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Published online June 15, 2007
Diabetes Care 30:2338-2340, 2007
DOI: 10.2337/dc07-0043
© 2007 by the American Diabetes Association
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Pathophysiology/Complications
Original Article

Is Pubertal Onset a Risk Factor for Blindness and Renal Replacement Therapy in Childhood-Onset Type 1 Diabetes in Japan?

Aya Morimoto, MD1, Rimei Nishimura, MD, MPH1,2, Toru Matsudaira, MD1, Hironari Sano, MD1, Naoko Tajima, MD1 for the Diabetes Epidemiology Research International Study Group*

1 Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
2 Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania

Address correspondence and reprint requests to Aya Morimoto, Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan. E-mail: aya{at}jikei.ac.jp

Abbreviations: RRT, renal replacement therapy


   INTRODUCTION
TOP
 INTRODUCTION
RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 APPENDIX
 References
 
We previously reported that mortality is worse for pubertal-onset type 1 diabetes than for the prepubertal-onset variety (1). Other studies have disparately reported that the risk for incipient microangiopathy in type 1 diabetic patients is higher during puberty than before puberty (2–4) or that the risk is similar (5,6). However, evidence regarding the relationship between puberty and advanced microangiopathy is limited (7). We therefore investigated the incidence of blindness and renal replacement therapy (RRT) by pubertal status at diagnosis.


   RESEARCH DESIGN AND METHODS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
RESULTS--
 CONCLUSIONS--
 APPENDIX
 References
 
A total of 1,408 type 1 diabetic patients diagnosed at <18 years of age were placed on insulin therapy within 1 month of diagnosis. They were chosen from two nationwide type 1 diabetes surveys (1,8,9). The patients were either 1) diagnosed between 1965 and 1969 and alive as of 1 January 1970 (the 1960s cohort) or 2) diagnosed between 1970 and 1979 and alive as of 1 January 1980 (the 1970s cohort). Follow-up for the 1960s and 1970s cohorts was initiated on 1 January in 1970 or 1980, respectively. Diagnosis in males aged ≥12 years and females aged ≥11 years was defined as pubertal onset, as earlier reported (1,2,5,9–11). The cohorts accounted for ~75% of all type 1 diabetic subjects in Japan (1,8,12).

Status of blindness and RRT as of 1 January 1995 was identified by questionnaires completed by attending physicians, with blindness defined as visual acuity of light perception or a worse state in at least one eye and RRT as either receiving dialysis or post–kidney transplantation status. Cumulative incidence rates of blindness and RRT were calculated using the Kaplan-Meier method and analyzed by log-rank tests. Logistic regression models were used to estimate the odds ratios (ORs) for these complications at 15 years of follow-up, with prepubertal/pubertal onset, sex, and 1960s/1970s (year of onset) included as predictor variables after adjusting for disease duration before follow-up. The study was approved by the institutional review board of Jikei University School of Medicine.


   RESULTS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
CONCLUSIONS--
 APPENDIX
 References
 
Subjects comprised 1,408 individuals (of whom 566 were male and 842 female) with 965 (417 male and 548 female) classified as prepubertal onset and 443 (149 male and 294 female) as pubertal onset. The age at diagnosis was 6.7 ± 3.0 and 13.5 ± 1.7 years for prepubertal and pubertal onset, respectively, and the follow-up was 16.1 ± 4.2 and 15.8 ± 5.2 years. Blindness developed in 52 prepubertal and 45 pubertal onset patients (P = 0.0003 by {chi}2 test) and RRT in 64 and 78 patients (P < 0.0001). The last confirmed complication status was used for 124 deceased patients and for 62 patients whose status as of 1995 was missing. The presence or absence of blindness or RRT was confirmed in 90.7 and 95.8%, respectively.

The cumulative incidence of blindness and RRT during follow-up was significantly higher in the pubertal-onset group than that in the prepubertal-onset group (Fig. 1A). However, analysis by whether the subject attained 18 years of age demonstrated no significant difference in cumulative incidence between these complications, regardless of age at onset (Fig. 1B).


Figure 1
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  		Figure 1— Cumulative incidence rates of blindness and RRT throughout the follow-up period (A) and after the age of 18 years (B). P values were calculated by log-rank test. —, pubertal onset; ----, prepubertal onset.

 
Logistic regression models revealed that the pubertal-onset group had a 2.15 times higher risk for blindness (95% CI 1.43–3.24, P = 0.0002) and a 4.00 times higher risk for RRT (2.74–5.84, P < 0.0001) than the prepubertal-onset group at 15 years of follow-up. Being in the 1960s cohort was a significant risk factor for blindness (OR 4.07 [95% CI 2.52–6.58], P < 0.0001) and RRT (3.13 [2.01–4.89], P < 0.0001). Sex was not a risk factor for either complication in these models.


