SEARCH

SEARCH BY CITATION

Keywords:

  • adolescent;
  • child;
  • obesity;
  • type 2 diabetes

Abstract

  1. Top of page
  2. Abstract
  3. Prevalence and incidence
  4. Epidemiology of obesity and other risk factors for type 2 diabetes
  5. Conclusions
  6. Conflict of interest
  7. References

Abstract:  Over the last decade, it has become apparent that type 2 diabetes extends not only into the young adult population but is also found in adolescents and even, occasionally, in children. The limited data that are currently available present a rather uncertain picture, with a rather wide range of prevalences and incidences of type 2 diabetes in children and adolescents. Not surprisingly, the majority of the cases, and the highest prevalences, have been found among ethnic groups known to be at high risk of adult type 2 diabetes. Nevertheless, even in European populations, where the prevalence of type 2 diabetes remains very low among children and adolescents and certainly is considerably smaller than type 1 diabetes, there are several cases reported. The risk factors for type 2 diabetes in children and adolescents are, as expected, similar to those seen in adults, with obesity being almost always present. In utero exposure to hyperglycemia now appears to be an additional risk factor to having a family history of diabetes and suggests that better management of diabetes in pregnancy and prevention of gestational diabetes may reduce the risk of diabetes developing in the offspring.

Type 2 diabetes has traditionally been viewed as a disorder of adults, most commonly seen in those who are middle-aged and elderly. Indeed, onset of diabetes after the age of 30 or 40 yr has frequently been used as both a clinical and a research tool to distinguish type 2 diabetes from type 1 diabetes. However, as the prevalence of type 2 diabetes has risen in recent decades, type 2 diabetes has appeared in younger adults and is now occurring in adolescents and youth. The information on the patterns and epidemiology of type 2 diabetes in youth is currently patchy, primarily because of the relative rarity of the disorder, the infrequency of formal registries to capture information on all cases, and the small number of appropriate, population-based studies available. Nevertheless, it is now clear that type 2 diabetes is an emerging problem among the youth of many societies around the world, particularly among those ethnic groups known to have high prevalences of type 2 diabetes in adults, although it has also been reported in low-prevalence European populations. The following discussion will present data on the patterns and epidemiology of type 2 diabetes in youth from studies around the world, drawing not only on the small number of population-based studies in which formal screening for undiagnosed cases has been included, but also on the rather larger number of clinic- and registry-based studies.

Prevalence and incidence

  1. Top of page
  2. Abstract
  3. Prevalence and incidence
  4. Epidemiology of obesity and other risk factors for type 2 diabetes
  5. Conclusions
  6. Conflict of interest
  7. References

In reviewing the data from observational studies, it should be noted that such studies are dependent on the accurate classification of diabetes type, but this is often far from simple. For example, diabetic ketoacidosis may occur at initial presentation in people who are eventually found to have type 2 diabetes (i.e., they have elevated C-peptide, an absence of islet cell or anti-GAD (glutamate decarboxylase) antibodies and can survive with adequate glycemic control without insulin therapy) (1), while the presence of obesity in a child developing autoimmune type 1 diabetes may lead to an erroneous diagnosis of type 2 diabetes (2).

Population-based studies

Population-based studies, in which all individuals within a geographical target area undergo blood glucose testing, represent the ideal method of determining the prevalence of diabetes, as they capture all the asymptomatic and undiagnosed cases, which may represent over 50% of the total number of cases within a given population. However, there are very few such studies available of type 2 diabetes in children and adolescents. Even in those that have been conducted, the use of the oral glucose tolerance test (OGTT) is uncommon, and the studies often lack the key data required to precisely differentiate type 2 diabetes from type 1 diabetes.

