BACKGROUND & AIMS: :To assess the changes in counterregulatory hormones overnight after an afternoon of structured exercise or sedentary activity in children with type 1 diabetes mellitus (T1DM), the Diabetes Research in Children Network (DirecNet) studied 50 children (10 to <18 yr) with T1DM in five clinical research centers on two separate days (with and without an afternoon exercise session) using a crossover design. Glucose, epinephrine, norepinephrine, cortisol, growth hormone (GH), and glucagon concentrations were measured hourly overnight. Nocturnal hypoglycemia [plasma glucose concentrations < or =70 mg/dL (3.9 mmol/L)] occurred more frequently on the nights following exercise (56 vs. 36%; p = 0.008). Mean hourly concentrations of most hormones did not differ between sedentary or exercise nights or between nights with or without hypoglycemia. Spontaneous nocturnal hypoglycemia only stimulated small increases in plasma epinephrine and GH concentrations and failed to cause a rise in norepinephrine, cortisol, or glucagon levels in comparison with values during the hour before or after hypoglycemia or other times during those same nights. Counterregulatory hormone responses to spontaneous nocturnal hypoglycemia were markedly decreased regardless of whether there was antecedent afternoon exercise in children with T1DM. Sleep-induced impairments in counterregulatory hormone responses likely contribute to the increased risk of hypoglycemia during the entire overnight period in youth with T1DM.

背景与目标： ：为了评估1型糖尿病（T1DM）儿童在一下午的结构性运动或久坐运动后过夜的反调节激素的变化，糖尿病儿童研究网络（DirecNet）研究了50名T1DM儿童（10至<18岁）在五个不同的临床研究中心，分别使用交叉设计，分别在两天中（有和没有下午运动课）。每小时每小时测量一次葡萄糖，肾上腺素，去甲肾上腺素，皮质醇，生长激素（GH）和胰高血糖素的浓度。夜间低血糖[血浆葡萄糖浓度<或= 70 mg / dL（3.9 mmol / L）]在运动后的夜晚更为频繁发生（56％vs. 36％； p = 0.008）。在久坐或运动的夜晚或有或没有低血糖的夜晚之间，大多数激素的平均小时浓度没有差异。自发性夜间低血糖症仅刺激血浆肾上腺素和GH浓度的小幅升高，而与低血糖症发生前或后一小时或夜间相同时间的值相比，未能引起去甲肾上腺素，皮质醇或胰高血糖素水平的升高。不管是否患有T1DM的儿童在下午进行先前的锻炼，对自发性夜间低血糖的逆调节激素反应均显着降低。睡眠诱发的反调节激素反应障碍可能导致T1DM青年在整个通宵期间发生低血糖的风险增加。

BACKGROUND & AIMS: :Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.

背景与目标： ：Beckwith-Wiedemann综合征（BWS）是一种先天性过度生长综合征，在新生儿期有时与高胰岛素血症性低血糖症（HH）相关。 Sotos综合征（SS）和Kabuki综合征（KS）是可能与HH并发的其他畸形综合征，但是，尚不清楚HH伴有这些综合征的详细临床特征。在此，我们在日本进行了全国范围的问卷调查。我们向347个围产期护理机构发送了有关这些综合征临床经验的主要问卷。结果，有222个部门或医院返回了问卷，BWS，SS和KS患者的总数分别为113、88和51。我们向31所机构中的这些综合症患者在婴儿期出现HH的情况下发送了第二份调查表。从机构返回的二次调查表中，BWS的患者人数分别为16名，SS的患者人数为9名，KS的患者人数为3名。然后，我们比较了患有和不患有这些畸形综合征的短暂性HH婴儿的临床特征。结果，与短暂性HH的非畸形婴儿相比，BWS，SS和KS患者显示出明显更大的体型，更低的Apgar评分，更高的HH胰岛素水平和更短的HH持续时间。我们建议，仔细观察HH的体征，即使不是特定于该综合征，对于产后BWS，SS和KS患者的诊断也很重要。 ©2016 Wiley Periodicals，Inc.

