Exam 1: Diabetes Flashcards
Diabetes Mellitus vs Diabetes Insipidus
Diabetes Mellitus - Disorder in blood glucose regulation
Diabetes Insipidus - Disorder in ADH regulation (regulation of water)
Exocrine VS Endocrine
Exocrine - secretion of a substance out thru a duct
Endocrine - secretion of a substance directly into bloodstream
Pancreas Tissue
- both exocrine and endocrine
- composed of two tissue type: Acini (exo) & Islet of Langerhans (endo)
Pancreas function
Exocrine - Synthesis and release of Acini
ex: Digestive enzymes (amylase, protease, lipase) and sodium bicarbonate
Endocrine - synthesis and release of hormones by specialized cells in Islets of Langerhans
ex: Regulate glucose - insulin (beta cells and amylin) / Glucagon (alpha cells) / Somatostatin (delta cells)
Pancreatic Hormones
Insulin - Beta cell - decrease blood glucose by allowing it to enter cells (uptake into cell)
Glucagon - Alpha cell - increase release of glucose from the liver into blood
Somatostatin - Delta cell - decrease gastro activity after meal - extends time in which food is absorbed so blood glucose doesn’t rise too quickly.
Maintenance of Blood Glucose: After a meal
After a meal: Blood glucose rises - insulin secreted
Glycogenesis: 2/3 of glucose stored in liver as glycogen, 1/3 used metabolic activity
Lipogenesis: when tissues are saturated with glycogen, glucose converted to fatty acids and stored as triglycerides in fat cells
Maintenance of Blood Glucose: Between Meals
Liver releases glucose to maintain blood glucose within normal limits
Glycogenolysis: glycogen broken down to release glucose
Gluconeogenesis - synthesis of glucose from amino acids, glycerol and lactic acid
Potassium uptake by cells
GIK mechanism explanation:
When insulin binds to cell - allows for glucose to enter cell, K+ enters with glucose. Therefore, with insulin secretion, more K+ enters cells
When potassium is too high, we can inject insulin to lower K+ levels in blood to REDUCE catabolism on muscles.
High potassium can cause arrhythmia
Hypoglycemia
low blood glucose (too much insulin) coma->death
Hyperglycemia
high blood glucose (too little insulin) polydipsia (thist) polyphagia (hungry) polyuria (too much urine)
Glucagon
secreted by alpha cells of pancreas (opposite of insulin) increases blood sugar.
acts primarily in liver - stimulates glycogenolysis and gluconeogenesis
Catecholamine and glucose
Epinephrine and norepinephrine: Fight or flights.
They mobilize glucose from glycogen stores during stress response
inhibit insulin
keeps blood sugar high/ Brain needs straight glucose to function
Growth Hormone and glucose
- Helps regulate/ maintain metabolic functions (from hypothalamus -> anterior pituitary)
- Antagonizes effects of insulin
- decreases cellular uptake and use of glucose (increases blood glucose) therefore stimulates more insulin secretion
- becomes cyclic process if prolonged can contribute to insulin resistance (can lead to diabetes and acromegaly/ giantism in youth)
Glucortocoid hormones
- Cortisol is main glucocorticoid (adrenal cortex)
- Regulate metabolism of glucose during stress response
- Can raise blood glucose significantly during all types of stress (physical, emotional ect)
- also released as a result of hypoglycemia
Gut Hormones (GLP 1 & GIP)
GLP 1 & GIP - mimic the action of somatostatin.
Incretin hormones - cause increase in insulin production in beta cells / messengers btwn GI tract and pancreas
GLP-1 decreases rate of digestion
GLP-1 (glucagon-like peptide-1) - release in small bowel
GIP (glucose dependent insulinotropic polypeptide) - released in jejunum
Amylin
Similar to somatostatin in mimic of actions.
