Neonatal onset diabetes mellitus: clinical analysis of 21 cases / 中国新生儿科杂志

Objective:To study the clinical characteristics of neonatal onset of diabetes mellitus.Methods:Neonatal onset diabetes mellitus infants admitted to Children's Hospital of Fudan University from January 2003 to December 2020 were selected for retrospective analysis. All clinical characteristics including the basic conditions, family history, clinical manifestations, laboratory examination, diagnosis and treatment were recorded and analyzed.Results:There were 21 cases of diabetes mellitus diagnosed during neonatal period, including 13 males and 8 females. There were 16 term infants and 5 premature infants with gestational age between 34 weeks and 40 weeks. The birth weight ranged from 1 420 g to 3 450 g, including 14 low birth weight infants, 2 very low birth weight infants and 13 small for gestational age infants. Four infants had family history of diabetes. All diabetic infants with onset time within 28 days after birth included 10 cases within 10 days, 4 cases between 11 days and 20 days, 7 cases between 21 days and 28 days. Hyperglycemia was the main feature of 21 infants, and their blood glucose was ≥11.1 mmol/L for many times, with a maximum of 41.98 mmol/L. Only 2 cases had ketoacidosis and 8 cases were complicated with infections. Genetic testing was performed in 6 neonates,2 cases of ABCC8 gene pathogenic variant, 1 case of KCNJ11 and 1 case of INS pathogenic variant, and 2 cases of negative results. Insulin was mainly used in the initial stage of treatment, and then orally glibenclamide was taken in 9 infants. After treatment, 15 patients had stable blood glucose and were discharged with medication. 5 infants were withdrawn the treatment and discharged, and 1 infant combined with other serious illness died after giving up the treatment by the parents.Conclusions:When diabetes is diagnosed during the neonatal period, it is helpful to choose the appropriate treatment and get good results.

Report of five cases of protein-sensitive hypoglycemia with literature review / 中华内分泌代谢杂志

Objective To summarize the clinical feature,gene mutations,diagnosis,treatment,and follow-up data of protein-sensitive hypoglycemia,so as to improve the clinical understanding of the disease.Methods Five patients were diagnosed with protein-sensitive hypoglycemia during June in 2015 and December in 2017 from the Department of Pediatric Endocrinology and Inherited Metabolic Diseases,Children's Hospital of Fudan University.Clinical data of 5 cases were summarized,including clinical manifestations,findings of protein sensitivity test,therapy effect and prognosis.The endocrine and metabolic panel was used to investigate the genetic cause of four patients.Related literatures of protein-sensitive hypoglycemia were reviewed,and the phenotypes,genotypes,and therapy effects were summarized.Results Among the 5 patients diagnosed with positive results of protein-sensitive hypoglycemia,three were found to harbor glutamate dehydrogenase 1 (GLUD 1) mutations (c.965G ＞ A,p.R322H:2 cases;c.943C ＞T,p.H315Y:1 case),and another one had complex heterozygous mutations in L-3-hydroxyacyl-CoA dehydrogenase (HADH,c.29G ＞ C,p.R10P;c.89T＞ A,p.V30E).5 patients were euglycemia without any medical support after low protein diet.In 18 literatures retrieved and this study,there were totally 161 cases of protein-sensitive hypoglycemia (149 cases with GLUD1 mutations and 10 cases with HADH mutations).Conclusions When a child was admitted because of hypoglycemia,the diagnosis of protein-sensitive hypoglycemia should be suspected if he or she also had postprandial hypoglycemia,with or without hyperammonemia.Protein sensitivity test is helpful for us to make the diagnosis of protein-sensitive hypoglycemia.

Novel heterozygous mutation of the IL2RA gene in one Chinese girl with immunodeficiency 41 with lymphoproliferation and autoimmunity and diabetes mellitus, insulin-dependent 10: One case report and literature review / 中华内分泌代谢杂志

Objective To report a case of immunodeficiency 41 with lymphoproliferation and autoimmunity (IMD41) and type 10 insulin-dependent diabetes mellitus(IDDM10), caused by mutations of the interleukin 2 receptor α(IL2RA)gene.Methods Clinical symptoms were colleted,while IL2RA gene was sequenced.Results Here we reported a girl of 7 years and 6 months old who came to our hospital presented with lymphadenovarix for 5 years,debilitation for 2 months and alternation of hyperglycemia and hypoglycemia for 20 days. She was subsequently diagnosed with fungal pneumonia and ANCA-associated vasculitis. All exons of IL2RA gene were sequenced. c.340C>T(p.Q114X,paternal,novel mutation),c.64G>A(p.E22X,maternal) were detected. After treatments of dihydrocortisone,voriconazole combined with diabetic diet plus raw cornstarch, the pulmonary lesions reduced, autoantibodies disappeared and the blood glucose returned to normal. Literature review suggested that totally 5 IL2RA gene mutation patients were reported, the major clinical features were recurrent infection(infection of lung, skin, gastrointestinal tract) and immune abnormalities ( such as lymph node disease, autoimmune disease, hepatosplenomegaly,and diabetes mellitus). Conclusion In cases of atypical clinical symptoms, whole exon sequencing helps early diagnosis.

