|Year : 2014 | Volume
| Issue : 2 | Page : 255-259
Study of puberty in type 1 diabetic boys
Abdalla M Attia1, Naglaa M Ghanayem2, Mostafa M El Najjar3, Doha A Taha1
1 Department of Dermatology, Andrology & STDs, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt
2 Department of Medical Biochemistry, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt
3 Department of Internal Medicine, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt
|Date of Submission||04-Apr-2013|
|Date of Acceptance||10-Jun-2013|
|Date of Web Publication||26-Sep-2014|
Doha A Taha
MBBCh, Department of Dermatology, Andrology & STDs, Quesna Hospital, Quesna, Menoufiya
Source of Support: None, Conflict of Interest: None
This work aimed to study puberty and its disorders - if any, in type 1 diabetes mellitus (T1D) boys.
T1D is a lifelong disease that may affect prepubertal boys. It is an autoimmune disease that destroys the insulin-producing cells of the pancreas, causing hypoinsulinemia. The effects of this disease on the different body systems and organs have received considerable attention from researchers and most of these are well known at present. Unfortunately, its effects on puberty, growth of sexual organs, and sexual maturation have not received such attention.
Patients and methods
A case-control study was carried out on 20 T1D boys, 14-18 years old, who were selected as the patient group. Another 20 healthy, age-matched volunteers were included as a control group. For both groups, the stage of sexual maturation - Tanner's stage and hormonal profile - follicle-stimulating hormone, luteinizing hormone (LH), prolactin, and total testosterone were measured and the growth parameters, including the weight, height, and BMI, were evaluated.
The patients included in this study had poor glycemic control. T1D caused marked retardation of puberty as 25% of the boys were still sexually immature. Follicle-stimulating hormone, LH, and total testosterone were lower in the T1D boys compared with the controls (significantly in the former and latter and insignificant for LH). Prolactin was significantly lower in the diabetic group. T1D boys showed lower growth parameters (weight, height, and BMI) than the controls.
According to our results, T1D boys showed markedly delayed puberty and lower growth parameters compared with the controls.
Keywords: Puberty, type 1 diabetes
|How to cite this article:|
Attia AM, Ghanayem NM, El Najjar MM, Taha DA. Study of puberty in type 1 diabetic boys. Menoufia Med J 2014;27:255-9
| Introduction|| |
Type 1 diabetes mellitus (T1D) was previously known as juvenile diabetes mellitus or insulin-dependent diabetes mellitus . It occurs in genetically predisposed individuals as a consequence of the immune-mediated destruction of pancreatic b cells that secrete insulin . This type of diabetes develops in children and young adults . Its incidence is increasing worldwide in both low and high social classes of populations .
It has increased two- to three-fold over the past half century by as yet unknown means. It is generally accepted that T1D is the result of gene-environment interactions, but such rapid increases in incidence are not explained by Mendelian inheritance .
Although T1D accounts for only 5-10% of all individuals with diabetes, it remains a serious chronic disorder, usually beginning earlier in life than type 2 diabetes, but with important short-term and long-term consequences .
In most of the cases, there is some degree of malnutrition, which results in hormonal modifications . It is considered a factor that potentially affects the onset of male and female puberty and pubertal development and maturity .
Impairment in linear growth and pubertal development continues to be a common complication of T1D in children and adolescents in many parts of the world . The earlier its onset, the longer and more severe the disease, and the greater the repercussion on growth and pubertal development .
Although there are several reports on growth problems of diabetic children, only a few studies have focused on sexual development in such boys and the results are controversial .
This work aims to study puberty and its disorders - if any, in T1D boys.
| Patients and methods|| |
This study was carried out on 40 participants classified into two groups: group A, patient group and group B, control group.
Group A included 20 randomly selected type I diabetic boys 14-18 years old. They were selected from the outpatient diabetic clinic for students of Health Insurance of Shebin El-Kom during the period from January to June 2012. Group B included 20 nondiabetic age-matched healthy boys selected from preparatory and secondary schools of the Menoufiya governorate.
All boys of both groups were subjected to the following: full assessment of history with a focus on the onset of diabetes mellitus, its duration, presence of complications, and treatment (for group A), a thorough general examination focusing on (a) medical problems including complications of diabetes, (b) secondary sexual characteristics - presence of gynecomastiad, measurement of span and height, and weight, and BMI, a thorough local examination focusing on
- Testes and spermatic cords,
- Distribution of pubic hair, and
- Determination of pubertal stage .
