonable A1C goal for nonpreg→ <7% (53 mmol/mol)
- More stringent goals (<6.5%)→ IF achievable w/out sig. hypos or other adverse effects
- LESS stringent goals (<8%)→ pts w/ hx of severe hypOglycemia, limtd life expect, or other cond’s that make <7% diff to attain
Glucose Monitoring
Self-monitoring
Reqs single drop of blood which can be w/drawn by lancet or by meter itself from fingertip or forearm
Glucose Monitoring
CHECK FREQUENTLY! (6-10x daily)
6-10x Daily
- BEFORE meals, 2hrs postprandial, BEFORE bedtime, 2AM (1x/month), when suspect LOW blood glucose, after treating LOW blood glucose until normoglycemic
- BEFORE exercise****→ exercise acts as insulin**
- Prior to critical tasks→ e.g. driving
Actions of Insulin
- INC storage of glucose as glycogen
- INC glucose utilization→ pulls glucose INTO cells
- Stimulates carrier mediated transport of glucose INTO cells
-
Incs triglyceride storage in adipose tissue and INCs triglyceride synthesis in Liver
- Lipogenic→ WHY its hard to lose weight on insulin**
- INCs PRO synthesis
Factors Regulating Insulin Release
Release stimulated by:
- Glucose
- Amino Acids, Fatty Acids
- Parasympathetic NS
-
Incretins
- Glucagon-like Peptide-1 (GLP-1)→ released into small intestine; Stims Beta cells in pancreas to release insulin*
Factors Regulating Insulin Release
Release inhibited by:
- SNS→ glucose TO muscle; bc we need it most when SNS “fight or flight” is revved up!!!!
- Somatostatin
- Glucagon*
- Epi*
- Glucocorticoids
- Growth Hormone (GH)
Effect on Hormones on Blood Glucose Lvls:
- DEC Blood Glucose→ Insulin (Main regulatory hormone)
- INC Blood Glucose→ Glucagon, Epi, Glucocorticosteroids, Growth Hormone (All Main counter-regulatory hormones)
see chart and notice main actions, main stimulus for secretion***
Insulin Molecule
Know the *, look @ picture
- *Produced in pancreatic Beta Cell
- PROinsulin→ Has C-chain
- When insulin released→ C-chain disassociates (not always in T2DM though)
Insulin production happens where???
Pancreas
Insulin production
Do NOT get hung up on this, read description, note picture
- Glucose enters beta cell via Glut 2 transporter→ undergoes metabolism producing ATP→ ATP blocks OUTflow of K+ ions→ membrane DEpolarization→ Depolarization opens voltage-gated Ca++ channels→ Ca++ influx→ Ca++ triggers exocytosis + insulin RELEASE***
Insulin Action
How does it get the Glucose INTO cell?
GLUT-4 vesicle
allows GLU mc to enter cell→ used for energy (ATP) OR stored (glycogen/triglycerides)
NOTE: Insulin Resistance is when cells NO LONGER RESPOND to this signal!!!!
Incretins
what are they?
Peptide hormones released from GI tract
- Glucagon-like insulinotropic peptide (GIP)
- Glucagon-like peptide-1 (GLP-1)
Incretins
Function
- Released when food ingested, EARLY stimulus to insulin secretion*
- INHIBIT pancreatic glucagon secretion
- SLOW rate of absorption of digested food→ REDUCE gastric emptying
- REDUCES appetite== wt loss
Exogenous Insulin
2 types:
- Basal Insulin→ think overnight, bw meals
- Prandial (mealtime) Insulin→ think limits spike in blood sugar AFTER meals
Exogenous Insulin:
Basal Insulin
-
Suppresses glucose production while fasting
- Overnight, bw meals
- Maintains nearly constant blood glu and day long insulin lvls
- ~50% of daily insulin needs
Exogenous Insulin
Prandial (mealtime) insulin
- LIMITS hypERglycemia after meals
- IMMEDIATE rise and sharp peak ~1 hr after injection
- 10-20% daily insulin req. @ ea meal
Types of Insulin
- Ultra short acting
- Regular
- Intermediate
- Peakless- LONG ACTING
Glycemic Recommendations for Adults WITH DM
- A1C→ <7%
- Preprandial capillary plasma glu→ 80-130 mg/dL
- Peak Postprandial cap. plasma glu→ <180 mg/dL
- Postprandial @ 2hrs→ <160 mg/dL
- Fasting blood glu→ 80-110mg/dL
- Bedtime→ 110-130 mg/dL
- 3AM→ >80 and <120 mg/dL
What lvl of blood glucose is DEADLY?
