Is there a reduction of congenital abnormalities in the offspring of diabetic pregnant women after folic acid supplementation? A population‐based case‐control study

The objective of the present study was to estimate the preventive effect of folic acid for structural birth defects (i.e. congenital abnormalities [CAs]) in the offspring of pregnant women with diabetes mellitus type 1 (DM-1). The occurrence of medically recorded DM-1 in pregnant women who had malformed fetuses/newborns (cases) and delivered healthy babies (controls) with or without folic acid supplementation was compared in the population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities. The case group included 22,843 offspring, and there were 79 (0.35%) pregnant women with DM-1, while the control group comprised of 38,151 newborns, and 88 (0.23%) had mothers with DM-1. Case mothers with DM-1 associated with a higher risk of total rate of CAs in their offspring (OR with 95% CI: 1.5, 1.1-2.0) compared to the total rate of CAs in the offspring of non-diabetic case mothers. This higher risk can be explained by four specific types/groups of CAs: isolated renal a/dysgenesis; obstructive CA of the urinary tract; cardiovascular CAs; and multiple CAs, namely caudal dysplasia sequence. However, there was no higher rate of total CAs in the children of pregnant women with DM-1 after folic acid supplementation; in addition, neural-tube defect and renal a/dysgenesis did not occur. However, this benefit cannot be explained by the CA reduction effect of folic acid during the critical period of major CAs. In conclusion, there was a certain reduction in maternal teratogenic effect of DM-1 after folic acid supplementation during pregnancy, but the explanation of this effect requires further study.     

Peptic ulcer disease with related drug treatment in pregnant women and congenital abnormalities in their offspring

Peptic ulcer disease (PUD) is a common disease which can also occur in pregnant women. However, the possible association of PUD and related drug treatments in pregnant women with the risk of structural birth defects (i.e. congenital abnormalities [CA]) in their offspring has not been estimated in controlled population‐based epidemiological studies. Thus, the prevalence of PUD in pregnant women who later delivered babies (cases) with different CA and in pregnant women who delivered newborns without CA (controls) was compared in the Hungarian Case‐Control Surveillance of Congenital Abnormalities. Controls were matched to cases. Of 22 843 cases with congenital abnormalities, 182 (0.80%) had mothers with reported/recorded PUD, while of 38 151 controls, 261 (0.68%) were born to mothers with reported/recorded PUD. However, PUD(?) based on maternal information and/or unspecified diagnostic criteria, and PUD(!) based on endoscopic diagnosis showed different variables of mothers and newborn infants. Thus, finally, 20 case mothers and 58 control mothers with PUD(!) and related drugs were evaluated in detail. There was no higher risk for total CA group in the offspring of mothers with PUD during pregnancy (adjusted OR with 95% CI: 0.6, 0.3‐0.9). Specific CA groups in cases were also assessed versus controls, but specified CA had no higher risk in the offspring of pregnant women with PUD and related drug treatments. In conclusion, a higher rate of CA was not found in the offspring of mothers with PUD.     

Effects of dietary counselling on food habits and dietary intake of Finnish pregnant women at increased risk for gestational diabetes – a secondary analysis of a cluster‐randomized controlled trial

The incidence of gestational diabetes mellitus (GDM) is increasing and GDM might be prevented by improving diet. Few interventions have assessed the effects of dietary counselling on dietary intake of pregnant women. This study examined the effects of dietary counselling on food habits and dietary intake of Finnish pregnant women as secondary outcomes of a trial primarily aiming at preventing GDM. A cluster‐randomized controlled trial was conducted in 14 municipalities in Finland, including 399 pregnant women at increased risk for developing GDM. The intervention consisted of dietary counselling focusing on dietary fat, fibre and saccharose intake at four routine maternity clinic visits. Usual counselling practices were continued in the usual care municipalities. A validated 181‐item food frequency questionnaire was used to assess changes in diet from baseline to 26–28 and 36–37 weeks gestation. The data were analysed using multilevel mixed‐effects linear regression models. By 36–37 weeks gestation, the intervention had beneficial effects on total intake of vegetables, fruits and berries (coefficient for between‐group difference in change 61.6 g day^?1, 95% confidence interval 25.7–97.6), the proportions of high‐fibre bread of all bread (7.2% units, 2.5–11.9), low‐fat cheeses of all cheeses (10.7% units, 2.6–18.9) and vegetable fats of all dietary fats (6.1% ‐units, 2.0–10.3), and the intake of saturated fatty acids (?0.67 energy‐%‐units, ?1.16 to ?0.19), polyunsaturated fatty acids (0.38 energy‐%‐units, 0.18–0.58), linoleic acid (764 mg day^?1, 173–1354) and fibre (2.07 g day^?1, 0.39–3.75). The intervention improved diet towards the recommendations in pregnant women at increased risk for GDM suggesting the counselling methods could be implemented in maternity care.     

