Maternal type 1 and gestational diabetes: postnatal differences in insulin secretion in offspring at preschool age

Background: It is well known that children born to mothers with diabetes in pregnancy are more likely to develop metabolic abnormalities in later life. Most prior studies have not differentiated between offspring of mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) or lack a control group of non‐exposed offspring. Subjects: Offspring of T1DM (n = 16), GDM (n = 22) and mothers without diabetes (n = 25) born at Oulu University Hospital. Aim: To assess insulin secretion and insulin resistance in the offspring of T1DM and GDM at preschool age in comparison with offspring of non‐diabetic mothers. Methods: Anthropometric measurements and intravenous glucose tolerance testing were performed. First‐phase insulin response (FPIR) and homoeostasis model assessment (HOMA) values were calculated. Pregnancy and birth data were analysed in relation to later metabolic parameters in all three groups using one‐way analysis of variance (anova ) and analysis of covariance (ancova ). Results: At a mean age of 4.9 yr, offspring of T1DM had increased fasting serum insulin concentrations (p = 0.044), FPIR (p = 0.034) and HOMA‐B values (p = 0.008) compared with offspring of GDM or with offspring of healthy controls (statistically non‐significant). The GDM gained least weight during pregnancy, and when adjusted for maternal weight gain during pregnancy, there were no statistically significant differences between study groups. Conclusions: Prenatal exposures to maternal type 1 and gestational diabetes may have different effects on postnatal glucose metabolism in the offspring assessed at a mean age close to 5 yr. Maternal weight gain in pregnancy may affect the postnatal glucose metabolism in the offspring.     

Effect of spontaneous gestational diabetes on fetal and postnatal hepatic insulin resistance in Lepr(db/+) mice

Infant macrosomia is a classic feature of a gestational diabetes mellitus (GDM) pregnancy and is associated with increased risk of adult obesity and type II diabetes mellitus, however mechanisms linking GDM and later disease remain poorly understood. The heterozygous leptin receptor-deficient (Lepr(db/+)) mouse develops spontaneous GDM and the fetuses display characteristics similar to infants of GDM mothers. We examined the effects of GDM on maternal insulin resistance, fetal growth, and postnatal development of hepatic insulin resistance. Fetal body weight on d 18 of gestation was 6.5% greater (p < 0.05) in pups from ad libitum-fed db/+ mothers compared with wild-type (WT) controls. Pair-feeding db/+ mothers to the intake of WT mothers normalized fetal weight despite less than normal maternal insulin sensitivity. More stringent caloric restriction reduced insulin and glucose levels below WT controls and resulted in fetal intrauterine growth restriction. The level of hepatic insulin receptor protein was decreased by 28% to 31% in both intrauterine growth restriction and fetuses from ad libitum-fed GDM mothers compared with offspring from WT mothers. In 24-wk-old adult offspring from GDM mothers, body weight was similar to WT offspring, however, the females from GDM mothers were fatter and hyperinsulinemic compared with offspring from WT mothers. Insulin-stimulated phosphorylation of Akt, a key intermediate in insulin signaling, was severely decreased in the livers of adult GDM offspring. Hepatic glucose-6-phosphatase activity was also inappropriately increased in the adult offspring from GDM mothers. These results suggest that spontaneous GDM in the pregnant Lepr(db/+) mouse is triggered by overfeeding, and this effect results in obesity and insulin resistance in the livers of the adult offspring. The specific decrease in Akt phosphorylation in livers of adult offspring suggests that this may be a mechanism for reduced insulin-dependent physiologic events, such as suppression of hepatic glucose production, a defect associated with susceptibility to type II diabetes mellitus.     

