The diagnosis of diabetes in a child is simple when the random plasma glucose (RPG) is >/- 11.1 mmol/L. Classifying the type of diabetes in children, however, can be challenging with the recent description of early-onset type 2 diabetes and the discovery of single gene disorders that cause defects in insulin secretion. Only a few years ago, all diabetic children were thought to have autoimmune type 1 diabetes. The development of type 2 diabetes in children has raised concern about the potential delay in diagnosing the life-threatening type 1 diabetes. Because physicians are dealing with an explosion of type 2 diabetes cases in adults, they may not recognize the urgency of diagnosis and referral of a child with type 1 diabetes. This article will guide the primary care physician in this diagnostic dilemma, and encourage immediate consultation with a specialized multidisciplinary pediatric diabetes team for a child with diabetes, regardless of the type.

How do I diagnose diabetes in a child?
When a child of any age presents with symptoms of polyuria and polydipsia, the physician must initially consider a diagnosis of type 1 diabetes. The symptoms, usually of acute onset and lasting only 1-2 weeks, may be accompanied by weight loss, fatigue or enuresis. Despite these symptoms, many clinicians have been fooled by how well these children appear. Moreover, the presentation in children younger than three years of age is even more difficult as the only signs they may show are irritability and soaked diapers. In these cases, the physician has to be very astute. Children with diabetic ketoacidosis (DKA) on presentation will look ill, with abdominal pain and vomiting being two of the cardinal symptoms. The telltale sign of DKA is dehydration with copious urine output.

On presentation, many children will have small to large ketones in the urine. This indicates ketonemia and ketonuria, but not usually DKA. The latter can only be confirmed with a capillary blood gas (pH < 7.35 and HCO₃ < 15) or by a low total venous CO₂ (if gases aren't available).

It's imperative to request an immediate random venous plasma glucose (RPG) to confirm the diagnosis of diabetes. If a stat RPG isn't available, a capillary random blood glucose (RBG) using a glucose machine in the office, or a urine dipstick, will give highly specific results. Any RPG >/- 11.1 mmol/L or glucosuria in a child indicates the need for immediate telephone referral to a pediatric centre with experience treating diabetes in children. Waiting for a fasting blood glucose result can mean a serious and dangerous delay in diagnosis and treatment of a symptomatic child.

How is treatment different in children?
The diagnosis of a serious life-threatening chronic disease in a child is associated with profound challenges for parents and siblings. For this reason, regional single-site multidisciplinary pediatric diabetes teams exist in every Canadian province to provide family centred specialized diabetes care in partnership with the family physician. Other major challenges in children are the complex developmental stages and school safety. The potential insulin regimes are the same in children as in adults. Children of all ages can use intensive diabetes management, including continuous insulin infusion by pump. The decision of the optimum insulin regime is best decided by a thorough discussion between the diabetes educators, physician and the family.

Compared to adults, there are major differences when managing DKA in children. The mortality in children associated with DKA is due to cerebral edema, a complication that rarely occurs in adults. Although the cause of cerebral edema remains controversial, treatment guidelines are constructed to limit the risk of this complication in children. The general principles for children include: slow rehydration, no bicarbonate, no insulin bolus, adequate potassium replacement and intensive metabolic and neurologic monitoring. This must always be done in consultation with a centre experienced in managing DKA in children. A recent edition of Canadian Diabetes, published by the Canadian Diabetes Association, featured an article on how to handle DKA in children, and was sent to all family physicians in Canada.

How do we classify childhood diabetes?
A detailed classification of diabetes is included in the 2003 clinical practice guidelines published by the Canadian Diabetes Association (available at www.diabetes.ca).

Type 2 diabetes occurs in adolescents with obesity, acanthosis nigricans, hypertension, dyslipidemia, and a strong family history of type 2 diabetes. The highest rates of type 2 diabetes occur in teens from Aboriginal, Indo-Asian, Hispanic and Caribbean backgrounds. These individuals rarely have acute symptoms of hyperglycemia, including polyuria, polydipsia and weight loss. Ketonuria, however, can be present and DKA may occur in type 2 diabetes when associated with another severe illness, i.e. serious infection.

In an adolescent, the classification of type 2 diabetes is made using the same clinical criteria as the risk factors listed above. The challenge in classification arises when an obese teen presents with acute symptoms of polyuria and polydipsia. The degree of hyperglycemia doesn't help to differentiate between type 1 and type 2 diabetes. A serum insulin or C-peptide level is also not useful, as these levels are usually low because of secondary beta-cell dysfunction due to persistent hyperglycemia. This is referred to as beta-cell glucotoxicity of type 2 diabetes. In these cases, absent islet cell antibody and other beta-cell specific immune markers (anti-GAD and anti-IL2) can help to confirm type 2 diabetes.

What about other types of diabetes?
The other major types of childhood diabetes are secondary diabetes and monogenetic diabetes, which was previously called maturity onset diabetes in youth (MODY). The secondary causes of diabetes are obvious by the patient history, and identified by routine screening of teens with cystic fibrosis, leukemia, renal transplant, or adolescents taking specific drugs such as high-dose, long-term glucocorticoids.

The single gene mutations responsible for diabetes have only recently been discovered and are estimated to account for up to 5% of all type 1 cases. Six types have been identified; the most common are glucokinase (GCK) deficiency and transcription factor diabetes.