BACKGROUND & AIMS: BACKGROUND:Risk of hypoglycemia is a major barrier to the implementation of tight blood glucose (BG) control in hospitalized patients. The objective of this study was to evaluate the changes in diabetes treatment after an episode of hypoglycemia. METHODS:The study was a retrospective data analysis of patients who received 50% dextrose for an episode of hypoglycemia. Data on immediate and subsequent changes in the antidiabetic medications the patients received were collected and evaluated by 2 diabetes specialists. RESULTS:Data from 52 patients were included in the study. Mean BG at the time of dextrose administration was 52.1 +/- 9.3 mg/dL (range 31-68). Mean BG during the 24 hours before the hypoglycemic episode was 137.5 +/- 57.0 mg/dL (range 63-287). Insulin dose was held at the time of the hypoglycemic episode in all 52 patients. Diabetes specialists agreed with this decision 100% of the time. Changes were subsequently made in the treatment of only 21 patients (40%), and diabetes specialists agreed with the changes made for 11 of these patients (52%). Thirty-one patients (60%) received no changes in treatment, and diabetes specialists agreed with that decision for 10 patients (32%). CONCLUSIONS:Provider response in making treatment changes after an episode of hypoglycemia is suboptimal. Standardized protocols to make changes in diabetes treatment after an episode of hypoglycemia need to be tested.

背景与目标： 背景：低血糖的风险是住院患者实施严格血糖（BG）控制的主要障碍。这项研究的目的是评估低血糖发作后糖尿病治疗的变化。
方法：该研究是回顾性数据分析，该患者接受了50％葡萄糖引起的低血糖发作。由两名糖尿病专家收集并评估了患者接受抗糖尿病药物治疗的即时和后续变化数据。
结果：来自52名患者的数据被纳入研究。右旋糖给药时的平均BG为52.1±9.3mg / dL（范围31-68）。低血糖发作前24小时的平均BG为137.5 /-57.0 mg / dL（范围63-287）。所有52例患者在降血糖事件发生时均保持胰岛素剂量。糖尿病专家100％地同意这一决定。随后仅对21例患者（40％）的治疗发生了变化，糖尿病专家同意对其中11例患者（52％）进行了变化。 31例患者（60％）没有接受任何治疗改变，糖尿病专家同意10例患者（32％）的决定。
结论：低血糖发作后改变治疗方案的提供者反应欠佳。低血糖发作后改变糖尿病治疗方法的标准化方案需要进行测试。

BACKGROUND & AIMS: AIMS:To develop and externally validate a prediction model for the 6-month risk of a severe hypoglycemic event among individuals with pharmacologically treated diabetes. METHODS:The development cohort consisted of 31,674 Kaiser Permanente Colorado members with pharmacologically treated diabetes (2007-2015). The validation cohorts consisted of 38,764 Kaiser Permanente Northwest members and 12,035 HealthPartners members. Variables were chosen that would be available in electronic health records. We developed 16-variable and 6-variable models, using a Cox counting model process that allows for the inclusion of multiple 6-month observation periods per person. RESULTS:Across the three cohorts, there were 850,992 6-month observation periods, and 10,448 periods with at least one severe hypoglycemic event. The six-variable model contained age, diabetes type, HgbA1c, eGFR, history of a hypoglycemic event in the prior year, and insulin use. Both prediction models performed well, with good calibration and c-statistics of 0.84 and 0.81 for the 16-variable and 6-variable models, respectively. In the external validation cohorts, the c-statistics were 0.80-0.84. CONCLUSIONS:We developed and validated two prediction models for predicting the 6-month risk of hypoglycemia. The 16-variable model had slightly better performance than the 6-variable model, but in some practice settings, use of the simpler model may be preferred.

背景与目标： 目的：建立并从外部验证在药物治疗的糖尿病患者中严重降血糖事件的6个月风险的预测模型。
方法：该开发队列由31,674名Kaiser Permanente Colorado成员进行药理治疗的糖尿病（2007-2015年）组成。验证队列由38,764位Kaiser Permanente Northwest成员和12,035位HealthPartners成员组成。选择了可以在电子健康记录中使用的变量。我们使用Cox计数模型过程开发了16变量和6变量模型，该过程允许每个人包含多个6个月的观察期。
结果：在这三个队列中，有850,992个6个月观察期和10,448个观察期，其中至少有一次严重的降血糖事件。六变量模型包含年龄，糖尿病类型，HgbA1c，eGFR，前一年发生降血糖事件的历史以及胰岛素的使用。两种预测模型均表现良好，对于16变量和6变量模型分别具有良好的校准和0.84和0.81的c统计量。在外部验证队列中，c统计量为0.80-0.84。
结论：我们开发并验证了两种用于预测6个月低血糖风险的预测模型。 16变量模型比6变量模型具有更好的性能，但是在某些实践设置中，可能更喜欢使用更简单的模型。

