Type 2 diabetes mellitus - non-insulin dependent, sugar dependent type

Normal blood glucose levels range from 2.3 to 6.0 mmol/l on an empty stomach. After a meal, the value should not exceed 7.8 mmol/l. If the norm is violated, this indicates the development of diabetes. Moreover, even with a confirmed diagnosis, it is quite possible to stabilize the indicator. To do this, you need to adjust your diet, engage in regular physical activity and give up bad habits.

Blood sugar levels: table by age

When people talk about normal sugar levels, they mean a certain concentration of glucose in a person’s blood. The indicator is measured in millimoles per liter (abbreviated mmol/l) and is determined during a blood test, which today can be done both in the hospital and at home.

The norm is presented as a range from 3.3 to 5.5 mmol/L, and not a specific value. It depends on various factors:

• age;
• state of the body;
• eating, drinking;
• lifestyle features.

However, there is no direct connection between gender and sugar levels. In this regard, the body of a man and a woman works approximately the same. Therefore, the table shows general data (assuming blood is taken from a finger on an empty stomach).

Small deviations (within a few tenths) are allowed. They are associated with lifestyle habits, food intake, smoking, alcohol and other habits.

Attention!

After eating, your sugar levels rise, which is completely normal. But even in this case, it should not exceed 7.8 mmol/l.

Diabetes mellitus is a disease that develops as a result of a relative or absolute deficiency of insulin or a disruption of its interaction with the receptor, resulting in hyperglycemia. It is characterized by a chronic course and a violation of all types of metabolism: carbohydrate, fat, protein, mineral and water-salt.

Risk factors for developing diabetes:

• Presence of diabetes in 1st degree relatives (parents, brothers, sisters)
• Impaired fasting glucose or glucose tolerance at previous examination
• Other clinical conditions that are associated with impaired glucose tolerance
• Presence of cardiovascular diseases
• Low physical activity
• In women - polycystic ovary syndrome, birth of a child weighing more than 4 kg, gestational diabetes
• BP > 140/90 or therapy for hypertension
• HDL cholesterol < 0.9 mM/l and/or triglycerides > 2.82 mM/l
• Testing for prediabetes and diabetes in asymptomatic adults is indicated if they are overweight (BMI greater than 25 kg/m2) and have one or more risk factors for diabetes. If there are no additional risk factors, the test should be performed starting at age 45 at intervals of 3 years.

There are two main types of diabetes mellitus:

• Type 1 diabetes mellitus (insulin-dependent, IDDM) occurs in 10-15% of all diabetic patients. Hyperglycemia develops as a result of insulin deficiency caused by autoimmune destruction of insulin-producing β-cells of the pancreas. The peak incidence was observed at the ages of 3-5 and 11-14 years.
• Type 2 diabetes mellitus (non-insulin dependent, NIDDM) is much more common (80-85% of cases). Hyperglycemia is caused by insulin resistance. The risk of morbidity is observed after 50 years of life.

Main differences between both forms of diabetes

In addition to type 1 and type 2 diabetes, there are other specific types of diabetes. Diabetes mellitus in such patients is a consequence of a certain primary disease (genetic or acquired), and this form of diabetes is often called secondary diabetes mellitus. The main causes are the following diseases:

• Genetic defects in β-cells or insulin action;
• Acromegaly (gigantism): GH interferes with the uptake of glucose into fat and muscle tissue by suppressing the action of insulin;
• Pheochromocytoma: the action of catecholamines is aimed at mobilizing glucose from the depot and suppressing the effects of insulin;
• Itsenko-Cushing syndrome: excessive secretion of cortisol inhibits glucose uptake in many tissues;
• Chronic pancreatitis or surgery on the pancreas causes tissue damage to the pancreas (including β-cells);
• Toxic effects on the pancreas of drugs and chemicals.

A normal pregnancy is accompanied by numerous hormonal changes that predispose to the development of hyperglycemia and, accordingly, to the development of diabetes. Up to 14% of pregnant women suffer from transient diabetes.

