MINISTRY OF HEALTH PROTECTION OF UKRAINEVynnitsa national medical university named after M.I.Pyrogov

«CONFIRM»on methodical meeting of endocrinology departmentA chief of endocrinology department, prof. Vlasenko M.V._________________“_31_”_august___ 2012 y

METHODOLOGICAL RECOMMENDATIONSFOR INDEPENDENT WORK OF STUDENTS

BY PREPARATION FOR PRACTICAL CLASSES

Scientific discipline Internal medicineМodule № 1 Basis of Internal medicine

substantial module №1 “Diagnostic, treatment and prophylactic basis of main endocrinology diseases”

Topic Topic №1: Diabetes mellitus. Prevalence. Classification. Pathogenesis of main clinical symptoms. Clinics. Laboratory and instrumental investigations. Differential diagnosis on syndrome (polydipsia and polyuria, hyperglycemia, glucosuria). Type 2 diabetes mellitus, features of the clinical course.

Course 4Faculty Medical № 1

Vynnitsa – 2012

METHODOLOGICAL RECOMMENDATIONSfor the students of 4-th course of medical faculty for preparation to the practical

classes from endocrinology

1.Тopic №1: Diabetes mellitus. Prevalence. Classification. Pathogenesis of main clinical symptoms. Clinics. Laboratory and instrumental investigations. Differential diagnosis on syndrome (polydipsia and polyuria, hyperglycemia, glucosuria). Type 2 diabetes mellitus, features of the clinical course.

2. Relevance of topic: It is probably fair to state that about 2 to 4 percentage of the world population is affected with diabetes mellitus (DM). The disease is more common in persons after age 45, in obese individuals, in certain ethnic groups, and in those with a positive family history of DM. The prevalence of DM in the world is very high. In 2010 230 million patients with DM was register in the world, 5% of them with type1 DM and 95% of them with type 2 DM (more than 200 million patients). Type 2 DM is a part of metabolic syndrome. They provoke deadly vascular accidents - stroke and myocardial infarction. DM leads to invalid complication (to blindness, to renal failure, diabetic food with gangrene and amputation of lower extremities). This patient can not work and early died.

3. Aim of lesson: - to learn etiology and pathogenesis of DM- to learn classification and pathogenic particularities of some forms of DM- to learn signs, symptoms and diagnostic criteria of DM

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. Morphology of the pancreas and physiologic particularities of the pancreas endocrine function.2. Regulation of glucose blood level.3. Pathogenesis of metabolic changes in patients with insulin insufficiency.4. Viruses with B-cell cytotropic action.

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 biologic effects of insulin.2. Definition of term “DM”.3. Epidemiological aspects of DM.4. The main causes of increasing frequency of DM.5. The role of virus infection in DM development.6. The role of autoimmune process and other damage factors of the pancreas in DM development.7. Pathogenesis of type I DM.8. Pathogenesis of type II DM.9. Differential diagnosis between type I and type II DM.10. Classification of DM by WHO (1985, 1999). 11. Pathogenesis of tropical diabetes.12. Pathogenesis and signs of gestation diabetes.13. Pathogenesis of DM which developed due to some status and syndromes.14. Stages of DM development.15. Risk factors of DM.16. Types of impaired glucose tolerance.17. The main signs and symptoms of DM and pathogenesis of them.18. Damaging of the skin and subcutaneous adipose tissue in patients with DM.19. Changes of the bones in the diabetics.20. Particularities of gastrointestinal tract changes in the patients with DM.21. Damaging of the cardiovascular system in patients with DM.22. Damaging of respiratory and urinary systems in patients with DM.23. Changes of the eyes in patients with DM.24. Laboratory diagnostic criteria of DM and impaired glucose tolerance.25. Stages of severity of DM , diagnostic criteria of each stage.26. Stages of DM compensation and diagnostic criteria of each stage.27. Duration of DM.

Short content of the theme.The term DM refers to the excretion of large quantities of sweet urine. Diabetes is an old

word for siphon and means “dieresis”, mellitus means “sweet”. The clinical syndrome known as DM comprises a wide variety of symptoms, physical findings and laboratory abnormalities, in which multiple etiologic factors are involved, the pathophysiology is partly understood and treatment is unsatisfactory. The hallmark of DM is hyperglycemia.

