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。

BACKGROUND & AIMS: OBJECTIVE:To assess the frequency of severe hypoglycemia in patients with non-insulin-dependent diabetes mellitus (NIDDM). METHODS:We surveyed a single diabetologist's clinical practice of consecutive patients with NIDDM during a 3-month period. RESULTS:Of the 262 study participants interviewed, 172 insulin-using and 90 sulfonylurea-using patients were asked whether they had ever had hypoglycemia severe enough to require the assistance of another person. Of the 90 sulfonylurea-treated patients with NIDDM, 3 (3.3%) reported experiencing severe hypoglycemia on one occasion only. Of the 172 insulin-utilizing patients, 13 (7.6%) had had severe hypoglycemic episodes--8 on one occasion only (5 of these had been iatrogenic circumstances and 3 had been precipitated by exercise or lack of food). Five insulin-requiring patients reported multiple bouts of severe hypoglycemia. With one exception, all patients were thin, and C peptide levels were low or undetectable. CONCLUSION:On the basis of this study, we conclude that severe hypoglycemia is extremely uncommon in NIDDM. When it occurs, it is usually accidental and seldom recurs. Patients with multiple bouts of severe hypoglycemia have almost complete insulin deficiency. Thus, aggressive treatment of NIDDM to avoid diabetic complications is rarely associated with severe hypoglycemia and is usually well tolerated.

背景与目标： 目的：评估非胰岛素依赖型糖尿病（NIDDM）患者严重低血糖的发生率。
方法：我们调查了一个糖尿病专家在3个月内连续NIDDM患者的临床实践。
结果：在接受采访的262名研究参与者中，有172名使用胰岛素的患者和90名使用磺酰脲的患者被问到他们是否曾经患有严重的低血糖症，需要其他人的帮助。在90例接受磺酰脲治疗的NIDDM患者中，有3例（3.3％）仅一次出现严重的低血糖。在172名使用胰岛素的患者中，只有13次（7.6％）仅出现一次严重的低血糖发作--8（其中5名是医源性情况，而3名是由于运动或缺乏食物导致的）。五名需要胰岛素的患者报告了多次严重低血糖发作。除了一个例外，所有患者都很瘦，C肽水平低或无法检测。
结论：根据本研究，我们得出结论，严重的低血糖症在NIDDM中极为罕见。当它发生时，通常是偶然的并且很少复发。多发严重低血糖的患者几乎完全缺乏胰岛素。因此，为避免糖尿病并发症而积极治疗NIDDM很少会伴有严重的低血糖症，并且通常具有良好的耐受性。

BACKGROUND & AIMS: OBJECTIVE:To review the causes of nonpancreatic tumor-associated hypoglycemia and report the first case of hypoglycemia attributable to a leiomyosarcoma, which did not cause hypoglycemia in its primary site but only after metastasizing. METHODS:A case report is presented of a 62-year-old man with a gastric leiomyosarcoma diagnosed and surgically treated 8 years previously, who was found to have 14 large, rounded masses in his liver and a blood glucose level of 19 mg/dL. Biopsy of the largest mass revealed a leiomyosarcoma. RESULTS:Evaluation of the cause of the hypoglycemia revealed that circulating insulin, connecting peptide, proinsulin, insulin-like growth factor-I (somatomedin C), and insulin-like growth factor-II levels were below normal, whereas the insulin-like growth factor-II prohormone concentration was increased twofold. Basal and corticotropin-stimulated serum cortisol values were normal. CONCLUSION:This is the first case report of hypoglycemia occurring only after metastasis of a leiomyosarcoma. A possible causal relationship between the hypoglycemia and the increased circulating insulin-like growth factor-II prohormone is suggested, and alternative explanations and treatment are discussed.

背景与目标： 目的：回顾非胰腺肿瘤相关性低血糖的原因，并报告首例由平滑肌肉瘤引起的低血糖病例，该病在原发部位并未引起低血糖，仅在转移后才引起。
方法：病例报告介绍了一位62岁的男子，该男子在8年前被诊断并通过手术治疗了胃平滑肌肉肉瘤，发现他的肝脏中有14个大的圆形肿物，血糖水平为19 mg / dL 。最大的活检显示平滑肌肉瘤。
结果：低血糖病因的评估显示，循环中的胰岛素，连接肽，胰岛素原，胰岛素样生长因子-I（somatomedin C）和胰岛素样生长因子-II水平低于正常水平，而胰岛素样生长因子因子-II激素浓度增加了两倍。基础和促肾上腺皮质激素刺激的血清皮质醇值正常。
结论：这是仅在平滑肌肉瘤转移后发生低血糖的第一例报道。提示低血糖与循环胰岛素样生长因子II激素水平升高之间可能存在因果关系，并讨论了其他解释和治疗方法。