DIAGNOSIS OF DIABETES MELLITUS The task of a laboratory examination if diabetes is suspected is to identify or confirm the presence of absolute or relative insulin deficiency in the patient. The main biochemical signs of insulin deficiency are: fasting hyperglycemia or an abnormal increase in glucose levels after meals, glycosuria and ketonuria. In the absence of symptoms, laboratory results alone provide an accurate diagnosis. The WHO Expert Committee recommends screening for the presence of diabetes in the following categories of citizens: 1) All patients over the age of 45 years (if the test result is negative, it is repeated every three years). 2) Younger patients with:

• Obesity;
• Hereditary burden of diabetes;
• High-risk ethnic/racial background;
• History of gestational diabetes mellitus;
• The birth of a child weighing more than 4.5 kg;
• Arterial hypertension;
• Previously identified impaired glucose tolerance or high fasting glycemia;

Blood glucose testing Testing the concentration of glucose in the blood is the most common method for diagnosing diabetes. Glucose is evenly distributed between plasma and blood cells, with some excess of its concentration in plasma. The glucose content in arterial blood is higher than in venous blood, which is explained by the continuous use of glucose by the cells of tissues and organs. This explains the advantage of studying glucose in plasma or serum of venous blood over its determination in capillary blood for diagnosing diabetes. Venous blood additionally reflects such an important point as the use of glucose by cells of tissues and organs. Therefore, for the diagnosis of diabetes, it is preferable to determine glucose in venous blood.

Reference values ​​for blood glucose concentrations

Glycosylated hemoglobin Glycosylated hemoglobin is formed as a result of a non-enzymatic reaction between hemoglobin A contained in red blood cells and serum glucose. The degree of glycosylation of hemoglobin depends on the concentration of glucose in the blood and on the duration of contact of glucose with hemoglobin (the lifespan of a red blood cell). Red blood cells circulating in the blood have different ages, therefore, to average the level of glucose associated with it, we focus on the half-life of red blood cells (60 days). There are at least three variants of glycosylated hemoglobins: HbA1a, HbA1b, HbA1c, but only the latter variant quantitatively predominates and gives a closer correlation with the severity of diabetes mellitus. The results of the study of glycosylated hemoglobin are assessed as follows:

• 4-6% indicate good compensation of diabetes in the last 1-2 months,
• 6.2-7.5% – satisfactory level,
• above 7.5% – unsatisfactory.

Unlike glucose, the level of glycosylated hemoglobin does not depend on physical activity, food intake, medications, or the patient’s emotions.

Relationship between blood glucose concentrations and glycosylated hemoglobin levels

Glucose tolerance test The most informative method for diagnosing diabetes is considered to be the dynamics of changes in the level of glucose in the blood of patients in response to a sugar load - the glucose tolerance test (glucose tolerance test). A glucose tolerance test should be performed in patients if the fasting plasma glucose level is from 6.1 to 7.0 nmol/l, as well as in persons with identified risk factors for the development of diabetes (diabetes mellitus in close relatives, birth of a large fetus, impaired tolerance history of glucose deficiency, obesity, hypertension). To carry out the test, the patient must receive a diet containing at least 125 g of carbohydrates for 3 days (all hospital food tables meet this requirement). The test is carried out in the morning after 10-14 hours of fasting. An initial blood sample is taken on an empty stomach, then the patient takes 75 g of glucose dissolved in 200 ml of water, and the child takes 1.75 g of glucose per 1 kg of weight, but not more than 75 g. The blood is taken again after 120 minutes and the samples are examined for glucose content (interpretation of test results, see below).

Examination of urine for glucosuria In healthy people, glucose entering the primary urine is almost completely reabsorbed in the renal tubules and is not determined in urine by conventional methods. When the glucose concentration increases above the renal threshold (8.88-9.99 mmol/l), glucose begins to enter the urine and glucosuria occurs. Glucose can be detected in the urine in two cases: with a significant increase in glycemia and with a decrease in the renal threshold for glucose - renal diabetes. In patients with diabetes mellitus, glucosuria is studied to assess the effectiveness of treatment and as an additional criterion for compensation of diabetes:

• In type 1 diabetes mellitus, urinary loss of 20-30 g of glucose per day is allowed.
• The criterion for compensation of type 2 diabetes mellitus is the achievement of aglucosuria.

Determination of glucose in urine is not usually used to diagnose diabetes mellitus. Moreover, with age, the renal threshold for glucose increases and in older people can be above 16.6 mmol/l before glucosuria appears.

