Pediatric Type 1 Diabetes Mellitus Workup
- Author: William H Lamb, MD, MBBS, FRCP(Edin), FRCP, FRCPCH; Chief Editor: Stephen Kemp, MD, PhD more...
The need for and extent of laboratory studies vary, depending on the general state of the child's health. For most children, only urine testing for glucose and blood glucose measurement are required for a diagnosis of diabetes. Other conditions associated with diabetes require several tests at diagnosis and at later review.
A positive urine glucose test suggests, but is not diagnostic for, type 1 diabetes mellitus (T1DM). Diagnosis must be confirmed by test results showing elevated blood glucose levels. Test urine of ambulatory patients for ketones at the time of diagnosis. See Urinalysis.
Ketones in the urine confirm lipolysis and gluconeogenesis, which are normal during periods of starvation. With hyperglycemia and heavy glycosuria, ketonuria is a marker of insulin deficiency and potential DKA.
Islet cell antibodies
Islet cell antibodies may be present at diagnosis but are not needed to diagnose type 1 diabetes mellitus. Islet cell antibodies are nonspecific markers of autoimmune disease of the pancreas and have been found in as many as 5% of unaffected children. Other autoantibody markers of type 1 diabetes are known, including insulin antibodies. Additional antibodies against islet cells are recognized (eg, those against glutamate decarboxylase [GAD antibodies]), but these may not be available for routine testing.
Thyroid function tests and antithyroid antibodies
Because early hypothyroidism has few easily identifiable clinical signs in children, children with type 1 diabetes mellitus may have undiagnosed thyroid disease. Untreated thyroid disease may interfere with diabetes management. Typically, hypothyroid children present with reduced insulin requirements and increased episodes of hypoglycemia; hyperthyroid children have increased insulin needs and a tendency toward hyperglycemia. Caution, therefore, is needed when initiating treatment as insulin requirements can change quite quickly. Check thyroid function regularly (every 2-5 years or annually if thyroid antibodies are present). Antithyroid antibody tests indicate the risk of present or potential thyroid disease.
Some children with type 1 diabetes mellitus may have or may develop celiac disease. Positive antigliadin antibodies, especially specific antibodies (eg, antiendomysial, antitransglutaminase) are important risk markers. If antibody tests are positive, a jejunal biopsy is required to confirm or refute a diagnosis of celiac disease. Once celiac disease is confirmed, the individual should remain on a gluten-free diet for life.
Lipid profiles are usually abnormal at diagnosis because of increased circulating triglycerides caused by gluconeogenesis. Apart from hypertriglyceridemia, primary lipid disorders rarely result in diabetes. Hyperlipidemia with poor metabolic control is common but returns to normal as metabolic control improves.
Beginning at age 12 years, perform an annual urinalysis to test for a slightly increased AER, referred to as microalbuminuria, which is an indicator of risk for diabetic nephropathy.
Renal function tests
If the child is otherwise healthy, renal function tests are typically not required.
Apart from transient illness-induced or stress-induced hyperglycemia, a random whole-blood glucose concentration of more than 200 mg/dL (11 mmol/L) is diagnostic for diabetes, as is a fasting whole-blood glucose concentration that exceeds 120 mg/dL (7 mmol/L). In the absence of symptoms, the physician must confirm these results on a different day. Most children with diabetes detected because of symptoms have a blood glucose level of at least 250 mg/dL (14 mmol/L).
Blood glucose tests using capillary blood samples, reagent sticks, and blood glucose meters are the usual methods for monitoring day-to-day diabetes control.
Glycosylated hemoglobin derivatives (HbA1a, HbA1b, HbA1c) are the result of a nonenzymatic reaction between glucose and hemoglobin. A strong correlation exists between average blood glucose concentrations over an 8- to 10-week period and the proportion of glycated hemoglobin. The percentage of HbA1c is more commonly measured. (Measurement of HbA1c levels is the best method for medium-term to long-term diabetic control monitoring.)
An international expert committee composed of appointed representatives of the American Diabetes Association, the European Association for the Study of Diabetes, and others recommended HbA1c assay for diagnosing diabetes mellitus. The committee recommended that an HbA1c level of 6.5% or higher be considered indicative of diabetes, with diagnostic confirmation being provided through repeat testing (unless clinical symptoms are present and the glucose level is >200 mg/dL). Glucose measurement should remain the choice for diagnosing pregnant women or be used if HbA1c assay is unavailable. The committee cited the following advantages of HbA1c testing over glucose measurement:
Captures long-term glucose exposure
Has less biologic variability
Does not require fasting or timed samples
Is currently used to guide management decisions
The Diabetes Control and Complications Trial (DCCT) found that patients with HbA1c levels of around 7% had the best outcomes relative to long-term complications. Most clinicians aim for HbA1c values of 7-9%. Values of less than 7% are associated with an increased risk of severe hypoglycemia; values of more than 9% carry an increased risk of long-term complications. The International Society for Pediatric and Adolescent Diabetes (ISPAD) recommends a target level of 7.5% (58 mmol/mol) or less for all children.
Normal HbA1c values vary according to the laboratory method used, but nondiabetic children generally have values in the low-normal range. At diagnosis, diabetic children unmistakably have results above the upper limit of the reference range. Check HbA1c levels every 3 months.
Many different methods of measuring HbA1c are available, and the variations between the different assays can be considerable and unpredictable.
A working group was established in 1995 by the International Federation of Clinical Chemists (IFCC) to find a better method of standardizing the various assays. This resulted in a global standard that is gradually being implemented. As a result, HbA1c will be reported as millimole per mole (mmol/mol) instead of as a percentage. The current target range of 7-9% is set to be replaced with values of 53-75 mmol/mol.
Microalbuminuria is the first evidence of nephropathy. The exact definition varies slightly between nations, but an increased AER is commonly defined as a ratio of first morning-void urinary albumin levels to creatinine levels that exceeds 10 mg/mmol, or as a timed, overnight AER of more than 20 mcg/min but less than 200 mcg/min. Early microalbuminuria may resolve. Glomerular hyperfiltration occurs, as do abnormalities of the glomerular basement membrane and glomeruli. Regular urine screening for microalbuminuria provides opportunities for early identification and treatment to prevent renal failure.
Oral Glucose Tolerance Test
Although unnecessary in the diagnosis of type 1 diabetes mellitus, an oral glucose tolerance test (OGTT) can exclude the diagnosis of diabetes when hyperglycemia or glycosuria are recognized in the absence of typical causes (eg, intercurrent illness, steroid therapy) or when the patient's condition includes renal glucosuria (see Glucose).
Obtain a fasting blood sugar level, then administer an oral glucose load (2 g/kg for children aged < 3 y, 1.75 g/kg for children aged 3-10 y [max 50 g], or 75 g for children aged >10 y). Check the blood glucose concentration again after 2 hours. A fasting whole-blood glucose level higher than 120 mg/dL (6.7 mmol/L) or a 2-hour value higher than 200 mg/dL (11 mmol/L) indicates diabetes. However, mild elevations may not indicate diabetes when the patient has no symptoms and no diabetes-related antibodies.
A modified OGTT can also be used to identify cases of MODY (which often present as type 1 diabetes) if, in addition to blood glucose levels, insulin or c-peptide (insulin precursor) levels are measured at fasting, 30 minutes, and 2 hours. Individuals with type 1 diabetes mellitus cannot produce more than tiny amounts of insulin. People with MODY or type 2 diabetes mellitus show variable and substantial insulin production in the presence of hyperglycemia.
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