Diabetes pathology

2021-01-27 12:00 AM

Dominant genetic factors are suggested after studying the same twins, if one person has diabetes, the other 100% will also have diabetes.

Define

According to the World Health Organization 1999: "diabetes mellitus is a multiple metabolic disorder characterized by chronic hyperglycaemia with the metabolic disorders of carbohydrates, fats, and proteins as a result of impairment. defect in insulin secretion, insulin activity defect or both ".

According to the World Health Organization 2002: “diabetes mellitus is a chronic disease caused by lack of pancreatic insulin production or ineffective insulin effects due to acquired and/or genetic causes with the result of hyperglycaemia blood. Hyperglycaemia damages many systems in the body, especially the blood vessels and nerves”.

According to the American Diabetes Association 2004: “Diabetes is a group of metabolic conditions characterized by hyperglycaemia due to impaired insulin secretion, impaired insulin activity, or both. Chronic hyperglycaemia in diabetes will cause damage, dysfunction or failure of many organs, especially the eyes, kidneys, nerves, heart and blood vessels ".

Epidemiology

30-50% of people with type 2 diabetes go undiagnosed.

The frequency of diabetes in the world: in the world, diabetes accounts for about 60-70% of endocrine diseases. In 1995 the countries with the highest number of people with diabetes and the number of people expected to have diabetes by 2025 were India (19 to 57 million), China (16 to 38 million), the United States (14 to 22 million); in which India is the country with the fastest growth rate.

1985: 30 million people have diabetes; 2000: 171 million; 2030: forecast 366 million; in which the majority of patients = 65 years old in developed countries and 45-64 years old in developing countries.

3.2 million people with diabetes die from diabetes complications every year, equivalent to 6 cases / minute.

Frequency of diabetes in the country:

2002: City: 4.4%, delta: 2.7%, midland: 2.2%, mountainous region: 2.1%.

Hanoi: 1991: 1.2%, 1999 - 2001: 2.42%, Hue City 1992: 0.96%, Ho Chi Minh City: 1993: 2.52 (0.4%.

According to the World Health Organization, in 2000, Vietnam had 791,653 people with diabetes and increased to 2,342,879 people by 2030.

Pathogenesis 

Type 1 diabetes mellitus

Factors: genetic, environmental, immunological.

Two stages of developing type 1 diabetes:

Stage 1: Creates a constant autoimmune response to isolated cells, expressed by the presence of autoantibodies GAD65, IAA, ICA, IA-2 (alone or in combination)

Stage 2: Progression from an autoimmune cell response to type 1 diabetes mellitus.

Genetic:

Type 1 diabetes with high association with frequent proliferation of HLA antigens, predominance of HLA in combination with type 1 diabetes varies by race, HLA B8, B14,15, B18, Cw3, DR3 and DR4 is found in racial white diabetes patients, while HLA DR3, DR4 are associated with type 1 diabetes in Asia, Africa and Latin America. HLA DR3 or DR4 was found in 95% of type 1 diabetes mellitus compared with 45-50% of racial white controls.

The study of homozygous twins suggests that the genetic effect in type 1 diabetes is less common than with type 2 diabetes. Only 30% of identical twins with type 1 diabetes will develop. become sick. This also suggests that environmental factors are related to the pathogenesis of diabetes. In contrast, identical twins of type 2 diabetes are more likely to occur within the first year of illness than siblings.

Environmental factors:

Type 1 diabetes results from infection and toxicity that damages the pancreas, and the immune system attacks and destroys pancreatic beta cells. Environmental factors associated with damage to pancreatic islet cell function include viruses (mumps, rubella, coxsackie B4 virus), toxic agents (nitrophényl-urea is toxic to mice), and cytotoxic agents. other cells such as hydrogen cyanide from damaged tapioca or cassava roots.

Immune factors:

Humoral immunity:

Circulating antibodies against pancreatic islet cells are found in the majority of patients with type 1 diabetes at the time of diagnosis (60 - 90%) and then decrease. There is also research that suggests that an islet cell autoantibody (ICA: islet cell autoantibody) is detected during the first 5 weeks after onset in 85-90% of type 1 diabetes. In addition,> 60% of antibodies. Insulin resistance was found prior to insulin therapy (autoantibody to insulin: IAA). There is also a KT against Tyrosine phosphatase IA-2 and IA2.

In addition, most of the anti-cytostatic antibodies are directed against Glutamic Acid Decarboxylase (GAD or GADA), an enzyme located in the beta cells of the pancreas. There is a similarity between the protein content of coxsackie virus containing 24 amino acid sequence similar to GAD65.

Cell immunity:

Also plays a role in type 1 diabetes pathogenesis: it has been studied in BB mice and thanks to monoclonal antibodies revealed lymphocytosis related to type 1 diabetes (suppressed T lymphocytosis, and an increase in helper T lymphocytes / inhibitory T lymphocytes). Very recent studies suggest that the immune pathology of pancreatic islets begins many years before clinical diagnosis; the immune process is slow and continuing.

Factors other than immunotherapy may influence the natural course of-cell failure in type 1 diabetes.

Type 2 diabetes

Genetic factors:

Dominant genetic factors are suggested after studying the same twins, if one person has diabetes, the other 100% will also have diabetes.

Environmental factors:

Age, obesity, and sedation are easy risk factors for diabetes. In obese type 2 diabetes, especially abdominal obesity, sedation often has a lack of insulin binding with the intracellular receptor and post-receptor, resulting in a loss of response to insulin.

In addition, type 2 diabetes commonly occurs in various high-risk populations, including insulin resistance, increased adipose tissue abnormalities, increased VLDL, such as fasting and postprandial insulin elevation, and hypertension. metabolic syndrome).

Insulin resistance in type 2 diabetes results from a variety of pathogenetic mechanisms. Most of this mechanism is probably the result of metabolic disorders such as hyperglycaemia, increased non-esterified fatty acids. On the other hand, recent studies in the pre-diabetes population show that insulin resistance in muscle tissue occurs very early in the development of the disease. Insulin receptor kinase, phosphatase is involved in insulin activity, glucose transporter and glycogen synthesis.