Developmental outcome of offspring of pregestational diabetic mothers

The aim of this study was to investigate the one-year developmental outcome of offspring of mothers with pregestational diabetes mellitus (PGDM). We prospectively evaluated 31 women with PGDM (21 with type 1 DM and 10 with type 2 DM) and 41 nondiabetic controls during pregnancy and for one year follow-up. Data showed that offspring of mothers with PGDM scored lower than controls in all aspects of development--mental, psychomotor, and exploration/orientation. Despite the good metabolic control of the mothers with PGDM, their offpsring showed a less favorable developmental outcome at one year than infants of nondiabetic mothers. MDI score and PDI score were significantly lower in the diabetic group than in the controls (91.04 vs 98.15, p<0.05 and 85.15 vs 95.54, p<0.05, respectively). In addition, the orientation/engagement score was lower in the diabetic group as compared with the nondiabetic group (41.04 vs 45.50, p<0.05). Whereas no significant difference was found between the type 1 and type 2 groups with regard to the MDI score, type 2 infants scored lower on the PDI than infants in the type 1 group (78.1 vs 89.3) but higher on the motor quality score (34.0 vs 31.3). These preliminary findings support the need for ongoing large scale developmental follow-up studies of offspring born to diabetic mothers in order to elucidate whether they have cognitive impairment later in life.     

Prevalence of metabolic markers of insulin resistance in offspring of gestational diabetes pregnancies

In utero hyperglycemia has been associated with insulin resistance (IR) in children; however, there are limited data in low-risk populations. The purpose of this study was to describe the prevalence of metabolic markers of IR in a primarily Caucasian cohort of gestational diabetes mellitus (GDM) offspring aged 7-11 yr (mean 9.1) and to correlate offspring with maternal indexes. Sixty-eight children were recruited through a follow-up study of women who participated in a randomized controlled trial of minimal intervention vs. tight glycemic control for GDM. All participants had a fasting plasma glucose (FPG), insulin, total cholesterol, high-density lipoprotein cholesterol (HDL-chol), triglyceride (TG) level, and a 2-h oral glucose tolerance test. We calculated homeostasis model assessment (HOMA) and recorded body mass index and waist circumference (WC). Criteria for metabolic syndrome for children included: FPG > 6.0 mmol/L, HDL-chol < 1.03 mmol/L, TG > 1.24 mmol/L, WC > 90% for age and gender, and 2-h glucose > 7.8 mmol/L. Among these children, 45 (66%), 17 (25%), 5 (7%), and 1 (1.5%) had zero, one, two, or three metabolic markers of IR, respectively. Hypertriglyceridemia (21%) was most prevalent, with no child having an elevated FPG. WC (p = 0.018) and TG (p = 0.005) were strong predictors of IR in the offspring after adjustment for age, gender, birthweight, family history, and maternal IR. Maternal and offspring HDL-chol, TG, WC, and HOMA but not fasting or 2-h glucose levels were significantly correlated. We conclude that metabolic markers of IR in children exposed to GDM may be present in the absence of abnormal fasting or 2-h glucose values. Screening strategies that focus on glucose levels may need to be reconsidered to institute early intervention with lifestyle changes for children at risk.     

Effect of Carelink, an internet-based insulin pump monitoring system, on glycemic control in rural and urban children with type 1 diabetes mellitus

Objective:  To determine whether use of the internet-based insulin pump monitoring system, Carelink, improved glycemic control in rural and urban children treated with insulin pump therapy.
Research design:  We reviewed records of 94 children treated with insulin pump therapy between the years 2004 and 2007 and compared glycemic control, diabetes self-care measures, frequency of clinic visits, and geographic location associated with Carelink use.
Results:  Carelink users showed improvement in hemoglobin A1c (HbA1c) levels [8.0 ± 0.1 (SE) vs. 7.7 ± 0.1 (SE), p = 0.002]. Carelink users uploaded pump and glucometer data 2.2 ± 1.8 (SD) times per month over 0.8 ± 0.4 (SD) yr. Patients who had no access to carelink software and were followed in a conventional manner showed no change in HbA1c levels [8.0 ± 0.2 (SE) vs. 8.1 ± 0.2 (SE), p = 0.17] during the study period. Carelink non-users, defined as patients who had Carelink access but did not use it, had a higher HbA1c level at the start of the study and did not change over the study period [8.9 ± 0.2 (SE) vs. 9.0 ± 0.3 (SE), p = 0.82]. Rural Carelink users showed improvement in HbA1c levels following Carelink use [7.9 ± 0.2 (SE) vs. 7.4 ± 0.2 (SE), p = 0.001], yet had significantly fewer clinic visits per year compared with urban patients [2.8 ± 0.2 (SE) vs. 3.5 ± 0.1 (SE), p = 0.001].
Conclusion:  Use of the Carelink system was associated with improved glycemic control in children with type 1 diabetes on insulin pump therapy.     

