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1.
Endocr J ; 70(4): 385-391, 2023 Apr 28.
Article in English | MEDLINE | ID: mdl-36696992

ABSTRACT

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.


Subject(s)
Autoantibodies , Diabetes Mellitus, Type 1 , Glutamate Decarboxylase , Insulin , Insulinoma , Humans , Diabetes Mellitus, Type 1/drug therapy , Male , Female , Child , Adolescent , Glycated Hemoglobin , Insulinoma/drug therapy , C-Peptide/blood , Insulin/therapeutic use
2.
Endocr J ; 70(7): 677-685, 2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37019657

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Type 1 , Hypoglycemia , Humans , Child , Blood Glucose , Blood Glucose Self-Monitoring , Hypoglycemic Agents/adverse effects , East Asian People , Hypoglycemia/chemically induced , Hypoglycemia/prevention & control , Insulin/adverse effects , Insulin Infusion Systems/adverse effects
3.
Pediatr Int ; 63(2): 154-159, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32744360

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Type 1 , Hypoglycemia , Adolescent , Blood Glucose , Blood Glucose Self-Monitoring , Child , Glucose , Humans
4.
Endocr J ; 67(10): 1055-1062, 2020 Oct 28.
Article in English | MEDLINE | ID: mdl-32565500

ABSTRACT

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.


Subject(s)
Blood Glucose Self-Monitoring , Blood Glucose/metabolism , Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Monitoring, Ambulatory , Adolescent , Child , Consensus , Diabetes Mellitus, Type 1/metabolism , Female , Glycated Hemoglobin , Humans , Infusion Pumps, Implantable , Insulin Infusion Systems , Japan , Male , Practice Guidelines as Topic
5.
Pediatr Diabetes ; 19(8): 1385-1392, 2018 12.
Article in English | MEDLINE | ID: mdl-30101568

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Schools , Students/statistics & numerical data , Urban Population , Adolescent , Child , Female , Humans , Incidence , Male , Retrospective Studies , Schools/statistics & numerical data , Schools/trends , Tokyo/epidemiology , Urban Population/statistics & numerical data , Urban Population/trends
6.
Pediatr Int ; 60(1): 35-40, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29110414

ABSTRACT

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.


Subject(s)
Glucose Intolerance/diagnosis , Glycosuria, Renal/diagnosis , Child , Female , Glucose Intolerance/epidemiology , Glucose Intolerance/urine , Glucose Tolerance Test , Glycosuria, Renal/epidemiology , Glycosuria, Renal/urine , Humans , Japan/epidemiology , Male , Mass Screening
7.
Endocr J ; 64(2): 133-140, 2017 Feb 27.
Article in English | MEDLINE | ID: mdl-27746408

ABSTRACT

This study implemented a randomized crossover design to evaluate the efficacy and safety of switching from insulin glargine (IGlar) to insulin degludec (IDeg) in 18 children (11 males, 7 females; age 11.0 ± 0.5 years) with type 1 diabetes. All subjects had previously used IGlar once daily at bedtime. We compared fasting plasma glucose (FPG) and HbA1c levels, frequencies of overall and nocturnal (2200 h - 0659 h) hypoglycemia, and basal insulin dose at the baseline with those measured during a 24-week period during which IGlar or IDeg was administered in combination with pre-meal rapid acting insulin analogues. IDeg was initially given at the same dose as IGlar but was subsequently titrated to achieve FPG levels of 90-140 mg/dL. There were no significant changes in FPG and HbA1c levels from the baseline during the 24-week study period with IGlar or IDeg. The daily basal insulin dose did not significantly differ with IGlar or IDeg. Although the frequencies of overall hypoglycemia were similar, nocturnal hypoglycemia significantly decreased at 12 and 24 weeks from the baseline with IDeg use (2 ± 0.4 vs. 0 ± 0.3, 0 ± 0.5 episodes/month, both P <0.05), whereas no significant change in the frequency of nocturnal hypoglycemia was observed with IGlar. No severe hypoglycemia occurred during the study period with either basal insulin analogues. These results suggest that IDeg, injected once at bedtime, may provide similar glycemic control as IGlar while better reducing the risk of nocturnal hypoglycemia in children with type 1 diabetes.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Drug Substitution , Hypoglycemic Agents/therapeutic use , Insulin Glargine/therapeutic use , Insulin, Long-Acting/therapeutic use , Adolescent , Blood Glucose/drug effects , Blood Glucose/metabolism , Child , Cross-Over Studies , Diabetes Mellitus, Type 1/epidemiology , Drug Substitution/adverse effects , Female , Humans , Hypoglycemia/blood , Hypoglycemia/chemically induced , Hypoglycemia/epidemiology , Incidence , Male , Treatment Outcome
8.
Pediatr Int ; 59(5): 647-649, 2017 May.
Article in English | MEDLINE | ID: mdl-28544684

