The Influence of Maternal Islet Beta-Cell Autoantibodies in Conjunction with Gestational Hyperglycemia on Neonatal Outcomes

Objective

To determine the predictive value of the presence of maternal islet beta-cell autoantibodies with respect to neonatal outcomes.

Methods

A total of 311 pregnant women with abnormal 75 g oral glucose tolerance test (OGTT) results were enrolled in this study. Maternal glutamic acid decarboxylase autoantibodies (GADA), islet cell autoantibodies (ICA) and insulin autoantibodies (IAA) were tested in fasting blood both on the day following the routine OGTT and before delivery. The birth weight, Apgar score, blood glucose and outcomes of each neonate were later evaluated and recorded.

Results

1. In this study, 33.9% of the pregnant women with gestational hyperglycemia had detectable levels of one or more types of anti-islet cell antibodies in the third trimester. The proportion of women who produced GADA and/or ICA was significantly higher in the group of women with gestational hyperglycemia than in the control group (P<0.05). The groups similarly differed in the proportion of women who tested positive for any anti-islet cell antibody (P<0.05). 2. Of the patients in our study, those who produced GADA exhibited an increase in uterine and umbilical arterial pulsatility indexes (PIs) during the third trimesters compared with the control group (P˂0.05). Additionally, an increased frequency of fetal growth restriction (FGR) was observed in the infants of women who produced IAA during pregnancy compared with those without autoantibodies (P˂0.05). 3. The rate of newborn admission to the neonatal intensive care unit (NICU) was significantly associated with the presence of maternal ICA during the third trimester (OR, 6.36; 95% CI, 1.22–33.26). 4. The incidence of neonatal asphyxia was associated with the presence of maternal GADA in both the second (OR, 10.44; 95% CI, 1.46–74.92) and the third (OR, 8.33; 95% CI, 1.45–47.82) trimesters.

Conclusion

Approximately one-third of the women with gestational hyperglycemia produced anti-islet cell antibodies. The incidence of FGR was higher in women with gestational hyperglycemia who produced IAA than in those without autoantibodies. Maternal ICA production in the third trimester was a risk factor for the subsequent admission of newborns to the NICU. Furthermore, the presence of maternal GADA placed the neonate at increased risk for asphyxia.     

Cytoplasmic islet-cell antibodies (ICA) and cytoplasmic complement- fixing antibodies (CF-ICA) in patients with newly detected and short-lasting diabetes mellitus type 1

The study aimed at assessing ICA and CF-ICA in the serum of patients with newly diagnosed and short-lasting diabetes mellitus type 1. Sixty patients with newly diagnosed diabetes type 1 (39 patients) and short-lasting diabetes of the same type (21 patients) aged between 2 and 34 years were classified. Anti-islet antibodies were detected with indirect immunoflourescence in specimens of fresh, frozen human pancreast in the tested group ICA were found in 53% of cases. At the time of diagnosis, ICA were found in 76% of children and in 14% of adult patients whereas respective data for diabetes mellitus lasting up to 2 years were 40% and 64%. Complement-fixing islet cytoplasmatic antibodies were found only in patients with ICA (47% of such cases). These antibodies were found in children with newly diagnosed diabetes mellitus (36%). In case of adults CF-ICA were detected in 7% of newly diagnosed diabetes mellitus cases and in 45% of cases with the disease lasting for 2 years. Titres of ICA ranged from 1:1 to 1:128 whereas titres CF-ICA from 1:1 to 1:8. No correlation between ICA titre and CF-ICA titre was noted.     

