Prediabetes and Adolescence—Trends, Causes, Effects, and Screening

US Endocrinology, 2016;12(2):94–8 DOI: https://doi.org/10.17925/USE.2016.12.02.94

Abstract:

Intermediate hyperglycemia, or prediabetes, is increasing worldwide, affecting people of all ages, including adolescents. Hormonal, physiological, psychological, and lifestyle changes in adolescence have been associated with disruptions in glucose homeostasis, such as decreased insulin sensitivity, insulin resistance, or the combination of both. As a rule, glucose homeostasis is ameliorated, in normal subjects, when puberty is completed. However, in susceptible individuals, like obese adolescents, or adolescents with a strong genetic background, there is a progression to type 2 diabetes onset. Thus, susceptible adolescents should be screened for prediabetes, using fasting plasma glucose, and glycated hemoglobin (HbA1c), and oral glucose tolerance testing. Prediabetic adolescents should be counseled for a healthy lifestyle including healthy dietary habits, increased physical activity, and/or stress management. Other pathological conditions should be adequately treated. Early recognition of prediabetes in adolescence will prevent type 2 diabetes onset, decreasing the diabetes-associated health burden in adult life. This review aims to revise the associations and elucidate on the gaps between prediabetes and adolescence, via a comprehensive review of the current medical literature.
Keywords: Prediabetes, adolescence, obesity, youth, childhood, puberty
Disclosure: Charikleia Stefanaki, Flora Bacopoulou, and Melpomeni Peppa have nothing to declare in relation to this article. No funding was received in the publication of this article.
Compliance with Ethics Guidelines: This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors.
Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.
Received: November 01, 2016 Accepted December 10, 2016
Correspondence: Charikleia Stefanaki, First Department of Pediatrics, Choremeio Research Laboratory, School of Medicine, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, 3 Thivon Street, Athens 11527, Greece. E: cstefanaki@gmail.com
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit.

ACCEPTED MANUSCRIPT -- This manuscript has been accepted for publication. The manuscript may undergo some minor revisions before it is published in its final form.

Diabetes is a worldwide health problem, and its prevalence is expected to rise in the coming years, not only in adults, but also in youth. The first stage is characterized by insulin resistance accompanied by a compensatory increase in insulin secretion; this stage can last several years, and it is called prediabetes. Patients with both impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) have insulin resistance, but the site of their predominant insulin resistance differs.1,2 Prediabetes is defined by the American Diabetes Association (ADA) as a fasting glucose concentration of 100–124 mg/dl, or a HbA1c value of between 5.7% and 6.4%, or a two-hour post-glucose tolerance concentration of 140–199 mg/dl. Therefore, prediabetes includes subjects with elevated fasting plasma glucose concentrations—IFG, and normal response to a glucose load, normal glucose tolerance, subjects with abnormal postprandial glucose excursion—IGT, but normal fasting glucose concentration, or a combination of the aforementioned.3 Those with IFG have predominantly hepatic insulin resistance, whereas those with IGT have predominantly muscle insulin resistance. The increased prevalence of obesity and diabetes mellitus dictates increased awareness and early identification of diabetes.

In Saudi Arabia, the prevalence of prediabetes was equal to 5.4%, based on oral glucose tolerance test (OGTT), and 21.9% based on HbA1c.4 According to epidemiological data from the UK, the prevalence rate of prediabetes in the general population increased from 11.6% to 35.3% from 2003 to 2011.5 An increase in prediabetes prevalence has also been observed in China, where prediabetes has risen to 15.5% in the general population.6 In a national cohort study of a representative sample of adolescents, it was estimated that the national population-based prevalence rates of IFG, IGT, and prediabetes among US adolescents aged 12–19 years were 13.1%, 3.4%, and 16.1%, respectively.7 In a recent report from the US, the prevalence of prediabetes increased from 9% to 23%.8 Worldwide, epidemiological trends demonstrate increases in the prevalence of prediabetes in the general population; adolescents seem to follow these trends, irrespectively of race. One of the most important and difficult stages in life is the transition from childhood to adulthood. This stage in life is called adolescence. It is characterized by various physical, emotional, social, and sexual developments. It is well established that the first two kinds of changes are due to developmental hormonal changes occurring during adolescence. These hormonal changes have been shown to be responsible for various effects on glucose metabolism.9,10

One of the most important and difficult stages in life is the transition from childhood to adulthood. This stage in life is called adolescence. It is characterized by various physical, emotional, social, and sexual developments. It is well established that the first two kinds of changes are due to developmental hormonal changes occurring during adolescence. These hormonal changes have been shown to be responsible for various effects on glucose metabolism.9,10

Because of a disturbing increase in obesity in adolescence over the past two decades, prediabetes and metabolic syndrome in adolescents have become major public health problems.11 However, screening and prevention of prediabetes in adolescence is often overlooked, leading to an increased rate of young adults with type 2 diabetes mellitus and metabolic syndrome. Much debate has taken place concerning the cut-off values of the revised impaired fasting glucose concentration levels.12 There is still no clear consensus on the definition of prediabetes, or metabolic syndrome in adolescents. We use the criteria of prediabetes in adults. However, there are only a few observational studies about prediabetes in adolescence.

In this review, we intend to unravel the associations between the endocrine physiology of adolescence and prediabetes, summarizing all the findings, and aspiring to contribute to the awareness of prediabetes during adolescence. We performed systematic research using PubMed, EBSCO, Google Scholar databases and ResearchGate site, in relation to adolescence and prediabetes.

Glucose and insulin metabolism in adolescence
Adolescence is characterized by the domination of luteinizing hormone (LH) concentrations over those of the follicle-stimulating hormone (FSH) under the stimulating effect of the hypothalamic gonadotropin-releasing hormone (GnRH). These changes lead to the secretion of sex steroids, namely estradiol in females and testosterone in males; development of secondary sexual characteristics; growth acceleration; lean and fat mass accumulation; and observed growth spurt. During this phase, a well-described physiological decrease in insulin sensitivity occurs, which resolves after completion of puberty, possibly independently of changes in body mass index (BMI).

Onset of adolescence, Tanner staging, and glucose metabolism
GnRH resides under the control of kisspeptin, its permissive neurokinin B, and its opposing dynorphin signals.13 GnRH does not seem to be implicated in glucose homeostasis derangement. On the contrary, the hypothalamic system of kisspeptins is implicated in the secretion of insulin, as they are highly abundant in the pancreas.14 Moreover, kisspeptins seem to have a protective role in gestational diabetes onset.15 On the other hand, it has been shown that ablation of dynorphin causes increase of fatty acid oxidation in male mice, reduction in adiposity, and increased weight loss during fasting, probably due to decreases in intestinal nutrient absorption.16 There has been no study performed about neurokinin B in relation with insulin resistance, or glucose intolerance, and dynorphin does not seem to essentially affect glucose homeostasis.17 Dynorphin seems to be implicated in the pathogenesis of obesity,18 and thus it affects only indirectly the pathogenesis of prediabetes in susceptible subjects.

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Keywords: Prediabetes, adolescence, obesity, youth, childhood, puberty