Diabetes Flashcards

Question

What is diabetes insipidue?

Answer 1

* defect in water reabsorption in the kidney- problem with ADH synthesis/utilization * **increase** UO (diluted urine- tasteless) * not associated with DM

Answer 2

Determine Type 2 vs Type 1 If C peptide is not present/low, then it is Type 1 DM

Answer 3

Type 1: * increase BG: insulin production inhibited Type 2: * increase BG: insulin use inhibited → insulin not used by cells

Answer 4

**Clinical diagnosis of diabetes mellitus: (know these numbers)** Typically these tests will be done multiple times 1. Fasting plasma glucose level (before AM meal) 1. **\>126mg/dL** (7mmol/L). 2. Normal levels \< 100mg/dL (5.6mmol/L) **or** 1. Plasma glucose levels in excess 1. **\>200mg/dL** (11mmol/L) after 2 hours during an OGTT **or** 1. Random glucose level (eaten w/ cortisol) 1. **\>200mg/dl** and **diabetic symptoms**. Normal Person: * Start: 90 * Take glucose → Glucose levels increase→ decrease * ~2 hrs after: lower than start (hungrier than started) Diabetic: * Start: HIGHER * Take glucose → levels increase → stay higher longer

Answer 5

* During pregnancy, hormonal changes can cause **increase** BG (fetus wants the glucose) * **Diagnosed if woman has:** (don’t need to know numbers, just that they are lower) * Fasting blood glucose level \> 95 mg/dL * 1-hour level \> 180 mg/dL (OGTT) * 2-hour level \> 155 mg/dL or * 3-hour level \> 140 mg/dL * Glucose levels are normally lower during pregnancy → **cutoff levels for dx in pregnancy are lower**.

Answer 6

* **Pathology:** * Typically between 24-28 weeks of pregnancy * fetus growing big/fast → needs more glucose/energy! → tells mom to **increase** BG * **Poorly controlled gestational diabetes:** ~400 BG * Glucose crosses placenta → giving baby hyperglycemia * **Consequences** → Unhealthy baby ( **increase** risk developing): * Short-term: * Hypoglycemia at birth (d/t sudden **decrease** in glucose supply) → PREVENT * Long-term: * HTN * CV dx

Answer 7

* **Normally:** * Resolves following childbirth * But dangerous for both mother and baby → baby becomes hypoglycemic * 2/3 chance GD will return in future pregnancies * \*warning sign that mom was prediabetic before pregnant\* → might return to prediabetic or diabetic after birth

Answer 8

**Pre-diabetes** * AKA: **impaired fasting glucose** (IFG) and/or **impaired glucose tolerance** (IGT) * ~Depending on the test used to diagnose it. Some people have both IFG and IGT. * **IFG:** **impaired fasting glucose** * **BG level: 100-125 mg/dL** after an overnight fast * not high enough to be classified as diabetes (~DM \>126) * **IGT:** **impaired glucose tolerance** * **BG level: 140-199 mg/dL** after 2-hour oral glucose tolerance test * not high enough to be classified as diabetes (~ DM \>200) * REVERSIBLE → prevent end organ disease * Population: ~40% U.S. adults → ages 40-74

Answer 9

* **Hypoglycemia** → took too much insulin (DM2) * **Diabetic ketoacidosis (DM1)** → not enough insulin * **Hyperosmolar hyperglycemic nonketotic syndrome (HHNKS or HONKS)** (DM2) * Osmolarity \> 290 (~350-400) → suck H2O out of cells * Hyperglycemia: osmolarity **INCREASE** d/t GLUCOSE (osmotic agent) * Nonketotic: no ketones in urine * **MEDICAL EMERGENCIES**

