DISORDER OF CARBOHYDRATE METABOLISM

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• DISORDER OFCARBOHYDRATE METABOLISM

Ph.D., MD, Assistant Professor Hanna Saturska
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molecular formula C12H22O11

• Major index which describes metabolism of
  carbohydrates, is a sugar level in blood.
• In healthy people it is
• 4,4-6,6 mmol/l.
• Sucrose is the organic compound commonly known
  as table sugar and sometimes called saccharose.
• The molecule is a disaccharide composed of
  the monosaccharides glucose and fructose 

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• glucose level in blood
• 3,3-5,5 mmol/l.
• GlucoseC6H12O6, also known as D-glucose, dextrose,
  or grape sugar) is a simple monosaccharide 
• Open-chain form
• Cyclic forms

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• This value is summary result of complicated
  interaction of many exogenous and endogenous
  influences.
• 1. The first it reflects a balance between

amount of glucose which is utilized by cells
amount of glucose which entrance in blood
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• 2. The second, glucose level in blood reflects
  an effect of simultaneous regulatory influence on
  carbohydrates metabolism of the nervous system
  and endocrine glands

adrenal cortex (adrenalin, noradrenalin) layer
pituitary gland (somatotropic thyreotropic
adrenocorticotropic hormones)
pancreas (insulin, glucagone, somatostatin)
thyroid (thyroxin, triiodthyronine)
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• Among enumerated hormones only insulin lowers
  glucose concentration in blood the rest of
  hormones increase it .
• The glucose concentration in blood describes
  carbohydrates metabolism both of healthy man and
  sick.
• Illnesses base of which is disorder of
  carbohydrates metabolism can flow with rise of
  glucose concentration in blood and with lowering
  of it.

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• Rise of glucose concentration is named
  hyperglicemia lowering hypoglicemia.
• For example, hyperglicemia is very typical for
  diabetes mellitus, hypoglycemia for
  glycogenosis.

hypoglicemia
hyperglicemia
diabetes mellitus
glycogenosis
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Diabetes mellitus

• Diabetes mellitus, often simply referred to as
  diabetesis a group of metabolic diseases in
  which a person has high blood sugar,
• either because the body does not produce enough
  insulin,
• or because cells do not respond to the insulin
  that is produced.

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• This high blood sugar produces the classical
  symptoms

polyuria (frequent urination),

• polydipsia (increased thirst)

• polyphagia (increased hunger).

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There are three main types of diabetes

• Type 1 diabetes results from the body's failure
  to produce insulin, and presently requires the
  person to inject insulin.
• (Also referred to as insulin-dependent diabetes
  mellitus,
• IDDM for short, and juvenile diabetes.)

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• Type 2 diabetes results from insulin resistance,
  a condition in which cells fail to use insulin
  properly, sometimes combined with an absolute
  insulin deficiency. (Formerly referred to as
  non-insulin-dependent diabetes mellitus, NIDDM
  for short, and adult-onset diabetes.)

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• Gestational diabetes is when pregnant women, who
  have never had diabetes before, have a high blood
  glucose level during pregnancy. It may precede
  development
• of type 2 DM.

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• Other forms of diabetes mellitus include
• congenital diabetes, which is due to genetic
  defects of insulin secretion,
• cystic fibrosis-related diabetes, steroid
  diabetes induced by high doses of
  glucocorticoids,
• several forms of monogenic diabetes.

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• As of 2000 at least 171 million people worldwide
  suffer from diabetes, or 2.8 of the population.
• Type 2 diabetes is by far the most common,
  affecting 90 to 95 of the diabetes population

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Feature Type 1 diabetes Type 2 diabetes
Onset Sudden Gradual
Age at onset Any age(mostly young) Mostly in adults
Body habitus Thin or normal Often obese
Ketoacidosis Common Rare
Autoantibodies Usually present Absent
Endogenous insulin Low or absent Normal, decreasedor increased
Concordancein identical twins 50 90
Prevalence Less prevalent More prevalent- 90 to 95 ofU.S. diabetics
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Type 1

• Type 1 diabetes mellitus is characterized by loss
  of the insulin-producing beta cells of the islets
  of Langerhans in the pancreas leading to insulin
  deficiency.

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• In 1869, while looking down the microscope, the
  Berlin physician Paul Langerhans discovered small
  islets of cells scattered throughout the
  pancreas. These cells are responsible for the
  production of insulin.