Boys with any chronic diseases (except T1D for group A), taking any drugs (except insulin for group A), who had undergone any operation that may affect his development or puberty, or with any anatomical or congenital anomalies of the genitalia were excluded.
Laboratory investigations: a blood sample was obtained from antecubital veins for the detection of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, total testosterone, and HbA1c.
A sample of 5 ml venous blood was collected from each boy. This sample was divided into two tubes: 2 ml was placed in an EDTA-containing tube for estimation of HbA1c (for group A) and 3 ml was placed in a plain tube, left to be clotted, and centrifuged. The obtained serum was kept frozen at -20°C for hormonal estimation. HbA1c was determined by quantitative colorimetric measurement of HbA1c as percent of total hemoglobin using kits supplied by Teco Diagnostics (USA) .
Quantitative measurement of FSH, LH, prolactin, and total testosterone was performed using an Immulite 2000 analyzer, which is a solid-phase, two-site chemiluminescent immunometric assay. The kit used was provided by Immulite 2000 (Diagnostic Products Corporation, USA) ,.
Student's t-test was used for continuous quantitative parametric variables and the Mann-Whitney U-test was used for nonparametric variables. Partial correlation coefficients for testing the association between variables were also determined. A P-value of less than 0.05 was considered statistically significant. Analyses were carried out on an IBM personal computer and using the statistical package SPSS version 16.
| Results|| |
The age of the boys in the patient group matched that of the boys in the control group (15.95 ± 1.3 vs. 15.90 ± 1.4 years, P > 0.05). The diabetic boys included in this study had markedly uncontrolled diabetes as their HbA1c was considerably elevated (9.6 ± 1.8%), whereas good control is indicated - according to the manufacturer, when HbA1c is less than 6.5%. T1D causes marked retardation of puberty as about one-quarter (25%) of the diabetic boys were still sexually immature, had not yet reached the Tanner's stage (stage V), whereas in the control group, 90% were sexually mature and only 10% were still immature. FSH, LH, and total testosterone levels were lower in the T1D boys compared with the controls [significant in the former (P < 0.05) and latter and insignificant for LH (P > 0.05)] [Figure 1],[Figure 2] and [Figure 3]. Prolactin was significantly (P < 0.05) lower in the diabetic group. T1D boys showed lower growth parameters as their weight, height, and BMI were less than those of the controls [significant for the first two (P < 0.05) and insignificant for the BMI (P > 0.05)].
| Discussion|| |
T1D is a relatively common disease. Its effects on the different body systems are known, but those on sexual development and maturation are still unclear .
The results of the study showed that about one-quarter (25%) of the T1D boys had pubertal delay compared with the controls, only 10% were sexually immature that is did not reach the final Tanner's stage (stage V) [Table 1]. These results are in agreement with Elamin et al.  and Rohrer et al. , who found and reported that full sexual maturation in T1D boys (stage V) is retarded and occurs at a mean age of 17.2 years ,. In contrast to this, Salerno et al.  found that T1D has no effect on puberty and sexual maturation.
|Table 1: Tanner's stages - sexual maturity in the patient group compared with the controls|
Click here to view
How does T1D cause pubertal delay and affect sexual maturity? The answer is unclear and more researches are required. It is considered to be because of hypoinsulinemia itself or because of the delayed release of GnRH, with subsequent delayed release of testosterone.
Insulin itself is known to affect the central nervous system functions including the reproductive axis. Normal serum insulin mediates the normal functions of the hypothalamic-pituitary-gonadal axis. Thus, low levels of insulin are considered to delay the function of this axis, with the subsequent delayed release of gonadotropin-releasing hormone (GnRH), leading to pubertal delay . Leptin is an adipocyte hormone that signals to the hypothalamus and the reproductive system as it stimulates GnRH release . The hypoinsulinemia in T1D is associated with hypoleptinemia . Insulin-like growth factor-1, which stimulates and promotes growth and puberty and has been proved to be a direct regulator of GnRH, was found to be low in T1D because of hypoinsulinemia . Poor glycemic control, elevated HbA1c, and inadequate replacement by adequate insulin are other factors believed to cause pubertal delay in these boys ,. We believe that this was the situation in the diabetic boys in our study; they had poor glycemic control and their HbA1c was markedly elevated.
Compared with the controls, we found significantly low FSH and total testosterone and insignificantly low LH.