-Cell dysfunction in type 2 diabetes: there are 5 disorders:

Insulin secretion disorders:

Reduced insulin response to glucose: early phase loss.

Rhythmic insulin secretion disorder: disturbance of the slow oscillating phase. Physiological insulin secretion consists of two types of fluctuations: rapid fluctuations (every 8-15 ', not related to glucose), slow fluctuations (every 80-120', closely related to the concentration of glucose).

Prinsulin metabolism abnormal: in type 2 billion proinsulin diabetes and intermediate/insulin metabolism products: increased.

Reduced-cell mass.

Amyloid (amylin) deposition in pancreatic islets. In 90% of cases of type 2 diabetes, it occurs early causing gradual loss of the volume of islet cells, especially β cells.

Role of insulin receptor substrate 2 (IRS 2: Insulin Receptor Substrate 2), NF-kB, mitochondrial dysfunction, oxidative stress.

Criteria for the diagnosis of diabetes

To diagnose diabetes, now people use the new World Health Organization standard for diagnosis in 1998 and have been redefined in 2002. Diagnosis determines diabetes if one of the three criteria below and must have at least two tests at two different times:

Any plasma glucose during the day ≥ 200 mg/dl (≥ 11.1 mmol / l), accompanied by three clinical symptoms including excessive urination, excessive drinking, unexplained weight loss.

Fasting plasma glucose ≥ 126 mg / dL (≥ 7mmol / l) (hunger means within 8 hours no sugar supply).

Plasma glucose two hours after oral administration of 75 g glucose ≥ 200 mg/dl (11.1 mmol / l) when testing oral glucose tolerance (OGTT). Intermediate stage:

Fasting blood glucose disorder (IFG: Impaired Fasting Glucose): when fasting blood glucose Go (FPG) ≥110 mg / dl (6.1 mmol / l) but <126 mg / dl (7.0 mmol / l).

Impaired Glucose Tolerance (IGT: Impaired Glucose Tolerance): when blood glucose 2 hours after OGTT (G2) ≥ 140 mg / dl (7.8 mmol / l), but <200 mg / dl (11.1 mmol / l) ).

Go <110 mg / dl (6.1 mmol / l): normal fasting glucose.

Go ≥ 126 mg/dl (7.0 mmol / l): provisional diagnosis is a follow-up of diabetes (definitive diagnosis must meet the above conditions).

Evaluate the results when testing oral glucose tolerance:

G2 <140 mg / dl (7,8 mmol / l): normal glucose tolerance.

G2 ≥ 140 mg / dl and <200 mg / dl (11.1 mmol / l): impaired glucose tolerance (IGT).

G2 ≥ 200 mg / dl (11.1 mmol / l): provisionally diagnosed with diabetes.

Note: The World Health Organization also uses capillary glucose to diagnose diabetes (attention should be paid to the accuracy of the capillary blood glucose meter); while the American Diabetes Association (ADA) only uses intravenous plasma glucose in diagnosing diabetes.

Classification of diabetes mellitus

The following is the 2004 American Diabetes Association (ADA) classification

Diabetes includes 2 main categories: type 1 and type 2 diabetes.

Type 1 diabetes mellitus (autoimmune and idiopathic)

Type 1 diabetes is characterized by beta-cell destruction of pancreatic Langerhans Island (autoimmune or idiopathic) and an almost absolute deficiency of insulin, making it susceptible to ketoacidosis if left untreated.

Onset age is most common in children and teenagers, however, can also be found in the 90s.

There are often genetic congenital factors and are associated with some environmental factors (viral infection during the fetal period, toxins ...).

Often combined with some other autoimmune diseases such as Basedow disease, Hashimoto's thyroiditis, Addison's disease.

Characterized by the presence of antibodies to GAD 65, anti-pancreatic islet cell antibody (ICA) or insulin resistance IAA, anti-tyrosine phosphatase antibody IA-2, IA-2 ((85-90% of cases) In some people (especially Asians and Africans) no evidence of an autoimmune phenomenon is found and is classified as "idiopathic type 1." The rate of beta-cell destruction varies widely, LADA (Latent Autoimmune Diabetes in Adults) can be delayed in adults.

LADA type diabetes mellitus (according to Diabetes 12.2005) :> 10% in people> 35 years old, 25% in people <35 years old.

Other names for LADA diabetes: latent type 1 diabetes, slow-progressing insulin-dependent diabetes, slow-onset insulin-dependent diabetes, slow-progressing type 1 diabetes, type 1 diabetes, 5, latent autoimmune diabetes in young adults (LADY-like), insulin-free autoimmune diabetes at diagnosis, LADA type 1 and type 2 diabetes mellitus, obesity type 2 diabetes antibodies, autoimmune diabetes in adults with slow cell failure (ADASP: Autoimmune Diabetes with Slowly Progressive β-cell failure).

LADA diagnostic standard:

≥ 30 years old.

Presence of at least 1 of 4 autoantibodies: ICA, GAD65, IA-2, IAA.

Insulin treatment is not required for 6 months after diagnosis.

Right at the time of diagnosis of diabetes mellitus, LADA has a dysfunction of TB β so there is a point of view on insulin use right from the moment of diagnosis. Most LADA patients require insulin within 6 years of being diagnosed, and in some cases insulin after 12 years. The greater the presence of autoantibodies, the faster the rate of cytopathic disorder (occurring more rapidly: ≥ 2 autoantibodies → cytoplasmic within 5 years; LADA has only ICA + or GADA + → disorder cell occurs later than (12 years), LADA has no presence of autoantibodies or only IA-2 + → cell function is not affected and remains conserved 12 years after diagnosis. guess.

Type 2 diabetes

Most commonly. Characterized by dysfunction or secretion of insulin: varies from predominant insulin resistance with relative insulin deficiency to predominant insulin secretion defect with insulin resistance.

Usually undiagnosed for many years because the level of hyperglycaemia is not severe, many cases are detected only by accident. Usually occurs in adults> 40 years old, but sometimes occurs in young, family members.

Most cases are accompanied by obesity and obesity itself aggravates insulin resistance. Many patients are not considered obese based on classical norms but have a large accumulation of fat in the abdomen.

