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The diagnosis of diabetes mellitus

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Discover here: Temporary hyperglycemia | Diagnostic criteria | Difficult situations | Type 1 without hyperglycemia | Screening

For the diagnosis of diabetes, we will only use the glycemic or glycosylated hemoglobin values taken from venous blood. After collection, the blood must be transported quickly to the laboratory. Here, the lab doctors will centrifuge the blood to obtain venous plasma. In the period between blood harvesting and its centrifugation, the red blood cells will consume the glucose surrounding them.

For this reason, the final blood glucose level measured by the laboratory will be falsely lowered by the consumption of glucose by erythrocytes on the way to the laboratory. After centrifugation, the lab doctors can sometimes safely store the obtained plasma for 24 hours, at room temperature.

If you want to keep it longer, you may use a refrigerator set at -20⁰ C. Using a freezer set at -80⁰C allows storage for decades. It is not acceptable to use the blood glucose values measured by a fingerstick glucometer or a Continuous Glucose Monitoring Systems (CGMS) to diagnose diabetes.

Temporary hyperglycemia, except diabetes

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Slightly increased values (+20%) above the diagnostic limit for diabetes may occur temporarily under conditions of significant stress, such as surgery, a severe cold or pneumonia, a fracture, etc. However, an intense psychological pressure (examination, quarrel, loss of a relative) is not taken into account here. It should not raise your blood sugar so high that it reaches the threshold of diabetes.

In the case of “stress” hyperglycemia (e.g. “hospital”), doctors will not use the glucose values to diagnose diabetes. Instead, they will periodically repeat them during and after the cessation of the suspected stressor. However, the persistence of high glycemic values after resolving the initial stress clarifies the situation and confirms the presence of diabetes.

Diagnostic criteria for diabetes

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Outside pregnancy and in the 1st trimester of pregnancy, the criteria are uniform, as set out below. In the 2nd and 3rd trimesters of pregnancy, doctors use particular rules, and the diagnosis obtained is gestational diabetes. You may diagnose diabetes based on any of the following four ways:

  1. Diabetes-specific symptoms and blood glucose at any time ≥200 mg/dl (11.1 mmol/l)
  2. Blood glucose in the morning, on an empty stomach ≥126 mg/dl (7 mmol/l)
  3. Blood glucose at 2 hours after 75 g of glucose ≥200 mg/dl (11.1 mmol/l)
  4. Glycosylated hemoglobin ≥6.5% (48 mmol/mol)

For criteria 2-4, it is necessary to repeat the test in the following days for confirmation. The diagnosis can be made only by the presence of at least two criteria from those listed in points 2-4. If you have only one positive test, you should repeat it to have two.

For example:

  1. Fasting blood glucose = 130 mg/dl (7.2 mmol/l). Repeat the next day, and if ≥126 mg/dl (7 mmol/l) comes out, the presence of diabetes is confirmed.
  2. Fasting blood glucose = 130 mg/dl (7.2 mmol/l) and glycosylated hemoglobin = 7.1% (54 mmol/mol). The diagnosis of diabetes is confirmed because there are already two criteria met.
  3. Fasting blood glucose = 130 mg/dl (7.2 mmol/l) and glycosylated hemoglobin = 6.1% (43 mmol/mol). Repeat only the fasting blood glucose the next day, whose values ≥126 mg/dl (7 mmol/l) confirm the presence of diabetes.

We will now discuss in more detail each of the four diagnostic criteria of diabetes.

Hyperglycemic crisis

The primary way to diagnose diabetes is to associate specific symptoms with very high blood sugar. Specific symptoms mean intense thirst, consuming a large amount of water and often urination, including at night. Very high blood sugar means ≥200 mg/dl (11.1 mmol/l), regardless of the time of measurement. This time can be, for example, even immediately after a meal.

Under these conditions, it is essential to determine the presence of ketone bodies. You can measure them with a special glucometer for ketone bodies or more directly, in the urine.

Determination of ketone bodies in urine involves the use of a strip that is coloured differently depending on the concentration of ketone bodies in the urine (widely used and relatively inexpensive). The presence of ketone bodies implies a visit to the emergency room of the nearest hospital to establish an antidiabetic treatment urgently.

Nausea and vomiting generally herald the appearance of ketone bodies and the imminence of diabetic ketoacidosis. Diabetic ketoacidosis is an acute complication of diabetes that, if left untreated, can lead to coma and even death.

Fasting blood glucose

Normal blood glucose, measured in the morning on an empty stomach (fasting blood glucose) is <100 mg/dl (5.6 mmol/l). Values ≥126 mg/dl (7 mmol/l) are considered diagnostic for diabetes. Your doctor will recommend a second measurement the next day, or within two weeks to avoid only temporarily elevated blood sugar values (e.g. analysis error). You can make the diagnosis of diabetes only if values ≥126 mg/dl (7 mmol/l) persists on the second determination.

Fasting blood glucose values in the range of 100-125 mg/dl (5.6-6.9 mmol/l) diagnose impaired fasting glucose (prediabetes). This is a form of impaired carbohydrate metabolism during fasting.