Teratogenic potential of pholedrine: A sympathomimetic vasoconstrictive drug – A population‐based case‐control study

Pholedrine was a frequently used drug for the treatment of severe hypotension in some countries, including Hungary. The possible teratogenic effect of pholedrine was not checked; therefore; the birth outcomes, particularly congenital abnormalities (CAs), of infants born to women treated with pholedrine during pregnancy, and pregnancy complications were evaluated in the population‐based large dataset of the Hungarian Case‐Control Surveillance System of Congenital Abnormalities. Cases with CA and their matched controls without CA born to mothers with pholedrine use during pregnancy were compared. Of 22 843 cases and 38 151 controls, 768 (3.4%) and 1509 (4.0%) were born to mothers with pholedrine treatment, respectively (adjusted odds ratios [OR] with 95% CI: 0.9, 0.8–1.0). There was no higher risk for any CA group in the offspring of mothers who used pholedrine during the second and/or third month of pregnancy (i.e. the critical period of most major CA). The mean gestational week at delivery and birthweight was similar in newborns of women with or without pholedrine treatment during pregnancy. The pattern of pregnancy complications was characteristic (lower incidence of preeclampsia/eclampsia, while higher incidence of severe nausea/vomiting and anemia), explained mainly by the underlying maternal hypotension. In conclusion, pholedrine treatment in pregnant women was not associated with a higher risk for CA or other adverse birth outcomes, such as preterm birth or low birthweight. The knowledge of the teratogenic potential of pholedrine may contribute to the evaluation of other sympathomimetic drugs.     

Psychomotor development in the children of mothers with type 1 diabetes mellitus or gestational diabetes mellitus

The purpose of this study was to examine psychomotor development in children born to mothers with type 1 diabetes mellitus (DM1) or gestational diabetes mellitus (GDM). The influence of metabolic control in pregnant diabetic mothers and complications during labor on their children's psychological and physical development was evaluated. The analysis included 59 children, 20 of mothers with GDM, 19 of mothers with DM1, and 20 children of healthy mothers. Clinical observations and medical history were recorded and children were assessed using the Brunet-Lezine Psychomotor Development Scale. Abnormalities were found more often in the children of mothers with DM1 whose illness was insufficiently controlled during pregnancy and of mothers with serious hypoglycemia while pregnant. Speech, eye-movement coordination and social aspects were affected.     

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.     

Teenage pregnancy in type 1 diabetes mellitus

Carmody D, Doyle A, Firth RGR, Byrne MM, Daly S, Mc Auliffe F, Foley M, Coulter‐Smith S, Kinsley BT. Teenage pregnancy in type 1 diabetes mellitus Younger maternal age at delivery has been linked to adverse reproductive outcomes. Pregnancy complicated by type 1 diabetes mellitus (T1DM) is also associated with adverse pregnancy outcomes. Optimising diabetic glycaemic control prior to pregnancy is known to reduce the rate of congenital abnormalities and improve pregnancy outcomes. Teenage pregnancies are not usually planned and little data exist on teenage pregnancy complicated by T1DM. We sought to identify the glycemic control achieved in teenage pregnancy with T1DM and to clarify if there is an associated increase in adverse pregnancy outcomes compared to those seen in older women with T1DM. We compared outcomes in 18 teenagers (TG) with 582 older women with T1DM (CON) from 1995–2007. TG booked to the combined diabetes‐obstetrical service at a median gestational age of 11 weeks (range 6–22) compared to 7 weeks in CON (range 4–40, p < 0.02). Glycaemic was worse in TG compared to CON at 13, 26 and 35 weeks gestation, despite higher insulin doses. First trimester miscarriage rate did not differ between groups. Major congenital anomaly rate was 6.2% (1/16) compared to 3.2% in CON. This preliminary study has demonstrated that pregnant teenage women with T1DM book later to specialised care and have worse glycaemic control in pregnancy compared to older women with T1DM. This group also appear to be more insulin resistant than older women in early pregnancy. Our data would suggest that teenagers with type 1 diabetes mellitus may constitute a high‐risk group for adverse pregnancy outcomes.     