Rarely ketoacidosis except when there is stress or infection.

Normal or high blood insulin levels in the case of predominant insulin resistance; or decreased insulin levels in the event of a defect in insulin secretion.

There is a clear family factor (perhaps due to genetics). Risk factors for type 2 diabetes include: older age, obesity, physical inactivity, hypertension, dyslipidaemia, family history of diabetes, history of gestational diabetes. morning and in certain ethnic groups at high risk of diabetes.

Other special types

Deficiency of beta-cell due to genetic defects: MODY1 to MODY 6. MODY (Maturity-onset diabetes of the young): due to a genetic defect that reduces beta-cell function causes insulin secretion. Usually occurs early (before the age of 25), characterized by a disorder of insulin secretion, while insulin activity is not affected or affected slightly. with mild hyperglycaemia. The most common type is MODY 3 due to a mutation in chromosome 12 in hepatocellular factor (HNF1 alpha).

Reduced insulin activity due to genetic defects: type A insulin resistance, atrophic diabetes mellitus, Rabson Mendenhall syndrome ...

Pancreatic exocrine diseases: fibrous pancreatitis, pancreatitis, trauma/removal of the pancreas, cancer, pancreatic fibrosis, iron pigmentation disease ...

Endocrine diseases: Cushing's syndrome, enlarged limbs, pheochromocytoma, glucagon tumours, hyperthyroidism, somatostatin tumours, aldosterone secretions ...

Drug-induced diabetes mellitus, chemicals: Vacor, pentamidine, nicotinic acid, corticosteroids, thyroid hormones, beta-agonists, alpha-sympathomimetic agonists, thiazide diuretics, Dilantin, alpha-interferon ...

Infections: congenital rubella, Cytomegalovirus ...

Uncommon forms of diabetes mediated immunity: autoantibodies to insulin receptors, stiffness syndrome ...

Some genetic syndromes are sometimes associated with diabetes: Down syndrome, Friedrich ataxia, Klinefelter syndrome, Turner syndrome, Huntington's dancing, Lawrence-Moon-Biedel syndrome, Dystrophy. , porphyria, Prader-Willi syndrome, Turner syndrome, Wolfram syndrome ...

Gestational diabetes

Gestational diabetes is a disorder of blood glucose tolerance of varying degrees, which begins or is first detected in pregnancy; whether using insulin or secretory alone for treatment and even when diabetes persists after birth. This definition does not preclude pre-existing impaired glucose metabolism or concomitant pregnancy that was not previously known.

Subclinical

Intravenous plasma glucose

Fasting, either any or 2 hours after the glucose tolerance test

oral route; valid as stated above in the diagnosis section.

Blood Insulin

Low, sometimes only traces in type 1 diabetes; conversely increased or normal or slightly low in type 2 diabetes.

C-peptide concentration

C-peptide is a component that bridges the two chains A and B of the proinsulin molecule produced by the pancreas. Proinsulin → Insulin + C peptide. C peptides help to evaluate endogenous insulin levels.

HbA1c

When blood glucose increases, the concentration of glucose in red blood cells increases, leading to an increase in HbA1c ratio. HbA1c allows the assessment of mean blood glucose concentration in the previous 2 months.

Fructosamine

The total amount of glucose-binding protein (especially albumin). Normal values ​​are 1 - 2.5 mmol / l, which varies according to the quantitative method. Fructosamine values ​​reflect the average blood glucose levels over the past two weeks.

Immunological - genetic tests

Genetics: can detect HLA-DR3 and / or HLA- DR4, HLA-DQ, HLA-DRB (14,15), HLA-DR / DQ antigens.

Immune humoral factor: Antibacterial islet cell antibody (ICA): a very important marker of the immune activity of type 1 diabetes. Anti-insulin antibody (IAA). Antibodies to Tyrosine phosphatase IA-2 and IA2 (K Antibodies to Glutamic Acid Decarboxylase (GAD65 or GADA65).

Bilan for complications or combination diseases

Cetoneuria: Indicated in severe decompensated diabetes, especially when cetone acidosis is suspected, often (+) in a coma with type 1 or type 2 severe decompensation due to some combination disease.

Electrocardiogram, chest scan, fundoscopy, retinal artery, Doppler ultrasound or lower limb artery if the stenosis is suspected, lipid balance, kidney function tests (urea, blood créatinine, microscopic albumin urine, proteinuria).

EMG electrocardiogram measurement, autonomic neuropathy probe test in the cardiovascular system, Holter measuring BP and 24-hour pulse.

Diagnose

Diagnosis of type 1 diabetes

Beginning of youth <40 years old.

Blood glucose increased according to the World Health Organization's diagnostic standards as mentioned above.

The clinical signs are loud: Urinary excess (osmotic hyperplasia), excessive drinking, overeating, weight loss, and asthénie.

The absolute reduction in insulin can lead to cétone infection and acid-cétone infection if left untreated (C-peptide <0.2ng / ml). Before absolute insulin reduction, the clinical severity dependent on the "sludge" insulin secretion was determined by measurement of blood insulin or C-peptide.

Antibody antibodies (+), and antibodies to anti-GAD (+).

Insulin-dependent treatment.

Circuit complications are common.

Concerning the HLA factor

Diagnosis of type 2 diabetes

Clinically, patients with type 2 diabetes have obvious clinical symptoms that occur after the age of 40, sometimes even earlier. Clinical signs are usually not as bleak as type 1, but can also be urinating a lot, drinking a lot, eating a lot (often with easy factors such as stress, infection ...), visual disturbances, especially signs due to hyperglycaemia such as a refractive index disorder, or there are already vascular and nerve complications. In these cases, hyperglycaemia is often combined with urinary glucose and the easy diagnosis is not necessary making the diagnostic test too complicated. Sometimes there are no symptoms at all, and the diagnosis requires systematic laboratory tests (30-50% of type 2 diabetes is undetected).

Symptoms

Acute complications

The specific acute complication in patients with type 2 diabetes is increased osmosis due to hyperglycaemia, hypoglycaemia, lactic acidosis; Type 1 diabetes mellitus is cetone acidosis.

