Diagnosis of Diabetes
November 14 : World Diabetes Day
According to WHO there are 220 million persons suffering from Diabetes in the World, most of them (80%) in the developing countries. In the year 2005, diabetes contributed to the deaths of over 1.1 million patients worldwide. These numbers are projected at 330-360 million by the year 2030. In the US, CDC data puts the number of diabetes patients at 26 million and over 400000 new cases detected each year. There is no treatment to reverse the course of the disease and patients have to take insulin or other drugs every day. The present knol deals with the diagnosis of diabetes through Fasting Blood Glucose, Glucose Tolerance Test, PostPrandial Blood Sugar Test, Glycosylated Hemoglobin HbA1c and Continuous Glucose Monitoring. The terms like hyperglycemia, hypoglycemia and normal blood levels are described. Links are provided to calculate your Body Mass Index BMI. Diabetic patients can manage the disease by diet, excercise and glycemic control through medicines and avoid diabetic complications.
Table des matières
- MATERIALS
- Introduction
- Glucose
- Glycosylation
- Types of diabetes
- What is the body mass index?
- DIAGNOSIS
- C – HYPERGLYCEMIA PROVOKED BY ORAL TEST:
Diagnosis of Diabetes
Glycemia - post prandiale glycemia - hyperglycemia - glycosylated hemoglobin
BY: Salim Djelouat and Krishan Maggon
Translated from : Le Diabète : Diagnostic et Prise en Charge Biologique
November 14 :
World Diabetes Day
Introduction
Emil Fischer won the Nobel Prize in 1902 in chemistry for the synthesis, structure and spatial configuration of glucose and its 16 different isomers. Glucose is (known as blood sugar, grape sugar, corn sugar, dextrose) essential for life and cell function in living organism.
Out of 16 different spatial configurations, only the D Glucose is biologically active and used.
The L glucose is inactive.
Glucose can exist in a open chain, spatial boat or chair configurations.
Of the 16 stereoisomers, only 7 exist in natural form and D Galactose and D Mannose are used by biological systems.
Glucose is manufactured from enzymatic hydrolysis of starch.
The storage form of glucose in biological system is Glycogen which provides a ready source of energy to cells.
Glycolysis and gluconeogenesis are the key metabolic pathways of glucose.
Out of 16 different spatial configurations, only the D Glucose is biologically active and used.
The L glucose is inactive.
Glucose can exist in a open chain, spatial boat or chair configurations.
Of the 16 stereoisomers, only 7 exist in natural form and D Galactose and D Mannose are used by biological systems.
Glucose is manufactured from enzymatic hydrolysis of starch.
The storage form of glucose in biological system is Glycogen which provides a ready source of energy to cells.
Glycolysis and gluconeogenesis are the key metabolic pathways of glucose.
Glucose
From Wikipedia http://en.wikipedia.org/wiki/Glucose
Sturcture of Glucose
| D-Glucose | |
|---|---|
 |  |
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Glycosylation
Glycosylation is the attachment of sugars like glucose to other biological macromolecules like proteins, amino acids, deoxy and robonucleic acids (DNA, RNA), lipids etc and can be enzymatic or nonenzymatic.
The enzymatic process is used by biological systems and living cells to produce and enhance protein functions, antigen detection and a variety of glycolipids, glycoproteins, enzymes, hormones and receptors.This is one of the key and essential regulatory function in life.
The non enzymatic glycosylation due to persistently high blood levels results in attachment of glucose to biological macromolecules like proteins and amino acids.
This impairs protein function and leads to diabetic complications as glycosylated proteins fail in their biological function resulting in diabetic neuropathy ( blindness), nephrotoxicity( kidney damage, glucose in urine), and leg ulcers.
This impairs protein function and leads to diabetic complications as glycosylated proteins fail in their biological function resulting in diabetic neuropathy ( blindness), nephrotoxicity( kidney damage, glucose in urine), and leg ulcers.
Glycosylated hemoglobin HbA1c is a good marker for the glycemic status of the diabetic patient during the past 3 months.