DM – is endocrine – metabolic disease, which develops due to absolute or relative insulin insufficiency and characterized by chronic hyperglycemia, changes of different systems and organs of patient.The action of insulinInsulin is an anabolic hormone (promotes the synthesis of carbohydrates, proteins, lipids and nucleic acids). The most important target organs for insulin action are:the liver, muscle and adipocytes. The brain and blood cells are unresponsive to insulin.The effects of insulin on carbohydrate metabolism include:

1) stimulation of glucose transport across muscle and adipose cell membranes;2) regulation of hepatic glycogen synthesis;3) inhibition of glucose formation – from glycogen (glycogenolysis) and – from amino-acid

precursors (glyconeogenesis).The result of these actions is a reduction in blood glucose concentration.Protein metabolism:1) the transfer of amino acids across plasma membranes;2) stimulation of protein synthesis;3) inhibition of proteolysis.Lipid metabolism:1) incorporation of fatty acids from circulating triglyceride into adipose triglyceride;2) stimulation of lipid synthesis;3) inhibition of lipolisis.Nucleic acids metabolism:

1) stimulation of nucleic acid synthesis by stimulating the formation of adenosine triphosphate (ATP), DNA and RNF.

Other effects:1) stimulation of the intracellular flew of potassium, phosphate and magnesium in the heart;2) inhibition of inotropic and chronoropic action (unrelated to hypoglycemia).

The action of insulin can be decreased by:- glucagon (stimulates glycogenolysis and glyconeogenesis);- somatostatin (inhibits secretion of insulin and regulates glucose absorption from alimentary tract

into blood);- glucocorticoids (decrease of glucose utilization by tissues, stimulate glycogenolysis and

glyconeogenesis, increase lipogenesis (in patients with insulinoresistancy));- katecholamines (adrenaline) (inhibits β-cells secretion, stimulates glycogenolysis and ACTH

secretion);- somatotropin (stimulates α-cells (which secret glucagon), increases activity of enzymes which

destroy the insulin, stimulates glyconeogenesis, increases of glucose exit from the liver veins into blood, decreases of glucose utilization by tissues);

- ACTH (stimulates glucocorticoides secretion and β-cells secretion);- thyroid hormones (increase glucose absorption into blood, stimulate glycogenolysis, inhibit fat

formation from the carbohydrates).

The diagnosis of DM is established on the basis of determination glucose blood level on empty stomach and after glucose load.

Oral glucose-tolerance test (ОGTT)

Glucose load: adult – per oral intake of 75 g glucose (or 100 g sugar), infant – 1,75g/kg body weight, but no more 75 g

Glucose in the capillary

blood, mmol/l

Normal Impaired tolerance to glucose

Fasting hyperglycemia

(impaired glycemia in fasted state)

Diabetes mellitus

fasting level (on an empty

stomach)

< 5,5

is less

< 5,5

< 6,1

5,5 – 6,1

5,5 – 6,1 ≥ 6,1

is more or equally

in one hour after glucose

load

< 8,9 -

-

-

in two hours < 7,8 7,8 – 11,1 < 7,8 ≥ 11,1

after glucose load

Pathophysiology of DM.

Insulin lack

Defective polymorphonuclear function → infection↑Hyperglycemia → glucosurea → polyurea → dehydration↓HyperosmolalityProteolysis → weight loss → muscle wasting → polyphagiaLipolysis → free fatty acid release → ketosis → acidosis

Classification of DM

- primary DM (genetic, idiopathic) divided into type1 and type2 DM

- secondary (symptomatic) DM – DM is the one of symptoms of other diseasese, divided into:

pancreatogenic DM – diseases of exocrine part of pancreas

endocrinopathy – diseases of endocrine glands with hyperproduction contrinsulin hormones:

- acromegaly – increase of somatotropine – hypophysaris DM

- thyrotoxicosis – increase of TSH, T3, T4 – thyrogenic DM

- Cusing disease and syndrome – increase of ACTH and glucocorticoids – steroid DM

- pheochromocetoma – increase of adrenalin, noradrenlin – adrenal DM

- glucaganoma – increase of glucagon

diabetes, induced by medications or toxic substances (DM may be caused by intake of contrinsulin drug, nonsteroid anti-inflammatory drug, beta-adrenoblockers, tiasid diuretics)

- DM in pregnant (gestational diabetes) – because placenta produce contrinsulin hormones

- DM, associated with genetic syndrome, autoimmunity diseases and nutritional disorders

Classification of DM and impaired glucose tolerance by WHO (1985).

