RESUMO
The aim of the study was to determine the pathogenesis of non-obese children with type 2 diabetes, and its relationship with fat distribution. The study participants included 36 obese children with type 2 diabetes (age: 13.5 years, BMI: 28.3, BMI percentile: 91.9) and 30 non-obese children with type 2 diabetes (age: 13.5 years, BMI: 23.1, BMI percentile: 74.0). The proportion of female participants was significantly higher in non-obese children than in obese children (73.3% vs. 41.7%, p < 0.001). Abdominal fat distribution, evaluated by subcutaneous fat (SF) area, visceral fat (VF) area, and the ratio of VF area to SF area (V/S ratio), measured using computed tomography, and serum lipid levels and liver function were compared between the two groups. Non-obese children with type 2 diabetes had significantly smaller SF area and also smaller VF area than obese children with type 2 diabetes (SF area: 158.3 m2 vs. 295.3 m2, p < 0.001, VF area: 71.0 m2 vs. 94.7 m2, p = 0.032). Whereas non-obese children with type 2 diabetes had significantly greater V/S ratio than obese children with type 2 diabetes (0.41 vs. 0.31, p = 0.007).The prevalence of dyslipidemia and liver dysfunction were similar in the two groups. In conclusion, non-obese children with type 2 diabetes had excess accumulation of VF despite a small amount of SF, which might be associated with glucose intolerance and other metabolic disorders.
Assuntos
Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Humanos , Feminino , Criança , Adolescente , Diabetes Mellitus Tipo 2/metabolismo , Gordura Subcutânea , Índice de Massa Corporal , Intolerância à Glucose/metabolismo , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/metabolismoRESUMO
Islet-cell associated antibodies are predictive and diagnostic markers for type 1 diabetes. We studied the differences in the early clinical course of children with type 1 diabetes with a single antibody and those with multiple antibodies against pancreatic ß-cells. Sixty-seven children with type 1 diabetes aged less than 15 years diagnosed between 2010 and 2021 were included in the study and subdivided into two subgroups: children who were single positive for either glutamic acid decarboxylase (GAD) antibodies (n = 16) or insulinoma-associated antigen-2 (IA-2) antibodies (n = 13) and those positive for both antibodies (n = 38) at diagnosis. We compared the patients' clinical characteristics, pancreatic ß-cell function, and glycemic control during the 5 years after diagnosis. All clinical characteristics at diagnosis were similar between the two groups. One and two years after diagnosis, children who tested positive for both antibodies showed significantly lower postprandial serum C-peptide (CPR) levels than those who tested positive for either GAD or IA-2 antibodies (p < 0.05). In other periods, there was no significant difference in CPR levels between the two groups. There was a significant improvement in glycosylated hemoglobin (HbA1c) levels after starting insulin treatment in both groups (p < 0.05), but no significant difference in HbA1c levels between the groups. Residual endogenous insulin secretion may be predicted based on the number of positive islet-cell associated antibodies at diagnosis. Although there are differences in serum CPR levels, optimal glycemic control can be achieved by individualized appropriate insulin treatment, even in children with type 1 diabetes.
