El desafío para el desarrollo del sistema nervioso central en la reproducción humana asociada con la diabetes / The challenge for the development of the central nervous system in human reproduction associated with diabetes

Introducción: Los hijos de madres con diabetes presentan una mayor incidencia de trastornos del neurodesarrollo como autismo, actividad cognitiva baja, déficit de atención, esquizofrenia y otras enfermedades del espectro autista. Objetivo: Explicar los mecanismos moleculares que subyacen en la aparición de los trastornos del neurodesarrollo en hijos de gestantes con diabetes. Métodos: Se llevó a cabo una revisión de la literatura que aparece en las bases de datos electrónicas Google, MEDLINE/PubMed y SciELO. Se revisaron artículos publicados entre los años 2000 y 2020. Las palabras clave utilizadas fueron: hiperglucemia, neurodesarrollo, malformaciones congénitas y epigenética. Resultados: Se pone de manifiesto el alto riesgo que representa la hiperglucemia durante el desarrollo intrauterino. El riesgo relativo que tienen los hijos de madres con diabetes pregestacional de presentar malformaciones del sistema nerviosos central es 15,5 veces mayor que en gestantes sin diabetes. El hipocampo es especialmente sensible a cambios en los niveles de glucosa. La diabetes materna puede dejar una impronta negativa para la capacidad de procesar información, adquirir habilidades y poseer un comportamiento social adecuado en la descendencia. Conclusiones: Las alteraciones en el metabolismo condicionadas por la hiperglucemia, el estrés oxidativo, la inflamación de bajo grado y las modificaciones epigenéticas crean un fatal engranaje que sustenta el desarrollo anómalo en hijos de gestantes con diabetes(AU)

Introduction: Children, whose mothers suffer from diabetes, have higher incidence of neurodevelopmental disorders such as autism, low cognitive activity, attention deficit, schizophrenia and other autism spectrum diseases. Objective: To explain the molecular mechanisms that underlie the appearance of neurodevelopmental disorders in children of pregnant women with diabetes. Methods: A review of the literature that appears in Google, MEDLINE/PubMed and SciELO electronic databases, was carried out. Articles published from 2000 to 2020 were reviewed. The keywords used were hyperglycemia, neurodevelopment, congenital malformations, and epigenetics. Results: The high risk that hyperglycemia represents during intrauterine development is highlighted. The relative risk that children of mothers with pregestational diabetes have of presenting malformations of the central nervous system is 15.5 times higher than in pregnant women without diabetes. The hippocampus is especially sensitive to changes in glucose levels. Maternal diabetes can leave negative print on the ability to process information, acquire skills and have appropriate social behavior in their children. Conclusions: Alterations in metabolism conditioned by hyperglycemia, oxidative stress, low-grade inflammation and epigenetic modifications create a fatal mechanism that supports abnormal development in children of pregnant women with diabetes(AU)

Association of Maternal History of Spontaneous Abortion and Stillbirth With Risk of Congenital Heart Disease in Offspring of Women With vs Without Type 2 Diabetes.