Postpartum thyroid dysfunction in Mid Glamorgan

A high prevalence of postpartum thyroid dysfunction has been reported in several countries, but there have been no systematic studies of its prevalence in Britain. Among a group of 901 consecutive, unselected pregnant women thyroid autoantibodies were detected in 117 (13%) at booking. The clinical course of postpartum thyroid dysfunction, factors associated with its development, and its likely prevalence were defined in 100 of these women with thyroid antibodies and 120 women with no such antibodies who were matched for age. None of the women had a history of autoimmune thyroid disease. Normal reference ranges for thyroid function during pregnancy and post partum were established in the 120 women negative for thyroid antibodies. On the basis of these observations postpartum thyroid dysfunction was observed in 49 (22%) of the 220 women studied, and the prevalence in the total group of 901 women was estimated to be 16·7%. Thyroid dysfunction, mainly occurring in the first six months post partum, was usually transient and included both destruction induced hyperthyroidism and hypothyroidism. The development of the syndrome was significantly related to smoking more than 20 cigarettes a day and the presence of thyroid microsomal autoantibodies at booking. Of the 16 women with a family history of thyroid disease in whom thyroid microsomal autoantibody activity was detectable at booking, 11 developed thyroid dysfunction. Age, parity, presence of goitre at presentation, duration of breast feeding, and the sex and birth weight of the infant were not associated with the development of postpartum thyroid dysfunction.The mood changes experienced by women post partum may in part be associated with altered thyroid function during this time.     

Gestational diabetes mellitus: a syndrome with phenotypic and genotypic heterogeneity

One hundred ninety-nine gravida with gestational diabetes mellitus (GDM) defined as "carbohydrate intolerance of varying severity with onset or first recognition during pregnancy" have been stratified into subgroups on the basis of fasting plasma glucose and evaluated for further phenotypic and genotypic heterogeneity. A significantly greater proportion of the women in all our groups were older and heavier than in a "control" population of 148 consecutive gravida with documented normal oral glucose tolerance. After correction for age and weight by covariate analysis, absolute insulinopenia in response to oral glucose could be demonstrated in all GDM groups, although exceptions were present in each. The incidence of diabetes in the mothers of our patients with GDM was 8-fold greater than in controls; the incidence in fathers did not deviate from control patterns. HLA-DR3 and DR4 antigens were more frequently present in GDM and the increase was statistically significant in blacks. At the time of diagnosis, cytoplasmic islet cell antibodies (ICA) were significantly more common in GDM associated with elevated fasting plasma glucose than in controls; the frequency of ICA was 18.4% (7/38) in women with fasting plasma glucose greater than or equal to 130 mg/dl. Our findings indicate that GDM entails genotypic as well as phenotypic diversity and may include patients with slowly-evolving Type I diabetes mellitus, as well as patients with Type II diabetes mellitus, and women with asymptomatic diabetes which antedated the pregnancy (i.e. pregestational diabetes mellitus). Appreciation of this heterogeneity should be incorporated into any evaluation of intervention strategies for women with GDM or into prognoses concerning their postpartum metabolic status.     

PPARalpha activation reverses adverse effects induced by high-saturated-fat feeding on pancreatic beta-cell function in late pregnancy

We examined whether the additional demand for insulin secretion imposed by dietary saturated fat-induced insulin resistance during pregnancy is accommodated at late pregnancy, already characterized by insulin resistance. We also assessed whether effects of dietary saturated fat are influenced by PPARalpha activation or substitution of 7% of dietary fatty acids (FAs) with long-chain omega-3 FA, manipulations that improve insulin action in the nonpregnant state. Glucose tolerance at day 19 of pregnancy in the rat was impaired by high-saturated-fat feeding throughout pregnancy. Despite modestly enhanced glucose-stimulated insulin secretion (GSIS) in vivo, islet perifusions revealed an increased glucose threshold and decreased glucose responsiveness of GSIS in the saturated-fat-fed pregnant group. Thus, insulin resistance evoked by dietary saturated fat is partially countered by augmented insulin secretion, but compensation is compromised by impaired islet function. Substitution of 7% of saturated FA with long-chain omega-3 FA suppressed GSIS in vivo but did not modify the effect of saturated-fat feeding to impair GSIS by perifused islets. PPARalpha activation (24 h) rescued impaired islet function that was identified using perifused islets, but GSIS in vivo was suppressed such that glucose tolerance was not improved, suggesting modification of the feedback loop between insulin action and secretion.     

