HbA1c Is Disproportionately Higher in Women and Older People With Type 1 Diabetes Compared With Flash Glucose Monitoring Metrics of Glycemic Control

Aims:Discrepancy between HbA1c and glucose exposure may have significant clinical implications. We sought to assess predictors of disparity between HbA1c and flash monitoring metrics and how these relate to microvascular complications.Methods:We conducted a cross-sectional study of adults with type 1 diabetes (n = 518). We assessed the relationship between clinic HbA1c and flash monitoring metrics, predictors of discrepancy between these measurements, and whether discrepancy was associated with microvascular complications.Results:Actual HbA1c and estimated HbA1c were strongly correlated (r = .779, P < .001). The likelihood of having a higher actual HbA1c than estimated HbA1c was greater with increasing age (OR = 1.055 per year, P < .001) and lower in men (OR = .208, P < .001). HbA1c was significantly lower in men (58 mmol/mol [51-67]) (7.5% [6.8-8.3]) compared to women (61 mmol/mol [54-70], P = .021) (7.7% [7.1-8.6]), despite no significant differences in any flash monitoring metrics. Whereas HbA1c was not different between younger (≤39 years) and older individuals (>39 years) despite significantly higher glucose exposure, in younger people, based on multiple flash monitoring metrics. Having a lower estimated than actual HbA1c was independently associated with a lower prevalence of retinopathy (OR = .55, P = .004).Conclusions:HbA1c appears to overestimate glucose exposure in women and older people with type 1 diabetes. This has potentially important clinical implications, as is hinted at by the independent relationship with retinopathy prevalence. It may also be of relevance when considering the use of HbA1c for the diagnosis of diabetes.     

基于MATLAB的CGMS数据整合分析软件的开发和在糖尿病合并低血糖时血糖波动特点研究上的使用

目的：观察低血糖血糖波动趋势,探究低血糖发生的特点。方法：通过矩阵实验室（MarxLabomtory,MATLAB）编程设计了与MmiMed解决方案（MiniMedSolutionsCGMSSensor,MSCS）的接口,利用MATLAB分析能力,实现大样本量的CGMS数据整合分析。结果：对829例CGMS数据进行筛选,符合研究条件405例,其中出现低血糖患者204例占50．62％。CGMS血糖监测系统与指测血糖在不同血糖范围均有较高一致性（P〈O．01）。低血糖患者整体血糖低于非低血糖患者,低血糖发生时间尤以半夜及午餐前居多。低血糖聚集发生时间平均在1点09分,标准差时间为5小时31分。不同年龄段低血糖患者比较．低血糖发生时间随年龄增长而提前（P〈O．01）。结论：MATLAB在大量CGMS监测数据处理具有速度快、设计灵活、使用方便等优点。低血糖的发生具有规律性,我们今后的研究方向是和低血糖发生可能相关的方向调节激素,神经内分泌的调节和脑生物钟的变化。     

Insulin detemir improves glycemic control and reduces hypoglycemia in children with type 1 diabetes: findings from the Turkish cohort of the PREDICTIVE™ observational study

Background: Insulin detemir is a basal insulin analog designed to produce a superior pharmacokinetic profile to basal formulations of human insulin. It has shown consistently improved tolerability in comparison to neutral protamine Hagedorn (NPH) insulin in adult cohorts, but there are relatively few publications involving pediatric cohorts. Methods: The efficacy and safety of insulin detemir in children with type 1 diabetes was assessed using data from the Turkish cohort of PREDICTIVE? (a large, multinational, observational) study. The children investigated were using basal–bolus therapy involving NPH insulin or insulin glargine at baseline but were switched to insulin detemir as part of routine clinical care by their physicians. Results: Twelve weeks of treatment with insulin detemir significantly reduced mean hemoglobin A1c (9.7–8.9%, p < 0.001) and mean fasting glucose [185–162 mg/dL (10.3–9 mmol/L), p < 0.01]. Fasting glucose variability was also lower after treatment with insulin detemir than previously (on either NPH or glargine, p < 0.05). The frequencies of total, major and nocturnal hypoglycemic events were significantly reduced with insulin detemir relative to baseline, with an estimated mean of 6.89 fewer events/patient/yr overall (p < 0.001) and 2.6 fewer nocturnal events/patient/yr (p < 0.01). Weight and insulin dose remained relatively unchanged. Conclusions: Twelve weeks of treatment with insulin detemir improved glycemic control and reduced hypoglycemia in children with type 1 diabetes. This improved tolerability might allow further dose titration and therefore additional improvements in glucose control.     