Importance: The associations of maternal history of spontaneous abortion (SA) and stillbirth with congenital heart disease (CHD) remain elusive. Objective: To evaluate the associations of maternal history of pregnancy loss with CHD in offspring and the role of maternal type 2 diabetes. Design, Setting, and Participants: This population-based cohort study included singleton live offspring born between January 1, 1977, and December 31, 2016, identified through Danish national health registries. Statistical analysis was performed from October 1, 2019, through September 1, 2021. Exposures: Maternal history of SA, with frequency varying from 1 or 2 to 3 or more episodes, and maternal history of single and multiple stillbirths. Main Outcomes and Measures: Overall CHD identified by hospital diagnosis. Cox proportional hazard regression was used to estimate the hazard ratio (HR) of CHD. Diabetes was evaluated as a potential confounder and a potential effect modifier. Results: Among 1 642 534 included offspring (mean [SD] age, 14.11 [8.39] years; 843 265 male [51.35%]), 246 669 (15.02%) were born to mothers with a history of SA and 9750 (0.59%) were born to mothers with a history of stillbirth. The HRs of CHD were 1.16 (95% CI, 1.13-1.20) for offspring with a maternal history of SA and 1.49 (95% CI, 1.32-1.68) for offspring with a maternal history of stillbirth. Significant dose-response associations were observed among offspring with a maternal history of 3 or more episodes of SA (HR, 1.60; 95% CI, 1.39-1.84) and those with maternal history of multiple stillbirths (HR, 2.75; 95% CI, 1.63-4.65). If only inpatient CHD cases were included, the risk of CHD was higher than that found in the main analysis, with HRs of 1.24 (95% CI, 1.19-1.30) for maternal history of SA and 1.78 (95% CI, 1.51-2.11) for maternal history of stillbirth. The observed associations were strengthened by maternal prepregnancy type 2 diabetes (HR for maternal history of SA, 1.65 [95% CI, 1.37-1.97]; HR for maternal history of stillbirth, 1.74 [95% CI, 1.06-2.85]). Conclusions and Relevance: These findings suggest that offspring born to mothers with a previous SA or stillbirth, especially multiple episodes, or with prepregnancy type 2 diabetes were at a higher risk of being diagnosed with CHD. These findings may help identify women at increased risk in whom detailed fetal heart assessment may be cost-effective and highlight the importance of screening for type 2 diabetes in women of reproductive age.

Monogenic diabetes caused by GCK gene mutation is misdiagnosed as gestational diabetes - A multicenter study in Portugal.

AIMS: Monogenic diabetes is an underdiagnosed type of diabetes mellitus, which can be harmful in pregnancy. We aim to estimate the prevalence of diabetes caused by the mutation of the glucokinase gene (GCK-MODY) in pregnant women diagnosed with gestational diabetes mellitus (GDM) and to characterize pregnant women with this suspicion. METHODS: A multicenter observational study with data prospectively collected from pregnancies with GDM was conducted. Two groups of pregnant women were considered: those with GCK-MODY criteria and those without those criteria. RESULTS: Of 18421 women with GDM, 3.6% (n = 730) had the GCK-MODY clinical criteria. A prevalence of 1.5% of GCK-MODY is estimated in women with GDM in Portugal, which is higher than in Northern European countries. Suspected GCK-MODY women had statistically higher odds of having neonates below the 25th percentile (OR = 1.23, 95%CI = 1.04-1.46, p = 0.016) and having prediabetes and diabetes in postpartum reclassification (OR = 2.11, 95%CI = 1.55-2.82, p < 0.001 and OR = 5.96, 95%CI = 3.38-10.06, p < 0.001, respectively). CONCLUSIONS: Higher odds of neonates below the 25th percentile was probably due to excessive insulin treatment in cases where both the mother and the fetus have the mutation. It is essential to consider the diagnosis of GCK-MODY in all women with GDM criteria for better management of diabetes in pregnancy.

Pregestational diabetes in pregnancy: Complications, management, surveillance, and mechanisms of disease-A review.

Diabetes is an increasingly common diagnosis among pregnant women. Pregestational diabetes is associated with an increase in many adverse pregnancy outcomes, which impact both on the woman and her fetus. The models of pregnancy care for women with diabetes are based largely on observational data or consensus opinion. Strategies for aneuploidy screening and monitoring for fetal well-being should be modified in women with diabetes. There is an increasing understanding of the mechanisms by which congenital anomalies and disorders of fetal growth occur, involving epigenetic modifications, changes in gene expression in critical developmental pathways, and oxidative stress. This knowledge may lead to pathways for improved care for these high-risk pregnancies.

Maternal diet modulates placental nutrient transporter gene expression in a mouse model of diabetic pregnancy.

