Download A chief of endocrinology department, prof. Vlasenko MV

MINISTRY OF HEALTH PROTECTION OF UKRAINE
Vynnitsa national medical university named after M.I.Pyrogov
«CONFIRM»
on methodical meeting of
endocrinology department
A chief of endocrinology
department, prof. Vlasenko M.V.
_________________
“_31_”_august___ 2012 y
METHODOLOGICAL RECOMMENDATIONS
FOR INDEPENDENT WORK OF STUDENTS
BY PREPARATION FOR PRACTICAL CLASSES
Scientific discipline
Мodule № 1
substantial module №1
Topic
Course
Faculty
Internal medicine
Basis of Internal medicine
“Diagnostic, treatment and prophylactic basis of
main endocrinology diseases”
Topic №4: Treatment of type 2 diabetes mellitus. Diet. Oral
hypoglycemic agents: inhibitors of alfa-glucosidase, glinides,
biguanides, thiozolidindiones (glitazones), sulfonilureas,
incretines. Indication and contraindication. Mechanism of
action. Side effects.
4
Medical № 1
Vynnitsa – 2012
METHODOLOGICAL RECOMMENDATIONS
for the students of 4-th course of medical faculty for preparation to the practical
classes from endocrinology
1.Тopic №4: Treatment of type 2 diabetes mellitus. Diet. Oral hypoglycemic agents: inhibitors of
alfa-glucosidase, glinides, biguanides, thiozolidindiones (glitazones), sulfonilureas,
incretines. Indication and contraindication. Mechanism of action. Side effects.
2. Relevance of topic: The management of patients may be difficult because of problems in
achieving of normal glucose control. Because 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.
Patient education is essential to ensure the effectiveness of the prescribed therapy, to
recognize indications for seeking immediate medical attention, and to carry out appropriate foot
care. On each physician visit, the patient should be assessed for symptoms and signs of
complications, including a check of the feet and the pulses and sensation in the feet and legs, and a
urine test for albumin. The serum creatinine levels should be assessed regularly (at least yearly) and
an ECG and complete ophthalmologic evaluation should be performed at least yearly. Coexistent
hypertension and hypercholesterolemia increases the risks for specific late complications and
requires special attention and appropriate treatment.
3. Aim of lesson:
- to know about common aims and strategy in treatment of Diabetes Mellitus type 2.
- to learn the specifc tactics of therapy (diet, oral antidiabetic drugs), the application of adequate
dose of oral hypoglycemic preparations in diabetic patients.
- to learn indications and contraindications, probability of side effects of oral antidiabetic drugs.
4. References
4.1. Main literature
1. Endocrinology. Textbook/Study Guide for the Practical Classes. Ed. By Petro M. Bodnar: Vinnytsya: Nova Knyha Publishers, 2008.-496 p.
2. Basіc & Clіnіcal Endocrіnology. Seventh edіtіon. Edіted by Francіs S. Greenspan, Davіd G.
Gardner. – Mc Grew – Hіll Companіes, USA, 2004. – 976p.
3. Harrison‘s Endocrinology. Edited J.Larry Jameson. Mc Grew – Hill, USA,2006. – 563p.
4. Endocrinology. 6th edition by Mac Hadley, Jon E. Levine Benjamin Cummings.2006. –
608p.
5. Oxford Handbook of Endocrinology and Diabetes. Edited by Helen E. Turner, John A. H.
Wass. Oxford, University press,2006. – 1005p.
4.2. Additional literature
6. Endocrinology (A Logical Approach for Clinicians (Second Edition)). William Jubiz.-New
York: WC Graw-Hill Book, 1985. - P. 232-236.