In the USA, the National Health and Nutrition Examination Survey (NHANES) III provided prevalence data (based on self-report and fasting glucose) on a national sample of 2867 adolescents aged 12–19 yr, collected between 1988 and 1994 (3). Thirteen adolescents were found to have diabetes, of whom four were considered to have type 2 diabetes, and all four were either non-Hispanic black or Mexican-American. Although the prevalence of type 2 diabetes is not given in the published reports, it can be calculated to be 0.13%. Unfortunately, differentiation between the types of diabetes was based only on the use of insulin, and so it is uncertain to what extent misclassification occurred. The NHANES data from 1999 to 2002 provide a much more recent update for the US population (4). The prevalence of diagnosed diabetes (types 1 and 2) was 0.5%, with 8 of 18 of these diabetes cases being classified as having type 2 diabetes (on the basis of not using insulin), and a further two cases, being on both insulin and tablets, and hence as probably having type 2 diabetes. Data from a single US school district (5) showed a diabetes prevalence of 0.4%, while a study surveying Mexican-American fourth graders found an overall type 2 diabetes prevalence of 0.3% (6), with both these studies using the OGTT for diagnosis. A study of eighth graders from four schools in the southern US, selected because of the high proportion of children from high-risk ethnic groups (56% Hispanic, mean age 13.6 yr), reported that 6.2% had impaired fasting glucose (IFG) (fasting plasma glucose (FPG) ≥ 6.1 mmol/L), 2.3% had impaired glucose tolerance (IGT), and 0.4% had undiagnosed diabetes (FPG ≥ 7.0 mmol/L) (7). Accurate surveillance of the Pima Indian population with regular OGTTs over the last 40 yr has shown rising rates of glucose intolerance (8). From 1967–1976 to 1987–1996, the prevalence of type 2 diabetes in youth increased from 2.4% in males and 2.7% in females to 3.8% in males and 5.3% in females, the highest rates reported in children to date. A study of American-Indian (AI) and Alaskan Native adolescents, using clinical data from across the Indian Health Service, reported that the prevalence of type 2 diabetes increased by 68% from 1990 to 1998 among those aged 15–19 yr (0.32 to 0.54%) (9).

SEARCH for Diabetes in Youth is a six-site study of population-based, physician-diagnosed diabetes in youth aged <20 yr in the USA and used clinical records, C-peptide levels, and autoantibodies to classify the type of diabetes. Among the 1349 cases of diabetes in children aged 0–9 yr, only 11 were classified as having type 2 diabetes (0.01 per 1000) (10). Among youth aged 10–19 yr, the highest prevalence of type 2 diabetes was observed among AI youth (1.74 per 1000), followed by African-American (AA) youth (1.05 per 1000), Asian/Pacific Islanders (APIs) youth (0.54 per 1000), Hispanic youth (0.48 per 1000), and non-Hispanic white youth (NHW) (0.19 per 1000). In this older age group, type 2 diabetes accounted for 76% of diabetes diagnosed among AI youth, but only 6% in the NHW youth (Fig. 1). More recent data from SEARCH provide information on the annual incidence of type 2 diabetes, which is reported as being very low (0.8 per 100 000) in the 0–9 yr age group, rising to 8.1 per 100 000 and 11.8 per 100 000 in 10–14 yr olds and 15–19 yr olds, respectively (11). Among the 15–19 yr olds, the incidence ranged from 5.6 per 100 000 in NHWs to 17.0–22.7 per 100 000 in Hispanics, AAs, and APIs, and 49.4 per 100 000 in AI youth. Among those aged 0–9 yr, type 1 diabetes accounted for 87–100% of all new cases of diabetes, but in the 10–19 yr old age group, type 2 diabetes accounted for between 15% (NHW) and 86% (AI) of all new cases (Fig. 1). Interestingly, Fig. 1 indicates that the proportion of cases that are due to type 2 diabetes has risen over time in each ethnic group, as all the incident cases (with the higher proportion of type 2 diabetes) occurred in 2000–2003, while the prevalent cases developed between 1982 and 2001. Notably, classification of diabetes type was undertaken in a uniform manner for all cases, and this rise in the proportion attributable to type 2 diabetes has occurred at a time when the incidence of type 1 diabetes is known to have risen.

image

Figure 1. Percentage of all prevalent and incident cases of diabetes that were classified as type 2 diabetes, according to ethnicity: the SEARCH study (10, 11). AA, African-American; AI, American Indian; API, Asian/Pacific Islander; NHW, non-Hispanic white.