A. Clinical classes.

I. 1) Type I DM (insulindependent diabetes);

2) Type II DM (non insulindependent diabetes):

- in persons with obesity (80-90%);

- in persons with normal weight.

II. DM which is secondary to some status and syndromes:

1) pancreatic diseases (chronic pancreatitis; tumor of pancreas);

2) endocrine diseases or hormonal abnormalities (pheochromocytoma, Cushing’s syndrome,

thyrotoxicosis and others);

3) drug exposures (glucocorticoids, thiazids, thyroid hormones, oral contraceptives);

4) a variety of a genetic syndromes;

5) insulin receptors’ abnormalities;

6) mixed status.

III. Tropical diabetes:

1) pancreatic diabetes (it develops due to fibrocalculosis or protein-deficiency);

2) pancreogenic diabetes (it develops secondary to hemochromatosis).

IV. Gestation diabetes.

V. Impaired glucose tolerance :

- in persons with obesity;

- in persons with normal weight;

- in persons with some syndromes and status.

B. Statistic risk factors (in patients with normal glucose tolerance but with high risk of DM

development):

- previous impaired glucose tolerance;

- potential impaired glucose tolerance.

The terms “ insulindependent diabetes” and “ non insulindependent diabetes “ characterize

pathogenetic mechanisms of development DM and next therapy.

Etiologic classification of DM (1999).I. Type 1 of DM (destruction of β-cells which mostly leads to absolute insulin insufficiency):

- autoimmune;- idiopathic.

II. Type 2 of DM (resistance to insulin and relative insulin insufficiency or defect of insulin secretion with or without resistance to insulin).

III. Other specific types:- genetic defects of β-cells function;- genetic defects of insulin action;- pancreatic diseases (chronic pancreatitis; trauma, pancreatectomy; tumor of pancreatic

gland; fibrocalculosis; hemochromatosis);- endocrine disease;- drug exposures;- infections and others.

IV. Gestation diabetes.(Gestation diabetes is defined as hyperglycemia diagnosed for the first time in pregnancy. It occurs in individuals who have an inherited predisposition to develop diabetes and may take the form of either type 1 or type 2 diabetes. Gestation diabetes is associated not only with increased rate of perinatal morbidity and neonatal mortality but also with high incidence of subsequent diabetes in mother. Treatment is with diet modification and insulin. Insulin does not cross placenta while oral hypoglycemic agents cross placenta and therefore contrindicated.)

Stages of DM development1. Prediabetes (risk factors or predispose factors):

- obesity;

- positive family history of DM;

- persons which were born with weight more than 4,0 kg;

- women in which: = were born children with weight more than 4,0 kg; =had abortions

and dead child in anamnesis;

- persons with:

= atherosclerosis, hypertension;

= autoimmune diseases;

= furunculosis;

= rubella, mumps, coxsackie virus, infectious hepatitis, cytomegalovirus, infection

mononucleosis.

1. Impaired glucose tolerance (latent DM).

2. Clinical manifestation of DM.

Absolute insulin insufficiency means that pancreas produce insulin in very low quantities or doesn’t produce it at all (due to destruction of beta-cells by inflammative, autoimmune process or surgery).Relative insulin insufficiency means that pancreas produces or can produce insulin but it doesn’t “work”. (The pathologic process can be on the next levels:- beta cells: they can be not sensitive for the high level of glycemia;- insulin: abnormal insulin, insulin antibodies, contrainsulin hormones, absence of enzyme, which

activates proinsulin (into insulin));- receptors (decreased receptor number or diminished binding of insulin).

Type I, or insulin-dependent diabetes mellitus (IDDM) is characterized by pancreatic islet beta cell destruction and absolute insulinopenia.