Hepatic glycogen synthase deficiency: an infrequently recognized cause of ketotic hypoglycemia

The glycogen storage diseases comprise several inherited diseases caused by abnormalities of enzymes that regulate the synthesis or degradation of glycogen. In contrast to the classic hepatic glycogen storage diseases that are characterized by fasting hypoglycemia and hepatomegaly, the liver is not enlarged in GSD0. Patients with GSD0 typically have fasting ketotic hypoglycemia without prominent muscle symptoms. Most children are cognitively and developmentally normal. Short stature and osteopenia are common features, but other long-term complications, common in other types of GSD, have not been reported in GSD0. Until recently, the definitive diagnosis of GSD0 depended on the demonstration of decreased hepatic glycogen on a liver biopsy. The need for an invasive procedure may be one reason that this condition has been infrequently diagnosed. Mutation analysis of the GYS2 gene (12p12.2) is a non-invasive method for making this diagnosis in patients suspected to have this disorder. This mini-review discusses the pathophysiology of this disorder, use of mutation analysis to diagnose GSD0, and the clinical characteristics of all reported cases of GSD0.     

Usefulness of insulin detemir in Japanese children with type 1 diabetes

Background: This multicenter observational study was conducted to investigate the efficacy and safety of insulin detemir (detemir) for diabetes management in Japanese children and adolescents. Methods: Data from the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes database were analyzed. Ninety children (32 boys, 58 girls; mean age, 11.9 ± 3.8 years) who transferred from a neutral protamine Hagedorn insulin or insulin glargine basal‐bolus regimen to detemir basal‐bolus therapy and who were observed for at least 12 months were identified. Clinical data obtained at 0, 3, 6, and 12 months were analyzed to determine the type of bolus insulin used, number and timing of detemir injections, detemir dose as a proportion of the total insulin dose, hemoglobin A1c (HbA1c), fasting blood glucose (FBG) and frequency of severe hypoglycemia. Results: Twelve months after switching to detemir, the detemir dose represented 39.8% of the total insulin dose, and 37.8% of patients were being treated with twice‐daily injections. HbA1c and FBG were significantly reduced from baseline at 3 and 6 months but not at 12 months. Considering the seasonal HbA1c variation in the Japanese population, a separate analysis was performed using data for 65 children (21 boys, 44 girls; mean age, 11.6 ± 2.9 years) who switched to detemir during the winter. Subset analysis showed significant HbA1c reductions from baseline at all specified times. The incidence of severe hypoglycemia during detemir treatment was 4.4 episodes per 100 patient‐years. Conclusions: Detemir is an effective and safe basal insulin for diabetes management in Japanese children and adolescents.     

新生儿低血糖脑损伤临床特征与脑电图监测

目的探讨新生儿低血糖脑损伤(HBD)时的脑电图(EEG)改变与临床预后关系,为HBD的诊断及预防提供依据。方法监测住院新生儿血糖并描记入院后24～72 h的EEG,低血糖新生儿于入院后2周再次EEG检查。分析比较低血糖新生儿与正常血糖新生儿,以及无症状性与症状性低血糖患儿EEG的异常率以及预后。结果入组100例新生儿,其中低血糖组52例,正常血糖组48例;低血糖组新生儿中症状性低血糖25例,无症状性低血糖27例。EEG异常率低血糖组新生儿73.1%(38/52),正常血糖组12.5%(6/48),两者差异有统计学意义(χ2=37.17,P<0.05)。低血糖组新生儿中,症状性低血糖组EEG异常率96%(24/25),无症状性低血糖组51.9%(14/27),两者差异有统计学意义(χ2=10.7,P<0.05)。新生儿血糖越低、持续时间越长,则EEG异常越严重。EEG中重度异常新生儿,大多遗留认知障碍、癫疒间、脑瘫等后遗症。结论新生儿HBD与低血糖的严重程度及持续时间密切相关。EEG能客观、直接地反映脑细胞的功能状态及损害程度,有助于早期评估脑损伤的程度及预后。     

中效胰岛素联合糖适平与预混胰岛素治疗2型糖尿病临床效果研究

目的 研究预混胰岛素血糖控制不佳的2型糖尿病患者改为糖适平与中效胰岛素联合降糖的效果.方法 选取我院收治的56例2型糖尿病患者,将其随机分为观察组以及对照组,观察组采用中效胰岛素联合糖适平治疗,对照组采用早晚两次注射预混胰岛素方式治疗,比较两组治疗后第5天患者的空腹血糖、平均餐后血糖、胰岛素用量及低血糖发生情况.结果 治疗后5d,观察组患者的空腹血糖、平均餐后2小时血糖均明显低于对照组,治疗后2个月复查糖化血红蛋白水平观察组明显低于对照组,组间比较差异有统计学意义(P＜0.05),两组胰岛素用量比较差异无统计学意义(P＞0.05),两组均出现1例低血糖.结论 中效胰岛素可以明显改善空腹血糖,但对餐后血糖控制欠佳者,联合糖适平治疗可以很好地克服这一问题,早晚两针中效胰岛素联合口服糖适平治疗降糖效果优于预混胰岛素治疗.     