   CONCLUSIONS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
APPENDIX
 References
 
Our main finding was that pubertal-onset type 1 diabetic patients had a higher risk for developing blindness and RRT than that for prepubertal-onset patients. A Swedish study reported similar results for end-stage renal disease (7). However, to date, there is no large-scale longitudinal prospective study investigating the influence of pubertal status at onset of disease on developing blindness. Furthermore, we demonstrated that attained age was a determinant of these advanced microangiopathies, regardless of age at onset.

Insulin resistance and abnormalities in the growth hormone/insulin-like growth factor-1 axis lead to poor metabolic control (13–15) and nephropathy (16–19) during puberty among type 1 diabetic patients. Glycemic control is poorer among pubertal-onset patients than among prepubertal-onset patients (13,20). These factors likely led to the development of blindness and RRT in later life.

There are some limitations in the current study. First, pubertal status was defined by age, not by Tanner stage, which was culturally difficult to determine in a population-based cohort in Japan. Because very few reliable reports had examined pubertal-onset age in Japan, as well as to compare our data with those previously published (1,2,5,9–11), we used the same definition of pubertal status by age. Second, glycemic status of the subjects was not addressed, as it was technically impossible to evaluate in a standardized manner in our questionnaire survey.

We conclude that special attention should be paid to those who develop type 1 diabetes during puberty, given their higher risk for late complications.


   APPENDIX
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 APPENDIX
References
 
The Diabetes Epidemiology Research International Study Group (Japan) includes the following members: Teruo Kitagawa, Naoko Tajima, Nobuo Matsuura, Takayoshi Toyota, Yoshio Ikeda, Itsuro Hibi, Eishi Miki, Hiroshi Maruyama, Masahiko Kawamura, Gen Isshiki, Akira Takeda, Kaichi Kida, Yasuko Kohno, Goro Mimura, Mayumi Aono, Shigeo Aono, Michihiko Maruyama, Shohei Harada, Susumu Konda, Tatsuhiko Urakami, Yasuko Uchigata, Nobuyuki Kikuchi, Koichi Kaino, Nigishi Hotta, Tomoyuki Kawamura, Yoshihiro Nakamura, Tomio Jinnouchi, Hideaki Jinnouchi, Naoki Fukushima, Koji Takemoto, Masakazu Haneda, Kenji Fujieda, Masae Minami, Masato Matsushima, Michihiko Maruyama, Kanae Shimizu, Rimei Nishimura, Keiko Asao, Hironari Sano, Toru Matsudaira, and Aya Morimoto.


   Acknowledgments
 
This study was supported by grants from the National Institutes of Health (DK-35905); the Ministry of Health and Welfare, Japan (H10-Kodomo-022); and the Ministry of Education, Culture, Sports, Science, and Technology, Japan (Wakate-B 14770186, 16790328).

The authors thank Dr. Keiko Asao and all members of the Diabetes Epidemiology Research International Study Group for their contribution to the study.


   Footnotes
 
Published ahead of print at http://care.diabetesjournals.org on 15 June 2007. DOI: 10.2337/dc07-0043.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

* A list of the Diabetes Epidemiology Research International Study Group members can be found in the APPENDIX. Back

Received for publication January 9, 2007. Accepted for publication June 8, 2007.


   References
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 APPENDIX
 References
 