Improved glycemic control and lower frequency of severe hypoglycemia with insulin detemir; long-term experience in 105 children and adolescents with type 1 diabetes

Objective:  To assess the effect of the insulin analog detemir on glycemic control and severe hypoglycemia in children and adolescents with type 1 diabetes.
Research design and methods:  A retrospective chart analysis was performed in 105 patients with type 1 diabetes after switching to insulin detemir between 2004 and 2007. In children below 12 yr of age (n = 53), evening neutral protomin hagedorn (NPH) insulin was replaced by insulin detemir if therapeutic goals were not reached and blood glucose levels were unpredictable or hardly controllable. In adolescents above 12 yr of age (n = 52), insulin detemir was started when changing to intensified insulin therapy.
Results:  In children below 12 yr of age, hemoglobin A1c (HbA1c) at start was 8.3 ± 0.8% and after 12 months of treatment with insulin detemir significantly lowered (7.6 ± 0.6%, p < 0.001). In the age-group above 12 yr of age at the start of the study, the improvement of HbA1c after 12 months of treatment was less pronounced (8.0 ± 1.2 vs. 7.6 ± 1.0%) but still significant (p < 0.01). The risk for severe hypoglycemia was significantly decreased compared with patients attending the outpatient clinic between 1995 and 2003 (4.8/100 patient years vs. 7.6/100 patient years, p = 0.003). From the beginning to the end of the follow-up period, body mass index dropped significantly in children below 12 yr of age but no effect was observed in adolescents.
Conclusions:  Use of insulin detemir allows a safe nocturnal glycemic control in children and adolescents with type 1 diabetes and is associated with significantly improved HbA1c levels and fewer severe hypoglycemic events. This makes insulin detemir a most valuable new tool for the treatment of children and adolescents with type 1 diabetes.     

Basal insulin and total daily insulin dose in children with type 1 diabetes using insulin pumps

Objective:  To assess the contribution of basal insulin to the total daily dose (CBITDD) and to identify the determinant factors in children with type 1 diabetes mellitus.
Study design:  Cross-sectional study in which the basal insulin requirement was established based on a memory read-out of insulin delivery from pumps. Factors such as glycated haemoglobin A1c (HbA1c), fasting C-peptide, standard deviation score of body mass index (sdsBMI) and demographic data were determined during routine hospital visits. Study group included a total of 90 well-controlled diabetic children with the mean HbA1c 6.6 ± 0.7 (5.2–7.9), age 10.4 ± 4.4 yr (1.1–17.9 yr), diabetes duration 3.0 ± 2.6 yr (0.3–10.9 yr) and sdsBMI 0.08 (−2.27 to 1.79), excluding patients with ketoacidosis or infectious diseases.
Results:  Correlations between CBITDD and age (r = 0.39 and p < 0.005) and diabetes duration (r = 0.61 and p < 0.0001) and an inverse correlation with C-peptide (r = −0.41 and p = 0.0001) were found. C-peptide-positive patients had a significantly lower percentage of basal insulin compared with C-peptide-negative patients (20.6 ± 11 vs. 31.6 ± 11.0%, respectively; p = 0.0004); yet, no significant difference in total insulin daily dose (0.65 ± 0.3 vs. 0.78 ± 0.2 U/kg/d, respectively) was observed.
Conclusions:  The percentage of basal insulin in diabetic children is below 50% and in well-controlled diabetic children is related to the fasting C-peptide level, age of patient and diabetes duration but not to HbA1c and sdsBMI.     

