Transcript of insulin therapy.

Treatment of Diabetes Mellitus
Dr. Vereshchahina Natalija
• The treatment of patients with DM is
very important and may be difficult
because of problems in achieving of
normal glucose control.
• There is good evidence that
hyperglycemia conveys risks for all
of the common long-term
complications of DM, which are the
major cases of excess morbidity and
mortality in diabetics.
Criteria of DM compensation
Indexes
Level of compensation
good
sufficient insufficient
Fasting
glycaemia
4,4 - 6,7
(mmol/l)
2 hours after
4,4 – 8,0
meals
Glucosurea (%)
0
Hb Alc (%)
< 6,5
Cholesterol
< 5,0
(mmol/l)
Triglycerides
< 1,7
(mmol/l)
HDL (mmol/l)
> 1,1
Body
mass males < 25
index (kg/m2)
females < 24
Blood pressure
< 135/85
< 7,8
> 7,8
< 10,0
> 10,0
0,5
6,5 – 8
> 0,5
>8
5,0 – 6,5
> 6,5
1,7 – 2,2
> 2,2
0,9 – 1,1
< 27
< 26
< 160/95
< 0,9
> 27
> 26
> 160/95
Prevention or delay of diabetes:
Life style modification
 Research studies have found that lifestyle changes can
prevent or delay the onset of type 2 diabetes among highrisk adults.
 These studies included people with IGT and other high-risk
characteristics for developing diabetes.
 Lifestyle interventions included diet and moderate-intensity
physical activity (such as walking for 2 1/2 hours each
week).
 In the Diabetes Prevention Program, a large prevention
study of people at high risk for diabetes, the development of
diabetes was reduced 58% over 3 years.
Prevention or delay of diabetes:
Medications
 Studies have shown that medications have been successful in preventing
diabetes in some population groups.
 In the Diabetes Prevention Program, people treated with the drug
metformin reduced their risk of developing diabetes by 31% over 3 years.
 Treatment with metformin was most effective among younger, heavier
people (those 25-40 years of age who were 50 to 80 pounds overweight)
and less effective among older people and people who were not as
overweight.
 Similarly, in the STOP-NIDDM Trial, treatment of people with IGT with the
drug acarbose reduced the risk of developing diabetes by 25% over 3
years.
 Other medication studies are ongoing. In addition to preventing
progression from IGT to diabetes, both lifestyle changes and medication
have also been shown to increase the probability of reverting from IGT to
normal glucose tolerance.
Management of
Diabetes Mellitus
Management of DM
• The major components of the treatment of
diabetes are:
A
• Diet and Exercise
B
• Oral hypoglycaemic
therapy
C
• Insulin Therapy
A. Diet
 Diet is a basic part of management in every
case. Treatment cannot be effective unless
adequate attention is given to ensuring
appropriate nutrition.
 Dietary treatment should aim at:
◦ ensuring weight control
◦ providing nutritional requirements
◦ allowing good glycaemic control with blood glucose
levels as close to normal as possible
◦ correcting any associated blood lipid abnormalities
A. Diet (cont.)
The following principles are recommended as dietary guidelines for
people with diabetes:
 Dietary fat should provide 25-35% of total intake of calories but saturated
fat intake should not exceed 10% of total energy. Cholesterol
consumption should be restricted and limited to 300 mg or less daily.
 Protein intake can range between 10-15% total energy (0.8-1 g/kg of
desirable body weight). Requirements increase for children and during
pregnancy. Protein should be derived from both animal and vegetable
sources.
 Carbohydrates provide 50-60% of total caloric content of the diet.
Carbohydrates should be complex and high in fibre.
 Excessive salt intake is to be avoided. It should be particularly restricted
in people with hypertension
and those with nephropathy.
Exercise
 Physical activity promotes weight reduction and
improves insulin sensitivity, thus lowering blood
glucose levels.
 Together with dietary treatment, a programme of
regular physical activity and exercise should be
considered for each person. Such a programme
must be tailored to the individual’s health status
and fitness.
 People should, however, be educated about the
potential risk of hypoglycaemia and how
to avoid it.
B. Oral Anti-Diabetic Agents
• There are currently four classes of oral antidiabetic agents:
i. Biguanides
ii. Insulin Secretagogues – Sulphonylureas
iii. Insulin Secretagogues – Non-sulphonylureas
iv. α-glucosidase inhibitors
v. Thiazolidinediones (TZDs)
B.1 Oral Agent Monotherapy
 If glycaemic control is not achieved (HbA1c >
6.5% and/or; FPG > 7.0 mmol/L or; RPG
>11.0mmol/L) with lifestyle modification within 1 –
3 months, ORAL ANTI-DIABETIC AGENT should
be initiated.
 In the presence of marked hyperglycaemia in
newly diagnosed symptomatic type 2 diabetes
(HbA1c > 8%, FPG > 11.1 mmol/L, or RPG > 14
mmol/L), oral anti-diabetic agents can be
considered at the outset together with lifestyle
modification.
Oral hypoglycemic agents.
• Inadequate control of hyperglycemia by the diet and
exercises interventions suggests the need for a
good glucose-lowering agent.
• Oral hypoglycemic agents are useful only in the
chronic management of patients with type 2 DM.
• The most commonly used are:
- the sulfanilureas,
- biguanides,
- alpha-glucosidase inhibitors,
- non-sulfanylureas insulin stimulators (glinides),
- thiosolidinediones (glitazones).
B.1 Oral Agent Monotherapy (cont.)
As first line therapy:
• Obese type 2 patients, consider use of metformin, acarbose
or TZD.
• Non-obese type 2 patients, consider the use of metformin or
insulin secretagogues
• Metformin is the drug of choice in overweight/obese
patients. TZDs and acarbose are acceptable alternatives in
those who are intolerant to metformin.