The prevalence of islet-cell antibodies and complement-fixing islet-cell antibodies in Japanese diabetics

The presence of complement-fixing islet-cell antibodies (CF-ICA) and islet-cell antibodies (ICA) was examined in 355 patients with different types of diabetes mellitus in the Japanese population by an indirect immunofluorescence test (IFT). The overall prevalence of ICA, which were stained as a homogenous cytoplasmic fluorescence in islet cells, was 7 per cent (5/67) in insulin-dependent (Type I) diabetics, 4 per cent (6/137) in noninsulin-dependent (Type II) diabetics treated with insulin and 2 per cent (1/58) in Type II diabetics treated with oral hypoglycemic agents. None of 84 Type II diabetics receiving diet alone and 9 diabetics associated with chronic pancreatitis had ICA. CF-ICA, which were stained as a "ring-shaped" fluorescence in a part of the cytoplasma, were demonstrated in 5 out of 12 cases (42%) whose sera possessed ICA. The lower prevalence and remarkably shorter persistence of ICA and CF-ICA in Japanese diabetics than those observed in Caucasian diabetics may be explained by the heterogenous immunological response in different races or possible heterogeneity of Type I diabetics.     

Free-Triiodothyronine to Free-Thyroxine Ratio Mediated the Effect of Prepregnancy Body Mass Index or Maternal Weight Gain During Early Pregnancy on Gestational Diabetes Mellitus

ObjectiveMaternal overweight or obesity during early pregnancy can increase the subsequent risk of gestational diabetes mellitus (GDM). However, whether these associations are mediated by thyroid hormones and their effect sizes is still unknown. This study aimed to identify the mediating effects of thyroid parameters between prepregnancy body mass index (BMI) or maternal weight gain during early pregnancy on the subsequent risk of GDM.MethodsThis prospective mother-infant cohort study was conducted from 2018 to 2019. A total of 2772 singleton pregnant women were included in the analysis. A questionnaire survey, anthropometric measures, and thyroid function testing were conducted during early pregnancy. Deiodinase activity was evaluated using the free-triiodothyronine-to-free-thyroxine ratio (FT3:FT4). The standard 75-g oral glucose tolerance test was performed during 24 to 28 weeks of gestation to diagnose GDM. A mediation analysis was performed using PROCESS 3.5 to examine the mediating effects of thyroid parameters between prepregnancy BMI or maternal weight gain during early pregnancy on the subsequent risk of GDM.ResultsThe FT3:FT4 ratio was a significant mediator between prepregnancy BMI or maternal weight gain and GDM, accounting for 16.5% and 18.6% of total effects, respectively. FT3 also mediated the association of prepregnancy BMI with GDM, accounting for 3.3% of the total effects. Thyroid-stimulating hormone suppressed the effects of prepregnancy BMI and maternal weight gain on GDM risk, and the proportion of their total effects was 2.4% and 6.4%, respectively.ConclusionDeiodinase activity, as indicated by the FT3:FT4 ratio, was the strongest mediator among thyroid parameters between prepregnancy BMI or maternal early weight gain and GDM.     

Association of Early Pregnancy Free and Total Triiodothyronine With the Subsequent Risk of Gestational Diabetes Mellitus

ObjectiveTo estimate the association of free triiodothyronine (FT3) and total triiodothyronine (TT3) in early pregnancy and subsequent gestational diabetes mellitus (GDM) risk and define appropriate TT3 thresholds for GDM screening.MethodsThis investigation is a hospital-based cohort study of pregnant women submitted to a universal thyroid function test before 24 weeks of gestation. GDM was diagnosed according to a 75-g oral glucose tolerance test. The association of maternal high FT3 and TT3 levels in early pregnancy with the risk of GDM was estimated using logistic regression. The potential nonlinear association was probed by the restricted cubic spline curve method.ResultsA total of 27 184 pregnant women and 3073 GDM cases were included in the analysis. FT3 and TT3 were associated with an increased subsequent risk of GDM in a nonlinear fashion. The adjusted odds ratios were 1.59 (95% confidence interval, 1.50-1.68) and 2.80 (95% confidence interval, 2.46-3.18) for FT3 and TT3 continuous levels, respectively. Associations were strong in euthyroid women, showed heterogeneity in women with mild thyroid dysfunction, and lacked in patients with overt hypothyroidism and hyperthyroidism. The TT3 thresholds of 1.5 and 2.0 ng/mL between 7 and 12 weeks of gestation and 1.6 and 2.1 ng/mL for 13 to 23 weeks of gestation effectively distinguished the subsequent risk of GDM.ConclusionThe increased FT3 and TT3 levels in early pregnancy were associated with a subsequent higher risk of GDM. These findings provide measures for early detection and potential prevention of GDM.     