Maternal phenylketonuria in Western Australia: pregnancy outcomes and developmental outcomes in offspring

OBJECTIVE: To examine the outcomes of phenylketonuric (PKU) pregnancies in Western Australia including birth characteristics and cognitive and behavioural outcomes in offspring. METHODS: A cross-sectional study of women and their offspring who were identified from the Western Australian Maternal PKU Program (WAMPKUP) from 1991 to 2000 was carried out. Cognitive assessments (K-BIT or Griffiths scales) were conducted on women and their children, and behavioural assessments (CBCL) were conducted on the children. RESULTS: Thirty pregnancies by nine women were registered on the WAMPKUP between 1991 and 2000. There were 16 live births, with one preterm delivery at 32 weeks. There were no congenital abnormalities. Five of the nine mothers and their nine children (aged 18 months-10 years) participated in developmental assessments. A linear relationship was shown between lower maternal IQ scores and later attainment of metabolic control in pregnancy (rs = -0.828; P = 0.01). There was significant correlation between lower offspring IQ scores and later attainment of metabolic control in pregnancy (rs = -0.734; P = 0.02). Correlation between maternal and offspring cognitive scores was not significant. Four of nine (44%) children rated in the clinical range for behavioural problems. Compared to children with no behavioural difficulties, these children had lower cognitive abilities (P = 0.05) and maternal metabolic control during pregnancy was poor (P = 0.05). CONCLUSIONS: Poor metabolic control in pregnancy is associated with poorer cognitive outcomes and increased behavioural difficulties in offspring of mothers with PKU. The results have implications for the implementation of appropriate dietary measures before conception in PKU pregnancies, and indicate a need for the establishment of multidisciplinary teams to follow up individuals with PKU to communicate the importance of pregnancy planning, to manage PKU pregnancies, and to follow up the offspring.     

Erythrocyte indicators of oxidative stress in gestational diabetes

Foetuses born to mothers with gestational diabetes are at increased risk of developing respiratory distress, foetal macrosomia, foetal anomalies and platelet hyperaggregability. High blood glucose level induces oxidative stress and decreases antioxidant defences. The present study discusses the possibility of lipid peroxidation and protein oxidation in both maternal and foetal erythrocytes as an indicator of oxygen radical activity. The level of lipid peroxidation and protein oxidation in erythrocytes was estimated in 20 mothers with gestational diabetes and their newborns. The maternal age varied between 19 and 42 y and foetal age ranged between 34 and 39 weeks. The proteolytic activities in the erythrocyte lysates obtained from mothers with gestational diabetes and their newborns were significantly greater [(mean ± SD) 24.41 ± 9.05 and 16.70 ± 3.36μM of amino groups/g haemoglobin, n = 20, respectively] than those from control group (10.18 ± 4.84 and 14.64 ± 6.21 μM amino groups/g haemoglobin, n = 15, respectively; p < 0:05 in both cases). Similarly erythrocyte malondialdehyde levels were significantly elevated in babies born to mothers with gestational diabetes (10.11 ±2.21 nM/g haemoglobin) when compared to controls (6.8 ± 3.75 nM/g haemoglobin) (p < 0:05). In the erythrocytes of mothers with gestational diabetes, malondialdehyde levels correlated significantly with glycated haemoglobin levels (p < 0:01). The results of this study indicate that the oxidative stress induced by gestational diabetes manifests as increased lipid peroxidation and protein oxidative damage in the erythrocytes of both mothers with gestational diabetes and their newborn infants.     

