Term
|
Definition
Insulin- short and long acting
Biguanides- metformin
Sulfonylureas/meglitinides- Glipizide, glyburide, glimepiride, repaglinide, nateglinide
GLP-1 ttherapies- exanetide, sitagliptin, saxagliptin
Thiazolidinediones- rosiglitazone, pioglitazone
Amylin analogue- pramlintide
α-glycosidase inhibitors- acarbose |
|
|
Term
|
Definition
Not a single disease entity, “group of metabolic disorders sharing the common underlying feature of hyperglycemia”
- Type 1 (insulin-dependent diabetes mellitus/IDDM)
- Type 2 (non insulin-dependent diabetes mellitus/NIDDM) |
|
|
Term
| Key Concepts of Diabetes Mellitus |
|
Definition
DM: disorder of carbohydrates, fat and protein metabolism caused by impaired cell synthesis or release of insulin, or by the inability of tissues to use glucose
Type 1 DM results from loss of cell function and absolute insulin deficiency (10% of cases)
Type 2 DM results from impaired ability of tissues to use insulin (insulin resistance) and an inadequate secretory response by cells (80-90% of cases) |
|
|
Term
| Clinical Features of DM Type 1 |
|
Definition
Develops during childhood or early adulthood
Insidious or rapid onset (patients symptomatic)
Polyuria (excessive urination due to excess sugar in urine; osmotic diuresis)
Polydipsia (excessive thirst; secondary to dehydration)
Polyphagia (excessive eating; secondary to low cellular stores of carbohydrates, fat and proteins; no insulin driven uptake) |
|
|
Term
| Clinical Features of DM Type 2 |
|
Definition
Increasingly more common in younger individuals with obesity
20-40% of patients have an affected 1st degree relative (60-80% concordance in monozygotic twins)
80% of patients are overweight
Exercise increases number and sensitivity of insulin receptors |
|
|
Term
|
Definition
16 million in US
Half undiagnosed
800,000 new diagnoses per year in US
54,000 die each year
Leading cause
End-stage renal disease
Adult onset blindness
Non-traumatic lower extremity amputation
Cardiovascular complications |
|
|
Term
|
Definition
Glycation is the nonenzymatic attachment of glucose to protein molecules
Also known as the browning reaction, it is what “crisps” the outside of a glazed ham, or turns the bread crust brown
Because the half life of red blood cells is several weeks, the degree of glycation of the hemoglobin molecules is a more integrated measure of blood glucose control than any single instantaneous measure of glucose.
Values below 5.7 are normal |
|
|
Term
| Endogenously Increase Insulin Levels |
|
Definition
Directly stimulate beta cell secretion
- Increase incretin levels (GLP-1)
- Increase amylin levels |
|
|
Term
| Exogenously Increase Insulin Levels |
|
Definition
|
|
Term
| Improve insulin sensitivity |
|
Definition
Decrease hepatic glucose production
Improve insulin sensitivity in muscle and adipose tissue |
|
|
Term
| Pharmacologic Treatment of Physiologic Problems in Diabetes |
|
Definition
A: Increase Insulin Levels
B: Improve insulin sensitivity
C: Delay carbohydrate absorption
D. Other (not known) mechanisms |
|
|
Term
| Mechanisms of metformin/ biguanides action |
|
Definition
Increases activity of AMP kinase in liver
Results in decreased production of glucose, fatty acids and cholesterol.
Increases glucose uptake in muscle
Best used for insulin resistant obese type 2 diabetics. |
|
|
Term
| Biguanides: Metformin effects in diabetics |
|
Definition
Reduces glucose levels without affecting insulin secretion
No risk of hypoglycemia due to excess insulin action
Often results in both weight loss and decreases in serum lipids
Adverse events include mild GI tract distress (minimized by gradually increasing dose) and lactic acidosis in those with hepatic, renol or respiratory insufficiency. |
|
|
Term
| Insulin Secretagogues: Sulfonylureas and Meglitinides |
|
Definition
Act by inhibiting the K-ATP channel. This depolarizes the beta cell and leads to increased insulin release.
Used since the 1950s
Can results in hypoglycemia if excess insulin released
Causes weight gain. Best for nonobese patients.
