Type 1 Diabetes Mellitus Children Research Articles

Are frequency and severity of sleep-disordered breathing in obese children and youth with and without type 2 diabetes mellitus different?

Obstructive sleep apnea (OSA) is a risk factor for insulin resistance and type 2 diabetes mellitus (T2DM) in adults. Data in children are limited. The aim was to study the frequency and severity of OSA and its association with cardiometabolic risk factors in obese children and adolescents with and without T2DM. In this prospective cross-sectional study, obese children and adolescents with and without T2DM underwent polysomnography and blood tests for fasting lipids, insulin, glucose, liver functions, and C-reactive protein. All participants completed a questionnaire on past and present sleep-disordered breathing (SDB). Results were compared between T2DM and obese non-diabetic controls matched for body mass index-standard deviation score (BMI-SDS) and also according to the glycemic status: T2DM, impaired glucose tolerance (IGT), and normal glycemic control. Eleven patients with T2DM (age 15.9±3.6years) and 30 BMI-SDS matched non-diabetic subjects (age 12.7±3.0years) were studied. Among the entire cohort, 45% had a history of snoring, 26% reported apneic episodes during sleep, and 65% had daytime fatigue. There were no significant between-group differences in SDB history or abnormal polysomnographic results [apnea-hypopnea index (AHI) >5/h]. The percentage of subjects with AHI >5/h was 45.5% in T2DM patients, 25% in obese patients with IGT, and 18.2% in obese patients without IGT, although the difference was not statistically significant (p=0.25). Plasma C-reactive protein levels were related to both glycemic status and OSA severity. The severity of OSA in obese children and adolescents is unrelated to the presence of diabetes. OSA may play a minor role in the development and progression of T2DM in children and adolescents. Further studies in larger cohorts are required.

Epidemiology of Childhood Type 1 Diabetes Mellitus in Nile Delta, Northern Egypt - A Retrospective Study

Ob­jec­ti­ve: The geographical incidence of type 1 diabetes mellitus (T1DM) varies widely worldwide. Both genetic and environmental factors have been implicated, although environmental factors are still speculative and elusive. More epidemiological studies are needed to uncover such factors. To date, there are no reported studies on the epidemiology of childhood T1DM in Nile Delta, Egypt. We aimed to define the incidence, prevalence and demographic characteristics of T1DM in children (0-18 years) living in the Nile Delta region, one of the most densely populated areas in Egypt.Methods: The study included all T1DM patients aged 0-18 years who lived in the Nile Delta region of Egypt and who were either diagnosed at or referred to Mansoura University Children’s Hospital (MUCH) between 1 January 1994 and 31 December 2011. The hospital files of the patients were reviewed. General population data on the 0-18 year age group in the Nile Delta governorates were also presented.Results: From a total of 1600 T1DM patients, 891 (55.7%) were females (p=0.000) and 935 (58.4%) were from rural areas (p=0.000). Calculated age-adjusted incidence of T1DM in 1996, 2006 and 2011 were 0.7, 2.0 and 3.1/105/year, respectively, while calculated age-adjusted prevalence of T1DM in the same years were 1.9, 15.5 and 26.8/105/year, respectively. Patients presented most frequently in the 5-10 year age group (p<0.000) and in winter months (p=0.009).Conclusion: In this first childhood T1DM epidemiology study in the Nile Delta region of Egypt, T1DM incidence and prevalence were found to show an increase over the past 18 years (1994-2011). Incidence and prevalence were higher in females and more cases were found to originate from rural areas.