孕期营养干预和代谢性危险因素对妊娠结局的影响

目的 探讨孕期营养干预和孕期代谢性危险因素对妊娠结局的影响。方法 研究对象为上海市国际和平妇幼保健院2010年5月至2012年4月接受常规产检并且分娩的孕妇。采用回顾性队列研究,在确诊为妊娠糖尿病(GDM)的孕妇中比较膳食干预组(接受膳食咨询) 和对照组(未接受膳食咨询)不良妊娠结局的差异,GDM诊断采用2010年国际糖尿病与妊娠研究组推荐标准。采用Logistics逐步回归分析母亲孕期危险因素对巨大儿发生的影响及作用大小。结果 ①10 421名孕妇的围生期信息进入数据分析。孕妇初诊时平均孕周20.8(19.4~22.4)周,初诊时空腹血糖(FBS)、三酰甘油(TG)和总胆固醇(CHOL)平均水平分别为(4.3±0.4)、(1.3±0.6)和(4.7±0.8) mmol·L-1,收缩压和舒张压的平均水平分别为(111.3±11.5)和(67.9±13.3)mmHg。高危孕妇的GDM的患病率为15.8%。新生儿平均出生体重(3 355.4±426.0) g,巨大儿发生率6.2%。②812名GDM孕妇中,干预组570例,对照组242例。两组孕妇年龄、文化程度、孕20周体重、初诊时血糖、血脂等基线水平均衡可比。干预组的新生儿出生体重、巨大儿发生率和妊娠期高血压发生率均低于对照组,分别为(3 347.4±19.6) vs (3 450.3±35.6) g(P=0.007)、6.7% vs 15.6%(P=0.001)和26.3% vs 47.9% (P<0.001)。随着营养干预次数的增加,孕中晚期体重增长量和新生儿出生体重均呈下降趋势(r=-0.126,P=0.003;r=-0.112,P=0.002),巨大儿的发生率也依次降低。③Logistic逐步回归分析显示,孕20周时体重(OR=1.08,95%CI:1.07～1.09)、孕中晚期体重增长量(OR=1.10,95%CI:1.07~1.12)和GDM(OR=1.63,95%CI:1.22~2.19)是巨大儿发生的危险因素。结论 对高危孕妇应考虑进行更早期的孕期危险因素管理以及膳食指导干预,控制孕期体重合理增长,有望减少不良妊娠结局的发生。     

母亲糖尿病及UCP2基因多态性与子代先天性心脏病关联的病例对照研究

目的 探讨母亲糖尿病、解偶联蛋白2基因（UCP2）多态性及两者的交互作用与子代先天性心脏病（CHD）的关系。方法 采用以医院为基础的病例对照研究,选择2018年3月至2019年8月在湖南省儿童医院确诊的464例单纯CHD患儿的母亲为病例组,选择同期住院、无先天畸形的504例患儿的母亲为对照组。通过问卷调查,收集相关暴露信息,同时采集母亲静脉血5 mL,用于UCP2基因多态性检测。采用多因素logistic回归分析探讨母亲糖尿病、UCP2基因多态性及两者交互作用与子代CHD的关联性。结果 多因素logistic回归分析显示,在控制混杂因素后,患有妊娠期糖尿病（OR=2.96,95% CI：1.57~5.59）、有妊娠期糖尿病史（OR=3.16,95% CI：1.59~6.28）和妊娠前患有糖尿病（OR=4.52,95% CI：2.41~8.50）均显著增加子代CHD的风险（P < 0.05）。母亲UCP2基因两个位点rs659366（T/C vs C/C：OR=1.49,95% CI：1.02~2.16;T/T vs C/C：OR=2.77,95% CI：1.67~4.62）和rs660339（A/A vs G/G：OR=2.19,95% CI：1.34~3.58）的多态性与子代CHD的风险存在关联（P < 0.05）。交互作用分析显示,UCP2基因两个位点（rs659366和rs660339）的多态性与母亲糖尿病在子代CHD发生中存在交互作用（P < 0.05）。结论 母亲糖尿病、UCP2基因多态性及其交互作用与子代CHD发病相关。     

Correlations between the intrauterine metabolic environment and blood pressure in adolescent offspring of diabetic mothers