Answer 10

* **Hyperglycemia and non enzymatic glycosylation** * increase glucose--\> glucose sticks to proteins * AGEs increase with age * **microvascular disease (RNC is micro...)** * diabetic retinopathy * diabetic neprotpathy * diabetic CARDIOMYOPATHY- most CV dx caused by MACROvascular dx * **Macrovascular disease \*\* big killers\*\*\*\* (PCS is MACRO... lots of cell towers)** * PAD * CAD * Stroke * **Increase activity of polyol/sorbitol pathway** * diabetic neuropathy- schwann cells swell--\> damage to cells they myelinate * cataracts- polyol pathway makes various sugar ETOH * increase BG--\> increase pathway activity--\> too much ETOH sugars--\> cause cell to swell * **other** * glaucoma--\> diabetic blind bc cataracts and diabetic neuropathy * infection- poor circulation

Answer 11

* Blood glucose = \< 70mg/dl * ~ Need lower before seeing effects * **MILD S/S:** * Hunger * Shakiness * Paleness * Blurry vision * Sweating * Anxiety * **SEVERE S/S:** * Extreme tiredness * Confusion * Dazed appearance * Seizures (~ \< 30) * Unconsciousness ® COMA® **DEATH** * Tx: conscious → candy bar, bread/unconscious → Dextrose drip

Answer 12

* Diabetic Ketoacidosis * Life-threatening **HYPERGLYCEMIA** * → could result in brain damage * Breakdown from fat/PRO for energy → **KETOSIS** * **Causes:** **Not getting insulin** * Untreated or undiagnosed DM (especially IDDM) * **decrease** insulin & **increase** glucagon → try to **increase** BG → break down fat → goes liver → makes ketones bodies * Non-compliance to DM Rx * infection or illness

Answer 13

* Fruity acetone breath * Acetone- types of ketone body (finger-nail polish remover) * Acetone: **LOW** boiling point → can exhale it! * Kussmaul’s breathing (deep, rapid, gasping) * Ex: Have metabolic acidosis → tx by RR * **Dehydration** * **INCREASE** osmolarity → H2O sucked out of cells → **increase** UO (cells dried out) * N/V, abdominal pain * Altered LOC * Combo from metabolic acidosis & **increase** osmolarity * Weakness, paresthesia

Answer 14

* **Severe hyperglycemia** * electrolyte imbalance * Metabolic acidosis → electrolyte imbalances * **+ ketones in urine (from hyperketonemia)**

Answer 15

**GFR = 125 ml/min** **Tmax = 300 mg/min** * **Filtered load= BG x GFR** **(CHANGE UNITS TO MATCH)** * **1 dL = 1 x 10^-1(0.1) L, =100 mL** **Example 1:** * Blood glucose = 80 mg/dl * Filtered load = 80 mg/dl \* 125 ml/min * change to 0.8 mg/mL\*125mL/min = 100 mg/min (all glucose reabsorbed, none in urine) **Example 2:** * Blood glucose = 300 mg/dl * Filtered load = 300 mg/dl \* 125 ml/min * change to 3 mg/mL\*125mL/min = 375 mg/min filtered load * 375 mg/min – 300 mg/min (Tmax) = **75 mg/min (not reabsorbed → Glucose in urine)** **Note: 1 mM of glucose = 18 mg/dL (mg % = mg/dL)**