Insulin Therapy in Children and Adolescents with Type 1 Diabetes

Treatment of type 1 diabetes mellitus (T1DM) requires lifelong administration of exogenous insulin. The primary goal of treatment of T1DM in children and adolescents is to maintain near-normoglycemia through intensive insulin therapy, avoid acute complications, and prevent long-term microvascular and macrovascular complications, while facilitating as close to a normal life as possible. Effective insulin therapy must, therefore, be provided on the basis of the needs, preferences, and resources of the individual and the family for optimal management of T1DM. To achieve target glycemic control, the best therapeutic option for patients with T1DM is basal-bolus therapy either with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). Many formulations of insulin are available to help simulate endogenous insulin secretion as closely as possible in an effort to eliminate the symptoms and complications of hyperglycemia, while minimizing the risk of hypoglycemia secondary to therapy. When using MDI, basal insulin requirements are given as an injection of long- or intermediate-acting insulin analogs, while meal-related glucose excursions are controlled with bolus injections of rapid-acting insulin analogs. Alternatively, CSII can be used, which provides a 24-h preselected but adjustable basal rate of rapid-acting insulin, along with patient-activated mealtime bolus doses, eliminating the need for periodic injections. Both MDI treatment and CSII therapy must be supported by comprehensive education that is appropriate for the individual needs of the patient and family before and after initiation. Current therapies still do not match the endogenous insulin profile of pancreatic β-cells, and all still pose risks of suboptimal control, hypoglycemia, and ketosis in children and adolescents. The safety and success of a prescribed insulin regimen is, therefore, dependent on self-monitoring of blood glucose and/or a continuous glucose monitoring system to avoid critical hypoglycemia and glucose variability. Regardless of the mode of insulin therapy, doses should be adapted on the basis of the daily pattern of blood glucose, through regular review and reassessment, and patient factors such as exercise and pubertal status. New therapy options such as sensor-augmented insulin pump therapy, which integrates CSII with a continuous glucose sensor, along with emerging therapies such as the artificial pancreas, will likely continue to improve safe insulin therapy in the near future.

Trace elements, magnesium, and the efficacy of antioxidant systems in children with type 1 diabetes mellitus and in their siblings.

Magnesium (Mg), selinium (Se), zinc (Zn), manganese (Mn), and copper (Cu) are involved in the mechanisms of antioxidant defense. Mn and Cu, which participate in the generation of reactive oxygen species (ROS), also have pro-oxidative properties. To evaluate the levels of Mg, Se, Zn, Mn, and Cu, as well as the effectiveness of antioxidant defense mechanisms in children with Type 1Diabetes Mellitus (T1DM) and in their siblings. The preliminary findings were originally reported in 2009 at the 35th annual conference of the International Society for Pediatric and Adolescent Diabetes (ISPAD) in Ljubljana, Slovenia. The study involved 87 children with T1DM, 2-19 years old, treated for T1DM for an average of 3.5 years. The sibling and control groups comprised 27 and 41 children, aged 4.5-16.5 years and 10.5-18 years respectively. The parameters named above were assessed in relation to metabolic compensation levels (HbA1C) and disease duration. Compared with the control group, T1DM children had lower plasma levels of Mg and Zn and higher levels of Cu; the siblings had lower levels of Zn; T1DM children had lower copper/zinc superoxide dismutase (CuZnSOD) activity; and both T1DM children and their siblings had higher catalase (CAT) activity and lower total antioxidant status (TAS) levels. There may be a correlation between impaired antioxidant status and Mg and Zn deficiency and increased Cu levels in T1DM children. Oxidative stress in T1DM is accompanied by alterations in enzymatic activity and non-enzymatic mechanisms of antioxidant defense. The decreased TAS levels noted in T1DM patients may impair the effectiveness of non-enzymatic antioxidant systems. The increased CAT activity and unimpaired selenium-dependent glutathione peroxidase (Se-GSHPx) activity point indirectly to enhanced ROS generation in T1DM children. The impaired antioxidant defense found in the siblings of T1DM patients may indicate that genetic factors play a role.

Glycemic Abnormalities in Adolescents

Glycemic abnormalities including prediabetes and Type 2 diabetes mellitus (T2DM) are emerging clinical problems in children and adolescents. Increased insulin resistance during pubertal development appears to uncover glycemic abnormalities. Pediatricians and physicians should be knowledgeable and conscious about the prevalence and progression of prediabetes to T2DM, the frequent mild or asymptomatic manifestation of T2DM in children and adolescents and the high risk of complications in these patients. Screening for glycemic abnormalities seems useful in high risk groups such as children and adolescents with obesity, family history of T2DM, and with clinical features suggestive of insulin resistance (hypertension, dyslipidemia, polycystic ovarian syndrome, or acanthosis nigricans). Modification of life style and reduction of obesity is still the prime target of prevention and early management of early glycemic abnormalities. However, use of hypoglycemic drugs is indicated when these measures fail to achieve adequate glycemic control.