OBJECTIVE: To investigate associations between maternal diabetes and blood pressure (BP), obesity, impaired glucose tolerance, and serum lipids in offspring and whether these parameters correlate with metabolism during pregnancy. STUDY DESIGN: Body mass index, BP, serum glucose, and insulin during an oral glucose tolerance test, and lipid concentrations were measured in 99 offspring of diabetic mothers (ODM) and 80 members of a control group. RESULTS: ODM were more obese (body mass index 22.5 +/- 5.6 vs 20.3 +/- 4.0 kg/m(2)) and had higher systolic (8 mm Hg) and mean arterial BP (4 mm Hg) but similar diastolic BP compared with the control group. ODM had higher 2-hour glucose (6.6 +/- 1.3 vs 5.7 +/- 0.9 mmol/L) and insulin (580 +/- 544 vs 377 +/- 239 pmol/L) concentrations but lower fasting concentrations of low-density lipoprotein (2.54 +/- 0.67 vs 2.82 +/- 0.70 mmol/L) and total cholesterol (4.01 +/- 0.80 vs 4.40 +/- 0.78 mmol/L). In both groups body mass index, triglycerides, and fasting and 2-hour glucose concentrations showed correlations with BP measurements. Fasting insulin was correlated with BP readings only in the ODM. Correlations were found between second- and third-trimester maternal free fatty acid concentrations and diastolic and mean arterial BP. Third-trimester beta-hydroxybutyrate was correlated with mean arterial BP. CONCLUSIONS: In ODM, abnormalities in weight and glucose tolerance are associated with abnormal maternal metabolism. Higher BP is an additional abnormality associated with fetal overnutrition.     

The change in ghrelin and obestatin levels in obese children after weight reduction

Aim: To investigate the role of ghrelin and obestatin in obesity mechanisms.
Methods: A total of 88 obese children and 25 normal children were enrolled. Moreover, 46 obese children took part in a summer camp for weight reduction. Fasting ghrelin, obestatin and other biochemical parameters were measured in all subjects and re-measured in 45 obese children finishing the camp.
Results: The ghrelin levels in the control and obese groups were 67.26 ± 23.41 pmol/L and 56.53 ± 15.97 pmol/L with a significant difference (p = 0.039), while the obestatin levels (89.41 ± 23.63 vs. 83.13 ± 17.21 pmol/L) were not significantly different (p = 0.083). The ghrelin/obestatin ratio in the controls was significantly higher than that in the obese group (p = 0.014). In the latter, fasting insulin and alanine aminotransferase were independent factors for ghrelin; fasting insulin, weight and gender were independent factors for obestatin and alanine aminotransferase was an independent factor for ghrelin/obestatin. Moreover, ghrelin, obestatin and ghrelin/obestatin increased after weight reduction (p < 0.05, respectively), and the increment in ghrelin and obestatin was associated with a decrement in insulin resistance.
Conclusion: These data suggest that ghrelin, obestatin and/or the ghrelin/obestatin ratio are associated with obesity in childhood.     

Endothelial progenitor cells and arterial functions in the late convalescence period of Kawasaki disease

Aim:  The relationship was investigated between endothelial progenitor cells (EPCs) level and arterial functions in the convalescence of Kawasaki disease (KD).
Methods:  Sixty-three children were divided into coronary artery lesion (CAL) group (group 1, n = 21), non-CAL group (group 2, n = 20) and control group (group 3, n = 22). EPCs were examined by flow cytometry and arterial functions (flow-mediated dilation [FMD], carotid artery stiffness index [SI]) were measured by ultrasound.
Results:  From group1 to group 3, FMD was 4.5%± 1.5%, 9.5%± 2.8% and 12.1%± 2.3% (p < 0.01 between any two groups); carotid artery SI was 4.10 ± 0.44, 3.81 ± 0.50 and 3.59 ± 0.46 (group 1 vs. group 2, p < 0.05; group 1 vs. group 3, p < 0.01; group 2 vs. group 3, p = 0.142) and the number of EPCs was 2.0 ± 0.6/μL, 4.2 ± 0.8/μL, 4.5 ± 0.7/μL (p < 0.01 for group1 vs. group 2 and group 1 vs. group 3; group 2 vs. group 3, p = 0.292). Multiple linear regressions analysis and correlation analysis identified that FMD and carotid artery SI were significant determinants of EPCs level and were all independently correlated with EPCs level.
Conclusions:  Our results indicate decreased EPCs are associated with arterial dysfunction in patients with CAL in the convalescence of KD. Our findings suggest EPCs may have a role in alteration of arterial functions.     