Autoantibodies Currently, IDDM is considered an autoimmune disease with destruction of β-cells of the pancreatic islets. Inducers of the autoimmune process in type 1 diabetes mellitus include Coxsackie B viruses, mumps, encephalomyelitis, rubella, etc. The detection of autoantibodies to islet cell antigens has the greatest prognostic significance in the development of type 1 diabetes mellitus. They appear 1-8 years before the clinical manifestation of diabetes. Their identification allows the clinician to diagnose prediabetes, select a diet and carry out immunocorrective therapy. Carrying out such therapy plays an extremely important role, since clinical symptoms of insulin deficiency in the form of hyperglycemia and associated complaints appear when 80-90% of insulin-producing β-cells are affected, and the possibilities of immunocorrective therapy during this period are limited. The high level of autoantibodies in the preclinical period and at the beginning of the clinical period gradually decreases over several years, until complete disappearance. The use of immunosuppressants in the treatment of type 1 diabetes also leads to a decrease in the level of autoantibodies.

Antibodies to insulin Antibodies to insulin belong to the IgG class. Antibody levels can be elevated in 35-40% of patients with newly diagnosed type 1 diabetes (i.e. not treated with insulin) and in almost 100% of children within 5 years from the time of onset of IDDM. The appearance of autoantibodies to insulin is based on hyperinsulinemia, which occurs in the initial stage of the disease, and the reaction of the immune system. Therefore, the determination of autoantibodies can be used to diagnose the initial stages of diabetes, its debut, erased and atypical forms (sensitivity - 40-95%, specificity - 99%). After 15 years from the onset of diabetes, autoantibodies to insulin are found in only 20% of patients. Long-term insulin therapy usually causes an increase in the number of circulating antibodies to the administered insulin drug. Autoantibodies are the cause of insulin resistance. However, there is not always a direct relationship between the level of antibodies and the degree of insulin resistance. Autoantibodies can also be detected in patients treated with oral antidiabetic drugs (in particular bucarban, glibenclamide). Determination of the level of autoantibodies can be used to assess the risk of developing diabetes over 5 years in first-degree relatives. In the presence of autoantibodies more than 20 units. The risk increases almost 8 times and is 37%; when autoantibodies to islet cell antigens and insulin are combined, it reaches 50%. The main antigen representing the main target for autoantibodies associated with the development of IDDM is glutamic acid decarboxylase, a β-cell membrane enzyme. Antibodies to glutamic acid decarboxylase (anti-GAD) are a very informative marker for diagnosing prediabetes, as well as identifying individuals at high risk of developing IDDM (sensitivity - 70%, specificity - 99%). Elevated levels of anti-GAD can be detected in patients 7-14 years before clinical manifestations of the disease. Over time, the level of anti-GAD decreases, and after years, antibodies are detected in only 20% of patients. Anti-GAD is found in 60-80% of patients with type 1 diabetes; their detection in patients with type 2 diabetes indicates the involvement of autoimmune mechanisms in the pathogenesis of the disease and serves as an indication for immunocorrective therapy.

Criteria for diagnosing diabetes mellitus Diabetes mellitus can be diagnosed if one of the following criteria is present:

• Clinical symptoms of diabetes (polyuria, polydipsia, unexplained weight loss) and an incidentally detected increase in plasma glucose concentration ≥11.1 mmol/l (≥200 mg%).
• Fasting plasma glucose level (no food intake for at least 8 hours) – ≥ 7.1 mmol/l (≥ 126 mg%).
• 2 hours after an oral glucose load (75 g glucose) – ≥ 11.1 mmol/l (≥ 200 mg%).

Diagnostic criteria for diabetes mellitus and other categories of hyperglycemia

WHO recommends using only venous plasma test results to make a diagnosis of diabetes mellitus

• normal fasting plasma glucose levels are up to 6.1 mmol/l (<110 mg%);
• fasting plasma glucose levels from 6.1 mmol/l (≥110 mg%) to <7.0 mmol/l (<128 mg%) are defined as impaired fasting glucose;
• fasting plasma glucose level > 7 mmol/l (> 128 mg%) is regarded as a preliminary diagnosis of diabetes mellitus, which must be confirmed according to the above criteria.