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Undoubtedly, the largest surveillance of type 2 diabetes in youth has been undertaken in Japan and Taiwan, where screening programs for renal disease, involving urine dipsticking of millions of schoolchildren, have been harnessed to screen for diabetes, by undertaking an OGTT in those with glycosuria. Significant methodological limitations apply with this design, as glycosuria is a relatively insensitive screening tool for diabetes, picking up only those with more severe hyperglycemia. In the most recent report from the Japanese study, involving almost 9 million children screened between 1974 and 2002 (12), the overall annual incidence of type 2 diabetes was 2.63 per 100 000. The annual incidence after 1981 was significantly higher than that before 1980 (1.73 per 100 000 vs. 2.76 per 100 000; p < 0.0001). However, there was no statistical change in the incidence of type 2 diabetes from 1981 to 2002. A further analysis of this study, extending to 2004 (13), has shown a fall in the incidence of type 2 diabetes in junior high school children, with the incidence declining from a high of approximately 7 per 100 000 between 1979 and 1994 to 3.7 per 1000 000 between 2000 and 2004. The authors relate this improvement to evidence of a fall in the prevalence of obesity, an improvement in diet, and increase in physical activity.

A screening program in which fasting blood glucose was measured in those with persistent glycosuria, carried out in 3 million students (aged 6–18 yr) in Taiwan (14), found the prevalence of undiagnosed diabetes to be 9.0 and 15.3 per 100 000 in boys and girls, respectively. The prevalence of undiagnosed diabetes was 62% higher in girls than boys, after adjustment for other factors, and the cases were most commonly identified between the ages of 12 and 14 yr. A 3-yr follow-up of the clinical outcomes of these cases showed that 54% had type 2 diabetes, 10% had type 1 diabetes, 9% had secondary diabetes, 20% were non-diabetic, and 8% had no definite diagnosis. The cases identified as having type 2 diabetes had a higher mean body mass index (BMI), cholesterol, and blood pressure than those with a normal fasting glucose, suggesting that even at this young age, cardiovascular risk was starting to rise in those with diabetes.

Another very large study recently reported data on over 70 000 17-yr-old Israeli military conscripts (15). Type 2 diabetes (diagnostic fasting, 2 h or random blood glucose, but not treated with insulin) was found in 0.036% of males and 0.01% of females. A study of Turkish adolescents, in which 1647 adolescents had a fasting plasma glucose, identified 1.96% with IFG, but no case of type 2 diabetes (16). Data from a Saudi Arabian study (17) showed that in the under-14-yr-old age group, type 2 diabetes was present in 0.12% and IGT in a further 0.25%. In those aged 14–29 yr, the prevalence of type 2 diabetes was 0.79%, while the prevalence of IGT was 0.21%. Considering the variations in age groups in the studies reported here, the Saudi data point to a relatively high prevalence, and as such are consistent with data in adults showing that the prevalence of diabetes in the Middle-East is probably higher than among any other populations, apart from Pacific Islanders and indigenous peoples from North America and Australasia (18). A school-based study of 2640 adolescents aged 12–19 yr in south India, using fasting blood glucose, found only one case of diabetes, giving a somewhat surprisingly low prevalence of 0.04%, despite almost one in five having a family history of diabetes (19).

Clinic-based and register studies

A large number of studies have published data collected from diabetes clinics and from diabetes registers. These have focused on providing estimates of the ratio of type 1 to type 2 diabetes, as well as descriptions of the phenotype of type 2 diabetes, and some have attempted to estimate the prevalence or incidence of type 2 diabetes, on the assumption that the cases in the clinic represent all those from within a definable population. While the strength of such studies is that the assignment of diabetes type is usually carried out by pediatricians (although not always in a uniform manner), it is often unclear how representative any particular clinic population is. Furthermore, publication bias almost certainly exists, in which clinics finding high rates of type 2 diabetes are likely to analyze and publish their data, while those with low rates of type 2 diabetes are less likely to do so. Regional and national registries should solve most of these problems. Changes in incidence rates over time also need to be interpreted cautiously. At least two factors that are unrelated to actual changes in the incidence of type 2 diabetes may contribute to apparent secular rises in the incidence of type 2 diabetes. First, assignment of diabetes type has varied over time, and while several years ago, almost all youth presenting with diabetes would be assumed to have type 1 diabetes, this is increasingly recognized to be incorrect, and the need for insulin as well as even the presence of diabetic ketoacidosis are now no longer taken to be diagnostic of type 1 diabetes. Second, there is likely to be an element of increasing awareness and surveillance that leads to better identification of undiagnosed type 2 diabetes.