Increased osmosis due to hyperglycaemia (HHS: Hyperglycemic Hyperosmolar State).

Usually occurs in the elderly. Decreased kidney function and thirst disorders are common in the elderly, increasing the severity and severity of this complication. Coma with an absorption of HT> 340 mOsm / Kg of water, no ketoacidosis. Clinical progression rapidly, dehydration, fever and consciousness disturbances (palpitations, coma, epilepsy convulsions). Intracellular and extracellular dehydration, mainly intracellular. Fast, shallow breathing, but without the smell of cetone.

Subclinical:

Blood glucose increases> 8g / l (44 mmol / l), can reach 20g / l, but always> 7g / l, blood sodium is very high (> 150mmol / l). Potassium can be normal or decreased due to glucose regulation by insulin, urinary cetone (-). Often with functional kidney failure, urea is always above 1.5 g / l.

Normal blood pH, unchanged alkaline reserve.

There are many ways to calculate increased permeability: (Na × 2) + G mmol / L> 320 mOsm / Kg water.

Lower blood glucose:

A symptom of concern, especially in elderly type 2 diabetic patients treated with sulfonylureas. If a diabetic patient has an automatic neurologic complication that causes a catecholamine secretion response, masking hypoglycaemic symptoms, the patient as well as the physician cannot be alert. Hypoglycaemia in elderly diabetic patients is the source of cerebral or coronary stroke, increasing the mortality of diabetes, even moderate hypoglycaemia, but if repeated many times is also very dangerous. and no recovery.

Lactic acidosis:

Occurs in elderly type 2 diabetes mellitus patients, often with impaired hepatocellular impairment, or renal failure, and often due to treatment with Biguanide. Rarely

Diabetic cetone acidosis (DKA: Diabetic Ketoacidosis):

Occurs in patients with type 1 diabetes, type 2 rare. Aura can be very discreet: fatigue, loss of appetite, vomiting. Pain in the epigastric region, lumbar specific. Excessive urination and increased thirst, and cetone> ++ urine are alarming symptoms, even in the absence of clinical symptoms. There are a few cases of severe cetone acidosis occurring over a few hours, or days, and the rate of appearance is a major factor in prognosis.

Clinical signs with dyspnea due to acidosis: 25 l / min tachycardia, 4-stroke dyspnoea of ​​Kussmaul. Consciousness disorder, usually without focal nerve sign and Babinski (-). There are signs of intracellular and extracellular dehydration. Gastrointestinal disturbances (vomiting, abdominal pain a lot, and diarrheal as a result of loss of electrolytes). The breath has a common odor of acetone and hypothermia. Dilated pupils.

Subclinical: Urinary glucose (++++) and urinary cetone (+++).

ECG: must be performed systematically as soon as the patient is admitted, assess the T-wave amplitude and see for cardiac conduction abnormalities corresponding to blood potassium

Blood Glucose: 3 - 5g / l - The form of ketones in the blood serum is very high

HCO3 decreased by <10 mEq / l, pH was close to 7.0 or lower (BT: 7.30).

Disorders of blood potassium: a normal first hour or increased, but decreases rapidly in the next 3 hours. Therefore, regular monitoring of the electrocardiogram is essential.

Chronic complications

Circuit complications:

Diabetic retinopathy:

The main cause of blindness. Including 2 phases: no proliferative diabetic retinopathy (NPDR: nonproliferative diabetic retinopathy) and proliferative diabetic retinopathy (PDR: proliferative diabetic retinopathy).

In addition to the complications of retinal microvascular, there are also the following complications in the eye: optical loss disorder that should be seen when blurred, colour disorder (green, yellow), cataract, neuritis, muscle paralysis ophthalmic, glaucoma (due to increased blood vessels in the iris to prevent the circulation of glasses from the anterior chamber to the back room)

Renal microvascular disease (diabetic nephropathy):

Usually occurs concurrently with retinopathy, the leading cause of progressive chronic kidney failure. The dominant symptom in the early stage is proteinuria, which appears after 10-15 years of diabetes onset, and is denoted by the first stage microscopic albumin.

In the stage with albumin - microscopic urinary, kidney biopsy will see the thickening of the capillary basal membrane with diffuse deposition in the glomerular interlayer. When these deposits are nodular, they are called fibrosis - nodular glomeruli Kimmelstiel and Wilson; This type of lesion is uncommon. After a long time, albumin urine increases gradually and appears urinary protein, if exceeding 5g / 24 hours. There may be a decrease in blood Protide, oedema specific to a nephrotic syndrome, and often a constant association with severe hypertension, with diabetic retinopathy and neuropathy.

Diabetic nerve complications:

Definition of diabetic neuropathy according to ADA 2005: "Presence of symptoms and/or signs of peripheral neurological dysfunction in diabetics after other causes have been ruled out" (Diagnosis of diabetic neuropathy is a re-diagnosis. Often combined with retinopathy, kidney disease constitutes the diabetic-specific "triopathie" (triopathie).

Acute sensory neuropathy: rare, occurs after a period of poor metabolic control (eg, ketoacidosis) or due to a sudden change in glucose control ("insulin neuritis"). Sensory symptoms are acute and prominent, nocturnal, with no neurological signs on physical examination.

Chronic sensory-motor polyneuropathy: also called asymmetric distal neuropathy. Most commonly,> 50% of cases. Play a major role in diabetic foot ulcer pathogenesis.

Clinical manifestations are mainly the feeling of a burning, stinging sensation, feeling of electric shock, paraesthesia, increased pain sensation and feeling of deep pain. Symptoms severe at night. Occurs mainly in the feet and lower extremities. 50% have no symptoms and are diagnosed only on examination; sometimes painless foot ulcers manifest.

Examination of loss of vibration sensations (using a treble 128 Hz), the sensation of pressure (using a single-fibre instrument 10g - 10g monofilament), pain and heat sensation, loss of tendon reflexes. Peripheral autonomic neurological disorders: feet cold or hot, sometimes varicose veins, dry skin, callus in the pressure area.