BACKGROUND & AIMS: OBJECTIVE:To review the presentation of hyperinsulinemic hypoglycemia of the infancy (HHI), its treatment and histology in Brazilian pediatric endocrinology sections. MATERIALS AND METHOD:The protocol analyzed data of birth, laboratory results, treatment, surgery, and pancreas histology. RESULTS:Twenty-five cases of HHI from six centers were analyzed: 15 male, 3/25 born by vaginal delivery. The average age at diagnosis was 10.3 days. Glucose and insulin levels in the critical sample showed an average of 24.7 mg/dL and 26.3 UI/dL. Intravenous infusion of the glucose was greater than 10 mg/kg/min in all cases (M:19,1). Diazoxide was used in 15/25 of the cases, octreotide in 10, glucocorticoid in 8, growth hormone in 3, nifedipine in 2 and glucagon in 1. Ten of the cases underwent pancreatectomy and histology results showed the diffuse form of disease. CONCLUSION:This is the first critic review of a Brazilian sample with congenital HHI.

背景与目标： 目的：回顾巴西小儿内分泌科婴儿高胰岛素血症性低血糖症（HHI）的表现，治疗方法和组织学。
材料与方法：该协议分析了出生，实验室结果，治疗，手术和胰腺组织学的数据。
结果：分析了来自六个中心的25例HHI病例：15例男性，3/25通过阴道分娩出生。诊断时的平均年龄为10.3天。关键样品中的葡萄糖和胰岛素水平平均为24.7 mg / dL和26.3 UI / dL。在所有情况下，静脉输注葡萄糖均大于10 mg / kg / min（M：19,1）。乙二氧化物使用15/25，奥曲肽10，糖皮质激素8，生长激素3，硝苯地平2，胰高血糖素1。十例进行了胰腺切除术，组织学结果显示疾病是弥漫性的。
结论：这是对巴西先天性HHI样本的首次评论家评论。

BACKGROUND & AIMS: : Objective: A severe hypoglycemia (SH) episode is an acute, high-stress moment for the caregivers of persons with diabetes (PWD). We compared the success rates of nasal glucagon (NG) and injectable glucagon (IG) administration for PWD-trained and untrained users in treating simulated SH episodes. Methods: Thirty-two PWD-trained users and 33 untrained users administered NG and IG to high-fidelity manikins simulating treatment of an SH emergency. Simulation rooms resembled common locations with typical diabetic supplies and stressor elements mimicking real-life SH environments. Success rate and time to administer glucagon were measured. Results: Of all the PWD-trained and untrained users, 58/64 (90.6%) could successfully deliver NG, while 5/63 (7.9%) could successfully deliver IG. For NG simulations, 28/31 (90.3%) PWD-trained users and 30/33 (90.9%) untrained users could successfully administer the dose (mean time 47.3 seconds and 44.5 seconds, respectively). For IG simulations, 5/32 (15.6%) PWD-trained users successfully injected IG (mean time 81.8 seconds), whereas none (0/31 [0%]) of the untrained users were successful. Reasons for unsuccessful administration of NG included oral administration and incomplete pushing of the device plunger. For IG, inability to perform reconstitution steps, partial dose delivery, and injection at an inappropriate site were the causes for failure. Conclusion: With or without training, the success rate for administering NG was 90.6%, whereas it was only 7.9% for IG. NG was easily and quickly administered even by untrained users, whereas training was necessary for successful administration of IG. NG may expand the community of caregivers who can help PWD during an SH episode. Abbreviations: IG = injectable glucagon; NG = nasal glucagon; PWD = person with diabetes; SH = severe hypoglycemia; T1D = type 1 diabetes; T2D = type 2 diabetes.

背景与目标： ：
客观的：
严重的低血糖（SH）发作是糖尿病患者（PWD）照护者的急性，高压力时刻。我们比较了接受PWD训练和未经训练的用户鼻腔胰高血糖素（NG）和可注射胰高血糖素（IG）的治疗成功率，它们均能治疗模拟的SH发作。
方法：
32名接受PWD训练的用户和33名未经训练的用户对模拟SH紧急情况的高保真人体模型进行了NG和IG给药。模拟室与普通地点相似，具有典型的糖尿病补给品和模拟现实生活中的SH环境的压力源。测量成功率和给予胰高血糖素的时间。
结果：
在所有经过PWD培训和未经培训的用户中，58/64（90.6％）可以成功提供NG，而5/63（7.9％）可以成功提供IG。对于NG模拟，28/31（90.3％）受PWD训练的用户和30/33（90.9％）未经训练的用户可以成功给药（平均时间分别为47.3秒和44.5秒）。对于IG模拟，受PWD培训的5/32（15.6％）用户成功注入了IG（平均时间81.8秒），而未经培训的用户则没有成功（0/31 [0％]）。 NG给药失败的原因包括口服给药和装置柱塞未完全推动。对于IG而言，无法执行重建步骤，部分剂量输送和在不合适的部位注射是失败的原因。
结论：
在有或没有经过培训的情况下，NG的成功率为90.6％，而IG的成功率为7.9％。即使未经培训的用户也可以轻松，快速地进行NG管理，而成功进行IG管理则必须进行培训。 NG可能会扩大在SH发作期间可以帮助PWD的看护者社区。缩写：IG =可注射胰高血糖素； NG =鼻胰高血糖素； PWD =糖尿病患者； SH =严重低血糖； T1D = 1型糖尿病； T2D = 2型糖尿病。