Elevated iron status and risk of gestational diabetes mellitus: A systematic review and meta‐analysis

The aim of this systematic review and meta‐analysis of observational studies was to assess the relationship between elevated iron status, measured as hemoglobin and ferritin levels, and the risk of gestational diabetes mellitus (GDM). The present study was recorded in PROSPERO (2013:CRD42013005717). The selected studies were identified through a systematic review of scientific literature published in The Cochrane Library and PubMed/MEDLINE databases from their inception until March 10, 2016, in addition to citation tracking and hand‐searches. The search strategy of original articles combined several terms for hemoglobin, ferritin, pregnancy, and GDM. OR and 95% CI of the selected studies were used to identify associations between hemoglobin and/or ferritin levels with the risk of GDM. Summary estimates were calculated by combining inverse‐variance using fixed‐effects model. 2468 abstracts were initially found during the search. Of these, 11 with hemoglobin and/or ferritin data were selected for the meta‐analyses. We observed that high hemoglobin (OR = 1.52; 95% CI: 1.23–1.88), as well as ferritin (OR = 2.09; 95% CI: 1.48–2.96) levels were linked to an increased risk of GDM. Low heterogeneity was observed in hemoglobin (I² = 33.3%, P = 0.151) and ferritin (I² = 0.7%, P = 0.418) meta‐analyses, respectively. Publication bias was not appreciated. High hemoglobin or ferritin levels increase the risk of GDM by more than 50% and more than double, respectively, in the first and third trimester. Therefore, determining of hemoglobin or ferritin concentration in early pregnancy might be a useful tool for recognizing pregnant women at risk of GDM.     

Impaired β‐cell sensitivity to glucose and maximal insulin secretory capacity in adolescents with type 2 diabetes

Elder DA, Woo JG, D’Alessio DA. Impaired β‐cell sensitivity to glucose and maximal insulin secretory capacity in adolescents with type 2 diabetes. Background: Adults with type 2 diabetes mellitus (T2DM) have broad impairments in β‐cell function, including severe attenuation of the first‐phase insulin response to glucose, and reduced β‐cell mass. In adolescents with T2DM, there is some evidence that β‐cell dysfunction may be less severe. Our objective was to determine β‐cell sensitivity to glucose and maximal insulin secretory capacity (AIR_max) in teenagers with T2DM. Methods: Fifteen adolescents with T2DM [11 F/4 M, age 18.4 ± 0.3 yr, body mass index (BMI) 39.8 ± 2.2 kg/m²] and 10 non‐diabetic control subjects (7 F/3 M, age 17.4 ± 0.5 yr, BMI 41.5 ± 2.2 kg/m²) were studied. T2DM subjects had a mean duration of diabetes of 48.8 ± 6.4 months, were treated with conventional therapies, and had good metabolic control [hemoglobin A1c (HbA1c) 6.7 ± 1.2%]. Insulin and C‐peptide were determined before and after a graded glucose infusion and after intravenous arginine at a whole blood glucose level of ≥22 mM. Results: The insulin response to increasing plasma glucose concentrations was blunted in the diabetic compared with control subjects (34.8 ± 11.9 vs. 280.5 ± 57.8 pmol/mmol; p < 0.0001), and AIR_max was also significantly reduced in the diabetic group (1868 ± 330 vs. 4445 ± 606; p = 0.0005). Conclusion: Even adolescents with well‐controlled T2DM have severe impairments of insulin secretion. These data support β‐cell dysfunction as central in the pathogenesis of T2DM in young people, and indicate that these abnormalities can develop over a period of just several years.     