Single-nerve pathology: uncommon, onset suddenly. Injury to the median nerve (5.8%), the cylindrical nerve (2.1%), the spinal nerve (0.6%), the common ligament nerve. Injury to the cranial nerve (III, V, VI, VII) is very rare (0.05%). Approximately one-third of patients present with compression of the nerve (cylindrical nerve, median nerve, fibular nerve and median nerve in the hand). Diabetic atrophy is common in older type 2 diabetic patients with severe pain, weakness, and muscle atrophy near the base of one or both sides.

Autonomic neuropathy:

Major vascular complications:

Symptoms of atherosclerosis of many large blood vessels: silent myocardial anaemia, myocardial infarction (50% death), occlusion of the lower extremities causing dry necrosis, osteomyelitis; occlusion of the foot; Legs, amputation must be done. Stroke. Renal artery obstruction: murmur in the renal artery can be detected; Consequences of hypertension, kidney failure.

Complications of infection

Easily susceptible to infections: tuberculosis, viral and bacterial infections, especially persistent and frequent recurrent urinary tract infections, especially low urinary tract, making it easier for retrograde pyelonephritis and kidney failure. Skin and mucosal infections: staphylococcal furunculosis, vulvitis, bursitis, sometimes it is this infection that causes the onset of diabetes.

Other complications

Hypertension:

Often combined with diabetes mellitus, sometimes before diabetes appears, or usually due to glomerulonephropathy, atherosclerosis; The most common frequency with type 2 diabetes is obesity because there is a correlation between obesity and hypertension.

Skin complications:

In addition to infected boils, the skin also has the following symptoms: atrophic atrophy, represented by nodules where the centre is atrophy, the surrounding area is purple, located in the finger or lower extremities, allergies skin caused by insulin, adipose tissue hypertrophy or atrophy of adipose tissue.

Diabetic feet:

Pathogenesis of diabetic foot infection: 3 factors combined.

Peripheral vascular pathology (microvascular and large blood vessels).

Peripheral neuropathy.

Immunodeficiency: due to decreased lymphocyte function, hyperglycemia, basal membrane thickening.

Classification of infection:

Low:

Surface ulcers.

Pus or serum discharge.

Necrosis is absent or very little.

There is no manifestation of systemic toxicity.

Moderate:

The ulcer surface is deeper.

Often there is a discharge of pus.

Moderate tissue necrosis.

Osteomyelitis may be present.

Mild systemic manifestations: fever, increased BC.

Severity:

Superficial or deeper ulcers (into subcutaneous tissue, bones, joints).

Suppurate.

Severe and widespread tissue necrosis.

Symptoms of severe systemic toxicity: acidosis, septicaemia.

Treatment

Treatment of type 1 diabetes

Treatment goals:

Eliminate symptoms, avoid long-term complications, by good blood glucose control, with HbA1c <7%, combined with lipid disorder correction, good protide, normal stable weight, and avoid cetone infection. Avoid developing degenerative complications (limiting acute and chronic complications).

Avoid therapeutic complications (atrophy of adipose tissue, hypoglycaemia) and educate patients about their disease.

General treatment and treatment strategy:

Educating patients about diabetes: Educating patients on how to use drugs, secretory secretions and drug complications, especially signs of hypoglycaemia for timely use such as using fast sugar or reporting to the doctor. Specialists know or immediately hospitalized.

Eating and exercising:

Diet: Patients with type 1 diabetes are usually thin, so they must increase their daily caloric requirements.

Moderate exercise and exercise, of course, a combination of insulin. Carefully monitor blood glucose and insulin dose because of the risk of hypoglycaemia.

Treatment with insulin:

Types of insulin used:

Regular insulin: Fast-acting; If subcutaneous injection works after 15-30 minutes, maximum effect after 1 hour, lasting 4-6 hours., should be injected before eating 20-30 minutes ..

Inject in many ways (intravenous, intramuscular, subcutaneous, peritoneal), each injection has a different duration of action, using a syringe, a pen

Insulin intermediate (NPH) (lasting> 8 hours and <24 hours). Effective after 1-2 hours, up to 4-5 hours.

Mixed NPH Insulin: A mixture of fast insulin and NPH type intermediate insulin. Market names are Mixtard 30 HM, Scillin 30 (human insulin biosynthesis) .... The drug begins to work after 30 minutes of injection, works up to 2-8 hours, lasts 24 hours.

The Mixtard 30 HM Penfill does the same thing.

Intermediate-acting insulin with zinc: Duration of action within 6 - 36 hours. The disadvantage is that it hurts the injection site, so the injection must be done in the thigh and buttocks

Slow acting insulin: Do not use in an injection pen, start working 2 hours 30 after injection, maximum 7 - 15 hours, last 24 hours, eg Monotard HM

Ultra-slow-acting insulin (ultra lente): The effect lasts 36 hours.

Beta cells secrete insulin: each cell has 10,000 or more particles, each seed contains 200,000 insulin molecules, and insulin is released into the blood only when the blood glucose is high after a meal.

The way of injection and injection: usually by the subcutaneous route, in case of acute complications such as ketoacidosis or increased osmosis, intravenous infusion, intravenous injection.

Note: Only fast insulin can be injected intravenously, but the intermediate types, acupuncture, zinc are not used intravenously.

How to store insulin: Insulin is stable at temperatures from 7 0 C - 27 0 C, but it is best to store 4 - 8 0 C, should not be injected immediately after taking it from the refrigerator.

Insulin side effects:

Lower blood glucose.

Immune reactions resulting from insulin therapy: Insulin allergy: in the form of urticaria. It is rare today because there is semi-biological insulin or human insulin.

Insulin resistance.

Fatty tissue dystrophy at the injection site: There are 2 manifestations: atrophy of subcutaneous adipose tissue; Subcutaneous adipose tissue hypertrophy is still an unavoidable problem.

Contradictory hyperglycaemia: Somogyi effect: insulin overdose lowers glucose, stimulates blood glucose-raising hormones (catecholamine, cortisol, glucagon), aggravating complications.

oedema: Due to the retention of salt and water.

Indications for insulin treatment:

Type 1 diabetes mellitus: Lifelong replacement therapy.

Type 2 diabetes: intensive or permanent treatment depending on complications or disease combination.

