[Show abstract][Hide abstract] ABSTRACT: Objective:
To investigate the clinical significance of falling insulin requirements in women with preexisting or overt diabetes in pregnancy.
Research design and methods:
A retrospective review of 139 pregnancies was conducted in women, with preexisting diabetes, delivering between January 2010 and January 2013. Women with falling insulin requirements of 15% or more from the peak total daily dose in late pregnancy were considered case subjects (n = 35). The primary outcome consisted of a composite of clinical markers of placental dysfunction, including preeclampsia, small for gestational age (SGA, ≤5th percentile for gestational age), stillbirth (>20 weeks), and premature delivery (≤30 weeks).
A total of 25.2% of women had >15% fall in insulin requirements with nulliparity as the only predictor at baseline (odds ratio [OR] 2.5 [95% CI 1.1-5.7], P = 0.03). Falling insulin requirements were associated with an increased risk of preeclampsia (OR 3.5 [1.1-10.7], P < 0.05) and the composite of clinical markers of placental dysfunction (4.4 [1.73-11.26], P = 0.002). Although falling insulin requirements were associated with higher rates of SGA (3.4 [1.0-11.3], P = 0.048), they were not associated with other adverse neonatal outcomes. However, there was a higher incidence of neonatal intensive care unit admission (15.5 [3.1-77.6], P = 0.001) and earlier delivery in this group (median 37.7 weeks [IQR 34.3-38.4] vs. 38.3 weeks [37.4-38.9], P = 0.014).
Falling insulin requirements, in women with preexisting diabetes, are associated with an increased risk of complications related to placental dysfunction. Further prospective studies are needed to guide clinical management.
Diabetes Care 07/2014; 37(10). DOI:10.2337/dc14-0506 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE
Vitamin D deficiency in pregnancy is associated with an increased risk of gestational diabetes mellitus (GDM) and neonatal vitamin D deficiency. We conducted a double-blind, randomized controlled trial of low-dose (LD) versus high-dose (HD) vitamin D supplementation to investigate the effects of vitamin D supplementation on glucose metabolism during pregnancy.RESEARCH DESIGN AND METHODS
Women with plasma 25-hydroxyvitamin D (25OHD) levels <32 ng/mL before 20 weeks' gestation were randomized to oral vitamin D3 at 5,000 IU daily (HD) (n = 89) or the recommended pregnancy dose of 400 IU daily (LD) (n = 90) until delivery. The primary end point was maternal glucose levels on oral glucose tolerance test (OGTT) at 26-28 weeks' gestation. Secondary end points included neonatal 25OHD, obstetric and other neonatal outcomes, and maternal homeostasis model assessment of insulin resistance. Analysis was by intention to treat.RESULTSThere was no difference in maternal glucose levels on OGTT. Twelve LD women (13%) developed GDM versus seven (8%) HD women (P = 0·25). Neonatal cord 25OHD was higher in HD offspring (46 ± 11 vs. 29 ± 12 ng/mL, P < 0.001), and deficiency was more common in LD offspring (24 vs. 10%, P = 0.06). Post hoc analysis in LD women showed an inverse relationship between pretreatment 25OHD and both fasting and 2-h blood glucose level on OGTT (both P < 0·001). Baseline 25OHD remained an independent predictor after multiple regression analysis.CONCLUSIONSHD vitamin D supplementation commencing at a mean of 14 weeks' gestation does not improve glucose levels in pregnancy. However, in women with baseline levels <32 ng/mL, 5,000 IU per day was well tolerated and highly effective at preventing neonatal vitamin D deficiency.
Diabetes care 04/2014; 37(7). DOI:10.2337/dc14-0155 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Insulin secretion increases in normal pregnancy to meet increasing demands. Inability to increase beta-cell function results in gestational diabetes mellitus (GDM). We have previously shown that the expression of the transcription factor ARNT (Aryl-hydrocarbon Receptor Nuclear Translocator) is reduced in the islets of humans with type 2 diabetes. Mice with a beta-cell specific deletion of ARNT (β-ARNT mice) have impaired glucose tolerance secondary to defective insulin secretion. We hypothesised that ARNT is required to increase beta-cell function during pregnancy, and that β-ARNT mice would be unable to compensate for the beta-cell stress of pregnancy. The aims of this study were to investigate the mechanisms of ARNT regulation of beta-cell function and glucose tolerance in pregnancy.