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Somato- statin

• Digestive enzymes include trypsin, chymotrypsin,
  pancreatic lipase, and pancreatic amylase, and
  are produced and secreted by acinar cells of the
  exocrine pancreas.

glukagon
insulin
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Type 2

• Type 2 diabetes mellitus is characterized by
  insulin resistance which may be combined with
  relatively reduced insulin secretion. The
  defective responsiveness of body tissues to
  insulin is believed to involve the insulin
  receptor. However, the specific defects are not
  known. Diabetes mellitus due to a known defect
  are classified separately. Type 2 diabetes is the
  most common type.
• In the early stage of type 2 diabetes, the
  predominant abnormality is reduced insulin
  sensitivity. At this stage hyperglycemia can be
  reversed by a variety of measures and medications
  that improve insulin sensitivity or reduce
  glucose production by the liver.

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Gestational diabetes

• Gestational diabetes mellitus (GDM) resembles
  type 2 diabetes in several respects, involving a
  combination of relatively inadequate insulin
  secretion and responsiveness. It occurs in about
  25 of all pregnancies and may improve or
  disappear after delivery. Gestational diabetes is
  fully treatable but requires careful medical
  supervision throughout the pregnancy. About
  2050 of affected women develop type 2 diabetes
  later in life.

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• When a woman has high blood sugar only while she
  is pregnant, it is a special type called
  Gestational Diabetes. Usually the blood sugar is
  kept in the normal range by insulin made by the
  body. Most of the time, pregnant women make more
  insulin to lower the blood sugar.

• However, some women cannot do this, and these are
  the women who
• develop gestational diabetes. This usually
  occurs in the second half of pregnancy.

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Symptoms

• Increased thirst
• Increased urination
• Weight loss in spite of increased appetite
• Fatigue
• Nausea and vomiting
• Frequent infections including those of the
  bladder, vagina, and skin
• Blurred vision
• Note Usually there are no symptoms.

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• People (usually with type 1 diabetes) may also
  present with diabetic ketoacidosis, a state of
  metabolic dysregulation characterized by the
  smell of acetone a rapid, deep breathing known
  as Kussmaul breathing nausea vomiting and
  abdominal pain and an altered states of
  consciousness.

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• A rarer but equally severe possibility is
  hyperosmolar nonketotic state, which is more
  common in type 2 diabetes and is mainly the
  result of dehydration. Often, the patient has
  been drinking extreme amounts of sugar-containing
  drinks, leading to a vicious circle in regard to
  the water loss.
• A number of skin rashes can occur in diabetes
  that are collectively known as diabetic
  dermadromes.

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Causes

• Type 1 diabetes is also partly inherited and then
  triggered by certain infections, with some
  evidence pointing at Coxsackie B4 virus. There is
  a genetic element in individual susceptibility to
  some of these triggers which has been traced to
  particular HLA genotypes (i.e., the genetic
  "self" identifiers relied upon by the immune
  system). However, even in those who have
  inherited the susceptibility, type 1 diabetes
  mellitus seems to require an environmental
  trigger.

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Causes

• The cause of diabetes depends on the type. Type 2
  diabetes is due primarily to lifestyle factors
  and genetics.

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Diagnosis

• Diabetes mellitus is characterized by recurrent
  or persistent hyperglycemia, and is diagnosed by
  demonstrating any one of the following
• Fasting plasma glucose level  7.0 mmol/L
  (126 mg/dL).
• Plasma glucose  11.1 mmol/L (200 mg/dL) two
  hours after a 75 g oral glucose load as in a
  glucose tolerance test.
• Symptoms of hyperglycemia and casual plasma
  glucose  11.1 mmol/L (200 mg/dL).
• Glycated hemoglobin (Hb A1C)  6.5
• Glycosylated hemoglobin and Glucose tolerance
  test

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Complications

• Diabetes doubles the risk of vascular problems,
  including cardiovascular disease.
• Glycated hemoglobin is better than fasting
  glucose for determining risks of cardiovascular
  disease and death from any cause
• The complications of diabetes mellitus are far
  less common and less severe in people who have
  well-controlled blood sugar levels.
• Wider health problems accelerate the deleterious
  effects of diabetes. These include smoking,
  elevated cholesterol levels, obesity, high blood
  pressure, and lack of regular exercise.