Types of diabetes
Type 1 Diabetes
About 10% of the diabetic patients suffer from this form of diabetes and are unable to make insulin.
This may be due to genetic defect, pancreas damage or diseases of pancreas.
These patients require lifelong injections of insulin and frequent and regular check ups of their blood sugar levels.
The earlier terms Juvenile Diabetes or insulin Dependent diabetes Mellitus IDDM are not used.
This may be due to genetic defect, pancreas damage or diseases of pancreas.
These patients require lifelong injections of insulin and frequent and regular check ups of their blood sugar levels.
The earlier terms Juvenile Diabetes or insulin Dependent diabetes Mellitus IDDM are not used.
Type 2 Diabetes
This is the major type of disease and 90% of diabetic patients have this form of the disease.
It was called Adult Onset diabetes or non Insulin Dependent diabetes NIDDM. In this form of disease, pancreas loses its ability gradually to make sufficient insulin to cope with high glucose levels.
It was called Adult Onset diabetes or non Insulin Dependent diabetes NIDDM. In this form of disease, pancreas loses its ability gradually to make sufficient insulin to cope with high glucose levels.
Gestational Diabetes
Observed in pregnant women late in the pregnancy and its resolves after the birth of the baby. These women have a higher tendency to develop Type 2 diabetes later in life.
Double Diabetes or Type 1.5 Diabetes
Many patients exhibit signs and symptoms of both forms of diabetes.
PreDiabetes
Persons with hypertension, sedentary lifestyle (lack of physical activity), overweight, frequent urination and elevated glucose levels have a high tendancy to develop Type 2 diabetes.
Number (in Millions) of Civilian/Noninstitutionalized Persons with Diagnosed Diabetes, United States, 1980–2006
CDC Fact sheet on Diabetes
http://www.cdc.gov/nccdphp/publications/aag/ddt.htm
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Diabetes Is Costly
- Total costs (direct and indirect) of diabetes: $174 billion.
- Direct medical costs: $116 billion.
- Indirect costs (related to disability, work loss, premature death): $58 billion.
- People with diagnosed diabetes have medical expenditures that are about 2.3 times higher than medical expenditures for people without diabetes.
Diabetes Is Preventable and Controllable
Recent studies show that lifestyle changes can prevent the onset of type 2 diabetes among those at high risk.
- For those with prediabetes, lifestyle changes, including at least 7% weight loss and at least 150 minutes of physical activity per week, can reduce the onset of type 2 diabetes by 58%.
- Blood glucose control reduces the risk for eye, kidney, and nerve diseases among people with diabetes by about 40%.
- Blood pressure control reduces the risk for heart disease and stroke among people with diabetes by 33%–50%. It also reduces the risk for eye, kidney, and nerve diseases by about 33%.
- Detecting and treating diabetic eye disease with laser therapy can reduce the risk for loss of eyesight by about 50%–60%. Comprehensive foot care programs can reduce amputation rates by 45%–85%.
For diabetic market and types of drug classes available for treatment go to
What is the body mass index?
The body mass index is a measure commonly used to determine overweight.
The definition by the WHO of a healthy weight is a BMI between 18.5 and 24.5.
A BMI over 25 kg/m2 is defined as overweight and a BMI of over 30 as obese while a BMI of 16 defines severe thinness.
Both conditions, severe thinness and severe obesity are live threatening conditions.
BMI Weight in Kg/ Height in meters2
With a Weight 100 Kg and Height 2 meters ie 100/4=25
BMI= 25
DIAGNOSIS
In diabetic patients high levels of glucose (Hyperglycemia) or low levels (Hypoglycemia) are medical emergencies which require urgent glucose measurements for diagnosis and therapeutic intervention.
Blood cells metabolize glucose resulting in a loss of 1-2 % per hour at room temperature.
This can be prevented for several hours by refrigeration.
Arterial, capillary or venous blood have comparable levels in a fasting person.
After meal, venous blood levels are lower by 10% than capillary or arterial blood.