Assuntos
Autoanticorpos , Diabetes Mellitus Tipo 1 , Glutamato Descarboxilase , Insulina , Insulinoma , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Masculino , Feminino , Criança , Adolescente , Hemoglobinas Glicadas , Insulinoma/tratamento farmacológico , Peptídeo C/sangue , Insulina/uso terapêuticoRESUMO
Prevention of hypoglycemia is an important strategy for glycemic management in patients with type 1 diabetes mellitus (T1D). Hypoglycemia is difficult to recognize at night while sleeping, particularly when using multiple daily injection (MDI) insulin therapy rather than sensor-augmented insulin-pump therapy. Therefore, it is possible that patients with T1D are at higher risk of nocturnal hypoglycemia when insulin is administered using an MDI regimen. We investigated nocturnal hypoglycemia in 50 pediatric patients with T1D on MDI insulin therapy using data from an intermittently scanned continuous glucose monitoring (isCGM) system. Hypoglycemia was observed on 446 of the 1,270 nights studied. Most of the hypoglycemic episodes were severe (blood glucose <54 mg/dL). On nights when hypoglycemia occurred, the blood glucose concentrations measured using finger-stick blood glucose monitoring (FSGM) before sleep and the next morning were lower than nights when hypoglycemia did not occur. However, few values were below the normal blood glucose range, suggesting that FSGM alone may be insufficient to detect nocturnal hypoglycemia. Approximately 7% of time was spent below the normal glucose range during the 10 hours from 21:00 to 7:00 the next morning. This result suggests that the patients on MDI insulin therapy could end up spending more time in hypoglycemia than is recommended by the American Diabetes Association (time below range <4.0% of time per day). Monitoring glucose levels overnight using an isCGM sensor may improve glycemic management via automatic detection of blood glucose peaks and troughs.
Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Humanos , Criança , Glicemia , Automonitorização da Glicemia , Hipoglicemiantes/efeitos adversos , População do Leste Asiático , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Insulina/efeitos adversos , Sistemas de Infusão de Insulina/efeitos adversosRESUMO
Since the 2018 ISPAD guidelines on this topic, follow-up of large cohorts from around the globe have continued informing the current incidence and prevalence of co-morbidities and complications in young adults with youth-onset type 2 diabetes (T2D). This chapter focuses on the risk factors, diagnosis and presentation of youth-onset T2D, the initial and subsequent management of youth-onset T2D, and management of co-morbidities and complications. We include key updates from the observational phase of the multi-center Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial, the SEARCH for Diabetes in Youth (SEARCH) study and new data from the Restoring Insulin Secretion (RISE) study, a head-to-head comparison of youth onset vs adult-onset T2D. We also include an expanded section on risk factors associated with T2D, algorithms and tables for treatment, management, and assessment of co-morbidities and complications, and sections on recently approved pharmacologic therapies for the treatment of youth-onset T2D, social determinants of health, and settings of care given COVID-19 pandemic.
Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Adolescente , Criança , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Incidência , Pandemias , Fatores de Risco , Adulto JovemRESUMO
Continuous glucose monitoring (CGM) has been widely used in children and adolescents as well as adults with type 1 diabetes. CGM metrics include three key measurements of target glucose: time in range (TIR: 70-180 mg/dL), time below range (TBR: <70 mg/dL), and time above range (TAR: >180 mg/dL). The primary goal of optimal glycemic control is to increase TIR to more than 70%, while simultaneously reducing TBR to less than 4%, while minimizing severe hypoglycemia to less than 1%, as proposed by the Advanced Technologies and Treatments for Diabetes (ATTD) panel. However, several studies have indicated that the TIR goal is quite difficult to achieve in pediatric patients who have remarkable interindividual and day-to-day glycemic variation due to their irregular lifestyles. Previous studies have demonstrated that patients without an automated insulin delivery system are unlikely to attain the recommended glycemic goals. On the other hand, reduction of hypoglycemia, particularly minimizing severe hypoglycemia, is a critical issue in the effective management of children with type 1 diabetes. Frequent episodes of severe hypoglycemia and hypoglycemia can cause lasting neurological damage. Accordingly, we propose reducing the TBR to less than 5%, rather than just targeting the TIR to more than 70%. In CGM metrics this should be the cardinal glycemic goal for pediatric patients who are either being treated with multiple daily injections of insulin or a conventional insulin pump, but who are not using an automated insulin delivery system.
Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adolescente , Adulto , Glicemia , Automonitorização da Glicemia , Criança , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Insulina/uso terapêuticoRESUMO
Beckwith-Wiedemann syndrome (BWS) is infrequently associated with adrenocortical carcinoma (ACC) or non-hormone-producing adrenal cytomegaly, but we recently, encountered a single case of adrenal cytomegaly in a patient with BWS, which was difficult to distinguish from androgen-producing adrenocortical carcinoma (ACC). Here, we describe the case of a 4-month-old female who presented with clitoromegaly, hemihypertrophy, and an adrenal mass identified during the prenatal period. The mass was located in detected at the left suprarenal region and detected at 20 weeks of gestational age. At birth, she also presented with clitoromegaly and elevated serum levels of 17α-hydroxyprogesterone, dehydroepiandrosterone, and testosterone at birth and experienced hyper-insulinemic hypoglycemia, which improved following diazoxide therapy. We initially suspected androgen-producing ACC with metastasis and the left adrenal mass was resected accordingly when the patient reached 4 months of age. However, histological examination revealed adrenal cytomegaly. Genetic analysis revealed paternal uniparental disomy, and the patient was finally diagnosed as having BWS. Resection of the left adrenal gland restored the serum androgen levels to normal physiological levels without any recurrence. While it is reasonably well known that BWS is sometimes accompanied by virilization due to androgen-producing ACC, our findings are among the first to suggest that adrenal cytomegaly can also increase androgen hormone production. Thus, we propose that adrenal cytomegaly should be considered one of the differential diagnoses when accompanied with hyperandrogenism in BWS patients.
Assuntos
Neoplasias do Córtex Suprarrenal , Doenças das Glândulas Suprarrenais , Carcinoma Adrenocortical , Síndrome de Beckwith-Wiedemann , Androgênios , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Dissomia UniparentalRESUMO
INTRODUCTION: Rotavirus (RV) is the major pathogen responsible for acute gastroenteritis in infants. Since RV vaccines were introduced, a substantial decline in the incidence of severe RV infection has been reported. However, some burden still exists, even in developed countries, including Japan. METHODS: We retrospectively surveyed 380 patients hospitalized for acute gastroenteritis from 2015 to 2019. In 2019, additional detailed clinical information of 21 patients with RV gastroenteritis was obtained to evaluate the efficacy of the RV vaccine. Nine fecal samples from those patients were collected to detect the RV genotypes. RESULTS: Our data showed an increasing trend in hospitalizations for severe RV gastroenteritis in children older than 5 years. According to the Vesikari clinical severity scores in the older group (≥5 years), the gastrointestinal symptoms in vaccinated patients were less severe than those in unvaccinated patients (p = 0.014). The genotype analysis revealed that G9P[8]I1 was the major genotype in the recruited patients in 2019. CONCLUSIONS: This report warns that children older than 5 years could be affected by severe RV infection and suggests prompt intervention for this age group, similar to that in infants. In the new period in which the RV vaccine is included in Japanese national immunization programs beginning October 2020, continuous monitoring of patient clinical characteristics and RV epidemiology is required to determine the role of vaccines.
Assuntos
Gastroenterite , Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Criança , Pré-Escolar , Fezes , Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle , Genótipo , Hospitalização , Humanos , Lactente , Japão/epidemiologia , Estudos Retrospectivos , Rotavirus/genética , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controleRESUMO
BACKGROUND: We aimed to investigate the significance of the C-peptide levels on a glucagon stimulation test (GST) conducted soon after diagnosis as a predictive marker for residual ß-cell function over time in Japanese children with type 1 diabetes (TD1). METHODS: We retrospectively enrolled 65 Japanese children (25 male, 40 female; age <16 years) with new-onset TD1. A GST was conducted within 1 month of diagnosis, when glucose toxicity improved. One- to 2-h postprandial serum C-peptide values were measured at 0, 3, 6, 12, 24, 36, 60, and 120 months after diagnosis. RESULTS: Receiver operating characteristic analysis showed that the cutoff values of peak serum C-peptide levels used to predict the complete destruction of ß-cells at 3, 6, and 12 months after diagnosis were all 0.20 ng/mL (area under the curve [AUC] 0.867, 95% confidence interval [CI] 0.745-0.990; AUC 0.774, 95% CI 0.634-0.914; and AUC 0.804, 95% CI 0.695-0.914, respectively); the values at 24, 36, and 60 months were 0.69 ng/mL (AUC 0.828, 95% CI 0.721-0.936), 0.60 ng/mL (AUC 0.777, 95% CI 0.636-0.918), and 0.70 ng/mL (AUC 0.848, 95% CI 0.715-0.982), respectively. On multivariate analysis, peak serum C-peptide level on a GST, diabetic ketoacidosis, age, and HbA1c level at diagnosis were associated with residual ß-cell function over time. CONCLUSIONS: Peak serum C-peptide levels on a GST conducted soon after diagnosis in Japanese children with TD1 could predict the time to decrease in postprandial serum C-peptide values to < 0.20 ng/mL.
Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Glicemia , Peptídeo C , Feminino , Glucagon , Humanos , Recém-Nascido , Insulina , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: We compared insulin resistance and glucose metabolism during growth hormone (GH) therapy between 43 short children born small-for-gestational age (SGA) and 42 children identify as growth hormone deficiency (GHD). METHODS: The study compared fasting plasma glucose (FPG), fasting immunoreactive insulin (IRI) and homeostasis model assessment insulin resistance index (HOMA-IR) during 24-month GH therapy between the two groups. RESULTS: Mean FPG, fasting IRI, and HOMA-IR values at 3-month GH therapy were significantly higher than those before and at 12- and 24-month GH therapy in both groups. These markers were significantly higher in short children born SGA than GHD children until 12-month GH therapy but were not different at 24-month GH therapy in both groups. CONCLUSIONS: The increased secretion of insulin observed in short children born SGA might be a compensatory mechanism for the prevention of hyperglycemia that can progress to diabetes mellitus. However, these metabolic markers gradually declined after 3 months of GH therapy and returned to baseline values at 24 months. These results suggest that short children born SGA have greater insulin resistance than GHD children at the early period of GH therapy, however, increased insulin resistance is improved over a long period.
Assuntos
Hormônio do Crescimento Humano , Resistência à Insulina , Estatura , Criança , Idade Gestacional , Hormônio do Crescimento , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade GestacionalRESUMO
BACKGROUND: We assessed the association between scanning frequency of flash glucose monitoring (FGM) and continuous glucose monitoring (CGM)-derived glycemic markers in children and adolescents with type 1 diabetes. METHODS: Subjects consisted of 85 children and adolescents with type 1 diabetes using FGM. We assessed the association between scanning frequencies of FGM- and CGM-derived metrics: Time in range (TIR) (70-180 mg/dL), time below range (TBR) (<70 mg/dL), time above range (>180 mg/dL), and other glycemic markers - laboratory-measured HbA1c and CGM-estimated glucose and HbA1c (eA1c) levels in the subjects. RESULTS: The mean number of scans was 11.5 ± 3.5 (5-20) times per day, and scanning was most frequently conducted during a period of 18-24 h. Scanning frequency showed significant positive correlation with TIR (r = 0.719, P < 0.0001) and inverse correlation with time above range (r = -0.743, P < 0.0001), but did not correlate with TBR. There were also significant inverse correlations between scanning frequency and glucose, HbA1c, and eA1c levels (r = -0.765, -0.815, and -0.793, respectively, P < 0.0001). CONCLUSIONS: Frequent glucose testing with FGM decreased hyperglycemia with increased TIR, but did not reduce TBR. Coping with a rapid fall of glucose and unexpected hypoglycemia with more advanced technology might contribute to a reduction in TBR.
Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adolescente , Glicemia , Automonitorização da Glicemia , Criança , Glucose , HumanosRESUMO
We assessed the significance of recommendations from the international consensus on continuous glucose monitoring (CGM)-derived metrics in Japanese children and adolescents with type 1 diabetes. Eighty-five patients (age, 13.5 ± 4.7 years) who wore the FreeStyle® Libre for a 28-day period were enrolled in this study. Seventy-three patients were treated with multiple daily injections of insulin and 12 with insulin pump therapy without using a sensor-augmented pump or a predictive low-glucose suspend-function pump. We evaluated the relationship between CGM-derived metrics: time in range (TIR: 70-180 mg/dL), time below range (TBR: <70 mg/dL), and time above range (TAR: >180 mg/dL), and laboratory-measured HbA1c and estimated HbA1c (eA1c) levels calculated from the mean glucose values. The TIR was 50.7 ± 12.2% (23-75%), TBR was 11.8 ± 5.8% (2-27%), and TAR was 37.5 ± 13.5% (9-69%). The TIR was highly correlated with HbA1c level, eA1c level, and TAR, but not with TBR. An HbA1c level of 7.0% corresponded to a TIR of 55.1% (95% CI: 53.7-56.5%), whereas a TIR of 70% corresponded to an HbA1c level of 6.1% (95% CI: 5.9-6.3%). The results of eA1c levels were similar to those observed for HbA1c levels. From these findings, we conclude that low rates of a recommended TIR of 70% may be due to less use of advanced technology and insufficient comprehensive diabetes care. Ethnic characteristics including lifestyle and eating customs may have contributed to the result. CGM-derived targets must be individualized based on ethnic characteristics, insulin treatment and diabetes care, and needs of individuals with diabetes.
Assuntos
Automonitorização da Glicemia , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Monitorização Ambulatorial , Adolescente , Criança , Consenso , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Hemoglobinas Glicadas , Humanos , Bombas de Infusão Implantáveis , Sistemas de Infusão de Insulina , Japão , Masculino , Guias de Prática Clínica como AssuntoRESUMO
For the increasing number of type 1 diabetes in Japan, after 1960, a greater supply of insulin was required, accordingly the availability of insulin gradually improved, The National Health Insurance approved self-injections of insulin at home in 1981. Afterwards, intensive insulin treatment with short-acting insulin and intermediate-acting insulin became widely used. Recombinant rapid-acting insulin analog was introduced in 1986 and long-acting insulin analog was introduced in 2003. In recent years, basal-bolus insulin regimens using these insulin analogs have become popular in children and adolescents with type 1 diabetes in Japan, which can improve the metabolic state and quality of life. This also will contribute to prevent the occurrence and progression of micro- and macro-vascular complications later in life.
Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemiantes , Insulina/uso terapêutico , Adolescente , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Japão , Qualidade de VidaRESUMO
Tall stature is usually defined as a height beyond 97th percentile or more than 2 SD above the mean height for age and sex in a defined population. Familiar tall stature, also known as constitutional tall stature, is the most common cause of tall stature. Overnutrition, obesity, also usually causes overgrowth. Tall stature by itself is not a pathological condition, however, there are a number of disorders associated with tall stature. Some genetic disorders and syndromes may be associated with mental retardation and various complications. Therefore, recognition of tall stature and revealing the underlying pathogenic causes and making the diagnosis are important not to miss the serious conditions and to provide adequate medical care and genetic counseling. Pathological causes for tall statute include endocrine disorders, such as excessive growth hormone secretion, hyperthyroidism, precocious puberty and lipodystrophy, chromosome disorders, such as Trisomy X (47, XXX female), Klinefelter Syndrome (47, XXY), XYY syndrome (47, XYY male) and fragile X syndrome, and syndromes and metabolic disorders, such as Marfan Syndrome, Beckwith-Wiedemann Syndrome, Simpson-Golabi-Behmel Syndrome, Sotos Syndrome and homocystinuria. Children may require growth-reductive treatment if the predicted adult height would be excessive and unacceptable. Some hormonal, high doses of sex steroids, or surgical, bilateral percutaneous epiphysiodesis of the distal femur and proximal tibia and fibula, treatment is currently available to reduce adult height.