Gestational diabetes.

Insulin therapy regimen:

For rapid insulin: Indicated in an emergency such as ketoacidosis, hyperosmotic coma (intravenous infusion, by intravenous seringue or pump). In addition, rapid insulin is often indicated when blood glucose fluctuations, difficult to control. Inject under the skin 30 minutes before eating. Multiple injections, or 2 or 3 quick shots before meals, or in combination with slow or mixed insulin in the evening

For insulin NPH: Or indicated in diabetes that blood glucose is stable, need to inject 2 nose/day: 1 in the morning and 1 in the afternoon. Or in combination with fast insulin in the technique of 3 or 4 injections: intermediate injection in the evening, rapid insulin injections in the morning, at noon and at night.

For mixed NPH insulin: This type is used in two ways:

Technique 2 injections/day: 2 injections mixed, choose this type of mixture with the aim of fast reducing blood glucose after eating, while slow-acting all day (nose during the day) and throughout the night. bright (night nose).

3-shot technique: fast insulin injection in the morning and noon, mixed nose injected before dinner, this technique is more effective than 2 doses.

For slow insulin. One-shot injection technique; indicated for diabetic patients with relatively limited insulin requirements

Immunosuppressants:

Immunosuppressive therapy in early-onset type 1 diabetes is progressive. Although there are a few cases of withdrawal or a decrease in insulin requirements, the majority of patients exhibit sugar intolerance. The most specific type of immunosuppressants is monoclonal KT, which is anti-specific on T-cell production. Some non-immunosuppressive drugs such as Probucol tend to depress free radicals, and Nicotinamide inhibits synthesis Poly (ADP ribose) (an enzyme that repairs damage to NAD) to impair the NAD-supplying cell.

Pancreatic transplant.

Treatment of type 2 diabetes

Treatment goals:

Good blood glucose control as noted above.

Treatment of combined risk factors (tobacco, blood pressure, dyslipidaemia).

Means of treatment:

Patient education.

Save time and be physically active, lose weight.

Glucose-lowering drugs: Including the following groups of oral anti-diabetic drugs:

The drug increases insulin secretion.

Sulfamides (Sulfonyl Uréase)

Metiglinide (Repaglinide) và D. phenylalanine (Nateglinide)

Biguanide: Increases tissue glucose use (muscle, fat cells).

Α-glucosidase inhibitors.

Other groups of drugs: It also creates good regulation of blood glucose through the intestinal mechanism, and reduces postprandial hyperglycemia. Or the Thiazolidinedione group that improves insulin resistance.

Practical application:

For type 2 diabetes, especially for younger people, energy retention and physical activity are the first choice. In patients with slightly increased blood glucose <200 mg/dl and HbA1c <8.5% should apply 4-6 exercise and secretion, if the blood glucose is not improved, then use oral hypoglycaemic drugs.

Diet:

Daily food ration:

Reduced calorie secretion in obese patients (20 kcal/kg/day).

Maintain calories in patients of normal weight (30 kg/kg/day).

Increased calories in thin patients (40 kg / kg / day)

Respect the balance between the following 3 foods:

Glucide: 50 - 55% (50%) of the daily calorie serving (that's the base serving size). Use fruit with every meal, but be limited. Delayed sugars or poly sugars (powdered ones) and those with fibre (dry légume) slow postprandial sugar rise because of their slow absorption. Limit the use of simple sugars (rapidly absorbed). Can use artificial sweeteners such as saccharine, Aspartame.

Lipide: 30-35% (35% average) of the daily calorie serving. Preference is vegetable oil.

Protide: 15% of the daily calorie serving.

Alcohol: Moderate alcohol consumption in diabetics is acceptable, provided that calorie/day is calculated (1g of alcohol for 7 calories) and should not be used on an empty stomach, easily lowering blood glucose.

Exercise, exercise:

Weight loss; Improved blood sugar during and after physical activity (decreased insulin resistance, increased peripheral insulin sensitivity). Decreases LDL-C, increases HDL-C. Beneficial effect on the heart. Maximize oxygen use, slows resting and exercise heart rate, and moderately reduces blood pressure.

Oral hypoglycaemic agents:

The drug works to stimulate insulin secretion:

Sulfonyl Uréase group: Metabolized in the liver, t1 / 2 differently, excreted by the bile or kidney, high blood protein ​​binding, the risk of hypoglycaemia due to stimulation of insulin secretion.

Effects of Sulfonyl uréase (SU). SU mainly stimulates the pancreas to secrete insulin.

Extra-pancreatic activity on hepatic glucose synthesis, glucose transport, glucagon release.

SU reduces insulin resistance and postprandial hypoglycaemia due to a decrease in glucose toxicity, and direct increase in hepatic potency, when blood glucose decreases, liver cells are more sensitive to insulin.

SU also works to increase post-receptor susceptibility.

SU drug groups:

Generation I:

Currently rarely used.

Chlorpropamide: Diabénèse 500mg / tablet (half-life is 36 hours).

Carbutamide: Glucidoral, 500mg tablets, The effect of 1/2 life is 45 hours. The effect lasts 24 - 60 hours. Dosage 1/2 - 1 tablet/day, using a single dose.

Generation II:

Gliclazide: Diamicron 80 mg, Prédian, Glucodex, Clazic, 80mg tablet. The effect of 1/2 life is 12 hours. The effect lasts 12 - 24 hours. Dosage 1-3 tablets / day. Use 2 times/day (before or during breakfast and dinner). For the elderly, reduce 1/2 dose.

Diamicron MR 30 mg, Clazic SR 30mg, slow-acting, once in the morning, 1-2 tablets/time

Glibenclamide: Daonil 5mg, Hémi-Daonil 2.5mg, Daonil faible 1,25mg (5 hours). Effects 1/2 life 6 - 16 hours. The effect lasts 12 - 24 hours. Usual dose 1-2vs / ng, can be increased 3v / ng. Drink right before the main meal. 1 - 3 times / day

Glipizide: Glibénèse, Minidiab: 1/2 life effect is 3-7 hours; effect lasts 6-12 hours; 5mg / tablet; dose 5 - 20mg / day, 2 times / day.

