DISORDER OF CARBOHYDRATE METABOLISM Ph.D., MD, Assistant Professor Hanna Saturska

DISORDER OFCARBOHYDRATE

METABOLISM

Ph.D.Ph.D., , MDMD,, Assistant ProfessorAssistant Professor HaHanna Saturskanna Saturska

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 

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

This value is summary result of complicated interaction of many exogenous and endogenous influences.

1. The first it reflects a balance between

amount of glucosewhich entrance in blood

amount of glucose which is utilized by cells

2. The second, glucose level in blood reflects an effect of simultaneous regulatory influence on carbohydrates metabolism of the nervous system and endocrine glands:

pituitary gland (somatotropic thyreotropic

adrenocorticotropic hormones)

adrenal cortex (adrenalin,

noradrenalin)layer

pancreas (insulin,

glucagone, somatostatin)

thyroid (thyroxin,

triiodthyronine)

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.

Rise of glucose concentration is named hyperglicemia lowering hypoglicemia.

For example, hyperglicemia is very typical for diabetes mellitus, hypoglycemia – for glycogenosis.

hyperglicemia hypoglicemia

diabetes mellitus glycogenosis

Diabetes mellitus Diabetes mellitus, often simply referred to

as diabetes—is 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.

This high blood sugar produces the classical symptoms:

polyuria (frequent urination),

polydipsia (increased thirst)

polyphagia (increased hunger).

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.)

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.)

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.

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.

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

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

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.

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.

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

insulin

glukagon

Somato-statin

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.

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 2%–5% of all pregnancies and may improve or disappear after delivery. Gestational diabetes is fully treatable but requires careful medical supervision throughout the pregnancy. About 20%–50% of affected women develop type 2 diabetes later in life.

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.

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.

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.

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.

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.

Causes

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

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

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.

Complications of diabetes mellitus

AcuteComplications of diabetes mellitus Diabetic ketoacidosis Hyperglycemia hyperosmolar state Hypoglycemia Diabetic coma Respiratory infections

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

Galactosemia This is hereditary illness. In it’s 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

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.

Glycogenosis type I – Girke’s disease. Girke’s 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 Girke’s disease stage of tearing phosphate group is blocked. There are no free glucose hypoglycemia occur.

Hypoglycemia arises. Attached to Girke’s disease glycogen is deponed in liver and kidneys.

Girke’s disease

Type ІІ glycogenosis – Pompe’s 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 it’s deficit glycogen accumulates at first in lysosomes and then in cytosole of hepatocytes and myocytes.

Type ІІІ glycogenosis – Cori’s disease, Forbs’ disease. This illness is named limitdecstrinosis. In it’s base lies a deficit of amylo-1,6-glucosidase. Degradation of glycogen pauses in sites of branching. Glycogen accumulates in liver and muscles. Cure is diet with big proteins maintenance.

Type ІV glycogenosis – Anderson’s disease. It is called by deficit of amilo-1,4,1,6-transglucosidase (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.

 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.

Type V glycogenosis – McArdel’s disease. It’s 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 VІ glycogenosis – Hers’ disease. Illness arises as result of insufficiency of hepatic phosphorilase complex. Glycogen accumulates in liver. Typical sign is hepatomegalia.

Type VІІ glycogenosis. Illness essence is in oppression of muscle phosphofrutkinase. Symptoms are similar to McArdles disease.