Serum lipid and lipoprotein composition in infants of diabetic mothers

Diabetes mellitus (DM) alters carbohydrate and lipid metabolism to a great extent. This study was planned to determine whether infants of insulin dependent and gestational diabetic mothers have abnormal lipid metabolism. Three groups of newborns were included in the study; group I consisted of 7 infants of diabetic mothers (IDM) with insulin dependent DM (Type 1 DM), group Il of 18 infants of gestational diabetic mothers and group III of 20 control neonates whose mothers had no history of DM. Total cholesterol (TC), triglyceride (TG) and high density lipoprotein-cholesterol (HDL-C) values in groups I and II were no different compared to those in group III (p>0.05). However, low density lipoprotein-cholesterol (LDL-C) and LDL-C/HDL-C ratio were similar between groups I and II (p>0.05) but significantly higher in both infants of type I diabetic mothers and gestational diabetic mothers compared to control infants (p<0.05). Apolipoprotein A-I (Apo A-1) and apolipoprotein B (Apo B) levels, Apo A-I/Apo B and HDL-C/Apo A-I ratios were similar in between groups. However, Apo B/LDL-C ratio was significantly lower in groups I and II compared to control group (p<0.05). In conclusion, diabetes in pregnant women causes a tendency to LDL hypercholesterolemia in the offspring. These infants should be longitudinally followed up to assess whether this observation imposes an increased risk for atherosclerosis for advanced ages.     

Current human T‐cell lymphotropic virus type 1 mother‐to‐child transmission prevention status in Kagoshima

The aim of this study was to assess the current human T‐cell lymphotropic virus type 1 (HTLV‐I) mother‐to‐child transmission (MTCT) prevention system in Kagoshima Prefecture. We investigated the rate of carrier pregnant women from obstetrics facilities in Kagoshima by mail in 2012 and compared our results with previous study results. We interviewed carrier pregnant women about their choices for infant nutrition, and we interviewed midwives about the follow‐up system. In 2012, 8719 screening tests were performed, covering 58.1% of all pregnant women in Kagoshima; the rate of carrier pregnant women was 1.3%. Of 59 carriers, 39 chose short‐term breast‐feeding. The HTLV‐I carrier rate among pregnant women in Kagoshima has declined. The current HTLV‐I MTCT prevention system in Kagoshima is effective, but not sufficient. To bring the nutrition methods to completion, various types of support are needed. Further studies will elucidate many unsolved problems concerning MTCT.     

Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria

Ururahy MAG, Loureiro MB, Freire‐Neto FP, Souza KSC, Zuhl I, Brandão‐Neto J, Hirata RDC, Doi SQ, Arrais RF, Hirata MH, Almeida MG, Rezende AA. Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria. Objective: To study the activation of an inflammatory cascade through leukocyte mRNA expression of TLR2, TLR4, MyD88, and pro‐inflammatory cytokines in individuals with childhood onset type 1 diabetes. Design and methods: Seventy‐six type 1 diabetic patients and 100 normoglycemic subjects (NG) 6 to 20 years old were recruited. Type 1 diabetic patients (DM1) were considered to have good (DM1G) or poor (DM1P) glycemic control according to the values of glycated hemoglobin. TLR2, TLR4, MyD88, interleukin ‐1β (IL‐1β), IL‐6, and tumor necrosis factor alpha (TNF‐α) mRNA expressions were measured in peripheral blood leukocytes (PBL) by real‐time polymerase chain reaction (PCR). Urea, creatinine, albumin, and total protein serum levels were determined. Urinary albumin‐to‐creatinine ratio (ACR) was calculated. Results: DM1 and DM1P patients showed higher glycated hemoglobin (10 and 11%, respectively) and serum glucose concentrations (208 and 226 mg/dL, respectively) compared to NG (Glycated hemoglobin: 7% and glucose: 76 mg/dL) (p < 0.05). PBL mRNA expressions of TLR2, MyD88, IL‐1β, IL‐6, and TNF‐α were higher in DM1 and TLR2, IL‐1β, and IL‐6 expressions were higher in DMP1 compared to NG (p < 0.05). In DM1, serum albumin and total protein were lower, while serum urea and ACR were higher in comparison to NG (p < 0.05). However, these differences compared to NG were more pronounced in DM1P, which included nine individuals with microalbuminuria. Conclusions: Increased mRNA expression of TLR2, MyD88, and pro‐inflammatory cytokines in leukocytes of patients with childhood onset type 1 diabetes indicates the development of a TLR2‐mediated pro‐inflammatory process, which may also be associated with an early inflammatory process in the kidney and the occurrence of microalbuminuria.     