These results are in agreement with those obtained by Baccetti et al. , who reported lower GnRH pulses in T1D, with subsequently lower FSH, LH, and testosterone, and Ballester et al. , who found that T1D may cause insulin-dependent decrease of FSH and LH, with subsequently reduced Leydig cell functions and testosterone production. Navarro-Casado et al.  speculated that in T1D, the mechanism of testosterone reduction might be a direct effect of excess glucose or its metabolites or defective gonadotropins or resistance to these hormones. López-Alvarenga et al.  and Schoeller et al.  reported blunted LH response to GnRH in T1D boys.
For unknown reasons, prolactin was found to be significantly lower in T1D boys compared with the controls. These results are in agreement with those reported by Hutson et al. , Benitez and PerezDiaz , and Iranmanesh et al. ., who attributed this to enhanced and increased dopaminergic tone in diabetics. Further studies are very essential in this respect.
The rate of growth and its parameters - weight, height, and BMI were found to be less in the patient group compared with the controls. The decrease was significant for weight and height, but insignificant for BMI [Table 2].
|Table 2: Growth parameters (weight, height, and BMI) in the patient group compared with the control group|
Click here to view
These results are in agreement with those reported by Wise et al. , Salerno et al. , Ahmed et al. , Elamin et al. , and Bonfig et al. , who found that T1D boys had lower growth compared with controls.
Pozo and Argente reported that the degree of affection of the growth parameters in T1D boys is proportional to the age of onset, duration of the disease, and its severity. The earlier its onset and more uncontrolled the disease, the greater the repercussion on growth and pubertal development . This was found to be the case in our patient group as they had a relatively long duration of the disease and it was markedly uncontrolled (they had markedly elevated HbA1c). Growth retardation in these boys may have been mostly because of malnutrition, hypoinsulinemia, hypoleptinemia, low testosterone levels, and low GH and insulin-like growth factor-1 .
In contrast to this, other authors failed to find any effect on growth in T1D boys ,,. This may be attributed to good control of the disease among the patients included in their studies and possibly because their patients were older.
| Conclusion|| |
According to our results, T1D boys showed markedly delayed puberty and lower growth parameters compared with the controls. T1D, which is a lifelong disease and mostly affects prepubertal boys, should be studied more intensively by investigators, especially in terms of the sexual and maturational problems at pubertal age and sexual and reproductive health later on. Further studies should be carried out with a larger number of diabetic boys.
| Acknowledgements|| |
The authors are indebted to all members who helped to complete this study.
Conflicts of interest
There are no conflicts of interest.
| References|| |
|1.||Alemzadeh R, Wyatt DT. Diabetes mellitus. In: Kliegman RM, (editors.) Nelson textbook of pediatrics. Philadelphia: Elsevier Saunders; 2007. |
|2.|| Duggan C, Wathins JB, Walken WA. Nutrition in pediatrics: basic science and clinical application. USA: PMPH; 2008. 619. |
|3.|| Kasper DL, Braunwald E, Hauser S, Dan L. Harrison′s principles of internal medicine. New York: Mc-Graw-Hill Professional; 2004. 2275. |
|4.|| Cariage ME, Jones TW, Silink M, Ping YJ. Diabetic care, glycemic control and complications in children with type 1 diabetes from Asia and the Western Pacific Region. J Diabetes Complications 2007; 21 :280-287. |
|5.|| MacFarlane AJ, Strom A, Scott FW. Epigenetics: deciphering how environmental factors may modify autoimmune type 1 diabetes. Mamm Genome 2009; 20 :624-632. |
|6.|| Daneman D. Type 1 diabetes. Lancet 2006; 367 :847-858. |
|7.|| Pozo J, Argente J. Delayed puberty in chronic illness. J Best Pract Res Clin Endocrinol Metab 2002; 16 :73-90. |
|8.|| Rohrer T, Stierkorb E, Heger S, et al. Delayed pubertal onset and development in German children and adolescents. EurJ Endocrinol 2007; 157 :647-653. |