This individuals are ketosis prone under basal conditions. The onset of the disease is generally in youth, but it can occur at any age. Patients have dependence on daily insulin administration for survival.Current formulation of the pathogenesis of type I DM includes the following:1. A genetic predisposition, conferred by diabetogenic genes on the short arm of chromosome C,

either as part of it or in close proximity to the major histocompatibility complex (MMHC) region (more than 95 % of type I diabetes individuals are HLA DR3, DR4 or DR3/DR4; on the other hand, HLA DR2 confers protection against the development of type I DM);

2. Putative environmental triggers (possibly viral infections (Coxsackie B, rubella, mumps) or chemical toxins (nitrosourea compounds)) that in genetically susceptible individuals might play a role in initiating the disease process.

3. An immune mechanism gone awry, either initiation of immune destruction or loss of tolerance, leading to slow, progressive loss of pancreatic islet beta cells and eventual clinical onset of type I diabetes.

Stages of type I DM development (by Flier, 1986).I. A genetic predisposition or changes of immunity.II. Putative environmental triggers.III. Active autoimmune insulities with β-cells destruction.IV. Progression of autoimmune insulities with destruction of >50 % of β-cells.V. Development of manifest DM.VI. Total β-cells destruction.

Type II or non-insulin-dependent DM (NIDDM) is the most common form of diabetes, accounting for 95 – 90 % of the diabetic population. Most investigators agree that genetic factors underlie NIDDM, but it is probably not caused by defects at a single gene locus. Obesity, diet, physical activity, intrauterine environment, and stress are among the most commonly implicated environmental factors which play a role in the development of the disease. In patients with type II DM mostly we can find relative insulin insufficiency (when pancreatic gland secrets insulin but it can have changed structure or weight, or circulating enzymes and antibodies destroy normal insulin, or there are changes of insulin receptors).

Pathogenetic and clinical difference of type I and type II DM.

Signs IDD NIDD1. Age Young (under 40) Old, middle (over 40)2. Beginning of disease Acute Gradual3. Duration Labile Stable4. Ketosis, ketoacidosis Often develops Rare develops5. Body weight Decreased or normal Obesity in 80-90%of

patients6. Treatment Insulin, diet Diet, oral hypoglycemic

agents or insulin 7. Degrees of severity Middle, hard Mild, middle, hard8. Season of disease beginning Frequently autumn-winter period Absent9. Connection with HBA-system Present Absent

10. Level of insulin and C-peptide Decreased or absent Frequently normal level

11. Antibodies to β-cells Present in 80-90% of patients on first week, month

Absent

12. Late complications Microangiopathies Macroangiopathies13. Mortality Less than 10% More than 20%14. Spreading 10-20% 80-90%

Clinical presentation.

Signs and symptoms.

The classic manifestation of type I DM include:- polyurea (once plasma glucose concentration exceeds the renal threshold

(about 180 ml/dl or 8 –9 mmol/l) glucosurea ensues. Osmotic

diuresis induced by glucose results in polyurea and subsequent

polydipsia);

- polidiosia (as more water is excreted, the body requires more water intake);

- polyphagia (this occurs to lack of energy);

- loss of weight (energy (calories) is lost as glucose in the urine. Loss of water

itself also contributes to weight loss. Increased proteolysis with

mobilization of aminoacids leads to enhancement of protein

catabolism and loss of weight, notably in muscle mass);

- fatigue and weakness (probably occur as a result of decreased glucose utilization and

electrolyte abnormalities);

- acidosis (develops due to increased lipolysis which cause the release of free

fatty acids, which are metabolized to ketones by the liver).

Presenting signs and symptoms of type II DM include: polyurea, polydipsia, polyphagia; the

majority of individuals (80 – 85 %) are obese, but it can also occur in lean persons.

Patients with DM are at risk if developing of chronic degenerative complications.

Physical examination.

Skin.

The skin is a common target of DM. Many lesions can be observed, but none is specific to

the disease, with the possible exception of necrobiosis lipoidica diabeticorum (it consists of skin

necrosis with lipid infiltration and is also characteristically found in the pretibial area. The lesions

resemble red plaques with distinct borders).

The most common skin lesion is diabetic dermopathy (it is characterized by brown, atrophic,

well-demarcated areas in the pretibial region which resemble sears), besides patients sometimes

have xanthoma diabeticorum, which is usually located on the buttocks, elbows and knees, look like

eruptions (but is not really diabeticorum since it occurs in the patients with lipoprotein

abnormalities, particularly hyperchylomicronemia, whether or not patient has DM)/

The skin is dry and itch. Infections of the skin by bacteria and fungi, candidiasis of the

external female genitalia, hyperkeratosis, nail disorders are common in the patients with DM but

nothing is specific with regard to their development.

