Acute clinical manifestation

Hyperglycemia itself can cause symptoms but usually only when blood glucose concentrations are approximately 180 mg per 100 ml (10 mmol per litre) or higher. When blood glucose concentrations increase, more glucose is filtered by the glomeruli of the kidneys than can be reabsorbed by the kidney tubules, resulting in glucose excretion in the urine. High glucose concentrations in the urine create an osmotic effect that reduces the reabsorption of water by the kidneys, causing polyuria (excretion of large volumes of urine). The loss of water from the circulation stimulates thirst. Therefore, patients with moderate or severe hyperglycemia typically have polyuria and polydipsia (excessive thirst). The loss of glucose in the urine results in weakness, fatigue, weight loss, and increased appetite (polyphagia). Patients with hyperglycemia are prone to infections, particularly vaginal and urinary tract infections, and an infection may be the presenting manifestation of diabetes.

There are two acute life-threatening complications of diabetes: hyperglycemia and acidosis (increased acidity of the blood), either of which may be the presenting manifestation of diabetes. In patients with type 1 diabetes, insulin deficiency, if not recognized and treated properly, leads to severe hyperglycemia and to a marked increase in lipolysis (the breakdown of lipids), with a greatly increased rate of release of fatty acids from adipose tissue. In the liver, much of the excess fatty acid is converted to the keto acids beta-hydroxybutyric acid and acetoacetic acid. The increased release of fatty acids and keto acids from adipose, liver, and muscle tissues raises the acid content of the blood, thereby lowering the pH of the blood. The combination of hyperglycemia and acidosis is called diabetic ketoacidosis and leads to hyperventilation and to impaired central nervous system function, culminating in coma and death. Patients with diabetic ketoacidosis must be treated immediately with insulin and intravenous fluids.

In patients with type 2 diabetes, high blood glucose concentrations can lead to very severe and prolonged hyperglycemia and to marked polyuria, with the loss of a large volume of fluid and a very high serum osmolality. These factors place patients with type 2 diabetes at a high risk of developing central nervous system dysfunction and vascular collapse (hyperglycemia coma). Ketoacidosis is usually not a problem in patients with type 2 diabetes because they secrete enough insulin to restrain lipolysis. Patients with hyperglycemic coma should be treated aggressively with intravenous fluids and insulin.

Diagnosis and treatment

Many people are unaware that they have diabetes. In 2012, for example, it was estimated that 8.1 million of 29.1 million American cases were undiagnosed. The disease is usually discovered when there are typical symptoms of increased thirst and urination and a clearly elevated blood sugar level. The diagnosis of diabetes is based on the presence of blood glucose concentrations equal to or greater than 126 mg per 100 ml (7.0 mmol per litre) after an overnight fast or on the presence of blood glucose concentrations greater than 200 mg per 100 ml (11.1 mmol per litre) in general. People with fasting blood glucose values between 100 and 125 mg per 100 ml (6.1 to 6.9 mmol per litre) are diagnosed with a condition called impaired fasting glucose (prediabetes). Normal fasting blood glucose concentrations are less than 100 mg per 100 ml (6.1 mmol per litre).

While the blood glucose concentrations used to define diabetes and impaired fasting glucose are somewhat arbitrary, they do correlate with the risk of macrovascular and microvascular disease. Patients with impaired fasting glucose are likely to have diabetes later in life. Oral glucose tolerance tests, in which blood glucose is measured hourly for several hours after ingestion of a large quantity of glucose (usually 75 or 100 grams), are used in pregnant women to test for gestational diabetes. The criteria for diagnosing gestational diabetes are more stringent than the criteria for diagnosing other types of diabetes, which is a reflection of the presence of decreased blood glucose concentrations in healthy pregnant women as compared with nonpregnant women and with men.

The duration and severity of hyperglycemia can be assessed by measuring levels of advanced glycosylation end products (AGEs). AGEs are formed when hemoglobin molecules in red blood cells undergo glycosylation (binding to glucose), and the bound substances remain together until the red blood cell dies (red blood cells live approximately 120 days). AGEs are believed to inflict the majority of vascular damage that occurs in people with diabetes. A glycosylated hemoglobin called hemoglobin subtype A1c (HbA1c) is particularly useful in monitoring hyperglycemia and the efficacy of diabetes treatments.

Treatment

Before the isolation of insulin in the 1920s, most patients died within a short time after onset. Untreated diabetes leads to ketoacidosis, the accumulation of ketones (products of fat breakdown) and acid in the blood. Continued buildup of these products of disordered carbohydrate and fat metabolism result in nausea and vomiting, and eventually the patient goes into a diabetic coma.

Treatment for diabetes mellitus is aimed at reducing blood glucose concentrations to normal levels. Achieving this is important in promoting well-being and in minimizing the development and progression of the long-term complications of diabetes. Measurements of HbA1c can be used to assess whether an individual’s treatment for diabetes is effective. Target values of HbA1c levels should be close to normal.