ABSTRACT

We evaluated the efficacy and safety of insulin glulisine (GLU) used for continuous s.c. insulin infusion (CSII) in 20 children with type 1 diabetes after 1 year of GLU treatment. There were no significant differences in mean plasma glucose before breakfast and before dinner between before and after using GLU, but the levels after breakfast and after dinner significantly improved, from 192.5 ± 31.7 to 162.0 ± 27.3 mg/dL for breakfast, and from 191.1 ± 33.3 to 161.1 ± 24.5 mg/dL for dinner (P < 0.01). Mean hemoglobin A1c significantly decreased (from 8.0 ± 0.8 to 7.7 ± 0.8%, P < 0.05), and the mean frequency of hypoglycemia significantly reduced after using GLU (from 8.3 ± 4.9 to 6.0 ± 3.4/month, P < 0.05). In conclusion, the use of GLU rather than other rapid-acting analogues for CSII might be an effective treatment option in children with type 1 diabetes.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin/analogs & derivatives , Child , Child, Preschool , Drug Administration Schedule , Female , Humans , Hypoglycemic Agents/therapeutic use , Injections, Subcutaneous , Insulin/administration & dosage , Insulin/therapeutic use , Male , Treatment Outcome
9.
Clin Pediatr Endocrinol ; 33(3): 113-123, 2024.
Article in English | MEDLINE | ID: mdl-38993716

ABSTRACT

This study aimed to examine the clinical characteristics of young children diagnosed with maturity-onset diabetes (MODY) using urine glucose screening at schools. The study participants were 70 non-obese children who were clinically diagnosed with type 2 diabetes through urine glucose screening at schools in Tokyo between 1974 and 2020. Of these children, 55 underwent genetic testing, and 21 were finally diagnosed with MODY: MODY2 in eight, MODY3 in eight, MODY1 in four and MODY5 in one. A family history of diabetes was found in 76.2% of the patients. Fasting plasma glucose levels did not differ between the different MODY subtypes, while patients with MODY 3, 1, and 5 had significantly higher levels of glycosylated hemoglobin and 2-hour glucose in an oral glucose tolerance test than those with MODY2. In contrast, most patients exhibit mild insulin resistance and sustained ß-cell function. In the initial treatment, all patients with MODY2 were well controlled with diet and exercise, whereas the majority of those with MODY3, 1, and 5 required pharmacological treatment within one month of diagnosis. In conclusion, urine glucose screening in schools appears to be one of the best opportunities for early detection of the disease and providing appropriate treatment to patients.

10.
J Diabetes Investig ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39230367

ABSTRACT

AIMS/INTRODUCTION: Coefficient of variation (CV) is an indicator for glucose variability in continuous glucose monitoring (CGM), and the target threshold of %CV in type 1 diabetes is proposed to be ≤36%. This study aimed to evaluate the clinical significance of CV in children and adolescents with type 1 diabetes. MATERIALS AND METHODS: Participants included 66 children with type 1 diabetes. A total of 48 participants were treated with multiple daily injections of insulin, and 18 with continues subcutaneous insulin infusion, using intermittently scanned CGM. The frequencies of the CGM metrics and glycosylated hemoglobin values were examined, and the significance of a threshold %CV of 36% was evaluated. RESULTS: The mean frequencies in time in range (TIR), time below range, %CV and the mean glycosylated hemoglobin value were 59.3 ± 16.1, 4.0 ± 3.5, 39.3 ± 6.2 and 7.3 ± 0.8%, respectively. The frequencies of participants who achieved a TIR >70% and a %CV of ≤36% were 24.1 and 27.3%, respectively. A total of 18 participants with a %CV of ≤36% had significantly higher TIR, lower time below range and lower glycosylated hemoglobin than the 48 with a %CV of >36% (72.6 ± 12.6 vs 52.4 ± 13.6, 2.4 ± 1.9 vs 4.6 ± 3.6, 6.9 ± 0.8 vs 7.4 ± 0.7%, respectively). CONCLUSIONS: Children and adolescents with type 1 diabetes using intermittently scanned CGM had difficulties in achieving the recommended targets of TIR and CV. However, the target %CV of ≤36% seems to be an appropriate indicator for assessing glycemic control and risk of hypoglycemia in pediatric patients with type 1 diabetes with any treatment.