The influence of physical activity on ghrelin and IGF‐1/IGFBP‐3 levels in children and adolescents with type 1 diabetes mellitus

Huber J, Fröhlich‐Reiterer EE, Sudi K, Suppan E, Weinhandl G, Jasser‐Nitsche H, Aigner R, Borkenstein MH. The influence of physical activity on ghrelin and IGF‐1/IGFBP‐3 levels in children and adolescents with type 1 diabetes mellitus. Objectives: The aim of the study was to determine the influence of regular physical activity on ghrelin and IGF‐1/IGFBP‐3 levels during a diabetes camp. Methods: Twenty‐eight children and adolescents (14 boys; mean age 12.1 yr) with type 1 diabetes mellitus (T1DM, mean duration of diabetes 4.8 yr) attending a 2‐wk diabetes camp that features increased regular physical activities have been studied. Serum levels of ghrelin (total and acylated), growth hormone (GH), insulin‐like growth factor‐1 (IGF‐1), insulin‐like growth factor‐bindng protein‐3 (IGFBP‐3) and insulin were measured in fasting state on day 1 and day 14. Improvement of metabolic control was documented by haemoglobin A1c (HbA1c). Glucose levels and insulin doses were determined daily. Results: Mean insulin dosage decreased from 0.87 to 0.78 U/kg/d, mean HbA1c levels decreased from 8.6 to 8.3%, but the changes were not statistical. There was a significant decline in total ghrelin. IGFBP‐3 and IGF‐1 decreased also significantly. Total basal ghrelin was inversely related to the change in IGFBP‐3. Conclusions: We hypothesize an association between ghrelin and metabolic control in T1DM. Higher ghrelin levels might be associated with poor metabolic control. The dynamic of IGFBP‐3 levels appears to be under the influence of basal ghrelin concentrations in T1DM.     

Pregnancy outcome in the Psammomys obesus gerbil on low- and high-energy diets

INTRODUCTION: Diabetes mellitus (DM) during pregnancy is associated with an increased risk for poor reproduction and a high rate of congenital malformations. The gerbil Psammomys obesus is a unique model for nutritionally induced Type 2 DM (T2DM) that enabled us to study the outcome of uncontrolled T2DM during pregnancy. METHODS: Female Psammomys on low-energy (LE) or high energy (HE) diet were studied. The blood glucose levels and weights of pregnant animals were determined. The offspring from the different groups were followed-up to weaning. RESULTS: Most of the HE-diet animals were diabetic (77%). There were no differences in the pregnancy rates in animals on both diets (32.7% in HE vs. 38.3% in LE). Pregnancy of the HE-diet group was longer than the LE-diet group (26.7 vs. 26.1 days), and litter average was reduced (2.7 vs. 3.0). At birth, the offspring of the HE-diet dams weighed less (5.2 vs. 7.2 g) and had smaller crown rump length (4.0 vs. 4.6 cm) These offspring also presented a 1-3 days delay in neuro-developmental parameters (first turn over, hair appearance, eye-opening and response to noise). However, from the fourth week of life they became diabetic, and from the third week they weighed more than the LE offspring. CONCLUSION: HE-diet caused diabetes, maternal complications and altered reproduction in Psammomys animals. The offspring of diabetic Psammomys presented birth weight and length changes as well as developmental delay.     