Industrial Application of Evolvable Block-Based Neural Network to Hypoglycemia Monitoring System

Insulin-dependent diabetes mellitus is classified as type 1 diabetes mellitus (T1DM), and it can be further classified as immune-mediated or idiopathic. It is dangerous and can result in unconsciousness, seizures, and even sudden death. The most common physiological parameters to be effected from a hypoglycemic reaction are heart rate and corrected QT interval of the electrocardiogram (ECG) signal. Considering the correlation between physiological parameters of an ECG signal and the status of hypoglycemia, a noninvasive hypoglycemia monitoring system is tested and introduced by proposing a hybrid particle-swarm-optimization-based block-based neural network (BBNN) algorithm. The proposed BBNN model offers advantages over conventional neural networks by performing the simultaneous optimization of both structure and weights. The hybrid particle swarm optimization with wavelet mutation searches for optimized structure and network parameters through particle information over a search space. All the actual data sets of 15 T1DM children were collected at the Department of Health, Government of Western Australia. Several experiments showed that the proposed BBNN performed well in terms of better sensitivity and specificity.

Socioeconomic factors associated with pediatric diabetic ketoacidosis admissions in Southern West Virginia

Diabetic Ketoacidosis (DKA) is a well-known complication in children with type 1 diabetes mellitus (T1DM) with a mortality rate estimated at 2%. A previous study identified that T1DM children of non-Caucasian race with Medicaid insurance had increased incidence of DKA admissions. The aim of this study is to identify the socioeconomic factors associated with DKA admissions in West Virginia (WV). Retrospective chart review of patients admitted to the paediatric intensive care unit with DKA in Charleston, WV from January 2007-December 2010. Included subjects were 1-18 years of age and those with type 1 diabetes of >6 months duration. Admission rates were compared with the normal population distribution in WV. The data collection tool included multiple socioeconomic factors and HbA1c. We reviewed a total of 167 patients with an admitting diagnosis of DKA; 57% were female, 43% male. Average age was 13.5 years ± 2.7; 56.4% were covered by Medicaid/Chips (WV state insurance) and 43.6% by commercial payers. 11.9% were African American and 88.1% were Caucasian. The average HbA1c was 10.85 ± 2.36%. Higher risks for DKA included those with HbA1c >14%, African American children (OR 17.4, CI 4-73) and children with Medicaid/Chips insurance (OR 9.3, 95% CI 1.1-76.2). This study identifies socioeconomic factors associated with children admitted for DKA in WV. Patients at higher risk for DKA include those with elevated HbA1c, African American race and those covered by Medicaid/CHIPS (thereby presumed lower socioeconomic status). Findings can be utilized to identify patients at highest risk for DKA and implementation of prevention strategies.

Correlation between blood glucose fluctuations and activation of oxidative stress in type 1 diabetic children during the acute metabolic disturbance period