Feasibility of domestic 18F-DOPA PET/CT scanning in the differential diagnosis of pancreatic lesions in children with hyperinsulinemic hypoglycemia / 中华儿科杂志

Objective@#To study the feasibility of 18F-fluoro-L-dihydroxyphenylalanine positron emission tomography/Computed tomography (18F-DOPA PET/CT) scanning in the localization and differential diagnosing of focal versus diffuse form of pancreas lesions in patients with hyperinsulinemic hypoglycemia (HH).@*Method@#Twenty-four patients were diagnosed with HH between January, 2016 and February, 2017 in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children′s Hospital of Fudan University using an integrated clinical and biochemical diagnostic protocol, domestic 18F-DOPA PET/CT imaging technique were applied after MRI and ultrasound failed to detect pancreas lesions. Pancreas 18F-DOPA standardized uptake values (SUV) were measured, and pancreas′ lesions were dually analyzed via visual method and pancreas percentage SUV method. Among these patients, 9 patients received surgical pancreatic lesion resections, the correlations among surgical outcomes, histopathological findings and 18F-DOPA PET/CT scan results were analyzed.@*Result@#Seven patients were detected with focal form of pancreas lesions, the mean peak of SUV was 4.7±1.7(2.6-7.1), and 17 patients were found to have diffuse form lesions after 18F-DOPA-PET/CT scanning. Among the 24 cases, 9 patients (7 showed focal and 2 showed diffuse 18F-DOPA PET/CT pancreatic uptake)were euglycemic without any medical support after surgery; the resected pancreatic tissue histopathological results were consistent with that of PET/CT imaging. Only one patient, who responded to medical treatment before surgery, had temporary hyperglycemia after operation.@*Conclusion@#Domestic 18F-DOPA PET/CT could successfully locate and differentiate the pancreatic lesions and thus improve the success of surgery.

Progress of diagnosis and clinical management of congenital adrenal hyperplasia / 中华实用儿科临床杂志

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders.Clinical manifestations can be hermaphroditism,pseudo-precocious puberty or acute infant adrenal crisis.The wide range of CAH symptom spectrums may lead to miss or misdiagnosis in those who had atypical clinical features.The common forms of CAH are caused by deficiency in 21-hydroxylase enzymes,11 β-hydroxylase,3β-steroid dehydrogenase,17α-hydroxylase and so on,while the most common form of CAH is 21-Hydroxylase deficiency (＞ 90％).The basic principal clinical management of CAH is lifelong therapy using corticosteroids.This paper review and summarize the recent progress on the diagnosis,principles of treatment and long-term prognosis of CAH.

A proposal for the cutoff point of waist-to-height for the diagnosis of metabolic syndrome in children and adolescents in six areas of China / 中华流行病学杂志

<p><b>OBJECTIVE</b>This study aimed to determine the optimal cutoff point of Waist-to-height (WHtR) for the diagnosis of metabolic syndrome (MS) in children and adolescents in six areas of China.</p><p><b>METHODS</b>Ninety thousand two hundred and eighty four children aged 6 to 15 years old from 6 areas, including Beijing, Tianjin, Zhejiang, Shanghai, Chongqing and Nanning in China, were surveyed in a random cluster sample. Receiver operating characteristic (ROC) curve analysis was employed to determine the optimal cutoff values of WHtR for detecting the children and adolescents with two or more risk factors of MS.</p><p><b>RESULTS</b>The optimal WHtR cutoff values derived from the ROC analysis was 85(th) and 80(th) percentiles in males and females, with 6-15 years of age, respectively. The sensitivity and specificity under these cutoff values were 35.78% and 85.41% in males and 49.21% and 79.87% in females, for 6-9 years of age, while the sensitivity and specificity were 49.60% and 85.90% in males and 47.01% and 80.07% in females for 10-15 years of age. The areas under the ROC curves (AUCs) for WHtR 85(th) percentile were 0.61 and 0.64 in males and females for 6-9 years of age, and 0.68 and 0.63 in males and females for 10-15 years of age. The AUCs for WHtR 85(th) percentile in both genders were significantly larger than that for WHtR 90(th) percentile for 10-15 years of age.</p><p><b>CONCLUSION</b>Our findings indicated that the 85(th) percentile of WHtR (0.48 in both genders for 6-9 years of age, 0.48 in males and 0.46 in females for 10-15 years of age) might be an appropriate cutoff to predict the children and adolescents with two or more risk factors.</p>