Impairment of endothelial function in women with a history of preeclampsia: an indicator of cardiovascular risk

Preeclampsia is a disorder of pregnancy diagnosed by gestational hypertension and proteinuria. Epidemiological evidence suggests that women who experience preeclampsia are at a greater risk of hypertension and heart disease later in life compared with women who had normal pregnancies. Our objective was to determine whether endothelial function is impaired in postpartum women with a history of preeclampsia in their first pregnancy. We measured forearm blood flow (FBF) by venous occlusion plethysmography in 50 healthy women: 16 with prior preeclampsia, 14 with a prior normotensive pregnancy, and 20 never pregnant controls. The postpartum women participated 6-12 mo after delivery. Heart rate (HR) and blood pressure (BP) were concurrently monitored on the contralateral arm. Hemodynamic variables were assessed at baseline and during a mental stress test known to elicit endothelium-dependent vasodilatation. We found that baseline FBF, HR, systolic BP, and diastolic BP did not significantly differ among the groups, whereas mean arterial pressure in the preeclamptic group was greater than that of the normal pregnancy group (P = 0.03). Stress-induced FBF (percent change over baseline) was reduced in the preeclamptic group compared with both the normal pregnancy and never pregnant groups (P = 0.06) and was significantly attenuated compared with women with prior normal pregnancies (91% vs. 147%, P = 0.006). These data demonstrate that women with a history of preeclampsia exhibit impaired endothelial function up to 1 yr postpartum. This observation may explain their increased risk for hypertension and cardiovascular disease.     

Diet-induced impaired glucose tolerance and gestational diabetes in the dog

Glucose metabolism was compared in dogs consuming a chow/meat diet throughout pregnancy (P group, n = 6) and dogs switched to a high-fat/high-fructose (HFF) diet during the 4th-5th gestational week (gestation ?9 wk; P-HFF group; n = 6). An oral glucose tolerance test (OGTT; 0.9 g/kg) was administered in the 6th-7th gestational week, and a hyperinsulinemic [0-120 min: 1.8 pmol·kg(-1)·min(-1) (low insulin); 120-240 min: 9 pmol·kg(-1)·min(-1) (high insulin)] euglycemic clamp was performed the following week. Nonpregnant (NP) female dogs underwent OGTTs but not clamp studies. All P-HFF dogs exhibited impaired glucose tolerance (IGT) or gestational diabetes (GDM), but only one P dog had IGT. Insulin concentrations in P and P-HFF dogs were significantly lower than in NP dogs 30 and 60 min after the OGTT. Therefore, mean islet size and area were evaluated in P and NP dogs. These values did not differ between groups, and proliferating endocrine cells were rare in pregnancy. During exposure to high insulin, glucose infusion rate and hindlimb glucose uptake were ～30% greater (P < 0.05) and net hepatic glucose output was more suppressed (-5.5 ± 6.1 vs. 7.8 ± 2.8 mg·100 g liver(-1)·min(-1), P < 0.05) in P than in P-HFF dogs. In conclusion, in the 2nd trimester the canine pancreas does not exhibit islet hypertrophy, hyperplasia, or neogenesis. Combined with the lack of pancreatic adaptation, a HFF diet during late pregnancy produces a canine model of IGT and GDM without hyperinsulinemia but exhibiting liver and muscle insulin resistance.     

Is subclinical hypothyroidism contributing dyslipidemia and insulin resistance in women with polycystic ovary syndrome?

