EXAM #2: TYPE DM-II Flashcards by Jonathan Kallevang

What is the key feature underlying the pathology of DM-II?

Relative insulin deficiency

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What ethnicity is DM-II most common in?

Hispanics

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What are the microvascular complications of DM-II?

1) Retinopathy
2) Neuropathy
3) Nephropathy

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What are the macrovascular complications of DM-II?

1) Cerebrovascular Disease
2) PVD
3) CAD

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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

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What is an impaired fasting glucose measurement?

100-125 mg/dL

*126+ is DM

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What is an impaired glucose tolerance test?

140-199 mg/dL

*200+ is DM

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What are the target organs for insulin?

Liver
Muscle
Fat

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What are the functions of insulin?

1) Glycogen formation
2) Protein synthesis
3) Lipid synthesis

*Generally, insulin is an anabolic hormone

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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

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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

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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

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What can cause a falsely elevated HbA1c?

Hemoglobinopathy (Sickle Cell)

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What can cause a falsely decreased HbA1c?

1) Recent transfusion

2) Anemia

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What is the key initial treatment option for DM-II?

Lifestyle changes

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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

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What patients are alpha-glucosidase inhibitors a good option for?

Patients with mild post-parandial hyperglycemia

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What are the side effects of alpha-glucosidase inhibitors?

1) GI upset
2) Bloating

*These drugs essentially give someone symptoms of lactose intolerance

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What is the contraindication to alpha-glucosidase inhibitors?

Malabsorption

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What is the MOA of the secretagougues?

Stimulation of insulin secretion

- Blocks ATP-dependent K+ channel of pancreatic beta cells

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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