Download Diabetes mellitus: classification, etiology, pathogenesis, diagnosis of

Diabetes mellitus: classification, etiology, pathogenesis, diagnosis of diabetes
1 and type 2.
Diabetes mellitus (DM) - diabetus mellitus - a heterogeneous system disorder caused by an absolute (I
type) or relative (II type) insulin deficiency, which in the beginning is a violation of carbohydrate, and
then all kinds of metabolism, eventually leading to the defeat of all the functional systems.
LED - is a syndrome of chronic hyperglycemia, is caused by the impact of genetic and zhchogennyh
factors.
Anatomical and physiological data of the pancreas and its hormones.
Pancreas (pancreas) is located behind the stomach, about the level I and 11 of the lumbar vertebrae.
Length = 15 cm Width - 3.2 cm, weight - 70-100 grams. The pancreas is composed of three parts: the
head, body and tail. The bulk of the exocrine pancreas is the part that produces the major part of the
pancreatic juice. About 1-3% by weight of the prostate accounts for endocrine tissues - pancreatic islets
(islets of Langerhans is 1-1.5 million) - a group of clusters of specialized cells. The blood supply is due to
pancreatic-duodenal artery and branches of the splenic artery. Pancreatic veins open directly into the
portal vein. Innervation by branches of the vagus and sympathetic nerves. In one island contains from 80
to 200 cells. In the islets of Langerhans are several types of cells: A-cell (25%) produce glucagon, B-cells
(60%) - insulin, D-cells (10%) - somatostatin and others are - 5%, which produce: vasoactive interstiralny
polypeptide (VIP), gastrointestinal peptide (GIP) and pancreatic polypeptide. B cells are located in the
center of the island, the other on the periphery.
Insulin - is a protein substance with a molecular weight - 6000. In the insulin molecule is 51 amino acid
residues of 16 different amino acids. Insulin molecule consists of two chains A and B, which are
connected by a disulfide (SS). Insulin is produced from proinsulin, under the influence of proteases.
Propnsulin consists of three lines (A, B and C). A and B - chains linked by disulfide bridges, C - peptide
binds A and B chains. The molecular weight of the proinsulin - 9000 daltons. The most potent stimulator
of insulin-glucose, which interacts with the receptor cytoplasmic membrane.
Insulin response to its impact, is biphasic: 1st - for 1-2 minutes. (Accumulated insulin), 2nd - starts after
5-10 minutes and lasts for up to 1 hour (synthesis).
Insulin in adults during the day for around 40. and into the portal vein of the liver and 80% there is
inactivated insulinazy influenced the rest of the protein binding, and some remains free in the blood.
The half-life of insulin is 30 minutes. besides liver insulin is inactivated in adipose tissue, muscle, kidney,
and placenta. In structure porcine insulin is very similar to human.
Insulin acts primarily on insulin-dependent tissues: liver, adipose tissue, muscle. Insulin has no effect on
- the kidneys, nervous tissue, lens, and red blood cells.
Insulin is an anabolic hormone that increases the synthesis of carbohydrates, proteins and fats, and
nucleic acids.
Its effect on carbohydrate metabolism:
- Increase glucose transport into the cells of insulin-dependent tissues
- Stimulation of glycogen synthesis
- Inhibition of gluconeogenesis and glycogenolysis in the liver.
On protein metabolism:
- Stimulates the transport of amino acids through cell
- Protein synthesis and inhibition of its decay.
On fat metabolism:
- Inclusion of fatty acids in adipose tissue triglycerides
- Stimulation of lipid synthesis
- Suppression of lipolysis
The biological effect of insulin is due to its ability to bind to specific receptors on the cell membrane of
the cytoplasm.
The number of insulin receptors is reduced by:
- Obesity
- An excess of glucocorticoids
- The presence of antibodies antiretseptornyh
- Acantosis nigicans
- In violation of intracellular glucose utilization.
Epidemiology. Of endocrine disease diabetes takes first place. Type II diabetes is especially prevalent
among the American Indians, in southern Italy, Germany, Poland, China and other countries, especially
among the population older than 40 years. SR on chasime and prevalence takes 3rd place in the general
morbidity, ie ¬ after cardiovascular diseases and cancer, and is 6.6%. At present in the world diabetes
affects 120 million people. In industrialized countries, every 10-15 years, the number of diabetic patients
by an average of 2 times. In 11.2% of the population in Western industrialized countries is determined
by impaired glucose tolerance (IBT) annually from 5.1% of them developing diabetes type II.
