E D I T O R I A L
Dancing With Many Different Ghosts
Treatment of youth with type 2 diabetes
M
y training in the treatment of type It feels as if we have accomplished more in The failure of “standard diet and exercise”
2 diabetes in children began when 1 h at the store than the 4 h in the clinic at treatment and conventional education
my father recounted stories of his the health center. Grocery store tours are approaches in this group has accelerated
experience in northern Canada as a fur not a new idea, but they are a vital com- the demand for clinical trials in children
trader with the Hudson’s Bay Company ponent of our education and work with of oral agents that have previously been
(HBC) in the 1930s. The Cree people the youth with type 2 diabetes. Appear- approved and used widely for adults with
lived in tents in the winter months and ances on unscheduled phone-in pro- type 2 diabetes. Through the Interna-
took them down in the summer and fall to grams on the community television tional Conference on Harmonization
go out on the land to hunt. The HBC store network and visits to the community rec- (ICH), the international community has
traded fur pelts for flour, lard, and saccha- reation center and school are also reveal- endorsed the importance of studying the
rine (sugar was much too expensive). ing. efficacy and safety of drugs in children to
Later, in the 1970s, as a medical student Other important lessons about type 2 discourage the use of drugs that have not
on an elective in northern communities, diabetes care are learned at summer been approved for use in children.
the itinerant dentist talked of the frustra- camp. With careful supervision and the As reported in this issue of Diabetes
tion at having to do so many dental ex- high physical activity of camp, the chil- Care, Dr. Ken Jones et al. (4) have cham-
tractions in young children with rotten dren demonstrate that daily average pre- pioned this process in five countries (the
teeth. My early “diabetes” training was meal blood glucose levels can decrease U.S., Russia, Belarus, Poland, and the
continuing with the stories told by the from 20 to 6 mmol/l in 2 weeks (1)! Ukraine) by completing the first study of
pregnant women who sat for hours to- They also teach us about the challenges of efficacy and safety of an oral drug in chil-
gether carving soapstone behind the hos- food access, their experience with food dren with type 2 diabetes. They enrolled
pital. The women had “come out” from preparation, their opportunities for recre- 82 youth with type 2 diabetes aged 10 –16
their communities to wait until after de- ation, their fears about diabetes and its years in a 16-week, randomized, placebo-
livery before returning home. They talked treatments, their personal perspective on controlled study of the effect of met-
of their hardships and sorrows, their chil- the losses, horrors, and tragedies related formin on fasting blood glucose (FBG)
dren and families, and living off the land. to diabetes complications in their fami- levels. The subjects were “counseled on
I’ve also learned from our northern lies, and the experience of their family dietary and exercise practices provided at
outreach clinics. We fly in small planes to with residential schools, substance abuse, each study visit.” The mean decrease in
small communities surrounded by rock, and relocation (2). To these experiences, I FBG from baseline was 2.4 mmol/l in the
lakes, rivers, and boreal forest. After our add my observations from visits to the study group. The drug was well tolerated.
afternoon clinics, we walk to the store schools and community clubs in the inner Short-term safety markers were normal.
along the frozen barren roads in winter or city. Recruitment of subjects for the study
the potholed, dust-covered roads shared The relevance of our experience in was difficult. Most were recruited by
with pickup trucks in spring. Several northern remote communities in Canada screening children at high risk for type 2
youth from our clinic show up. We walk to youth living in large urban centers in diabetes. They were offered immediate re-
around the aisles together as a group—the other parts of Canada, the U.S., and other cruitment to the study. There were 10
teens, doctor, dietitian, nurse, and social countries in the world may not be readily dropouts, with only 4 of these from ad-
worker. We read labels of snack foods and apparent. But observation and feedback verse events. The rescue criteria were
compare prices of fresh, frozen, and from many colleagues indicate remark- stringent, with the subjects requiring res-
canned products. Elders express their able similarities in our youth with type 2 cue to metformin if FBG was 12.8
concern about diabetes in their commu- diabetes. I am sure that the face of disen- mmol/l at 2 weeks, 10 mmol/l at 4
nity and especially about the fate of the franchisement and child poverty is inter- weeks, and 7.8 mmol/l at 6 weeks. Suc-
children. We scrutinize the checkout national. cess of standard diet and exercise coun-
counter to see how many cartons of soda The treatment of type 2 diabetes in seling in the placebo group was low, with
pop and chips are going through. We children and adolescents is a huge chal- 26 of 36 subjects requiring rescue. Only 4
learn that two of the teens with us are lenge because of the diverse linguistic, of the 36 subjects in the study group re-
responsible for buying groceries every geographic, cultural, social, economic, quired rescue. In addition, on the basis of
week for their family of seven. The dieti- and political barriers that influence the the results of an interim analysis at the
tian assesses and makes a mental note of access to, acceptance of, and outcome of point when 50% of the subjects had com-
their arithmetic skills, reading skills, treatment (3). The consequences of NOT pleted 8 weeks of the study, the data
knowledge of nutrition, and food prepa- achieving therapeutic goals in childhood safety monitoring board recommended
ration. The event is spontaneous and fun. will be devastating in young adult life. that the study be terminated early. The
DIABETES CARE, VOLUME 25, NUMBER 1, JANUARY 2002 237
Editorial
results were based on an analysis of the What is the chance that the youths HEATHER J. DEAN, MD, FRCPC
change in FBG from baseline to the last will take the drug on a daily long-term
visit of the double-blind portion of the basis? In a recent study of metformin in From the Department of Pediatrics, University of
study for each subject, even if that last visit obese adolescents for 6 months, only Manitoba, Winnipeg, Manitoba, Canada.