Kabuki syndrome with midgut malrotation and hyperinsulinemic hypoglycemia: A rare co‐occurrence from Thailand

Kabuki syndrome (KS) is a rare heterogeneous phenotypic genetic syndrome, characterized by hypotonia, developmental delay and/or intellectual disability with typical facial features. It is challenging to diagnose KS in newborn and young infant. We report a Thai girl who presented with two rare co‐occurrence phenotypes, hyperinsulinemic hypoglycemia and midgut malrotation. She had not have distinctive facial dysmorphism during neonatal period. At 4 months of age, she had poor weight gain with some facial features suggestive KS. Singleton whole exome sequencing (WES) was carried out followed by Sanger sequencing of the supposed variant. The result indicated a novel de novo heterozygous KMT2D mutation, c.15364A>T (p.Lys5122*), confirming KS. Our patient revealed rare clinical manifestations from the diverse population and address the benefit of WES in establishing early diagnosis of KS before typical facial gestalt exhibited, which allows timely and appropriate management to maximize developmental achievement.     

Carnitine palmitoyltransferase deficiencies

Carnitine palmitoyltransferase (CPT) deficiencies are common disorders of mitochondrial fatty acid oxidation. The CPT system is made up of two separate proteins located in the outer- (CPT1) and inner- (CPT2) mitochondrial membranes. While CPT2 is a ubiquitous protein, two tissue-specific CPT1 isoforms-the so-called "liver" (L) and "muscle" (M) CPT1s-have been shown to exist. Amino acid and cDNA nucleotide sequences have been identified for all of these proteins. L-CPT1 deficiency (13 families reported) presents as recurrent attacks of fasting hypoketotic hypoglycemia. Two L-CPT1 mutations have been reported to date. M-CPT1 deficiency has not been hitherto identified. CPT2 deficiency has several clinical presentations. The "benign" adult form (more than 150 families reported) is characterized by episodes of rhabdomyolysis triggered by prolonged exercise. The prevalent S113L mutation is found in about 50% of mutant alleles. The infantile-type CPT2 deficiency (10 families reported) presents as severe attacks of hypoketotic hypoglycemia, occasionally associated with cardiac damage commonly responsible for sudden death before 1 year of age. In addition to these symptoms, features of brain and kidney dysorganogenesis are frequently seen in the neonatal-onset CPT2 deficiency (13 families reported), almost always lethal during the first month of life. More than 25 CPT2 mutations (private missense or truncating mutations) have hitherto been detected. Treatment is based upon avoidance of fasting and/or exercise, a low-fat diet enriched with medium chain triglycerides and carnitine ("severe" CPT2 deficiency). Prenatal diagnosis may be offered for pregnancies at a 1/4 risk of infantile/severe-type CPT2 deficiency.     

Mutations in the Genes Encoding the Transcription Factors Hepatocyte Nuclear Factor 1 Alpha and 4 Alpha in Maturity‐Onset Diabetes of the Young and Hyperinsulinemic Hypoglycemia

Maturity‐onset diabetes of the young (MODY) is a monogenic disorder characterized by autosomal dominant inheritance of young‐onset (typically <25 years), noninsulin‐dependent diabetes due to defective insulin secretion. MODY is both clinically and genetically heterogeneous with mutations in at least 10 genes. Mutations in the HNF1A gene encoding hepatocyte nuclear factor‐1 alpha are the most common cause of MODY in most adult populations studied. The number of different pathogenic HNF1A mutations totals 414 in 1,247 families. Mutations in the HNF4A gene encoding hepatocyte nuclear factor‐4 alpha are a rarer cause of MODY with 103 different mutations reported in 173 families to date. Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. The HNF4A MODY phenotype has been expanded by the reports of macrosomia in ～50% of babies, and more rarely, neonatal hyperinsulinemic hypoglycemia. The identification of an HNF1A or HNF4A gene mutation has important implications for clinical management in diabetes and pregnancy, but MODY is significantly underdiagnosed. Current research is focused on identifying biomarkers and developing probability models to identify those patients most likely to have MODY, until next generation sequencing technology enables cost‐effective gene analysis for all patients with young onset diabetes.