  1. Nishimura R, Tajima N, Matsushima M, LaPorte RE, the Diabetes Epidemiology Research International Study Group: Puberty, IDDM, and death in Japan. Diabetes Care 21:1674–1979, 1998[Abstract]
  2. Kostraba JN, Dorman JS, Orchard TJ, Becker DJ, Ohki Y, Ellis D, Doft BH, Lobes LA, LaPorte RE, Drash AL: Contribution of diabetes duration before puberty to development of microvascular complications in IDDM subjects. Diabetes Care 12:686–693, 1989[Abstract]
  3. Olsen BS, Sjolie AK, Hougaard P, Johannesen J, Marinelli K, Jacobsen BB, Mortensen HB; Danish Study Group of Diabetes in Childhood: The significance of the prepubertal diabetes duration for the development of retinopathy and nephropathy in patients with type 1 diabetes. J Diabetes Complications 18:160–164, 2004[Medline]
  4. Dahlquist G, Rudberg S: The prevalence of microalbuminuria in diabetic children and adolescents and its relation to puberty. Acta Paediatr Scand 76:795–800, 1987[Medline]
  5. McNally PG, Raymond NT, Swift PG, Hearnshaw JR, Burden AC: Does the prepubertal duration of diabetes influence the onset of microvascular complications? Diabet Med 10:906–908, 1993[Medline]
  6. Donaghue KC, Fung AT, Hing S, Fairchild J, King J, Chan A, Howard NJ, Silink M: The effect of prepubertal diabetes duration on diabetes: microvascular complications in early and late adolescence. Diabetes Care 20:77–80, 1997[Abstract]
  7. Svensson M, Nystrom L, Schon S, Dahlquist G: Age at onset of childhood-onset type 1 diabetes and the development of end-stage renal disease: a nationwide population-based study. Diabetes Care 29:538–542, 2006[Abstract/Free Full Text]
  8. Diabetes Epidemiology Research International Mortality Study Group: Major cross-country differences in risk of dying for people with IDDM. Diabetes Care 14:49–54, 1991[Abstract]
  9. Asao K, Sarti C, Forsen T, Hyttinen V, Nishimura R, Matsushima M, Reunanen A, Tuomilehto J, Tajima N: Long-term mortality in nationwide cohorts of childhood-onset type 1 diabetes in Japan and Finland. Diabetes Care 26:2037–2042, 2003[Abstract/Free Full Text]
  10. Porta M, Dalmasso P, Grassi G, Marena S, Maurino M, Passera P, Trento M: Pre-pubertal onset of type 1 diabetes and appearance of retinopathy. Diabetes Metab 30:229–233, 2004[Medline]
  11. Kostraba JN, Dorman JS, LaPorte RE, Kuller LH, Orchard TJ, Becker DJ, Drash AL: The investigation of age at onset as a risk factor for mortality in persons with insulin-dependent diabetes mellitus using Cox proportional hazards models. Am J Epidemiol 133:67–72, 1991[Abstract/Free Full Text]
  12. Tajima N, LaPorte RE, Hibi I, Kitagawa T, Fujita H, Drash AL: A comparison of the epidemiology of youth-onset insulin-dependent diabetes mellitus between Japan and the United States (Allegheny County, Pennsylvania) Diabetes Care 8 (Suppl 1):17–23, 1985
  13. Amiel SA, Sherwin RS, Simonson DC, Lauritano AA, Tamborlane WV: Impaired insulin action in puberty: a contributing factor to poor glycemic control in adolescents with diabetes. N Engl J Med 315:215–219, 1986[Abstract]
  14. Acerini CL, Williams RM, Dunger DB: Metabolic impact of puberty on the course of type 1 diabetes. Diabetes Metab 27:S19–S25, 2001[Medline]
  15. Simpson HL, Jackson NC, Shojaee-Moradie F, Jones RH, Russell-Jones DL, Sonksen PH, Dunger DB, Umpleby AM: Insulin-like growth factor I has a direct effect on glucose and protein metabolism, but no effect on lipid metabolism in type 1 diabetes. J Clin Endocrinol Metab 89:425–432, 2004[Abstract/Free Full Text]
  16. Amin R, Williams RM, Frystyk J, Umpleby M, Matthews D, Orskov H, Dalton RN, Dunger DB: Increasing urine albumin excretion is associated with growth hormone hypersecretion and reduced clearance of insulin in adolescents and young adults with type 1 diabetes: the Oxford Regional Prospective Study. Clin Endocrinol (Oxf) 62:137–144, 2005[Medline]
  17. Amin R, Schultz C, Ong K, Frystyk J, Dalton RN, Perry L, Orskov H, Dunger DB: Low IGF-I and elevated testosterone during puberty in subjects with type 1 diabetes developing microalbuminuria in comparison to normoalbuminuric control subjects: the Oxford Regional Prospective Study. Diabetes Care 26:1456–1461, 2003[Abstract/Free Full Text]
  18. Cummings EA, Sochett EB, Dekker MG, Lawson ML, Daneman D: Contribution of growth hormone and IGF-I to early diabetic nephropathy in type 1 diabetes. Diabetes 47:1341–1346, 1998[Abstract]
  19. Hovind P, Lamberts S, Hop W, Deinum J, Tarnow L, Parving HH, Janssen JA: An IGF-I gene polymorphism modifies the risk of developing persistent microalbuminuria in type 1 diabetes. Eur J Endocrinol 156:83–90, 2007[Abstract/Free Full Text]
  20. Schultz CJ, Konopelska-Bahu T, Dalton RN, Carroll TA, Stratton I, Gale EA, Neil A, Dunger DB, the Oxford Regional Prospective Study Group: Microalbuminuria prevalence varies with age, sex, and puberty in children with type 1 diabetes followed from diagnosis in a longitudinal study. Diabetes Care 22:495–502, 1999[Abstract]

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This Article
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