Subcutaneous adipose tissue.

The abdomen type of obesity is common in patients with type II DM. Sometimes generalized

subcutaneous adipose tissue atrophy can be observed in diabetics.

Osteoporosis and osteoarthropaphy can be find in patients with DM also.

Gastrointestinal tract.

Paradontosis, gastritis with decreased secretion ability, gastroduodenitis, hepatosis and

diarrhea are common in patients with DM.

Cardiovascular system (CVS).

Involvement of CVS, particularly the coronary circulation, is common in patients with DM.

The heart, arteries, arterioles, and capillaries can be affected. Cardiovascular changes tend to

occur earlier in patients with DM when compared with individuals of the same age. Several factors

play a role in the high incidence of coronary artery disease seen in patients with DM. These include

age of the patient, duration and severity of the diabetes, and presence of other risk factors such as

hypertension, smoking and hyperlipoproteinemia. It has been suggested that in some patients with

DM, involvement of the small vessels of the heart can lead to cardiomyopathy, independent of

narrowing of the major coronary arteries. Myocardial infarction is responsible for at least half of

deaths in diabetic patients, and mortality rate for the diabetics is higher than that for nondiabetics of

the same age who develop this complication.

Hypertension is common in patients with DM, particularly in the presence of renal disease (as

a result of atherosclerosis, destruction of juxtaglomerular cells, sympathetic-nervous-system

dysfunction and volume expansion).

Atherosclerosis of femoral, popliteal and calf larger arteries may lead to intermittent

claudication, cold extremities, numbness, tingling and gangrene.

Respiratory system.

Mucomycosis of the nasopharinx, sinusitis, bronchitis, pneumonia, tuberculosis are more

common in patients with diabetes than in nondiabetics.

Kidneys and urinary tract.

Renal disease include diabetic nephropathy (lesson 3), necrosing renal papillitis, acute tubular

necrosis, lupus erythematosus, acute poststreptococcal and membranoproliferative

glomerulonephritis, focal glomerulosclerosis, idiopathic membranous nephropathy, nonspecific

immune complex glomerulonephritides, pyelitis, pyelonephritis, cystitis and others. Obviously,

these abnormalities, with exception of diabetic nephropathy, are not at all peculiar to DM and can

be observed in many other conditions.

Eyes.

Complications of the eyes include: ceratities, retinatis, chorioretinatis, cataracts. The last one

occurs commonly in the patients with long-standing DM and may be related to uncontrolled

hyperglycemia (glucose metabolism by the lens does not require the presence of insulin. The

epithelial cells of the lens contain the enzyme aldose reductase, which converts glucose into

sorbitol. This sugar may be subsequently converted into fructose by sorbitol dehydrogenase.

Sorbitol is retained inside the cells because of its difficulty in transversing plasma membranes. The

rise in intracellular osmolality leads to increased water uptake and swelling of the lens).

The diagnosis of DM.

The diagnosis of DM may be straightforward or very difficult. (The presence of the marked

hyperglycemia, glucosuria, polyuria, polydipsia, polyphagia, lethargy, a tendency to acquire

infections, and physical findings consistent with the disease should offer no difficulty in arriving at

the correct diagnosis. On the other hand, mild glucose intolerance in the absence of symptoms or

physical findings does not necessarily indicate that DM is present.)

The diagnosis of DM include:

1. Clinical manifestations of DM.

2. Laboratory findings.

1) fasting serum glucose (if the value is over 6,7 mmol/l (120 mg/dl) on two or more separate days,

the patient probably has DM);

2) the glucose tolerance test (GTT):

If the diagnosis is still in doubt, then perform a GTT.Conditions for performing an oral GTT have been standardized:

- no special dietary preparation is required for an oral GTT unless the patient has been ingesting

<150 gm/day of carbohydrate. Then give 150 – 200 gm carbohydrate daily for 3 days prior to

test;

- unrestricted physical activity should proceed the test;

- test is performed in the morning, following overnight fast of 10 to 16 hours;