We aimed to analyze lipid parameters and determine the need for a 2-hour oral glucose tolerance test (OGTT) for the identification of IR and impaired glucose tolerance test (IGT) in subclinical hypothyroidism (SCH) women with and without polycystic ovary syndrome (PCOS). 20 patients with PCOS and SCH consisted of Group I and 39 patients with PCOS and normal thyroid function consisted of Group II and 53 healthy women with normal thyroid function consisted of Group III. Triglyceride levels were 143.26?±?99.86?mg/dL in group 1 and 88.56?±?37.56?mg/dL in group 2 and 83.71?±?31.94?mg/dL in group 3 which were statistically significant. Total cholesterol, HDL- cholesterol, LDL-cholesterol were found similar between the groups. Fasting insulin levels were 12.45?±?8.62 μU/mL in group 1 and 8.60?±?5.35 μU/mL in group 2 and 7.04?±?3.55 μU/mL in group 3 which were statistically significant (P?=?0.027). HOMA-IR were 2.92?±?2.34 in group 1 and 1.95?±?1.52 in group 2 and 1.60?±?0.86 in group 3 which were statistically significant (P?=?0.046). This study showed that women with PCOS and subclinical hypothyroidism should be evaluated for dyslipidemia and Insulin resistance.     

Women With Hypertensive Pregnancies Have Difficulties in Regaining Pre‐pregnancy Weight and Show Metabolic Disturbances

The aim was to determine maternal weight gain and body composition during pregnancy and 3 months postpartum in women with uncomplicated singleton and twin pregnancies and in women with gestational diabetes (GDM) and gestational hypertension (GH). This prospective study includes four groups of subjects: those with an uncomplicated pregnancy (n = 32), those with a diagnosis of GH (n = 28), those with a diagnosis of GDM (n = 52), and those with twin pregnancy (n = 11). Their body compositions were estimated by a bioimpedance analysis and fasting lipids and glucose levels were determined during the pregnancy and 3 months after pregnancy. Women with GDM were 11.7 kg heavier than the reference group before pregnancy, whereas weight before pregnancy was not different in other investigated groups. Weight loss after delivery was attenuated in GH group. Percentage body fat remained elevated in women with GDM (34.1 ± 7.0%) and hypertension (31.5 ± 6.4%) at 3 months after pregnancy. Also their total cholesterol and low‐density lipoprotein (LDL)‐cholesterol levels as well as fasting glucose remained elevated in comparison to values of the reference group. In conclusion, women with hypertensive pregnancies, though not overweight before pregnancy, gain and retain excess gestational weight and this leads to metabolic abnormalities similar to those seen in women GDM. Thus, postpartum period appears to be critical for weight management and interventional programs are called for.     

Influence of hyperglycemia during and after pregnancy on postpartum vascular function

Endothelial dysfunction is commonly observed in women with a previous diagnosis of gestational diabetes mellitus (GDM). Whether arterial stiffness is also related to pregnancy and/or postpartum glucose intolerance has not been determined. We examined the influence of GDM during pregnancy and hyperglycemia in the postpartum period on arterial function. Thirty postpartum women were stratified into one of three groups: 1) normoglycemic pregnancy, normoglycemic postpartum (NORM), 2) GDM during pregnancy, normoglycemic postpartum (GDM-N); and 3) GDM during pregnancy, hyperglycemic postpartum (GDM-H). Ten never-pregnant controls were also recruited (Control). All measures were made at 2 mo postpartum or in the early follicular phase in Control women. Arterial stiffness was assessed by pulse wave velocity (PWV) and brachial and carotid artery distensibility. Endothelial function was determined by flow-mediated dilation (FMD). PWV was not different between the four groups. Distensibility of the brachial and carotid arteries was lower in GDM-N women (brachial: 1.1 × 10(-3) mmHg(-1) ± 3.6 × 10(-4); carotid: 2.0 × 10(-3) ± 3.3 × 10(-4)) and GDM-H (brachial: 1.4 × 10(-3) mmHg(-1) ± 4.1 × 10(-4); carotid: 1.8 × 10(-3) mmHg(-1) ± 5.0 × 10(-4)) compared with NORM women (brachial: 3.4 × 10(-3) mmHg(-1) ± 7.0 × 10(-4); carotid: 3.9 × 10(-3) ± 7.4 × 10(-4)). However, only brachial artery distensibility returned to Control levels by 2 mo postpartum in the NORM women. FMD was lower in previously GDM women (GDM-N: 4.1% ± 2.3; GDM-H: 4.4% ± 0.9) compared with NORM women (10.8% ± 1.3; P < 0.01). These findings suggest that the vascular function of women in the early postpartum period is influenced by GDM during pregnancy and the persistence of clinical and/or subclinical hyperglycemia after delivery.     

