7. How is diabetes mellitus managed? Discuss oral hypoglycemic agents and insulin.

DM TYPE 1
Insulin Treatment
Human Insulin and Insulin Analogs are available for insulin replacement therapy. Insulins
also are classified by the timing of their action in your body specifically, how quickly they start to
act, when they have a maximal effect and how long they act.Insulin analogs have been developed
because human insulins have limitations when injected under the skin.

Characteristics of Insulin
Insulins are categorized by differences in:

Onset

Peak

Duration

Concentration

Route of delivery
TYPES OF INSULIN
Fast-acting insulin:

Is absorbed quickly from your fat tissue (subcutaneous) into the bloodstream

Is used to control the blood sugar during meals and snacks and to correct high
blood sugars
Includes:
Rapid Acting Insulin Analogs (Insulin Aspart, insulin Lyspro, Insulin Glulisine) which
have an onset of action of 5 to 15 minutes, peak effect in 1 to 2 hours and duration of
action that lasts 4-6 hours. With all doses, large and small, the onset of action and the time
to peak effect is similar, The duration of insulin action is, however, affected by the dose
so a few units may last 4 hours or less, while 25 or 30 units may last 5 to 6 hours. As a
general rule, assume that these insulins have duration of action of 4 hours.
Regular Human Insulin which has an onset of action of 1/2 hour to 1 hour, peak effect in
2 to 4 hours, and duration of action of 6 to 8 hours. The larger the dose of Regular, the
faster the onset of action, but the longer the time to peak effect and the longer the duration
of the effect.
Intermediate-acting insulin:

Is absorbed more slowly, and lasts longer

Is used to control the blood sugar overnight, while fasting and between meals

Includes:
NPH Human Insulin which has an onset of insulin effect of 1 to 2 hours, a peak effect of 4
to 6 hours, and duration of action of more than 12 hours. Very small doses will have an
earlier peak effect and shorter duration of action, while higher doses will have a longer
time to peak effect and prolonged duration.
Long-acting insulin:

Is absorbed slowly, has a minimal peak effect, and a stable plateau effect that lasts
most of the day

Is used to control the blood sugar overnight, while fasting and between meals
Includes:
Long acting insulin analogs (Insulin Glargine, Insulin Detemir) which have an onset of
insulin effect in 1 1/2-2 hours. The insulin effect plateaus over the next few hours and is
followed by a relatively flat duration of action that lasts 12-24 hours for insulin detemir and
24 hours for insulin glargine.

TABLE OF
ACTION

INSULIN

INSULIN ADMINISTRATION
Injection
Insulin syringe:
This is the most common insulin delivery method. The classic injection device is an insulin
syringe. The plastic, disposable syringes currently are available in three sizes, and hold up
to 30, 50 or 100 units of insulin. The needles are fine (up to 31 gauge) with lengths ranging
from 3/16th of an inch for infants, to inch or more for adults. The insulin is injected into
the layer of fat (subcutaneous tissue) just under the skin.
Insulin Pen:
A popular alternative to the insulin syringe is an insulin pen. An insulin pen has a
replaceable reservoir of insulin called a cartridge, a replaceable needle to puncture the
skin and to deliver insulin to the subcutaneous tissue, a dial to choose the insulin dose,
and a mechanical pumping or insulin release mechanism. These may be disposable
devices or re-useable devices with disposable insulin cartridges. They are very convenient
for active individuals taking multiple injections, as well as those who are visually or
dexterity-challenged.

Continuous Subcutaneous Insulin Infusion Device:

Continuous subcutaneous insulin infusion (CSII) devices (also known as insulin pumps)
are the most sophisticated form of insulin delivery. These are small, computerized devices
that are programmed to deliver insulin under the skin. The insulin pump is durable and
lasts for years, but the insulin supply and certain pump components (insulin reservoir,
tubing and infusion set) are changed every few days.

Infusion
Human regular insulin may be injected directly into the vein in a hospital setting under
close medical supervision only. Insulin is added to intravenous fluids, and the insulin dose
and blood sugar are strictly monitored. The intravenous route of delivery is ONLY given
under a doctors orders in a hospital to facilitate the management of diabetes during
surgery or an intensive care stay.
TYPE 1 NON INSULIN THERAPY
Pramlintide (Symlin)
Pramlintide is an injected medicine for people with type 1 and type 2 diabetes that helps
control blood sugar levels after eating. Pramlintide resembles the hormone, amylin that is
normally released along with insulin from the pancreatic beta cells. In type 1 diabetes,
amylin levels are absent because the pancreatic beta cells have been destroyed.
Pramlintide lowers glucagon during a meal, slows food emptying from the stomach and
curbs the appetite.