Effect of a low glycaemic index diet in gestational diabetes mellitus on post‐natal outcomes after 3 months of birth: a pilot follow‐up study

A low glycaemic index (LGI) diet during pregnancy complicated by gestational diabetes mellitus (GDM) may offer benefits to the mother and infant pair beyond those during pregnancy. We aimed to investigate the effect of an LGI diet during pregnancy complicated with GDM on early post‐natal outcomes. Fifty‐eight women (age: 23–41 years; mean ± SD pre‐pregnancy body mass index: 24.5 ± 5.6 kg m^?2) who had GDM and followed either an LGI diet (n = 33) or a conventional high‐fibre diet (HF; n = 25) during pregnancy had a 75‐g oral glucose tolerance test and blood lipid tests at 3 months post‐partum. Anthropometric assessments were conducted for 55 mother–infant pairs. The glycaemic index of the antenatal diets differed modestly (mean ± SD: 46.8 ± 5.4 vs. 52.4 ± 4.4; P < 0.001), but there were no significant differences in any of the post‐natal outcomes. In conclusion, an LGI diet during pregnancy complicated by GDM has outcomes similar to those of a conventional healthy diet. Adequately powered studies should explore the potential beneficial effects of LGI diet on risk factors for chronic disease.     

Gestational diabetes mellitus and glucose intolerance among Mexican pregnant adolescents

There is an increasing incidence of type 2 diabetes mellitus (DM) among adolescents (especially females), and the serum glucose concentrations in pregnant women <25 years during a 3-h oral glucose tolerance test (3-h OGTT) seem to be lower than those of pregnant women >25 years. Among 115 Mexican pregnant adolescents (<18 years) we analyzed their serum glucose concentrations during: a) 1-h 50-g glucose challenge test (GCT) performed at 24-28 weeks of gestation (n = 103) or at 29-35 weeks of gestation (n = 12); b) A standard 3-h OGTT performed 3-5 days later. Eight adolescents had an abnormal GCT, three of whom also had an abnormal 3-h OGTT. Sixteen adolescents (13 with previously normal GCT) had an abnormal 3-h OGTT, 15 classified as GGI and one as gestational DM (GDM). Serum glucose concentrations in adolescents with GGI were higher than in adolescents with normal 3-h OGTT: a) at 60 and 120 min during the 3-h OGTT (p < 0.001); and b) when expressed as the area under the glucose curve (p < 0.001). Adolescents with GGI had serum glucose concentrations during the 3-h OGTT similar to adult, non-diabetic pregnant Mexican women. It is suggested that GGI in pregnant adolescents may represent an early sign of a future deterioration in glucose metabolism, leading to a higher risk for GDM in future pregnancies and/or type 2 DM in adulthood. Thus, the current criteria to diagnose GDM in adults may not completely apply to adolescents, especially in ethnic groups with high risk for glucose abnormalities and considering the frequency of multiparous adolescents, especially in developing countries.     

Characterization of 33 488 children and adolescents with type 1 diabetes based on the gender‐specific increase of cardiovascular risk factors

Schwab KO, Doerfer J, Marg W, Schober E, Holl RW. Characterization of 33 488 children and adolescents with type 1 diabetes based on the gender‐specific increase of cardiovascular risk factors. Objectives: Characterization of children with type 1 diabetes (T1DM) regarding number and gender distribution of cardiovascular risk factors (cvRF) and of total cholesterol/high‐density lipoprotein cholesterol ratio (TC/HDL‐C ratio) for risk assessment. Methods: 33488 patients ≤18 years were included in this cross‐sectional analysis and placed into 5 categories by their number of cvRF. Dyslipidemia (TC >200 mg/dL, >5.17 mmol/L; and/or HDL‐C <35 mg/dL, <0.91 mmol/L; and/or LDL‐C >130 mg/dL, >3.36 mmol/L), elevated systolic and/or diastolic blood pressure (BP) ≥90th percentile, obesity >97th percentile, active smoking, and HbA1c ≥7.5% were considered as cvRF. Results: 65% had no or 1 cvRF. HbA1c ≥7.5% was the most frequently occurring cvRF followed by BP ≥90th percentile, dyslipidemia, smoking, and BMI >97th percentile. Age at diabetic onset ranged from 7.7 to 9.2 years and diabetes duration from 4.1 to 6.6 years. CvRF showed differences in disfavour of females except smoking and HDL‐C <35 mg/dL (0.91 mmol/L). Rate of females was 45% with 0 cvRF and 60% with 4 to 5 cvRF. TC/HDL‐C ratio showed no clear association to the number of cvRF. Conclusions: 35% of a pediatric T1DM population develops 2 or more cvRF thus increasing their cv risk in adulthood. With increasing numbers of cvRF, the percentage of girls is rising from 45% to 60% which might contribute to an assimilation of survival rates in female and male adults. TC/HDL ratio does not predict the extent of cardiovascular risk in pediatric T1DM.     