• If monotherapy fails, a combination of TZDs, acarbose and
metformin is recommended.
If targets are still not achieved,
insulin secretagogues may be added
Sulfanilureas include:
• first generation: Tolbutamide, Chlorpropamide,
Tolazemide, Acetohexamide (now are not used in
treatment of the diabetics);
• second generation: Glibenclamide (Maninil (3,5 mg,
5 mg), Daonil (5 mg)), Gliquidon(Glurenorm (0,03),
Minidiab (5 mg)), Gliclazide (Diamicron (0,08)),
Glipizide;
• third generation: Glimepiride (Amaryl (1 mg, 2 mg).
Contrandications to sulfanilureas usage
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type 1 DM;
blood diseases;
acute infections, heart, cerebral diseases;
trauma;
pregnant diabetics or lactation;
III – IV stages of angiopathy (but
Glurenorm can be used in patients chronic
renal failure, because of gastrointestinal
tract excretion);
coma and precoma.
Action of biguanides
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inhibition of gastrointestinal glucose
absorption;
decreasing of glyconeogenesis, lipogenesis;
enhancing glucose transport into muscle
cells;
increasing the quantity of insulin’s receptors;
stimulation of anaerobic and partly aerobic
glycolis;
anorrhexogenic effects.
Indications to biguanides usage
• Obese patients with type 2 DM, with
middle severity of the disease without
ketosis.
• They can be used with the combination of
sulfanilureas when sulfonylureas alone
have proved inadequate to treat DM.
Contraindications to biguanides usage
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type 1 DM;
heart and lung disease with their insufficiency
(chronic heart and lung failure);
status with hypoxemia;
acute and chronic liver and kidney diseases with
decreased function;
pregnant diabetics, lactation;
old age;
alcoholism;
coma and precoma.
Action of non-sulfanylureas
insulin stimulator.
• Stimulation of insulin production at meal
times;
• very rapid absorbtion from the intestine
and metabolizing in the liver;
(plasma half-life is less than 1 hour).
Indications for insulin therapy
1. All patients with type 1 DM.
2. Some patients with type 2 DM:
• uncontrolled diabetes by diet or oral
hypoglycemic agents;
• ketoacidosis, coma;
• acute and chronic liver and kidneys disease with
decreased function;
• pregnancy and lactation;
• II – IV stages of angiopathy;
• infection diseases;
• acute heart and cerebral diseases;
• surgery.
Insulin preparations of
short action
Insulin
Monodar Indar
Humodar R (полусинт.) Indar
Humodar RR(рекомб) Indar
Humodar R100 Indar
Humodar R100R Indar
Farmasulin HN Farmak
Actrapid (МС, НМ)
Novo-Nordisk
action
beginning
maximum duration
30 min
1-3h
5-8h
Insulin preparations of
intermediate action
Insulin
action
beginning
Monodar B Indar
Humodar B Indar
Farmasulin Н NР Farmak 1 – 1,5 h
Protaphan (МС, НМ)
Novo-Nordisk
Insuman basal Aventis
Humulin NPH Lilly
Monotard НМ Novo-Nordisk
maximum duration
6-8h
12 – 18 h
Insulin preparations of
long action
Insulin
action
beginning
Farmasulin НL Farmak
Ultralente Humulin Lilly
Ultratard НМ
3–4h
МC Suinsulin Ultralong
maximum
duration
10 -12 h
24 – 30
h
Indar
Glargine (Lantus)Aventis
Detemir
Levemir
24 h
(human analog, recombinant)
Secretion of insulin in health people
3
Breakfast
Concentration of insulin
2,
Meal secretion
3
Lunch
Dinner
1,5
1
0,5
7.00
12.00
0
Basal secretion
19.00
24.00
7.00
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Some peculiarities of insulin
therapy:
insulin acts faster when is administrated i/v;
subcutaneous and intramuscular absorption of
insulin is decreased in the dehydrated or
hypotensive patients;
it is necessary to change
the insulin injection site
(because the absorption is more rapid
from the new sites);
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the most rapid absorption from
the abdomen;
exercise accelerates insulin absorption (before
planned exercise program patient has to decrease insulin dose or
take more caloric diet).
Side effects (complications)
of insulin therapy.
1. Hypoglycemia.
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- This complication represents insulin excess and it
can occur at any time (frequently at night
(common symptom: early-morning headache)).
- Precipitating factors:
irregular ingesting of food;
extreme activity;
alcohol ingestion;
drug interaction;
liver or renal disease;
hypopituitarism;
adrenal insufficiency.
Side effects (complications) of
insulin therapy.
- Treatment (preventing coma):
• to eat candy or to drink
sweet orange juice
(when the symptoms develop);
• to receive intravenous glucose;
• 1 mg of glucagon administrated
subcutaneously;
• gradual reduction of insulin dose in future.
Clinical presentation.
Hypoglycemia
Treatment
Insulin–treated patients are advised
If the symptoms of hypoglycemia develop,
the patients have to drink a glass of fruit
juice or water with 3 tbsp. of table sugar
added or to eat candy, and to teach their
family members to give such treatment if
they suddenly exhibit confusion or
inappropriate behavior:
1. glucagon 0,5 – 1 unit (0,5 – 1 ml) s/c, i/m or i/v.
If the patient does not respond to 1 unit of
glucagon within 25 minutes, further injections
are unlikely to be effective, and are not
recommended;
2. an i/v injection of 20 or 100 ml of 40 %
glucose, followed by a continuous infusion of 5
% glucose (10 % glucose may be needed) until
it clearly can be stopped safely;
3. glucocorticoids and adrenaline are helpful as
well.