Several studies in the USA have reported increases in the incidence of type 2 diabetes. Data from the medical records of 735 AA and Latino children with insulin-treated diabetes in Chicago (20), showed that type 2 diabetes (based on a clinical diagnosis of type 2 or the presence of markers of insulin resistance or a BMI at diagnosis >27 kg/m2) incidence rates rose by 9% per year from 1985 to 1994, and that the incidence was higher in AAs than Latinos (15.2 vs. 10.7 per 100 000 per year). Presentation was typically around puberty, and 62% of those with type 2 diabetes were girls. Among 1027 consecutive diabetic patients attending a diabetic clinic in Cincinnati (21), a 10-fold increase in type 2 diabetes (defined on clinical criteria, including being non-ketosis prone) incidence rates, from 0.7 per 100 000 per year in 1982 to 7.2 per 100 000 per year in 1994, were observed. Onset was again typically around puberty for type 2 diabetes, and the female : male ratio was 1.7:1. Among 569 children and adolescents presenting to a Florida clinic with diabetes between 1994 and 1998 (22), the proportion with type 2 diabetes (as indicated in medical records) rose from 9.4% of new cases to 20% of new cases over the 5-yr period. Within the group as a whole, being Hispanic, black, or female significantly increased the likelihood of having type 2 diabetes. Similarly, from 1997 to 1999, a study of persons referred to a diabetic clinic in Thailand (23) reported a rise from 5 to 17% in the proportion with type 2 diabetes (as indicated in medical records).

A detailed study from the only pediatric diabetic clinic serving an Australian population of approximately 2 million has documented a rise in the incidence of type 2 diabetes among children aged 0–17 yr (24). Between 1990 and 2002, average annual rises of the incidence of type 2 diabetes (defined by clinical findings, C-peptide level, and an absence of autoantibodies) of 23% in the indigenous population and 31% in the non-indigenous population were observed. By the end of the study period, the estimated annual incidences were approximately 16 per 100 000 in the indigenous population and 1 per 100 000 in the non-indigenous population, which compared to an incidence of just over 20 per 100 000 per year for type 1 diabetes in children nationally. Among the 43 children identified during the study period with type 2 diabetes, the peak age at diagnosis was 13–14 yr, and 65% were girls. In an analysis of 14–20-yr-olds attending an adolescent diabetes clinic in New Zealand, the prevalence of type 2 diabetes (defined as non-ketosis prone and absence of autoantibodies) within the clinic population rose from 1.8% in 1996 to 11.0% in 2002 (25). While only 12.5% of new cases of diabetes were classified as type 2 diabetes in 1997–1999, this figure rose to 35.7% for 2000–2001. Among the 18 patients with type 2 diabetes attending the clinic in 2002, all were either Maori or Pacific Islanders, and in contrast to most other studies, only 50% were female, perhaps reflecting the fact that most of the patients in this study developed diabetes after puberty (mean age of onset 15 yr), while most other studies report populations with a slightly younger diabetes onset, much closer to puberty. Indeed, Taiwanese data reveal that the female bias decreases with increasing age, and within the 16- to 18-yr-old group, the incidence of diabetes was equal in males and females (14).

While there seems to be much evidence of increasing incidence and prevalence of type 2 diabetes among youth in the USA and in other populations, it is possible that this is predominantly a feature of high-risk ethnic groups. A series of studies from Europe indicate that type 2 diabetes remains a rarity in these populations. Well-designed studies from Germany, Austria, France, and the UK (26–28) all show type 2 diabetes accounting for only 1–2% of all cases of diabetes. A survey in which 177 British pediatric diabetes centers reported information on all children (aged 0–16 yr) with diabetes found that less than 1% of all cases were due to type 2 diabetes (defined using the presence of clinical or laboratory evidence of insulin resistance), and the risks of type 2 diabetes were higher in South Asians and in girls (29). In another study from the UK and Ireland (30) between 2004 and 2005, 2665 pediatricians, along with diabetes specialist nurses, provided monthly reports on all new cases of diabetes among children under 17 yr of age. The annual incidence of type 2 diabetes [defined as raised insulin (or C-peptide) and/or the absence of autoantibodies] was estimated to be 0.53 per 100 000, ranging from 0.35 per 100 000 in whites to 1.25 per 100 000 and 3.9 per 100 000 in those of South Asian and black origins, respectively. A single center in France (27) reported that only 2% of 382 children (aged 1–16 yr) with diabetes had type 2 diabetes (diagnosed on the basis of the absence of a need for insulin therapy to ensure survival, absence of autoantibodies, and absence of a human leukocyte antigen DQ genotype associated with a high risk of type 1 diabetes mellitus). Using a national register in Austria, Rami et al. (31) showed that of all newly diagnosed cases of diabetes under the age of 15 in the 3 years from 1999 to 2001, 1.5% of cases were due to type 2 diabetes (defined as overweight at diagnosis, a family history of type 2 diabetes, evidence of insulin resistance, lack of ketonuria at onset, and absence of autoantibodies), giving an incidence of 0.25 per 100 000 per year, which is only one-tenth of the incidence reported in the US SEARCH study (11).