Diabetes in the mother during pregnancy is a risk factor for birth defects and perinatal complications and can affect long-term health of the offspring through developmental programming of susceptibility to metabolic disease. We previously showed that Streptozotocin-induced maternal diabetes in mice is associated with altered cell differentiation and with smaller size of the placenta. Placental size and fetal size were affected by maternal diet in this model, and maternal diet also modulated the risk for neural tube defects. In the present study, we sought to determine the extent to which these effects might be mediated through altered expression of nutrient transporters, specifically glucose and fatty acid transporters in the placenta. Our results demonstrate that expression of several transporters is modulated by both maternal diet and maternal diabetes. Diet was revealed as the more prominent determinant of nutrient transporter expression levels, even in pregnancies with uncontrolled diabetes, consistent with the role of diet in placental and fetal growth. Notably, the largest changes in nutrient transporter expression levels were detected around midgestation time points when the placenta is being formed. These findings place the critical time period for susceptibility to diet exposures earlier than previously appreciated, implying that mechanisms underlying developmental programming can act on placenta formation.

Management and Outcomes of Maturity-Onset Diabetes of the Young in Pregnancy.

Maturity-onset diabetes of the young (MODY) is a group of monogenic disorders that accounts for 1% to 5% of diabetes. The most common mutations are those in the hepatocyte nuclear factor-1-alpha (HNF-1-alpha) and in the glucokinase (GCK) genes. Although management of MODY is well established, no guidelines currently exist for management during pregnancy. Both maternal glycemic control and fetal mutation status are factors that may influence outcomes during pregnancy. The primary aim of this project was to describe cases of MODY during pregnancy to highlight the clinical implications of management of this disorder during pregnancy. The Ottawa Hospital is the primary referral centre for high-risk obstetrical patients, including those with diabetes in pregnancy, in Ottawa, Canada. Referrals between 2008 and 2018 were reviewed and a case series of three women and five pregnancies is described. Together with the illustrative cases, a literature review of MODY in pregnancy is used to highlight clinical considerations unique to MODY in pregnancy. We describe 5 pregnancies with MODY-2 (GCK mutation) and MODY 3 (HNF-1-alpha mutation). Important issues identified included monitoring of fetal growth and individualization of maternal glycemic control, particularly in cases where fetal mutation status is unknown. Management of MODY in pregnancy is challenging and there is little evidence to guide recommendations. Fetal growth can be used to guide management of maternal glycemic targets when fetal mutation status is unknown.

Turning conceptual systems maps into dynamic simulation models: An Australian case study for diabetes in pregnancy.

BACKGROUND: System science approaches are increasingly used to explore complex public health problems. Quantitative methods, such as participatory dynamic simulation modelling, can mobilise knowledge to inform health policy decisions. However, the analytic and practical steps required to turn collaboratively developed, qualitative system maps into rigorous and policy-relevant quantified dynamic simulation models are not well described. This paper reports on the processes, interactions and decisions that occurred at the interface between modellers and end-user participants in an applied health sector case study focusing on diabetes in pregnancy. METHODS: An analysis was conducted using qualitative data from a participatory dynamic simulation modelling case study in an Australian health policy setting. Recordings of participatory model development workshops and subsequent meetings were analysed and triangulated with field notes and other written records of discussions and decisions. Case study vignettes were collated to illustrate the deliberations and decisions made throughout the model development process. RESULTS: The key analytic objectives and decision-making processes included: defining the model scope; analysing and refining the model structure to maximise local relevance and utility; reviewing and incorporating evidence to inform model parameters and assumptions; focusing the model on priority policy questions; communicating results and applying the models to policy processes. These stages did not occur sequentially; the model development was cyclical and iterative with decisions being re-visited and refined throughout the process. Storytelling was an effective strategy to both communicate and resolve concerns about the model logic and structure, and to communicate the outputs of the model to a broader audience. CONCLUSION: The in-depth analysis reported here examined the application of participatory modelling methods to move beyond qualitative conceptual mapping to the development of a rigorously quantified and policy relevant, complex dynamic simulation model. The analytic objectives and decision-making themes identified provide guidance for interpreting, understanding and reporting future participatory modelling projects and methods.

Maternal Weight Variation in Different Intrauterine Environments: An Important Role of Hypertension.