Continuous monitoring with GlucoWatch and monitoring devices revealed that glucose levels were different in different parts of the body like arms and legs.
Blood cells metabolize glucose resulting in a loss of 1-2 % per hour at room temperature.
This can be prevented for several hours by refrigeration.
Arterial, capillary or venous blood have comparable levels in a fasting person.
After meal, venous blood levels are lower by 10% than capillary or arterial blood.
Continuous monitoring with GlucoWatch and monitoring devices revealed that glucose levels were different in different parts of the body like arms and legs.
Chemical methods for measurements of glucose rely on the reducing action of glucose on a chemical coupled to a chromophore resulting in change of colour.
These are alkaline Copper Test or Alkaline ferricyanide reaction.
Due to effect of various interefering factors, these tests have now been replaced by more accurate enzymatic tests.
The chemical agents are now mainly used in cheap strips for rapid diagnosis od glucose in urine.
These are alkaline Copper Test or Alkaline ferricyanide reaction.
Due to effect of various interefering factors, these tests have now been replaced by more accurate enzymatic tests.
The chemical agents are now mainly used in cheap strips for rapid diagnosis od glucose in urine.
Glucose oxidase has been used but Glucose Hexokinase is more specific than oxidase and is ued currently to measure glucose.
Strips impregnated with these enzymes are used by diabetics for self measurements of glucose through various meters and devices (drop of blood from finger tip).
Strips impregnated with these enzymes are used by diabetics for self measurements of glucose through various meters and devices (drop of blood from finger tip).
FASTING BLOOD GLUCOSE
A1 - Interest of the dosage :
Measurement of blood glucose after 8 hour of fasting provides a good indicator of the disease status and for detection and confirmation of new cases.
It was previously measured as whole blood but the standard method now is to measure it in plasma(serum).
It was previously measured as whole blood but the standard method now is to measure it in plasma(serum).
The conversion factor is Whole blood Glucose Levels = 1.15 Plasma glucose levels
Divide mg/dL results by 18 or multiply by 0.055 = mmole/L
Multiply mmole/dL results by 18 or divide by 0.055 = mg/dL
A2 – Blood Samples
Glycemia, glycosuria and glycorachia are technical emergencies which require the dosage measurement within an hour, after blood collection. The sampling of blood is made by a venous draining generally in the fold of the elbow. The patient has to be on an empty stomach for 12 hours, and avoid smoking before the examination.
The glycemia can be carried out indifferently on serum (dry tube) or plasma (by using an anticoagulant).
The hemolysis does not interfere with the strength (the concentration of sugar is the same in blood and plasma).
Increasingly glucose made from whole blood collected on micro capillary heparin (10 μl sufficient).
The glycemia can be carried out indifferently on serum (dry tube) or plasma (by using an anticoagulant).
The hemolysis does not interfere with the strength (the concentration of sugar is the same in blood and plasma).
Increasingly glucose made from whole blood collected on micro capillary heparin (10 μl sufficient).
If glucose analysis can be done only after one (01h) hour, the blood must be collected on a mixture of fluoride-oxalate (with both anti glycolytic, anticoagulant and hemolysis).
In hospitals, it is necessary to be wary of classic drip of glucose serum or of quite other drug treatments which interfere with glucose measurements.
In hospitals, it is necessary to be wary of classic drip of glucose serum or of quite other drug treatments which interfere with glucose measurements.
A3 - Normal results :
- At the adult normal values are:
0, 60 - 1, 10 g/l is 3, 36 - 6, 16 mmol / l.
- To new born normal values are:
0, 20 - 0, 8 g/l is 1, 12 - 4, 48 mmol / l.
