Clinical and prognostic analysis of seven cases of neonatal congenital hyperinsulinemia / 中国小儿急救医学

Objective:To explore the clinical features, treatment, prognosis and genetic mutation in neonatal congenital hyperinsulinemia(CHI).Methods:Neonates with CHI admitted to the neonatal intensive care unit of Hebei Provincial Children′s Hospital from February 2017 to August 2020 were selected, and their clinical characteristics, diagnosis and treatment, prognosis and genetic mutation were retrospectively analyzed.Results:A total of seven neonates were enrolled.The average gestational age was(38.1±1.5)weeks with two cases gestational age<37 weeks.The mean birth weight was(3 608±906)g with three cases birth weight>4 000 g. The common clinical manifestations included lethargy, poor feeding, cyanosis, seizures, and tremble.Non-specific manifestations were observed in two premature infants, whose blood glucose were found very low during the routine monitoring at 1 hour and 3 hours after birth respectively.Among the seven cases, six cases needed high glucose infusion rate(GIR)[>10 mg/(kg·min)] to maintain the serum glucose at the normal level from the beginning.Only one case needed lower GIR[3-5 mg/(kg·min)] on admission while gradually increased to 8 mg/(kg·min) maximumly during hospitalization.All seven neonates were treated with diazoxide orally, and two cases(2/7) were effective, including one case who discontinued the drug at six months after birth with normal blood glucose level.The remaining five neonates(5/7) were diazoxide resistant due to mutations in the ABCC8 gene encoding the K ATP+ -channel of the pancreatic beta cell and then treated with octreotide.Two cases(2/5) of them were effective to octreotide and the other three cases(3/5) were both diazoxide and octreotide resistant.One case died after withdrawal from the treatment and the other one lost follow-up.The other five cases were followed up until now.Normal neurological development were found in three cases.Two cases were found with epilepsy and moderate developmental delay in language and social competence ability during the follow up.Mutations in ABCC8 were the most common in seven cases, of which six cases were heterozygous mutation of ABCC8 and one case was heterozygous mutation of GLUDI. Conclusion:The clinical manifestations of CHI are non-specific.The blood glucose level of the high-risk neonates should be timely monitored.Neonates who needs lower GIR[<8 mg/(kg·min)] at the early stage can not be completely excluded CHI.Some CHI cases may self-resolved after several months.Molecular diagnosis can identify the pathogenic genes, which is important to achieve accurate diagnosis and treatment, and thus improve the prognosis of patients with CHI.

Congenital Hyperinsulinemia of Infancy: Role of Molecular Testing in Management and Genetic Counseling

Congenital hyperinsulinemia (CHI) is a genetically and clinically heterogenous disorder. In addition to the standard care of management of the proband, genetic counseling regarding the risk of recurrence in the future siblings is an important part in the management of the disorder. The counseling needs identifcation of accurate etiology and is challenging due to the complexity of the molecular mechanisms of CHI. This case highlights the importance of molecular testing which not only helped in planning the management of the proband with CHI but also helped in providing genetic counseling for which the family had consulted the medical genetics department.

Mutations in K ATP channel genes and congenital hyperinsulinemic hypoglycemia / 国际儿科学杂志

Congenital hyperinsulinemic hypoglycemia(CHH)is a group of rare heterogeneous diseases with hypoglycemia as the main clinical manifestation caused by insulin imbalance and excessive secretion.It is the most common cause of persistent hypoglycemia in infants and children.Related gene mutations were detected in about 40% of patients, among which inactivating mutations in ABCC8 or KCNJ11 genes are the most common.Delay in diagnosis and improper treatment can cause permanent brain damage in infants and children with CHH.Therefore, early identification and correct diagnosis and treatment are important and essential to prevent brain damage in infants and children with CHH.This article reviews the molecular pathogenesis of CHH caused by K ATP gene inactivation mutations, the impact of ABCC8 or KCNJ11 gene mutations on the pathological types of pancreas, the severity of hypoglycemia and the choice of clinical treatment options in children with CHH, as well as the latest progress in clinical diagnosis and treatment of CHH, in order to improve clinicians′ awareness of CHH.