OBJECTIVE: Different intrauterine environments may influence the maternal prepregnancy body weight (BW) variation up to 6 months postpartum. The objective of the present study was to verify the association of sociodemographic, obstetric, nutritional, and behavioral factors with weight variation in women divided into four groups: hypertensive (HM), diabetic (DM), smokers (SM), and control mothers (CM). METHODS: It was a convenience sample of 124 postpartum women recruited from 3 public hospitals in the city of Porto Alegre, state of Rio Grande do Sul, Brazil, between 2011 and 2016. Multiple linear regressions and generalized estimating equations (GEE) were conducted to identify the factors associated with maternal weight variation. For all GEE, the maternal weight measurements were adjusted for maternal height, parity, educational level, and the type of delivery, and 3 weight measurements (prepregnancy, preceding delivery, and 15 days postpartum) were fixed. RESULTS: A hierarchical model closely associated the maternal diagnosis of hypertension and a prepregnancy body mass index (BMI) classified as overweight with maternal weight gain measured up to the 6th month postpartum (the difference between the maternal weight at 6 months postpartum and the prepregnancy weight). These results showed that the BW of the HM group and of overweight women increased ∼ 5.2 kg 6 months postpartum, compared with the other groups. Additionally, women classified as overweight had a greater BW variation of 3.150 kg. CONCLUSION: This evidence supports the need for specific nutritional guidelines for gestational hypertensive disorders, as well as great public attention for overweight women in the fertile age.

OBJETIVO: Diferentes ambientes intrauterinos podem influenciar a variação de peso corporal pré-gestacional materno até 6 meses pós-parto. O objetivo do presente estudo foi verificar a associação de fatores sociodemográficos, obstétricos, nutricionais e comportamentais com a variação de peso em mulheres divididas em quatro grupos: hipertensas (HM), diabéticas (DM), tabagistas (SM) e controles (CM). MéTODOS: Amostra de conveniência de 124 puérperas recrutadas em 3 hospitais públicos da cidade de Porto Alegre, Rio Grande do Sul, Brasil, entre 2011 e 2016. Regressões lineares múltiplas e modelos de equações de estimativas generalizadas (GEE) foram realizados para identificar os fatores associados à variação do peso materno. Para todas as GEE, as medidas de peso materno foram ajustadas para a estatura materna, paridade, escolaridade e tipo de parto, e três medidas de peso (pré-gravidez, anterior ao parto e 15 dias pós-parto) foram fixadas. RESULTADOS: Um modelo hierárquico associou o diagnóstico materno de hipertensão e o índice de massa corporal (IMC) pré-gestacional de sobrepeso com ganho de peso materno medido até o 6° mês pós-parto (diferença entre o peso materno aos 6 meses pós-parto e o peso pré-gestacional). Estes resultados mostraram que o grupo HM e mulheres com sobrepeso aumentaram o peso corporal em ∼ 5,2 kg 6 meses pós-parto, em comparação com os demais grupos. Além disso, as mulheres classificadas com sobrepeso tiveram uma variação maior de peso corporal, de 3,150 kg. CONCLUSãO: Evidenciou-se a necessidade de diretrizes nutricionais específicas para distúrbios hipertensivos gestacionais, bem como de maior atenção dos serviços de saúde públicos para mulheres com excesso de peso em idade fértil.

Pregestational Diabetes in Pregnancy.

Diabetes is a common chronic condition in women of reproductive age. Preconception care is crucial to reducing the risk of adverse maternal and fetal outcomes, such as hypertensive disorders, abnormal fetal growth, traumatic delivery and stillbirth, associated with poor glycemic control. Insulin is the preferred medication to optimize glucose control in women with pregestational diabetes. Frequent dose adjustments are needed during pregnancy to achieve glycemic goals, and team-based multidisciplinary care may help. Postpartum care should include lactation support, counseling on contraceptive options, and transition to primary care.

Malformations among infants of mothers with insulin-dependent diabetes: Is there a recognizable pattern of abnormalities?