β-ARNT females were mated with floxed control (FC) males and FC females with β-ARNT males.
During pregnancy, β-ARNT mice had a marked deterioration in glucose tolerance secondary to defective insulin secretion. There was impaired beta-cell proliferation in late pregnancy, associated with decreased protein and mRNA levels of the islet cell-cycle regulator cyclinD2. There was also reduced expression of Irs2 and G6PI. In contrast, in control mice, pregnancy was associated with a 2.1-fold increase in ARNT protein and a 1.6-fold increase in cyclinD2 protein, and with increased beta-cell proliferation.
Islet ARNT increases in normal murine pregnancy and beta-cell ARNT is required for cyclinD2 induction and increased beta-cell proliferation in pregnancy.
PLoS ONE 10/2013; 8(10):e77419. DOI:10.1371/journal.pone.0077419 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diabetes in pregnancy is linked to development of obesity in the offspring, but the mechanisms are not fully understood. Gestational diabetes mellitus (GDM) occurs when beta cells are unable to compensate for the normal insulin resistance of late pregnancy. In this study, we used a murine model of beta cell dysfunction to examine the effects of maternal GDM on phenotype in male offspring with and without an inherited predisposition for beta cell dysfunction.
Beta cell-specific aryl-hydrocarbon receptor nuclear translocator-null (βArnt) mice develop GDM from beta cell dysfunction. βArnt and control female mice were used to induce GDM and non-diabetic pregnancies, respectively.
Offspring from GDM pregnancies became spontaneously obese on a normal-chow diet. They were heavier than offspring from non-diabetic pregnancies, with increased body fat. Respiratory exchange ratio (RER) was higher, indicating decreased capacity to switch to lipid oxidation. Metabolic rate in GDM offspring was decreased prior to onset of obesity. The phenotype was more pronounced in βArnt GDM offspring than in GDM offspring of control genotype, demonstrating an interaction between genotype and pregnancy exposure. βArnt GDM offspring had increased hypothalamic neuropeptide Y (Npy) and decreased pro-opiomelanocortin (Pomc) expression. Weight, body fat, insulin sensitivity and RER in all mice, and hypothalamic Npy in βArnt mice were significantly correlated with AUC of maternal late pregnancy glucose tolerance tests (p < 0.01), but not with litter size, maternal weight, triacylglycerol or pre-pregnancy glycaemia.
In βArnt mice, exposure to GDM and inheritance of genetic beta cell dysfunction had additive effects on male offspring obesity; severity of the offspring phenotype correlated with maternal glycaemia.
[Show abstract][Hide abstract] ABSTRACT: Women with previous gestational diabetes mellitus (GDM) are at increased risk of developing type 2 diabetes; this risk is higher in non-Caucasian women. This study explored the beliefs, attitudes, social support, environmental influences and other factors related to diabetes risk behaviours among Arabic, Cantonese/Mandarin, and English speaking women with recent GDM.
Women living in the Sydney metropolitan area (Australia) who had GDM 6-36 months previously were included. In-depth semi-structured telephone interviews on women's experiences and perceptions of GDM and the lifestyle risk factors for developing type 2 diabetes were conducted in the language participants spoke at home (n=20 Arabic, 20 Cantonese/Mandarin, 17 English). Data were analysed for underlying themes using NVivo software.
Mental distress, role perceptions, social support and cultural expectations were major issues related to women's struggles to find the right balance between the large proportion of household and child care responsibilities and leading a healthy lifestyle.
Women's ability to follow a healthy lifestyle is embedded in their psychological wellbeing and the social and cultural context of their lives. The study highlights the need for a holistic approach that ensures personal support and access to services as well as lifestyle specific programs.
Health promotion journal of Australia: official journal of Australian Association of Health Promotion Professionals 08/2010; 21(2):130-7. · 0.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is unclear if people who develop stress hyperglycaemia have underlying abnormal glucose metabolism, an exaggerated hormonal response to stress, or both. Similarly, it is unknown whether stress hyperglycaemia predicts future glucose intolerance.
To determine the relationship between illness severity and plasma cortisol concentration with the degree of hyperglycaemia in subjects experiencing acute myocardial infarction (AMI), and their later glucose metabolic status.