11.
J Clin Endocrinol Metab ; 109(9): 2358-2365, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-38373250

ABSTRACT

CONTEXT: Thyroglobulin (Tg), encoded by TG, is essential for thyroid hormone synthesis. TG defects result in congenital hypothyroidism (CH). Most reported patients were born before the introduction of newborn screening (NBS). OBJECTIVE: We aimed to clarify the phenotypic features of patients with TG defects diagnosed and treated since the neonatal period. METHODS: We screened 1061 patients with CH for 13 CH-related genes and identified 30 patients with TG defects. One patient was diagnosed due to hypothyroidism-related symptoms and the rest were diagnosed via NBS. Patients were divided into 2 groups according to their genotypes, and clinical characteristics were compared. We evaluated the functionality of the 7 missense variants using HEK293 cells. RESULTS: Twenty-seven rare TG variants were detected, including 15 nonsense, 3 frameshift, 2 splice-site, and 7 missense variants. Patients were divided into 2 groups: 13 patients with biallelic truncating variants and 17 patients with monoallelic/biallelic missense variants. Patients with missense variants were more likely to develop thyroid enlargement with thyrotropin stimulation than patients with biallelic truncating variants. Patients with biallelic truncating variants invariably required full hormone replacement, whereas patients with missense variants required variable doses of levothyroxine. Loss of function of the 7 missense variants was confirmed in vitro. CONCLUSION: To our knowledge, this is the largest investigation on the clinical presentation of TG defects diagnosed in the neonatal period. Patients with missense variants showed relatively mild hypothyroidism with compensative goiter. Patients with only truncating variants showed minimal or no compensative goiter and required full hormone replacement.


Subject(s)
Congenital Hypothyroidism , Genetic Association Studies , Neonatal Screening , Thyroglobulin , Humans , Congenital Hypothyroidism/genetics , Congenital Hypothyroidism/diagnosis , Female , Male , Thyroglobulin/genetics , Infant, Newborn , Japan/epidemiology , Child, Preschool , Mutation, Missense , Infant , Child , Phenotype , Genotype , HEK293 Cells , East Asian People
12.
J Diabetes Investig ; 13(1): 185-190, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34143544

ABSTRACT

AIMS/INTRODUCTION: We examined the impact of scanning frequency with flash glucose monitoring on glycemic control in children and adolescents with type 1 diabetes. MATERIALS AND METHODS: The study included 85 patients, aged 14.0 ± 0.5 years, with type 1 diabetes. The median time in the target glucose range (TIR) and glycosylated hemoglobin (HbA1c) values were 50.0 ± 1.4% and 7.5 ± 0.1%, respectively. RESULTS: The median scanning frequency using flash glucose monitoring was 12.0 ± 0.4 times/day. Scanning frequency showed a significant positive correlation with TIR and an inverse correlation with HbA1c. Scanning frequency was identified to be the determinant of TIR and HbA1c by using multivariate analysis. The participants whose scanning frequency was <12 times/day were categorized as the low-frequency group (n = 40), and those who carried out the scanning >12 times/day were categorized as the high-frequency group (n = 45). Patients in the high-frequency group were more likely to be treated with insulin pumps compared with those in the low-frequency group; however, this difference was not significant (21.3 vs 5.3%, P = 0.073). The high-frequency group showed significantly greater TIR than the low-frequency group (57 ± 1.6 vs 42 ± 1.7%, P = 0.002). Furthermore, the high-frequency group showed significantly lower HbA1c levels than the low-frequency group (6.8 ± 0.1 vs 8.0 ± 0.1%, P < 0.001). CONCLUSIONS: These findings showed that patients with a higher scanning frequency had better glycemic control, with greater TIRs and lower HbA1c levels, compared with those with a lower scanning frequency. Scanning frequency of >12 times/day might contribute to better glycemic outcomes in real-world practice in children with type 1 diabetes.