Can cause “sulfa” rash |
|
|
Term
| Sulfonylureas and Metformin Effects are |
|
Definition
|
|
Term
| Glucagon Like Peptide (GLP-1 aka incretin) |
|
Definition
GLP-1 released from the GI tract with meals
Augments insulin release; inhibits glucagon release
Can inject direct agonist (exenatide) or block degradation by protease DPP-4 inhibitors (sitagliptin; saxagliptin; oral administration)
Minimal risk of hypoglycemia |
|
|
Term
|
Definition
PPARgamma activators; Rosiglitazone, Pioglitazone
PPAR-gamma is a transcription factor
Makes cells more sensitive to insulin
Redirects fatty acids from liver/muscle to adipose tissue; decreases plasma triglycerides
Reduces inflammation
Adverse events are weight gain, edema, increased cardiovascular risk |
|
|
Term
|
Definition
Pramlintide
Amylin is released from beta cells with insulin
Slow gastric emptying (delays glucose peak) and decreases glucose release from liver (suppresses glucagon release)
Deficient in both type I and II diabetes
Decreases appetite through CNS effects
Injected subcutaneously pre-prandially
Significant GI tract adverse events. |
|
|
Term
| Inhibition of Glucose Absorption |
|
Definition
Blockade of α-glucosidase by acarbose
Decreases rate of starch breakdown in GI tract
Delays glucose absorption
Take with meal
Often combined with other drugs
Diminishes peak glucose and peak insulin |
|
|
Term
|
Definition
May lower triglycerides
No effects on weight
Can cause bloating, flatulance. More sugar for intestinal flora to digest.
Contraindicated for inflammatory bowel disease |
|
|
Term
| Two categories of Insulin |
|
Definition
| Basal and Prandial (Fast acting) |
|
|
Term
| Biguanides: Metformin effects in diabetics |
|
Definition
Reduces glucose levels without affecting insulin secretion
No risk of hypoglycemia due to excess insulin action
Often results in both weight loss and decreases in serum lipids
Adverse events include mild GI tract distress (minimized by gradually increasing dose) and lactic acidosis in those with hepatic, renol or respiratory insufficiency. |
|
|
Term
| Insulin Secretagogues: Sulfonylureas and Meglitinides |
|
Definition
Act by inhibiting the K-ATP channel. This depolarizes the beta cell and leads to increased insulin release.
Used since the 1950s
Can results in hypoglycemia if excess insulin released
Causes weight gain. Best for nonobese patients.
Can cause “sulfa” rash |
|
|
Term
| Mechanisms of metformin/ biguanides action |
|
Definition
Increases activity of AMP kinase in liver
Results in decreased production of glucose, fatty acids and cholesterol.
Increases glucose uptake in muscle
Best used for insulin resistant obese type 2 diabetics. |
|
|
Term
| Glucagon Like Peptide (GLP-1 aka incretin) |
|
Definition
GLP-1 released from the GI tract with meals
Augments insulin release; inhibits glucagon release
Can inject direct agonist (exenatide) or block degradation by protease DPP-4 inhibitors (sitagliptin; saxagliptin; oral administration)
Minimal risk of hypoglycemia |
|
|
Term
|
Definition
PPARgamma activators; Rosiglitazone, Pioglitazone
PPAR-gamma is a transcription factor
Makes cells more sensitive to insulin
Redirects fatty acids from liver/muscle to adipose tissue; decreases plasma triglycerides
Reduces inflammation
Adverse events are weight gain, edema, increased cardiovascular risk |
|
|
Term
|
Definition
Pramlintide
Amylin is released from beta cells with insulin
Slow gastric emptying (delays glucose peak) and decreases glucose release from liver (suppresses glucagon release)
Deficient in both type I and II diabetes
Decreases appetite through CNS effects
Injected subcutaneously pre-prandially
Significant GI tract adverse events. |
|
|
Term
| Inhibition of Glucose Absorption |
|
Definition
Blockade of α-glucosidase by acarbose
Decreases rate of starch breakdown in GI tract
Delays glucose absorption
Take with meal
Often combined with other drugs
Diminishes peak glucose and peak insulin |
|
|
Term
|
Definition
May lower triglycerides
No effects on weight
Can cause bloating, flatulance. More sugar for intestinal flora to digest.
Contraindicated for inflammatory bowel disease |
|
|