Hormonal profile and glucose tolerance in late pregnancy and postpartum

Oral glucose tolerance, plasma insulin and basal levels of glucagon, hGH, hPRL, hPL, TSH, T4, T3, thyroxine-binding globulin (TBG), cortisol, corticosteroid-binding globulin (CBG) and estriol were measured in 23 normal pregnant women in late gestation (31 +/- 0.4 weeks of pregnancy). Twelve of these subjects could be re-examined 14 +/- 2 weeks postpartum. Blood glucose was lower basal and after glucose load (100 g) in the pregnant group. Fasting plasma insulin and glucose-induced insulin release were higher in pregnancy. The insulinogenic index and the beta cell response were significantly greater antepartum, while peripheral insulin activity was unchanged. The insulin:glucagon ratio as well as TSH and hGH showed no significant differences between ante- and postpartum values. However, T4, T3, TBG, cortisol, CBG, estriol, hPRL and hPL were significantly higher during gestation than after delivery. T4:TBG and T3:TBG ratios were much lower antepartum, while the cortisol:CBG ratio was comparable ante- and postpartum. To our knowledge this is the first report in which such an extensive hormonal and metabolic analysis was performed in the same women ante- and postpartum. It could be shown that glucose tolerance is not worsened during pregnancy in healthy subjects. The higher gestational insulin values are discussed with respect to the various significant hormonal changes.     

The combination of antibodies to GAD-65 and IA-2ic can replace the islet-cell antibody assay to identify subjects at risk of type 1 diabetes mellitus.

First-degree relatives of type 1 diabetic patients are at increased risk of developing diabetes and, until recently, islet cell antibodies (ICA) have represented the major risk marker used for identification of individuals at increased risk for subsequent progression to diabetes. In order to determine the value of antibodies to GAD-65 and IA-2ic to identify individuals at high risk for type 1 diabetes mellitus, we measured both autoantibodies and ICA in 1436 first-degree relatives of patients with type 1 diabetes. In addition, the sera were analyzed for thyroid, adrenal and gastric-parietal cell autoantibodies as markers for possible polyendocrine involvement. GAD-65 Abs were found in 135 out of 1436 (9.4%) first-degree relatives and in 57 of 98 (58.2%) ICA-positive subjects. IA-2ic were detected in 52 of 1436 (3.6%) first-degree relatives and in 44 of 98 (44.8%) ICA-positive relatives. IA-2ic and/or GAD-65 were detected in 73 of 98 (74.5%) ICA-positive relatives. Interestingly, antibodies to GAD-65 and/or IA-2ic were present in 91.2% of individuals with more than 20JDF-units. Anti-IA-2ic and GAD-65 were positively correlated with high levels of ICA. Anti-IA-2ic and GAD-65 were found in 19% and 48.5% of subjects with ICA levels of 5-20JDF-u but in 68.8% and 76.5% of individuals with ICA of 40JDF-u or more, respectively (p < 0.001), compared to subjects with ICA levels less than 5 JDF-u. When autoantibody frequencies among the relatives were analyzed according to relationship to the proband, the offspring and siblings had a higher frequency of ICA and IA-2ic (p<0.05) than the subgroup of parents. A significant association was observed between IA-2ic and thyroid antibodies. In addition, higher levels of IA-2ic were found in relatives with positive TPO antibodies (p < 0.001); this correlation was particularly strong in offspring and siblings (p < 0.01). Determination of GAD-65 and IA-2ic antibodies may be considered as an alternative to primary ICA-screening, enabling the screening of large populations.     