Generation III:

Glimepiride (Amaryl *, Amarel *) tablet 1mg, 2mg, 3mg. The effect of 1/2 life is 5 - 8 hours. The effect lasts 12-24 hours, the dose is 1mg / ng, can be increased gradually in steps of 1mg, 2mg, 3mg, 4mg, 6mg, increasing time by interval 1-2 weeks; The usual dose is 1-4 mg / ng. Drink before breakfast or meal, take a single dose of the day.

Glinide: stimulates insulin secretion when blood glucose is high, so it can regulate glucose in meals, control blood sugar after eating. Including:

Répaglinide (Novonorm *, Prandin *): 0.5mg, 1mg, 2mg tablet; dose 4mg / day in two divided doses, 15 minutes before meals. Lasts 3 hours.

D-phenylalanine (Natéglinide). Starlix *, 60 - 120mg tablets, 60-120mg dose / timex 3 times / day, given before eating; lasted 1 hour 30 minutes.

Biguanides:

Metformin (Dimethyl biguanide):

Fast-acting metformin: Glucophage, Siofor, Fordia, 500mg tablet,

Slow acting metformine: Glucophage retard (Metformine HCL) 850mg; Siofor 850mg; Fordia 850mg

Glucophage for the first dose of 500mg, 2-3 times/day; drink with or after eating; After 10-15 days, Glucophage retard can be replaced with 850mg, 2 times/day.

Glucinan, Stagid: dose 2 - 3 tablets/day, taken with meals.

Effects: Does not stimulate insulin secretion, so there is no side effect of lowering blood sugar. However, due to many mechanisms of action, it still reduces the effect of fasting blood sugar, especially after eating; The drug has a dominant effect on the liver, reduces liver sugar neoplasm, improves post-receptor response, increases glucose consumption in target cells, regulates blood lipid disorder, and reduces appetite threshold. Priority indication for type 2 diabetes mellitus

Medications that inhibit intestinal glucose absorption:

Acarbose: Glucobay, Glucor *. 50mg, 100mg tablets. The dose is increased gradually 50 mg (3 times / day, orally at the beginning of food.

Voglibose (Basen *) 2nd generation. Tablet 0.2mg, 0.3mg. Dose 0.2mg, 3 times / day, right before eating

Benfluorex: (Mediator):

Effects: similar to Metformin, 150 mg tablets. Dose: 1-3 tablets / day (gradually increasing the dose), starting 1-2, 3 tablets / day.

Thiazolidinedione:

Good indication in type 2 diabetes, non-fatty insulin-resistant type 2.

Effects: Increases insulin sensitivity, reduces glucose, TG, increases HDL.

New classes of drugs:

Glitazones act on receptors, reduce insulin resistance directly in target tissues, reduce blood glucose, but easily gain weight. These include Rosiglitazone (Avandia) and Pioglitazone, started in France in 2000.

Avandia (Rosiglitazone maleate): 4 mg/day, after 12 weeks if better blood sugar control is needed, it can be increased by 8 mg/day. Use when hungry or full. Point:

Type 2 diabetes does not control blood sugar well after secretion and exercise.

Combination with SU or metformin when diabetes 2 is treated with secretion and SU or metformin without good stabilization of blood glucose

Contraindicated in heart failure grade 3 - 4 (NYHA), liver failure or liver disease with ALT> 2.5 times BT. Side effects: oedema due to salt and water retention, anaemia, the return of ovulation in the premenopausal period

Treatment of insulin in type 2 diabetes:

Temporary insulin therapy (also known as type 2 diabetes that requires insulin or invokes insulin (insulin-nécessitant, insulinorequérant):

Treat insulin in patients with type 2 diabetes when:

Symptoms worsened, despite chemotherapy and oral hypoglycemic drugs.

Sign 4 more: thirst, urinate a lot, drink a lot, eat a lot and be thin.

Urinary cystitis (+++).

Severe and chronic hyperglycaemia (> 3g / l), (HbA1c> 7% despite maximal oral drug therapy (causing increased sugar toxicity).

Pain in many lower extremities.

Situations that require insulin:

Infections.

Surgical intervention.

(Purpose to avoid the blood glucose imbalance associated with some serious illnesses such as infection or surgical intervention).

Or in patients with type 2 diabetes who are being treated with drugs that increase the glucose (such as corticoids ..).

Or gestational diabetes.

In most of these cases, insulin use is done in the hospital or at home, blood glucose is regularly monitored for insulin dose adjustments. Depending on the response, the doctor will decide to stop insulin and return on oral antidiabetic therapy.

Indications of insulin in this case can be alone or in combination with oral antidiabetic drugs.

If insulin <40UI, Glucophage 2 capsules/day, morning and evening, then 3v / ng, insulin decreases from 2 - 4 UI every 2 days.

Long-term (ultimate) insulin therapy: Is indicated in the following cases:

Kidney, liver, heart disease, or eye complication, cannot continue on oral antidiabetic drugs.

Or because diabetes has progressed for many years, chronic blood glucose imbalance. The pancreas does not produce enough insulin.

How to use insulin in type 2 diabetes: Insulin can replace pills or a combination of two types of insulin and an oral drug called combination therapy. The insulin dose is adapted according to blood glucose. The number of injections is the same as in type 1.

Treatment of diabetes complications

There are many complications, both acute and chronic, some of the cardiovascular complications such as hypertension, coronary artery disease, kidney disease is presented in the specialist treatment sections. Here we only briefly discuss the treatment of common acute complications such as ketoacidosis, hyper-osmotic coma, chronic complications such as neurological complications.

Complications of acidosis-ketones (acidocetose):

This treatment is carried out in special centres, and specialized, closely monitored

Resists dehydration and provides salt:

To re-establish fluid in the extracellular field and increase volume. Be aware of the patient's weight before acidosis: if 10% of the weight is lost, compensate for fluid equal to the lost weight. For example, a patient 60 kg, losing 10% of weight, compensates for 6 litres: 3 litres in the first 6 hours and 3 litres in the next 24 hours, including:

Isotonic saline solution: 1-2 litres in the first 2 hours.

