Parental diabetes, pubertal stage, and extreme obesity are the main risk factors for prediabetes in children and adolescents: a simple risk score to identify children at risk for prediabetes

Objectives:  The current worldwide increase of prediabetes defined as impaired fasting glucose or impaired glucose tolerance and type 2 diabetes mellitus (T2DM) coincides the increase of obesity. However, it is unclear that which children have an increased risk and should be screened for prediabetes.
Methods:  We studied 437 overweight children and adolescents to identify risk factors for prediabetes. A risk score for prediabetes was calculated using logistic regression. This score was examined in a second, independent cohort of 567 overweight children and adolescents. History of T2DM in parents and grandparents, degree of overweight, age, pubertal stage, birth weight, hypertension, dyslipidemia, acanthosis nigricans, and abdominal obesity were considered as potential risk factors.
Results:  The frequency of prediabetes was 6% in sample 1 and 17% in sample 2. The strongest association was observed for history of parental diabetes with an adjusted odds ratio (aOR) of 9.5 [95% confidence interval (CI) 2.5–36.4] in sample 1 and 6.3 (95% CI 3.7–10.7) in sample 2, followed by pubertal stage with an aOR of 5.5 (95% CI 0.7–45.4) in sample 1 and 6.2 (95% CI 2.4–15.6) in sample 2, and by extreme obesity with an aOR of 5.0 (95% CI 1.7–15.3) in sample 1 and 3.3 (95% CI 2.0–5.4) in sample 2.
Conclusions:  The main risk factors for prediabetes were parental diabetes, pubertal stage, and extreme obesity. Screening for prediabetes seems meaningful in subjects with either a parental history of diabetes or a combination of extreme obesity and pubertal stage and detected nearly 90% of the overweight children and adolescents with prediabetes.     

Obesity and associated cardiovascular risk factors in Iranian children: A cross-sectional study

BACKGROUND: Obesity is a growing public health problem in developing countries considering its association with cardiovascular risk factors. Relationship between childhood obesity and these risk factors has not been attested in the Iranian population before. The aim of the present study was to investigate frequency of cardiovascular risk factors and their association with severity of obesity in a sample of Iranian obese children. METHODS: A total of 13 086 children aged 7-12 years were screened and those with waist circumference = 90th percentile of their age were invited for further evaluations. Participants were divided into two groups of overweight or obese according to International Obesity Task Force criteria. Cardiovascular risk factors were defined as high fasting total cholesterol, high low density lipoprotein, low high density lipoprotein, high triglycerides, and systolic or diastolic hypertension. These factors were compared between obese and overweight children and their correlations with body mass index and other measures of obesity were tested. RESULTS: Of 532 children (274 boys, mean age 9.5 +/- 1.3) enrolled in the study, 194 were overweight and 338 were obese. Mean levels of triglyceride and Apo-lipoprotein B in obese children were significantly higher than overweight participants. A total of 81.9% of obese children and 75.4% of overweight children had at least one cardiovascular risk factor. There were significant correlations between body mass index and systolic blood pressure, diastolic blood pressure, serum triglyceride, and Apo-lipoprotein B levels (P values <0.01). CONCLUSION: The high prevalence of cardiovascular risk factors in overweight and obese children and positive correlation of these factors with severity of obesity emphasizes the need for prevention and control of childhood obesity from early stages.     

Impaired glucose tolerance and risk factors for progression to type 2 diabetes in youth

Abstract:  Impaired glucose tolerance and impaired fasting glucose represent two potentially reversible prediabetes conditions. Previous reports from various regions across the globe indicate that both conditions may be relatively common in obese children and adolescents. The major factor driving the development of compromised glucose metabolism in obese youth is severe insulin resistance. This severe insulin resistance has been strongly associated with specific patterns of lipid partitioning. Severe obesity along with continued weight gain, specifically in obese youth belonging to ethnic minorities, have been shown to be associated with deterioration of glucose tolerance over short periods of time. As obesity-related insulin resistance in the pediatric age-group is associated with the development of altered glucose metabolism and other elements of the metabolic syndrome, severely obese youth are a high-risk group for the development of type 2 diabetes and may benefit most from preventive interventions such as environmental changes that promote increased physical activity.     

Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes

Despite the increased prevalence of type 2 diabetes mellitus (T2DM) in the pediatric population, there is limited information about the relative effectiveness of treatment approaches. This article describes the rationale and design of a National Institutes of Health-sponsored multi-site, randomized, parallel group clinical trial designed to test the hypothesis that aggressive reduction in insulin resistance early in the course of T2DM is beneficial for prolongation of glycemic control, as well as improvement in associated abnormalities and risk factors. Specifically, the trial compares treatment with metformin with two alternate approaches, one pharmacologic (combining metformin treatment with rosiglitazone) and one combining metformin with an intensive lifestyle intervention program. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study recruits 800 patients over a 4-yr period and follows them for a minimum of 2 yr and maximum of 6 yr. Patients are 10-17 yr of age, within 2 yr of diagnosis of diabetes at the time of randomization, lack evidence of autoimmunity, and have sustained C-peptide secretion. The primary outcome is time to loss of glycemic control, defined as a hemoglobin A1c >8% for 6 consecutive months. Secondary outcomes include the effect of the alternative treatments on insulin secretion and resistance, body composition, nutrition, physical activity and fitness, cardiovascular risk monitoring, microvascular complications, quality of life, depression, eating pathology, and resource utilization. TODAY is the first large-scale, systematic study of treatment effectiveness for T2DM in youth. When successfully completed, this study will provide critical new information regarding the natural history of T2DM in youth, the benefits of initiating early aggressive treatment in these patients, and the efficacy of delivering an intensive and sustained lifestyle intervention to children with T2DM.     

Cardiovascular risk factors in Australian indigenous and non-indigenous children: A population-based study

Aim:   Indigenous people have a two- to tenfold increased risk of premature death from cardiovascular disease. We aimed to determine whether some key risk factors for cardiovascular disease occur more commonly in Aboriginal than non-Aboriginal Australian children.
Methods:   Children were enrolled from primary schools throughout New South Wales, the state with the highest number of Aboriginal people. Associations between ethnicity, gender, birthweight, socio-demographic status and hypertension, obesity, baseline and persistent albuminuria were determined.
Results:   A total of 2266 children (55% Aboriginal) were enrolled. Mean age was 8.9 years (±3.8 years). Obesity (body mass index ≥2 standard deviations) was detected in 7.1%, systolic hypertension (blood pressure >90th percentile) in 7.2%, diastolic hypertension in 5.9%, baseline albuminuria (albumin : creatinine ≥3.4 mg/mmol) in 7.3% and persistent albuminuria in 1.5% with no differences between Aboriginal and non-Aboriginal children. Hypertension was less common with increasing social disadvantage (trend P  < 0.02). Increasing body mass index standard deviation was strongly associated with systolic and diastolic hypertension (both P  < 0.0001).
Conclusions:   Many risk factors for cardiovascular disease are already common in young children but not more prevalent in Aboriginal than in non-Aboriginal children. In all children, overweight and obesity have the strongest association with hypertension, but social disadvantage appears protective for hypertension. Our findings suggest that risk for cardiovascular health disparities seen in indigenous adults manifests beyond childhood and that a window of opportunity exists to prevent some of these outcomes.     

Rapid progression of type 2 diabetes and related complications in children and young people—A literature review

Type 2 diabetes (T2D) is suggested to progress faster in children and young people vs type 1 diabetes (T1D) in the same age group and T2D in adults. We reviewed the evidence base for this. A literature search was performed of PubMed‐indexed publications between 2000 and 2018, for the terms “pediatric” and “T2D.” Results were combined and filtered for those relating to “progression.” Searches of abstract books from Latin American and Asian congresses were performed to include these populations. Pediatric populations were defined as <25 completed years of age. Of the articles and congress abstracts found, 30 were deemed relevant. Dividing the studies into categories based on how T2D progresses, we found the following: (a) yearly beta‐cell function deterioration was shown to be 20% to 35% in children with T2D compared with 7% to 11% in adults with T2D, despite similar disease durations; (b) retinopathy progression was likely dependent on diabetes duration rather than diabetes type; however, nephropathy, neuropathy and probably hypertension progressed faster in youth‐onset T2D vs T1D. Nephropathy progression was similar to adults with T2D, allowing for disease duration. Youth with T2D had a worse cardiovascular (CV) risk profile than youth with T1D, and a faster progression to CV death. (c) Progression to treatment failure was faster in youth‐onset T2D vs adult‐onset T2D. Substantial evidence exists for faster progression of T2D in pediatric patients vs T1D or adult‐onset T2D. New treatments targeting the pathology are needed urgently to address this issue.     

