Download of insulin therapy.

Diabetes mellitus
Principles of
treatment. Changes in
teeth and jaws,
mucous membranes.
as.-prof. Vereshchahina N.Y.
The main principles of DM therapy




Maintenance of metabolic status at normal level or as
close to normal as possible (especially blood glucose
and lipid concentration). Achievement of DM
compensation.
Achievement and maintenance of normal or
reasonable body weight.
Maintenance (preservation)
of working capacity.
Prophylaxis of acute and chronic complications.
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
The main principles of diet.

Normal-calorie diet in patients
with type 1 DM (35-50 kcal/kg of
ideal weight (weight = height –
100)) and low-calorie diet in
obese persons (mostly in patients
with type 2 DM (20 – 25 kcal/kg of
ideal weight)). We try to decrease
weight in obese patients on 1-2
kg/month by such diet.
The main principles of diet
 Balanced
diet (diet should
include physiologic meal
components: carbohydrate
comprises 50 – 60 % of total
calories, fat – 24 – 25 % and
protein – 16 – 15 %).
The main principles of diet.
Regimen has to be consist of 4 – 5 – 6 small
feedings a day.
(The most frequent regimen consists of 4 feedings
a day, in which:
- breakfast comprises 30 % of total calories,
- dinner – 40 %,
- lunch – 10 %,
- supper – 20 %.
Sometimes patients need second breakfast (when
they have a tendency to develop
hypoglycemia). In such case it comprises15 %
of the total calories and we decrease the
quantity of calories of the first breakfast and
dinner).

Exclusion of high-calorie carbohydrates (sugar,
biscuits, white bread, alcohol).

The main principles of diet.

Increasing the quantity of high fiber-containing foods (fruits
(exclusion: banana, grapes), vegetables, cereal grains, whole
grain flours, bran. Patients need 40 g fibers per day

Limiting of meat fat, butter, margarine in diet, decrease red
and brown meats, increase poultry and fish, encourage skim
milk-based cheeses. Should be used skim or low-fat milk, not
more than 2 – 3 eggs weekly.

Alcohol should be avoided as much as possible because it
constitutes a source of additional calories, it may worsen
hyperglycemia, and it may potentiate the hypoglycemic
effects of insulin and oral hypoglycemic agents.
The
recommended
food pyramid for
the persons
having type 2
diabetes.
Methods of treatment DM
Diet.
Oral hypoglycemic agents or insulin
(indications for each vary with the type
of DM and severity of the disease).
Exercise program.
Phytotherapy (plant’s therapy).
Nontraditional methods of treatment.
Education
Education of the patients
about the nature of the disease, the importance of its control, all
aspects of self-management and routine practices to minimize the
development or severity of the diabetes’ complications.
Physician has to educate, motivate and monitor progress.
Patient must understand the importance of life-style changing.




the nature of DM and importance of
metabolic control;
the principles and importance of good
nutrition and reasonable exercise
program;
the principles of adequate foot, dental and
skin care;
treatment of DM during the periods of
illness;
Self - control
Physician has to
educate: - techniques
of insulin
administration and
measurement of urine
and blood glucose
level (if taking insulin)
Patient’s education.


recognition of hypoglycemia, its causes
and methods of prevention;
the importance of general and specific
measures to minimize in the best
possible way diabetic complications
and maintain of good overall health.
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).
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).
Commonly used sulphonylureas
2 nd generation drugs (mg)
Glibenclamid
(Maninil,
Euglucan, Daonil, Glinil,
Gilamat, Gliben, Glucoven)
Glibornurid (Glutrid)
Gliquidon
(Glurenorm,
Beglicor)
1;
1-2
1,75;
3,5; 5
25
25-75
30
30120
Gliclazid
(Diamicron, 80
Diabeton, Predian, Glizid)
30
Diabeton MR
Glipizid
(Minidiab, 5
Glucontrol, Antidiab)
3 rd generation drugs (mg)
Glimepirid (Amaryl)
1-4
1224
8-12
8-12
80320
30120
20
8-12
24
4
24
8-12
Without hepatoand nephrotoxic
effects, metabolism through the
intestinum
Normalizes
microcirculation, blood
aggregation
Action of sulfanilureas
1. Influence on the pancreatic gland:
increasing of the β-cells sensitivity to the glucose
and as a result higher secretion of insulin;