Address correspondence to Dr. Heather Dean,
was after only 2 weeks of the study. An un- three subjects withdrew (5). We know Department of Pediatrics, Health Sciences Centre,
fortunate occurrence in this study was that adolescents with renal transplants FE-319 685 William Ave., Winnipeg, Manitoba R3E
that the two study groups differed in their and type 1 diabetes miss their medica- 0Z2, Canada. E-mail: hdean@cc.umanitoba.ca.
baseline FBG, despite randomization by tions even if it means losing their trans- H.J.D. has received honoraria/consulting fees
permuted block design. A greater number from Pfizer and Eli Lilly for the clinical trials of prod-
plant or life-threatening diabetic ucts used in the treatment of diabetes.
of youth (20/40 50%) randomized to ketoacidosis. Teens with type 2 diabetes,
the placebo group had a baseline FBG in addition to adolescent risk-taking and
11.1 mmol/l compared with the met- defiant behaviors, have other reasons to Acknowledgments — I am indebted to my
formin group (9/42 21%). It is impos- refuse medications. These reasons in- colleagues, Drs. Elizabeth Sellers and Mike
sible to evaluate whether more youth in clude lack of symptoms, fear that the Moffatt, for sharing my passion to help this
the metformin group had passed the res- complications of diabetes are caused by group of youth and discussing the content of
cue criteria simply because their baseline pills and insulin, fear of pills or needles, a this editorial. I also appreciate the help of Jake
FBG was lower, and also whether more feeling of hopelessness, a lack of empow- MacDonald and Rupert Ross in expressing that
subjects in the metformin group had passion in words.
erment, and low self-esteem.
passed the 8-week point when the study Is there a way to create more effective
was terminated. In the final analysis, only diabetes education programs that will ad- ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●
3 subjects in the placebo group and 19
dress lifestyle factors in a more therapeu- References
subjects in the metformin group com-
tic manner for this age group? There are 1. Anderson K, Dean HJ: The effect of diet
pleted the 16-week study. The rescue and exercise on a native youth with poorly
many parallels in the justice systems in
with study drug precluded an intent-to- controlled NIDDM. Beta Release 14:105–
Canada and the U.S. In his 1992 book
treat analysis at 16 weeks. 106, 1990
entitled Dancing With a Ghost, Rupert Ross
This study is an important first step in 2. Bussidor I, Bilgren-Reinhart U: Night Spir-
our understanding of the pharmacologic wrote that in order for courts to deal ef- its: The Story of Relocation of the Sayisi
treatment of type 2 diabetes in youth. fectively with young offenders, court per- Dene. Winnipeg, Canada, University of
Which children would benefit most from sonnel must understand the reasons why Manitoba Press, 1997
metformin? Are there subgroups of youth conventional systems fail these young 3. Dean HJ, Moffatt MEK: Care of aboriginal
who would benefit more from short-term people (6). children with type 2 diabetes: A head-to-
Our diabetes personnel must under- head debate regarding the roles of the pe-
insulin or another oral agent as first line of diatric specialty team and the primary
therapy? According to the protocol used stand the reasons why conventional diet
and exercise systems fail youth with type health care team. Canadian J Diabetes Care
in the Jones study, a youth with an FBG of 24:28 –33, 2000
18 mmol/l at diagnosis who achieves an 2 diabetes. We need to improve our com- 4. Jones KE, Arslanian S, Peterokova VA,
FBG of 9 mmol/l after 6 weeks of intense munication and cross-cultural skills. We Park J-S, Tomlinson MJ: Effect of met-
effort to modify their lifestyle would be a need to understand the impact of sys- formin in pediatric patients with type 2
candidate for “rescue” with metformin. Is temic elements and determinants of diabetes: a randomized controlled trial.
the potential benefit of adding metformin health on diabetes care for youth. We Diabetes Care 25:89 –94, 2002
at this point justified over enthusiastic need to accept the central importance of 5. Freemark M, Bursey D: The effects of met-
and supportive encouragement in life- decision making around the goals of the formin on body mass index and glucose
teen and family. It is not negligent to wait intolerance in obese adolescents with fast-
style changes? What is the impact of add- ing hyperinsulinemia and a family history
ing metformin versus continued a few more weeks or months before con- of type 2 diabetes. Pediatrics 107:E55,
counseling on the youth’s self-esteem? On sidering pills or insulin in a youth who is 2001
glycemic control at 1 year? On family dy- making progress. We need to be able to 6. Rupert Ross: Dancing With a Ghost: Explor-
namics, the adolescent-parent relation- accept unique, individual time frames for ing Indian Reality. Butterworth-Heineman,
ship, and family economics? achieving therapeutic goals. 1992
238 DIABETES CARE, VOLUME 25, NUMBER 1, JANUARY 2002