BACKGROUND & AIMS: :The medical records of six cases of nesidioblastosis were examined to determine the diagnostic approach, treatment, and neurologic sequelae. All six patients were male, and their ages at the onset of the disease ranged from one day to six months (mean 3.36 +/- 2.5 mo.). Initial clinical features were seizure, cyanosis, poor feeding, and apnea. Other subsequent symptoms were developmental delay, hyperactivity, and cold sweating. The Birth weight of the neonatal onset group was heavier than the postneonatal onset group (4.4 +/- 0.3 vs 3.26 +/- 0.04 kg). Before the diagnosis of hyperinsulinism, steroids of ACTH proved effective for seizure control. Initially, hyperinsulinemia (serum insulin greater than 10 microU/ml) was detected in four cases, but another two cases also showed hyperinsulinism by insulin/glucose(I/G) ratio greater than 0.3 during the fasting test. The glucagon response performed in 2 cases, showed normal and partial responses. Euglycemia was obtained by near total pancreatectomy (95% pancreatic resection)without malabsorption or persistent diabetes. In one case, nesidioblastoma coexisted with nesidioblastosis. Developmental delay was noted in three cases. In this group, the mean duration between symptom onset and operation was longer than the group without developmental delay (1.25 +/- 0.47 vs 0.38 +/- 0.19 yr).

背景与目标： ：检查了6例奈瑟氏成纤维细胞病的病历，以确定诊断方法，治疗方法和神经系统后遗症。所有六名患者均为男性，发病年龄从一天到六个月不等（平均3.36 /-2.5个月）。最初的临床特征是癫痫发作，发，进食不良和呼吸暂停。其他随后的症状是发育延迟，多动和冷汗。新生儿发作组的出生体重较新生儿发作后组重（4.4 /-0.3对3.26 /-0.04 kg）。在诊断高胰岛素血症之前，ACTH类固醇已被证明可有效控制癫痫发作。最初，在四例中检测到高胰岛素血症（血清胰岛素大于10 microU / ml），但在禁食测试中，另外两个案例也显示胰岛素/葡萄糖（I / G）比大于0.3导致高胰岛素血症。胰高血糖素反应2例，显示正常和部分反应。通过近全胰切除术（95％胰腺切除术）获得正常血糖，无吸收不良或持续性糖尿病。在一种情况下，nesidioblastoma与nesidioblastosis共存。在三例中注意到发育迟缓。在该组中，症状发作和手术之间的平均持续时间长于没有发育延迟的组（1.25 /-0.47 vs 0.38 /-0.19年）。

BACKGROUND & AIMS: :Insulin-induced hypoglycemia in rats may lead to stimulated brain activity and if severe enough, they may develop a stupor-coma condition. In this study, the effects of insulin-induced hypoglycemia on brain phospholipid metabolism were examined in rats which were prior injected with (32)Pi. Three hours after insulin injection (1 or 5 units/100 g body wt, i.p.), there was an increase (25%) in radioactivity of the lipid phase of cerebral cortex, but radioactivity in the cerebellum tended to decrease instead. Radioactivity in the aqueous phase of cortex was not altered after insulin injection, but that in the cerebellum was decreased by 30%. Differences were observed in labeling of individual phospholipids in response to the hypoglycemic treatment. A marked decrease in labelled phosphatidate was observed in the cerebellum from the hypoglycemic samples, but not in the cerebral cortex. In the cortex, hypoglycemic condition resulted in an increase in (32)Pi uptake into the phospholipids. However, the differences in the amount of label among individual phospholipids suggest that phosphatidylinositol and phosphatidylcholine are turning over more rapidly than other phospholipids. The hypoglycemic rats also showed a 3-fold increase in the brain free fatty acid level, but the level of diacylglycerol was not changed. Results thus suggested a correlation between the free fatty acid release and the increased turnover of phosphatidylinositol and phosphatidylcholine during brain stimulation due to insulin-induced hypoglycemia.