stimulation of the exocytosis of insulin by
insulocytes;
2. Nonpancreatic influence:

increasing number of the receptors to insulin;

normalization of receptors’ sensitivity to insulin;

increasing of glucose transportation inside
muscle cells;

stimulation of glycogen synthesis;

decreasing of glycogenolysis and
glyconeogenesis;

decreasing of glucagon secretion and others.

Indications to sulfanilureas usage

patients with type 2 DM (over the age of
35 – 50 years) who do not suffer severe
metabolic abnormalities
(hyperglycemia), ketosis or
hyperosmolality;

duration of diabetes less than 15 years.
Contrandications to sulfanilureas usage







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.
Commonly used
biguanides
Name of drug
Metformin
(Dianormet,
Siofor,
Metfogamma,
Metfordar)
Glucophage Forte
Buformin (Adebit)
Buformin Retard
Dose in
1 tabl.
0,25;
0,5
0,5;
0,85
0,05
0,17
Daily
dose
0,5-1,5
0,5-2,0
0,1-0,2
0,170,34
Duration
of
action
(hours)
8-10
12-14
8-10
12-14
Action of biguanides






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








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.
Side effects of biguanides



allergy;
gastrointestinal tract disorders;
lactoacidosis.
Alpha-glucosidase inhibitors
Name of drug
Duration of
action(hour
s)
0,05; 0,1 0,15-0,6 2,7-9,6
Dose in
1 tabl.
Acarbosa
(Glucobay, Glucor,
Prandase, Precose)
Miglitol
0,025;
0,05;
0,1
Guar
(Guarem)
Daily
dose
0,05-0,3 2-4
Gum 5,0 (gra- 15-30
nules)
-
Action of alpha-glucosidase inhibitors



inhibition of gastrointestinal tract absorption
(blocation of α-glucozidase);
lowering of pastprandial glucose level (postprandial
“spikes” in blood glucose are increasingly implicated
as a major cause of cardiovascular complications);
partly reducing fasting glucose levels by indirectly
stimulating insulin secretion in patients who retain βcell function (and acarbose has a protective effect
on β-cells).
Indications to alphaglucosidase inhibitors usage
 DM
type 2 with or without obesity, when diet
and exercises are no effective;
 DM with significant violations of glycaemia
during a day;
 Secondary sulfanilureas failure;
 Insulin resistance;
 Allergic reactions to other hypoglycemic drugs;
 Hypercholesterolemia.
Contrandications to alphaglucosidase inhibitors
 type
1 DM;
 Chronic gastrointestinal disorders: pancreatitis,
colitis, hepatitis.
Side effects of alphaglucosidase inhibitors
- flatulence, abdominal bloating, diarrhea.
Non-sulfanylureas insulin
stimulators
Duration
Dose in Daily
Name of drug
of action
1 tabl. dose
(hours)
Repaglinid
0,001;
0,004- 3 - 4
(Novonorm, Roglid)
0,002;
0,009
(meglitinide analogs)
0,003;
0,004
Nateglinid (Starlix)
0,06;
0,18- 1,5 - 3
(D-Phenilalanine-derivative) 0,12;
0,54
0,18
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 to non-sulfanylureas insulin stimulator.
- can be used in elderly with type 2 DM (due to
short half-life) and in renal impairment (because it
is metabolized in liver).
Contraindications to nonsulfanylureas insulin stimulator.
- as for the sulfanilureas
Side effects of non-sulfanylureas insulin
stimulator.
- hypoglycemia, transient elevation of liver enzymes,
rash and visual disturbances.
Commonly used thiozolidinediones
Dose
Name of drug
in 1
tabl.
Rosiglitazone
0,002;
(Avandia,
Roglit, 0,004;
Rosinorm)
0,008
Pioglitazone (Actos, 0,015;
Pionorm)
0,03;
0,045
Daily
dose
Duration
of action
(hours)
0,0040,008
0,0150,03
Up to 24
hours
Action of thiozolidindiones