Background Studies have shown that complications in type 1 diabetes mellitus (T1DM) in children are mainly due to oxidative stress (OS). Lipid peroxidation is the main marker of OS and iso-prostaglandin is a reliable biomarker of lipid peroxidation in type 2 diabetes mellitus (T2DM). However, there have been few studies on OS in T1DM children with hyperglycemia and glucose fluctuations. Methods We prospectively enrolled 23 newly diagnosed T1DM patients and 23 age and sex matched healthy controls in Beijing Children's Hospital from May 2010 to January 2011. They were treated with continuous subcutaneous insulin injection (CSII) and monitored by continuous glucose monitoring system (CGMS). Twenty-four-hour urine samples were collected to measure the concentration of 8-iso prostaglandin F2α (8-isoPGF2α). Samples taken from diabetic children were collected at days 8 to 10 after insulin treatment. Intraday glucose fluctuations were assessed by mean amplitude of glucose excursions (MAGE), largest amplitude of glycemic excursions (LAGE), standard deviation of blood glucose (SDBG) and number of glycemic excursions (NGE). The correlations between glucose parameters and the index of oxidative stress were analyzed. Results Urine 8-isoPGF2α in the T1DM group was higher than that in the control group ((967.70±412.68) ng vs. (675.23±354.59) ng, P=0.019). There was a correlation between urine 8-isoPGF2α level and MAGE (r=0.321, P=0.039), a significant correlation between low-density lipoprotein and urine 8-isoPGF2α level (r=0.419, P=0.03). There was no significant correlation between urine 8-isoPGF2α level and blood pressure, glycosylated hemoglobin (HbA1c), fasting C-peptide or other lipid indices. Conclusion A correlation between urine 8-isoPGF2α levels and MAGE and low-density lipoprotein was found in children newly diagnosed with T1DM.

Trends in the Incidence of Childhood Type 1 Diabetes Mellitus in Beijing Based on Hospitalization Data from 1995 to 2010

Objectives: To study the incidence trend of type 1 diabetes mellitus (T1DM) in children in Beijing from 1995 to 2010, to compare it with incidences reported worldwide and to predict the requirement of medical resources in the future. Methods: This study involved newly diagnosed T1DM cases younger than 15 years of age in the Beijing Children's Hospital from January 1995 to December 2010. We calculated the incidence of T1DM children in Beijing according to hospitalization data and Beijing's population. We defined it as the underestimated incidence rate (UE-IR). Results: The UE-IRs of T1DM ranged from around 0.88/100,000 to 2.37/100,000 for children in Beijing younger than 15 years of age from 1995 to 2010. The UE-IR increased faster in boys (1.47 times) and in the age group of 0-4 years (1.89 times) after 2003. The UE-IR was greatest in children aged 5-9 years (1.81/100,000) followed by the age of puberty (10-14 years, 1.76/100,000). The predicted number of new T1DM cases in Beijing will increase 1.97 times over the next 10 years. Conclusions: The incidence trend of T1DM was increasing gradually in those younger than 15 years of age in Beijing. The incidence of younger children and boys grew faster. The 5- to 14-year-old children represented a high-risk population of T1DM. The number of predicted new T1DM cases will grow rapidly. This means that we should train more health care providers for pediatric diabetes patients, in order to achieve high-quality medical care and to be able to prevent or postpone chronic complications.

Эпидемиологические и экологические показатели сахарного диабета 1 типа у детей и подростков Краснодарского края

Aims. to investigate the influence of environmental pollution on epidemiology of type 1 diabetes mellitus (T1DM) in children and adolescents of Krasnodar Region. Materials and Methos. Epidemiologic study was based on regional T1DM register data and official reports by medical facilities (form #112). Environmental survey was conducted according to the method of Shashel et al. Results. Epidemiologic study revealed increasing prevalence of T1DM among children and adolescents of Krasnodar Region for the period from 2000 to 2012 yy. Average prevalence of T1DM was estimated at 68.08 (children) and 135.78 (adolescents), and incidence at 10.08 and 17.01 per 100 000 inhabitants, respectively. Epidemiologic trend quantitatively correlates with ecological disturbance in resident areas of the population in question. Areas recognized as adverse environment reported a 2.8?3.2-fold increase in T1DM appealability as measured against neighboring areas with favourable ecologic environment. Conclusion. Higher levels of environmental pollution drive both incidence and prevalence of T1DM in children and adolescents of Krasnodar Region, plausibly through induction of autoimmune process in the pancreas.

Динамика основных эпидемиологических показателей сахарного диабета 1 типа у детей и подростков в Российской Федерации (2001–2011 гг.)