Neurocognitive functioning in preschool‐age children with type 1 diabetes mellitus

Patiño‐Fernández AM, Delamater AM, Applegate EB, Brady E, Eidson M, Nemery R, Gonzalez‐Mendoza L, Richton S. Neurocognitive functioning in preschool‐age children with type 1 diabetes mellitus. Neurocognitive functioning may be compromised in children with type 1 diabetes mellitus (T1DM). The factor most consistently implicated in the long‐term neurocognitive functioning of children with T1DM is age of onset. The pediatric literature suggests that glycemic extremes may have an effect on the neurocognitive functioning of children, but findings are mixed. The purpose of this study was to compare the neurocognitive functioning of young children with T1DM diagnosed before 6 yr of age and healthy children (i.e., without chronic illness). Additionally, in the children with T1DM, we examined the relationship between their neurocognitive functioning and glycemic control. Sixty‐eight (36 with T1DM and 32 without chronic illness) preschool‐age children (M age = 4.4 yr ) were recruited and administered a battery of instruments to measure cognitive, language, and fine motor skills. Children with T1DM performed similar to the healthy controls and both groups' skills fell in the average range. Among children with diabetes, poor glycemic control [higher hemoglobin A1c (HbA1c)] was related to lower general cognitive abilities (r = ?0.44,p < 0.04), slower fine motor speed (r = ?0.64,p < 0.02), and lower receptive language scores (r = ?0.39,p < 0.04). Such findings indicate that young children with T1DM already demonstrate some negative neurocognitive effects in association with chronic hyperglycemia.     

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.     

Global summary of maternal and newborn vitamin D status – a systematic review

Pregnant women and newborns are at increased risk of vitamin D deficiency. Our objective was to create a global summary of maternal and newborn vitamin D status. We completed a systematic review (1959–2014) and meta‐analysis of studies reporting serum 25‐hydroxyvitamin D [25(OH)D] concentration in maternal and newborn populations. The 95 identified studies were unevenly distributed by World Health Organization (WHO) region: Americas (24), European (33), Eastern Mediterranean (13), South‐East Asian (7), Western Pacific (16) and African (2). Average maternal 25(OH)D concentrations (nmol L^?1) by region were 47–65 (Americas), 15–72 (European), 13–60 (Eastern Mediterranean), 20–52 (South‐East Asian), 42–72 (Western Pacific) and 92 (African). Average newborn 25(OH)D concentrations (nmol L^?1) were 35–77 (Americas), 20–50 (European), 5–50 (Eastern Mediterranean), 20–22 (South‐East Asian), 32–67 (Western Pacific) and 27–35 (African). The prevalences of 25(OH)D <50 and <25 nmol L^?1 by WHO region in pregnant women were: Americas (64%, 9%), European (57%, 23%), Eastern Mediterranean (46%, 79%), South‐East Asian (87%, not available) and Western Pacific (83%, 13%). Among newborns these values were: Americas (30%, 14%), European (73%, 39%), Eastern Mediterranean (60%, not available), South‐East Asian (96%, 45%) and Western Pacific (54%, 14%). By global region, average 25(OH)D concentration varies threefold in pregnant women and newborns, and prevalence of 25(OH)D <25 nmol L^?1 varies eightfold in pregnant women and threefold in newborns. Maternal and newborn 25(OH)D concentrations are highly correlated. Addressing vitamin D deficiency in pregnant women and newborns should be a global priority. To protect children from the adverse effects of vitamin D deficiency requires appropriate interventions during both pregnancy and childhood.