Metabolism & Diabetes Flashcards
Normal blood glucose levels
4-7 mmol/L
Glycogen
long-term storage of glucose
Where is glycogen produced
skeletal muscle
liver
Glycogenolysis
breakdown of glycogen to glucose in the liver
maintain blood glucose livers between meals (fasting state)
Glycogenesis
conversion of glucose –> glycogen
Gluconeogenesis
glucose synthesis from non-carbohydrate sources (fatty acids & amino acids)
Glycolysis
breakdown of glucose –> ATP production
Hypoglycemia definition
abnormally low blood glucose levels
<4.0 mmol/L
Hyperglycemia definition
abnormally high blood glucose levels
>10.0 mmol/L
Hypoglycemia symptoms
early: tremors mood changes (irritability, anxiety) nausea hunger cool, clammy skin weakness, fatigue dizziness, vision changes tachycardia
late: decreased LOC confusion, inattention seizures behavior changes, lack of coordination
Hyperglycemia symptoms
hunger thirst dehydration fatigue kussmaul respirations reduced weight poor wound healing polyuria blurred vision fatigue (high blood glucose, low cellular glucose) paresthesia
Polyphagia
increased hunger
Polydipsia
increased thirst
Blood glucose tests
glycated hemoglobin (HgbA1C) random blood glucose test oral glucose tolerance test fasting glucose test (>8 hours) capillary blood glucose monitoring (self-monitoring)
Glycated hemoglobin
glucose adheres to hemoglobin molecules
used to measure average blood glucose levels over a 3 month period
Lifespan of RBC’s
120 days
Insulin
hormone produced by pancreatic B cells increases glycolysis increases glycogenesis increases lipogenesis increases protein synthesis
Glucagon
hormone produced by pancreatic alpha cells increases glycogenolysis increase gluconeogenesis increase lipolysis increase ketogenesis
Counterregulatory hormones
sympathetic catecholamines - epinephrine, norepinephrine
cortisol
glucagon
growth hormone
Diabetes definition
metabolic disorder resulting in body’s inability to blood glucose levels. can be caused by insulin deficiency or resistance
Type 1 Diabetes
10% of cases early onset absolute insulin deficiency usually requires insulin therapy results from autoimmune destruction of pancreatic b cells
Type 2 Diabetes
90% of cases
adult onset
relative insulin deficiency + insulin resistance
can be managed with lifestyle changes, pharmacologic treatment
eventually may require insulin therapy
Insulin resistance
cells are unable to respond to insulin leading to impaired glucose regulation
can be caused by decreased # of insulin receptors or glucose transporters
Causes of Hypoglycemia
poor nutrition medication (too much insulin) insulin antagonist deficiency increased exercise stress (mental, physical, illness)
Ketogenesis
free fatty acids are converted into ketones by the liver
distributed in the bloodstream to be used as an alternate energy source by body cells
Diabetes complications
endothelial injury –> atherosclerosis
nephropathy
peripheral neuropathy
perfusion issues –> decreased wound healing
development of chronic conditions (stroke, hypertension, hyperlipidemia)
retinopathy
Diabetes & Vascular changes
glucose is inflammatory –> damage endothelium & basement membrane
cause stiffening/thickening of blood vessels –> reduced compliance
Diabetic Ketoacidosis
hyperglycemic state >13.8 mmol/L more common with type-1 diabetes low serum bicarbonate low arterial pH urine/serum ketones
Types of diabetes
Type 1
Type 2
Gestational
Other
Ethnic groups at risk of T2DM
Indigenous
African
Hispanic/Latino
Asian
Modifiable Risk Factors
Diet (high fat, high calorie) Weight Exercise Chronic conditions (HTN, malabsorption, vitamin D deficiency) Chronic stress Medication
Non-modifiable risk factors
Age
Family history/genetics
Acanthosis nigricans
velvety darkening of skin
commonly found in neck, axilla, groin folds
Diagnostic tests
blood glucose tests antibody testing lipid analysis renal function CRP protein
15/15 Rule
used to treat hypoglycemia
15 grabs of quick-acting carbohydrate every 15 min
severe hypoglycemia = 30 g carb
Types of Insulin
short-acting
intermediate
long-term
rapid-acting
Macronutrients
large organic molecules
carbohydrates
proteins
fats
Micronutrients
vitamins & minerals