BACKGROUND & AIMS: BACKGROUND:In persons with type 1 diabetes (T1D), hypoglycemia is the major limiting factor in achieving optimal glycemic control. All persons with T1D are at risk for hypoglycemia (blood glucose level < 70 mg/dl), which is life-threatening and accompanied by serious physical and psychological symptoms, resulting in profound fear of hypoglycemia (FOH) and reduced quality of life. Young adults with T1D are at risk for FOH and have worse glycemic control and self-management behavior than other age groups with T1D. FOH also results in increased glycemic variability (GV). A major gap exists in how to manage FOH. Our overall objective is to reduce FOH and improve diabetes self-management, glycemic control, and GV in young adults with T1D to reduce or delay diabetes complications and improve quality of life. We aim to (1) determine the feasibility and acceptability of an eight-week cognitive behavioral therapy (CBT)-based Fear Reduction Efficacy Evaluation (FREE) intervention in young adults with T1D who experience FOH; and (2) determine the impact of the FREE intervention, compared to an attention control group, on the outcomes FOH, self-management, glycemic control (A1C), and glycemic variability (continuous glucose monitoring recordings). METHODS/DESIGN:A randomized controlled trial in 50 young adults aged 18 to 35 years with T1D will be used. Eligible subjects will be randomized to the intervention program (Fear Reduction Efficacy Evaluation [FREE]) or attention control group. A one-week run-in phase is planned, with baseline measures of FOH, self-management behavior, A1C, and real-time continuous glucose monitoring recordings (RT-CGM) to calculate GV for both groups. The intervention group will participate in eight weekly individual one-hour sessions using CBT and exposure treatment for specific fears. RT-CGM and a daily FOH diary will be used as feedback cues as part of the FREE program. The attention control group will participate in eight weekly individual one-hour diabetes self-management education (DSME) sessions and wear a RT-CGM device (to measure GV only) over 8 weeks. At completion, FOH will be measured, and RT-CGM recordings will be analyzed to determine differences between the FREE and control groups. DISCUSSION:Findings from this proposed pilot study will serve as the foundation for a larger trial to reduce FOH and improve self-management, glycemic control, and GV. TRIAL REGISTRATION:ClinicalTrials.gov: A cognitive behavioral therapy (CBT) intervention to reduce fear of hypoglycemia in type 1 diabetes, NCT03549104. Registered June 7, 2018.

背景与目标： 背景：在1型糖尿病（T1D）患者中，低血糖是实现最佳血糖控制的主要限制因素。所有患有T1D的人都有发生低血糖症的风险（血糖水平<< 70 mg / dl），这会危及生命，并伴有严重的生理和心理症状，导致对低血糖症（FOH）的严重恐惧和生活质量下降。与其他患有T1D的年龄组相比，患有T1D的年轻成人有发生FOH的风险，并且血糖控制和自我管理行为较差。 FOH还导致血糖变异性（GV）增加。如何管理FOH存在重大差距。我们的总体目标是减少患有T1D的年轻成年人的FOH并改善其自我管理，血糖控制和GV，以减少或延迟糖尿病并发症并改善生活质量。我们的目的是（1）确定在经历FOH的年轻T1D成年人中，基于八周认知行为疗法（CBT）的恐惧减少功效评估（FREE）干预的可行性和可接受性； （2）与关注对照组相比，确定FREE干预对结果FOH，自我管理，血糖控制（A1C）和血糖变异性（连续血糖监测记录）的影响。
方法/设计：将对50名年龄在18至35岁的T1D的年轻人进行随机对照试验。符合条件的受试者将被随机分配至干预计划（减少恐惧效能评估[FREE]）或注意力控制组。计划了一个为期一周的磨合期，其中包括FOH，自我管理行为，A1C和实时连续葡萄糖监测记录（RT-CGM）的基线测量，以计算两组的GV。干预小组将参加八周的每周一小时的单独课程，使用CBT和暴露疗法治疗特定的恐惧。作为免费计划的一部分，RT-CGM和每日FOH日记将用作反馈提示。注意力控制小组将参加八周的每周一小时的个人糖尿病自我管理教育（DSME）课程，并在八周内佩戴RT-CGM设备（仅用于测量GV）。完成后，将对FOH进行测量，并对RT-CGM记录进行分析，以确定FREE和对照组之间的差异。
讨论：这项拟议中的初步研究的结果将作为一项较大的试验的基础，以降低FOH并改善自我管理，血糖控制和GV。
试验注册：ClinicalTrials.gov：一种认知行为疗法（CBT）干预措施，可减轻1型糖尿病患者对低血糖症的恐惧，NCT03549104。 2018年6月7日注册。