BACKGROUND: Infants of diabetic mothers have been shown in several studies to have an increased frequency of malformations. In previous studies, an increased frequency of several specific malformations has been noted, including anencephaly, bilateral renal agenesis, and double outlet right ventricle. Surveillance, used to identify all malformed infants in a consecutive sample of births, can identify a distinctive pattern of malformations among the affected infants. METHODS: The infants of insulin-dependent, pregestational diabetic mothers were identified in the daily review of the medical records of each newborn infant with a malformation and her/his mother's medical record. Infants of mothers with gestational diabetes were excluded. The frequency of each malformation was compared to that among the malformed infants of nondiabetic mothers. RESULTS: One hundred and eighty-three malformed infants of diabetic mothers were identified among the 289,365 births. The most notable malformations were: neural tube defects (anencephaly, 9%), heart defects (transposition of great arteries, 4%), bilateral renal agenesis or dysgenesis (6%), and vertebral anomalies (hemivertebrae, 4%). CONCLUSIONS: There was a recognizable pattern of malformations and characteristics of infants of diabetic mothers, although there was variation in the pattern among affected infants. Some of the malformations in the diabetic embryopathy can be identified in prenatal screening by ultrasound. More important, their occurrence can be reduced significantly by the mother achieving much better control of her diabetes mellitus prior to conception.

Disparities in Care for Publicly Insured Women With Pregestational Diabetes.

OBJECTIVE: To investigate the association among public health insurance, preconception care, and pregnancy outcomes in pregnant women with pregestational diabetes. METHODS: This is a retrospective cohort of pregnant women with pregestational type 1 or type 2 diabetes from 2006 to 2011 in Massachusetts-a state with universal insurance coverage since 2006. Women delivering after 24 weeks of gestation and receiving endocrinology and obstetric care in a multidisciplinary clinic were included. Rates of preconception consultation, our primary outcome of interest, were then compared between publicly and privately insured women. We used univariate analysis followed by logistic regression to compare receipt of preconception consultation and other secondary diabetes care measures and pregnancy outcomes according to insurance status. RESULTS: Fifty-four percent (n=106) of 197 women had public insurance. Publicly insured women were younger (median age 30.4 compared with 35.3 years, P<.01) with lower rates of college education (12.3% compared with 45.1%, P<.01). Women with public insurance were less likely to receive a preconception consult (5.7% compared with 31.9%, P<.01), had lower rates of hemoglobin A1C less than 6% at the onset of pregnancy (37.2% compared with 58.4%, P=.01), and experienced higher rates of pregnancies affected by congenital anomalies (10.4% compared with 2.2%, P=.02) compared with those with private insurance. In adjusted analyses controlling for educational attainment, maternal age, and body mass index, women with public insurance were less likely to receive a preconception consult (adjusted odds ratio [OR] 0.21, 95% CI 0.08-0.58), although the odds of achieving the target hemoglobin A1C (adjusted OR 0.45, 95% CI 0.20-1.02) and congenital anomaly (adjusted OR 2.23, 95% CI 0.37-13.41) were similar after adjustment. CONCLUSION: Despite continuous access to health insurance, publicly insured women were less likely than privately insured women to receive a preconception consult-an evidence-based intervention known to improve pregnancy outcomes. Improving use of preconception care among publicly insured women with diabetes is critical to reducing disparities in outcomes.

Unexpected regulation of miRNA abundance during adaptation of early-somite mouse embryos to diabetic pregnancy.

Maternal diabetes is one of major causes of congenital malformations in offspring, but the underlying mechanism is still unclear. MiRNAs play an important role in transcriptional and post-transcriptional regulation of gene expression. However, no miRNA expression profiling of hyperglycemic offspring are thus far available. Female mice were made diabetic with streptozotocin, treated with slow-release insulin tablets, and mated. MiRNA expression profiling with Next Generation Sequencing on the SOLiD5 platform was performed on 8 control and 5 hyperglycemic embryonic day (ED)8.5 and 9 control and 6 hyperglycemic ED9.5 embryos. Differential expression was analyzed with the Wald test. On ED8.5, the abundance of expressed miRNAs was similar in control and hyperglycemic ED8.5 embryos. The spectrum of expressed miRNAs had not changed in ED9.5 embryos, but the abundance of most miRNAs increased ∼5-fold in control embryos. However, hyperglycemic D9.5 embryos were unable to mount this increase in prevalence. Only 3 miRNAs were differentially expressed in control and hyperglycemic ED9.5 embryos, but their putative target genes were underrepresented in the Jackson database of genes causing cardiovascular or neural malformations.

Maternal Lipids May Predict Fetal Growth in Type 2 Diabetes Mellitus and Gestational Diabetes Mellitus Pregnancies.