When conducting a glucose tolerance test, the following indicators are important:

• Normal glucose tolerance is characterized by a plasma glucose level 2 hours after a glucose load of <7.8 mmol/L (<140 mg%);
• An increase in plasma glucose concentration 2 hours after a glucose load ≥ 7.8 mmol/L (≥ 140 mg%), but below 11.1 mmol/L (<200 mg%) indicates impaired glucose tolerance;
• A plasma glucose level 2 hours after an oral glucose load > 11.1 mmol/l (> 200 mg%) indicates a preliminary diagnosis of diabetes mellitus, which must be confirmed according to the criteria given above.

To evaluate the results of the glucose tolerance test, 2 indicators are calculated: hyperglycemic and hypoglycemic coefficients:

• Hyperglycemic – the ratio of glucose content after 30 or 60 minutes (the largest value is taken) to its level on an empty stomach. Normally, this coefficient should not be higher than 1.7.
• Hypoglycemic – the ratio of glucose levels after 2 hours to its fasting level. Normally, this coefficient should be less than 1.3.

If the patient does not have impaired glucose tolerance, but the value of both or one of the coefficients exceeds normal values, the glucose load curve is interpreted as “doubtful”. Such a patient should be advised to abstain from carbohydrate abuse and repeat the test after 1 year.

Recommended laboratory tests to establish the diagnosis of DIABETES MELLITUS

First level tests Blood

• The amount of glucose in venous blood
• Amount of glucose after exercise (vein)
• Glycosylated hemoglobin
• Fructosamine

Urine

• Amount of glucose
• Acetone in urine

Second level tests (differential diagnosis of diabetes)

• Blood insulin level
• Blood C-peptide level (fasting)
• Autoantibodies to cells of the islets of Langerhans
• Autoantibodies to insulin
• Autoantibodies to glutamic acid decarboxylase
• Immunogenetic typing (HLA)
• DR3-B8
• DR4-B15
• B15
• DR4
• Dw4

Third level tests (diagnosis of diabetes complications) Hypoglycemic coma

• Blood insulin level
• Blood glucose level

Diabetic nephropathy (tests at least once every 4-6 months)

• Microalbuminuria
• Protein in urine (proteinuria)
• Study of 24-hour urine protein (rate of increase in proteinuria)
• Rehberg test (creatinine clearance)
• Hypercreatininemia
• Hypoalbuminemia
• Apolipoprotein A1
• Apolipoprotein B (Apo B)
• Triglycerides
• Cholesterol
• HDL cholesterol
• LDL cholesterol

Diabetic macroangiopathy

• Hyperglycemia
• Hyperinsulinemia
• Total cholesterol (increased levels)
• Triglycerides (increased levels)
• High density lipoproteins
• Accelerated thrombus formation (see “diagnosis of thrombophilia”)
• Microalbuminuria
• Proteinuria

Plan for laboratory examination of a patient diagnosed with DIABETES MELLITUS

Laboratory tests at the first visit and at annual follow-up Blood

• The amount of glucose in plasma
• Amount of glucose after exercise
• Glycosylated hemoglobin
• Fructosamine
• Apolipoprotein A1
• Apolipoprotein B (Apo B)
• Triglycerides
• Cholesterol
• HDL cholesterol
• LDL cholesterol
• Creatinine
• Electrolytes (K/Na/Cl)
• Blood insulin level
• Blood C-peptide level

Urine

• Glucosuria
• Acetone in urine
• Microalbuminuria
• Ketonuria
• Bacteriuria
• Urine sediment

Laboratory tests at follow-up visit (every 3 months) Blood

• The amount of glucose in plasma
• Amount of glucose after meals
• Glycosylated hemoglobin
• Triglycerides
• Cholesterol
• HDL cholesterol
• LDL cholesterol

Urine

• Glucosuria
• Proteinuria

Assessing the effectiveness of diabetes treatment (diabetes compensation criteria)

Types of blood glucose curves during the glucose tolerance test. Changes in glucose concentration during hyperinsulinism (1); in healthy individuals (2); with thyrotoxicosis (3); with mild form (4) and severe form (5) of diabetes mellitus.