BACKGROUND & AIMS: :Recurrent episodes of hypoglycemia impair sympathoadrenal counterregulatory responses (CRRs) to a subsequent episode of hypoglycemia. For individuals with type 1 diabetes, this markedly increases (by 25-fold) the risk of severe hypoglycemia and is a major limitation to optimal insulin therapy. The mechanisms through which this maladaptive response occurs remain unknown. The corticotrophin-releasing factor (CRF) family of neuropeptides and their receptors (CRFR1 and CRFR2) play a critical role in regulating the neuroendocrine stress response. Here we show in the Sprague-Dawley rat that direct in vivo application to the ventromedial hypothalamus (VMH), a key glucose-sensing region, of urocortin I (UCN I), an endogenous CRFR2 agonist, suppressed (approximately 55-60%), whereas CRF, a predominantly CRFR1 agonist, amplified (approximately 50-70%) CRR to hypoglycemia. UCN I was shown to directly alter the glucose sensitivity of VMH glucose-sensing neurons in whole-cell current clamp recordings in brain slices. Interestingly, the suppressive effect of UCN I-mediated CRFR2 activation persisted for at least 24 hours after in vivo VMH microinjection. Our data suggest that regulation of the CRR is largely determined by the interaction between CRFR2-mediated suppression and CRFR1-mediated activation in the VMH.

背景与目标： 反复发作的低血糖会损害对随后的低血糖发作的交感肾上腺反调节反应（CRR）。对于患有1型糖尿病的个体，这显着增加了严重低血糖症的风险（增加了25倍），并且是最佳胰岛素治疗的主要限制。发生这种适应不良反应的机制仍然未知。神经肽及其受体（CRFR1和CRFR2）的促肾上腺皮质激素释放因子（CRF）家族在调节神经内分泌应激反应中起关键作用。在这里，我们在Sprague-Dawley大鼠中表明，体内应用将尿皮质素I（UCN I）（一种内源性CRFR2激动剂）的腹侧下丘脑（VMH）直接导向腹膜下丘脑（VMH），这种抑制作用被抑制了（约55-60％） ，而CRF（主要是CRFR1激动剂）将CRR放大（约50-70％）至低血糖症。已显示UCN I直接改变脑切片中全细胞电流钳记录中VMH葡萄糖敏感神经元的葡萄糖敏感性。有趣的是，在体内VMH显微注射后，UCN I介导的CRFR2激活的抑制作用持续至少24小时。我们的数据表明，CRR的调节很大程度上取决于VMH中CRFR2介导的抑制与CRFR1介导的激活之间的相互作用。

BACKGROUND & AIMS: :Autoimmune hypoglycemia is characterized by hyperinsulinemia, fasting hypoglycemia, and the presence of insulin auto- antibodies without previous exposure to exogenous insulin. We experienced a case of autoimmune hypoglycemia without diabetes mellitus or any evidence of insulinoma. The insulin auto-antibody and insulin receptor auto-antibody were present. We diagnosed the patient as having autoimmune hypoglycemia and treated with glucocorticoid. After treatment, the hypoglycemic symptoms were resolved. However, four months later, the patient was readmitted with transient diabetic ketoacidosis. After recovery, he showed no signs of diabetes mellitus. We believe that insulin auto-antibodies may play a role in autoimmune hypoglycemia and diabetic ketoacidosis, but its role and mechanism are not precisely known. Further studies are needed to define the action mechanisms and the functions of insulin auto-antibodies: here we present case with a relevant literature.