饮食疗法对妊娠期糖尿病孕妇血脂代谢动态变化的研究

目的:探讨脂代谢紊乱在妊娠期糖尿病(GDM)中的作用,为妊娠期糖尿病的预防及指导临床干预提供理论依据。方法:观察妊娠期糖尿病患者和糖耐量正常孕妇血脂水平及胰岛素抵抗程度差异,分析妊娠期糖尿病患者饮食治疗前后的血脂及炎症标志物的动态变化,于孕12W、24W及36W分别抽取两组孕妇空腹静脉血,测定糖、脂代谢指标及炎症标志物水平,计算血浆致动脉粥样硬化指数(atherogenic index of the plasma,AIP);应用稳态模型胰岛素抵抗指数(HOMA-IR)及胰岛分泌功能指数(HBCI),评价胰岛素抵抗指数(IR)程度及胰岛功能。结果:(1)GDM组的C肽、FINS、HOMA-IR明显高于糖耐量正常组(normal glucose tolerance,NGT)组(p0.05),GDM组HBCI指数低于NGT组(p0.05)。(2)干预组与对照组比较,12W时,TC、TG、HDL、LDL差异均无统计学意义(p0.05);24W及32W差异均有统计学意义(p0.05),均较对照组高。(3)对GDM组中TC、TG、HDL、LDL、AIP、hs-CRP、N及WBC值进行分析,TG、TC、LDL、AIP、hs-CRP、N及WBC值24W较36W及12W高(p0.05);HDL水平24W较36W及12W低(p0.05)。(4)NGT组中TG、TC、LDL、AIP、hs-CRP、N及WBC值36W较24W及12W高(p0.05);HDL水平36W较24W及12W高(p0.05)。结论:GDM孕妇存在着明显的胰岛素抵抗和胰岛β细胞分泌功能受损。GDM孕妇合并较正常妊娠更为严重的炎症反应,血脂水平明显升高,饮食治疗后对改善IR有益,提示在妊娠期糖尿病患者中,通过适当的饮食治疗进而对血糖及血脂的调整可以显著减少母儿并发症。     

The effect of high-intensity breastfeeding on postpartum glucose tolerance in women with recent gestational diabetes

Background

Although breastfeeding is expected to reduce the incidence of diabetes in women with gestational diabetes, the effect has not been clearly confirmed. We examined whether or not high-intensity breastfeeding reduces the incidence of abnormal glucose tolerance and investigated the effect of high-intensity breastfeeding on insulin resistance during the first year postpartum in Japanese women with current gestational diabetes.

Methods

In this retrospective study, we included women with gestational diabetes who underwent postpartum 75 g oral glucose tolerance test during the first year (12-14 months) postpartum from 2009 to 2011 at a single tertiary perinatal care center in Japan. High-intensity breastfeeding was defined as the condition in which infants were fed by breastfeeding alone or 80% or more of the volume. We investigated the effect of high-intensity breastfeeding on the prevalence of postpartum abnormal glucose tolerance and the postpartum homeostasis model of assessment of insulin resistance (HOMA-IR), after controlling for confounders, including prepregnancy obesity and weight changes during pregnancy and postpartum.

Results

Among 88 women with gestational diabetes, 46 (52%) had abnormal glucose tolerance during the postpartum period. High-intensity breastfeeding women (n?=?70) were significantly less likely to have abnormal glucose tolerance than non-high-intensity breastfeeding women (n?=?18) (46% vs. 78%, p?=?0.015). High-intensity breastfeeding was also associated with a lower HOMA-IR at 12-14 months postpartum than non-high-intensity breastfeeding (1.41?±?1.02 vs. 2.28?±?1.05, p?=?0.035). Those associations remained significant after controlling for confounders. At least six months of high-intensity breastfeeding had a significant effect on lowering both the abnormal glucose tolerance prevalence and HOMA-IR compared with non-high-intensity breastfeeding.