Aims. To evaluate key epidemiology trends for type 1 diabetes mellitus (T1DM) in children and adolescents of Russian Federation during 2001?2011 yy. Materials and Methods. Dynamics of incidence, prevalence and mortality from T1DM were assessed for national population and, separately, for all federal regions over the 2001?2011 yy. based on the questionnaires developed in the Institute of Paediatric Endocrinology (Endocrinology Research Centre) and data from the State Register of Diabetes Mellitus. Results. 18,392 children aged 0 to 14 years and 8934 adolescents with T1DM were registered in Russian Federation by 01.01.2012. T1DM incidence in 2011 was estimated at 2407 among children and 1276 among adolescents. Mean T1DM prevalence across the Federation reached 72.8, incidence 12.43 (3.39?14.06) and mortality 0.07 (0.0?0.26) per 100,000 of relevant population (r.p.). Incidence rate for 2001?2011 indicates a 30% increase for past 11 years with average annual increase of 2.82%. According to the prognosis developed from these data, in 5 years T1DM incidence among children will reach 13.61 per 100,000 of r.p. Highest incidence was registered in Ural Federal Region (17.43 per 100,000 of r.p.) that assumed this position from North-Western federal region with 15.42 per 100,000 of r.p. as of 01.01.2010). T1DM incidence in adolescents is estimated at 15.26 per 100,000 r.p. with prevalence of 92.6 per 100,000 r.p. Incidence rate increased by 10.5% during past 6 years with average annual increase of 0.97%. Conclusion. This survey indicates that key epidemiological trends for T1DM in children and adolescents of Russian Federation correspond to average world parameters.

Incidence of type 1 diabetes mellitus in Turkish children from the southeastern region of the country: a regional report.

Objective: Variability in the incidence of type 1 diabetes mellitus (T1DM) related to geographical region, ethnic background, gender, and age indicates a need for further epidemiological studies. To date, there are no reported studies on the incidence of T1DM in the pediatric age group from the Southeastern region of Turkey. To define the incidence, demographic and clinical characteristics of T1DM in children 0-14 years of age in Diyarbakir, one of the largest cities in the Southeast region of Turkey.Methods: Hospital files of patients with the diagnosis of T1DM were reviewed. Data of all patients diagnosed between 1 June 2010 and 31 May 2011 were evaluated. Population data on the 0-14 age group were obtained from the Turkish Statistical Institute (TSI) reports.Results: From a total of 41 T1DM patients, 24 (58.5%) were female (male: 41.5%) with a male/female ratio of 1.4. The overall annual incidence of T1DM was 7.2/105, being 8.7/105 in females and 5.7/105 in males. The peak incidence was found to occur at age 5-9 years in the girls and 10-14 years in the boys. Mean age at diagnosis was 8.1±3.8 years. Rate of presentation with diabetic ketoacidosis was 65.9%. Patients applied most frequently in spring and winter months.Conclusions: In this first T1DM incidence study on the pediatric age group in Diyarbakir, Turkey, T1DM incidence was found to be similar to that in countries with low-middle incidence. Conflict of interest:None declared.

Endothelial progenitor cells are related to glycemic control in children with type 1 diabetes over time.

OBJECTIVEThe risk of cardiovascular death before the age of 40 is 20-fold higher in patients with type 1 diabetes mellitus (T1DM). Endothelial progenitor cells (EPCs) predict cardiovascular morbidity and mortality in patients without diabetes. We hypothesized that EPCs are modified in children with T1DM and are related to characteristics of T1DM such as glycemic control.RESEARCH DESIGN AND METHODSChildren (n = 190; 156 T1DM subjects and 34 control subjects) were included in an observational cohort study and matched for age and sex. EPCs were enumerated by flow cytometry at the beginning (cross-sectional) and 1 year later (longitudinal). To analyze changes of variables during the observation, Δ values were calculated.RESULTSEPCs were significantly reduced in T1DM children versus control subjects (609 ± 359 vs. 1,165 ± 484, P < 0.001). Multivariate regression modeling revealed that glycated hemoglobin A1c (HbA1c) was the strongest independent predictor of EPCs (β = −0.355, P < 0.001). Overall glycemic control at the beginning and end of study did not differ (7.8 ± 1.2 vs. 7.8 ± 1.2 relative %, P = NS), but we observed individual HbA1c changes of −4.30/+3.10 relative %. The strongest EPC increase was observed in the patients with the most favorable HbA1c lowering during the 1-year follow-up. Accordingly, the strongest EPC decrease was demonstrated in the patients with the strongest HbA1c worsening during the time period.CONCLUSIONSThis is the first prospective study demonstrating diminished EPCs in children with T1DM. The association of better glycemic control with an increase in EPC numbers within 1 year suggests that a reduction of the high cardiovascular disease burden might be mediated likewise.