Diabetes is suspected when 2 fasting glucose measurements on different days give high values >1, 27 g/l (to take into account the ethnic group of populations, diets, of reactive employing laboratories …)
A4 - Abnormal results :
1 - A patient who probably did not observe overnight fast
2 - With a type 1 diabetes
3 - With an acute pancreatites or chronic pancreatic disease which often led to the diabetes
4 - With a endocrine origin: pheochromocytome, hypercorticism, treatment by corticoids, acromegale, hyperthyroid, pancreatic tumor secreting
5 - With causes of a latent diabetes; hyperglycemic pregnancy, infection, stresses, drugs
1 - With an overdose of drugs hypoglycémiants in the diabetic
2 - With malnutrition or a prolonged young person
3 - With a secretion by the organization of an insulin excess (insulinomist, polyadénomatose)
4 - With a endocrinienne insufficiency (suprarenal, hypophyseal)
5 - With a hepatic disorder (acute hepatitis, acute alcoholic intoxication)
6 - With a disorder of the metabolism at the child or the new born one (galactosemy, glycolysis, intolerance with the fructose)
7 - With an infection (in particular an acute malaria)
A5 - Physiological variations of the hypo and hyperglycemia :
1 - The basic glycemia of the healthy subject with fasting for at least 10 hours and in balanced cabohydrate food (250 to 300 g/day) ranges between 4 to 5,25 mmol/L.
2 - One can talk about hypoglycemia only for one value repeated with several examinations and which must be lower than 2,75 mmol.
3 - The hyperglycemia diabetic is evoked as soon as the basic value exceeds usually 6 mmol with fasting.
4 - In the 2 hours post prandiale test, after a normal meal, the “upper range of glucose” of the healthy subject should not exceed 6,5 mmol.
Between 6,5 and 7,5 mmol, one cannot affirm a diabetes and in this case it is necessary to practice a caused hyperglycemia. It is a sign of prediabetic state.
5 - In the infant one notices a very clear physiological hypoglycemia (between 1,75 and 2,25 mmol) between 3rd and the 8th hour.
This hypoglycemia is stabilized around 2,75 mmol with the 48e hour.
During 01 year, the glycemia of the infant remains rather unstable with fasting and is around 2,75 mmol.
A6 - Pathological variations of the glycemia :
From 16 to 17 mmol, a hyperglycemia leads to coma in diabetic patients, but actually, no limit can be fixed with precision. In the L.C.R, the normal glycorachie borders 2,5 mmol, its significant lowering and at the same time as that of chlorides, is a faithful sign of meningitis, than it that one is nature or causes.
A7 - Conversion of the results :
A - mmol x 0,18 = g/l
B - g/l x 5,56 = mmol B - GLYCEMIA POST-PRANDIALE:
B1 - Which is the difference between the fasting glucose and post-prandial glucose.
The two tests do not measure the same mechanism of load in glucose by the human body.
1 - The fasting glucose represents the production of sugar by the liver starting from stored sugars and lipids (mechanism of the glyconeogenesis).
2 - The post-prandiale glucose tests yields the capacity of the liver and the muscles to absorb glucose introduced with the nutrients and of its storage as glycogen.
In the event of diabetes or of a provision to diabetes, normally the two mechanisms of studies are generally failing, but one more than the other (especially on the level of storage).
The evaluation of diabetes and especially its assumption of responsibility require another type of examination much more objective than the analysis of the glycemia with jeun, it is the glycemia post-prandiale.
B2 - Study of th physiology of sugar in blood?
At a “normal” individual, the glycemia only varies very little in the course of the day (according to the food modes). After a meal, one notes a light rise in the glycemia (it is what is called the glycemia post-prandiale).
This rise does not last and drops back quickly.
The rate of glycemia returns to the normal.
To an individual diabetic or predisposing with a diabetes, this glycemia post-prandiale will last much longer, more than 2 hours after the meal and its rate can range from 1,40g/liter to 2g/liter
B3 - Why glycemia post-prandiale is important to know?
As one already said, a rate of glycemia post-prandiale, testifies to an imbalance of the regulation of sugar in blood. Other studies showed, when the post-prandiale increases, the risks of complication of the diabetes also increase, it is thus a factor more important to know than the glycemia with jeun to predict the coronary accidents and the cardiovascular accidents.
B4 - Increment post-prandiale?