Progress on Correlation Between Type 2 Diabetes Mellitus and Malignant Tumors / 肿瘤防治研究

Type 2 diabetes mellitus and malignant tumors are two kinds of chronic diseases with tremendous impact on human health. Numerous epidemiological and clinical studies have shown that type 2 diabetes mellitus increases the risk of liver, pancreatic, endometrial, gallbladder, colorectal and breast cancers. Hyperglycemia can promote cancer cell proliferation, migration, invasion and immune escape through a variety of direct and indirect mechanisms. Insulin resistance and hyperinsulinemia can activate multiple signal transduction pathways through insulin/IGF-I signaling axis and promote tumorigenesis. Sustained chronic inflammatory responses can promote the development of cancer through DNA damage and pro-inflammatory factors. Gut microbiome dysbiosis is closely related to the occurrence of several gastrointestinal tumors. This paper reviews the progress on the correlation between type 2 diabetes mellitus and the progression of malignant tumors and the possible mechanisms.

Genetic variants in the SLC16A11 gene are associated with increased BMI and insulin levels in nondiabetic Chilean population

ABSTRACT Objective: To study the association of SLC16A11 gene variants with obesity and metabolic markers in nondiabetic Chilean adults. Materials and methods: This cross-sectional study included 263 non-diabetic adults. The genotype of the rs75493593 polymorphism of SLC16A11 gene was performed by real-time PCR. It's association with adiposity markers (body weight, BMI, waist circumference and fat mass percentage), metabolic markers (glucose, insulin, HOMAIR, leptin, total cholesterol, LDLc, HDLc, triglycerides, ALT, GGT and hsCRP) and blood pressure was analyzed by linear regression. Results: The minor allele (T) of the SLC16A11 gene (rs75493593) has a frequency of 29.7% among Chileans. Risk genotypes (GT and TT) were associated with a significant 1.49 mU/l increase in plasmatic insulin for each copy of the minor allele (95% CI: 0.12, 2.87, p < 0.05). This association remained significant after adjusting for socio-demographic variables, physical activity and smoking (1.36 mU/l, 95% CI: 0.16, 2.58 p < 0.05), but was lost when BMI was included as a confounding factor. Higher BMI was also significantly associated with polymorphic genotypes in SLC16A11, independent of socio-demographic variables. Conclusion: The minor allele of the SLC16A11 gene (T) is highly prevalent among Chileans and is associated with increased insulin and BMI in nondiabetic individuals. These findings suggest that the genetic variant in SLC16A11 is not only associated with type 2 diabetes as previously shown in Mexicans, but is also related to early metabolic alterations in healthy subjects that may lead to type 2 diabetes.

Correlation between intrahepatic triglyceride content quantified by proton magnetic resonance spectroscopy and glucose metabolism / 中华内科杂志