7. Іnternatіonal Textbook of Dіabetes Mellіtus (Ed by R.A. Defronzo, E. Ferrannіnі, H. Keen,
P. Zіmmet. John Wіley & Sons, Ltd. England, 2004. – Vol. 1 – 1100p., Vol. 2 – 1913p.
8. Joslіn’s Dіabetes Mellіtus. Selected Chapters from the 14-th ed. Edіted by C. Ronald Kahn,
et al. Lіppіncott Wіllіams & Wіlkіns, USA, 2006. – 328p. Manual of Endocrinology and
Metabolism (Second Edition)/ Norman Lavin. – Little, Brown and Company.- Boston-New
York-Toronto-London, 1994. - P. 519-527, 561-574.
9. The diabetic foot. 2nd edition. Edited by A.Veves, J.M.Giurini, F.W. LoGerfo (ebs), Humana
Press, Totowa, New Jersey,2006. – 224p.
Basic Level.
1. Etiology and pathogenesis of DM.
2. Pathomorphologic changes in organs and systems in patients with DM.
3. Medical preparations, which can be used in diabetics.
Students’ Independent Study Program.
You should prepare for the practical class using the existing text books and lectures. Special
attention should be paid to the following:
1. The main principles of DM therapy.
2. Diet therapy in patients with DM.
3. The role of exercise program in diabetics.
4. Plant’s hypoglycemic agents.
5. The main principles of patient’s education.
6. Indications and contraindications to oral hypoglycemic agents’ administration.
7. Sulfanilurea preparations of I, II, III generations: mechanism of action.
8. Side effects of sulfanilurea therapy.
9. Biguanide preparations: mechanism of action.
10. Indications and contraindications to biguanide usage.
11. Side effects of biguanide therapy.
12. Acarbose: action, indications, contraindications, side effects.
13. Incretines (Glucagon-like peptide – 1, DPP-4 inhibitors): action, indications, contraindications,
side effects.
14. Creating an individual menu.
15. Phytotherapy in Diabetes Mellitus type 2.
16. Exercise in Diabetes Mellitus
17. Physiotherapeutic approach, refexotherapy in Diabetes Mellitus type 2.
1.
2.
3.
4.
1.
2.
3.
4.
5.
6.
Short content of the theme.
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.
Treatment of DM has to be individualized and includes:
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 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 differing life-style.
Diet is the keystone of the treatment of the DM.
1. Balanced diet (diet should include physiologic meal components: carbohydrate comprises 50 –
60 % of total calories, fat – 24 – 25 % and protein – 16 – 15 %).
2. Normal-calorie diet in patients with type I DM (35-50 kcal/kg of ideal weight (weight = height
– 100)) and low-calorie diet in obese persons (mostly in patients with type II DM (20 – 25
kcal/kg of ideal weight)). We try to decrease weight in obese patients on 1-2 kg/month by such
3.
4.
5.
6.
7.
diet. (Obesity leads to insensitivity of muscle and adipose tissue to insulin, presumable as the
result of decreased binding of insulin to its plasma membrane receptor. Hyperglycemia is the
face of increased insulin secretion and hyperlipoproteinemia are secondary to this abnormality.
The defect in insulin binding and secretion is corrected by weight reduction.)
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).
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.
Distributing of the BU in accordance with day’s energy need
Meal
Type of physical activity
Obesity
Easy
Middle
Hard
1st breakfast
2nd breakfast
Dinner
Snack
Supper
Late supper
Total
2
2
4
1
2
1
12
Products
Rye bread
Wheat bread
Macaroni
Porridge (buckwheat,
oat, rice, wheat)
Non-fat milk
Potato
Cabbage
Cucumbers
Tomatoes
Bananas
4
2
5
2
3
1
17
5–6
3
6–8
2–3
5
2
23–27
1–2
1
2–3
1
1–2
–
6–9
Products equivalent to 1 BU
Volume
Mass, g
Energy value
(kcal)
1 piece
25
50
1 piece
20
60
2 soupspoons
45
55
2 soupspoons
50
251
1 glass
1/2
250
200
450
350
250
90
70
50
65
50
45
50
Sometimes (mostly in obese diabetics) achievement and maintenance of normal body weight
may be enough to eliminate the need for oral hypoglycemic agents or insulin.