The increment post-prandial, still called the glycemic excursion post-prandiale or called the delta post-prandiale, is the difference observed between the glycemia with fasting and the glycemia post-prandiale.
Examples:
1e example:
If one takes, a glycemia with fasting proportioned has 1.40g/l and a glycemia post-prandiale proportioned with 2.00g/l the delta glycemic is of 0.60g/l.
In this example, the interest of the treatment is cause of a drop in this glycemia post-prandiale
Second example:
If one proportions a glycemia with fast with 1.80g/l and a glycemia post-prandiale with 2.00g/l (it is noticed that the meal did not make too much increase the rate), in case the interest of the treatment is cause a drop in the glycemia with fast
This is why, the monitoring of the effectiveness of the treatments passes at the same time by the regular proportioning of the glycemia to jeun, which must be lower than 1,26 g/l, and by proportioning, from time to time, of the GPP, which must be lower than 1,40 g/l.
B5 - Recommendations for patients for glucose measurements away?
The recommendations are:
• Patients must take a normal meal, which is not too rich, high calorie nor too low in sugar and fats (and not to say to him will eat and returns)
• And to present itself two hours after to the laboratory for blood sample.
B6 - Normal and abnormal results of glycemia post-prandiale (OGTT)
a - Normal value :
The normal value of the glycemia post-prandiale must be lower than 1.50g/l is 8.34 mmol/l, (value given as an indication, to refer to the medical analysis laboratories)
b - Abnormal value :
The abnormal value of the glycemia post-prandiale is higher than the normal value is: 1.50g/l is 8.34 mmol/l
C – HYPERGLYCEMIA PROVOKED BY ORAL TEST:
Oral glucose tolerance test OGTTC 1–What east the interest of the hyperglycemia provoked by oral way (OGTT)
Its interest is the early detection of sweet diabetes, with an analysis of the functional hypoglycemia, because they know that the diagnostic interest of glycemia on an empty stomach limits itself in practice to two definite situations:
- confirmation of an obvious diabetes with value(stock) the habitually upper limit 6.5 mmol
- confirmation of an organic hypoglycemia with habitually lower value is 2.75 mmol
- diagnoses of a gestationnel diabètes
- a reactional hypoglycemia
C2 - What are precautions to be taken before practicing a hyprglycaemia provoked by oral way (OGTT)
The patient must be in regime glucidique balanced (250 has carbohydrates 300g) in 3 days, which precedent test and must take no medicine such as:
- corticoids
- diuretics
- oestroprogestatifs
C3 - What are the modalities of sample and of analyses?
1. The patient must be on an empty stomach and it since at least 10
2. Make a first sample of blood (zero time)
3. Weigh the sick man
4. Make him ingest a sweet preparation (1g of sugar by kilogram weighty)
5. The patient must be sitting down or of preferences lengthen
6. To go about things later has samples and it, every ½ the hours during 3: am.
7. Dose different samples
8. Draw the curve
C4 - Which are the normal values?
The normal values of the hyperglycemia caused by oral way are identical has those of the glycemia post-prandiale, measured after 2 hours of the ingestion of glucose (see the methods of sampling and analyses).
C5 - Reading and interpretation of the results?
The results are given only as an indication, référencier at the laboratories, which carry out the analyses.
Example of interpretation:
1 - For a normal state:
- After 60 mn : 1.60 g/l is 8.90 mmol
- After 90 mn : 1.40 g/l is 7.78 mmol
- After 120 mn : 1.10 g/l is 6.11 mmol
2 - for a meadow diabetes :
- Glycémie zero : 1.35 g/l is 7.5 mmol
- Then 120 mn : 1.60 g/l is 9 mmol
- After 3h : 1.35 g/l is 7.5 mmol
3 - confirmed diabetes:
- glycemia zero : more 1.98g/l is 11 mmol
- After 2 heurs : more 2.25g/l is 12.5 mmol
- After 3 a.m. : 1.53 g/l is 8.5 mmol
Only an experienced doctor and having necessary competences will be entitled to the interpretation of the results.
