KEYSTONE, COLO. — Efforts directed at lifestyle modification without concomitant drug therapy in adolescents with type 2 diabetes are “a waste of time,” Dr. Philip S. Zeitler said at a conference on the management of diabetes in youth.
The disease in teens differs in key ways from the classical form arising in middle age or later. Adolescents with type 2 diabetes are more obese.
They have more severe lifestyle abnormalities. While 90% of all diabetes cases are type 2, it's mainly a disease of the elderly, and to a lesser extent of middle age. It's a disease that's largely the result of an unhealthy lifestyle: obesity, sedentary behavior, and a bad diet. Classically it takes decades and decades of these conditions before a person develops type 2 diabetes.
When type 2 diabetes arises in teens—that's 2–5 decades earlier than in the majority of affected individuals—it's believed to be because they've gotten an earlier start on obesity and sedentary behavior and are more extreme in their expression of these risk factors than older patients. These are kids who typically have missed out on the years of highly active running around all day that other kids experience. They have a diet heavily weighted to fast foods, snack foods, and convenience foods. The developmental course of their disease has been compressed due to more intense risk factor levels than in older adults.
Being born to a mother whose pregnancy was complicated by diabetes is an additional potent risk factor for early-onset type 2 diabetes and associated disorders, Dr. Zeitler said in a later interview.
Comorbidities including sleep apnea, fatty liver disease, ovarian hyperandrogenism, and orthopedic issues appear to be more common than in adult type 2 diabetics, probably because of the teens' more intense life- style abnormalities.
And of course adolescents live in families that often may lack social and economic resources and serve as “enablers” of the type 2 diabetic teen's pervasively disordered lifestyle. They may not be ready to provide the sort of support needed for lasting change.
To these factors, add the developmental challenges intrinsic to adolescence, the powerful role peer pressure exerts, and the substantial likelihood that severe depression or other significant psychiatric issues may be present in the type 2 diabetic teen, and it becomes apparent that attempts at lifestyle change in this patient population need to be combined with effective drug therapy, according to Dr. Zeitler of the University of Colorado, Denver.
For specific pharmacologic options targeting blood sugar, one should start is with metformin. For the moment, it's the only approved drug for pediatric type 2 diabetes. It's safe, effective, familiar, and at $20–$30 per month, relatively inexpensive. It results in weight loss, mildly improved lipid profiles, and reduction in hirsutism and menstrual irregularities in females, as well as improved blood glucose control. Lactate acidosis has long been a theoretic worry, but a 40,000-patient metaanalysis showed no increase in risk even when metformin was prescribed despite contraindications (Arch. Intern. Med. 2003;163:2594–602).
Dr. Zeitler offered his personal treatment algorithm, which he termed “unscientific but rational”: Start metformin in new-onset nonketotic teens in relatively good control as defined by an HbA1c of 10% or less. The dose is 500 mg/day, titrated as tolerated to 2,000 mg/day with increases of not more than 500 mg weekly. Also, introduce standard diabetes education with added emphasis on weight loss and lifestyle modification. In new-onset patients in poor control without acidosis, start metformin along with Lantus insulin at 15–30 units four times daily, weaning the patient off insulin as tolerated once control of blood glucose level is attained, he said at the conference sponsored by the University of Colorado and the Children's Diabetes Foundation, Denver.
Acidotic patients are best managed as in type 1 diabetes until the acidosis is reversed. Then start metformin and insulin, later weaning off insulin as tolerated.
Dr. Zeitler readily turns to insulin because it works, it conveys a message that the youth has a serious illness worthy of treatment compliance, and preliminary evidence suggests early use of insulin may preserve beta-cell function. Other drug options have major drawbacks:
▸ Thiazolidinediones. Pediatric approval is anticipated despite lingering concerns about hepatotoxicity, but Dr. Zeitler does not expect this drug class to have a big impact on glycemic control. Type 2 diabetic teens tend to fall into two categories: those who respond well to metformin and lifestyle measures, and those who don't—in which case adding a glitazone is insufficient. However, there may be beneficial nonglycemic effects of these agents that will create a place for them in the future.