This analysis comprised 55 patients from the HI-5 Study--a randomized control trial of insulin-glucose infusion therapy for AMI patients with hyperglycaemia.
Blood glucose level (BGL) as well as total and free cortisol levels on admission were measured. Patients not previously known to have diabetes were assessed for abnormal glucose metabolism following discharge.
Patients with ST segment-elevation myocardial infarction (STEMI) and higher peak creatinine kinase level had a higher mean admission total and free cortisol level. As many as 38.5% of subjects were found to have newly diagnosed glucose intolerance at follow up. After multiple logistic regression, admission BGL was found to be a positive predictor (P = 0.027) whereas total cortisol level (P = 0.01) was a negative predictor for glucose intolerance.
Both the level of hyperglycaemia and cortisol levels on admission are predictive for the subsequent abnormal glucose tolerance development in hyperglycaemic AMI patients. Hyperglycaemia in patients who are more unwell (i.e. higher cortisol) reflects the stressed state rather than underlying glucose intolerance. Conversely, if the patient is less sick (i.e. lower cortisol), hyperglycaemia is more likely to reflect underlying glucose intolerance.
[Show abstract][Hide abstract] ABSTRACT: To determine the effects of insulin infusion and blood glucose levels during acute myocardial infarction (AMI) on electrocardiographic (ECG) features of myocardial electrical activity.
ECGs at admission and 24 h were examined in a randomized study of insulin infusion vs. routine care for AMI patients with diabetes or hyperglycaemia. Results were analysed according to treatment allocation and also according to average blood glucose level.
ECG characteristics were similar at admission in both groups. Patients allocated to conventional treatment had prolongation of the QT interval (QTc) after 24 h but those receiving infused insulin did not. In patients with a mean blood glucose in the first 24 h > 8.0 mmol/l, new ECG conduction abnormalities were significantly more common than in patients with mean blood glucose <or= 8.0 mmol/l (15.0% vs. 6.0%, P < 0.05).
Prevention of QTc prolongation by administration of insulin may reflect a protective effect on metabolic and electrical activity in threatened myocardial tissue. Abnormalities of cardiac electrical conduction may also be influenced by blood glucose.
Diabetic Medicine 03/2009; 26(2):174-6. DOI:10.1111/j.1464-5491.2008.02630.x · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study investigated postpartum dietary behaviors among women with recent gestational diabetes mellitus (GDM), the cognitive and social factors related to these, and preferred types of lifestyle support, in order improve the development of diabetes prevention strategies for this group.
Participants were a random sample of 226 women diagnosed with GDM in the prior 6 to 24 months. Telephone surveys were used to evaluate dietary behaviors, self-efficacy, social support, perceived barriers to healthy eating, and preferred methods of lifestyle support.
Only 5% of the respondents consumed 5 servings/day of vegetables and 44% consumed 2 or more servings/day of fruit. Fried food was eaten at least twice per week by 26% of women and 50% usually consumed full-fat milk. Higher vegetable consumption was associated with self-efficacy to cook healthy foods, reporting that a healthy diet is not a difficult change and that dislike of healthy foods by other household members is not a barrier. Fruit consumption was positively related to self-efficacy when busy and when not reporting a dislike of healthy foods by others at home. Advice from a dietitian and telephone support from a health educator were the most preferred forms of health assistance.
Dietary risks factors are prevalent among women with recent GDM. Confidence and skills in cooking healthy foods, along with family food preferences and time pressures, are important influences on eating habits. Dietary change programs, informed by the beliefs and circumstances of this high-risk population, need to be developed.
The Diabetes Educator 09/2008; 34(5):807-14. DOI:10.1177/0145721708323641 · 1.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hyperglycaemia in the period following myocardial infarction is associated with increased mortality and there is some evidence that its treatment can improve survival. However, it remains unclear as to what the ideal glucose targets might be. This study examined observational data taken from a previously reported randomised controlled trial of insulin therapy for myocardial infarction (The Hyperglycaemia: Intensive Insulin Infusion In Infarction Study), to determine optimal glucose levels for this period. Capillary glucose readings were recorded at 8 standard time points for 234 subjects in first 24h after myocardial infarction. Survival over 6 months was analysed according to whether 80% of each subject's glucose readings were below specified glucose thresholds (Achievers) or not (Non-Achievers). We found that the glucose threshold at which there was greatest separation in mortality between Achievers and Non-Achievers was at 8mmol/L [144mg/dL] (6 month mortality 1.6% vs. 9.1%, p=0.05). Therefore subjects who maintained the majority of their blood glucose levels below 8mmol/L following myocardial infarction had optimal survival outcomes. We suggest that this might be an appropriate glucose target to aim for in the peri-infarct period.