act as enzyme co-factors
Major Minerals
Calcium Phosphorous Magnesium Sodium Potassium Chloride
Older Adult Malnutrition RF
impaired chewing (dentures, muscle weakness) decreased saliva production, dysphagia decreased sense of taste/appetite elongated esophagus impaired swallowing d/t muscular atrophy decreased metabolic function of liver, pancreas, gallbladder chronic conditions medications socioeconomic status
Underweight BMI
<18.5
Overweight BMI
25-29.9
Obesity Class I BMI
30-34.9
Obesity Class II BMI
35-39.9
Obesity Class IV BMI
> 40
Protein deficiency
impaired tissue repair
decreased liver proteins (clotting factors, inflammatory proteins, plasma proteins)
Carbohydrate deficiency
weight loss due to gluconeogenesis
ketoacidosis
Fat deficiency
impaired plasma membranes
decreased steroid hormone synthesis?
Folate
important for CNS development
Carotenoids
help prevent macular degeneration
Vitamin A
important for vision
Obesity & Chronic Conditions
T2DM Coronary heart disease Hypertension Stroke Respiratory problems Sleep apnea Fatty liver disease Gallbladder disorder Asthma
Nutritional Diagnostic Tests
serum albumin & pre-albumin (low albumin = low protein intake) blood glucose tests lipid profile (total cholesterol, triglyceride)
Islet of langerhans cells
beta cells
alpha cells
delta cells
F/PP cells
Delta cells
release somatostatin
inhibits insulin/glucagon release & slows down gastric motility for adequate absorption
F/PP cell
produce pancreatic polypeptide
regulates GI secretions, liver glycogen storage, pancreatic release
Proinsulin
insulin formed in beta cells by cleaving proinsulin –>
insulin & C-peptide
Glucose cellular transport
glucose cannot cross the plasma membrane (large particle)
requires glucose transporter (protein carrier) to cross the cell membrane
Glucose transporters
GLUT-4 = skeletal & adipose tissue GLUT-2 = beta cells & liver cells GLUT-1 = loc in brain. does not require insulin activation
Sodium glucose cotransporters
SGLT-1 = small intestine SGLT-2 = renal tubule
Postprandial
following a meal
Lipase
enzyme that breaks down triglycerides –> glycerol + fatty acids
Amylin
co-secreted with insulin by beta cells
1) decrease postprandial glucagon secretion
2) promoting satiety
3) decreasing gastric emptying (slows glucose absorption)
Incretins
GI hormones released after a meal
consist of glucagon-like peptide 1 (GLP) and Gastric inhibitory peptide (GIP)
Epinephrine function
maintain blood glucose levels during stress
increase metabolism
increase glycogenolysis in liver & skeletal muscle
decrease insulin release
increase lipolysis of adipose tissue
Growth Hormone function
increase protein synthesis
increase lipolysis
decrease cellular uptake of glucose
T2DM Impaired Beta Function
1) reduced b cell mass
2) increased apoptosis, reduced regeneration
3) beta cell exhaustion (d/t hyperinsulinemia)
High FFA Complications
pancreatic beta cell dysfunction decrease glucose uptake decreased glycogen storage decreased hepatic insulin sensitivity non-alcoholic fatty liver disease
Adiponectin
hormone released by adipose tissue
increase tissue sensitivity to insulin
decreased triglyceride content
increased free fatty acid energy use
increase in adipose tissue = decreased adiponectin production
Acute Diabetic Complications
diabetic ketoacidosis
hyperglycemic hyperosmolar state (HHS)
hypoglycemia
Hyperglycemic Hyperosmolar State (HHS)
increased osmolarity of blood hyperglycemia >33.3 mmol/L shift in fluid compartments (ICF --> ECF) results in pseudohyponatremia (d/t fluid dilution) dehydration polyuria polydipsia hunger hypotension, tachycardia
DKA S/S
hyperglycemia > 13.8 mmol/L polyuria polydipsia nausea/vomiting fatigue stupor/coma abdominal pain/tenderness fruity breath hypotension, tachycardia Kussmaul breathing
DKA Treatment
increase blood volume
increase tissue perfusion
reduce blood glucose
treat acidosis, F/E imbalances
Somogyi Effect
insulin-induced hypoglycemia –> increase in counterregulatory hormones
usually occurs overnight –> hyperglycemic in the morning
Dawn Phenomenon
high fasting blood glucose between 5am-9am w/o preceding hypoglycemia
related to circadian rhythm of glucose tolerance?