Several possible explanations exist for the much lower numbers of type 2 diabetes reported in these European studies, compared with many other studies. First, this may accurately reflect the differences between populations and may arise from the relatively small numbers of people from high-risk ethnic groups in these European populations. Second, there may be a greater degree of underdiagnosis of type 2 diabetes in parts of Europe than in other parts of the world, although such a difference is not an obvious feature of adult-onset type 2 diabetes. Third, it is noteworthy that most of these European studies draw data from national or regional registers or from a large, national collection of diabetes centers. By comparison, the reports from single centers may be biased to the small number that by chance or because of their particular population, have seen rapid rises in their numbers with type 2 diabetes. However, even the population-based data from the USA (4) showed a prevalence of diagnosed type 2 diabetes among 12- to 19-yr-olds that was approximately 1000-fold higher than the estimates based on the British data (32) on 0- to 16-yr-olds (0.2 vs. 0.0002%). It seems unlikely that such a huge difference exists or can be because of ethnic differences, as even the prevalence in British South Asian children was only 0.001% (32), but the full explanation for these discrepancies remains uncertain.

Epidemiology of obesity and other risk factors for type 2 diabetes

  1. Top of page
  2. Abstract
  3. Prevalence and incidence
  4. Epidemiology of obesity and other risk factors for type 2 diabetes
  5. Conclusions
  6. Conflict of interest
  7. References

The etiology of type 2 diabetes in children and adolescents has only come under scrutiny in the last few years, and consequently, the literature is not as robust as for adults. However, data so far available suggest, as would be expected, that many of the risk factors that have been identified for adult type 2 diabetes also apply to children and adolescents. Some of the more important factors are discussed below.

Obesity, diet, and activity

On a global basis, the rise in type 2 diabetes rates seems to mirror the growth in urbanization and economic development. Closely associated with this is the increase in overweight and obesity. Indeed, as has been described many times in studies of adults, there is a strong relationship, in children and adolescents, between obesity and the prevalence of type 2 diabetes.

Studies from Japan have demonstrated parallel rises in type 2 diabetes incidence in children and levels of obesity from 1975 to 1995 (33) (Fig. 2). Of note is that over this time period, there have also been significant increases in fat and animal protein intake among Japanese youth, now mirroring the kind of westernized diets consumed by Japanese-Americans (34).

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Figure 2. Incidence of type 2 diabetes, and prevalence of obesity in Japanese children, 1976–1995 (33).

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In the USA, the National Longitudinal Survey of Youth, a prospective cohort study conducted from 1986 to 1998 showed that over this time period, the overweight prevalence increased annually by 3.2% in NHWs, 5.8% in AAs, and 4.3% in Hispanics. Thus by 1998, 21.5% of AAs, 21.8% of Hispanics, and 12.3% of NHW were overweight (35).

A more recent study of nearly 5000 children in the USA has shown that during 1999–2000, 15% of 6- to 19-yr-olds were overweight, compared with 11% in 1994–1998. The biggest rises were recorded in AA and Mexican-American adolescents (36). A two- to fourfold increase in the prevalence of obesity from 1985 to 1997 has also been reported in Australian children aged 7–15 yr (37).