Assuntos
Estatura , Transtornos do Crescimento , Adolescente , Algoritmos , Estatura/genética , Criança , Cromossomos Humanos X , Doenças do Sistema Endócrino/complicações , Síndrome do Cromossomo X Frágil/complicações , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/genética , Transtornos do Crescimento/terapia , Humanos , Hipertireoidismo/complicações , Deficiência Intelectual/etiologia , Síndrome de Klinefelter/complicações , Hipernutrição/complicações , Puberdade Precoce/complicações , Valores de Referência , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/complicações , TrissomiaRESUMO
PURPOSE OF REVIEW: The economic burden of diabetes in Japan is already serious and will become greater in the future. We review the economic impact of diabetes in Japan to examine viable options for mitigating its effects. RECENT FINDINGS: Medical costs for diabetes have been increasing by US $1 million annually, reaching US $11 million in 2009, of which US $7 million was accounted for by people aged 65 years or older. The quality of treatment of diabetes in Japan is higher than in other regions in the world. This can be more effective for achieving glycemic control, but is also more expensive compared with conventional treatment. Because of the high cost of diabetes in Japan, a coordinated response is needed. Intervention trials for people with prediabetes aimed at preventing the occurrence of diabetes seem to be the most cost-effective method for lowering the medical costs of diabetes, rather than the use of new, expensive antidiabetic drugs in patients with established diabetes.
Assuntos
Diabetes Mellitus/economia , Diabetes Mellitus/epidemiologia , Custos de Cuidados de Saúde/tendências , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/prevenção & controle , Intervenção Médica Precoce , Feminino , Humanos , Hipoglicemiantes/economia , Hipoglicemiantes/uso terapêutico , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Estado Pré-Diabético , Prevalência , Adulto JovemRESUMO
PURPOSE OF REVIEW: To review clinical characteristics of pediatric type 2 diabetes in Japan. RECENT FINDINGS: It is well recognized that Asian populations, particularly the Japanese, have a higher incidence of childhood type 2 diabetes. Of note, most Asian populations show a higher incidence of pediatric type 2 diabetes than that of type 1 diabetes. However, a current report in the USA demonstrated a dramatic increase in the incidence of young people with type 2 diabetes in recent years. The USA could have a much higher incidence of type 2 diabetes than Japan, possibly due to environmental and behavioral factors. The clinical features of Japanese young people with type 2 diabetes might have some differences from type 2 diabetes in other pediatric populations. Japanese children with type 2 diabetes are likely to be thinner than Caucasian children. Approximately 10-15% Japanese patients with type 2 diabetes exhibit normal weight with milder insulin resistance and substantial insulin secretion failure. Autoimmunity is not associated with the etiology of type 2 diabetes. Some genetic background and environmental factors, different from those in Caucasians, could play a role in the development of type 2 diabetes in Japanese children. Considering these characteristics, we must consider adequate therapy and management for young people with type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Autoimunidade , Criança , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Humanos , Incidência , Japão/epidemiologia , Estilo de Vida , Programas de Rastreamento , Fatores SocioeconômicosRESUMO
OBJECTIVE: To analyze changes in the annual incidence of school students with type 2 diabetes detected by urine glucose screening at schools in the Tokyo Metropolitan Area during 1975-2015. METHODS: Trend in temporal changes in the annual incidence rate were analyzed using a joinpoint regression model and the joinpoints. Annual percent change (APC) was calculated for each segmented line regression. Average annual percent change (AAPC) was also calculated for the whole period analyzed. RESULTS: In total, 301 students, including 64 primary school students and 237 junior high school students, were diagnosed with type 2 diabetes. The overall incidence of type 2 diabetes (per 100 000/year) during the entire study period was 2.58 in all students, 0.80 in primary school students, and 6.41 in junior high school students. AAPC during the entire study period was estimated at -1.5 (not significant), and the incidence significantly increased during 1975-1982 (APC = 17.49, P < 0.05), but tended to decrease during 1982-2015 (APC = -1.01). In primary school students, the incidence significantly increased during1975-2010 (APC = 3.30, P < 0.05), and tended to decrease during 2010-2015 (APC = -29.61). In junior high school students, the incidence did not