<20 mg/dL
Adverse Effects of Insulin
HypOglycemia
WHEN can this occur?
- If insulin too high, missed meal, *strenuous exercise (remember exercise acts as insulin!!!!)
Adverse Effects of Insulin
HypOglycemia
S/S
- HA, fatigue, hunger, TACHYcardia, sweating, anxiety, confusion, weakness, faintness, coma (<20mg/dL)
Another Adverse Effect of Insulin
Rebound hypERglycemia
- Rebound HIGH blood glu lvl in response to LOW blood glu
- Ex. high blood sugar in morning due to excess amt of insulin during night
Adverse effects of insulin
Wt. Gain
Remember insulin is Lipogenic
- Insulin→ INC triglyceride storage in adipose tissue and INCs triglyceride synthesis in liver→ Lipogenic
- hard to lose wt on insulin*
HypOglycemia Risk Factors
Inc’ing age, delayed or reduced food intake, Long standing disease, recent hypoglycemic episode, Infx (sugar loves infx’s), alcohol intake
HypOglycemia Protocol
2 Rules:
- If pt on pump→ IMMEDIATELY discontinue insulin infusion
- Rule of 15****
HypOglycemia Protocol
Rule of 15
When does this kick in/when start it?
If blood glucose is 70mg/dL or BELOW******
If blood glucose is 70mg/dL or BELOW******
WHAT RULE?
RULE OF 15
HypOglycemia Protocol
Rule of 15
If blood glucose is 70mg/dL or BELOW:
- Eat 15g carbs→ Recheck glucose lvl in 15mins→ If not ABOVE 70, eat another 15g carbs→ Test again in 15mins→ if not ABOVE 70, eat another 15g carbs and call MD
- NOTE: 15g CHO= 4oz juice or soda (NOT DIET!!!!!), 1 Tbl of table sugar or honey***
Comparison bw HypOglycemia vs HypERglycemia
Chart first
See chart
NOTE: Both have COMA in common….
HypOglycemia vs HypERglycemia
HypO→
- Nervous, shaky
- Hungry
- HA
- Confused
- Cold clammy skin
- TACHYcardia
- Irritability
- Coma
HypOglycemia vs HypERglycemia
HypER→
Note that these all make sense bc now blood is flooded w/ sugar…..TOO MUCH SUGAR CIRCULATING IN BLOODSTREAM!!!!
- Weak, tired
- Freq. urination*
- INCd thirst*
- DECd appetite
- Blurry vision
- Fruity breath*
- Itchy dry skin
- SZ’s
- Coma
Modes of Insulin Administration
Subcutaneous Injections
- Site must be rotated
- Lower abdomen, upper outer arms, upper outer thighs, buttocks
- Rate of injection FASTER into abdomen vs arm or leg***
Modes of Insulin Administration
Subcutaneous Injection
Guidance in Therapy aka we do NOT want to INC the rate of absorption when they are in therapy so there are precautions we can take to ensure this does not happen and they become hypOglycemic!!!
- ***DO NOT USE:
- hot packs, water therapy, infrared, US near inj site, or Exercise→ ALL accelerate absorption
- Also NO massage in area
- HEAT INCs absorption== BAD!