Risk factors:
- Heredity
- Pathological pregnancy (toxicosis, miscarriage, large fetus, stillbirth, frequent abortions)
- The weight of a child born> 4.5 kg
- GB, atherosclerosis
- Acute and chronic stress
- Nutritional factors (abuse of refined carbohydrate foods, fat)
- Viral disease
- Seasonal factors
- Excessive use of cyanide with food (in the form of cassava) and lack of protein.
Classification of diabetes (WHO, 1999) A clinical classes.
I. Type I diabetes mellitus (destruction of B cells. Usually leading to absolute failure)
I. A) 1OI \ 1M \ 1SHY
2.Idiopatichesky
II. Diabetes mellitus type II (the preferential ™ resistance to insulin deficiency relative to predominantly
secretory defect with insulin resistance or not)
III.
IV. Other specific types
A. Genetic defects (3-cell function
l. MODY-3 (xpomocoma 12. Gene HNF-la)
2.MODY-2 (xpomocoma 7, glucokinase gene)
3.MODY-1 (chromosome 20 gene HNF-4a)
4. Mitochondrial DNA mutation
5 Others
B. Genetic defects in insulin action
1. rezistsntnost insulin type A
2. leprechaunizm
3. -Mendenhall syndrome Rabsona
4. lipoatrofichesky diabetes
5. other (Diseases of the exocrine pancreas
I. pancreatitis 4. Cystic Fibrosis
2. injury / pancreatectomy 5. gemahromatoz
3. neoplasia 6. fibrokalkuleznaya pankreatopatiya
I) endocrinopathy
II. Gestational diabetes.
I diabetes and diabetes type II are two different nosological forms (etiologically pathogenetically
clinically, as well as for therapeutic approaches). Key pathogenetic link that unites them is the
development in both types of diabetes syndrome of chronic hyperglycemia.
Comparative characteristics of the main types of diabetes
Type of diabetes type 1 diabetes VOS
Synonym for juvenile diabetes, insulin-dependent diabetes adult diabetes, diabetes obesity, non-insulin
dependent diabetes
Usually age 30 (two peaks of disease 14 and 25 years) is usually> 40 years
Genetic data from the Association of haplotypes HLA, concordance in monozygotic twins - 40% of the
association with haplotypes NGA missing concordance in monozygotic - 95-100%
Body weight Obesity Obesity is not 80%
1 Omsk often sudden onset, and in 5-15% of cases manifests ketoacidosis develops gradually. often
subclinical late complications is often detected at diagnosis
Insulin is vital not normally required
Diagnostics. A key criterion in the diagnosis of diabetes is the level of blood glucose (hyperglycemia) on
an empty stomach. To diagnose diabetes in the presence of clinical signs, once is enough to detect
increase in blood glucose levels greater than 10 mmol / L at any time. Further investigation in these
cases is not required. Similarly, the diagnosis of diabetes is established, if the second study, the level of
fasting blood glucose greater than or equal to 6.7 mmol / l. Limit values for the cases developed oral
glucose tolerance test with 75 g glucose levels in 250 ml of water for 5 minutes. (For children of 1.75 g /
kg body weight, but not more than 75 g.).
The principal laboratory indicators to differentiate the types of diabetes, as well as the need to establish
the formation of insulin in diabetes type II is the level of C-peptide. Levels of C-ieptida less than 0.4 nmol
/ L, indicating a high probability of demonstration CD-I. Levels of C-peptide is most useful to investigate
the background of stimulated samples. Received the largest allocation of test i. Iokagonom. Glucagon 1
mg injected substances, after which the level of C-peptide in serum samples studied lo injection and
after 6 minutes. after it. The concentration of fasting C-peptide> 0.6 nmol / L and> 1.1 nmol / l after
stimulation shows sufficient activity of B cells. Level of stimulation of C-peptide less than 0.6 and shows
the need for exogenous insulin. The test is not informative if manifested in decompensated diabetes.
Laboratory methods, in addition to diagnosing diabetes, were essential in the assessment of
compensation for the disease. The most fundamental measure is the level of glycated hemoglobin NA1S
Compensation criteria of diabetes.