Laboratory diagnosis of complications of diabetes mellitus Diabetic nephropathy (DN) is currently the leading cause of high morbidity and mortality in patients with diabetes. The frequency of its development ranges from 40 to 50% in patients with insulin-dependent diabetes (IDDM) and from 15 to 30% in patients with non-insulin-dependent diabetes (NIDDM). The danger of this complication is that developing quite slowly and gradually, DN goes unnoticed for a long time, since clinically it does not cause a feeling of discomfort in the patient. And only at a pronounced (often terminal) stage of kidney pathology does the patient develop complaints related to intoxication of the body with nitrogenous wastes; however, at this stage it is not always possible to radically help the patient. Therefore, the main task of a general practitioner, endocrinologist or nephrologist is to timely diagnose DN and carry out adequate pathogenetic therapy as early as possible. In the pathogenesis of DN, changes that develop in the structure of the glomerular basement membrane and capillaries are important, which leads to disruption of hemodynamic parameters of renal function. They manifest themselves in an increase in glomerular filtration rate during the period of manifestation and the first years of diabetes. Due to relaxation of the afferent and narrowing of the efferent arterioles, intraglomerular pressure increases, which has a damaging effect on the surface of endothelial cells, both through increased mechanical stress and through an increase in the permeability of the basement membranes of the glomerular capillaries for lipids and various protein components of the plasma. Disruption of the normal structure of the glomerular barrier contributes to the proliferation of mesothelial cells with the deposition of lipids and proteins, thickening of the basement membrane, increased formation of the extracellular matrix and sclerosis of the renal tissue. As sclerotic changes progress, glomerular occlusion and renal tubular atrophy develop. Hyperfiltration (more than 140 ml/min/1.73 m2), observed in the initial stages of DN, is replaced by hypofiltration, which is accompanied by an increase in creatinine and urea in the blood serum and the appearance of clinical symptoms of renal failure. DN in the first years after the manifestation of diabetes occurs latently. This period lasts about 10-15 years, and only then does proteinuria, clinical signs of renal failure appear, and at the end of the disease - symptoms of uremia, combined with anemia, acidosis, and arterial hypertension.

Classification of stages of development of diabetic nephropathy (according to Mogensen S. E.)

Algorithm for screening and management of diabetic nephropathy (from the moment of diagnosis)

In what cases should you get checked?

You need to check for sugar levels in cases where the following symptoms are observed:

• frequent thirst;
• frequent urination;
• dry skin, itching;
• dry mucous membranes;
• frequent infectious diseases;
• deterioration of vision (decreased sharpness);
• fast fatiguability;
• decreased performance.

Checks are also carried out as planned, for example, during a medical examination, passing a commission, as part of a medical examination program, etc. Patients with diabetes regularly test their blood sugar - in some cases, daily monitoring is required.

The relationship between glucose levels, cholesterol and body weight

Type 2 diabetes mellitus is almost always accompanied by obesity, hypertension and hypercholesterolemia. When performing a venous blood test in diabetics, cholesterol levels are assessed, with a mandatory distinction between the amount of low-density lipotropes (“bad cholesterol”) and high-density lipotropes (“good cholesterol”). BMI (body mass index) and blood pressure (blood pressure) indicators are also determined.

With good compensation of the disease, normal weight is recorded, according to height, and slightly exceeded blood pressure measurement results. Unsatisfactory (poor) compensation is a consequence of the patient’s regular violation of the diabetic diet, incorrect therapy (the glucose-lowering drug or its dosage is incorrectly selected), and non-compliance by the diabetic with the work and rest regime. The glycemic level reflects the psycho-emotional state of the diabetic. Distress (constant neuropsychological tension) causes an increase in glucose levels in the blood.

How to accurately determine your sugar level

You can reliably determine your blood sugar level at home (using a glucometer) or in the hospital (by taking a biochemical blood test). In the first case, you need to purchase a device and take measurements. The procedure is done in literally 1 minute.

The analysis cannot be carried out at any time and in any condition, since the results will be inaccurate. Before donating blood, you must go at least 12 hours without food or drink, including:

• juices (even without sugar);
• tea;
• coffee.

Also during this period you should avoid chewing gum, physical and emotional stress (including entertainment, entertainment, sports). It is recommended to drink only water. To make it easier to withstand this period, you need to not eat anything in the evening, and immediately donate blood for analysis in the morning.

Attention!

2 days before the analysis, exclude liver and kidneys, alcoholic beverages from the diet, limit meat, fish, tea and coffee. Also, during this time you should not engage in physical activity.

Hypoglycemia and hyperglycemia: what to do?