Conclusions

In Japanese women with gestational diabetes, high-intensity breastfeeding ≥6 months had a protective effect against the development of abnormal glucose tolerance during the first year postpartum through improving insulin resistance, independent of obesity and postpartum weight change.

     

Short-term exercise training early in life restores deficits in pancreatic β-cell mass associated with growth restriction in adult male rats

Fetal growth restriction is associated with reduced pancreatic β-cell mass, contributing to impaired glucose tolerance and diabetes. Exercise training increases β-cell mass in animals with diabetes and has long-lasting metabolic benefits in rodents and humans. We studied the effect of exercise training on islet and β-cell morphology and plasma insulin and glucose, following an intraperitoneal glucose tolerance test (IPGTT) in juvenile and adult male Wistar-Kyoto rats born small. Bilateral uterine vessel ligation performed on day 18 of pregnancy resulted in Restricted offspring born small compared with sham-operated Controls and also sham-operated Reduced litter offspring that had their litter size reduced to five pups at birth. Restricted, Control, and Reduced litter offspring remained sedentary or underwent treadmill running from 5 to 9 or 20 to 24 wk of age. Early life exercise increased relative islet surface area and β-cell mass across all groups at 9 wk, partially restoring the 60-68% deficit (P < 0.05) in Restricted offspring. Remarkably, despite no further exercise training after 9 wk, β-cell mass was restored in Restricted at 24 wk, while sedentary littermates retained a 45% deficit (P = 0.05) in relative β-cell mass. Later exercise training also restored Restricted β-cell mass to Control levels. In conclusion, early life exercise training in rats born small restored β-cell mass in adulthood and may have beneficial consequences for later metabolic health and disease.     

Differentially Expressed MicroRNAs in Postpartum Breast Cancer in Hispanic Women

The risk of breast cancer transiently increases immediately following pregnancy; peaking between 3-7 years. The biology that underlies this risk window and the effect on the natural history of the disease is unknown. MicroRNAs (miRNAs) are small non-coding RNAs that have been shown to be dysregulated in breast cancer. We conducted miRNA profiling of 56 tumors from a case series of multiparous Hispanic women and assessed the pattern of expression by time since last full-term pregnancy. A data-driven splitting analysis on the pattern of 355 miRNAs separated the case series into two groups: a) an early group representing women diagnosed with breast cancer ≤ 5.2 years postpartum (n = 12), and b) a late group representing women diagnosed with breast cancer ≥ 5.3 years postpartum (n = 44). We identified 15 miRNAs with significant differential expression between the early and late postpartum groups; 60% of these miRNAs are encoded on the X chromosome. Ten miRNAs had a two-fold or higher difference in expression with miR-138, miR-660, miR-31, miR-135b, miR-17, miR-454, and miR-934 overexpressed in the early versus the late group; while miR-892a, miR-199a-5p, and miR-542-5p were underexpressed in the early versus the late postpartum group. The DNA methylation of three out of five tested miRNAs (miR-31, miR-135b, and miR-138) was lower in the early versus late postpartum group, and negatively correlated with miRNA expression. Here we show that miRNAs are differentially expressed and differentially methylated between tumors of the early versus late postpartum, suggesting that potential differences in epigenetic dysfunction may be operative in postpartum breast cancers.     

The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients

Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests including mixed-meal tolerance test, human leukocyte antigen alleles, hemoglobinA1c, lipids, thyroid function and islet autoantibodies were conducted. The frequency of islet-specific autoantibody in newly diagnosed T1DM patients (duration shorter than half year) was 73% in East China. According to binary logistic regressions, autoantibody positivity, longer duration and lower Body Mass Index were the risk factors of islet failure. As the disease developed, autoantibodies against glutamic acid decarboxylase declined as well as the other two autoantibodies against zinc transporter 8 and islet antigen 2. The decrease of autoantibodies was positively correlated with aggressive beta cell destruction. Autoantibodies can facilitate the identification of classic T1DM from other subtypes and predict the progression of islet failure. As there were obvious heterogeneity in autoantibodies and clinical manifestation in different phenotypes of the disease, we should take more factors into consideration when identifying type 1 diabetes mellitus.