Good Acceptable Poor Indicator
Fasting glucose mmol / l 4,4-6,7 <7.8> 7.8
Blood glucose after a meal 4,4-8,9 <10.0> 10.0
NA1S. % <8.5 8.5-9,5> 9.5
Glucose in urine% 0 ± 5,0> 5,0
Total cholesterol, mmol / L <5.2 <6.5> 6.5
JIIIBII cholesterol, mmol / L> 1,1 ± 0,9 <0,9
Fasting Triglycerides, mmol / L <U <2,2> 2,2
BMI, kg / m "- men - women <25 <24 ± 27 ± 26> 27> 26
A / 1. mm. Hg. Art. ± 149/90 ± 160/95> 160/95
Etiology. Distinguish genetically determined (inherited) and genetically conditioned form of diabetes.
According to modern theories of heredity is determined by two or more genes (polygenic inheritance)
and implemented with the participation of endogenous and exogenous factors. Found that the
phenotype caused by the split in the IDDM and NIDDM.
- Viral infection. Suggest that under the influence of some viruses (measles, mumps epidemic. Coxsackie,
smallpox, etc.) can be selective damage / destruction / B cells
pancreatic islets, which have a genetic predisposition to such a defeat.
- Seasons (typical seasonality in DOS th winter and early spring).
- Toxic substances - N-nitrosamine in canned meat, tobacco, and other rodantitsy
- Trauma (acute and cron.), Infection, surgery.
- Stress (acute and chronic).
- Some pathological antigens HLA - systems that are located on the second chromosome of HLA system,
located on the D, DR, DQ loci increase susceptibility to the development of type I diabetes in particular
antigens: DW3, DRW3, DW4, DRW4. The presence of B8, 3 haplotype increase the risk of development.
Type 1 diabetes 2-3 times, the presence of antigens B7 and B2 increase of diabetes-ta.
The causes of type II diabetes are more likely to be - obesity, atherosclerosis, which lead to the
development of diabetes with genetic conditions and proceed hyperinsulinemia and insulin resistance.
In the development of type II determining role belongs to heredity.
Pathogenesis. The pathogenesis is a relative or absolute deficiency of insulin, and reduced sensitivity of
insulin-dependent tissues.
When I type a violation of insulin secretion in both phases, but the content of C-peptide, to some extent
preserved. It should be noted that this figure is an indicator of reserve capacity of the pancreas. When I
type the sensitivity of insulin receptors is high, but the insulin activity of the blood is reduced, which is
accompanied by a positive response to zhyugenno insulin. At the heart of Type I diabetes is the
development of antibodies to the B-cells of the islets Lapgergansa (cytoplasmic, cell-surface,
immunnopretsipitiruyuschie, organospeiificheskoe) that promote infiltration -> destruction -> death of
B-cells. These changes can be detected before clinical signs of type I diabetes. Violations of humoral
immunity in the pathogenesis of type I diabetes is given less importance, though autoantibodies to islet
cells, and antibodies to insulin and glutamate decarboxylase in some combination is detected in the
majority of patients with type I, and their titer decreased with increasing duration of disease. The death
of approximately 75% of B cells leads to a decrease in glucose tolerance. The destruction of 80-90% of
the functional ability of B cells leads to the clinical manifestation of type I diabetes.
Depending on the pathogenetic features of type I diabetes is divided into two subtypes: IA and I B.
Subtype IA associated with a defect of antiviral immunity, so pathogenetic factor is a viral infection that
causes destruction of the beta cells of the islets of the pancreas. When "viral" diabetes found in the
blood circulating autoantibodies to islet tissue. Usually after 1-3 years antibodies disappear.
1B diabetes is 1-2% in relation to all patients with diabetes. This subtype is considered as a
manifestation of autoimmune disease, as evidenced by the frequent combination! B type with other
autoimmune endocrine and endocrine diseases. Circulating autoantibodies to islet tissue to detect
clinical detection of diabetes and are present in the blood of patients in k'chsnpe almost the whole
period of the disease. 1B is associated with the pathogenesis of genetically determined defect partially
immune surveillance, ie a deficiency of T-suppressor cells, which normally prevent the development
forbidnyh clones of T-lymphocytes directed against the body's own tissue proteins.
The difference between IA and 1B confirms acquisition in IA - HLA B, 5, DR4; at 1B - HhAB8, DR3. Thus,
the subtype IA due to a violation of the immune response to some exogenous (viruses) and 1B - organ
specific autoimmune disease.
Pathogenetically type II diabetes is a heterogeneous group of metabolic disorders, namely TGO
determines its clinical heterogeneity.