Type 2 Diabetes Mellitus in Children and Youth

Type 2 diabetes mellitus (T2DM) which used to be a disease of adults is now seen commonly at an early age in children and adolescents. T2DM is now an important diagnostic consideration in children who present with signs and symptoms of diabetes. The emerging epidemic of obesity in children throughout the world and the resultant insulin resistance contributes to the increasing prevalence of T2DM in this population. The recommended treatment options include metformin and insulin. Optimal glycemic control is essential considering the lifelong nature of the disease and therefore, the increased risk of long term complications - both microvascular and macrovascular. This review article summarizes the classification, diagnosis, pathogenesis, management, complications and screening of T2DM in children, incorporating and contextualizing guidelines from various professional associations.

The risk of early cardiovascular disease in Lithuanian diabetic children and adolescents: A type 1 diabetes register database based study

AimsThe aim was to assess the frequency and correlates of selected cardiovascular disease risk factors among Lithuanian children and adolescents with type 1 diabetes mellitus (T1DM). MethodsA cohort of 539 T1DM children was investigated. Total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), glycated haemoglobin (HbA1c) was determined. ResultsThe mean of HbA1c was 8.5±1.8%. Overweight was present in 72 (13.4%, 95% CI 10.6–16.9) and 113 (21.0%, 95% CI 17.5–25.3) had arterial hypertension. Hypercholesterolemia was diagnosed in 120 (22.3%; 95% CI 18.6–26.7), decreased HDL in 22 (4.1%; 95% CI 2.7–6.2), high LDL in 79 (14.7%; 95% CI 11.8–18.3), and high TG in 96 (17.8%, 95% CI 14.7–21.9) subjects. There were positive linear correlations between TG and high HbA1c levels (r=0.192; p<0.001), and between LDL and high HbA1c levels (r=0.238; p<0.001). Two cardiovascular risk factors were present 14.3%, three risk factors in 6.9%, four in 2.4% and five in 0.9%. The frequency of two cardiovascular risk factors was higher among 10–17-year-old T1DM patients than among 1–9-year-old children (27.0% vs. 13.3% respectively, p<0.01). ConclusionThe frequency of cardiovascular risk factors is common in young people with T1DM and was associated with poor glycaemic control.

Management of Newly Diagnosed Type 2 Diabetes Mellitus (T2DM) in Children and Adolescents