背景与目标： ：胰岛素引起的大鼠低血糖症可能导致大脑活动受刺激，如果足够严重，它们可能发展为昏迷状态。在这项研究中，在预先注射（32）Pi的大鼠中检查了胰岛素诱导的低血糖对脑磷脂代谢的影响。胰岛素注射后三小时（1或5单位/ 100 g体重，腹腔注射），大脑皮层脂质相的放射性增加（25％），但小​​脑的放射性却趋于下降。注射胰岛素后，皮质水相中的放射性没有改变，但小脑中的放射性降低了30％。在对降血糖治疗的反应中，在单个磷脂的标记上观察到差异。在低血糖样本的小脑中观察到标记的磷脂酸酯显着减少，但在大脑皮层中未观察到。在皮质中，低血糖症导致磷脂中（32）Pi的摄取增加。但是，各个磷脂之间的标记量差异表明，磷脂酰肌醇和磷脂酰胆碱的翻转速度比其他磷脂快。降血糖的大鼠脑中游离脂肪酸水平也增加了3倍，但二酰基甘油的水平没有改变。因此结果表明，由于胰岛素引起的低血糖，在大脑刺激期间游离脂肪酸的释放与磷脂酰肌醇和磷脂酰胆碱的周转率增加之间存在相关性。

BACKGROUND & AIMS: :GH secretion by the pituitary is the result of the balance between the stimulatory effect of GHRH and the inhibitory effect of SS. Patients with mutations in GHRH receptor (GHRH-R) gene (GHRH-R) offer a unique model to study the mechanism of action of different GH secretion stimuli. In the past, we have demonstrated a small but significant GH response to a GH secretagogue (GHRP-2) in a homogenous cohort of patients with severe GH deficiency (GHD) due to a homozygous null mutation in GHRH-R (IVS1+1G-->A). Now, we sought to determine if we could detect a GH response to hypoglycemia (ITT: insulin tolerance test) or clonidine (CL) in these patients. Nine young GHD subjects underwent both ITT and CL tests, and 2 additional subjects underwent only CL test. There was a small but significant GH increase during ITT, but not during CL test. These results indicate that a minimal albeit significant GH response to ITT can occur despite complete lack of GHRH-R function.

背景与目标： 垂体：GH的分泌是GHRH的刺激作用与SS的抑制作用之间平衡的结果。具有GHRH受体（GHRH-R）基因（GHRH-R）突变的患者提供了一个独特的模型来研究不同GH分泌刺激的作用机理。过去，由于GHRH-R的纯合无效突变（IVS1 1G-- > A）。现在，我们试图确定我们是否可以在这些患者中检测到对低血糖（ITT：胰岛素耐受性测试）或可乐定（CL）的GH反应。 9名GHD青年受试者同时接受了ITT和CL测试，另外2名受试者仅接受了CL测试。在ITT期间，GH的增加很小但很明显，但在CL测试期间却没有。这些结果表明，尽管完全缺乏GHRH-R功能，对ITT的GH响应却很小，尽管显着。

BACKGROUND & AIMS: :A case of acute pancreatitis and hypoglycemia-associated convulsions following rotavirus gastroenteritis, occurring in a previously healthy 2-year, 8-month-old girl, is reported. Rotavirus infection was demonstrated both by detection of virus particles in stools by electron microscopy and Rotazyme Abbott, and by detection of specific serum IgM and IgG antibodies. Pancreatitis was revealed by raised serum amylase and lipase levels and by ultrasonographic findings. Moreover, transient islet cell antibodies were found. No abnormalities were revealed by clinical and laboratory follow-up studies. As suggested by this case report, further investigations on the possible pancreatic involvement by rotavirus may be helpful.

背景与目标： ：据报道，一名先前健康的2岁8个月大女孩发生轮状病毒胃肠炎后发生急性胰腺炎和低血糖相关性惊厥。通过电子显微镜和Rotazyme Abbott检测粪便中的病毒颗粒，以及检测特异性血清IgM和IgG抗体，证明了轮状病毒感染。血清淀粉酶和脂肪酶水平升高以及超声检查发现胰腺炎。此外，发现了短暂的胰岛细胞抗体。临床和实验室随访研究未发现异常。正如该病例报告所建议的那样，进一步研究轮状病毒可能引起的胰腺受累可能是有帮助的。