背景与目标： 自身免疫性低血糖症的特征是高胰岛素血症，空腹低血糖症和存在胰岛素自身抗体，而无需事先接触外源胰岛素。我们经历了一例自身免疫性低血糖症，无糖尿病或胰岛素瘤的任何证据。存在胰岛素自身抗体和胰岛素受体自身抗体。我们诊断出该患者患有自身免疫性低血糖症，并接受糖皮质激素治疗。治疗后，降血糖症状得以缓解。然而，四个月后，该患者因暂时性糖尿病酮症酸中毒而再次入院。康复后，他没有显示出糖尿病的迹象。我们认为胰岛素自身抗体可能在自身免疫性低血糖和糖尿病性酮症酸中毒中起作用，但其作用和机制尚不清楚。需要进一步的研究来确定胰岛素自身抗体的作用机制和功能：在此我们提供相关文献资料。

BACKGROUND & AIMS: :Glycogen storage disease is a rare congenital disorder that can lead to hypoglycemic events. This article focuses on a patient in acute distress secondary to hypoglycemia that failed to respond to initial interventions. Because symptoms can be similar to severe hyperglycemia, a thorough history and physical examination are key to prompt diagnosis and appropriate management.

背景与目标： ：糖原贮积病是一种罕见的先天性疾病，可导致降血糖事件。本文重点关注因低血糖继发于急性窘迫的患者，该患者对初始干预措施没有反应。由于症状可能与严重的高血糖相似，因此全面的病史和体格检查对于及时诊断和适当管理至关重要。

BACKGROUND & AIMS: During hypoglycemia, cerebral blood flow (CBF) does not increase significantly until peripheral glucose levels are very low (2.0 mmol/l), that is, well below the blood glucose threshold for impairment of cognitive function (3.0 mmol/l). Because increased rates of cerebral blood flow will increase glucose transport, a failure of flow to rise earlier, before brain function is threatened, might be considered maladaptive. To examine the influence of inducing an earlier rise in CBF during hypoglycemia, eight healthy volunteers participated in three studies using a randomized, placebo-controlled design. In all three studies, a hyperinsulinemic (60 mU x m2 x min(-1)) clamp was used to maintain blood glucose levels at 4.5 mmol/l for 60 min. Thereafter, for EUG-ACZ, blood glucose was maintained at 4.5 mmol/l from 60 to 170 min and at 90 min from the start of this study, and 1-g acetazolamide i.v. was given to induce an early rise in CBF; for HYPO-ACZ, glucose was lowered over 20 min to 2.8 mmol/l and kept at that level for 90 min, and acetazolamide was given 90 min from the start of this study; and for HYPO-CON, glucose was treated as in HYPO-ACZ, and matching placebo was given in place of acetazolamide. Injection of acetazolamide was associated with a 30% rise in right (95% CI 24-34%) and left (20-32%) middle cerebral artery velocity (an index of CBF) during euglycemia without any change in hypoglycemia awareness or counterregulatory hormone levels. When glucose was lowered to 2.8 mmol/l, acetazolamide caused a similar rise in middle cerebral artery velocity in the HYPO-ACZ study. However, all subjects were less "aware" of hypoglycemia, had fewer adrenergic symptoms (sweating, palpitations, tremors; all P < 0.05), and had lower plasma epinephrine levels (1,026 vs. 1,790 pmol/l; -764 [437 to 1,097] pmol/l, point estimate of difference [95% CI]; P < 0.001), compared with the HYPO-CON study, whereas levels of other counter-regulatory hormones and norepinephrine were similar. Cognitive function (latency of the P300 evoked response) was unaffected by increasing CBF. In conclusion, enhanced rates of cerebral blood flow at the onset of systemic hypoglycemia are associated with diminished perception of low blood glucose levels and attenuation of the epinephrine counterregulatory response. These findings suggest that augmenting cerebral blood flow leads to an enhanced rate of substrate delivery to the central nervous system.