Epidemiologic study on current pubertal development in Chinese school-aged children / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To survey the current status of pubertal development of Chinese children and to compare the precocious puberty prevalence of different regions.</p><p><b>METHODS</b>A cross-sectional epidemiological study was conducted on 18 707 children and adolescents aged 6≊18 y with male/female ratio of 9 812/8 895 from 6 representative geographical areas in China, including Beijing, Tianjin, Hangzhou, Shanghai, Chongqing and Nanning. The height, weight, waist circumference (WC), hip circumference(HC) and sexual maturation states (Tanner stages: breast stages for girls and testicular volume for boys) of children and adolescents were measured. Probit analysis was used to calculate the median age and 95% confidence interval (CI) for onset of breast and testicular development. The prevalence of precocious puberty of different regions and BMI, waist circumference of different groups were compared.</p><p><b>RESULTS</b>Breast development before 8 y was observed in 2.91% of girls, and testicular volume 4 ml or more before 9 y was observed in 1.74% of boys. The median age of onset of Tanner stages 2 for breast development in girls was 9.69 y (95% CI: 9.63≊ 9.75); the median age of onset of puberty as indicated by Tanner stages 2 for testicular development in boys was 11.25 y (95%CI:11.19≊ 11.30). The prevalence of precocious puberty (43 girls and 37 boys) was 0.43% (80/18 707). The prevalence of precocious puberty in northern region was higher than that in southwest region (0.736% compared with 0.282% P<0.05). There was no difference in onset age of precocious puberty in girls among three regions; but the onset age of precocious puberty in boys was earlier in east China [(7.4±0.28)y]. The SD values of BMI and waist-to-hip ratio (W/H) in precocious puberty children were higher than those in the peer normal children. There was no difference in BMI,waist circumference and waist-to-hip ratio in the precocious puberty children among different regions.</p><p><b>CONCLUSION</b>The current diagnostic criteria of precocious puberty are suitable for the children in the survey areas. The prevalence and the onset age of precocious puberty are various in different regions. A positive association between obesity and precocious puberty is found both in boys and girls.</p>

Genetic analysis of neonatal diabetes mellitus and its influence on treatment outcome / 中华内分泌代谢杂志

Fourteen neonatal diabetes mellitus(NDM)patients were recruited. 9 patients were treated with glyburide and the other 5 with insulin. ABCC8, KCNJ11, and INS genes were sequenced in 6 of them. Gene mutations were found in 2, 1, and 1 cases in these genes, respectively. One case with 6q24 hypomethylation and another without known mutation were also found. 8 out of 9 patients treated with glyburide reached euglycemia(88.9%). The other 5 patients with insulin therapy either died or lost contact. The results suggest that glyburide therapy is effective in neonatal diabetes mellitus, while insulin therapy may contribute to poor compliance.

Effect of human growth hormone antagonist on diabetic nephropathy in mice / 中华内分泌代谢杂志

Objective To investigate the effect of human growth hormone antagonist (GHA) on diabetic nephropathy in mice. Methods Thirty nine C57BL male mice were divided into five groups: normal control, diabetic control, two GHA diabetic mice groups, human growth hormone (hGH) diabetic group. Diabetic mice were induced with Streptozotocin. hGH, GHA1 〔del(1 4), G120R, K168A, E174A, C182S, del(186 191) Cys 1〕 and GHA2 〔H21A, G120R, E174A〕, were respectively administered subcutaneously to diabetic mice for eleven weeks, the effects of them on body weight, urinary protein excretion and renal morphology in mice of all groups were observed. Results All diabetic mice showed growth retardation including hGH and GH antagonist groups when comparing with their nondiabetic mice. The results of kidney histology showed a significant increase in glomerular area 〔hGH:(4289?798)?m 2, DM:(4226?894)?m 2,GHA1:(3511?717)?m 2, GHA2:(3428?919)?m 2, Normal control:(3399?573)?m 2〕 and cell proliferation (hGH:37.4?5.5, DM:34.5?6.4, GHA1:31.1?6.5, GHA2:29.2?6.5, Normal control:29.0?6.0) in hGH and DM control groups compared with two GH antagonist groups and normal control group, but the expansion of mesangial area with increased extracellualar matrix existed in all diabetic mice, no significant difference was observed among diabetic groups. No statistical difference was found among diabetic groups in urinary protein excretion. Conclusion hGH may aggravate glomerular hypertrophy and mesangial cell proliferation in diabetic mice, and hGH antagonists are effective in preventing diabetic mice glomerular hypertrophy, mesangial cell proliferation and maintaining integrity of kidney normal morphology in diabetic mice.