GCK deficiency is associated with mild, stable hyperglycemia from infancy, but isn't linked to any long-term complications and requires no pharmacologic intervention. Consider GCK deficiency in Caucasian children previously diagnosed with type 1 diabetes and who have low insulin requirements (< 0.5 U/kg/d) and a remarkably stable HbA1c in the 6-7% range. There may also be a family history of type 2 diabetes for several generations without any complications. Until more physicians become familiar with this diagnosis, it's probably best for these patients to wear a MedicAlert ID to inform healthcare professionals of their benign condition, and to avoid unnecessary investigations and treatment.

The most common form of transcription factor diabetes is a mutation in the hepatic nuclear factor-1 alpha (HNF-1a). This form mimics type 1 diabetes and is most likely to be misclassified as such since affected individuals aren't obese. The key features are a family history suggesting autosomal dominant inheritance of 'type 1' diabetes with onset before age 25, and negative circulating islet cell specific antibodies. These individuals have severe hyperglycemia and develop severe microvascular complications. Treatment with insulin is conventional, but the recent successful use of agents that stimulate insulin secretion, such as the sulphonylurea drugs, have inspired sensational personal testimonials in these cases.

Molecular diagnostic testing for single gene mutations causing diabetes is still not widely available in Canada because of cost and the exploding demand for molecular testing. In such instances, refer patients to a diabetes centre.

Why is it so important to classify diabetes?
In the case of type 1 diabetes, educators will carefully explain autoimmunity and its connection with other autoimmune diseases. Patients and their families must understand the absolute permanent insulin deficiency in type 1 diabetes to recognize the relationship between glucose and ketones and the need for lifelong insulin. Initial treatment of both type 1 and type 2 diabetes may be insulin; however, the discussion about insulin therapy for both types is vastly different. Children with type 1 diabetes need to realize that insulin is required for survival and that oral agents aren't an option. On the other hand, teens with the type 2 form can negotiate a plan for changing their lifestyle and set a date to stop the insulin. They'll learn that their survival doesn't depend on insulin. Adolescents with GCK deficiency require no treatment and those with HNF mutations can start with insulin or a sulphonylurea drug. Investigation and management of these rare conditions should be done by a specialized diabetes team.

At diagnosis, it's critical to communicate effectively with the family. The correct classification of diabetes has a direct impact on diabetes education, family counselling, treatment options, outcomes and eligibility for research protocols.

When should I think about type 2 diabetes?
In children, screen for type 2 diabetes mellitus in those who present with risk factors during any medical encounter. The major risk factors include obesity, age (>/- 10 years), acanthosis nigricans, ethnic background and family history of type 2 diabetes. The offspring of mothers with pre-pregnancy type 2 diabetes or gestational diabetes are especially at high risk for type 2 diabetes. These risk factors are also useful to clinically classify diabetes. Keep in mind, though, that these children rarely have symptoms. Most with type 2 diabetes are identified by a fasting plasma glucose (FPG) screening >/- 7.0 mmol/L. A few with normal FPG values require a glucose load to make the diagnosis of diabetes with a blood glucose >/- 11.1 mmol/L two hours after a 75-g glucose load.

How does its treatment differ from adults?
There must be a strong, concerted initial effort to help these patients modify their lifestyle behaviour instead of turning to pharmacotherapy. If this doesn't work, insulin therapy, using a simple b.i.d. regime of pre-mix insulin for 6-8 weeks, is effective in treating severe hyperglycemia (HbA_1C > 9%) and inducing a temporary remission of the relative insulin deficiency and hyperglycemia. Short-term success in normalizing blood glucose levels is vital for adolescents. None of the oral drugs used in type 2 diabetes are approved for use in children younger than 18 years, therefore, prescriptions for these agents are presently off-label in this population. A discussion of sexual activity and other risky behaviours, including alcohol, driving, drug use and smoking is also important. Many youths with type 2 diabetes have experience in dealing with diabetes complications in their extended families, and the misunderstandings and myths must be carefully dissected with them to achieve any therapeutic benefit from interventions.

Is treatment indicated for impaired glucose tolerance?
The simple answer is no. This will remain a very controversial topic, however, until there's some evidence of long-term benefit of drug treatment in children. Central to any treatment plan must be a very strong, family-centred strategy to support lifelong behaviour modification instead of drug therapy. The same can be said for young obese girls with polycystic ovary disease, a state of ovarian hyperandrogenemia associated with insulin resistance and hyperinsulinemia. In these patients, weight loss is the necessary outcome of therapy. Drugs that reduce insulin resistance are only a temporarily solution to the problem, especially since fertility isn't an immediate goal of therapy in teens.

Where does the family doctor fit in?
The most important role of the family physician is to diagnose diabetes in a child with classical symptoms, and immediately contact a physician with expertise in the care of children with diabetes by telephone to plan the optimum treatment plan. This is an international standard of care. The family doctor has a vital role in identifying adolescents at risk for type 2 diabetes during any medical encounter, and in arranging appropriate screening tests. Once a child is diagnosed with diabetes — either type 1 or type 2 — the primary physician will continue to provide comprehensive care for other members of the family, psychologic support for the siblings and parents, and primary care for the child with diabetes, including immunizations and management of intercurrent (i.e. respiratory, gastrointestial and febrile) illnesses.