Dosing
When you have type 1 diabetes, the initial dose of pramlintide is 15 micrograms (2.5 units
on the insulin syringe), taken before meals. After 3 days, if you tolerate the medicine, the
dose may be increased to 30 micrograms (5 units on the insulin syringe) before meals.
The dose can be increased every three days as tolerated to a maximum dose of 60
micrograms before each meal. The meal must contain at least 30 grams of carbohydrate.
Pramlintide is available in a vial and pen form.

The most common side effects are:

Nausea
Vomiting
Headache
Low blood sugar

DM TYPE 2
Type 2 diabetes treatment focuses on ways to control the blood sugar, lower the insulin
resistance, and increase insulin levels.
Oral Agents for Type 2 Diabetes
SULPHONYLUREAS

Sulphonylureas increase the amount of insulin that is produced by your pancreas. The
sulfonylurea class of drugs quickly became the mainstay of treatment for type 2 diabetes.
Although newer agents have recently entered the marketplace, sulfonylureas still play a
primary role in pharmacologic management of type 2 diabetes. It include:

glibenclamide

gliclazide

glimepiride

glipizide

gliquidone
You may be prescribed one of these medicines if you can't take metformin, or if you aren't
overweight. Alternatively, you may be prescribed sulphonylurea and metformin if metformin
doesn't control blood glucose on its own.
Sulphonylureas can increase the risk of hypoglycaemia (low blood sugar), because they
increase the amount of insulin in your body. They can also sometimes cause side effects
including weight gain, nausea and diarrhea.
METFORMIN
Metformin is a biguanide agent that lowers blood glucose primarily by decreasing hepatic
glucose output and reducing insulin resistance. Metformin is used as monotherapy or in
combination with sulfonylureas for management of type 2 diabetes. When used as
monotherapy, metformin does not cause hypoglycemia and is thus termed an
antihyperglycemic. The use of metformin is contraindicated in patients with renal
insufficiency. Normal renal function should be confirmed 48 hours after the procedure
before restarting metformin therapy. Extreme caution should be used in patients with
severe hepatic dysfunction and hypoxemic states (e.g., severe chronic obstructive
pulmonary disease, congestive heart failure). Hemogloblin, hematocrit, red blood cell
indexes and renal function should be monitored at least annually in patients taking
metformin.

ALPHA-GLUCOSIDASE INHIBITORS
Alpha-glucosidase inhibitors, such as acarbose (Precose) and miglitol (Glyset), are
indicated as monotherapy or in combination with sulfonylureas for management of type 2
diabetes. These agents inhibit the breakdown of complex carbohydrates and delay the
absorption of monosaccharides from the gastrointestinal tract. Acarbose and miglitol
should be titrated over two to three weeks to minimize flatulence and other gastrointestinal
side effects that commonly lead to discontinuation of these agents. Alpha-glucosidase
inhibitors are contraindicated in patients with inflammatory bowel disease, partial intestinal
obstruction, a predisposition to intestinal obstruction, colonic ulceration and other
gastrointestinal disorders.

TROGLITAZONE
The thiazolidinediones are a unique drug class of insulin sensitizers that promote skeletal
muscle glucose uptake. Troglitazone reduces insulin resistance. Troglitazone is beneficial
in patients requiring large daily amounts of insulin (more than 30 units per day) whose
diabetes is still uncontrolled. A reduction of up to 50 percent in total daily insulin dosage is
possible with drug titration. Troglitazone is also effective when used in combination with
other oral agents, thereby potentially delaying the need to start insulin therapy.
The U.S. Food and Drug Administration recently ruled that troglitazone should only be
used in combination with other diabetic therapies. The effectiveness of oral contraceptives
may be decreased with troglitazone administration. Liver function must be monitored every
month for the first eight months of treatment and every other month for four months
thereafter.
REPAGLINIDE
Repaglinide (Prandin) is a benzoic acid derivative and the first of the non-sulfonylurea
meglitinides introduced in early 1998. The mechanism of action and side effect profile of
repaglinide are similar to those of the sulfonylureas. This agent has a rapid onset of action
and should be taken with meals two to four times daily. Repaglinide is a suitable option for
patients with severe sulfa allergy who are not candidates for sulfonylurea therapy. The drug
is used as monotherapy or in combination with metformin. It should be titrated cautiously in
elderly patients and in those with renal or hepatic dysfunction

Causes of Hyperglycemia and Action of Oral Antidiabetic Agents

References
American Academy of Physicians Organization
http://www.aafp.org/afp/1999/0515/p2835.html
Diabetes Education Online University of California, San Francisco http://dtc.ucsf.edu/typesof-diabetes/type2/treatment-of-type-2-diabetes/medications-and-therapies/