Released along with insulin from beta cells
Same effects as GLP-1: Decreases glucagon ->which decreases liver glucose production
slows rate food empties stomach
Diabetes
Disorder of carbohydrates, protein and fat metabolism - “the running through of sugar”
many factors for cause
absolutely (type 1) or relative insulin deficiency
Insulin resistance, cells cannot take up insulin as well. can be exo or endo
Diabetic Comorbidities
For children and adolescents with T1D
nephropathy hypertnesion dyslipidemia celiac disease hypothyroidism
Types of diabetes
type 1 - absolute insulin deficiency
type 1.5 - LADA
type 2 - insulin sensitivity/ secretion deficiency/ inappropriate gluconeogenesis (higher genetic risk vs type 1)
GDM - gestional diabetes (within pregnancy)
Type 1 Manifestations
Hyperglycemia & Glucosuria (sugar in urine)
Three P’s: Polyuria, Polydispsia, polyphagia
Weight loss and increased appetite blurred vision fatigue paresthesia skin infections
Glucosuria
When blood glucose is high - Glomerulus not able to filter high glucose, capacity of proximal convoluted tubule is exceeded. Glucose stays in urine, this exerts osmotic pressure, pulls fluid into filtrate, urine is watered down. Results in cellular dehydration and polyuria.
Pathogenesis of Type 2
- Genetic predispositions
- Environmental factors
-Central Obesity (visceral fat)
(causes free fatty acids = decrease in insulin production, alpha and beta cells get “burnt out”)
- Increase in hepatic glucose output in pancreas (but cells not getting it)
- Increased absorption of glucose in gut (cells still not getting enough)
Manifestations of type 2
Hyperglycemia and Glucosuria
- symptoms appear insidiously (slower)
- only 2 P’s: Polyuria and Polydipsia (both occurs slowly)
- vision problems, fatigue
- Chronic skin infections
Diagnostics tests for diabetes
- Random/casual plasma glucose test (not fasting) and not informative, unless extreme
- Fasting plasma glucose (8-12hrs)
- 2hr plasama glucose - given glucose, then checking sugar after 2 hrs (below 140)
- oral glucose tolerance test, check every hour to watch blood sugar go up then down (done for 3 hrs usually on pregnant women for GD)
Diagnostic Criteria
A1C > or = 6.5%
FPG > or = 126 mg/dl
2Hr plasma glucose > or = 200mg/dl
should all be repeated for proper diagnosis
Glycosylated Hemoglobin (HgA1C)
Glycohemoglobin = blood glucose bound to hemoglobin in RBC
this measure amount bound to RBC and is directly proportional to glucose exposure over 120 lifespan of RBC
oxygen carrying ability of RBC
reflected glucose levels over 2-3 months
7% or less is target goal
Ex: A1C of 6% = 135mg/dl
Urine Glucose & Urine Ketones
This test only reflects urine glucose levels
- influenced by renal threshold for glucose, fluid intake and urine concentration
- Not a recommended measurement for glucose levels
Urine Ketones: remains important part of monitoring diabetic control, especially for type 1 prone to DKA (an early sign, if you have high blood sugar)
C-Peptide Assay
- This test is an indicator for pancreatic beta cell function
- C-peptide is connecting peptide (with insulin production) sections A&B
- Proinsulin (inactive form of insulin) is that is connected with C-peptide (A&B)
- C-peptide breaks apart and gives active insulin (C-peptide stays in blood)
- C-Peptide indicates type of diabetes ( no c peptide, then type 1)
C-peptide Assay Pt. 2
-Glucagon is given and C-peptide is measure before and after glucagon stimulation.