Gestational diabetes and offspring body disproportion

Aim:  It has been demonstrated that females born large for gestational age (LGA) in weight but not length are at increased risk of being obese at childbearing age. We addressed the question whether women with gestational diabetes mellitus (GDM) are at increased risk of giving birth to such infants.
Methods:  Birth characteristics of 884 267 infants of non-diabetic mothers and 7817 of mothers with GDM were analysed. LGA was defined as birth weight or birth length >2 standard deviation scores for gestational age. Multiple logistic regression analysis was performed.
Results:  The odds ratio (OR) for a woman with GDM to give birth to an LGA infant that was heavy alone was four times increased (OR: 3.71, 95% CI: 3.41–4.04). Furthermore, in the population of mothers giving birth to LGA infants, the proportion heavy alone was 68% in the group of women with GDM compared with 64.4% in the group of non-diabetic women. The risks were independent of gender of the foetus.
Conclusion:  Women with GDM have an almost four times higher risk of delivering an LGA infant that is heavy alone. The noted disproportion between weight and length in infants of such mothers may have an impact on the risk of later obesity.     

Infants of diabetic mothers

Advances in the management of the mother with diabetes have reduced the rate of morbidity and mortality for her infant. Aggressive control of maternal glycemic status is warranted, because most morbidities are epidemiologically and pathophysiologically closely linked to fetal hyperglycemia and hyperinsulinemia. The burgeoning public health problem of overweight and obesity in children will likely result in an increased incidence of metabolic syndrome X, characterized by insulin resistance and type II diabetes in adulthood. An early manifestation of this may be glucose intolerance during pregnancy in overweight women without diabetes. Clinicians must continue to have a high degree of suspicion for the diagnosis of diabetes during gestation and screen offspring of women with gestational diabetes for neonatal sequelae.     

Characteristics of glycemic control in young children with type 1 diabetes

Abtract: Background: The Diabetes Control and Complications Trial (DCCT) demonstrated that the rate-limiting step to the intensification of diabetes management in adolescents and adults was hypoglycemia. Young children were presumed to be at even greater risk for hypoglycemia with severe consequences, particularly if they had HbA1c levels < 8%.
Subjects: A retrospective chart review was performed on 148 patients with type 1 diabetes on insulin injection therapy who were < 8 yr of age (mean age 5.7 ± 1.5, mean diabetes duration 3.0 ± 1.4 yr) followed quarterly from July 1999 to June 2001.
Methods:  The subjects were divided into two groups based on their mean HbA1c values (< 8 vs. ≥ 8%) averaged over the 2-yr time period. The following variables were analyzed comparing the two groups: age, duration of diabetes, insulin dose, severe hypoglycemic episodes, episodes of diabetic ketoacidosis (DKA), percentage of glucose levels above, within, and below the target range, and number of diabetes home-management competencies obtained.
Results:  Patients with HbA1c < 8% spent more time within target range (40.0 vs. 29.5%, p = 0.0001) and less time above their target range (36.9 vs. 51.2%, p = 0.0003). There was no difference in the percentage of glucose levels below target (23.2 vs. 19.4%, p = NS), percentage of severe hypoglycemic episodes (3 vs. 7 episodes per 100 patient-yr, p = NS), or episodes of DKA (1 vs. 3 episodes per 100 patient-yr, p = NS) between the two groups. Subjects with lower HbA1c levels had acquired more home-management competencies (4.0 vs. 3.5, p = 0.01).
Conclusions:  If families are competent in fundamental diabetes management, young children can achieve HbA1c levels < 8.0% without increasing the risk of hypoglycemia.     