BACKGROUND & AIMS: :We previously showed, through direct neural recording in conscious rats, that hypoglycemia increases adrenal sympathetic nerve activity (SNA) both acutely and 24 hours following the second of 2 daily antecedent hypoglycemic episodes. Nonetheless, antecedent hypoglycemia impaired catecholamine responsiveness to subsequent acute hypoglycemia. Here we hypothesized that antecedent, nonhypoglycemic adrenal sympathetic stimulation by leptin would impair acute adrenal catecholamine responsiveness to subsequent hypoglycemia. We also hypothesized that acute leptin administration (after 2 days of antecedent hypoglycemia) would enhance adrenal SNA and thereby enhance catecholamine responsiveness to concurrent hypoglycemia. Leptin or saline was administered to normal rats in repeated subcutaneous injections for 2 days prior to acute insulin-induced hypoglycemia. In contrast to our hypothesis, antecedent leptin did not change catecholamine responsiveness or glycemic change in response to subsequent acute insulin administration. In additional studies, intravenous leptin or saline was acutely administered beginning 1 hour before insulin-induced hypoglycemia. All rats had been exposed to antecedent hypoglycemia. In these experiments, acute leptin did not alter catecholamine responses to insulin or glycemic change during or after termination of insulin. We conclude that antecedent nonhypoglycemic sympathetic stimulation by leptin does not alter subsequent catecholamine or glycemic responses to insulin. Moreover, concurrent leptin does not enhance catecholamine responses to insulin in rats exposed to antecedent hypoglycemia.

背景与目标： ：我们之前通过在有意识的大鼠中进行直接神经记录表明，低血糖症会在每日两次前两次降血糖发作的第二天和第二个小时后的24小时内，迅速增加肾上腺交感神经活动（SNA）。尽管如此，先前的低血糖症会损害儿茶酚胺对随后的急性低血糖症的反应性。在这里我们假设瘦素的先行非降血糖肾上腺交感刺激会损害急性肾上腺儿茶酚胺对随后的低血糖反应。我们还假设急性瘦素给药（先天性低血糖2天后）会增强肾上腺SNA，从而增强儿茶酚胺对同时发生的低血糖的反应性。在急性胰岛素诱发的低血糖之前，通过皮下注射连续2天向正常大鼠施用瘦素或生理盐水。与我们的假设相反，瘦素在随后的急性胰岛素治疗中并未改变儿茶酚胺反应性或血糖变化。在其他研究中，在胰岛素诱发的低血糖发生前1小时开始静脉注射瘦素或生理盐水。所有大鼠均暴露于先前的低血糖症。在这些实验中，急性瘦素在胰岛素终止期间或终止后未改变儿茶酚胺对胰岛素的反应或血糖变化。我们得出结论，瘦素之前的非降血糖交感神经刺激不会改变随后的儿茶酚胺或对胰岛素的血糖反应。此外，并发瘦素不能增强儿茶酚胺对暴露于先前低血糖的大鼠的胰岛素反应。

BACKGROUND & AIMS: BACKGROUND:The persistent hyperinsulinemic hypoglycemia is characterized by clinical symptoms that occur when the blood glucose levels drop below the normal range. Two pathological situations cause this clinical problem: The presence of a tumor of the pancreas secreting excessive amounts of insulin, known as insulinoma, and congenital beta-cell hyperplasia in the pancreas in children and noninsulinoma pancreatogenic hypoglycemia syndrome in adults. PATIENTS AND METHODS:Clinical characteristic and surgical outcome of a group of 20 patients operated on for this hypoglycemic syndrome; 18 for insulinoma and two for nesidioblastosis in children was studied. RESULTS:eight of the insulinomas were in the head of the pancreas, two in the body, and the remaining eight in the tail. The surgical technique was enucleation in nine cases, local resection in one case because of suspicious malignancy, and distal pancreatectomy in eight cases. Both children with nesidioblastosis underwent 85% pancreatectomy with splenic preservation. There was no mortality in the study, but three patients developed a low-volume pancreatic fistula after head enucleation. CONCLUSIONS:Negative results in diagnostic localization together with the small size of the insulinoma represent a poor combination for successful surgery. The intraoperative ultrasonography is the method of choice for the identification of the tumor, as it is able to identify nonpalpable lesions.