Subject(s)
Blood Glucose Self-Monitoring/methods , Diabetes Mellitus, Type 1/blood , Glycemic Control/statistics & numerical data , Time Factors , Adolescent , Blood Glucose/analysis , Child , Child, Preschool , Diabetes Mellitus, Type 1/drug therapy , Female , Glycated Hemoglobin/analysis , Glycemic Control/methods , Humans , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Insulin Infusion Systems , Male , Multivariate Analysis
13.
J Diabetes Investig ; 13(10): 1745-1752, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35532954

ABSTRACT

AIMS/INTRODUCTION: The aim of the study was to compare two continuous glucose monitoring (CGM) systems, intermittently scanned CGM (isCGM) and real-time CGM (rtCGM), to determine which system achieved better glycemic control in pediatric patients. MATERIALS AND METHODS: We carried out a retrospective cohort study of children and adolescents with type 1 diabetes, and compared the time in range (70-180 mg/dL), time below range (<70 mg/dL) and time above range (>180 mg/dL), and estimated glycated hemoglobin levels between patients on isCGM and rtCGM. RESULTS: Of the 112 participants, 76 (67.9%) used isCGM and 36 (32.1%) used rtCGM for glycemic management. Patients on rtCGM had significantly greater time in range (57.7 ± 12.3% vs 52.3 ± 12.3%, P = 0.0368), and had significantly lower time below range (4.3 ± 2.7% vs 10.2% ± 5.4%, P < 0.001) than those on isCGM, but there was no significant difference in the time above range (37.4 ± 12.9% vs 38.0% ± 12.5%, P = 0.881) or the glycosylated hemoglobin A1c levels (7.4 ± 0.9% vs 7.5 ± 0.8%, P = 0.734) between the two groups. CONCLUSIONS: Pediatric patients with type 1 diabetes on rtCGM also showed more beneficial effects for increase of time in range, with a notable reduction of time below range compared with those on isCGM. Real-time CGM might provide better glycemic control than isCGM in children with type 1 diabetes.


Subject(s)
Diabetes Mellitus, Type 1 , Adolescent , Blood Glucose , Blood Glucose Self-Monitoring , Child , Diabetes Mellitus, Type 1/drug therapy , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/therapeutic use , Retrospective Studies
14.
Bioorg Med Chem ; 19(8): 2726-41, 2011 Apr 15.
Article in English | MEDLINE | ID: mdl-21435887

ABSTRACT

Nitrosamines are potent carcinogens and toxicants in the rat and potential genotoxins in humans. They are metabolically activated by hydroxylation at an α-carbon atom with respect to the nitrosoamino group, catalyzed by cytochrome P450. However, there has been little systematic investigation of the structure-mutagenic activity relationship of N-nitrosamines. Herein, we evaluated the mutagenicity of a series of 7-azabicyclo[2.2.1]heptane N-nitrosamines and related monocyclic nitrosamines by using the Ames assay. Our results show that the N-nitrosamine functionality embedded in the bicyclic 7-azabicylo[2.2.1]heptane structure lacks mutagenicity, that is, it is inert to α-hydroxylation, which is the trigger of mutagenic events. Further, the calculated α-C-H bond dissociation energies of the bicyclic nitrosamines are larger in magnitude than those of the corresponding monocyclic nitrosamines and N-nitrosodimethylamine by as much as 20-30 kcal/mol. These results are consistent with lower α-C-H bond reactivity of the bicyclic nitrosamines. Thus, the 7-azabicyclo[2.2.1]heptane structural motif may be useful for the design of nongenotoxic nitrosamine compounds with potential biological/medicinal applications.