Diabetes research and clinical practice 07/2008; 80(3):411-5. DOI:10.1016/j.diabres.2008.01.021 · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity in women of reproductive age is increasing at an unprecedented rate in western societies. Maternal obesity is associated with an unequivocal increase in maternal and fetal complications of pregnancy. Excessive maternal weight gain in pregnancy also appears to be an independent risk factor, regardless of prepregnancy weight. Few guidelines exist regarding appropriate weight gain in pregnancy in obese women. We review the association of maternal obesity with pregnancy complications. We also suggest that appropriate diet and lifestyle intervention can enable women with severe prepregnancy obesity to safely achieve quite strict targets for limited weight gain in pregnancy.
Australian and New Zealand Journal of Obstetrics and Gynaecology 07/2008; 48(3):228-35. DOI:10.1111/j.1479-828X.2008.00860.x · 1.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the last 10 years, there has been considerable interest in the administration of insulin as part of the management of myocardial infarction. This review examines the clinical trials of insulin infusion for myocardial infarction in the era of reperfusion therapy, and discusses the implications of the recently completed HI-5 (Hyperglycaemia: Intensive Insulin Infusion In Infarction) study. The clinical trials of insulin therapy for myocardial infarction can be divided into those with a primary aim of delivering insulin (insulin focus), and those with a primary aim of achieving tight glycaemic control (glycaemia focus). The evidence suggests that protocols with an insulin focus do not improve the outcome of myocardial infarction. However, the trials with a glycaemia focus are inconclusive and it remains possible that glycaemic control is beneficial.
[Show abstract][Hide abstract] ABSTRACT: Type 2 diabetes is frequently familial. Hyperglycaemia in pregnancy might act in addition to genetic factors to cause diabetes in the children of mothers with gestational diabetes mellitus (GDM). The first manifestation of this in female offspring is likely to be GDM in their own pregnancies. We compared the incidence of GDM in daughters of diabetic mothers and diabetic fathers to determine if in utero exposure to hyperglycaemia increased the risk of a diabetes-prone phenotype in offspring.
We analysed the outcome of a GDM screening programme in women with a family history of diabetes in their mother (n = 535), father (n = 566), both parents (n = 77) or neither (n = 4672).
GDM was twice as common in the daughters of diabetic mothers (11%) than diabetic fathers (5%, P = 0.002). Women with two diabetic parents were no more likely to have GDM than women with only a diabetic mother.
Genetic predisposition to GDM should be equally shared by daughters of diabetic mothers and fathers. An excess of maternal transmission of diabetes is consistent with an epigenetic effect of hyperglycaemia in pregnancy acting in addition to genetic factors to produce diabetes in the next generation.
Diabetic Medicine 12/2006; 23(11):1213-5. DOI:10.1111/j.1464-5491.2006.01979.x · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study examined the hypothesis that low birth weight is associated with changes in regional lipid deposition as well as insulin sensitivity in adult twins. Eleven adult female twin pairs were studied by magnetic resonance to determine regional adiposity. Their insulin sensitivity was assessed by the homeostasis model assessment. There were significant associations between birth weight and current homeostasis model assessment value (r=-0.528, P=.012), abdominal visceral (r=-0.581, P=.005), and subcutaneous fat volumes (r=-0.638, P=.001) if the group of 22 subjects were analyzed as individuals. There were no significant associations of the intratwin pair difference in birth weight and differences between adult twins in these same variables possibly because of limited patient numbers. Reduced birth weight does confer an increased risk of abdominal adiposity as well as insulin resistance in twin populations as it does in the general population.
[Show abstract][Hide abstract] ABSTRACT: There is conflicting evidence regarding the benefit of intravenous insulin therapy on mortality following acute myocardial infarction (AMI). The goal of the current study was to determine whether improved glycemic control, achieved through an insulin/dextrose infusion with a variable rate of insulin, reduces mortality among hyperglycemic patients with AMI.