In India, a recent study found that the age-adjusted prevalence of being overweight among 13- to 18-yr-olds was around 18%. Prevalence rates increased with age and decreasing physical activity and with higher socioeconomic status (38). Other factors, also thought to be important among Indian Asians, are low birth weight (LBW) and insulin resistance (39). In Canada, 48–51% of indigenous children aged 4–19 yr were found to have a weight >90th percentile (40). Currently, some 85% of children with type 2 diabetes are either overweight or obese at diagnosis (41).

A recent longitudinal study showed a marked decline in physical activity in adolescent girls, with 56% of black and 31% of white girls aged 16–17 yr having no habitual leisure-time physical activity (42). Pregnancy, cigarette smoking, higher BMI, and lower parental education at baseline were all associated with a subsequent decline in physical activity. Another study highlighting racial differences in physical activity levels found that white students in the USA have generally higher physical activity levels than other ethnic groups, with boys usually more active than girls, whatever the race (43).

Overall in the USA, only 50% of young people aged 12–21 yr are regularly involved in physical activity, with some 25% admitting to no physical activity at all. Even in schools, there is a decline in physical education, with participation rates down from 41.6% in 1991 to 24.5% in 1995 (44).

A recent detailed study on 1732 9- and 15-yr-olds, related a composite metabolic score (including insulin resistance, lipids, blood pressure, obesity, and fitness) to physical activity assessed objectively by accelerometry (45). The risk of having an elevated metabolic score only began to fall when more than 60 min/d of moderate activity was accumulated, suggesting that the current targets of 30 min/d may be inadequate.

Ethnicity

Ethnicity is widely recognized as an important risk factor in the development of type 2 diabetes in adults. The data so far available would suggest that, if anything, the influence of ethnicity is even stronger for youth-onset than for adult-onset type 2 diabetes. Higher prevalences have been seen in Asians, Hispanics, indigenous people (USA, Canada, Australia), and AAs, with some of the highest rates in the world being observed among Pima Indians (14, 46).

Family history

Many studies show a strong family history among affected youth with 45–80% having at least one parent with diabetes and 74–100% having a first- or second-degree relative with type 2 diabetes (41, 47). Children with diabetes are also more likely to have a family history of cardiovascular disease (CVD), with one study showing that up to 28% have a positive family history of CVD (48).

The Bogalusa Heart Study (49) has shown that children of individuals with type 2 diabetes were more likely to be obese and have higher blood pressures, fasting insulin, glucose, and triglycerides. In a study among Pima Indians, it was shown that the cumulative incidence of type 2 diabetes was highest in offspring if both parents had diabetes (50).

Intra-uterine environment

The intra-uterine environment has been increasingly recognized as being an important contributor to disease both in childhood and in adult life. Both LBW (<2500 g) and high birth weight are associated with the development of type 2 diabetes in later life (51, 52), including among children as young as 10 yr (53), and both genetic and environmental factors are likely to be involved in mediating this relationship. The hypothesis linking LBW to diabetes has been termed the thrifty phenotype and suggests that the fetal response to intra-uterine malnutrition leads to insulin resistance and impaired beta cell development, as well as to LBW, with the metabolic abnormalities increasing the risk of diabetes later in life. Studies of monozygotic and dizygotic twins have shown that the lower-birth-weight twin has a greater risk of diabetes in adulthood, suggesting the importance of environmental and intra-uterine factors (54, 55). Birth weight may also be influenced by genetic factors, with a recent study suggesting that paternal type 2 diabetes may play a role (56). Children born to a father with type 2 diabetes weighed an average of 186 g less than children from non-diabetic parents. This was not affected by birth order, father’s height, or social class. No significant differences were seen in birth weight of offspring between diabetic and non-diabetic mothers.

A recent nationwide survey from Taiwan has shown a U-shaped curve for birth weight and risk of type 2 diabetes in childhood (Fig. 3), in which the risk was increased in those with either high birth weight (≥4000 g) [odds ratio (OR), 1.78; 95% confidence interval (CI), 1.04–3.06] or LBW (<2500 g) (OR, 2.91; 95% CI, 1.25–6.76) (57). This held true after taking into account age, sex, and family history of type 2 diabetes. The likelihood is that the two extremes of birth weight represent two separate types of risk for diabetes – the thrifty phenotype for LBW, and the genetic, and possibly, environmental risk associated with high birth weight and maternal diabetes during pregnancy.