So, the diet should be planned in such way that the patient can follow it for the rest of his or her life
without starving or becoming malnourished.
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, acarbose, repaglinides.
Oral antidiabetic drugs
1. Preparations of sulfonylureas
1st generation: Acetohexamide
Tolbutamide
Tolazamide
Chlorpropamide 2nd generation: Glibenklamide
Glipizide
Glikvidone
Gliklazide
Glimeperide
2. Postprandial stimulators of insulin secretion:
• Meglitinide analogs (Repaglinide)
• Phenylalanine derivative (Nateglinide)
3. Biguanides (Metformin)
4. Thiazolidinediones (Rosiglitazone, Pioglitazone)
5. Preparations, slowing down absorption of carbohydrates (Acarbose, Miglitol)
6. Incretines (Glucagon-like peptide – 1, DPP-4 inhibitors)
Sulfanilureas include:
- first generation: Tolbutamide, Chlorpropamide, Tolazemide, Acetohexamide (now are not used
in treatment of the diabetics);
- second generation: Glibenclamide (Maninil), Glipizide (Glurenorm), Gliquidon;
- third generation: Glimepiride (Amaryl).
Action:
1) influence on the pancreatic gland:
- increasing of the β-cells sensitivity to the glucose and as a result higher secretion of glucose;
- 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:
1) patients with type 2 DM (over the age of 35 – 50 years) who do not suffer severe metabolic
abnormalities (hyperglycemia), ketosis or hyperosmolality;
2) [duration of diabetes less than 15 years.]
Contraindications.
1) type 1 DM;
2) blood diseases;
3) acute infections, heart, cerebral diseases;
4) trauma, major;
5) pregnant diabetics or lactation;
6) III – IV stages of angiopathy (but Glurenorm can be used in patients chronic renal failure,
because of gastrointestinal tract excretion);
7) coma and precoma.
Side effects.
1) hypoglycemia (hypoglycemic effect of sulfanilureas will be the most obvious in 7 – 12 days
from the beginning of the treatment);
2) allergy;
3) influence on gastrointestinal tract (nausea and others);
4) leucopenia (decreasing of the quantity of white blood cells, platelets);
5) primary or secondary failure. (Primary failure defined as an inadequate response during the first
month of treatment with maximum dosage, occurs in approximately 5 % of patients. Secondary
failure is defined as a recurrence of hyperglycemia after an initial satisfactory response.
Secondary failure may be due to nonadherence to eihter diet or sulfanilurea therapy, to disease
progression, or to loss of efficacy of the agent.)
Biguanides include:
Metformine (Siofor), Adebit, Bufarmin.
Action:
1) inhibition of gastrointestinal glucose absorption;
2) decreasing of glyconeogenesis, lipogenesis;
3) enhancing glucose transport into muscle cells;
4) increasing the quantity of insulin’s receptors;
5) stimulation of anaerobic and partly aerobic glycolis;
6) anorrhexogenic effects.
Indications:
Obese patients with type 2 DM, with middle severity of the disease without ketosis.
Contraindications:
1) heart and lung disease with their insufficiency (chronic heart and lung failure);
2) status with hypoxemia;
3) acute and chronic liver and kidney diseases with decreased function;
4) pregnant diabetics, lactation;
5) old age;
6) alcoholism;
7) coma and precoma.
Side effects.
1) allergy;
2) gastrointestinal tract disorders;
3) lactoacidosis.
Acarbosa.
Action:
1) inhibition of gastrointestinal tract absorption (blocation of α-glucozidase);
2) lowering of pastprandial glucose level (postprandial “spikes” in blood glucose are increasingly
implicated as a major cause of cardiovascular complications);
3) partly reducing fasting glucose levels by indirectly stimulating insulin secretion in patients who
retain β-cell function (and acarbose has a protective effect on β-cells).