Answer 16

- Fast/no food → BG **decrease** → liver mobilize glycogen → glucose (lasts ~1 day) - **increase** Glucagon → fat cells mobilize FFA→ FFA in blood → go to liver → beta-oxidation of fat → **increase** ketones released * Liver: makes Acetyl-CoA * Acetyl-CoA + HMG-CoA synthase → **acetoacetate** * **Acetoacetate:** MAJOR ketone “ketone acid” * Released from liver as: “Ketone Bodies/Ketone Acids” * Acetone- Ketone (not an acid) * B-hydroxybutyrate- Acid (not a ketone) * Body (& brain) use ketones as FUEL → takes longer for liver to ketone production * **Normal person:** * Ketones → stimulate insulin secretion in b-cells * Glucagon will be controlled/modulated (enough to keep FFA release sufficient to keep ketone body production sufficient) ~ wont be hungry after fast after few days * No fxing b-cells → glucagon (DM1) * Depletion of oxaloacetate via high rates of gluconeogenesis slows entry of acetyl-CoA into Krebs Cycle. * Under these conditions, acetyl-CoA is converted into ketone bodies for use by: * Brain * Heart * Kidney * Liver * Ketone bodies include: acetoacetate, acetone, and β-hydroxybutyrate. * Cannot make glucose from fat – you can make acetoacetate which can be used as fuel * Ketogenesis generates ketone bodies from acetyl-CoA, releasing the CoA to participate in β-oxidation. The enzymes involved, HMG-CoA synthase and lyase, are unique to hepatocytes; mitochondrial HMG-CoA is an essential intermediate. The initial product is acetoacetic acid, which may be enzymatically reduced to β-hydroxybutyrate by β-hydroxybutyrate dehydrogenase, or may spontaneously (nonenzymatically) decompose to acetone, which is excreted in urine or expired by the lungs.

Answer 17

* Glucose elevation: Osmotic agent * HHS: in**crease** 58.1 (in osmolarity → just from glucose) * DKA: **increase** 38.5 * Osmolarity * HHS: 380 (90 mOsm \> normal osmolarity) **increase** * Sucks H2O out of cells (brain) → cause coma → death * DKA: 323 ( DKA \> normal) * Not as much as HHS * pH * HHS: 7.3 (barely acidotic) * **DKA: 7.12 (severely acidotic)** * Bicarb (follow with degree of acidosis) * HHS: 18 * DKA: 9.4 * C-peptide → insulin should be **increased** so should see **increase** C-Peptide if making insulin * HHS: 1.14 ( **increased** x 5 \> normal) * DKA: 0.21 (LOW- B-cell depletion) * Anion Gab * HHS: normal (11) * DKA: **increase** → d/t metabolic acidosis * **\*HHNKS** not that big of acidosis, but **increase** osmolarity, due to excessive glucose, dehydrating the cells **Both:** **increase** in BG, osmolarity **Different**: C peptide, pH, Bicarb, and anion gap

Answer 18

**EMERGENCY** * Higher BG → worse outcome for HHNKS * Mortality rate is function of BG * \>1000 BG → Mortality rate ~10-30% * Tx: LARGE dose of insulin * dka is easier to manage...

Answer 19

**Advanced Glycosylation of End-products (AGEs)** * More glucose = more protein cross linking, (remember hgb is protein) * these also are why the proteins are rigid and lose flexibility (stiff joints) * AGE receptors – finding these and macrophaging/destroys them=== inflammation (atherosclerosis, retinopathy, neuropathy) **Glucose binds to sidechains of proteins** * increase glucose have → increase binding * Shifts, happens quickly * **Over time:** irreversible binding → Amadori product * **Amadori product → \*crosslinks\* → crosslinked protein** * Crosslinked protein: * Useless, problematic * Macrophages: have receptor → Receptor for Advanced Glycosylation End Products (RAGE) * Finds proteins that have been crosslinked → destroys them * **Higher BG → faster the reaction** * Ex: BG 100 → can keep up with rate * Ex: BG 400 → 4x faster buildup: * Cant clear glycosylated end products fast enough (AGEs) * Activated macrophages trying to clear AGEs → chronic inflammation in body

Answer 20

**HbA1c – glycosylated Hemoglobin** **Hemaglobin**: most common glycocylated end protein (AGE) * HbA1c = measure of how much glycocylation of Hgb in blood * Average over the last 1-2 weeks (sources say 90 days) GOAL: 7% → 170 (mean plasma glucose) **A1c Test:** * **Normal: \< 5.7** * Pre-diabetes: 5.7- 6.4% * **Diabetes: \> 6.5%** * **DM dx: GOAL \< 7**

