DIABETES MELLITUS, CRITERIA.
- A normal fasting blood glucose – 60-100 mg/dl, in diabetes mellitus – 10-15% higher– 70-125 mg/dl.
- Glucosuria is observed if glucose level > 180 mg/dl.
- Kenoturia. Hydroxybutyrate and other acetones and acetoacetates.
- Microalbuminuria – 30-300 mg/day.
- HbA1c (normal – 5-6 %) – elevation during 120 days.
- Glycoalbumin (4- 6,5%) – elevation during 14 days.
DIABETES MELLITUS. DIAGNOSING.
- Fasting blood glucose – 126 mg/dl
- Blood glucose level at any time – 200 mg/dl + symptoms
- Blood glucose level following the 2-hour glucose tolerance test– 200 mg/dl
- HbA1c > 6.5 %
DIABETES MELLITUS. CLASSIFICATION.
- Diabetes mellitus type I
- Diabetes mellitus type II
- Diabetes associated with pancreatic b-cell defects
– MODY 1: mutation in the gene (HNF-4 alpha), rarely, the diabetes of the young.
– MODY 2: mutation associated with the glucokinase synthesis, very rarely.
– MODY 3: mutation of the gene (HNF-1 alpha), the most common.
– MODY 4: mutation of the gene (HNF-1), very rarely.
– MODY 6: mutation of the gene (HNF-1 alpha), the most common.
– defect in mitochondrial DNA.
- Genetic defect in the insulin action
– Type A insulin-resistance
– Leprechaunism or Donohue syndrome
– Rabson-Mendenhall syndrome
– Lipoatrophic diabetes
- Pancreatic endocrine diseases
- Drug- or chemical-induced diabetes mellitus
- Genetic syndromes ( Down, Terner, Klinefelter)
- TYPE I DIABETES MELLITUS
- Viral infections (parotitis, roseola, coxsackievirus в4), toxins (pesticides, cyanides), autoimmune processes.
- Hla b18, в8, в15, вк3, вк4 – common, hla dqw 3.1 – rarely.
- Genetic predisposition is not significant. The incidence in identical twins is 50%.
DIABETES MELLITUS TYPE II
- Antibodies to insulin receptors
- Reverse regulation dysfunction associated with hyperinsulinism
- Lack of sensitivity of target organs to insulin in obese patients, in patients with normal body weight. The loss of early-phase insulin secretion.
CHARACTERISTICS OF DIABETES MELLITUS TYPE I AND II
|CHARACTERISICS||Type I||Type II|
|Genetic markers||6 th chromosome||Not known|
|Age in disease onset||< 20||> 40|
|The disease onset||Fast||Gradual|
|Honeymoon period (remission phase)||Yes||No|
|Body weight||Normal-decreased||Normal – increased|
|Plasma insulin||Normal-decreased||Normal – increased|
|Antibodies to islet cells and insulin||Often||No|
|HLA genetic markers||Yes||No|
|Chronic complications||Through the years||In diagnostics|
|Acute complications||Ketoacidosis||Hyperosmolar coma|
INSULIN RESISTANCE, OBESITY AND LIFESTYLE.
Insulin resistance is manifested by the decreased sensitivity of peripheral tissues to insulin. Insulin facilitates the glucose transport from blood to cells. Insulin is essential for the intra-cellular transport of glucose into insulin-dependent tissues such as muscle and adipose tissue, otherwise the glucose deficit in cells will occur. In this case the glycogenesis (the process of glucose synthesis from fatty acids) and glycogenolysis processes (glycogen breakdown with subsequent glucose release) will be activated. Transported into blood, the glucose will increase glycaemia level. If a person leads sedentary lifestyle, therefore, muscles do not work and do not burn glucose, losing the habit of utilizing it. Glucose unclaimed by muscles results in increased blood glucose level.
The glucose transporter function is increased by insulin activity and active muscle work, therefore, the increased physical activity in diabetes II type results in decreased blood glucose level due to increased glucose uptake by muscles.
Sedentary lifestyle requires increased insulin secretion for balancing blood sugar level. Hyperinsulinemia increase the appetite and results in obesity.
High-calorie diet containing great amount of carbohydrates and fats aggravate the obesity. Person is going round in circles: hypodynamia – aggravated obesity – greater hypodynamia – aggravated obesity. The term visceral (abdominal) obesity defines excessive fat accumulation around the organs within the abdominal cavity is associated with obesity in insulin resistance conditions. Abdominal fat oxidize very quickly and may be dangerous due to the increased risk of atherosclerosis and cardiovascular diseases.