Objective:To investigate the correlation between intrahepatic triglyceride content (IHTC) and glucose metabolism in patients with non-alcoholic fatty liver disease (NAFLD) diagnosed by proton magnetic resonance spectroscopy ( 1H-MRS). Methods:A total of 239 subjects without diabetes mellitus were previously enrolled and underwent 1H-MRS scans. Anthropometric indexes including height, weight, waist and blood pressure, and laboratory findings as plasma glucose (PG), insulin (INS), C-peptide (CP), liver enzymes [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyl transpeptidase (GGT)] and lipid profiles were collected. According to IHTC levels, participants were divided into three groups: the non-NAFLD group (IHTC<5.56%), the mild NAFLD group (IHTC 5.56%-<33%), and the moderate and severe NAFLD group (IHTC ≥ 33%). The clinical characteristics of each group were analyzed, and the correlation between IHTC and glucose metabolism were assessed. Results:Compared with those in the non-NAFLD group, male proportion, waist, 120 min postprandial PG (PG120), CP, liver enzymes and total cholesterol (TC) levels were greater in the NAFLD group, whereas insulin sensitivity index-Cederholm (ISI-Cederholm) and high density lipoprotein cholesterol (HDL-C) levels were lower in the NAFLD groups. Subjects in the moderate and severe NAFLD group had higher levels of 120 min postprandial INS (INS120) and Stumvoll indexes, and lower ISI-Cederholm than those in the mild NAFLD group [80.37 (57.68, 112.70) mU/L vs.110.50(71.78, 172.80)mU/L, 1453(1178, 1798)vs.1737(1325, 2380), 358(297, 446) vs.441(318, 594), 2.27(2.01, 2.53) vs.2.06(1.81, 2.39), respectively, all P<0.05]. Correlation analyses showed that IHTC was significantly positively correlated with waist hip ratio (WHR), PG120, INS120, HOMA insulin resistance (HOMA-IR), Stumvoll 1st-insulin secretion, Stumvoll 2nd-insulin secretion, ALT, AST, GGT and TC ( r=0.197, 0.274, 0.334, 0.162, 0.199, 0.211, 0.406, 0.361, 0.215, and 0.196, respectively, all P<0.05), and negatively correlated with ISI-Cederholm and HDL-C ( r=-0.334, and-0.237, respectively, all P<0.05). Furthermore, a multiple linear stepwise regression analysis indicated that ISI-Cederholm (Standardized β =-0.298, P<0.001) and Stumvoll 1st insulin secretion (Standardized β = 0.164, P = 0.024) were independent factors of IHTC. Conclusions:Peripheral insulin resistance occurs in the early stage of NAFLD and becomes worse with the progression of the disease. IHTC was independently associated with insulin sensitivity and first-phase insulin secretion.

Effect of metformin use in pregnancy on pregnancy outcomes of women with polycystic ovary syndrome complicated with euglycemia and hyperinsulinemia / 中华内分泌代谢杂志

Objective:To explore the effect of metformin during pregnancy on pregnancy outcomes of women with polycystic ovary syndrome (PCOS) complicated with euglycemia and hyperinsulinemia.Methods:One hundred and thirty PCOS pregnant patients complicated with euglycemia and hyperinsulinemia admitted to the Second Affiliated Hospital of Chongqing Medical University from January 2017 to December 2019 were selected and divided into two groups, the treatment group was treated with metformin during pregnancy, and the control group was treated with lifestyle intervention. Pregnancy outcomes, pregnancy complications, delivery complications, first cesarean section rate, length, gestational age, weight, and blood glucose of the newborn were compared.Results:The incidence of early pregnancy loss (23.8% vs 6.0%, P=0.040), embryo damage(23.8% vs 4.5%, P=0.001), and premature rupture of membrane(21.3% vs 8.1%, P=0.047) in the treatment group were lower than those in the control group. There were no statistically significant differences in pregnancy complications, first cesarean section rate, length, weight, and blood glucose of the newborn and other adverse pregnancy outcomes ( P>0.05). Conclusion:Metformin therapy during pregnancy in PCOS patients can effectively reduce the incidence of early pregnancy loss, embryo damage , and premature rupture of membrane, improve pregnancy outcomes, and have no effect on the length, weight, and blood glucose of the newborn, with high safety and no obvious adverse events.

Mechanism of insulin resistance in obesity: a role of ATP / 医学前沿

Obesity increases the risk of type 2 diabetes through the induction of insulin resistance. The mechanism of insulin resistance has been extensively investigated for more than 60 years, but the essential pathogenic signal remains missing. Existing hypotheses include inflammation, mitochondrial dysfunction, hyperinsulinemia, hyperglucagonemia, glucotoxicity, and lipotoxicity. Drug discoveries based on these hypotheses are unsuccessful in the development of new medicines. In this review, multidisciplinary literature is integrated to evaluate ATP as a primary signal for insulin resistance. The ATP production is elevated in insulin-sensitive cells under obese conditions independent of energy demand, which we have named "mitochondrial overheating." Overheating occurs because of substrate oversupply to mitochondria, leading to extra ATP production. The ATP overproduction contributes to the systemic insulin resistance through several mechanisms, such as inhibition of AMPK, induction of mTOR, hyperinsulinemia, hyperglucagonemia, and mitochondrial dysfunction. Insulin resistance represents a feedback regulation of energy oversupply in cells to control mitochondrial overloading by substrates. Insulin resistance cuts down the substrate uptake to attenuate mitochondrial overloading. The downregulation of the mitochondrial overloading by medicines, bypass surgeries, calorie restriction, and physical exercise leads to insulin sensitization in patients. Therefore, ATP may represent the primary signal of insulin resistance in the cellular protective response to the substrate oversupply. The prevention of ATP overproduction represents a key strategy for insulin sensitization.