- NOTE: Rise in ambient temp also causes INC in insulin absorption as much as 50% w/ INC of 15*C. Cold does OPPOSITE
Modes of Administration
- Portable pen injectors
- Jet injectors
- Dry powder inhaled insulin
- External pump
- Implantable pump→ sx implanted on L. side of abdomen
Insulin Pump + CGM (Continuous Glucose Monitoring)
see pics
Mode of Admin
Other example
see pics
Agents of Type II DM
Metformin
MOA, Indications, ADRs
-
MOA: Inhibits gene expression for gluconeogenesis (prod of glucose)
- Reduces gluconeogenesis in liver
- Stims glycolysis in peripheral tissue→ improves glucose utilization in SK MM
- Reduce CHO absorption
- INC fatty acid oxidation
- Reduce circulating LDLs and VLDLs, and triglycerides
- INC insulin binding to its receptor
- Modest wt loss****
- Does NOT cause hypOglycemia
- Indications: drug of first choice→ UNLESS renal and hepatic issues
- ADRs: mild→ nausea, diarrhea, rarely lactic acidosis
FUN FACT:** Recent data shows it helps **reduce rate of cx in pts w/ T2DM and may reduce mortality**
Agents for Type II DM
Sulfonylureas
MOA, ADRs
- MOA: Insulin secreatogues→ Blocks ATP sensitive K+ channels, facilitates insulin (by Ca+ flood) release, suppresses glucagon, BUT stimulates appetite/caues wt. gain
- ADRs: HypOglycemia (esp elderly), mild wt gain, binds to albumen (if w/ other drug, warfarin→ drug-drug interaction)
Agents for Type II DM
Thiazolidinediones (glitazones)
MOA, ADRs
-
MOA: Insulin sensitizers (gets cells to recognize insulin)
- INC insulin sensitivity in mm, liver, adipose tissue→ improves insulin resistance
- Improves lipid and cholesterol lvls
- may delay progress. of dis.
- ADRs: fluid retention, wt gain, incd risk fx’s, possible risk of bladder cx w/ Actos (ex. of drug)
Agents for Type II DM
Incretin Mimetics
MOA, ADRs
-
MOA: glucagon-like peptide (GLP-1) analog
- INCd secretion of insulin
- Beta cells bathed in GLP, cell morphology was maintained and slowed cell death
- Additional→ inhibits glucagon secretion, suppress appetite
- ADRs: nausea, vom, diarrhea, risk of mild-mod hypOglycemia when used w/ sulfonylurea so reduce sulfonylurea dose
Summary of Incretin Actions on Diff Target Tissues
NOTE: Cardiac protective*
Agents for Type II DM
Pipeptidyl Peptidase-4 (DPP-4) Inhibitors
MOA, ADRs
-
MOA: competitively inhibit DPP-4 enzyme, slows incretin degradation-potentiating glucagon-like peptide-1 (GLP-1)
- Reduces HgA1C by .7-.9%
- ADRs: nasopharynigitis, nausea
Agents for Type II DM
SGLT2 Inhibitors (NEWEST*)
MOA, ADRs
-
MOA: Sodium glucose cotransporter 2 (SGLT2) inhibitor preventing the resportion of glucose in kidney→ results in INCd urinary glucose excretion, and a lowering of blood glucose lvls
- SOME wt loss*
- ADR: UTI, yeast infx (bc urine full of sugar), incd LE amps?
Drug Effects on Glycemic Control
Type II DM
Chart
see chart
Drug Effects on Glycemic Control
Type II DM
Drug Class: Sulfonylureas/meglitinides
MOA?
INC insulin release
Drug Effects on Glycemic Control
Type II DM
Drug Class: Metformin***
KNOW THIS ONE!!!!
MOA?
DEC gluconeogenesis/INC insulin sensitivity
Drug Effects on Glycemic Control
Type II DM
Drug Class: Thiazolidinediones
MOA?
Insulin Sensitizers
Drug Effects on Glycemic Control
Type II DM
Drug Class: Incretins: exenatide, DPP-4 Inhibitors
MOA?
Beta cell and Non-Beta cell effects: preserve Beta cell function and enhance insulin release
Drug Effects on Glycemic Control
Type II DM
Insulin
Replacement bc body no longer producing (Beta cells (in pancreas) no longer producing)
Inc insulin Release
Sulfonylureas/meglitinides
Dec gluconeogenesis/INC insulin sensitivity
Metformin***
Insulin Sensitizers
Thiazolidinediones (PPAR-Beta agonists)
Prevent glucose reabsorption from Kidneys
SGLT2 Inhibitors
B-Cell and NON-B cell effects: preserve beta cell function and enhance insulin release
Incretins: exenatide, DPP-4 inhibitors
Replaces insulin body no longer producing
Insulin
Drug Effects on Glycemic Control
Type II DM
Drug Class: SGLT2 Inhibitors
MOA?
Prevent glucose reabsorption from Kidneys