背景与目标： 低血糖期间，直到周围的葡萄糖水平非常低（2.0 mmol / l），即远低于认知功能受损的血糖阈值（3.0 mmol / l），脑血流量（CBF）才会显着增加。因为脑血流量的增加会增加葡萄糖的转运，所以在脑功能受到威胁之前，血流量的上升较早就会失败，这可能被认为是适应不良的。为了检查在低血糖期间诱导CBF提前升高的影响，八名健康志愿者使用随机，安慰剂对照设计参加了三项研究。在所有三项研究中，均使用高胰岛素（60 mU x m2 x min（-1））钳将血糖水平维持在4.5 mmol / l达60分钟。此后，对于EUG-ACZ，从研究开始60至170分钟和90分钟，血糖维持在4.5 mmol / l，1-g乙酰唑胺静脉注射。被给予诱导脑血流量的早期上升;对于HYPO-ACZ，从20分钟开始将葡萄糖降低至2.8 mmol / l，并​​在该水平下保持90分钟，并从研究开始90分钟开始给予乙酰唑胺。对于HYPO-CON，与HYPO-ACZ一样处理葡萄糖，并给予匹配的安慰剂代替乙酰唑胺。在正常血糖期间，注射乙酰唑胺会导致右中脑动脉速度（95％CI 24-34％）和左中脑动脉速度（CBF指数）增加30％，而对低血糖的认识或调节激素没有任何变化水平。在HYPO-ACZ研究中，当葡萄糖降低至2.8 mmol / l时，乙酰唑胺会引起大脑中动脉速度的类似升高。但是，所有受试者对低血糖的“认识”较少，肾上腺素能症状（出汗，心pit，震颤；所有P <0.05）较少，血浆肾上腺素水平较低（1,026对1,790 pmol / l； -764 [437至1,097] ]]> pmol / l，与HYPO-CON研究相比，差异点估计值[95％CI]； P <0.001），而其他抗调节激素和去甲肾上腺素的水平相似。认知功能（P300诱发反应的潜伏期）不受CBF增加的影响。总之，系统性低血糖发作时脑血流量的增加与对低血糖水平的感知减弱以及肾上腺素反调节反应的减弱有关。这些发现表明，脑血流量的增加导致底物向中枢神经系统输送的速率增加。

BACKGROUND & AIMS: OBJECTIVE:To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes using basal insulin (≥42 units/day) plus oral antihyperglycemic drugs (OADs). RESEARCH DESIGN AND METHODS:EDITION 2 was a multicenter, open-label, two-arm study. Adults receiving basal insulin plus OADs were randomized to Gla-300 or Gla-100 once daily for 6 months. The primary end point was change in HbA1c. The main secondary end point was percentage of participants with one or more nocturnal confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemic events from week 9 to month 6. RESULTS:Randomized participants (n = 811) had a mean (SD) HbA₁c of 8.24% (0.82) and BMI of 34.8 kg/m(2) (6.4). Glycemic control improved similarly with both basal insulins; least squares mean (SD) reduction from baseline was -0.57% (0.09) for Gla-300 and -0.56% (0.09) for Gla-100 (mean difference -0.01% [95% CI -0.14 to 0.12]), with 10% higher dose of Gla-300. Less nocturnal confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemia was observed with Gla-300 from week 9 to month 6 (relative risk 0.77 [95% CI 0.61-0.99]; P = 0.038) and during the first 8 weeks. Fewer nocturnal and any time (24 h) hypoglycemic events were reported during the entire 6-month period. Weight gain was lower with Gla-300 than with Gla-100 (P = 0.015). No between-treatment differences in safety parameters were identified. CONCLUSIONS:Gla-300 was as effective as Gla-100 and associated with a lower risk of hypoglycemia during the night and at any time of the day.

背景与目标： 目的：比较使用基础胰岛素（≥42单位/天）和口服胰岛素的新型甘精胰岛素300单位/毫升（Gla-300）和甘精胰岛素100单位/毫升（Gla-100）在2型糖尿病患者中的疗效和安全性抗高血糖药（OADs）。
研究设计与方法：第2版是一项多中心，开放标签的两臂研究。接受基础胰岛素加OAD的成年人每天随机分配一次Gla-300或Gla-100，持续6个月。主要终点是HbA1c的变化。主要的次要终点是从第9周到第6个月有一次或多次夜间确诊（≤3.9mmol / L [≤70mg / dL]）或严重的降血糖事件的参与者百分比。
结果：随机分组的参与者（n = 811）的平均（SD）HbA₁c为8.24％（0.82）和BMI为34.8 kg / m（2）（6.4）。两种基础胰岛素对血糖的控制也有相似的改善。 Gla-300与基准线相比，从基准的最小平方均方差（SD）降低为-0.57％（0.09），Gla-100降低为-0.56％（0.09）（均差-0.01％[95％CI -0.14至0.12]），其中10 Gla-300的剂量增加了％。从第9周到第6个月，Gla-300的夜间确诊较少（≤3.9mmol / L [≤70mg / dL]）或严重低血糖（相对危险度0.77 [95％CI 0.61-0.99]； P = 0.038）和在头8周内。在整个6个月的时间内，夜间事件和任何时间（24小时）的降血糖事件均较少。 Gla-300的体重增加低于Gla-100的体重增加（P = 0.015）。没有发现安全参数之间的治疗差异。
结论：Gla-300与Gla-100一样有效，并且在夜间和白天的任何时间都有较低的低血糖发生风险。