In my practice, I have to make the diagnosis of diabetes in children about once every four or five years. Each time has been agonizing.

Usually the child has weight loss and awakens at night to urinate. The parents are concerned and a simple urine test confirms the diagnosis. It is a difficult time for everyone. The parents might have suspected the diagnosis, but the child is usually totally oblivious and will need a period of adjustment.

Drs. Michael Freemark and Robert Benjamin from the Duke Children’s Division of Endocrinology tell us about the disease and what parents and children can expect once diagnosed.

-- Dennis Clements MD, PhD, MPH

Diabetes was first described by the Greek physician Aretaeus in the first century AD, but it was not until the discovery of insulin by Banting, Best, and Collip in 1922 that it became possible to treat the disease effectively.

Despite the emergence of type 2 diabetes as a problem in obese adolescents, most children with diabetes have a form of the disease that we call type 1 diabetes.

Type 1 diabetes results from the body’s own (autoimmune) destruction of the pancreatic beta cells, the manufacturing plants for insulin. As beta cells are lost progressively over weeks, months, or years, the body loses its ability to produce insulin in response to sugar and other foodstuffs.

The lack of insulin prevents the entry of sugar into fat and muscle cells, and thereby increases sugar levels in the circulation. Because sugar cannot enter cells it cannot be used for energy; consequently the body breaks down fat and muscle to sustain the critical needs of life. The breakdown of fat causes the accumulation of “ketones,” which are acids that in excess can prove highly dangerous to the heart and irritating to the stomach.

Meanwhile sugar is transported to the kidney, where it washes water and other important chemicals into the urine. Thus the symptoms of uncontrolled diabetes are excessive urination and compensatory drinking, weight loss (from water loss and fat breakdown), and nausea and vomiting (from acid buildup). All of these symptoms are reversed by insulin.

Causes of Childhood Diabetes

Why does a child develop type 1 diabetes? Despite thousands of studies, we simply don’t know. Diabetes runs in certain families, and investigations in humans and experimental animals point to important contributions of gene families that control the body’s immune response. However, even an identical twin of a child with type 1 diabetes has only a 30 to 50 percent chance of developing the disease.

This suggests that there are environmental triggers that promote the disease in people who are genetically prone. Indeed, the rates of type 1 diabetes in young children have been increasing for the past 50 years, for reasons that are presumably environmental in nature. The environmental triggers have not been determined; possibilities include viral infections, toxins, and early introduction of certain foods.

Can diabetes be prevented safely in children who come from families at risk? Not at this time. Current studies are investigating the roles of vitamin D and cereal proteins in the development of childhood diabetes, and some studies suggest that prolonged breast-feeding might be helpful in preventing diabetes. Better evidence on this issue should emerge in the next decade.

Treatments

For many years insulin injections were the mainstay of therapy for type 1 diabetes. Technological advances have made the process easier for children and their families and have improved glucose control.

The insulin pump is a good example; it provides a continuous infusion of insulin throughout the day and night and can be used to administer extra insulin at meals. Duke’s Division of Endocrinology was the first to use insulin pumps in infants and toddlers; this made it far easier to control a baby’s blood sugars and reduced the rates of dangerous hypoglycemia. Following our publication, pumps are nowused routinely in young children throughout the developed world.

A major new development is continuous glucose monitoring. A device inserted under the skin monitors blood sugars every three to five minutes.

Intensive efforts are now underway to develop systems in which the continuous monitors communicate effectively and safely with insulin pumps; in theory, one day the system will monitor sugar levels instantaneously and “tell” the pump exactly how much insulin to deliver at any given time. This will take much of the guesswork out of diabetic control and will reduce the risks of short- and long-term complications.

Complications

Complications are what make diabetes so dangerous. The good news is that improvements in blood sugar control clearly reduce the rates of eye disease (retinopathy), kidney disease (nephropathy), and nerve damage (neuropathy) and improve quality of life; recent findings suggest that reductions in hemoglobin A1c, a measure of sugar control over the past three months, also reduce the long-term risks of heart disease and stroke.

The not-so-good news is that cardiovascular complications may be prevented only with very intensive and strict control of blood sugars, which may increase the dangers of hypoglycemia. In this respect, the “artificial pancreas” systems that integrate continuous monitors, hypoglycemic alarms, and pump therapy may provide a safe and effective approach.

Type 1 diabetes is also associated with a variety of other conditions that may impact childhood growth and development; these include hypothyroidism and celiac disease.

At Duke we were the first to demonstrate the screening of diabetic children for celiac disease could detect abnormalities in growth and bone mineral content and that institution of a gluten-free diet could restore normal bone development. We suspect that screening for celiac disease in type 1 diabetes will soon be applied universally.

The best way to prevent complications of diabetes would be to cure the disease itself. This is going to be a long process, given that we don’t even know what causes diabetes in the first place.

Transplants of pancreas or bone marrow can restore insulin production but require life-long suppression of the body’s immune system; this places a child at risk for life-threatening infections and cancer in later life. So we need better approaches.

A recent exciting study in mice showed that insertion of three beta cell genes into non-beta cells in the pancreas was able to convert the non-beta cells to beta cells, restore insulin production, and reverse diabetes. Such an approach might be applied to diabetic children and adults in the future.

Prior to the discovery of insulin the development of type 1 diabetes in a child was a death notice. Today, children with diabetes can live long lives and can, with lots of effort and with a few exceptions, do anything that they want to do. But ongoing research in the field will no doubt make them healthier and happier in the future.

-- Michael Freemark, MD, and Robert Benjamin, MD, are physicians in Duke Children's Division of Endocrinology.

-- Dennis Clements, MD, PhD, MPH, is the chief of primary care pediatrics at Duke Children's Hospital.