Subjects suffering AMI with either known diabetes or without diabetes but blood glucose level (BGL) > or =7.8 mmol/l were randomized to receive insulin/dextrose infusion therapy for at least 24 h to maintain a BGL <10 mmol/l or conventional therapy.
A total of 240 subjects were recruited. Insulin/dextrose infusion did not reduce mortality at the inpatient stage (4.8 vs. conventional 3.5%, P = 0.75), 3 months (7.1 vs 4.4%, P = 0.42), or 6 months (7.9 vs. 6.1%, P = 0.62). There was, however, a lower incidence of cardiac failure (12.7 vs. 22.8%, P = 0.04) and reinfarction within 3 months (2.4 vs. 6.1%, P = 0.05). When analyzed by mean BGL achieved during the first 24 h, mortality was lower among subjects with a mean BGL < or =8 mmol/l, compared with subjects with a mean BGL >8 mmol/l (2 vs. 11% at 6 months, P = 0.02).
We did not find a reduction in mortality among patients who received insulin/dextrose infusion therapy. However, it remains possible that tight glycemic control with insulin therapy following AMI improves outcomes.
Diabetes Care 04/2006; 29(4):765-70. DOI:10.2337/diacare.29.04.06.dc05-1894 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, we examined patterns of postpartum physical activity among women with recent gestational diabetes mellitus (GDM) and psychosocial factors related to this behavior that could be addressed in diabetes prevention interventions.
A random sample of women who had attended diabetes clinics in Sydney, Australia, in the past 6-24 months for treatment of GDM were surveyed by telephone. Variables measured included physical activity behaviors, self-efficacy, social support, and barriers to participation.
Of 226 women who completed the survey (mean age 33.4 years), 26.5% were classified as sedentary, and only 33.6% reported sufficient physical activity as recommended by health authorities. Walking was the most popular physical activity, and most women reported no other moderate- or vigorous-intensity activity. Lack of assistance with child care (49.1%) and insufficient time (37.6%) were the most common barriers to physical activity. The type of social support most often reported was verbal encouragement (39.1%), with more than half of the women never receiving assistance with housework or others exercising with them. Self-efficacy for physical activity was lowest when women were under time pressure or tired. Multivariate analyses showed that sufficient physical activity was associated with high social support (odds ratio 2.5 [95% CI 1.21-3.79]) and high self-efficacy (2.09 [1.06-3.20]).
The prevalence of sufficient physical activity was found to be low and strongly related to social support and self-efficacy. This is an important group to whom diabetes prevention strategies can be targeted.
Diabetes Care 12/2005; 28(11):2650-4. DOI:10.2337/diacare.28.11.2650 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
We conducted a randomized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications.
We randomly assigned women between 24 and 34 weeks’ gestation who had gestational diabetes to receive dietary advice, blood glucose monitoring, and insulin therapy as needed (the intervention group) or routine care. Primary outcomes included serious perinatal complications (defined as death, shoulder dystocia, bone fracture, and nerve palsy), admission to the neonatal nursery, jaundice requiring phototherapy, induction of labor, cesarean birth, and maternal anxiety, depression, and health status.
The rate of serious perinatal complications was significantly lower among the infants
of the 490 women in the intervention group than among the infants of the 510 women in the routine-care group (1 percent vs. 4 percent; relative risk adjusted for maternal age, race or ethnic group, and parity, 0.33; 95 percent confidence interval, 0.14 to 0.75; P=0.01). However, more infants of women in the intervention group were admitted to the neonatal nursery (71 percent vs. 61 percent; adjusted relative risk, 1.13; 95 percent confidence interval, 1.03 to 1.23; P=0.01). Women in the intervention group had a higher
rate of induction of labor than the women in the routine-care group (39 percent vs. 29 percent; adjusted relative risk, 1.36; 95 percent confidence interval, 1.15 to 1.62; P<0.001), although the rates of cesarean delivery were similar (31 percent and 32 percent, respectively; adjusted relative risk, 0.97; 95 percent confidence interval, 0.81 to 1.16; P=0.73). At three months post partum, data on the women’s mood and quality of life, available for 573 women, revealed lower rates of depression and higher scores, consistent
with improved health status, in the intervention group.
Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman’s health-related quality of life.
New England Journal of Medicine 06/2005; 352:2477‐86.. · 55.87 Impact Factor