AIM: During diabetic pregnancy, complex metabolic changes occur in the lipid profile. The aim of the study was to determine the predictive values of maternal serum lipid levels on large-for-gestational age newborns during the third trimester in pregnancies of women with type 2 diabetes mellitus (DM2) and gestational diabetes mellitus (GDM). MATERIAL AND METHODS: Data of forty three pregnancies of women with DM2 and two hundred women with GDM were analyzed. The analysis encompassed the following parameters: age, body mass index (BMI), lipid parameters, HbA1c in first, second and third trimester of pregnancy, preeclampsia and baby birth weight. RESULTS: DM2 and GDM groups showed statistically significant differences in the following variables: total lipids, triglycerides, total cholesterol, BMI, age, baby birth weight, incidence of SGA and preterm delivery (9.4 ± 2.3 vs. 11.0 ± 2.3 mmol/L, 2.4 ± 1.4 vs. 3.4 ± 1.6 mmol/L, 5.5 ± 1.2 vs. 6.4 ± 1.4 mmol/L, 30.6 ± 5.4 vs. 26.9 ± 5.2 kg/m2, 34 ± 7.8 vs. 31.5 ± 5.6 years, 3183 ± 972 vs. 3533 ± 699 g., 20% vs. 7.5%, 27.9 vs. 14%, respectively, p < 0.05). Linear multiple regression analysis demonstrated that triglycerides, LDL-C and total cholesterol were independent predictors of LGA (p < 0.05). CONCLUSION: Triglycerides and LDL-C in the third trimester of pregnancy are independent predictors for fetal macrosomia in DM2 and GDM pregnancies. Thus, the maternal serum triglycerides and LDL-C levels determined in the maternal blood taken in the third trimester of pregnancy may indentify women who will give birth to LGA newborns.

Factors Associated with Periodontal Disease in Pregnant Diabetic Women.

There have been an association between systemic diseases and hormonal changes particularly diabetes which has been cited as a risk factor in the progression of periodontitis in pregnant women. The incidence and severity of periodontal diseases are increasing at a higher rate and a common condition in pregnant diabetic women among Bangladeshi population. This cross sectional study included 200 pregnant women who were selected from gynecological department and examined at the dental unit. The clinical parameters used were the Silness and Loe plaque index (PI), gingival scores and periodontal status and any relationship to socio demographic variables (age, occupation, level of education and urban or rural residence) and clinical variables (gestation period, previous pregnancy, type of diabetes and periodontal maintenance) were evaluated. The results showed that these clinical parameters increased concomitantly with an increase in the stage of pregnancy and in women with multiple pregnancies. Increased age, lower level of education, unemployment and patients residing in rural areas were associated with significantly higher gingival scores and periodontal measures. Women with increased age and multiple pregnancies usually have less interest to frequent periodontal maintenance showing a significant statistical relation between an increased age and changes in gingival and periodontal status; however no significant association was found between increased age and plaque index. It is concluded that gingival inflammatory symptoms are aggravated during pregnancy in diabetic women and are related to different clinical and demographic variables.

Insulin resistance in pregnancy complicated by type 1 diabetes mellitus. Do we know enough?

Insulin resistance (IR) is defined clinically as the inability of a known quantity of exogenous or endogenous insulin to increase glucose uptake and utilization. In recent years the increasing role of IR in the pathogenesis of type 1 diabetes mellitus (T1DM) related complications has been taken into account. The aim of this article is to discuss the possible role of IR in pregnancy complicated by T1DM. At the moment, there is no doubt that IR is not only frequently observed in T1DM patients, but also is a separate risk factor of several complications in nonpregnant patients. The role of IR in pregnancy complicated by T1DM has not been widely studied yet. However, data from the studies on different populations showed that IR may predispose to such conditions as miscarriage, preeclampsia and macrosomia. Interestingly all of these are more frequently diagnosed in women with T1DM in comparison to healthy subjects. The literature on the role of IR in human pregnancy is relatively rich. However despite its significance in pathophysiology of T1DM and its complications in general population, there is a lack of understanding of how it affects maternal and fetal health in pregnancy complicated by this disease. Nonetheless, based on the available literature, IR may be proposed as an additional factor modifying pregnancy outcome in woman with T1DM. Therefore, measures that might reduce IR such as good glycemic control and control of weight gain should be recommended for every woman with T1DM, optimally when planning but also throughout the pregnancy

Gestational diabetes: a red flag for future Type 2 diabetes in pregnancy? A retrospective analysis.