Research progress of insulin resistance and hyperinsulinemia promoting pancreatic cancer / 预防医学

@#Pancreatic cancer is a common digestive tract carcinoma. It is strongly occult and lack of early diagnostic indicators, and the patients have quite low survival rates. The pathogenesis of pancreatic cancer remains unclear. It has been reported that smoking, family history, diabetes mellitus and obesity are associated with the incidence of pancreatic cancer; moreover, type 2 diabetes mellitus (T2DM) often occur as a comorbidity. Insulin resistance and compensatory hyperinsulinemia are the main metabolic characteristics of T2DM, which play an important role in the development and progression of pancreatic cancer. The molecular mechanisms of insulin resistance and hyperinsulinemia promoting pancreatic cancer are reviewed in this paper, in order to provide the evidence for the prevention and treatment of pancreatic cancer.

Obesidade na infância e adolescência / Obesity in childhood and adolescence

A obesidade é uma doença crônica e multifatorial com sérias repercussões na saúde. O excesso de peso na infância aumenta o risco de obesidade na adolescência e na vida adulta. A obesidade é uma das principais causas de hipertensão arterial em crianças e adolescentes. No sexo feminino, os problemas ginecológicos relacionados com a obesidade incluem as desordens menstruais e a diminuição da fertilidade na adolescência e na vida adulta. O controle dessa patologia evita a sua evolução para formas crônicas e graves, que acarretaria novos transtornos e consequências para essas jovens. A mudança de hábitos alimentares e a realização de atividade física são a principal linha de tratamento. O tratamento medicamentoso é reservado para portadoras de obesidade grave que apresentam comorbidades associadas e que não respondem às mudanças do estilo de vida. (AU)

Obesity is a chronic and multifactorial disease with serious repercussions on health. Overweight in childhood increases the risk of obesity in adolescence and adulthood. Obesity is one of the main causes of high blood pressure in children and adolescents, among others. In women, gynecological problems related to obesity include menstrual disorders and decreased fertility in adolescence and adulthood. The control of this pathology prevents its evolution to chronic and severe forms that would cause new disorders and consequences for these young women. The main line of treatment is to change eating habits and encourage physical activity. Drug treatment is reserved for patients with severe obesity, who have associated comorbidities and who do not respond to changes in lifestyle.(AU)

Soluble insulin receptor and metabolic syndrome

The metabolic syndrome describes a group of signs that increase the likelihood for developing type 2 diabetes mellitus, cardiovascular diseases and some types of cancer. The action of insulin depends on its binding to membrane receptors on its target cells. We wonder if blood insulin could travel bound to proteins and if, in the presence of hyperinsulinemia, a soluble insulin receptor might be generated. We used young adult Wistar rats (which have no predisposition to obesity or diabetes), whose drinking water was added 20 % of sugar and that were fed a standard diet ad libitum for two and six months. They were compared with control rats under the same conditions, but that had running water for consumption. At two months, the rats developed central obesity, moderate hypertension, high triglyceride levels, hyperinsulinemia, glucose intolerance and insulin resistance, i.e., metabolic syndrome. Electrophoresis of the rats’ plasma proteins was performed, followed by Western Blot (WB) for insulin and for the outer portion of the insulin receptor. The bands corresponding to insulin and to the receptor external part were at the same molecular weight level, 25-fold higher than that of free insulin. We demonstrated that insulin, both in control animals and in those with hyperinsulinemia, travels bound to the receptor outer portion (ectodomain), which we called soluble insulin receptor, and that is released al higher amounts in response to plasma insulin increase; in rats with metabolic syndrome and hyperinsulinemia, plasma levels are much higher than in controls. Soluble insulin receptor increase in blood might be an early sign of metabolic syndrome.