Agonist to the receptors of the nucleus PPARγ of the
fat, muscle tissues and the liver;
Increasing of the glucose passage to these tissues;
Increasing of insulin synthesis in the β-cells;
Increasing of the insulas amount;
Increasing of glycogen synthesis in the liver;
Decreasing of gluconeogenesis;
Decreasing of triglycerides;
Indications to thiozolidindiones usage
 DM
type 2, when diet and exercises are no
effective;
 Using with sulfanilureas, biguanides in case of their
insufficient efficacy
(however, at present, only pioglitazone is
approved for use in combination with insulin)
From the history of insulin
 1921
Banting and Best extracted insulin from
pancreatic gland of newborn cow
 1955 - Sanger established molecular structure of
insulin
 1964 – Katsoyanis (USA), 1965 - Tzan (Germany)
synthesized human insulin
From the history of insulin
From the history of insulin
Banting
1891 - 1941
Macleod
1876 - 1935
Best
1899 - 1978
Collip
1893 - 1965
From the history of insulin
Leonard Tompson
before and after beginning of insulintherapy and adult
Teodor Raide
before and after beginning of insulintherapy and adult
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
ultrashort action
(human analog, recombinant)
Insulin
action
beginning maximum
duration
2-10 min
3-5h
NovoRap
id NovoNordisk
Humalog
Lilly
Epaidra
40 - 50 min
Insulin preparations of
short action action
Insulin
beginning maximu duratio
m
n
Monodar Indar
Humodar R (полусинт.)
Indar
Humodar RR(рекомб)
Indar
Humodar R100 Indar
Humodar R100R Indar
Farmasulin HN Farmak
Actrapid (МС, НМ)
Novo-Nordisk
30 min
1-3h 5-8h
Insulin preparations of intermediate action
Insulin
action
beginning
maximu
m
Monodar B Indar
Humodar B Indar
Farmasulin Н NР Farmak 1 – 1,5 h 6 - 8 h
Protaphan (МС, НМ)
Novo-Nordisk
Insuman basal Aventis
Humulin NPH Lilly
Monotard НМ Novo-
duration
12 – 18
h
Insulin preparations of long action
Insulin
action
beginning
Farmasulin НL Farmak
Ultralente Humulin Lilly
Ultratard НМ
3–4h
МC Suinsulin
Ultralong Indar
Glargine (Lantus)Aventis
Detemir
maximum duratio
n
10 -12 h
24 – 30
h
24 h
Initiation and modification of insulin
therapy
 It
is started as soon as possible in an attempt to “rest”
the damaged islet cells and help to “induce” a
remission (“honeymoon” phase).
 The
-
-
daily insulin requirement in patients:
on the first year of the disease is 0,3 – 0,5 unite of insulin
per kilogram of body weight (0,5 – if the patient with
ketosis or DKA);
on the next years is 0,6 – 0,8 – 1,0 unite/ kg of body
weight.
1 Unite
 It
is activity of 0,04082 mg of crystalic insulin
(standart)
3
Secretion of insulin in health people
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
Initiation and modification
of insulin therapy
We can use traditional or multiple
component insulin program. The last
is better.
Advantages include the following:
 hypoglycemic reactions may be
decreased or prevented because
smaller doses of insulin are needed;
 more physiologic match of insulin to
meals is achieved.
 It
Initiation and modification
of insulin therapy
using three or four shots of shortacting insulin (1/3 of total daily
dose) plus intermediate-acting
(2/3 of total daily dose) insulin
daily.
 2/3 of the total daily dose we give
before breakfast, 1/3 in the
evening and then make
correction due to the glucose
blood level. Insulin doses should be
given 30 minutes before meals to
allow for adequate absorption of
regular insulin.
Other commonly used insulin treatment
algorithms