The pathogenesis of type II diabetes is a violation of insulin secretion and reduce or decrease the
sensitivity of insulin receptors in insulin-dependent tissues. With type II is a sharp \ menshenie insulin
secretion in the first phase of secretion, ie because of reduced sensitivity glucoreceptors B cells of the
pancreas. In the blood is determined by a rule or - hyperinsulinemia and poor response to exogenous
insulin administration, ie there is a decrease or reduction of insulin receptors. Pathophysiological rod
type II diabetes is insulin resistance (decreased insulin-mediated glucose disposal tissues), which is
implemented on the background of the secretory dysfunction of B cells.
Several distinct mechanisms of the secretory dysfunction of islets apparatus.
• Normally, insulin secretion occurs periodically in short waves, with significant variations determined
his level every 10-20 minutes. Fluctuations reduced sensitivity of insulin receptors in the norm. In
diabetes type II, these oscillations are absent and the level of insulin is repeatedly raised.
• Very slow "early" release of insulin secretion in response to increased levels of glucose to the blood, ie,
Phase I is virtually absent, phase 2 is in response to hyperglycemia continuously in tonic mode, and
despite the excessive secretion of insulin, blood glucose levels on a background of insulin resistance is
not normalizes.
Glucagon secretion is acyclic, ie, its level increases with increasing blood glucose, and vice versa.
• An important pathophysiological role premature evacuation "immature" vesicles in cells. The released
not split proinsulin to C-peptide and insulin completely and has atherogenic effects on blood vessels and
cause atherosclerosis and metabolic syndrome.
Hyperinsulinemia and therefore a constant supply of excess glucose into the cell reduces the sensitivity
of first and then blocks insulin receptors, however, and are suppressed by postreceptor mechanisms. On
one side of the incoming glucose and body fat stored in adipose tissue. This in turn further increases
insulin resistance, on the other hand is broken lipolysis, which contributes to obesity. Due to continuous
hyperglycemia insulin secretion for many years kept at the highest level. In the final stage of B-cell
depleted.
SD II - is primarily II diabetes with obesity, ie B. Under SD II II nonobese diabetic (DM II A) is often hidden
slowly progressive type I diabetes or latent autoimmune diabetes of adults (LADA). Compared with PB
these patients is somewhat younger, they hardly reached the diabet, assigned maximum dose glucoselowering drugs (SSP), which requires transfer of patients on insulin therapy. In 70-80% of cases of LADA
can detect high titers of antibodies to islet cells.
SD II (type MODY) - a type II diabetes in young, often occurs without obesity.
Insulin stops the disposal of glucose by cells, due to the insufficiency of transporter protein - gluten-4.
Insulin deficiency is accompanied by a sharp deterioration in metabolism, especially \ glovodnogo
exchange and others. Disrupted by glycolysis, glycogen synthesis, resulting in sharply \ islpchivaegsya
glucose levels after meals. More prolonged and severe insulin deficiency is accompanied by increased
gluconeogenesis, lipolysis, proteolysis. Insulin deficiency contributes to the conversion of glucose in
insulin-dependent tissues, ie increased polyol pathway of glycolysis, accompanied by the acquisition of
sorbitol, fructose, which mainly accumulate in the walls of blood vessels, lens, in neural tissue, which
contributes to further development of angiopathy, neuropathy. Also increased glycation of blood
proteins, ie along the vessels (in small vessels on the basal membrane accumulates in large quantities
glycoproteins, hemoglobin, albumin). Because of the metabolic products of protein decreased
protective proteins, which contributes to susceptibility to infections and poor wound healing.
Tropical diabetes associated with malnutrition:
a) fibrokaltsinozom pancreas
b) without fibrokaltsinoza.
Occurs more frequently in children and adolescents and is associated with protein deficiency and usually
associated with developing countries, where use in food tropical root crops (cassava, tapioca, cassava,
etc.) containing cyanide glycosides (limarin). When their hydrolysis in the body is the end product of
shotspnat that can cumulated in the body and to the B-cytotoxic effect.
Type 1: the beginning of a sharp, sudden. Key features - hyperglycemia and glycosuria. Develops in
ispoinom 35, for labile. Propensity to ketoacidosis, the compensation only insulin therapy and diet
therapy.
By severity is divided into moderate and severe forms
• Average characterized the need for insulin replacement (regardless of dose) in patients with
uncomplicated diabetic retinopathy or presence of I, II, nephropathy stage I-III, peripheral neuropathy
without significant pain and ulcers.
• Severe combined with retinopathy II-III, IV-V nephropathy stage, peripheral neuropathy with severe
pain and trophic ulcers, encephalopathy, severe manifestations of autonomic neuropathy, a tendency
toward ketoacidosis, recurrent coma for labile. In the presence of these manifestations of
microangiopathy, the need for insulin and blood glucose levels are not considered.