The diagnosis of impaired fasting blood glucose (IFG) results in a significant increase in the risk for cardiovascular disease and diabetes. This risk is manifested especially in the presence of obesity and dyslipidemia.

Postprandial blood glucose

In general, the blood sugar does not exceed 140 mg/dl during the day. The exact value of the normal threshold is set only for the glucose tolerance test. In this test, 75 g of glucose is ingested or less sometimes, depending on the child’s weight (1.75 g/kg body weight, but a maximum of 75 g). You may add the squeezed juice of half a lemon, for taste.

Normal blood glucose collected from a vein at 2 hours is <140 mg/dl (7.8 mmol/l). Values ≥200 mg/dl (11.1 mmol/l) are the diagnostic criteria for diabetes. In the particular case of the child, doctors use this test very rarely. The reason is that it can sometimes lead to very high blood sugar levels.

Blood glucose values at 2 hours in the oral glucose tolerance test, with values of 140-199 mg/dl (7.8-11.0 mmol / l) diagnose impaired glucose tolerance (IGT). This form of prediabetes is an alteration of carbohydrate metabolism in the postprandial period.

Prediabetes significantly increases the risk of diabetes and cardiovascular disease. Prediabetes is often associated with high blood fat and high blood pressure in what is called “metabolic syndrome”.

Glycosylated hemoglobin

Glycosylated hemoglobin has a dedicated chapter. In short, it represents the proportion of “anemic” hemoglobin that has “sugared” due to blood glucose. The normal value of glycosylated hemoglobin is <5.7% (39 mmol/mol). Values that reach and exceed 6.5% (48 mmol/mol) diagnose diabetes, most often accompanied by high venous blood sugar. Glycosylated hemoglobin values of 5.7-6.4% (39-47 mmol/mol) diagnose prediabetes.

Diagnosis of diabetes in unclear situations

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When the blood changes at a very high rate or the hemoglobin has structural changes (from birth), you cannot use glycosylated hemoglobin for diabetes diagnosis. Examples of such situations are sickle cell anemia, recent blood loss, treatment with hormones to stimulate blood production (erythropoietin), HIV infection… In these conditions, only the criteria based on the determination of blood glucose can be used.

Substantial doubts may arise regarding the diagnosis and classification of diabetes when blood glucose levels are persistent in the diabetes range, but immediately above the threshold of diagnosis. The absence of any symptoms increases this doubts even further.

A close follow-up of the patient is mandatory. Also, the patient will receive diabetes diagnostic testing every three months. A glucose tolerance test should be carefully indicated in this case, as it may lead to significant hyperglycemia.

Correct classification is the natural next step after the diagnosis of diabetes. Classifying diabetes is not always easy. Children can have many other types of diabetes besides the classic form of type 1 diabetes.

Diagnosis of type 1 diabetes with normal blood sugar

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Type 1 diabetes has a dedicated chapter. Significant details about the current topic can be found primarily in the section dedicated to the stages of type 1 diabetes. Type 1 diabetes has a period of evolution with normal blood sugar values, that can sometimes last for many years. If there are grade 1 relatives with diabetes (e.g. sibling), you should perform the test for the presence of type 1 diabetes in its pre-hyperglycemic phase.

Testing for stages 1 and 2 of type 1 diabetes involves the determination of the following antibodies specific for type 1 diabetes in the blood:

  • GAD65 (glutamic acid decarboxylase antibodies)
  • IAA (anti insulin antibodies)
  • IA2A (anti tyrosine phosphatase antibodies)
  • ZnT8 (anti zinc transporter 8 antibodies)

The presence of at least three antibodies, with their persistence at a repeat testing after 3-6 months puts the diagnosis of type 1 diabetes in its pre-hyperglycemic phase (stage 1). The immediate consequence is to refer the patient to a centre with vast experience in the field of type 1 diabetes and its pre-hyperglycemic stages.

Screening for type 2 diabetes in healthy children

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Overweight or obese children have a significantly increased risk of developing type 2 diabetes. Because type 2 diabetes in children can evolve for a long time without symptoms, it is imperative to seek it out in all children at risk actively.

Testing for type 2 diabetes starts at age ten years old in all overweight or obese children who additionally meet at least one of the following conditions:

  1. The mother had diabetes during pregnancy with this child
  2. Grade 1 or 2 relatives with type 2 diabetes
  3. Race or ethnicity at risk (African American, Hispanic)
  4. Signs or diseases associated with insulin resistance

The main signs of insulin resistance are the following:

  • Acanthosis nigricans (blackened skin on the back of the neck)
  • Hypertension
  • Dyslipidemia
  • Polycystic ovary syndrome
  • Low birth weight, typically if recovered very quickly after birth

Testing can start earlier than ten years if puberty has already occurred. In children, being overweight means having a BMI above the 85th percentile. Obesity begins at a BMI above the 95th percentile.

Diabetes screening involves the use of any of the four standard diagnostic criteria (see above). If the result is normal, you should repeat testing within three years. If the result shows prediabetes, you must renew screening within one year.

References

  1. American Diabetes Association Guideline 2020
  2. ISPAD Clinical Practice Consensus Guidelines 2018
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