Single prebreakfast injection of intermediateacting insulin.
Intermediate-acting insulin: prebreakfast
injection of 2/3 total daily dose, 1/3 of daily
dose before dinner.
Combination of intermediate- and shortacting insulin:
single prebreakfast injection of 2/3
intermediate-acting + 1/3 of short-acting;
2/3 – before breakfast, 1/3 – before dinner; 2/3
– intermediate-acting, 1/3 – short-acting.
Other commonly used
insulin treatment algorithms


Short-acting insulin ½ hour before each
meal and a small dose of intermediateacting insulin at bedtime.
Combination of long-acting (in
prebreakfast time) and short-acting
insulin (1/2 hour before each meal.)
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);
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).
Future directions in improving
glycemic control:
 nasal
insulin preparations;
 pancreatic transplantation;
 islet replacement therapy;
 genetically engineered
pseudo-beta-cells.
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.
Hypoglycemia
It is a syndrome characterized
by symptoms of sympathetic
nervous system stimulation or
central nervous system
dysfunction that are
provoked by an abnormally
low plasma glucose level.
Hypoglycemia represents
insulin excess and it can
occur at any time.
Precipitating factors
 irregular
ingestion of
food;
 extreme activity;
 alcohol ingestion;
 drug interaction;
 liver or renal disease;
 hypopituitarism and
adrenal insufficiency.
Clinical presentation
1.
2.
3.
4.
5.
6.
7.
1. adrenergic symptoms (they are
attributed to increased sympathetic
activity and epinephrine release):
sweating,
nervousness,
faintness,
palpitation
sometimes hunger;
2. cerebral nervous system manifestations:
confusion, inappropriate behavior (which
can be mistaken for inebriation); visual
disturbances, stupor, coma or seizures.
(Improvement in the cerebral nervous
system manifestations will be with a rise in
blood glucose.)
A common symptom of
hypoglycemia is the early
morning headache, which
is usually present when the
patient awakes.
Patients should be familiar
with the symptoms of the
hypoglycemia but some of
them are not heralded by
symptoms.
Physical examination
1.
2.
3.
4.
The skin is cold, moist.
Hyperreflexia can be elicited.
Hypoglycemic coma is commonly associated with
abnormally low body temperature
Patient may be unconsciousness.
Laboratory findings
1. Low level of blood glucose
Treatment
Insulin–treated patients are advised
to carry sugar lumps, candy, or glucose tablets at all
time.
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:
Treatment
1.
2.
3.
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;
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;
glucocorticoids and adrenaline are helpful as well.
Side effects (complications) of insulin therapy
6. Lipodystrophy.
- It is atrophy or hypertrophy
of the adipose tissue, which
occur at the site of insulin
injection.
- Treatment:
 changing the site of
injection;
 the usage of human insulin.
Exercise program.
 Exercise
is an excellent adjunct to
diet therapy, but it is very
ineffective when used as the sole
weight-reducing modality.
 Exercises
must be clearly planned
and depend on patient’s abilities
and the physical condition,
exclusion of the competition’s
elements.
Exercise program.
 Exercises
may be valuable adjunct to the
management of the DM by:
 lowering blood glucose concentration;
 decreasing insulin requirements;
 potentiation the beneficial effects of diet and
other therapy.
 To prevent hypoglycemia, patients should carefully
monitor glucose level and taking of insulin. Mostly
they need to reduce the insulin dosage by 20 – 25
% on the day that strenuous exercises is planned.
Plant’s therapy
(phytotherapy).



hypoglycemic action;
treatment of chronic
diabetics complications;
influence on the immune
reactivity.
Sank you
for
attention!