Type II diabetes - has been gradually and without symptoms of decompensation. Patients more often
turn to other professionals about the abrasions to the dermatologist, itching in the vagina - a
gynecologist, neurologist - pain and legs, etc. Lose weight slightly, sometimes gain weight, diagnosed
incidentally. Occur in patients older than 40 years, there has been frequent combination with
atherosclerosis and obesity. Sometimes the disease debut hyperosmolar coma. Within a stable, no
inclination to ketoacidosis and hypoglycemic states against diet alone or in combination with CSP.
Divided by severity:
- A mild form characterized by the possibility of compensation by diet alone, a combination with
retinopathy I st., Nephropathy. I st. transient neuropathy.
- Moderate - compensation with MSP combination with retinopathy II, III-IV nephropathy Art., Transient
neuropathy
- Severe - compensation is achieved with the help of BSC or periodic insulin.
- Combined retinopathy II-III century. and nephropathy IV-V century., severe manifestations of
peripheral and autonomic neuropathy, encephalopathy. Occasionally, a severe form of diabetes
diagnosed in patients compensating diet, if you have the above symptoms microangiopathy and
neuropathy.
Status of carbohydrate metabolism characterized by compensation and decompensation
subkompesatsiey.
- Compensation - it is for the SD, which under the influence of treatment achieved normoglycemia and
aglyukozuriya
- Subindemnification - for diabetes, accompanied by moderate hyperglycemia (blood glucose less than
13.9 mmol'l. Glycosuria <50 g / day and no acetonuria)
- Decompensation - for diabetes, where the amount of blood glucose> 13.9 mmol / L in urine> 50 g'sutki
and in the presence of ketosis.
Metabolic syndrome (MS)
MS is predstadiey II diabetes, and differs from the latter lack a stable hyperglycemia, insulin resistance
because in this stage can be overcome by hyperinsulinemia. Weight loss with advanced exercise and
adequate diet may reduce risk of diabetes II by 30-50%, even at this stage.
MS includes the following major components:
• Insulin resistance
• hyperinsulinemia and high levels of C-peptide
• impaired glucose tolerance (IGT)
• hypertriglyceridemia
• reducing the level of high density lipoproteins (HDL) or increase (LDL), abdominal type of obesity
• Hypertension
• hyperandrogenism in women
• often elevated NA1S and fructosamine, microalbuminuria, impaired purine metabolism,
hypernatremia polycythemia.
1. others
11.Geneticheskie syndromes, sometimes combined with diabetes
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1. Balabolkin MI Endocrinology, Moscow, 1998
2. Vladimir Potemkin Endocrinology, Moscow, 1999.
3. Grandparents II Endocrinology, Moscow, 2000.
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frequent errors in diagnosis and treatment of diseases of the endocrine system. Separate chapters are
devoted to diseases of pituitary, thyroid, parathyroid, obesity, osteoporosis, etc.
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More:
1. Edited by EA Kholodova Handbook of Clinical Endocrinology. Minsk. Belarus, 1996.
2. Therapeutic Handbook (Washington, translated from English), 1996 (section endocrinology).
3. Edited by Starkova NT, Manual of Endocrinology, Medicine, 1996
4. Edited by H. Lavin, Endocrinology. Practice. Moscow, 1999.
5. Endocrinology. Diabetes. Fadeev PA A Reference Guide. 2009.
6. I.B.Manuhin, L.G.Tumilovich, M.A.Gevorkyan. Gynecological endocrinology in 2012. lectures on
gynecological endocrinology.
7. A.V.Kartelishev, Alexander Rumyantsev, N.S.Smirnova Actual problems of obesity in children and
adolescents. 2010.
8. AN ham. Emergency Endocrinology. 2011. diagnosis and treatment of emergency conditions
associated with endocrine diseases, outlines coma in patients with diabetes mellitus.
9. A.M.Mkrtumyan, A.A.Nelaeva. Emergency Endocrinology. 2010.
10. N. A.Petunina, L.V.Truhina. Thyroid disease. 2011.
11. G.M.Kronenberg, Sh.Melmed, K.S.Polonski, P.R.Larsen. Thyroid disease. Williams Textbook of
Endocrinology. 2010.
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hypertension. Williams Textbook of Endorcinology, 11th edition. 2010.
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1. "Internet Portal: HINARI»; 2. medscape.com; 3. Alltheweb.com; 4. Yahoo.com.
5. E-medicine.com.