This test delineates type 1 from type 2 (type 2 more c peptide)
Also monitors recovery after excision of insulinoma (rising c peptide levels due to pancreas tumor, over production of c-peptide)
Categories of increased risk for diabetes
- Impaired Fasting Glucose (IFG)
- Impaired Glucose Tolerance (IGT)
- A1C 5.7-6.4% (considered pre-diabetes)
All also risk factors for cardiovascular disease
Testing Criteria for Asymptomatic adults
- every 3 years after age 45, regardless of weight
- overweight or obease adults and 1 or more risk factors
- relative with diabetes
- high risk ethnicity
- hypertension
- dyslipidemia
- cardiovascular disease
- Hx of prediabetes
- insulin resistance (sever obesity)
Testing Criteria for Asymptomatic children
- every 3 years starting at 10 or onset of puberty
- BMI >85th percent or >120% of ideal height AND 1 risk factor
- relative with diabetes
- high risk ethnicity
- insulin resistance (sever obesity)
- if mother had Gestational diabetes
Metabolic Syndrome or “Syndrome X”
- central obesity “apple shaped body”
- Fasting triglycerides > 150mg/dl
-Low HDL cholesterol:
Men <40mg/dl
Women <50mg/dl
- BP >130/85
- Fasting glucose >110mg/dl
increased risk of atherosclerosis, stroke, heart disease, early death
Gestational Diabetes
- 7% of pregnancies
-50% with:
family hx
glycosuria
stillbirth
fetal anomalites
advanced maternal age
Risk factors:
- increased complications
- mortality
- fetal abnormalities
- hypoglycemia
- polycythemia
- hyperbilirubinemia
Treatment:
- blood glucose monitoring
- nutritional guidance
Risk for Gestational Diabetes
- testing starts at first prenatal visit
- women with clinical characteristics consistent with high risk of GDM (obesity, fam history) should do glucose testing
- If no GDM, should be retested btwn 24 and 28 weeks
- Avg risk women should get tested at 24-28 weeks
Diabetic Diet
- Same healthy goals as healthy people
- achievement optimal lipid levels
- Understand the glycemic index, diabetics need to stay away from high GI foods
- avoid simple carbs (white flour and sugar)
Nutrition therapy: Type 1
- Adjusted eating schedule with monitoring of blood glucose before and after meals
- calculate amount of carbs they are eating per meal and give insulin based on how many carbs
- each diabetic has insulin ratio to carbs
Nutrition therapy: Type 2
- Hypo-caloric diets and weight loss are important
- individually based diets
- spacing of meals and spreading of carbs throughout the day
- EAT HEALTHY
Treatment: Exercise
- Improves glucose tolerance
- need to be watchful for hypoglycemia
Insulin treatment
- insulin is destroyed in GI track (never PO, always SubQ injection)
- Categorized by onset, peak and duration
- rapid, short, intermediate and long acting
Sites of action of Oral Antidiabetic agents (Type 2)
a-glucoside inhibitors (decrease glucose absorption)
Biguanides and Thiazolidinediones (decrease hepatic glucose output)
Sulfonylureas and meglitinides (increase insulin secretion)
Thiazolidinediones and Biguanides (increase peripheral glucose uptake)
Pancreatic transplant
- reserved for health people
- can restore carb metabolism to normal rates
- can improve quality of life
- current research: transplant of islet cells
Acute Complications of Diabetes
- DKA (Diabetic ketoacidosis) - occurs primarily with Type 1
- HHNK (hyperosmolar hyperglycemia non ketotic syndrome) Primarily with type 2 diabetes. Blood has lots of glucose, but no ketones.
- Somogyi Effect
- Dawn Phenomenon
- Hypoglycemia
Hyperglycemia
- High Blood Sugar (high blood osmolarity)
- Body tried to dilute blood, shifts water from cells and cells get dehydrated
- too much sugar exceed renal threshold, osmotic dieresis, body dehydration
- Increased thirst and heart rate. Less circulating volume, warm dry skin
DKA (Diabetic ketoacidosis)
- Not making insulin, or not enough. Most typical in type 1
- Acute, life threatening and dramatic
- Onset, less than a day.
- Polyuria and polydipsia. Nausea, vomiting, high high blood sugar
Precipitating factors:
- failure to take insulin
- physical and emotional stressors
- pregnancy
- insulin pump failure
DKA (Diabetic ketoacidosis)
Pathophysiology
- inadequate insulin, no cells take up glucose properly, high Blood sugar
- liver tries to help, raising blood glucose more
- renal threshold met, excess glucose excreted in urine with water leading to dehydration
- protein and fat broken down in emergency metabolism
- ketones produced as byproduct, creating acidic blood
- Highly osmolar blood. you feel like shit.