背景与目标： 背景：持续性高胰岛素血症性低血糖的特征是当血糖水平降至正常范围以下时出现的临床症状。有两种病理情况导致此临床问题：儿童胰腺中存在分泌过量胰岛素的肿瘤（称为胰岛素瘤），儿童胰腺中先天性β细胞增生，成人非胰岛素瘤性胰腺源性低血糖综合征。
病人和方法：20例因这种低血糖综合征而手术的患者的临床特征和手术结果；小儿胰岛素瘤为18例，奈瑟成纤维细胞为2例。
结果：8例胰岛素瘤位于胰头，其中2例位于胰头，其余8例在尾巴。手术技术为摘除9例，因可疑恶性肿瘤局部切除1例，远端胰腺切除术8例。两名患有神经纤维母细胞病的儿童均接受了85％的保留脾脏的胰腺切除术。该研究没有死亡率，但是三名患者的头部摘除后出现了低容量的胰瘘。
结论：诊断定位的阴性结果以及小尺寸的胰岛素瘤代表了成功手术的不良组合。术中超声检查是鉴别肿瘤的首选方法，因为它能够鉴别出不可触及的病变。

BACKGROUND & AIMS: BACKGROUND:Hypoglycemia is a common complication of insulin therapy in patients with Type 1 Diabetes Mellitus (DM). Awareness of hypoglycemic symptoms helps patients to recognize hypoglycemia and initiate self-treatment. Impaired Awareness of Hypoglycemia (IAH) exposes patients to severe hypoglycemia, which could be associated with seizures and unconsciousness. This study aimed to assess IAH, frequency of hypoglycemia, severe hypoglycemia and intensity of hypoglycemic symptoms among children and adolescents with Type 1 DM in North of Jordan. METHODS:Data were collected from 94 children and adolescents with Type 1 DM. Clarke's and Edinburgh surveys were used to assess IAH and individual symptoms of hypoglycemia, respectively. Frequency of hypoglycemia and other related information were obtained by self-reporting or from medical records. RESULTS:16.0% of participants were having IAH, 66.0% of participants reported recurrent hypoglycemia (>once/month) and 18.0% of participants developed ≥1 severe hypoglycemia during the previous year. IAH was not associated with age, gender, duration of DM, HbA1c, insulin regimen, adherence to insulin or development of severe hypoglycemia (p-values> 0.05). Instead, IAH was associated with frequency of hypoglycemia during the previous 6 months (p-value< 0.01). Hunger, tiredness, dizziness, drowsiness, inability to concentrate, trembling and weakness were the most common symptoms felt by participants when they develop hypoglycemia. Hunger was the only common symptom that was significantly higher in children compared to adolescent (p-value < 0.01). CONCLUSIONS:This study has reported low prevalence of IAH in children and adolescents with Type 1 DM in North of Jordan. IAH was more common in subjects with more frequent hypoglycemia.

背景与目标： 背景：低血糖症是1型糖尿病（DM）患者胰岛素治疗的常见并发症。意识到降血糖症状有助于患者识别低血糖症并开始自我治疗。低血糖意识（IAH）受损使患者暴露于严重的低血糖症中，这可能与癫痫发作和神志不清有关。这项研究旨在评估约旦北部患有1型DM的儿童和青少年的IAH，低血糖发生率，严重低血糖症和降血糖症状的强度。
方法：收集了94例1型糖尿病儿童和青少年的数据。 Clarke和爱丁堡的调查分别用于评估IAH和低血糖的个体症状。低血糖发生频率和其他相关信息可通过自我报告或从医疗记录中获得。
结果：16.0％的受试者患有IAH，66.0％的受试者报告反复低血糖（>一次/月），并且18.0％的受试者在上一年出现≥1的严重低血糖。 IAH与年龄，性别，DM持续时间，HbA1c，胰岛素治疗方案，胰岛素依从性或严重低血糖的发生无关（p值> 0.05）。相反，IAH与前6个月的低血糖发生率相关（p值结论：该研究报告了约旦北部患有1型DM的儿童和青少年中IAH的患病率较低。 IAH在低血糖症患者中更为常见。

BACKGROUND & AIMS: OBJECTIVE:Identify factors predictive of severe hypoglycemia (SH) and assess the clinical utility of continuous glucose monitoring (CGM) to warn of impending SH. RESEARCH DESIGN AND METHODS:In a multicenter randomized clinical trial, 436 children and adults with type 1 diabetes were randomized to a treatment group that used CGM (N = 224), or a control group that used standard home blood glucose monitoring (N = 212) and completed 12 months of follow-up. After 6 months, the original control group initiated CGM while the treatment group continued use of CGM for 6 months. Baseline risk factors for SH were evaluated over 12 months of follow-up using proportional hazards regression. CGM-derived indices of hypoglycemia were used to predict episodes of SH over a 24-h time horizon. RESULTS:The SH rate was 17.9 per 100 person-years, and a higher rate was associated with the occurrence of SH in the prior 6 months and female sex. SH frequency increased eightfold when 30% of CGM values were ≤ 70 mg/dL on the prior day (4.5 vs. 0.5%; P < 0.001), but the positive predictive value (PPV) was low (<5%). Results were similar for hypoglycemic area under the curve and the low blood glucose index calculated by CGM. CONCLUSIONS:SH in the 6 months prior to the study was the strongest predictor of SH during the study. CGM-measured hypoglycemia over a 24-h span is highly associated with SH the following day (P < 0.001), but the PPV is low.