Skeletal muscle lipid accumulation in obesity, insulin resistance, and type 2 diabetes

In addition to obesity, many factors, including the distribution of body fat, contribute to the development of insulin resistance and type 2 diabetes mellitus (T2DM). Lipid contained within skeletal muscle as triglyceride is a parameter of regional fat accumulation thought to be an important link among obesity, insulin resistance, and type 2 diabetes, even in the pediatric population. Intramuscular triglycerides can also be a fuel source for healthy muscle during periods of physical activity. Thus, the balance between storage and efficient utilization of muscle triglycerides is likely a key to a better understanding of the interaction between dysregulated fat and glucose metabolism by muscle in both adults and children. This review examines the evidence that muscle lipid accumulation is linked with insulin resistance and type 2 diabetes of both adults and children. In addition, we explore the potential mechanisms for muscle lipid accumulation as well as the effects of weight loss and physical activity on muscle lipid. Further defining the links between muscle lipid accumulation and insulin action should help develop more effective strategies to prevent or treat type 2 diabetes and other obesity-associated disorders.     

Double or hybrid diabetes associated with an increase in type 1 and type 2 diabetes in children and youths

Abstract:  The increase in the incidence of type 1 diabetes (T1D), especially in children <5 yr of age, reported over the past decade can be attributed to changes in environmental factors (either quantitative or qualitative) rather than to an effect of genetic factors operating in such a short period of time. The notable increase in the incidence of type 2 diabetes (T2D) in children and adolescents is very likely the consequence of an increasing sedentary lifestyle and an increase in obesity, which has been occurring in developed countries. An increase in the number of children and adolescents with a mixture of the two types of diabetes has recently come to light (i.e., subjects who are obese and/or with signs of insulin resistance as well as positive for markers of autoimmunity to β cells), although the epidemiological data supporting such a conclusion are sparse. Under the current classification, it is difficult to define the type of diabetes affecting these young subjects, who might be classified as T2D because they are obese and insulin resistant but also as T1D because of the presence of autoantibodies to β cells. These subjects show an overlapping diabetes phenotype typical of both T1D and T2D, suggesting that the current classification of diabetes should be revised to take into account this new form of diabetes, which has been called 'double diabetes' or 'hybrid diabetes'. In this review, we report recent findings on the increasing rates of all forms of diabetes in the young population, including unpublished data collected in Russia.     

Feasibility and compliance in a nutritional primary prevention trial in infants at increased risk for type 1 diabetes

Aim: The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) was launched to determine whether weaning to a highly hydrolysed formula in infancy reduces the incidence of type 1 diabetes in children at increased genetic disease susceptibility. We describe here the findings on feasibility and compliance from the pilot study. Methods: The protocol was tested in 240 children. The diet of the participating children was assessed by self‐administered dietary forms, a structured questionnaire and a food record. Blood samples were taken and weight and height measured at birth and at 3, 6, 9, 12, 18 and 24 months. Results: A majority of the subjects (84%) were exposed to the study formula at least for 2 months. Linear growth or weight gain over the first 2 years of life was similar in the two study groups. The levels of IgA and IgG antibodies to cow’s milk and casein were higher in the cow’s milk–based formula group than in the hydrolysed formula group during the intervention period (p < 0.05), reflecting the difference in the intake of cow’s milk protein. Conclusion: This randomized trial on infant feeding turned out to be feasible, and dietary compliance was acceptable. Valuable experience was gained for the planning and sample size estimation of the study proper.     

