Week 9 Flashcards
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)