Subject(s)
Bridged Bicyclo Compounds/pharmacology , Heptanes/pharmacology , Mutagens , Nitrosamines/antagonists & inhibitors , Animals , Humans , Hydroxylation , Mutagenicity Tests , Nitrosamines/toxicity , Rats , Structure-Activity Relationship
15.
Clin Pediatr Endocrinol ; 29(2): 63-68, 2020.
Article in English | MEDLINE | ID: mdl-32313374

ABSTRACT

We investigated the effect of zinc supplementation on growth and serum IGF-1 levels in 10 prepubertal Japanese children with idiopathic short statures, who had serum zinc levels of less than 80 µg/dL. Subjects were started on oral zinc supplementation at a dose of 25 mg once daily. In three children, the doses were increased by 50 mg once daily during the study period of 12 mo. The serum zinc levels rose in all subjects and reached a normal range (beyond 80 µg/dL). However, it was found that zinc supplementation did not promote growth. Although the mean IGF-1 standard deviations significantly increased, the majority did not reach the normal range. There were no significant adverse events other than mild gastrointestinal symptoms in 4 out of 10 subjects during the supplementation period. The most likely reason why growth was not promoted is that the zinc supplementation dosage was not enough to stimulate IGF-1 generation and subsequent growth velocity.

16.
J Diabetes Investig ; 11(4): 1010-1013, 2020 Jul.
Article in English | MEDLINE | ID: mdl-31960584

ABSTRACT

We present the case of a 12-year-old Japanese girl, who was positive for markers of both maturity-onset diabetes of the young and latent autoimmune diabetes in youth. She was initially diagnosed with maturity-onset diabetes of the young 1 based on the molecular analysis, and she later developed an autoimmune response, leading to ß-cell-associated antibody-positive diabetes. She was treated with incretin-associated drugs and maintained adequate glycemic control. Pathophysiologically, there was an overlap between the two different types of diabetes, because the hyperglycemia and ß-cell stress seen in non-autoimmune diabetes can cause ß-cell autoimmunity over time.


Subject(s)
Autoantibodies/immunology , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 2/immunology , Insulin-Secreting Cells/immunology , Child , Comorbidity , Female , Humans
17.
Horm Res Paediatr ; 93(4): 251-257, 2020.
Article in English | MEDLINE | ID: mdl-32950993

ABSTRACT

INTRODUCTION: We evaluated the frequencies of various glycemic markers derived from continuous glucose monitoring in Japanese children and adolescents with type 1 diabetes and assessed the significance of hypoglycemia duration. METHODS: We enrolled 85 children and adolescents (36 boys and 49 girls) with type 1 diabetes who used FreeStyle® Libre in the present study. Frequencies of blood glucose levels as time within target range (TIR; 70-180 mg/dL), time below target range (TBR; <70 mg/dL), time below extreme hypoglycemia range (TBER; <54 mg/dL), and time above range (TAR; >180 mg/dL) were assessed during a 3-month study period. Furthermore, we evaluated the intraday frequencies of TBR and TBER. RESULTS: The mean frequencies of TIR, TBR, and TAR were 52.7 ± 11.3%, 10.8 ± 5.4%, and 36.5 ± 10.8%, respectively, whereas the mean frequency of TBER was 1.1 ± 0.9% (0-3.0%); there was no clinical episode of severe hypoglycemia. The mean frequency of TBR was significantly greater in 0-6 h (16.9 ± 5.2%) than in 6-12 h (7.8 ± 2.9%) and 18-24 h (6.8 ± 4.8%; p < 0.01) time zones, respectively. DISCUSSION/CONCLUSION: We found similar TIR and comparatively higher TBR frequencies, particularly during sleep, than those that were previously reported. Possible reasons for the higher frequency of TBR include differences in the quality of insulin treatment and diabetes care between the present study and the European studies. The utilization of advanced technologies, such as a predictive low-glucose suspend-function pump or closed-loop therapy, can reduce the frequency of TBR, with a consequent increase in TIR frequency and comprehensive improvement in glycemic control.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 1 , Hypoglycemia , Insulin , Adolescent , Child , Child, Preschool , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Female , Humans , Hypoglycemia/blood , Hypoglycemia/drug therapy , Insulin/administration & dosage , Insulin/pharmacokinetics , Japan , Male
18.
J Diabetes Investig ; 10(5): 1382-1384, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30758915

ABSTRACT

We present the case of an 8-year-old girl with type 1 diabetes who developed severe allergic contact dermatitis by using FreeStyle® Libre. A patch test was carried out using a piece of the adhesive part of the sensor of the FreeStyle® Libre, and subsequently by using the potential contact allergens in the sensor, isobornyl acrylate. She reacted positively to the adhesive part of the sensor, and also reacted positively to isobornyl acrylate with three different concentrations, 0.1%, 0.05% and 0.01%, over 48-h, 72-h and 7-day periods. The FreeStyle® Libre is a useful and less invasive device that can be used for continuous glucose monitoring in patients with diabetes. In contrast to the remarkable advantages, allergic contact dermatitis caused by isobornyl acrylate in the adhesive part of FreeStyle® Libre is one of the potential adverse events.