AIMS: This study sought to understand the relationship between Type 2 diabetes in pregnancy and previous gestational diabetes (GDM), and determine whether a previous pregnancy with GDM was associated with subsequent better pregnancy planning. METHODS: A retrospective review of medical records of women with Type 2 diabetes in pregnancy was conducted at three teaching hospitals to ascertain whether they had earlier GDM, and to determine whether this is associated with differences in measures of pregnancy planning and diabetes management. RESULTS: Of 172 index pregnancies affected by Type 2 diabetes, in 76 (44%) cases, the mother had a previous history of GDM. Within this cohort, a diagnosis of 'overt diabetes in pregnancy', made on the basis of a GTT result during pregnancy in the WHO diabetic range with persistent diabetes post partum, was more common among women who had previous GDM than women who had not had GDM (20% vs 7%, P = 0.02). Women who previously had GDM did not exhibit a higher incidence of preconception planning or folate supplementation. CONCLUSIONS: It is common for women with Type 2 diabetes in pregnancy to have had GDM previously. The diagnosis of GDM is an opportunity to improve future pregnancy planning and outcomes for women with Type 2 diabetes in pregnancy. This goal is yet to be realized.

Diabetes in low-resourced countries.

Maternal and newborn health poses one of the greatest health challenges in the developing world. Many low-income countries are now experiencing a demographic and epidemiological transition and changing of lifestyles. Thus, apparent "Western" diseases such as diabetes and obesity have been reaching the Third World countries. There is a paucity of reliable data on diabetes in pregnancy in many low-income countries. Adequate information about maternal and perinatal mortality and morbidity as a consequence of diabetes in pregnancy is scarce. This chapter presents evidence of the magnitude and impact of diabetes in pregnancy. Additionally, we discuss interventions in screening and managing diabetes in pregnancy in these specific patient populations.

Maternal diabetes mellitus and the origin of non-communicable diseases in offspring: the role of epigenetics.

Offspring of diabetic mothers are susceptible to the onset of metabolic syndromes, such as type 2 diabetes and obesity at adulthood, and this trend can be inherited between generations. Genetics cannot fully explain how the noncommunicable disease in offspring of diabetic mothers is caused and inherited by the next generations. Many studies have confirmed that epigenetics may be crucial for the detrimental effects on offspring exposed to the hyperglycemic environment. Although the adverse effects on epigenetics in offspring of diabetic mothers may be the result of the poor intrauterine environment, epigenetic modifications in oocytes of diabetic mothers are also affected. Therefore, the present review is focused on the epigenetic alterations in oocytes and embryos of diabetic mothers. Furthermore, we also discuss initial mechanistic insight on maternal diabetes mellitus causing alterations of epigenetic modifications.

Genetics and diagnosis of central diabetes insipidus.

Most of the central diabetes insipidus cases seen in general practice are acquired but the rare cases of hereditary autosomal dominant or recessive neurohypophyseal diabetes insipidus have provided further cellular understanding of the mechanisms responsible for pre-hormone folding, maturation and release. Autosomal dominant central diabetes insipidus is secondary to the toxic accumulation of vasopressin mutants as fibrillar aggregates in the endoplasmic reticulum of hypothalamic magnocellular neurons producing vasopressin. As well, Trpv1(-/-) and Trpv4(-/-) mice have shed new light on the perception of tonicity through the stretch receptors TRPVs expressed both in central and peripheral neurons. The genomic information provided by sequencing the AVP gene is key to the routine care of these patients and, as in other genetic diseases, reduces health costs and provides psychological benefits to patients and families. In addition, simple, inexpensive blood and urine measurements together with clinical characteristics and brain magnetic resonance imaging (MRI) could distinguish between central, nephrogenic and polydipsic cases.