- tissue breakdown continues, more ketosis, more acidosis, shock, coma and death
DKA continued:
- Hyperosmolar cells, dehydration
- Water loss exceed glucose and electrolyte loss
- decrease profusion to kidneys, they shut down, deadly cycle
- blood glucose increase over and over
DKA manifestations
Physical:
- Dehydration
- Tachy
- low BP
- ketosis
- fruity breath
- fatigued
- stupor
- deep irregular breathing
Lab results:
- 250-600 mg/dl blood glucose
- ketones in blood and urine
- K+ high or low depending, but no K+ is very bad
- decrease bicarbonate
- ketonemia and ketonuria
- Increased BUN
Cell starvation
no glucose for ATP production
breakdown of far/protein stores
liver produces ketones
ketoacidosis sets in
DKA Treatment
- Fluid replacement
- IV insulin
- K+ replacement
- Bicarbonate if pH <7.2 but cautiously bc of CNS acidosis
- 5% dextrose added when glucose <250 (avoid massive fluid shifts)
- monitor vitals and labs
HHNK
- happens with type 2
- relative insulin insufficiency
- more insidious (happens slowly) 50% mortality rate
- cannot develop DKA
-Precipitating factors: stress, insulin intolerance, hemodialysis, tube feeding -elderly with renal insufficency -drugs (steroids, diuretics) -infection
HHNK Manifestation
- Worse dehydration than DKA
- Extreme thirst
Neurologic symptoms:
- coma
- babinski refleck abnormal
- paralysis
- sensory impairment
- hyperthermia
- hemianopia
- seizures
Lab results:
- High serum glucose (higher than DKA)
- NO ketosis
- lacticacidosis sometimes
- blood pH still relatively normal
HHNK treatment and complications
-restore intravascular volume with normal saline
- IV insulin
- K+ replacement
Complications:
- Thrombosis (from hyperosmolar blood that is more sticky)
- embolus
- pneumonia
- ARDS
Insulin shock (AKA Hypoglycemia)
- Glucose lower that 50mg/dl
ANS response:
-parasympathetic: hunger, nausea, hypotension, bradycardia
-sympathetic: anxiety, sweating, vasconstriction, tachycardia
Neuroglyconpenia: Altered cerebral function d/t cell starvation
- headaches
- coma
- slurred speech
At risk:
- Beta blockers can block symptoms
- error in insulin dose
- increase exercise
Treat:
with carbs! snacks ect…
for emergency: Glucagon injection
Somogyi Effect
- Rebound effect in type 1 and type 2.
- too much insulin, results in hyperglycemia down the road.
- Overcorrection by the body.
- Unrecognized hypoglycemia at night, the body responds, hyperglycemia in the AM. and cycle continues
- Need to restructure doses.
Dawn Phenomenon
- Pre-dawn hyperglycemia without antecedent hypoglycemia (more common in type 1)
- due to changes in circadian rhythms
- liver reacts to cortisol in AM release
- GH a possible factor
- Usually mild
Tissues MOST affected by elevated blood glucose
- Body cells not dependent on insulin to use glucose, most affected by elevated glucose levels:
- RBCs
- Glomerular cells
- Central and peripheral nerves
- blood vessel cells
Long Term Damage of Diabetes
-Eyes
-Kidney
-Nerves
-Heart and Blood Vessels
(cardiac disease, hypertension, atherosclerosis)
Chronic Complications of Diabetes: Macrovascular
Hyperglycemia - Metabolic injury to large vessels:
Heart: Coronary artery disease, MI, CHF
Brain: Cerebrovascular disease, TIA, CVA, cognitive impairment
Extremities: Ulceration, Gangrene, Amputation
Chronic Complications of Diabetes: Microvascular
Hyperglycemia:
Eye: Retinopathy, cataract, glaucoma, blidness
Kidney: Nephropathy, microalbuminuria, gross albumininuria, kidney failure
Nerves: Neuropathy, peripheral, autonomic, amputation
Classification of Peripheral Neuropathies
SOMATIC: polyneuropathies
- paresthesias
- impaired sensation
- diminished reflexes
Mononeuropathies
-involvement of mixed nerve trunk, motor nerves affects
Amyotrophy
muscles weakness and wasting
AUTONOMIC: impaired vasomotor function -postural hypotension -impaired GI function -Cranial nerve involvement
Cardiovascular Disease
- Major cause of death for diabetics
- Accelerated atherogenesis
- onset earlier age
- increased total cholesterol
- abnormal platelets
Management:
-control HTN, quit smoking, weight loss, diet, exercise
Eye Disease
Leading cause in blindness -Retinopathy
-Glaucoma, cataracts, blurred vision, takes 2 months to have vision return to normal after diagnosis
Nephropathy
- Not all diabetics develop this
- HTN and Smoking increase risk
- Kidney gets bigger and GFR increases
- Kidney tubules get leaky, GFR rate decreases due to spilling protein. Avoid things hard on kidney.
- Dialysis or transplant sometimes needed
Neuropathy
- most common disabler
- not cause of death, but decrease in quality of life
- gangrene and underlying infection
- nerve damage means dont feel wounds! Check your feet and extremities regularly