Contraindications:
Chronic gastrointestinal disorders: pancreatitis, colitis, hepatitis.
Side effects:
flatulence, diarrhea.
Algorithm of the management of type 2 DM by WHO
1st step – diet, physical activity and metformin 2 g per day
2nd step – 1st step + add sulfonilureas (glimepiride)
3rd step – 2nd step + add basal insulin
4th step – metformin 2 g per day + intensive insulinotherapy.
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.
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).
1) hypoglycemic action;
2) treatment of chronic diabetics complications;
3) influence on the immune reactivity.
Patient’s education.
1) the nature of DM and importance of metabolic control;
2) the principles and importance of good nutrition and reasonable exercise program;
3) the principles of adequate foot, dental and skin care;
4) treatment of DM during the periods of illness;
5) techniques of insulin administration and measurement of urine and blood glucose level (if
taking insulin);
6) recognition of hypoglycemia, its causes and methods of prevention;
7) the importance of general and specific measures to minimize in the best possible way diabetic
complications and maintain of good overall health.
I.
Tests and Assignments for Self-assessment.
Multiple Choice.
Choose the correct answer/statement:
1. What oral hypoglycemic agent can be used in patient with chronic renal failure?
A. Maninil
B. Glurenorm
C. Metformin
2. What group of oral hypoglycemic agents have to be used in patient with type 2 DM without
obesity?
A. Sulfanilureas.
B. Biguanides.
C. Acarbose.
3. The patient with Diabetes Mellitus type 2 is treated by Ma-ninile in a dose of 20 mg/day. When
he had pneumonia, he increased the dose of insulin to 16 UNITS to intesify the restorative
processes before dinner. A week later the patient showed the defection in behaviour: aggressiveness, sometimes laughed loudly. Communication with patient is diffcult, her look is
meaningless, signifcant sweating, tachycardia, the arterial blood pressure - 220/120 mm Hg.
Defne the reason of the state of the patient:
A. Hypoglycemia
B. Crisis in course of pneumonia
C. Intolerance of medicines
D. Allergy to insulin
E. Specifc features of the patient’s character
4. The patient of 52 years during random checkup has the fasting level glycemia - 7.2 mmol/l, the
glucosuria - 0.5 g/l. Body height -167 cm, body weight - 92 kg. Defne initial tactics of
treatment:
A. Diet with carbohydrate restriction
B. Insulin
C. Biguanides
D. Incretines
E. Sulfonylureas of 2 generation
Answer: 1 – B. 2 – A. 3 – A. 4 – A,C,D.
Real-life situations to be solved:
Patient R., 62 years, obese, without complaints. Fast serum glucose level is 9,4 mmol/l. What is
your diagnose and treatment?
Answer: Type 2 DM (first time found). Low-calorie diet and biguanides.
A 45-yer-old female who has had diabetes mellitus for 5 years and was treated only by diet,
complains on weight loss, polyuria, polydipsia, weakness. The fasting serum glucose level 13,2
mmol/L. What is your diagnose and treatment?
Answer: Type 2 DM, moderate serity, subcompensative stage. Diaet and sulfanilureas (maninil).
Students Practical Activities.
Work 1 : Students’ group is divided into 2 sub-groups, that work near the patients’ bed: ask the
patients on organs and systems, take anamnesis of the disease , anamnesis of life, make objective
exam. With the teacher’s presence. In the class-room they discuss the patients, learn data of
laboratory and instrumental exam. of these patients.
1.To group the symptoms into the syndromes.
2.To find out the leading syndrome and make differential diagnosis.
3.To formulate the diagnosis.
4.To make a plan of treatment.
Methodological recommendation prepared assistant, c.m.s. Chernobrova O.I.
It is discussed and confirm on endocrinology department meeting
" 31 " august 2012 y. Protocol № 1.