背景与目标： 目的：确定可预测严重低血糖（SH）的因素，并评估连续血糖监测（CGM）来警告即将发生的SH的临床实用性。
研究设计和方法：在一项多中心随机临床试验中，将436名1型糖尿病儿童和成人随机分为使用CGM（N = 224）的治疗组或使用标准家庭血糖监测（N = 212）的对照组。 ），并完成了12个月的随访。 6个月后，原始对照组开始CGM，而治疗组继续使用CGM 6个月。在12个月的随访中，使用比例风险回归对SH的基线危险因素进行了评估。 CGM衍生的低血糖指数用于预测24小时内的SH发作。
结果：SH的发生率为每100人年17.9，而较高的发生率与前6个月的SH发生以及女性有关。前一天，当CGM值的30％≤70 mg / dL时，SH频率增加了八倍（4.5对0.5％； P <0.001），但阳性预测值（PPV）低（<5％）。曲线下的降血糖面积和CGM计算的低血糖指数的结果相似。
结论：研究前6个月的SH是研究期间SH的最强预测因子。 CGM在24小时内测量的低血糖与第二天的SH高度相关（P <0.001），但PPV较低。

BACKGROUND & AIMS: :The objective of this study was to investigate the relationship between plasma and brain glucose levels during euglycemia and hypoglycemia in healthy subjects and patients with type 1 diabetes mellitus (T1DM). Hyperinsulinemic euglycemic (5 mmol/L) and hypoglycemic (3 mmol/L) [1-(13)C]glucose clamps were performed in eight healthy subjects and nine patients with uncomplicated T1DM (HbA(1c) 7.7 ± 1.4%). Brain glucose levels were measured by (13)C magnetic resonance spectroscopy. Linear regression analysis was used to fit the relationship between plasma and brain glucose levels and calculate reversible Michaelis-Menten (MM) kinetic parameters. Brain glucose values during euglycemia (1.1 ± 0.4 μmol/g vs. 1.1 ± 0.3 μmol/g; P = 0.95) and hypoglycemia (0.5 ± 0.2 μmol/g vs. 0.6 ± 0.3 μmol/g; P = 0.52) were comparable between healthy subjects and T1DM patients. MM kinetic parameters of combined data were calculated to be maximum transport rate/cerebral metabolic rate of glucose (T(max)/CMR(glc)) = 2.25 ± 0.32 and substrate concentration at half maximal transport (K(t)) = 1.53 ± 0.88 mmol/L, which is in line with previously published data obtained under hyperglycemic conditions. In conclusion, the linear MM relationship between plasma and brain glucose can be extended to low plasma glucose levels. We found no evidence that the plasma to brain glucose relationship or the kinetics describing glucose transport over the blood-brain barrier differ between healthy subjects and patients with uncomplicated, reasonably well-controlled T1DM.

背景与目标： ：这项研究的目的是研究健康受试者和1型糖尿病（T1DM）患者在正常血糖和低血糖期间血浆与脑葡萄糖水平之间的关系。高血糖正常血糖（5 mmol / L）和低血糖（3 mmol / L）[1-（13）C]葡萄糖钳夹法在8例健康受试者和9例单纯T1DM（HbA（1c）7.7±1.4％）患者中进行。脑葡萄糖水平通过（13）C磁共振波谱法测量。使用线性回归分析来拟合血浆和脑葡萄糖水平之间的关系，并计算可逆的迈克尔斯-门腾（MM）动力学参数。在正常血糖（1.1±0.4μmol/ g vs. 1.1±0.3μmol/ g; P = 0.95）和低血糖（0.5±0.2μmol/ g vs. 0.6±0.3μmol/ g; P = 0.52）期间的脑葡萄糖值之间具有可比性健康受试者和T1DM患者。组合数据的MM动力学参数计算为最大葡萄糖转运速率/脑代谢速率（T（max）/ CMR（glc））= 2.25±0.32和最大转运量一半时的底物浓度（K（t））= 1.53± 0.88 mmol / L，与先前在高血糖条件下获得的数据相符。总之，血浆和脑葡萄糖之间的线性MM关系可以扩展到低血糖水平。我们没有发现证据表明血浆与脑部葡萄糖之间的关系或描述通过血脑屏障进行葡萄糖转运的动力学在健康受试者和未受复杂控制且合理控制的T1DM患者之间存在差异。