Insulin resistance in children and adolescents with type 1 diabetes mellitus: relation to obesity

BACKGROUND: Insulin resistance is well recognized both in type 1 diabetes mellitus (T1DM) and in obesity. Studies concerning the relation between insulin resistance and overweight in T1DM have not yet been carried out. METHODS: Degree of overweight [standard deviation score-body mass index (SDS-BMI)] and daily insulin doses per weight (ID/kg), per body surface (ID/m2), and per ideal body weight (ID/IW) were recorded in 4124 children aged between 5 and 20 yr with a duration of T1DM of 4-5 yr and an adequate metabolic control [hemoglobin A1c (HbA1c) <8.0%]. SDS-BMI was compared between insulin-resistant (ID/kg > or = 1.0) and insulin-sensitive (ID/kg <1.0) children. The ID/kg, ID/m2, and ID/IW were compared between obese (SDS-BMI >1.9) and non-obese children. Multivariate linear regression analysis was conducted for the dependent variables ID/kg, ID/m2, and ID/IW, including age, gender, SDS-BMI, and HbA1c as independent variables. RESULTS: The 882 insulin-resistant children did not differ significantly (p = 0.447) with respect to SDS-BMI (median +0.38) compared to the 3242 insulin-sensitive children (median SDS-BMI +0.42). The ID/kg was significantly (p = 0.031) lower in the obese children compared to the non-obese children (median 0.80 vs. 0.83), while ID/m2 (median 31.0 vs. 26.2) and ID/IW (median 1.17 vs. 0.85) were significantly (p < 0.001) increased in the obese children. In multivariate linear regression analysis, SDS-BMI was significantly (p < 0.001) associated with an increase in ID/m2 and ID/IW and a decrease in ID/kg. CONCLUSIONS: T1DM children with insulin resistance based on ID/kg are not more overweight than insulin-sensitive children with T1DM. ID/m2 and ID/IW seem to reflect a better tool than ID/kg to describe the influence of overweight on insulin resistance in T1DM.     

儿童2型糖尿病和糖调节异常筛查方案的研究

目的评价及比较在不同特征人群中进行2型糖尿病（T2DM）和糖调节异常（IGR）筛查的效果及成本，优化和推荐儿童青少年T2DM筛查方案。方法采用分层整群随机抽样方法获取19 593例北京市中小学生，用空腹指末梢血糖（FCBG）对其进行T2DM和IGR筛查，FCBG异常者（≥5.6 mmol·L-1）采用1999年WHO口服葡萄糖耐量试验标准进行诊断。并参照美国糖尿病协会建议儿童青少年T2DM筛查的高危对象标准和Dean提出的诊断标准进行T2DM的分型诊断。将研究人群分为一般人群、超重/肥胖和肥胖组，分别计算回访率、血糖异常阳性率、直接医疗成本和确诊每例成本，根据成本 效果推荐儿童青少年T2DM筛查方案。结果一般人群组，FCBG异常者回访率为47.97%(225/469)，超重/肥胖和肥胖组FCBG异常者回访率分别为59.29%（83/140）和68.00%（51/75），差异有统计学意义。一般人群组T2DM/IGR确诊率最低，为1.67/1 000例；总花费11.21万元和确诊每例T2DM/IGR的花费0.35万元，最高。肥胖组T2DM/IGR确诊率最高，为8.09/1 000例；总花费1.62万元和确诊每例T2DM/IGR的花费0.11万元，最低，较一般人群组分别下降85.55%和68.57%。超重/肥胖组介于两者之间。肥胖、超重/肥胖与一般人群组相比，肥胖组有2例T2DM（33.33%，2/6）漏诊，超重/肥胖组没有T2DM 漏诊。建议在超重/肥胖组中进行T2DM和IGR筛查。进一步选择除超重/肥胖外，与T2DM相关的危险因素（黑棘皮病、T2DM家族史和青春期），随调查对象具有危险因素数量的增加，患病危险性增加，筛查依从性增高，T2DM/IGR确诊率升高，筛查总成本和每例成本降低，但是从调查对象具有3个或以上危险因素开始，对T2DM/IGR筛查敏感度下降，与在一般人群组筛查相比，在4个危险因素人群中进行筛查，将有83.33%的T2DM得不到确诊。结论 本大样本研究以成本 效果分析说明：在儿童中符合健康经济学的T2DM筛查方案是在达到超重标准，同时具有1个以上危险因素（黑棘皮病、T2DM家族史和青春期）儿童青少年中进行目的性筛查。