METABOLIC SYNDROME. DEFINITION.
Metabolic syndrome is a complex of metabolic, hormonal and clinical abnormalities arising from obesity and insulin resistance. This special condition of patient is not considered to be a nosological entity but rather a risk factor resulting in the development of such dangerous diseases as diabetes II type, severe obesity, hypertension, ischemic heart disease, atherosclerotic vascular disease, gout, polycystic ovarian syndrome, erectile dysfunction, liver steatosis.
METABOLIC SYNDROME. CRITERIA
- Obesity, waist circumference >94 сm in men and > 84 сm in women,
- Triglyceride level > 150 mg/dl
- Hdl level < 40 mg/dl
- Ap > 130/85
- Fasting glucose level > 100 mg/dl
- Obesity, most commonly associated with insulin resistance
- High insulin level
- High LDL and triglyceride level
- Serum protein, TNF, C-reactive protein level
Insulin resistance is a pathological condition in which cells fail to respond normally to the hormone insulin available in blood in sufficient concentrations. According to present-day ideas, the resistance of peripheral tissues (muscle, adipose, hepatic) to insulin underlies a pathogenesis of type II diabetes. Biological effects of insulin may be divided into 4 groups:
VERY FAST (SECONDS): hyperpolarization of cell membranes, changes in glucose and ion transport through membranes;
FAST (MINUTES): activation or inhibition of enzymes, resulting in prevailance of anabolic proceess (glycogenesis, lypogenesis, protein synthesis) and inhibition of catabolic process;
SLOW (MINUTES TO HOURS): increased absorption of aminoacids by cells, selective induction or repression of enzymatic synthesis;
THE SLOWEST (FROM HOURS TO DAYS): cell mitogenesis and replication (DNA synthesis, gene transcription).
Insulin resistance is not only the parameter which characterizes the metabolism of carbohydrates, but also includes the measurement of fat and protein metabolism, endothelial functions, genes expression, etc.
There are many diseases and conditions accompanied by insulin resistance as follows:
PHYSIOLOGICAL INSULIN RESISTANCE (adolescence, pregnancy, high-fat diet, nocturnal sleep);
METABOLIC (diabetes mellitus (DM) II type, obesity, decompensated diabetes mellitus I type, significant nutritional deficiency, alcohol abuse);
ENDOCRINE (thyrotoxicosis, hypothyreosis, Cushing syndrome, acromegalia, pheochromocytoma);
NON-ENDOCRINE (essential hypertension, hepatic cirrhosis, rheumatoid arthritis, trauma, burns, sepsis, surgical interventions).
INSULIN RESISTANCE. ETIOLOGY.
Prereceptor. Production of incomplete insulin molecule is genetically conditioned.
Receptor. Decreased receptor quantity (target organs for insulin – liver, muscles, adipose tissue)
Postreceptor. Decreased cellular metabolic activity of insulin.
Decreased tyrosine kinase activity
Decreased glucose transporters
Decreased activity of pyruvate dehydrogenase and glycogen synthase
Synthes is of insulin antagonists (antibodies to insulin, contrinsular hormones)
GLUCOSE TOLERANCE TEST
- Fasting glucose level -100-126 mg/dl
- Family history of diabetes mellitus
- Unexplained retinopathy, neuropathy
- Nephropathy, hypercholesteremia, diseases of coronary vessels, peripheral vascular disease, cerebrovascular diseases, especially in adults under 50 years old.
- Glycosuria even if blood glucose level is normal.
- Spontaneous abortions, premature birth, abundance of water at pregnancy, still birth, big fetus, history of gestational toxicosis.
- Gestational diabetes
- Reactive hypoglycemia
- Glucose 75 g + water 300 ml shall be orally administered during 5 minutes with subsequent measurement of blood sugar: at once, 1 hour later and 3 hours later.
- Within 0-2 hours – >200 mg/dl – diabetes
- Glucose level within 140-199 mg/dl – glucose intolerance (attention should be paid as diabetes is diagnosed in 40 % of cases).
- Glucose level within 140-199 mg/dl and fasting glucose level within 100-126 mg/dl – impaired glucose tolerance
- 3 hours – glucose level < 60 mg/dl – reactive hypoglycemia.