significantly change during the entire study period (APC = 0.06). CONCLUSIONS: We found increasing trend in the overall incidence of school students with type 2 diabetes during 1975-1982, but a decreased tendency in recent years. This could be due to changes observed during the same time period in the primary school students. Lifestyle changes might contribute to improved incidence of childhood type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Instituições Acadêmicas , Estudantes/estatística & dados numéricos , População Urbana , Adolescente , Criança , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Instituições Acadêmicas/estatística & dados numéricos , Instituições Acadêmicas/tendências , Tóquio/epidemiologia , População Urbana/estatística & dados numéricos , População Urbana/tendênciasRESUMO
BACKGROUND: Mutations in causative genes for neonatal diabetes or maturity-onset diabetes of the young have been identified in multiple patients with autoantibody-negative type 1 diabetes (T1D). OBJECTIVES: We aimed to clarify the prevalence and phenotypic characteristics of monogenic abnormalities among 89 children with autoantibody-negative insulin-requiring T1D. METHODS: Mutations in 30 genes were screened using next-generation sequencing, and copy-number alterations of 4 major causative genes were examined using multiplex-ligation-dependent probe amplification. We compared the clinical characteristics between mutation carriers and non-carriers. RESULTS: We identified 11 probable pathogenic substitutions (6 in INS , 2 in HNF1A , 2 in HNF4A , and 1 in HNF1B ) in 11 cases, but no copy-number abnormalities. Only 2 mutation carriers had affected parents. De novo occurrence was confirmed for 3 mutations. The non-carrier group, but not the carrier group, was enriched with susceptible HLA alleles. Mutation carriers exhibited comparable phenotypes to those of non-carriers, except for a relatively normal body mass index (BMI) at diagnosis. CONCLUSIONS: This study demonstrated significant genetic overlap between autoantibody-negative T1D and monogenic diabetes. Mutations in INS and HNF genes, but not those in GCK and other monogenic diabetes genes, likely play critical roles in children with insulin-requiring T1D. This study also suggests the relatively high de novo rates of INS and HNF mutations, and the etiological link between autoimmune abnormalities and T1D in the non-carrier group. Carriers of monogenic mutations show non-specific phenotypes among all T1D cases, although they are more likely to have a normal BMI at diagnosis than non-carriers.
Assuntos
Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-beta Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/genética , Insulina/genética , Mutação , Criança , Pré-Escolar , Estudos de Coortes , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Estudos de Associação Genética , Testes Genéticos , Fator 1-alfa Nuclear de Hepatócito/química , Fator 1-beta Nuclear de Hepatócito/química , Fator 4 Nuclear de Hepatócito/química , Heterozigoto , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/química , Insulina/uso terapêutico , Japão , MasculinoRESUMO
OBJECTIVE: The reason for center differences in metabolic control of childhood diabetes is still unknown. We sought to determine to what extent the targets, expectations, and goals that diabetes care professionals have for their patients is a determinant of center differences in metabolic outcomes. RESEARCH DESIGN AND METHODS: Children, under the age of 11 with type 1 diabetes and their parents treated at the study centers participated. Clinical, medical, and demographic data were obtained, along with blood sample for centralized assay. Parents and all members of the diabetes care team completed questionnaires on treatment targets for hemoglobin A1c (HbA1c) and recommended frequency of blood glucose monitoring. RESULTS: Totally 1113 (53% male) children (mean age 8.0 ± 2.1 years) from 18 centers in 17 countries, along with parents and 113 health-care professionals, participated. There were substantial differences in mean HbA1c between centers ranging from 7.3 ± 0.8% (53 mmol/mol ± 8.7) to 8.9 ± 1.1% (74 mmol/mol ± 12.0). Centers with lower mean HbA1c had (1) parents who reported lower targets for their children, (2) health-care professionals that reported lower targets and more frequent testing, and (3) teams with less disagreement about recommended targets. Multiple regression analysis indicated that teams reporting higher HbA1c targets and more target disagreement had parents reporting higher treatment targets. This seemed to partially account for center differences in Hb1Ac. CONCLUSIONS: The diabetes care teams' cohesiveness and perspectives on treatment targets, expectations, and recommendations have an influence on parental targets, contributing to the differences in pediatric diabetes center outcomes.