Subject(s)
Acrylates/adverse effects , Blood Glucose Self-Monitoring/adverse effects , Camphanes/adverse effects , Dermatitis, Allergic Contact/etiology , Diabetes Mellitus, Type 1/blood , Blood Glucose Self-Monitoring/instrumentation , Child , Diabetes Mellitus, Type 1/drug therapy , Female , Humans , Hypoglycemic Agents/therapeutic use , Prognosis
19.
Diabetes Metab Syndr Obes ; 12: 2281-2288, 2019.
Article in English | MEDLINE | ID: mdl-31807041

ABSTRACT

PURPOSE: The aim was to investigate the characteristics of abdominal fat distribution in Japanese adolescents with type 2 diabetes mellitus. PATIENTS AND METHODS: Eighty-six Japanese adolescents with simple obesity or type 2 diabetes mellitus treated between 2002 and 2018 were included. The subjects were classified into the simple obesity group (SO group, n=38) and type 2 diabetes mellitus group (DM group, n=23) by matching average age and gender ratio. The metabolic parameters VFA, SFA, and V/S ratio were compared between the 2 groups. Multivariate logistic regression analysis was performed to identify clinical factors associated with type 2 diabetes mellitus. Linear regression analysis was performed between hemoglobin A1c (HbA1c) and visceral fat area (VFA), subcutaneous fat area (SFA), or VFA-to-SFA ratio (V/S ratio) among all enrolled subjects. Finally, correlation analyses were performed to determine the relationships between VFA, SFA, and V/S ratio and metabolic parameters of the DM group. For the metabolic parameters, serum lipids, alanine aminotransferase (ALT), and HbA1c were measured without fasting. The VFA and SFA at umbilical level were investigated using computed tomography. RESULTS: VFA and V/S ratio in DM group were higher than those in SO group (p=0.04 and p<0.01, respectively). SFA in DM group was lower than that in SO group (p<0.01). VFA and SFA, and non-high density lipoprotein (HDL) cholesterol were identified as being independently associated with type 2 diabetes mellitus (odds ratio, 1.05, 0.98, and 1.04, respectively, p<0.05). HbA1c was correlated with VFA and V/S ratio (p<0.01). In DM group, VFA and SFA were positively correlated with systolic blood pressure (p<0.01), ALT (p<0.05), total cholesterol (p<0.05), and non-HDL cholesterol (p<0.01); however, V/S ratio was not correlated. CONCLUSION: Abdominal fat distribution in Japanese adolescents with type 2 diabetes mellitus was different from those with simple obesity and might associate with glucose and lipid metabolism.

20.
Brain Dev ; 40(7): 592-595, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29606344

ABSTRACT

BACKGROUND: Neurological manifestations caused by hypoglycemia range from reversible focal deficits and transient encephalopathy to irreversible coma or death. Recently, high signal intensity lesions in the splenium of the corpus callosum on diffusion-weighted magnetic resonance imaging were reported in adults experiencing hypoglycemia. However, patients presenting with agraphia are rare. SUBJECT AND METHODS: We examined a 17-year-old left-handed female patient with type 1 diabetes who exhibited transient left agraphia with a reversible splenium lesion of the corpus callosum on diffusion-weighted imaging caused by hypoglycemia, which was improved with blood glucose management alone. CONCLUSION: This rare case indicates that agraphia, a sign of callosal disconnection syndrome, can result from a reversible splenial lesion of the corpus callosum caused by hypoglycemia.


Subject(s)
Agraphia/diagnostic imaging , Agraphia/etiology , Corpus Callosum/diagnostic imaging , Hypoglycemia/complications , Hypoglycemia/diagnostic imaging , Adolescent , Agraphia/physiopathology , Agraphia/therapy , Corpus Callosum/physiopathology , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/diagnostic imaging , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 1/therapy , Diffusion Magnetic Resonance Imaging , Female , Humans , Hypoglycemia/physiopathology , Hypoglycemia/therapy
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