The two most common short-term complications of diabetes are blood sugar levels falling below the recommended target range or becoming too high. If your blood sugar levels are too high, the condition is called hyperglycemia. The condition of low blood sugar is called hypoglycemia (or simply “hypo”).

Both hyper- and hypoglycemia can ultimately lead to the development of short- and long-term complications. Thus, persistently high blood sugar levels can lead to serious complications in the long term. This is why it is critical to monitor your blood sugar levels and promptly take the steps necessary to keep your blood sugar levels within the recommended range. A continuous glucose monitoring system, the main purpose of which is to make everyday life with diabetes easier, can be a true assistant in this regard.

Analysis results: normal blood sugar level and deviation

As a result of the analysis, the exact value of glucose in the blood will be obtained:

1. If it exceeds 6.1 mmol/l on an empty stomach, this indicates the onset of diabetes mellitus.
2. If after eating or sweet drinks the value is more than 7.8 mmol/l, this also indicates diabetes.

Moreover, the study is carried out at least 2 times - only in this case (subject to confirmation of an overestimated value) can a diagnosis be reliably made.

What is the dawn effect?

Due to the fact that from 12 am to 3 am the body does not need insulin, the pancreas does not produce this biologically active compound. That is why, in the time period from 3 to 8 am, there is a sharp jump in blood glucose levels. Patients with diabetes mellitus have a more difficult time experiencing the morning dawn phenomenon, since their pancreas is not able to produce the physiological norm of insulin. A person diagnosed with type 2 diabetes will have higher blood sugar in the morning than blood sugar before bed. At the same time, glycemia remains stable throughout the night, but due to fluctuations in glucose levels in the pre-morning time, the patient experiences lack of sleep and sleep becomes polyphasic.

Blood sugar and type of diabetes

However, it is impossible to determine the type of diabetes (first or second) by the sugar level. The type of disease is not related to the result of the analysis, but to the causes of the pathology:

1. Type 1 diabetes is the most severe form, occurring in 10% of cases. It is an insulin-dependent pathology, when the main cause is associated with insufficient secretion of the hormone insulin. Treatment is lifelong injections of this substance with constant monitoring of sugar.
2. Type 2 diabetes is a less severe form and occurs in 90% of cases. This is acquired non-insulin-dependent diabetes. It is due to the fact that cells perceive insulin worse, which is why glucose does not penetrate into them and remains in the blood, which leads to an increase in levels.

Both forms of the disease are fraught with danger to the health and even life of the patient. If you do nothing, your health will worsen, which may lead to adverse consequences:

• destruction of blood vessels;
• serious metabolic disorder (ketoacidosis);
• heart attack;
• stroke;
• problems with vision and hearing;
• coma;
• limb amputation;
• bacterial and fungal skin infections;
• impotence.

What to do if you are diagnosed with type 2 diabetes?

In recent years, there has been a particularly wide spread of this pathology in the world, often causing various complications. When a patient has high sugar in type 2 diabetes or this disease is only suspected, he needs to consult an endocrinologist. Mandatory screening includes:

• blood tests from a finger and vein;
• oral glucose tolerance test (OGTT);
• determining the level of glycated hemoglobin (HbA1C).

"Diary of a Diabetic"

To control the disease, simply measuring sugar is not enough. It is necessary to regularly fill out the “Diabetes Diary”, which records:

• glucometer readings;
• time: eating, measuring glucose levels, taking hypoglycemic medications;
• name of: foods eaten, drinks drunk, medications taken;
• the number of calories consumed per serving of food;
• dosage of hypoglycemic drug;
• level and duration of physical activity (workouts, housework, gardening, walks, etc.);
• the presence of infectious diseases and medications taken to eliminate them;
• the presence of stressful situations;
• In addition, blood pressure measurements must be recorded.

Since one of the main tasks for a patient with type 2 diabetes is weight loss, weight indicators are entered into the diary daily. Detailed self-monitoring allows you to track the dynamics of diabetes. Such monitoring is necessary to determine the factors influencing the instability of blood sugar, the effectiveness of the therapy, and the effect of physical activity on the well-being of a diabetic. After analyzing the data from the Diabetes Diary, the endocrinologist, if necessary, can adjust the diet, dose of medications, and intensity of physical activity. Assess the risks of developing early complications of the disease.

The “self-monitoring diary” can be in paper or electronic form