Preventive Effects of Enicostemma littorale Blume Extract against Dexamethasone Induced Insulin Resistance in Wistar Rats.

Background: Insulin resistance is a pathological condition in which physiological levels of insulin produce only subnormal biological responses. In such instances, β cells of the pancreas produce more insulin but the cells in other body tissues are resistant to insulin leading to hyperinsulinemia, and subsequent hyperglycemia further results in metabolic syndrome. Aim and Objectives: This study was aimed to evaluate the hydro-alcoholic extract of Enicostemma littorale (ELE) in preventing dexamethasone 8mg/kg induced insulin resistance. Materials and Methods: Thirty-six male Wistar rats were categorized into Group I plain control that received distilled water, Group II dexa control that received dexamethasone 8mg/kg. Group III and Group IV received dexamethasone 8 mg/kg along with Metformin 500 mg/kg and 1g/kg respectively. Group V and VI received dexamethasone along with ELE 2.5 g/kg and 3.5 g/kg respectively. At the end, the fasting and repeated blood samples were collected at 30, 60 and 120 min for the esti tion of post Intraperitoneal Glucose Tolerance Test (IPGTT), serum glucose and insulin. Data were utilized for the assessment of the homeostasis model of assessment for insulin resistance and sensitivity, Gutt, Matsuda, fasting glucose to insulin ratio and disposition indices. Results: All insulin sensitivity indices were worsened in dexa control group as compared to plain control (P<0.05). ELE 3.5 g/kg significantly lowered fasting glucose and insulin compared to metformin 1 g/kg (P<0.05), and significantly prevented the fall of insulin sensitivity indices compared to dexa control group (P<0.05). Glycosuria and ketonuria were also absent in ELE 3.5 g/kg group. Conclusion: ELE 3.5 g/kg showed efficacy in preventing insulin resistance evidenced by improved insulin sensitivity indices comparable with that of metformin 1 mg/kg.

Effectiveness of Aqueous Extract of Fenugreek Seeds and Flaxseed on Polycystic ‎Ovarian Syndrome in Female Rats

Polycystic ovarian syndrome (PCOS) is a disease impacting adult female in which its main features are hyperandrogenism, insulinresistance (IR), hyperinsulinemia, which enhances the probability of getting type 2 diabetes and cardiovascular disease. This study aimed toestimate the antidiabetic effect of fenugreek and the anti-androgenic effect of flaxseed and use the combination of both to treat polycysticovarian syndrome in female rats. Forty Wistar rats were divided into five groups each contained eight rats, Group I: normal control, therats in Group II-V received Estradiol valerate (4mg/kg in 0.4ml Sesame oil i.p.). Then, Group II served as PCOS control. The rats in GroupIII were given fenugreek aqueous extract (100 mg/kg), Group IV received flaxseed aqueous extract (300 ml/kg) and Group V administered acombination of both extracts, for 60 consecutive days after PCOS conformation, extracts were given orally. The results showed that theEstradiol Valerate induced a dignified increase in glucose, insulin, insulin resistance, lipid profile, aspartate aminotransferase (AST),alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (GGT), and body weight in comparison to control. Moreover, anoutstanding rise in serum LH, FSH, testosterone and a decrease in progesterone level, with no change in estradiol was detected.Furthermore, a significant rise in lipid peroxidation accompanied by an insignificant increase in nitric oxide, a significant decline insuperoxide dismutase, catalase, and glutathione reductase activities in ovarian homogenates were also noted. Supplementation of fenugreekand flaxseed significantly attenuated these parameters. The results showed the beneficial effect of fenugreek and flaxseed in improving theimpairment of IR and hyperandrogenism with corresponding disrupted parameters in polycystic ovarian syndrome.

