EXAM #2: TYPE DM-II Flashcards
What is the key feature underlying the pathology of DM-II?
Relative insulin deficiency
What ethnicity is DM-II most common in?
Hispanics
What are the microvascular complications of DM-II?
1) Retinopathy
2) Neuropathy
3) Nephropathy
What are the macrovascular complications of DM-II?
1) Cerebrovascular Disease
2) PVD
3) CAD
What are the criteria for the diagnosis of DM-II?
1) Sx. (P’s) of DM with any blood sugar greater than 200 mg/dL
2) Fasting blood sugar greater than 126 mg/dL on 2X OCCASIONS
3) Two-hour glucose tolerance test greater than 200 mg/dL
4) HBa1c greater than 6.5%*
*Note that this must be done in a lab using a standard assay
What is an impaired fasting glucose measurement?
100-125 mg/dL
*126+ is DM
What is an impaired glucose tolerance test?
140-199 mg/dL
*200+ is DM
What are the target organs for insulin?
- Liver
- Muscle
- Fat
What are the functions of insulin?
1) Glycogen formation
2) Protein synthesis
3) Lipid synthesis
*Generally, insulin is an anabolic hormone
Outline the sequences of pathologic changes that underlie DM-II?
1) Insulin resistance
2) Hyperinsulinemia
3) Compensated insulin resistance with normal blood sugar
4) Impaired glucose tolerance
5) Beta cell failure
Why do DM-II patients eventually require insulin?
- Beta cell failure from natural history of DM-II
- Fasting insulin decreases and patients start to need insulin around 10 years post diagnosis
What does the HbA1c correlate with?
Relative blood sugars over the course of 3 months/ 90 days
*e.g. 6.5= roughly 120-150 mg/dL
What can cause a falsely elevated HbA1c?
Hemoglobinopathy (Sickle Cell)
What can cause a falsely decreased HbA1c?
1) Recent transfusion
2) Anemia
What is the key initial treatment option for DM-II?
Lifestyle changes
What is the MOA of the alpha-glucosidase inhibitors e.g. acarbose?
- Inhibits enzymes that convert ingested carbohydrates to monosaccharides for absorption
- Decreased carbohydrate absorption from the gut
What patients are alpha-glucosidase inhibitors a good option for?
Patients with mild post-parandial hyperglycemia
What are the side effects of alpha-glucosidase inhibitors?
1) GI upset
2) Bloating
*These drugs essentially give someone symptoms of lactose intolerance
What is the contraindication to alpha-glucosidase inhibitors?
Malabsorption
What is the MOA of the secretagougues?
- Stimulation of insulin secretion
- Blocks ATP-dependent K+ channel of pancreatic beta cells
What are the major classes of secretagougues?
1) Traditional sulfonylureas
2) Meglitinides
What are the first generation sulfonylureas?
1) Chlorpropamide
2) Tolbutamide
What are the second generation of sulfonylureas?
1) Glyburide
2) Glipizide
3) Glimiperide
What are the meglitinides?
1) Repaglinide
2) Nateglinide
What are the side effects of the secretagougues?
1) Hypoglycemia
2) Weight gain
What are the contraindications to the secretagougues?
1) Severe renal disease
2) Hepatic disease
What is the MOA of the Biguanides?
1) Increases the number and affinity of insulin receptors
2) Decreases hepatic glucose output
3) Decreases glucose absorption from the gut
4) Increased glucose uptake in fat and skeletal muscle
List the Biguanides.
Metformin/Glucophage
What are the side effects associated with the Biguanides?
1) GI upset
2) Lactic acidosis
What are the contraindications to the Biguanides?
1) CDK with creatinine greater than 1.5
2) CHF
3) Liver disease
What is the MOA of the TZDs?
- PPAR-gamma agonists
- Increase peripheral glucose uptake
- Causes FFA to shunt into the subcutaneous tissue
- Decreases insulin resistance/ increases sensitivity
List the TZDs.
1) Pioglitazone
2) Rosiglitazone
What are the side effects of the TZDs?
1) Fluid retention
2) Weight gain
3) Heart failure
What are the contraindications to the TZDs?
1) CHF (stage III or IV)
2) Severe liver disease
What is the MOA of incretin?
- Incretin is released in response to glucose in the gut
- Stimulates secretion of insulin from the beta cells
What is the incretin mimetic?
Exanetide
What are the side effects of Exanetide?
1) Hypoglycemia
2) Nausea
What are the contraindications to Exanetide?
1) ESRD
2) Severe gastric disease
What is the function of the DPP-4 enzyme?
Degradation of incretin
What is the MOA of the DPP-4 inhibitors?
Prevents the degradation of incretin
List the DPP-4 inhibitors.
1) Siltagliptin
2) Saxagliptin
3) Linagliptin
What is unique about the DPP-4 inhibitors?
Very well tolerated with very limited side effect profile
*Only causes nasal congestion
What is the MOA of Pramlintide?
Decreases post-parandial glucagon
What are the side effects of Pramlintide?
1) Hypoglycemia
2) Nausea
What are the contraindications to Pramlintide?
1) Gastroparesis
2) Hypoglycemia unawareness
How much will a 2x drug oral therapy lower the HbA1c?
1.2-1.8%
How much will adding a 3rd drug decrease the HbA1c in oral therapy?
1.4-1.7%
What are the indications for insulin in the DM-II patient?
1) Severe hyperglycemia at presentation
2) Hyperglycemia despite max. dose of oral agents
3) Decompensation
4) Surgery
5) Pregnancy
6) Renal disease
7) Allergy or serious reaction or oral agents
What is the typical insulin regimen when oral agents fail?
1) Continue oral agents
2) Add a single bedtime injection of NPH or Lantus
*Titrate to achieve fasting blood glucose less than 100 mg/dL
Who needs to be screened for DM?
- Anyone over 45
- Younger than 45 IF:
1) Overweight
2) Family history of DM
3) High risk ethnic group
4) Hx. of gestational DM
5) PCOS
6) Previous IGT, IFG