Over the past 3 decades, the prevalence of childhood obesity has increased dramatically in North America, ushering in a variety of health problems, including type 2 diabetes mellitus (T2DM), which previously was not typically seen until much later in life. The rapid emergence of childhood T2DM poses challenges to many physicians who find themselves generally ill-equipped to treat adult diseases encountered in children. This clinical practice guideline was developed to provide evidence-based recommendations on managing 10- to 18-year-old patients in whom T2DM has been diagnosed. The American Academy of Pediatrics (AAP) convened a Subcommittee on Management of T2DM in Children and Adolescents with the support of the American Diabetes Association, the Pediatric Endocrine Society, the American Academy of Family Physicians, and the Academy of Nutrition and Dietetics (formerly the American Dietetic Association). These groups collaborated to develop an evidence report that served as a major source of information for these practice guideline recommendations. The guideline emphasizes the use of management modalities that have been shown to affect clinical outcomes in this pediatric population. Recommendations are made for situations in which either insulin or metformin is the preferred first-line treatment of children and adolescents with T2DM. The recommendations suggest integrating lifestyle modifications (ie, diet and exercise) in concert with medication rather than as an isolated initial treatment approach. Guidelines for frequency of monitoring hemoglobin A1c (HbA1c) and finger-stick blood glucose (BG) concentrations are presented. Decisions were made on the basis of a systematic grading of the quality of evidence and strength of recommendation. The clinical practice guideline underwent peer review before it was approved by the AAP. This clinical practice guideline is not intended to replace clinical judgment or establish a protocol for the care of all children with T2DM, and its recommendations may not provide the only appropriate approach to the management of children with T2DM. Providers should consult experts trained in the care of children and adolescents with T2DM when treatment goals are not met or when therapy with insulin is initiated. The AAP acknowledges that some primary care clinicians may not be confident of their ability to successfully treat T2DM in a child because of the child's age, coexisting conditions, and/or other concerns. At any point at which a clinician feels he or she is not adequately trained or is uncertain about treatment, a referral to a pediatric medical subspecialist should be made. If a diagnosis of T2DM is made by a pediatric medical subspecialist, the primary care clinician should develop a comanagement strategy with the subspecialist to ensure that the child continues to receive appropriate care consistent with a medical home model in which the pediatrician partners with parents to ensure that all health needs are met.

Management of Type 2 Diabetes Mellitus in Children and Adolescents

Over the last 3 decades, the prevalence of childhood obesity has increased dramatically in North America, ushering in a variety of health problems, including type 2 diabetes mellitus (T2DM), which previously was not typically seen until much later in life. This technical report describes, in detail, the procedures undertaken to develop the recommendations given in the accompanying clinical practice guideline, "Management of Type 2 Diabetes Mellitus in Children and Adolescents," and provides in-depth information about the rationale for the recommendations and the studies used to make the clinical practice guideline's recommendations. A primary literature search was conducted relating to the treatment of T2DM in children and adolescents, and a secondary literature search was conducted relating to the screening and treatment of T2DM's comorbidities in children and adolescents. Inclusion criteria were prospectively and unanimously agreed on by members of the committee. An article was eligible for inclusion if it addressed treatment (primary search) or 1 of 4 comorbidities (secondary search) of T2DM, was published in 1990 or later, was written in English, and included an abstract. Only primary research inquiries were considered; review articles were considered if they included primary data or opinion. The research population had to constitute children and/or adolescents with an existing diagnosis of T2DM; studies of adult patients were considered if at least 10% of the study population was younger than 35 years. All retrieved titles, abstracts, and articles were reviewed by the consulting epidemiologist. Thousands of articles were retrieved and considered in both searches on the basis of the aforementioned criteria. From those, in the primary search, 199 abstracts were identified for possible inclusion, 58 of which were retained for systematic review. Five of these studies were classified as grade A studies, 1 as grade B, 20 as grade C, and 32 as grade D. Articles regarding treatment of T2DM selected for inclusion were divided into 4 major subcategories on the basis of type of treatment being discussed: (1) medical treatments (32 studies); (2) nonmedical treatments (9 studies); (3) provider behaviors (8 studies); and (4) social issues (9 studies). From the secondary search, an additional 336 abstracts relating to comorbidities were identified for possible inclusion, of which 26 were retained for systematic review. These articles included the following: 1 systematic review of literature regarding comorbidities of T2DM in adolescents; 5 expert opinions presenting global recommendations not based on evidence; 5 cohort studies reporting natural history of disease and comorbidities; 3 with specific attention to comorbidity patterns in specific ethnic groups (case-control, cohort, and clinical report using adult literature); 3 reporting an association between microalbuminuria and retinopathy (2 case-control, 1 cohort); 3 reporting the prevalence of nephropathy (cohort); 1 reporting peripheral vascular disease (case series); 2 discussing retinopathy (1 case-control, 1 position statement); and 3 addressing hyperlipidemia (American Heart Association position statement on cardiovascular risks; American Diabetes Association consensus statement; case series). A breakdown of grade of recommendation shows no grade A studies, 10 grade B studies, 6 grade C studies, and 10 grade D studies. With regard to screening and treatment recommendations for comorbidities, data in children are scarce, and the available literature is conflicting. Therapeutic recommendations for hypertension, dyslipidemia, retinopathy, microalbuminuria, and depression were summarized from expert guideline documents and are presented in detail in the guideline. The references are provided, but the committee did not independently assess the supporting evidence. Screening tools are provided in the Supplemental Information.