Acanthosis nigricans as a clinical marker of insulin resistance among overweight adolescents

PURPOSE: Acanthosis nigricans (AN) is a hyperpigmented dermatosis associated with obesity and insulin resistance (IR). There is no consensus whether AN extension scoring offers added value to the clinical estimation of IR. In this study we aimed to assess and score AN using both a short and an extended version of the scale proposed by Burke et al. and analyze the relationships of both versions with hyperinsulinemia and IR. METHODS: We analyzed data from 139 overweight adolescents (body mass index ≥85th percentile) aged 12–18 with (n=67) or without (n=72) AN who were followed at a pediatric obesity clinic. RESULTS: Adolescents with AN had higher levels of insulin (d=0.56, P=0.003) and HOMA-IR (d=0.55, P=0.003) compared to those without. Neither the short nor the extended versions of AN scores explained either hyperinsulinemia (β=1.10, P=0.316; β=1.15, P=0.251) or IR (β=1.07, P=0.422; β=1.10, P=0.374). The presence of AN alone predicted hyperinsulinemia and the presence of IR in 7.3% (β=2.68, P=0.008) and 7.1% (β=2.59, P=0.009) of adolescents, respectively. CONCLUSIONS: Screening for AN at the neck and axilla is a noninvasive and cost-effective way to identify asymptomatic overweight adolescents with or at risk of developing IR.

Molecular Basis of Pathogenesis of Diabetes Mellitus Type 2- a New Perspective

Decreased insulin secretion due to beta cell dysfunction of the pancreas and defective utilization of insulin due to insulin resistance / Hyperinsulinemia are two important issues in the pathogenesis of DM2. There are many explanations in the literature to account for these two observed phenomena and their interrelationship. DM2 is believed to occur due to a complex interplay of environmental andBehavioural factors in genetically predisposed persons. Among the prominent theories explaining the pathogenesis of DM2, the viscera- Portal hypothesis, the Ectopic fat hypothesis and the adipose tissue as an endocrinal gland are prominent. Besides, the role played by oxidative stress, metabolic stress, mitochondrial dysfunction, endoplasmic reticulum stress, etc. are also advanced. It is felt that basic to and at the core of all the observed facts, is the shift of energy metabolism from normal glycolysis to B- oxidation of fats. Hence, how B - oxidation prevails over glycolysis is the fundamental issue to be addressed together with its interrelationships with insulin resistance, as to which is the cause and which is the effect. At the molecular level, an attempt to find answers to the above questions is made in this paper.To this extent, the Randle fatty acid cycle (Substrate competition theory of Randle) is suitably modified and applied to explain the switch of Energy metabolisms in DM2 .Defective disulfide bond formation of the insulin receptor which makes it physiologically ineffective, is suggested as the cause of the insulin resistance where as the prevailing molecular mechanisms stress on post-receptor signaling defect. The cause and effect of both are discussed. This line is considered to be a departure from traditional approaches broached above and briefly outlined in this article.

The combination of canagliflozin and omega-3 fatty acid ameliorates insulin resistance and cardiac biomarkers via modulation of inflammatory cytokines in type 2 diabetic rats

The present study was carried out with the hypothesis that combination of canagliflozin and omega-3 fatty acid may have potential effect on insulin level, insulin resistance, cardiac biomarkers, inflammatory cytokines and histological studies in type 2 diabetes mellitus (DM). Type 2 DM was induced by injecting nicotinamide (120 mg/kg, i.p.) 15 min before STZ (60 mg/kg) injection. Canagliflozin (5 and 10 mg/kg) and omega-3 fatty acid (300 mg/kg) were given for 28 days after confirmation of diabetes. Biochemical estimations revealed elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines in diabetic group. Daily dosing of alone canagliflozin and omega-3 fatty acid slightly reduced elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines (IL-1β, IL-2, and TNFα), whereas canagliflozin and omega-3 fatty acid combination has reduced these biochemical parameters significantly when compared with diabetic group. Similarly in diabetic group the levels of cardiac biomarkers such as lipid profile, LDH, CKMB and troponin were significantly increased. Elevated levels of cardiac biomarkers were significantly reduced after daily dosing of alone canagliflozin and omega-3 fatty acid. Canagliflozin and omega-3 fatty acid combination has offered better improvement in cardiac biomarkers compared to alone canagliflozin and omega-3 fatty acid. Histopathological analysis also supported the above hypothesis that combination therapy (canagliflozin and omega-3 fatty acid) offered better protection against degenerative changes in β-cells of pancreas as compared to alone treatment with these drugs. Thus the present study revealed that canagliflozin and omega-3 fatty acid can be used as potential combination therapy in type 2 DM along with cardiac complication.