The addition of rosiglitazone to insulin in adolescents with type 1 diabetes and poor glycaemic control: a randomized-controlled trial

Objective:  To evaluate the effect of rosiglitazone, an insulin sensitizer, on glycaemic control and insulin resistance in adolescents with type 1 diabetes mellitus (T1DM)
Research design and methods:  Randomized, double-blind, placebo-controlled crossover trial of rosiglitazone (4 mg twice daily) vs. placebo (24 wk each, with a 4 wk washout period). Entry criteria were diabetes duration >1 yr, age 10–18 yr, puberty (≥Tanner breast stage 2 or testicular volume >4 mL), insulin dose ≥1.1 units/kg/day, and haemoglobin A1c (HbA1c) >8%. Responses to rosiglitazone were compared with placebo using paired t -tests.
Results:  Of 36 adolescents recruited (17 males), 28 completed the trial. At baseline, age was 13.6 ± 1.8 yr, HbA1c 8.9 ± 0.96%, body mass index standard deviation scores (BMI-SDS) 0.94 ± 0.74 and insulin dose 1.5 ± 0.3 units/kg/day. Compared with placebo, rosiglitazone resulted in decreased insulin dose (5.8% decrease vs. 9.4% increase, p = 0.02), increased serum adiponectin (84.8% increase vs. 26.0% decrease, p < 0.01), increased cholesterol (+0.5 mmol/L vs. no change, p = 0.02), but no significant change in HbA1c (−0.3 vs. −0.1, p = 0.57) or BMI-SDS (0.08 vs. 0.04, p = 0.31). Insulin sensitivity was highly variable in the seven subjects who consented to euglycaemic hyperinsulinaemic clamps. There were no major adverse effects attributable to rosiglitazone.
Conclusion:  The addition of rosiglitazone to insulin did not improve HbA1c in this group of normal weight adolescents with T1DM.     

母亲妊娠糖尿病与子代孤独症谱系障碍发生风险的关联分析

目的 探讨母亲妊娠糖尿病暴露与子代孤独症谱系障碍（autism spectrum disorder,ASD）发生的关联。方法 采用病例对照研究方法,招募221例ASD儿童与400例健康儿童纳入研究。采用问卷调查及访谈形式收集儿童一般情况、家庭社会经济学特征、母亲孕产史、母亲孕期疾病暴露等情况,采用多因素logistic回归分析探讨母亲妊娠糖尿病暴露与子代ASD发生的关联,并探讨子代性别和妊娠糖尿病暴露对子代ASD的发生是否存在交互作用。结果 ASD组母亲妊娠糖尿病患病比例显著高于对照组（16.3% vs 9.4%,P=0.014）。校正性别、胎龄情况、出生方式、产次、母亲文化程度等变量后,母亲妊娠糖尿病暴露是子代ASD发生的危险因素（OR=2.18,95%CI:1.04～4.54,P=0.038）;在校正以上变量的基础上,进一步校正孕早期复合维生素服用、孕前3个月叶酸服用和辅助生殖等变量后,结果趋势未发生改变,但未见统计学意义（OR=1.94,95%CI:0.74～5.11,P=0.183）。妊娠糖尿病暴露与子代性别对子代ASD的发生存在交互作用（P<0.001）;性别分层分析显...     

Diabetic patient and reproduction

Current views and opinions on pregnancy in diabetic mothers are presented. Special attention is paid to carbohydrate metabolism, pregestational diabetes mellitus (PGDM), gestational diabetes mellitus (GDM) and unclear heterogenous etiology of gestational diabetes mellitus (GDM). Suggestions for identification, diagnosis and treatment of GDM with an emphasis on early screening strategy are given. Obstetrical management and possible perinatal complications are discussed.