Serum dipeptidyl peptidase 4 activity in children with type 1 diabetes mellitus

It is poorly understood whether dipeptidyl peptidase 4 (DPP4) activity is altered and how DPP4 contributes to glycemic control in patients with type 1 diabetes mellitus (T1DM). The aim of this study was to measure serum DPP4 activity and to assess its relationships to metabolic variables in T1DM children. Serum DPP4 activity was determined using a fluorometric assay in 43 T1DM and 26 control children. Serum DPP4 activity was significantly higher in T1DM children than in controls (3.57 ± 0.99 vs. 2.67 ± 0.77 U/mL, p<0.001). In the T1DM children, DPP4 activity was not correlated with HbA1c, blood glucose, or diabetes duration. A significant negative correlation was found between DPP4 activity and serum adiponectin levels in the T1DM group (r=-0.35, p<0.05). Serum DPP4 activity was increased in the T1DM children, whereas it was not associated with glycemic control. Given the negative correlation between serum DPP4 and adiponectin levels, further investigations are warranted to elucidate the role of DPP4 on insulin sensitivity in T1DM children.

High prevalence of celiac disease in Swedish children and adolescents with type 1 diabetes and the relation to the Swedish epidemic of celiac disease: a cohort study

Aim. The aim was to determine the prevalence and clinical and temporal relationship of celiac disease (CD) in a population of Swedish children with type 1 diabetes mellitus (T1DM) before, during, and after the Swedish epidemic of CD (birth cohorts 1984–1996). Methods. Retrospective chart review between 1995 and 2005 was conducted of 1151 children (0–18 years old, born 1981–2004) with T1DM. Results. A prevalence of 9.1% (95% CI: 7.2–11.2) of CD in T1DM children was found. No significant difference in prevalence of CD was observed in different birth years, in contrast to the Swedish epidemic of CD. Sixty-two percent of children diagnosed with CD after T1DM onset had pathological levels of antibodies within the first 24 months. The presence or absence of gastrointestinal symptoms had no predictable value for biopsy-confirmed CD or not. Conclusion. The onset of CD in the T1DM population does not follow the pattern of the general population during the Swedish epidemic of CD. The shared genetic component in the human leukocyte antigen region in cases with comorbidity of CD and T1DM may overrule other CD-causing factors in the general population. Children with T1DM should be screened for CD at diagnosis and repeatedly at least during the first 2 years, even if asymptomatic.

Psychological characteristics of Korean children and adolescents with type 1 diabetes mellitus.

PurposeThis study investigates the behavioral and emotional characteristics of Korean children and adolescents with type 1 diabetes mellitus (T1DM) as compared to healthy controls, and examines whether their psychological status is associated with glycemic control, insulin regimens, or disease duration.MethodsA total of 37 Korean children and adolescents with T1DM, aged 6-17 years, and 38 sex- and age-matched healthy controls were included in this study. Psychological distress was assessed using the Korean child behavior checklist (K-CBCL) and children's depression inventory (CDI) after the subjects and their parents were interviewed.ResultsThe CDI and K-CBCL scores were significantly higher in T1DM subjects compared to normal controls. The T1DM subjects with "poorly controlled" blood glucose (glycosylated hemoglobin ≥8%) and "old patients" (disease duration ≥1 year) had a tendency to show higher CDI and K-CBCL scores. There were no significant differences in CDI and K-CBCL scores between the intensive and conventional insulin therapy groups.ConclusionChildren and adolescents with T1DM seem to have inferior psychological adjustment to their normal counterparts, which might be associated with glycemic control and disease duration. Psychological evaluation and intervention should be considered in the management of T1DM in children and adolescents.