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Figure 3. Risk of developing youth-onset type 2 diabetes according to birth weight (57).

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A study from India found that insulin resistance in children was inversely related to birth weight (58). Children with LBW were also more likely to develop hypertension and dyslipidemia later. In comparison with White Caucasian babies, Indian babies are lighter, have more subcutaneous fat (59), and higher cord insulin and leptin levels (60). The propensity to fat deposition seems to extend to Indian children born in the UK, who appear to have a greater tendency to central adiposity compared with their white Caucasian counterparts (61). A study examining 152 South African children aged 7 yr found an inverse correlation between birth weight and insulin secretion following an OGTT (62). In addition, children with LBW but high weights at 7 yr, had higher insulin concentrations and indices of obesity compared with those with LBW, who remained at a low weight by 7 yr of age. There was also a positive correlation between weight velocity and insulin resistance, as measured by the homeostasis model.

LBW followed by catch-up growth in childhood appears to carry a particularly high risk of subsequent diabetes, as shown in both animal experimental (51, 63) and human observational studies (64–66). A recent prospective, population-based survey from India found that subjects with IGT or type 2 diabetes as adults tended to have LBWs but accelerated increases in BMI from 2 to 12 yr (67).

Recent data have shown that exposure to maternal diabetes in utero is a significant risk factor for obesity, impaired glucose tolerance, and type 2 diabetes in youth, independent of any effect that is transmitted genetically. In a prospective study, Silverman et al. (68) followed a cohort of offspring of diabetic mothers and found that, although neonatal macrosomia disappears after the first year of life, by the age of 8 yr, almost half of the offspring have a weight greater than the 90th percentile. A direct correlation was found between amniotic fluid insulin concentration at 32–34 wk of pregnancy and obesity at ages 6 and 8 yr, suggesting a possible mechanism of this excessive growth (69). Investigators also measured glucose and insulin concentrations, fasting and 2 h after oral glucose yearly from the age of 1.5 yr. On their most recent evaluation (age 12.3 yr), offspring of diabetic mothers had a significantly higher prevalence of IGT than an age- and sex-matched control group (19.3 vs. 2.5%), and two offspring had developed type 2 diabetes.

There is evidence that the excess obesity and type 2 diabetes in offspring of diabetic mothers is not solely because of genetic factors. Within Pima Indian families with non-diabetic offspring, BMI was significantly higher (+2.6 kg/m2) in the 62 siblings born after their mothers were diagnosed with type 2 diabetes (exposed to the diabetic intra-uterine environment) than in the 121 siblings born before (70). Similarly, within the same Pima Indian family, siblings born after the mother’s diagnosis of diabetes had over a threefold higher risk of developing diabetes at an early age than siblings born before the diagnosis of diabetes in the mother (odds ratio 3.0; p < 0.01). As these differences were not seen in the families of diabetic fathers, it is unlikely that these findings are because of cohort or birth order effects. Among Pima Indian youth of Arizona, exposure to maternal diabetes in pregnancy and obesity accounted for most of the dramatic increase in type 2 diabetes prevalence over the last 30 yr (8). Obesity itself is a long-term consequence of such exposure in this population. The actual extent to which exposure to maternal diabetes in utero and obesity account for the development of type 2 diabetes in other populations, however, is unknown.

Conclusions

  1. Top of page
  2. Abstract
  3. Prevalence and incidence
  4. Epidemiology of obesity and other risk factors for type 2 diabetes
  5. Conclusions
  6. Conflict of interest
  7. References

The emerging evidence of the presence of type 2 diabetes in children and adolescents, while still imprecise, is entirely consistent with the increasing prevalence of type 2 diabetes in adults, the falling age of onset of type 2 diabetes in adults, and the rapidly increasing prevalence of obesity in both adults and children. In addition to accurately describing the prevalence of type 2 diabetes in children and adolescents, several challenges lie ahead. These include improving the ability to distinguish type 2 from type 1 diabetes in adolescents and identifying interventions that will succeed in making the necessary lifestyle changes in obese adolescents with type 2 diabetes.

References

  1. Top of page
  2. Abstract
  3. Prevalence and incidence
  4. Epidemiology of obesity and other risk factors for type 2 diabetes
  5. Conclusions
  6. Conflict of interest
  7. References
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