Aims of management
► To achieve near normal glycaemia
- Short term- to prevent symptoms of hyper & hypo
- Long term- to prevent complications
► Good quality of life, near normal life expectancy
Types of Insulin
► Short acting - Soluble / Neutral insulin
Insulin aspart
Insulin lispro
► Intermediate acting - Isophane
► Long acting - Insulin Zinc suspension
new insulin analogue - Glargine
Detemir
► Biphasic- mixture of short and intermediate
Biphasic lispro
Biphasic Isophane
Types of Insulin
Insulin | Lispro Aspart | Neutral/ regular | Isophane | ultratard | Glargine |
Onset | 10-20′ | 30′ | 1h | 4h | 2-4h |
Peak | 1h | 1-3h | 4-6h | 6-18h | peak less |
Duration | 3-5h | 4-8h | 8-14h | 24h | 20-24h |
Soluble insulin / neutral /clear
► Names - Human actrapid/ Humulin S
► Species- Bovine, porcine, human
► Following s/c injection
Onset of action – 30 min
Peak- 1-3 hours
Duration- 4-8 hours
► Only insulin suitable for intravenous route –plasma half life < 5 min, required continuous infusion
► Used in diabetes Ketoacidosis
Sites of injections - Subcutaneous
► Thighs
► Upper buttocks
► Abdomen
► Arms
Important to rotate the site
Rate of absorption may be significantly different – faster from arm and abdomen than from thigh and buttock
Routes of Administration
► Subcutaneous for long term regular use
► Intravenous infusion in acute conditions- diabetes Ketoacidosis, Perioperative period, Hyperosmolar Nonketotic state ONLY NEUTRAL/ CLEAR INSULIN CAN BE USED
► Continuous subcutaneous insulin infusion via pump – neutral
► Intraperitoneal – Peritoneal dialysis patients
► Inhaled insulin- experimental
Untoward effect of insulin
► Hypoglycaemia
► Weight gain- anabolic hormone
► Lipohypertrophy- injection to same site
► Insulin oedema
► Transient deterioration in retinopathy
► Insulin neuritis – actively regenerating neurone, uncommon
► Postural hypotension
Recurrent Hypo
► ? Required dose adjustment
► ? Right insulin/ injection technique
► ? Meal/ fasting related
► ? Injections sites
► ? Exercise
► Unexplained - ?autonomic neuropathy
Sick day rules
never stop insulin
monitor more frequently
maintain your hydration
Check for ketones
Know when & how to call for help
Oral Medications to Treat Type 2 Diabetes
Major Classes of Medications
sensitize the body to insulin +/- control hepatic glucose production
stimulate the pancreas to make more insulin
slow the absorption of starches
Thiazolidinediones
Biguanides
Sulfonylureas
Meglitinides
Alpha-glucosidase
inhibitors
Thiazolidinediones
► ↓ insulin resistance by making muscle and adipose cells more sensitive to insulin. They also suppress hepatic glucose production.
► Efficacy
↓ fasting plasma glucose ~1.9-2.2 mmol/L
Reduce A1C ~0.5-1.0%
6 weeks for maximum effect
► Other Effects
Weight gain, oedema
Hypoglycemia (if taken with insulin or agents that stimulate insulin release)
Contraindicated in patients with abnormal LFT or CHF
Improves HDL cholesterol and plasma triglycerides; usually LDL neutral
► Medications in this Class: pioglitazone (Actos), rosiglitazone (Avandia), [troglitazone (Rezulin) - taken off market due to liver toxicity]
Biguanides
► Biguanides ↓ hepatic glucose production and increase insulin-mediated peripheral glucose uptake.
► Efficacy
Decrease fasting plasma glucose 60-70 mg/dl (3.3-3.9 mmol/L)
Reduce A1C 1.0-2.0%
► Other Effects
Diarrhea and abdominal discomfort
Lactic acidosis if improperly prescribed
Cause small decrease in LDL cholesterol level and triglycerides
No specific effect on blood pressure
No weight gain, with possible modest weight loss
Contraindicated in patients with impaired renal function
Medications in this Class: metformin (Glucophage), metformin hydrochloride extended release (Glucophage XR)
Sulfonylureas
► Sulfonylureas increase endogenous insulin secretion
► Efficacy
Decrease fasting plasma glucose 3.3-3.9 mmol/L
Reduce A1C by 1.0-2.0%
► Other Effects
Hypoglycemia
Weight gain
No specific effect on plasma lipids or blood pressure
Generally the least expensive class of medication
► Medications in this Class:
First generation : chlorpropamide , tolazamide, acetohexamide , tolbutamide
Second generation : glyburide , glimepiride , glipizide
Meglitinides
► stimulate insulin secretion (rapidly and for a short duration) in the presence of glucose.
► Efficacy
↓ peak postprandial glucose
↓ plasma glucose 3.3-3.9 mmol/L
↓ HbA1C 1.0-2.0%
► Other Effects
Hypoglycemia (may be less than with sulfonylureas if patient has a variable eating schedule)
Weight gain
No significant effect on plasma lipid levels
Safe at higher levels of serum Cr than sulfonylureas
► Medications in this Class: repaglinide , nateglinide
Alpha-glucosidase Inhibitors
► Alpha-glucosidase inhibitors block the enzymes that digest starches in the small intestine
► Efficacy
↓ peak postprandial glucose 2.2-2.8 mmol/L
↓ fasting plasma glucose 1.4-1.7 mmol/L
Decrease A1C 0.5-1.0%
► Other Effects
Flatulence or abdominal discomfort
No specific effect on lipids or blood pressure
No weight gain
Contraindicated in patients with inflammatory bowel disease or cirrhosis
► Medications in this Class: acarbose , miglitol
Combination Therapy for Type 2 Diabetes
Sulfonylurea + Biguanide
Glyburide + Metformin - Glucovance
Glipizide + Metformin - Metaglip
Thiazolidinedione + Biguanide
Rosiglitazone + Metformin - Avandamet
Chart
Clinic Checklists
► Glycaemic control- home monitoring, HbA1c, inj site, hypo
► Diet, exercise, Smoking, alcohol
► BP
► Weight
► Macrovascular- CVA, IHD
► Microvascular- Retinopathy, microalbuminuria, neuropathy
► Foot
► Lipid profile, renal function, TSH
Special circumstances
► Intercurrent illness
► Peri-operative period
► Pregnancy
► Childhood and adolescents
► Others- travelling across time zones
Exercise
Alcohol
Driving
Dr K S Myint
Specialist Registrar