|9.|| Elamin A, Hussein O, Tvemo T. Growth, puberty and final height with type 1 diabetes. J Diabetes Complications 2006; 20 :252-256. |
|10.||Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970; 1 :13-23. |
|11.||Gonen G, Rubenstein A. Haemoglobin A1c in diabetes mellitus. Diabetology 1978; 15 :18. |
|12.||Santner S, Santen R, Kulin H, Demers L. A model for validation of radioimmunoassay kit reagents: measurement of follitropin and lutropinin blood and urine. Clin Chem. 1981; 27 :1892-1895. |
|13.||Babson AL. The IMMULITE automated immunoassay system. J Clin Immunoassay 1991; 14 :83-88. |
|14.||Salerno M, Argentina A, Di Mayo S, et al. Pubertal growth, sexual maturation and final height in children with IDDM, effects of age at onset and metabolic control. Diabetes Care 1997; 20 :721-724. |
|15.||Schoeller EL, Scion S, Motley KH. The effects of type 1 diabetes on the hypothalamic, pituitary and testes axis. Cell Tissue Res 2012; 349 :839-847. |
|16.||Watanobe H. Leptin directly acts within the hypothalamus to stimulate gonadotropin-releasing hormone secretion in vivo in rats. J Physiol (Lond) 2002; 545 :255-268. |
|17.||Fujikawa T, Chuang JC, Sakata I, Ramadori G, Coppari R. Leptin therapy improves insulin-deficient type 1diabetes by CNS-dependent mechanisms in mice. Proc Natl Acad Sci USA 2010; 107 :17391-17396. |
|18.||Hiney JK, Srivastava VK, Pine MD, Dees WL. Insulin-like growth factor-I activates KiSS-1 gene expression in the brain of the prepubertal female rat. Endocrinology 2009; 150 :376-384. |
|19.||Wise JE, Kolb EL, Sauder SE. Effect of glycemic control on growth velocity in children with IDDM. Diabetes Care 1992; 15 :826-830. |
|20.||Ahmed ML, Connors MH, Drayer NM, Jones JS, Dunger DB. Pubertal growth in IDDM is determined by HbA1c levels, sex, and bone age. Diabetes Care 1998; 21 :831-835. |
|21.||Baccetti B, La Marca A, Piomboni P, et al. Insulin-dependent diabetes in men is associated with hypothalamo-pituitary derangement and with impairment in semen quality. Hum Reprod 2002; 17 :2673-2677. |
|22.||Ballester J, Muñoz MC, Domínguez J, et al. Insulin-dependent diabetes affects testicular function by FSH- and LH-linked mechanisms. J Androl 2004; 25 :706-719. |
|23.||Navarro-Casado L, Juncos-Tobarra MA, Cháfer-Rudilla M, et al.. Effect of experimental diabetes and STZ on male fertility capacity: study in rats. J Androl 2010; 31 :584-592. |
|24.||López-Alvarenga JC, Zariñán T, Olivares A, et al. Poorly controlled type I diabetes mellitus in young men selectively suppresses luteinizing hormone secretory burst mass. J Clin Endocrinol Meta 2002; 87 :5507-5515. |
|25.||Hutson JC, Stocco DM, Campbell GT, Wagoner J. Sertoli cell function in diabetic, insulin-treated diabetic and semi-starved rats. Diabetes 1983; 32 :112-116. |
|26.||Benitez A, PerezDiaz J. Effect of streptozotocin-diabetes and insulin treatment on regulation of Leydig cell function in the rat. Horm Metab Res 1985; 17 :5-7. |
|27.||Iranmanesh A, Veldhuis JD, Carlsen EC. Attenuated pulsatile release of prolactin in men with insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1990; 71 :73-78. |
|28.||Bonfig W, Kapellen T, Dost A, et al. Growth in children and adolescents with type 1 diabetes. J Pediatr 2012; 160 :900-903. |
|29.||D′Annunzio G, Cortona L, Vitali L, Pessino P, Lorini R. Final height attainment in girls and boys with insulin dependent diabetes mellitus. Diabetes Res Clin Pract 1994; 24 :187-193. |
|30.||Pitukcheewanont P, Alemzadeh R, Jacobs WR, Jones BH, Eberle AJ. Does glycemic control affects growth velocity in children with insulin-dependent diabetes mellitus? Acta Diabetol 1995; 32 :148-152. |
|31.||Jos J, Meteyer I, Farkas D, Oberkampf B. Growth of children with insulin-dependent diabetes: study of 104 cases. Arch Pediatr 1996; 3 :218-228. |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]
|This article has been cited by|
||Methylation pattern variation between goats and rats during the onset of puberty
| ||C Yang,J Ye,Y Liu,J Ding,H Liu,X Gao,X Li,Y Zhang,J Zhou,X Zhang,W Huang,F Fang,Y Ling |
| ||Reproduction in Domestic Animals. 2018; |
|[Pubmed] | [DOI]|