Eye complications
retinopathy
glaucoma
cataracts
CNS complications
dizziness/syncope impaired sensory/motor function (d/t damage to myelin) --> increased risk for injury, foot ulcers decreased somatic sensation painful diabetic neuropathy autonomic neuropathy
Vascular complications
atherosclerosis
microangiopathy –> cerebral infarction, hemorrhage
hypertension
GI complications
impaired gastric emptying
diarrhea
constipation
GU complications
urinary retention
UTI
erectile dysfunction
Autonomic neuropathy
sympathetic/parasympathetic dysfunction
decreased vasomotor function (controls HR & smooth muscle tone)
decreased cardiac response
inability to empty bladder –> stasis, infection
impaired GI motility
sexual dysfunction
Diabetic FPG (mmol/L)
> /= to 7.0
Diabetic A1C %
> /= to 6.5%
Prediabetic A1C %
6.0-6.4
First line treatment for T2DM
Metformin
decrease risk of diabetes-rel deaths
does not cause weight gain
excreted unchanged by kidneys
Sulfonylureas Pharmacodynamics
MOA: bind to K+ channels on pancreatic B-cells
increase insulin production
increase number of insulin receptors
increase insulin receptor sensitivity
increase effect of ADH on renal cells (collecting duct)
CVD treatment for Diabetic pts
statin
acei/arb
asa
White fat
long-term storage of adipoctyes
Brown fat
fat tissue with metabolic properties
generate heat
Glucagon-like peptide 1 (GLP-1)
released by L cells in distal small intestine
1) stimulate insulin secretion (glucose dependent)
2) inhibit glucagon secretion
3) inhibit gastric emptying
4) promote satiety
5) increase insulin sensitivity
Gastric Inhibitory peptide (GIP)
aka glucose-dependent insulinotropic polypeptide
released by K cells in jejunum
1) stimulate insulin secretion (glucose dependent)
2) increase postprandial glucagon release
Factors stimulating hunger
ghrelin
low blood glucose
Factors promoting satiety
incretins (GLP-1, GIP) CCK insulin fatty meals leptin
Somatostatin
released by pancreatic delta cells
decrease insulin & glucagon release
Obesity phenotype
central, abdominal (apple)
peripheral (pear)
Basal insulin
Background insulin. Used to maintain blood glucose levels in fasting state. Longer-acting
Prandial Insulin
Shorter-acting. Used to maintain blood glucose levels in a fed state. Prevent spike in blood sugar after meals
Types of basal insulin
take effect in a few hours. longer half-life.
intermediate-acting
long-acting
Types of prandial insulin
take effect in under an hour. shorter half-life.