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Complications of diabetes mellitus
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AcuteComplications of diabetes mellitus

• Diabetic ketoacidosis
• Hyperglycemia hyperosmolar state
• Hypoglycemia
• Diabetic coma
• Respiratory infections

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Chronic Complications of diabetes mellitus

• Angiopathy Chronic elevation of blood glucose
  level leads to damage of blood vessels
• The endothelial cells lining the blood vessels
  take in more glucose than normal, since they do
  not depend on insulin.

Fundus photo showing scatter laser surgery for
diabetic retinopathy
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• Galactosemia
• This is hereditary illness. In its base lies an
  blockade of galactose metabolism. In organism
  intermediate metabolits accumulate. There are two
  the main forms of galactosemia on base of
  transferase insufficiency and on base of
  galactokinase insufficiency.

transferase insufficiency
galactokinase insufficiency
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• Glycogenoses
• Simple carbohydrates deposit in organism as
  polysaccharides. In muscles and liver accumulates
  glycogen. It consist of 4 of liver weight and 2
  of muscles weight. Muscles glycogen is used
  as of ready fuel source for immediate
  guaranteeing by energy. Liver without
  interruption provides cerebrum and erythrocytes
  with glucose .
• Synthesis and splitting of glycogen are exactly
  adjusted and coordinated processes. Attached to
  immediate need in glucose ?cells of pancreas
  secret glucagone. It activates adenylatcyclase of
  hepatic cells. Adenilatcyclase stimulates
  derivation of cAMP. Under action of cAMP takes
  place activation of proteinkinase and this enzyme
  raises activity glycogenphosphorilase and
  oppresses activity of glucogensynthase.

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• Glycogenosis type I Girkes disease. Girkes
  disease cause deficit of glucose-6-phosphatase.
  This enzyme provides 90 of glucose which
  disengages in liver from glycogen.
• It play central role in normal glucose
  homeostasis. Glucose which disengages attached
  to disintegration of glycogen or is derivated in
  process of gluconeogenesis obligatory goes over
  stage of glucose-6-phosphate.
• Enzyme glucose-6-phosphatase tears away a
  phosphate group from glucose. There free glucose
  is formed it goes out in blood.
• Attached to Girkes disease stage of tearing
  phosphate group is blocked. There are no free
  glucose hypoglycemia occur.
• Hypoglycemia arises. Attached to Girkes disease
  glycogen is deponed in liver and kidneys.

Girkes disease
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• Type ?? glycogenosis Pompes disease. Illness
  is related to deficit of lysosomal enzyme sour
  maltase, or ?-1,4-glucosidase. This enzyme slits
  glycogene to glucose in digestive vacuoles.
  Attached to its deficit glycogen accumulates at
  first in lysosomes and then in cytosole of
  hepatocytes and myocytes.
• Type ??? glycogenosis Coris disease, Forbs
  disease. This illness is named limitdecstrinosis.
  In its base lies a deficit of amylo-1,6-glucosida
  se. Degradation of glycogen pauses in sites of
  branching. Glycogen accumulates in liver and
  muscles. Cure is diet with big proteins
  maintenance.
• Type ?V glycogenosis Andersons disease. It is
  called by deficit of amilo-1,4,1,6-transglucosidas
  e (branching enzyme). As result of this There is
  derivated anomalous glycogen with very long
  branches and rare points of branching. It is not
  exposed to degradation and accumulates in liver,
  heart, kidneys, spleen, lymphatic nods, skeletal
  muscles.
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Glycogen storage disease II (Micro)
The myofibers are engorged with glycogen. On
cross sections the myofibrils are pushed to the
periphery. Despite the thick walls, this is not
hypertrophy. These patients present with
congestive failure.
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• Type V glycogenosis McArdels disease. Its
  cause is deficit of phosphorilase of myocytes.
  Typical pain displays in muscles after physical
  loading. Glycogene does not slit only in muscles.
  Here it accumulates. In liver mobilization of
  glycogen comes normal.
• Type V? glycogenosis Hers disease. Illness
  arises as result of insufficiency of hepatic
  phosphorilase complex. Glycogen accumulates in
  liver. Typical sign is hepatomegalia.
• Type V?? glycogenosis. Illness essence is in
  oppression of muscle phosphofrutkinase. Symptoms
  are similar to McArdles disease.

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Thank you for your attention!