Insulin and Hypoglycemic Agents
Treatment Approaches
1) limit carb intake
2) weight loss and exercise
3) insulin for type I; for type II when fasting glucose > 250 mg/dl
Insulin Preparations
- administered subQ, IM, and IV
- Onset/duration
Ø Regular insulin – 0.5hr/5-7hrs
Ø Isophane insulin & Lente Insulin – 1-2hrs/24-30hrs
Ø Protamine Zinc Insulin, Ultralente insulin – 4-8 hrs/24-36 hrs
- Complications of Insulin Therapy
1) resistance – anti-insulin Abs, anti-receptor Abs
2) allergic reactions
3) hypoglycemia – iatrogenic
4) lipodystrophy at site of injection
5) drug interaction causing hypoglycemia
- insulin and EtOH
- insulin & propranolol
Criteria
Normal blood glucose fasting < 110 mg/dl
Criteria for diagnosis of Diabetes Mellitus
· Symptoms + casual plasma glucosa > 200 md/dl
- FPG > 126 mg/dl
- 2hr PG> 200 mg/dl during OGTT
Criteria for Impaired Fasting Glucose
- FPG > 110 and < 126 mg/dl
Loose Control
- 130 mg/dl fasting
- 180 mg/dl after meal
Tight Control
- 110 mg/dl fasting
- 150 mg/dl after meal
Oral Hypoglycemic Agents
The Sulfonylureas and Non-sulfonylurea – Tolbutamide, Glipizide, Glyburide, Chlorpropamide, Repaglinide
- Tolbutamide and Chlorpropamide are 1st generation
- Glipizide & Glyburide are 2nd generation
- 2nd generations generally have longer duration and only require once daily dose therapy; lower side effects, also
- Non-sulfonylurea (Repaglinide) reaches peak plasma levels quicker, and is rapidly metabolized in liver to inactives; fewer reports of hypoglycemia than with the sulfonylureas
- Mechanism
Ø increase the sensitivity of b- cell to glucose
Ø inhibit ATP-gated K channel on the Beta cell which stimulates Insulin Secretion
- Toxicity
Ø Low 1/15000 patients
Ø Decreased I uptake by the thyroid, ADH-like effect, GI, disulfiram like action (not with 2nd generations), CV (especially with tolbutamide)
Ø DO NOT USE IN PREGNANCY
- Therapeutic Uses
Ø only in Diabetes Type II
Ø only if weight reduction and diet ineffective or unable to take insulin (can give in combo with insulin)
Insulin Sensitizers – Biguanides (metformin), Thiazolidinediones (troglitazone, rosiglitazone)
- improve the sensitivity of the peripheral tissues to Insulin
Biguanides – Metformin
- decreases blood glucose levels
- no risk of hypoglycemia
- unknown mechanism
- CI: renal impairment
- Side effects
1) Lactic acidosis, GI, decreased Vit B12 absorption
Thiazolidinediones – Troglitazone, Rosiglitazone
- reduce plasma glucose, insulin, triglycerides in rodents
- Toxicity
1) liver toxicity
Tags: Diabetes mellitus, Hypoglycemia, Impaired Fasting Glucose, insulin, Insulin Sensitizers - Biguanides, Isophane insulin, Lente Insulin, lipodystrophy, metformin, Oral Hypoglycemic Agents, Protamine Zinc Insulin, rosiglitazone, Thiazolidinediones, troglitazone, Ultralente insulin