C6 - Conclusion?
The test of the hyperglycemia caused by oral way is not useful when the glycemia with jeun is higher than 1.50g/l is 8.34 mmol/l.
When the glycemia is lower than this value and if one does not note any disorder of the use of sugar by the organization, this test can be useful.
The normal values of the hyperglycemia caused by oral way are identical to those of the glycemia post-prandiale, measured after 2 hours of the ingestion of glucose (see the methods of sampling and analyses).
D - HAEMOGLOBIN GLYCOSYLEE OR HEAMOGLOBIN GLYQUEE OR A1c HAEMOGLOBIN:
D1- What call you one haemoglobin glycosylee?
Haemoglobin , is a protein present in the red globules and it is it, which gives the red color to blood.
Its role is to transport the oxygen of the lungs towards all fabrics.
As all proteins, haemoglobin is likely to be modified by the fixing of molecules of oses and mainly glucose.
This fixing can be carried out on various categories of Hb, of which HbA1, which is made up of 4 sub-groups:
- HbA1a1 (fixing of the fructose 1-6 diphosphate) HbA1a2 (glucose-6-phosphate)
- HbA1b (pyruvate)
- And especially HbAIc which fixes the molecule of glucose and thus related to the average concentration of glucose in the blood which will be the subject of proportioning of glycosylée hemoglobin.
D2- Why proportion haemoglobin glycosylee?
The proportioning of glycosylée haemoglobin is an index of reference in order to judge good balance of the diabetes.
Moreover, it at shown summer that by improving this balance, it was possible to prevent and to even stop the evolution of certain complications of the diabetes namely: ocular complications, renal complications, neurological complications…
The proportioning of glycosylée haemoglobin thus remains the proportioning most interesting for the monitoring and the assumption of responsibility of diabetes.
D3 - What east th importance of the blood sample in the proportion of the hemoglobin glycosylee?
They know that the life of a red cell is of 120 days.
When a blood test is going to be practiced, there is going to be a mixture of young people and old red cells.
Therefore our sample is going to be composed (be made up) of too few loan of globules having an average life of 60 days.
The glucose, which is present in instant, in the blood, is going to settle on the haemoglobin.
The proportion of the glycosylée haemoglobin practiced in the course of 2 last month’s therefore, is going to reflect the medium level of glycemia.
More glycemia will be high more the rate of the glycosylée haemoglobin will be high.
D4 – What are the conditions of a good sample?
- To take a sample at the level of the elbow, in a tube containing an anticoagulant
- sample at the woman must be made far from menstrual period
- specify if the sick man has classes of a treatment of anemia by iron deficiency
- to specify if the sick man did not suffer blood transfusion
- to specify the treatment in the course of DIABETIC
- the jeun is not compulsory
D5 - Which are the normal values?
The normal values of glycosylée haemoglobin are expressed as a percentage and represents at a healthy individual:
- 2 to 5.5% of total haemoglobin.
D6 - Which are the abnormal values?
a - In a well-balanced diabetic, glycosylée haemoglobin must be with the lower part of 6.1%
b - In a badly balanced diabetes, glycosylée haemoglobin is with the top from 6.2 to 6.3% and can even reach 15% of total haemoglobin.
D7 - Which are the patological variation?
a - Increase :
- hyperglycemia in the 120 days which preceded proportioning
- impaired renal function
b - Reduction :
- night hypoglycemia prolonged or passed unperceived
- hemorrhage or hemolytic disease
Glyquée haemoglobin is advised in more all the 3 to 6 months, its proportioning is not standardized, i.e. the values can vary from one laboratory to another.
Continuous Glucose Monitoring
A diabetic patient must monitor his own bloogd glucose several times a day by placing a drop of blood from finger tip on a strip of paper impregnated with glucose measuring enzymes.
The color change is read by a Glucose Meter.
The color change is read by a Glucose Meter.
The most important issue is trend and not high accuracy
Hyperglycemia High levels of Glucose
Hypoglycemia Low levels of Glucose.
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