rapid-acting
short-acting
Intermediate Insulin PK
ex: insulin NPH
onset: 1-2 hours
peak: 5-8 hours
duration: 14-18
Long-acting Insulin PK
ex: insulin glargine
onset: up to 6 hours
peak: unknown
duration: 30 hours
Short-acting Insulin PK
ex: insulin regular (IV only), humulin R
onset: 0.5-1 hour
peak: 2-4 hours
duration: 5-8 hours
Rapid-acting Insulin PK
ex: insulin aspart, lispro
onset: 10-15 min
peak: 60-90 min
duration: 4-5 hours
Correctional insulin
insulin that is administered on an ad-hoc basis, when fasting blood glucose levels exceed clinical parameters
uses rapid-acting or short-acting insulin
used as an adjunct with basal insulin
Insulin:Glucagon ratio
hormone levels are determined in relation to one another
decreased insulin = relative increase in glucagon
increased insulin = relative decrease in glucagon
Insulin & Alcohol
alcohol increases insulin secretion and gluconeogenesis
risk factor for hypoglycemia
Basal metabolic rate
energy used to maintain body processes at rest (temperature, autonomic function, muscle tone, etc)
Energy expenditure
basal metabolism 60%
physical activity 25%
non-exercise activity 7% (ADLs)
food digestion 8%
Antidiabetic drug classes
sulfonylureas biguanides dpp-4 inhibitors thiazolidiediones sglt-2 inhibitors human amyliln incretin mimetic meglitinide GLP-1 agonist
Sulfonylureas MOA & TE
MOA: bind to K+ channels on pancreatic B cells causing depolarization –> insulin release.
increase # of insulin receptors on cell membrane. increase effect of ADH –> dilute blood glucoses by increasing water retention.
increase insulin production
decrease insulin resistance
inhibit glucose absorption from the GI tract and glycogenolysis
*targets the pancreas
Biguanide MOA & TE
MOA: acts on the liver to decrease glucose production. increases cellular uptake of glucose. decreases GI absorption of glucose. increases sensitivity to insulin.
lowers blood glucose but does not cause blood
*targets the liver
Obesity assessment
BMI (>25 overweight, >30 obese) waist circumference (measures abdominal obesity) height, weight measurements health history cardiometabolic risk age SE status blood pressure lab tests (lipid profile, blood glucose, ALT)
BMI equation
kg/height^2
Risky waist circumference
>/= 102 cm in men >/= 88 cm in women
Obesity co-morbidities
obstructive sleep apnea non-alcoholic fatty liver disease T2DM hypertension cardiovascular disease osteoarthritis GERD polycystic ovary syndrome
Obesity treatment
first line: lifestyle modifications
medications (manage chronic conditions)
bariatric surgery (extreme)
5 A’s of obesity
ask for permission to discuss weight assess risk factors/health status advise on health risks agree on realistic goals assist with appropriate resources & healthcare providers
Obesity & cardiometabolic risk assessment
blood pressure (both arms) blood glucose (A1C, fasting blood glucose) lipid panel (total cholesterol, triglycerides, LDL/HDL) ALT (nonalcoholic fatty liver disease)
Osmotic Diuresis
increased excretion in water
Drug-drug Insulin interactions
beta-blockers: can mask symptoms of hypoglycemia
corticosteroids, thyroid supplements, estrogen: may increase insulin demand
alcohol, ace-is, mao-i’s, oral hypoglycemic agents: decrease need for insulin
Drug-drug Metformin interactions
acute/chronic alcohol ingestion or iodine contrast media: increase risk of lactic acidosis
digoxin, morphine, CCBs, vancomycin: compete for elimination pathways
furosemide: may increase fx of metformin
nifedipine: increased absorption
Cardiovascular benefits of Metformin
decrease lipid profile (triglcyerides)
decrease body weight
modulate endothelial function
Drug-drug Glyburide interactions
diuretics, corticosteroids, oral contraceptives, estrogen, thyroid: may decrease fx
alcohol, androgens, clarithoycin, MAOis, NSAIDS, warfarin: may increase risk of hypoglycemia
beta-blockers: may mask symptoms of hypoglycemia
Neuroglycopenia
shortage of glucose in the brain. usually caused by hypoglycemia
Severe hypoglycemia
<2.8 mmol/L
may cause unconsciousness
Treatment for severe hypoglycemia
IV: administer D50% W
SC: glucagon
Diabetes foot care
annual foot exam daily inspection for wounds, sores, infection trim toenails ---> file sharp edges avoid going barefoot well-fitting shoes, change socks daily