- subjects should remain seated, without prior coffee or smoking;

- blood for glucose determination is obtained from an antercubital vein before glucose ingestion

and every 30 minutes far 2 hours after ingestion ;

- the amount of glucose given is 75 g for adults (100 g pregnant women, and 1,75 g/kg of ideal

body weight for children). Patient have to drink glucose dissolved in 250 ml of water;

- the criteria for diagnosing diabetes in pregnant adults are:

a) a fasting serum glucose more than 6,7 mmol/l (120 gm/dl);

b) a 2-hour postprandial serum glucose over 11,1 mmol/l (200 gm/dl);

- the criteria for diagnosing of impaired glucose tolerance are:

a) a fasting serum glucose more than 5,5 mmol/l (100 gm/dl);b) a 2-hour postprandial serum glucose more than 7,8 mmol/l (140 gm/dl) but less than

11,1 mmol/l (200 gm/dl).

The major indication for an oral GTT is to exclude or diagnose DM (mostly type II) in those suspected of having diabetes although fasting or symptomatic hyperglycemia is absent; e.g., in patients with a clinical condition that might be related to undiagnosed DM (e.g., polyneuropathy, retinopathy). Various conditions (other than DM) and drugs can cause abnormalities in the oral GTT. The criteria of DM do not apply to patients treated with drugs that can impair glucose tolerance (e.g., thiazids, glucocorticoids, indometacin, nicotinic acid, oral contraceptives containing synthetic estrogenes) or to patients who develop nausea, sweating, faintness or pallor during the test, or to have infections, hepatic, renal and endocrine disease that impairs glucose tolerance.3) islet cell antibody levels will be positive prior to any insulin administration in 60 – 80 % of

patients with type I DM;

4) C-peptide (it is not affected by antibodies to exogenous insulin and is used to distinguish type I

and II DM if there is still a need after clinical determination);

5) glucose level in urine;

6) glycohemoglobin (this test is an indicator of blood sugar control during the previous 2-to-3-

month period);

7) acetonurea;

8) blood lipids and others.

3. Instrumental investigations usually are used to diagnose chronic complications of DM.

Degrees of severity of DM.1. Mild degree:

1) compensation can be achieved by diet;2) fast serum glucose is less than 8.4 mmol/l;3) glucosuria less than 20 gr./l (2 %);4) proneness to ketosis does not occur; long-term (chronic) complications are rare or only

functional stages can be observed.2. Moderate degree:

1) compensation can be achieved by oral hypoglycemic agents (in patients with type II DM) or insulin (in patients with type I DM);

2) fast serum glucose is 8.4 to 14.0 mmol/l;3) glucosuria is 20 to 40 gr./l (2 – 4 %);4) ketosis can occur; long-term (chronic) complications can be observed (but not last stages).

3. Severe degree:1) compensation can be achieved by insulin or oral hypoglycemic agents;

2) fast serum glucose is over 14,0 mmol/l;3) glucosuria is over 40 gr./l (4 %);4) ketosis is common and last stages of long-term (chronic) complications are present.

Stages of compensations:1. Compensation.2. Subcompensation.3. Decompensation.

Criteria of compensative stage.1. Patient hasn’t diabetic complains.2. Fast serum glucose level is normal (but can be under 8.0 mmol/l in patients which haven’t

complications and under 11.0 mmol/l in patients with long-term complications).3. Glucose in urine is absent.4. Glucose level fluctuation is under 4.4-5.5 mmol/l during the day .5. Comatose and precomatose status are absent.

Criteria of subcompensative stage.1. Patient may have diabetic complains.2. Fast serum glucose is high.3. Glucosuria is present.4. Glucose level fluctuation is over 4.4-5.5 mmol/l during the day.5. Comatose or precomatose status are absent.

Criteria of decompensative stage:1. Comatose or precomatose status are present.

Duration of DM1. Stabile (glucose level fluctuation is under 4.4-5.5 mmol/l during the day and comatose or

precomatose status are absent).2. Labile (glucose level fluctuation is over 4.4-5.5 mmol/l during the day or comatose and

precomatose status are present).