Then stop replacing with 5% dd glucose, even 10% if glucose <2g / l, including:

2 litres over the next 4 hours.

3 litres in the next 12 hours.

Insulin treatment:

Fast insulin can give doses up to 300 UI.

Dosage: 5 - 10 UI / hour fast insulin by electric seringue. Or bolus 10 UI; If passing is not possible, then intramuscular injection (avoid high dose).

Electrolyte balance:

Bicarbonate: Indicated with caution because of the risk of hypokalaemia:

If breathing frequency> 26 l / min.

If blood pH is reduced by <7.10, only bicarbonate is required. Otherwise, it will cause metabolic alkalosis reaction once the ketones are metabolized. The metabolic alkalosis changes potassium metabolism, increasing the risk of arrhythmias

Dose 500 - 750 ml of isotonic bicarbonate (be careful not to pass it alone

Bicarbonate, which must give the same isotonic salt).

Time:

Potassium may be provided after treatment, depending on electrolytes and ECG variability.

Other treatments:

Antibiotic.

Treatment of the aetiology.

Prevent complications from gastrointestinal bleeding due to embolism.

Complications of coma increase osmosis

Compensation:

Dehydration due to increased osmosis usually reaches 10-11 litres / 24, loss of both extracellular and intracellular. It is, therefore, necessary to provide large volumes of water, but it is difficult because according to the theory of hypotonic, fast, readily available water for immediate use (distilled water and isotonic glucose), the patient must be in the special department completely. (there is a risk of rupture of red blood cells). Practices usually use isotonic salt: 0.9% sodium chlorure, 1-2 liters in the first 1-2 hours. Then compensate for hypotension 0.45%. The amount of rehydration solution maybe 6-8 litres / 12 hours, with rest in the next 24 or 48 hours.

Insulin:

Immediate injection, a lower dose of acidocetose acidosis; first 10 - 15 UI, then 1 - 2 UI every 1/2 hour using power séringue. If electric séringue is not available, the usual dose of séringue is 5 - 10 UI, repeated every 2 hours, if the blood glucose <200 mg%, the glucose 5% or 5% dextrose must be administered, but the blood glucose must be maintained 250 - 300 mg%, avoid cerebral oedema.

Regulates blood potassium:

Carefully monitor the electrolytes to see if there is hypokalaemia, if any, for potassium 10-30mmol / L

Heparin:

For early to avoid embolism, to change the prognosis.

Antibiotic:

Treat primary or secondary infections.

Treatment of the cause:

Shock resistant:

Dobutamine vasomotor 5-15 μg / kg / min, or dopamine 3-5 μg / kg / min.

Plasma pass.

In summary: In the first 36 hours the following goal must be achieved:

Blood glucose nearly 250 mg%

HT osmolality is close to <320 mOsm / kg water.

The amount of NT decreased by nearly 50 ml/hour.

Treatment of diabetic neurological complications

Aldo-réductase inhibitors:

Sorbinil: Treated for 1 year, with good clinical improvement, and proved to be effective for the onset of neuropathy, but results are limited in length, severe lesions.

Torestat: Also gives good results after 6 months of treatment, with no serious side effects.

Myo-inositol: Increases neurotransmission, but does not prevent sorbitol stasis.

Sorbitol-dehydrogenase inhibitors: Reducing oxidation of sorbitol to Fructose by substance S.0773 is a prodrug provided by Geinsen et al., Dose 100 mg/kg/day / 3d.

Treatment of postural hypotension

In the first time, usually to change the state of hypovolemia, in combination with drugs. The most effective treatment is

Mineral-corticoids such as Fludrocortisone, a dose of 100 - 300 (g / day (with a high salt menu, 2-6 g of salt/day).

Metoclopramide (primperan): dopaminergic antagonist, 10mg dose of primperan / tablet x 3 times / day.

Pre-synaptic alpha-adrenergic receptor antagonists:

Yohimbin 2mg tablet, 4mg dose 3 times / day.

Be careful in patients with a history of stroke.

Dihydroergotamine: a vasoconstrictor, in addition to migraine therapy, also for orthostatic hypotension due to the antihypertensive effect of serotonin 5 HT2 receptors, but high doses have adrenergic receptor agonist effects and serotonin effects. 

Tamik *, 3mg tablet x 2 capsules / day, while eating.

Seglor * capsule 5mg, ikaran LP * 5mg tablet, dose 10mg / day, divided by 2.

Beta-bloquant should not be combined.

Beta inhibitors: In a very small number of patients with increased beta receptors, propranolol is indicated (low dose).

Alpha 1 agonist: If you have failed to use these drugs, use an alpha 1 agonist such as midodrine (Lutron). Dose 2.5-4 mg every 6 hours, usually in combination with dihydroergotamine and caffeine.

The agonist of somatostatin has a long effect: for hard-to-treat postural hypotension, occurring in the postprandial period, use Octreotide at a dose of 0.1-0.5 g / kg subcutaneously in the morning or dark.

Prostaglandin synthesis inhibitors: such as indomethacin, ibuprofen, are also capable of altering postprandial hypotension in diabetic patients.

Treatment of gastroparesis

Gastroparesis causes nausea, or vomiting is treated.

Metoclopramide (primperan), dopamine antagonist, 10mg tablets, 4 times/day, but if the stomach is paralyzed, it must be administered by injection because of poor drug absorption in the stomach.

Other drugs such as:

Cisapride (prepulside *): May increase acetylcholine release from the pineal nerve (plexus myenteric), stimulate gastric and duodenal movement, dose 10-40 mg 30 minutes before meals

Dopaminobloquant: Domperidone (motilium), improves gastric arrhythmia, 20mg / tablet, dose 10-40 mg / day, maybe 80mg / day in four divided doses, for 30 minutes before eating.

Cholinergic agonists (sympathomimetic): Bethanechol chloride 10mg, 2 times / day.

Cholinesterase inhibitors: pyridostigmine bromide 1-2 mg/day, can reduce dry mouth.

Erythromycin: stimulates motilin receptors, stimulates gastric spasm after meals and hunger.

If all fails, jejunum surgery can be done, and intestinal feeding.

Treatment of diabetic diarrhoea: