Week 9 Flashcards
(28 cards)
Type 1 (insulin-dependent / Juvenile onset)
Due to complete lack of insulin production
– Beta cells of pancreas destroyed by autoimmune rxn,
triggered by a viral infection
Type 2 (insulin-resistant)
Insulin levels normal or elevated
– Insufficient functional insulin receptors
– In later stages, pancreas may fail, insulin levels fall
– Frequently related to obesity & sedentary lifestyle
Insulin, glucose
and the liver
Liver stores excess glucose as a polymer (glycogen) for later use/release • Insulin is used to signal plentiful blood glucose – Normally, insulin triggers many tissues to use glucose up • Muscle can use glucose or fats, can store some glucose as glycogen – Brain, RBCs are dependent on glucose (always) – Insulin is a protein hormone • Glucagon (another hormone) signals low glucose
hyperglycemia
Short term: can lead to frequent urination,
increased thirst, blurred vision, fatigue,
headache
• More severe: ketoacidosis, diabetic coma
• Long-term
– Increased MI, stroke risk
– diabetic retinopathy/blindness
– Poor circulation, poor wound healing, neuropathy
– Glycated proteins in blood
Glycated hemoglobin (Hb1Ac)
• measures long-term average blood sugar
levels over 3 months
– high levels (>5.5%) indicate chronic
hyperglycemia, diabetes
– Higher levels (>8%) indicate poorly controlled
diabetes
– Some clinical trials indicate Hb1Ac <7% in
diabetics is linked to hypoglycemic episodes
Hypoglycemia
Headache, fatigue, dysphoria
– Rarely: seizures, unconsciousness
• Glycemic balance greatly
influenced by diet, exercise
• Also affected in diabetic patients by insulin
injections, other drugs
– Cannot match continuous physiological control
• Insulin pumps allow continuous insulin infusion,
frequent adjustment of levels
– Expensive, take a lot of patient motivation to use
effectively (calorie counting, manual adjustment)
Insulin injections
Usually done sc
– in thigh, abdomen, upper arm
• Absorption rates may vary between sites
– Insulin cannot be taken orally (protein, gets digested)
• Local lipohypertrophy (common side-effect)
– Stimulates local uptake of glucose by neighboring
adipocytes & conversion of glucose into fat
• Insulin shots have imprecise, see-saw effects
– Insulin is available in short, intermediate & long-acting
forms
Short-acting “regular” insulin
Humulin R (or Novolin R)
– Clear liquid
• Onset ½ hr, peak effect in 2-5 hours
– Delay while sc injection diffuses into bloodstream
– Insulin tends to aggregate into inactive dimers/hexamers
• in concentrated solution; dilution slowly reactivates these
• Lispro (Humalog)
– Engineered variant of insulin with two amino acids (lysine
and proline) swapped vs human insulin
– does not aggregate: faster onset, faster degradation
– Inject just before a meal, or to treat hyperglycemic crisis
Intermediate-acting Insulin
Cloudy suspension of tiny insulin crystals
– onset in 1-4 hours, peak levels of insulin in the blood in 6-12 hours
– Made by precipitating insulin with another small protein,
protamine
– NPH (“Neutral Protamine Hagendorn”)
• Humulin N (& Novolin N)
• Combination drug: Humulin 70/30 (& Novolin 70/30)
– Short acting 30%, immediate glucose control before meal
– NPH 70% for baseline glucose control for 6-8h
glargine (Lantus)
Engineered “long-acting” form of insulin
• Can be used along with Lispro for post-prandial
blood glucose control
• Despite ads, many people take it bid
– NPH is bid also
• Regardless of combination, most patients often
experience hyper/hypo-glycemic periods
– More frequent injections less convenient, but better
• Reduced long-term side-effects, too (eg neuropathy)
Type 1/2 revisited
Type 1 diabetes is treated by insulin injections
• Type 2 diabetes can require insulin injections,
but other, oral medications are preferred
– These drugs can increase insulin sensitivity, or
increase natural insulin production
– Rigorous low-sugar diet and regular exercise can
control blood sugar in early-stage type 2 diabetics
• Often unsuccessful due to patient motivation—it’s hard!
glipizide (Glucotrol)
Oral medication
• increases insulin release from beta cells,
promoting uptake of blood sugar
– Often loses efficacy as disease progresses
• may need insulin injections, higher insulin levels
– Can cause increased appetite and weight gain
• Patients are often already overweight
• Raising insulin levels manages symptoms, but may
aggravate the underlying problem: insulin resistance
metformin (Glucophage)
Most common oral drug for type 2 diabetes – generic versions available • Increases sensitivity of liver (and muscle) receptors for glucose, decreases liver production of glucose • Does not cause hypoglycemia, may cause initial weight loss (usually regained later)
Glitazone drugs
pioglitazone (Actos) [& rosiglitazone (Avandia)]
– available generic
• increase sensitivity of insulin receptors
primarily in the muscle and adipocytes
– More uptake of glucose into those tissues
– Not in liver (main glucose organ) but still good
• Possible increased risk of heart failure, MI have
reduced sales
– FDA panel conflict of interest controversy, lawsuits
GLP-1 is an Incretin:
Incretins: Natural small proteins /hormones – Similar to glucagon & insulin Stimulates beta cells of pancreas to release insulin • Inhibits alpha cells of pancreas from releasing glucagon • Slows stomach emptying into duodenum – Also causes some nausea – Weight loss can result • Very short t ½ (under 20 minutes)
GLP-1 receptor agonists
mimic its function
Most are modified versions of GLP-1
– Proteins, so must be injected to work
– liraglutide (Victoza) daily injection
• Also approved in a higher dose as Saxenda, for weight loss
– Dulaglutide (Trulicity) 1x per week injection
• sitagliptin (Januvia) is an small molecule that inhibits
inactivation of natural GLP-1
– Oral drug, 1x daily
• FDA warnings: possible pancreatitis, thyroid cancer?
• Typically not typically first line drugs
– May be added along with metformin
Afrezza is an inhaled medication that delivers a
short-acting form of insulin
GLP-1 receptor agonists work by
stimulating beta cells, inhibiting alpha cells, and slowing stomach emptying into the duodenum
Metformin (Glucophage) works by
Increasing the sensitivity of insulin receptors, primarily in the liver (also in muscle)
Glitazone drugs like pioglitazone (Actos) work by
Increasing the sensitivity of insulin receptors, primarily in muscle and adipocytes
Humulin N and Novolin N are both
Intermediate-acting forms of insulin, to provide stable basal levels of insulin in the blood
NOT Short-acting forms of insulin, for injection immediately prior to a meal
dulaglutide (Trulicity) has this advantage over other incretin-related diabetes medications
It is a once-per week injection
Type 2 diabetes results from:
insufficient functional insulin receptors, due to being overweight and sedentary
Local lipohypertrophy results from
Increased conversion of glucose into fat, from repeat injections of insulin at the same site