Differential diagnosis of DM is hold on 3 group of complaints: polydipsia and polyuria, normoglycemic glucosuria, hyperglycemic glucosuria

1 group – diseases with polydipsia and polyuria:

- diabetes insipidus

- chronic pyelonephritis

- hyperparathyroidism

- hyperaldosteronism (Conn`s syndrome)

- idiopathic polydipsia

2 group – diseases with normoglycemic glucosuria (glucose blood level is normal, but we see glucosuria, because the kidney threshold is damage)

- chronic pyelonephritis

- pregnancy (placental lactogen)

- phosphate-diabetes

- idiopathic glucosuria

3 group – diseases with hyperglycemic glucosuria (hyperglycemia above the kidney threshold leads to glucosuria)

- transitory hyperglycemia (alimentary and stressful (myocardial infarction, labors, acute infections, acute renal failure and other)

- all endocrinopathy with hyperproduction contrinsulin hormones (acromegaly, thyrotoxicosis, Cusing disease and syndrome, pheochromocetoma, glucaganoma)

- pancreatogenic diabetes (chronic pancreatitis, hemochromatosis)

- hepatitis, liver cirrhosis

Tests and Assignments for Self-assessment.Multiple Choice.Choose the correct answer/statement:1. What organ is not responsive to insulin?

A. Liver.B. Muscle.C. Brain.D. Connective tissue.

2. The effects of insulin include:A. Inhibition of proteolysis.B. Inhibition of glycogenesis.C. Stimulation of glycogenolysis.D. Stimulation of glyconeogenesis.E. Stimulation of lipolysis.

3. Patient L., 62 years, obese, has DM for 3 years, is treated by maninil. What is your diagnosis?A. Type I DM.B. Type II DM.C. Tropical DM.4. A 30-year-old female in her first trimester of pregnancy complains on polyuria, polydipsia,

nausea, vomiting, and anorexia. One year ago, a fasting plasma glucose 8,8 mmol/L was found. At the time she is obese. She was treated with a diet and an oral hypoglycemic agent which resulted in a reduction in plasma glucose to normal. She had pregnancy and delivery 3 years ago, and glucose level was normal diagnosis of the current pregnancy was made 9 weeks ago. A grandmother and uncle have diadetes. What is your diagnosis?

A. Type I DM and pregnancy.B. Type II DM and pregnancy.C. Gestation diabetes.D. None of the above.5. The results of the glucose tolerance test: a fasting serum glucose is 6,6 mmol/l , 2-hour

postprandial serum glucose is 14,1 mmol/l. What is your diagnosis?A. Normal.B. Impaired glucose tolerance.C. Diabetes mellitus.

6. The results of the glucose tolerance test: a fasting serum glucose is 6,6 mmol/l , 2-hour postprandial serum glucose is 9,8 mmol/l. What is your diagnosis?

A. Normal.B. Impaired glucose tolerance.C. Diabetes mellitus.

7. The results of the glucose tolerance test: a fasting serum glucose is 5,4 mmol/l , 2-hour postprandial serum glucose is 7,6 mmol/l. What is your diagnosis?

A. Normal.B. Impaired glucose tolerance.C. Diabetes mellitus.

Answer: 1 – C. 2 – A. 3 – B . 4 – B. 5 – C. 6 – C. 7 – A.

Real-life situations to be solved:

The patient R., 20 years, complains on polydipsia, polyurea, weight loss. The disease begins after mumps. During examination was found dry skin, furunculosis, liver enlargement. 1. Previous diagnosis?

2. What is the most obvious pathogenetic mechanism of the development of the disease?II. In patient with Cushing’s syndrome was found diabetes mellitus. What type of DM has patient due to pathogenesis?Answer:1. Diabetes mellitus. 2. Virus. II. Non-insulin-dependent DM.

Patient K., 56years, has DM for 2 years. He is treated by diet. In last two month he breaks dietary regimen. During examination was found: the glycemia achieves to 10,5 mmol/l, daily glucosuria is 25 gr. What is your diagnosis?Answer: Type II DM, mild degree of severity in subcompensation stage.

Patient U.,22 years, has DM for 6 years. He is treated by insulin (42 Units daily). Duration of diabetes is labile. Three years ago was diabetic coma. Glycemia level is18,3 mmol/l. Glucosuria –30 g/l. Acetonurea. What is your diagnosis?Answer: Type I DM, severe degree in decompensation stage.

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.