Glucose

Diagnose diabetes mellitus; evaluate disorders of carbohydrate metabolism including alcoholism; evaluate acidosis and ketoacidosis; evaluate dehydration, coma, hypoglycemia of insulinoma, neuroglycopenia. A fasting glucose ≥125 mg/dL on more than one occasion is adequate for the diagnosis of diabetes mellitus. An OGTT is not necessary in this setting. Infants, especially with tremor, cyanosis, convulsions, and respiratory distress should have stat glucose, particularly if there is maternal diabetes, postmaturity, asphyxia, hemolytic disease of the newborn, or possible sepsis. Babies too large or small for gestational age should also have glucose in the first 24 hours of life. Random blood sugars can be used to monitor therapy in diabetics or evaluate presence of insulinoma.1,2

Mild glucose impairment can exist with fasting glucose within the normal range. Measurement of plasma glucose without spinal fluid glucose can miss neuroglycopenia. To the extent that innovative new methods deviate from reference methods, such alternative techniques may be unreliable for certain patient care needs.3 Fingerstick glucose determination in shock are lower than venous glucose and are dangerously misleading.4

Recent evidence revealed a diurnal variation in FPG, with mean FPG higher in the morning than in the afternoon, indicating that many cases of undiagnosed diabetes would be missed in patients seen in the afternoon. Glucose concentrations decrease ex vivo with time in whole blood because of glycolysis. The rate of glycolysis, reported to average 5% to 7% [~0.6 mmol/L (10 mg/dL)] per hour, varies with the glucose concentration, temperature, white blood cell count, and other factors. Glycolysis can be attenuated by inhibition of enolase with sodium fluoride (2.5 mg fluoride/mL of blood) or, less commonly, lithium iodoacetate (0.5 mg/mL of blood). These reagents can be used alone or, more commonly, with anticoagulants such as potassium oxalate, EDTA, citrate, or lithium heparin. Although fluoride maintains long-term glucose stability, the rate of decline of glucose in the first hour after sample collection in tubes with and without fluoride is virtually identical. (Note that leukocytosis will increase glycolysis even in the presence of fluoride if the white cell count is very high). After four hours, the glucose concentration is stable in whole blood for 72 hours at room temperature in the presence of fluoride. In separated, nonhemolyzed, sterile serum without fluoride, the glucose concentration is stable for fourteen days at 25°C and 4°C.

Glucose can be measured in whole blood, serum, or plasma, but plasma is recommended for diagnosis. The molality of glucose (ie, amount of glucose per unit water mass) in whole blood and plasma is identical. Although red blood cells are essentially freely permeable to glucose (glucose is taken up by facilitated transport), the concentration of water (kg/L) in plasma is ~11% higher than that of whole blood. Therefore, glucose concentrations in plasma are ~11% higher than whole blood if the hematocrit is normal. Glucose concentrations in heparinized plasma are reported to be 5% lower than in serum. The reasons for the latter difference are not apparent but may be attributable to the shift in fluid from erythrocytes to plasma caused by anticoagulants. The glucose concentrations during an OGTT in capillary blood are significantly higher than those in venous blood [mean of 1.7 mmol/L (30 mg/dL), equivalent to 20% to 25%], but the mean difference in fasting samples is only 0.1 mmol/L (2 mg/dL).

Although methods for glucose analysis exhibit low imprecision at the diagnostic decision limits of 7.0 mmol/L [(126 mg/dL), fasting] and 11.1 mmol/L [(200 mg/dL), postglucose load], the relatively large intraindividual biological variability (CVs of ~5% to 7%) may produce classification errors. On the basis of biological variation, glucose analysis should have analytical imprecision <3.4%, bias <2.6%, and total error <8.0%.1,2

Like a fasting glucose level >125 mg/dL, a two-hour postprandial glucose >200 mg/dL is virtually diagnostic of diabetes mellitus and obviates the need for a glucose tolerance test. An oral glucose tolerance test (OGTT) is not necessary in the setting of sufficiently high fasting and two-hour postprandial results.

Other causes of high glucose (serum or plasma) include nonfasting specimen; recent or current IV infusions of glucose; stress states such as myocardial infarct,5 brain damage, CVA,6 convulsive episodes, trauma, general anesthesia; Cushing disease; acromegaly; pheochromocytoma; glucagonoma; severe liver disease; pancreatitis; drugs (thiazide and other diuretics, corticoids, many others are reported to affect glucose).

The danger of hypoglycemia (low glucose) is lack of a steady supply of glucose to the brain (neuroglycopenia).

Causes of low glucose: Excess insulin, including rare insulin autoimmune hypoglycemia, surreptitious insulin injection, and sulfonylurea use; glycolysis in specimens overheated or old; serum permitted to stand on clot in red-top tube for chemistry profile. Very prompt removal of plasma and analysis is needed in cases of marked leukocytosis. Hypoglycemia should be confirmed by specimens drawn in fluoride tubes (gray-top tubes).

With hypoglycemia, symptoms must be correlated with plasma glucose.

Three major groups of hypoglycemia are defined: reactive, fasting, and surreptitious. The reactive group includes alimentary hyperinsulinism, prediabetic, endocrine deficiency, and idiopathic functional groups.7 Postprandial hypoglycemia may occur after gastrointestinal surgery, and is described with hereditary fructose intolerance, galactosemia, and leucine sensitivity.

-Pancreatic islet cell tumors (insulinomas) − cause hypoglycemia in fasting individuals or after exercise. Measurement of simultaneous glucose, C-peptide, and insulin levels at the time of spontaneous hypoglycemia help to differentiate insulinoma from other conditions. The glucose:insulin ratio is useful in the diagnosis of insulinoma: insulin levels inappropriately increased for plasma glucose. An intravenous tolbutamide test with plasma glucose and serum insulin determinations may be used for evaluation of insulin-secreting islet cell tumors. The test is positive in approximately 75% of patients with these tumors.7 Glucagon and leucine stimulation tests are less frequently utilized.

-Extrapancreatic tumors−rare bulky fibromas, sarcomas, mesotheliomas, and carcinomas, including hepatoma and adrenal tumors

-Adrenal insufficiency (Addison disease), including congenital adrenal hyperplasia

-Hypopituitarism, isolated growth hormone or ACTH deficiency

-Starvation, malabsorption−but starvation does not cause hypoglycemia in normal persons

-Drugs including insulin (see above), oral hypoglycemic agents, and alcoholism, especially with starvation. Ethanolism is a common cause of hypoglycemia. Other drugs can depress glucose levels.

-Liver damage, including fulminant hepatic necrosis (hepatitis, toxicity), and severe congestive failure