Answer 21

DCCT was a trial with DM1 linking relationship of HbA1c to risk of microvascular complications GOAL: ¯**decrease**BG → see what happened \*See: decrease **BG (HbA1C %) → complications** decrease Ex: HbA1C 6% → no complications HbA1C 11%: * **13 X RELATIVE RISK** of retinopathy * **11 X realative risk of nephropathy (compared normal)** * **Problem**: Study done on DM1 * DM2 → meds don’t **decrease** complication risks like DM1 meds (insulin) does (curve not applicable for DM2 pts)

Answer 22

* Leaky BV in retina → retinal damage! * Arterials/capillaries in retina start leaking/falling apart → BLINDNESS * Hemmorage * Leaking, etc * **Leading cause of blindness.** * Diabetics → more likely to develop eye problems * Ex: cataracts, glaucoma * **Retinal damage → largest cause of blindness.** * Prevalence: * **\*type 1** (40%) → d/t being diabetic longer * type 2 (20%).

Answer 23

* Cataracts of the crystalline lens with opacification * more frequent in DM * \*occurs to everyone with age… * treatment- cataract replacement but no txmt retinopathy * Increased sorbitol and increased proteins in the lens

Answer 24

* Leading cause of kidney failure * Leakiness of glomerular capillaries * microalbuminuria-proteinuria. * Leaking in big capillary beds → GLOMERULUS * Causes → * **decrease**GFR * **increase** Protein leaking (microalbuminuria/proteinuria) * **Leading cause of kidney failure.** * Type 1 & 2 diabetes at risk * ~ 30% pts w/ DM develop diabetic nephropathy * Poor control of BP → greatest rate of progression * ~ macrovascular damage * DAMAGE * Proteinuria--\> damage to glomerulus * damage to proximal tubule too * Treatment: once proteinuria dx--\> * keep BP under control c ACE/ARB * Uncontrolled DM--\> dialysis * afer dialysis or transplantation--\> DM pts tend to do worse than those w/o DM * **Consequences of diabetic nephropathy**: * Glomerulosclerosis * tubulointerstitial fibrosis * Arteriolar sclerosis * Renal failure * Hypertension → exacerbates * Tx: ACEI & ARBs → **decrease**remodeling from HTN * ACE/ARBS great TXMT HTN and reduce risk for diabetic neprhoparthy, even in people that aren't HTN * cardiovascular disease

Answer 25

* Nodular lesions → large wods of glycocylated proteins * Loops have degenerated → become large loop * Problems: (2) * **decrease** surface area for filtration and GFR will fall * **increase** radius → more likely to rupture * Pressure increase in large capillary → cause glomerular membrane/capillary to rupture → bleed → clot → turn to fibrin caps (#4 pic) * Fibrin caps → **increase** SA loss * Result → #3 pic * Small amount of glomerulus left with functional capillaries * Large wods of protein (where mesangial cells were) * Large loops (microaneurysma) ~microaneurysms → leak * ¯decrease GFR * ****increase **Protein in urine**

Answer 26

* Inability to feel pain in foot (diabetic neuropathy) * **decrease** BF to lower extremities → ¯**decrease** immune response to infection * **Peripheral neuropathy** * causes either pain or loss of feeling in the toes, feet, legs, hands, and arms (schwann cell degeneration) * “**diabetic foot**” * Blisters and sores appear on numb areas of foot → pressure or injury goes unnoticed. * Not tx injuries promplty→ infection may spread to the bone → lead to amputation * **Autonomic neuropathy** * Changes: * digestion, bowel and bladder function, **sexual response**, and perspiration. * Affect nerves serving heart and control BP * **Focal neuropathy** * results in sudden weakness of one nerve, or a group of nerves, causing muscle weakness or pain. * Any nerve in the body may be affected. * Ex: Schwann cells innervate the lower neurons of neuromusclar junction * Repeated insult → paralysis Start: Numbness/tingling → progresses…

Answer 27

* Diabetics have accelerated atherosclerosis (extensive and involve peripheral vasculature) * Predisopose to complication of gangrene → amputation