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.

Metformin improves glucose metabolism and serum levels of lipoprotein derived hormones in obese children with hyperinsulinemia / 中国生化药物杂志

Objective To explore metformin improves hyperinsulinemia in obese children, glucose metabolism, serum lipid derived hormone levels. Methods 40 cases of healthy children were selected and included in the control group, 40 cases of mild, moderate and severe obese children in the obese group, moderately obese group, obese group given category; metformin in obese children orally for 3 months, then in each group of body mass index (BMI), the learning situation of adipose derived hormones, blood glucose levels were detected and compared. Results Compared the condition of blood glucose metabolism and body weight obviously, obesity group and control group before treatment there are very significant differences after treatment, the obese group appeared to be improved, indicates that the difference is obvious(P<0.05). Compare the hormone levels of serum leptin and adiponectin are visible in before the treatment and health examination Significant differences after the treatment showed some improvement, but the resistin in the treatment had no obvious improvement. Conclusion The application of metformin improves hyperinsulinemia in obese children with sugar metabolism, visible analysis of serum adipose derived hormones, the patients with improvement of glucose metabolism has a positive effect, while improving the serum hormone level, reduce patient weight (BMI), so it is worthy of clinical use.

Hyperinsulinemic Hypoglycemia of Infancy due to Novel HADH Mutation in Two Siblings.

Background: Hyperinsulinemia is the commonest cause of persistent hypoglycemia in infancy. Inactivating mutations in the genes ABCC8 and KCNJ11 are the commonest cause. Mutation in the HADH gene, which encodes the short-chain-L-3-hydroxyacyl-CoA dehydrogenase, is a rare cause. Case characteristics: Two Indian sisters who presented with hyperinsulinemic hypoglycemia of infancy. Observation/Intervention: A novel homozygous missense mutation in the HADH gene was identified in both the sisters, while the parents were found to be heterozygous carriers. Outcome: Establishment of molecular diagnosis, optimization of therapy and counseling of parents regarding risk of recurrence in future pregnancy. Messages: HADH mutations are rare causes of hypoglycemia and can be mitigated with diazoxide and appropriate dietary therapy if identified early.

Relación entre la insulinorresistencia y el síndrome de ovario poliquístico y sus comorbilidades metabólicas / Relationship between Insulin Resistance and Polycystic Ovary Syndrome and Its Metabolic Comorbidities

Introducción: el síndrome de ovario poliquístico es un desorden de etiología multifactorial, caracterizado por un cuadro clínico heterogéneo y a veces subclínico que dificulta su manejo y diagnóstico. Se vincula a varias comorbilidades sobre todo de tipo metabólicas, donde la insulinorresistencia puede jugar un papel relevante. Objetivo: describir la relación que existe entre la insulinorresistencia y la génesis del síndrome de ovario poliquístico y de algunas de sus comorbilidades metabólicas. Conclusiones: la insulinorresistencia guarda una estrecha relación con la génesis del síndrome de ovario poliquístico, así como en el desarrollo de algunas de sus comorbilidades metabólicas (diabetes mellitus tipo 2, dislipidemia, hígado graso no alcohólico y síndrome metabólico), las que deben ser identificadas y tratadas precoz y adecuadamente(AU)

Introduction: Polycystic ovary syndrome is a disorder of multifactorial etiology, characterized by a heterogeneous clinical and subclinical, which sometimes makes handling and diagnosis difficult, and it is linked to several metabolic comorbidities especially those insulin resistant that may play a significant role. Objective: Describe the relationship between insulin resistance and the genesis of polycystic ovarian syndrome and some of its metabolic comorbidities. Conclusions: Insulin resistance is closely related to the genesis of polycystic ovary syndrome, as well as the development of some of its metabolic comorbidities (diabetes mellitus Type 2, dyslipidemia, nonalcoholic fatty liver disease and metabolic syndrome), which must be identified and timely and properly treated(AU)