Distinguishing between Type 1 and Type 2 diabetes in children can be a challenge

The hallmark clinical symptoms of diabetes include polyuria and polydipsia. Nocturia and fatigue are also common.

Primary care providers play an invaluable role in the diagnosis of diabetes in children.

The hallmark clinical symptoms of diabetes include polyuria and polydipsia. Nocturia and fatigue are also common. If the hyperglycemia has been long-standing, weight loss occurs at presentation. Glycosuria and ketonuria also may be present at the time of diagnosis.

About a third of patients with Type 1 diabetes will present with diabetic ketoacidosis (DKA). Symptoms of DKA include abdominal pain, nausea, vomiting and Kussmaul respirations.

“Recognition of the signs and symptoms of DKA is very important, because this can be a life-threatening complication of diabetes,” said Prasanthi P. Gandham, M.D., a pediatric endocrinologist at Norton Children’s Endocrinology, affiliated with the UofL School of Medicine, and the Wendy Novak Diabetes Institute.

Glucose and A1C levels often rise well before the clinical onset of diabetes symptoms.

“Astute clinicians might be able to actually make a diagnosis before a child presents with DKA. And if we can spare them that complication … that would be our ultimate goal,” Dr. Gandham said during a recent continuing medical education opportunity, “The General Provider and Diabetes.”

A diagnosis of diabetes requires two abnormal lab tests: Fasting plasma glucose greater than 126 mg/dL, a two-hour postprandial glucose of 200 mg/dL during an oral glucose tolerance test using a glucose load of 1.75 grams per kilo to a max of 75 grams of glucose dissolved in water, or a hemoglobin A1c level of 6.5% or greater.

If a patient has classic symptoms of hyperglycemia such as polyuria, polydipsia or nocturia, and if they are in a hyperglycemic crisis, a random plasma glucose greater than 200 mg/dL in addition to the symptoms is adequate for diagnosis.

Differentiating between Type 1 and Type 2 diabetes in children

“One of the biggest challenges that we all face today as clinicians is differentiating between Type 1 and Type 2 diabetes,” Dr. Gandham said. “Given the current obesity epidemic, distinguishing between Type 1 and Type 2 diabetes in children can be quite difficult. Overweight and obesity are common in children with Type 1 diabetes, and diabetes-associated autoantibodies and ketosis may be present in pediatric patients with features of Type 2 diabetes.”

Additionally, DKA at onset of Type 2 diabetes occurs more commonly in children than it does in adults. About 6% of patients ages 10 to 19 with Type 2 diabetes present with DKA.

In Type 1 diabetes, there is absolute insulin deficiency, while in Type 2 diabetes, there is relative insulin deficiency and often peripheral insulin resistance as well.

Type 1 diabetes occurs due to cellular mediated autoimmune destruction of beta cells. There are multiple genetic predispositions to autoimmune beta cell destruction and an environmental factor that triggers autoimmune destruction of the beta cells, though this environmental trigger remains poorly understood.

Autoimmune destruction of beta cells probably begins months to maybe even years before the onset of symptoms, with the rate of beta cell destruction tending to be more rapid in children and adolescents, compared with adults. Diabetes typically becomes clinically apparent when approximately 90% of the beta cell mass is destroyed.

Antibodies used to assess for Type 1 diabetes include islet cell autoantibodies, GAD65, insulin, IA-2 antibodies and, more recently, the zinc transporter 8 autoantibodies.

C-peptide and insulin levels at the time of diagnosis, before insulin therapy has been initiated, also can have a lot of clinical utility. In Type 1 diabetes, C-peptide and insulin levels are expected to be low and sometimes are undetectable at the time of diagnosis.

Risk factors for Type 2 diabetes include adiposity, family history of diabetes, female gender assignment at birth and low socioeconomic status. In young people, Type 2 diabetes also results in much more rapid beta cell destruction than in adults, frequently putting them at risk for accelerated development of long-term microvascular and even macrovascular complications of diabetes.

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To refer a patient to Norton Children’s Endocrinology, visit Norton EpicLink and choose EpicLink referral to Pediatric Endocrinology/Diabetes Mellitus.

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“Initial management of diabetes, no matter whether the underlying diagnosis is Type 1 or Type 2 diabetes, should be targeted toward management of hyperglycemia as well as any metabolic derangements that are present, such as ketonuria or ketosis,” Dr. Gandham said.

If a diagnosis of Type 2 diabetes is suspected based on phenotypic features and clinical history, a child with an A1C less than 8.5% and no acidosis or ketosis reasonably can be started on metformin monotherapy while pancreatic autoantibody results are pending. If A1C is above 8.5%, with no acidosis or ketosis, then the child should receive basal insulin therapy in addition to metformin, typically at about 0.5 mg/kilo per day, while awaiting autoantibody results. Children with more significantly elevated A1C levels may require a full multiple daily injections (MDI) insulin regimen with both basal and bolus insulin.

If the antibodies are negative, metformin can be titrated up to 2,000 mg/day, with blood sugars monitored closely. If they return positive, then metformin can be discontinued, and the child should be transitioned to MDI therapy, according to Dr. Gandham.

“I think the real key here is that if you have a child and a diagnosis of diabetes has been made, even if a diagnosis of Type 2 diabetes is suspected, obtaining pancreatic autoantibodies is really paramount to making the appropriate management decisions,” Dr. Gandham said.

Referring providers and others with questions about next steps in a child’s care can contact the multidisciplinary team at the Wendy Novak Diabetes Institute, part of Norton Children’s Endocrinology.

“We’re always happy to talk to anybody in the community — providers, families — and we can help make a decision about whether the child needs to be referred to the ER [emergency room], or if we’re able to bring them into our office for an urgent outpatient visit to start them on appropriate therapy with insulin and any oral anti-hyperglycemic agents that they may need,” Dr. Gandham said.

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