Assuntos
Instituições de Assistência Ambulatorial/normas , Atitude do Pessoal de Saúde , Diabetes Mellitus Tipo 1/terapia , Hemoglobinas Glicadas/metabolismo , Criança , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , Masculino , Pais/psicologia , Pediatria/normasRESUMO
Fulminant type 1 diabetes mellitus (FT1DM) is a subtype of type 1 diabetes mellitus characterized by a remarkably abrupt onset. In Japan, FT1DM accounts for approximately 20% of acute-onset adult type 1 diabetes mellitus cases; however, reports of pediatric-onset FT1DM are rare. We aimed to determine the frequency and clinical characteristics of FT1DM in Japanese children and adolescents by conducting a 2-phase questionnaire survey among the members of the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) regarding their clinical experience with FT1DM. Responses were obtained from 54 of the 79 participating hospitals (68.4%). Of these, 8 hospitals managed a total of 15 pediatric patients with FT1DM (4 patients in each of 2 hospitals, 2 patients in 1 hospital, and 1 patient in each of 5 hospitals). The distribution of patient age was biphasic, with peaks in children younger than 5 years and older than 8 years of age. The clinical characteristics of FT1DM in this population (such as the duration from onset of symptoms to diagnosis, severity of symptoms, preceding flu-like episodes, and abnormal laboratory data) did not differ from those of patients with adult-onset FT1DM. The frequency of pediatric-onset FT1DM is low compared with that of adult-onset FT1DM. The genetic background and susceptibility patterns of pediatric patients with FT1DM may differ from those typical of adults with FT1DM, but both age groups share similar clinical characteristics.
Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Adolescente , Idade de Início , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/diagnóstico , Feminino , Humanos , Incidência , Lactente , Japão/epidemiologia , Masculino , Prevalência , Índice de Gravidade de Doença , Inquéritos e Questionários , Avaliação de SintomasRESUMO
BACKGROUND: We conducted an annual urine glucose screening program at schools, and diagnosed schoolchildren with diabetes at an early stage of the disease. We also identified some cases of renal glucosuria (RG), based on positive urine glucose with normal glucose tolerance. METHODS: During 2000-2015, 3 309 631 schoolchildren participated in the screening program. The positive rate for glucosuria in the first test was approximately 0.1%, whereas on repeat urine test it was approximately 0.05%. In total 350 schoolchildren were positive for glucosuria on detailed examination. Oral glucose tolerance test (OGTT) was also used to evaluate glucose intolerance. RESULTS: One hundred and two schoolchildren (29.7%) were diagnosed with diabetes, whereas RG was identified in 246 (70.3%) with normal glucose metabolism. In regard to the characteristics of RG, the percentage of boys was 50.3%, and the mean age at diagnosis was 11.2 ± 2.4 years. Twenty-eight children (11.4%) were overweight (body mass index standard deviation score [BMI-SDS] > +2.0 SD), whereas five (2.0%) were underweight (BMI-SDS < -2.0 SD). First-degree family history was suspected in 176 cases (71.5%). All RG subjects had normal glucose tolerance in the absence of insulin resistance and decreased insulin secretion (homeostasis model assessment for ß-cell function, 78.8 ± 59.5%) on OGTT. CONCLUSIONS: RG is not rare in Japanese schoolchildren with glucosuria. This disorder seems to have a strong genetic background, and to involve less growth retardation and weight loss than expected despite continuous excretion of glucose in urine.