Moderate intensity sports and exercise is associated with glycaemic control in women with gestational diabetes.

AIM: To assess the association of regular, unsupervised sports and exercise during pregnancy, by intensity level, with glycaemic control in women with gestational diabetes (GDM). METHODS: Prospective cohort study of 971 women who, shortly after being diagnosed with GDM, completed a Pregnancy Physical Activity Questionnaire assessing moderate and vigorous intensity sports and exercise in the past 3 months. Self-monitored capillary glucose values were obtained for the 6-week period following the questionnaire, with optimal glycaemic control defined≥80% values meeting the targets<5.3mmol/L for fasting and <7.8mmol/L 1-hour after meals. Logistic regression estimated the odds of achieving optimal control; linear regression estimated activity level-specific least square mean glucose, as well as between-level mean glucose differences. RESULTS: For volume of moderate intensity sports and exercise ([MET×hours]/week), the highest quartile, compared to the lowest, had significantly increased odds of optimal control (OR=1.82 [95% CI: 1.06-3.14] P=0.03). There were significant trends for decreasing mean 1-hour post breakfast, lunch and dinner glycaemia with increasing quartile of moderate activity (all P<0.05). Any participation in vigorous intensity sports and exercise was associated with decreased mean 1-hour post breakfast and lunch glycaemia (both P<0.05). No associations were observed for fasting. CONCLUSION: Higher volumes of moderate intensity sports and exercise, reported shortly after GDM diagnosis, were significantly associated with increased odds of achieving glycaemic control. Clinicians should be aware that unsupervised moderate intensity sports and exercise performed in mid-pregnancy aids in subsequent glycaemic control among women with GDM.

Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis.

Therapeutic response to metformin, a first-line drug for type 2 diabetes (T2D), is highly variable, in part likely due to genetic factors. To date, metformin pharmacogenetic studies have mainly focused on the impact of variants in metformin transporter genes, with inconsistent results. To clarify the significance of these variants in glycemic response to metformin in T2D, we performed a large-scale meta-analysis across the cohorts of the Metformin Genetics Consortium (MetGen). Nine candidate polymorphisms in five transporter genes (organic cation transporter [OCT]1, OCT2, multidrug and toxin extrusion transporter [MATE]1, MATE2-K, and OCTN1) were analyzed in up to 7,968 individuals. None of the variants showed a significant effect on metformin response in the primary analysis, or in the exploratory secondary analyses, when patients were stratified according to possible confounding genotypes or prescribed a daily dose of metformin. Our results suggest that candidate transporter gene variants have little contribution to variability in glycemic response to metformin in T2D.

The Kaiser Permanente Northern California research program on genes, environment, and health (RPGEH) pregnancy cohort: study design, methodology and baseline characteristics.

BACKGROUND: Exposures during the prenatal period may have lasting effects on maternal and child health outcomes. To better understand the effects of the in utero environment on children's short- and long-term health, large representative pregnancy cohorts with comprehensive information on a broad range of environmental influences (including biological and behavioral) and the ability to link to prenatal, child and maternal health outcomes are needed. The Research Program on Genes, Environment and Health (RPGEH) pregnancy cohort at Kaiser Permanente Northern California (KPNC) was established to create a resource for conducting research to better understand factors influencing women's and children's health. Recruitment is integrated into routine clinical prenatal care at KPNC, an integrated health care delivery system. We detail the study design, data collection, and methodologies for establishing this cohort. We also describe the baseline characteristics and the cohort's representativeness of the underlying pregnant population in KPNC. METHODS: While recruitment is ongoing, as of October 2014, the RPGEH pregnancy cohort included 16,977 pregnancies (53 % from racial and ethnic minorities). RPGEH pregnancy cohort participants consented to have blood samples obtained in the first trimester (mean gestational age 9.1 weeks ± 4.2 SD) and second trimester (mean gestational age 18.1 weeks ± 5.5 SD) to be stored for future use. Women were invited to complete a questionnaire on health history and lifestyle. Information on women's clinical and health assessments before, during and after pregnancy and women and children's health outcomes are available in the health system's electronic health records, which also allows long-term follow-up. DISCUSSION: This large, racially- and ethnically-diverse cohort of pregnancies with prenatal biospecimens and clinical data is a valuable resource for future studies on in utero environmental exposures and maternal and child perinatal and long term health outcomes. The baseline characteristics of RPGEH Pregnancy Cohort demonstrate that it is highly representative of the underlying population living in the broader community in Northern California.

A Longitudinal HbA1c Model Elucidates Genes Linked to Disease Progression on Metformin.

One-third of type-2 diabetic patients respond poorly to metformin. Despite extensive research, the impact of genetic and nongenetic factors on long-term outcome is unknown. In this study we combine nonlinear mixed effect modeling with computational genetic methodologies to identify predictors of long-term response. In all, 1,056 patients contributed their genetic, demographic, and long-term HbA1c data. The top nine variants (of 12,000 variants in 267 candidate genes) accounted for approximately one-third of the variability in the disease progression parameter. Average serum creatinine level, age, and weight were determinants of symptomatic response; however, explaining negligible variability. Two single nucleotide polymorphisms (SNPs) in CSMD1 gene (rs2617102, rs2954625) and one SNP in a pharmacologically relevant SLC22A2 gene (rs316009) influenced disease progression, with minor alleles leading to less and more favorable outcomes, respectively. Overall, our study highlights the influence of genetic factors on long-term HbA1c response and provides a computational model, which when validated, may be used to individualize treatment.

Genetic variants in transcription factors are associated with the pharmacokinetics and pharmacodynamics of metformin.

One-third of type 2 diabetes patients do not respond to metformin. Genetic variants in metformin transporters have been extensively studied as a likely contributor to this high failure rate. Here, we investigate, for the first time, the effect of genetic variants in transcription factors on metformin pharmacokinetics (PK) and response. Overall, 546 patients and healthy volunteers contributed their genome-wide, pharmacokinetic (235 subjects), and HbA1c data (440 patients) for this analysis. Five variants in specificity protein 1 (SP1), a transcription factor that modulates the expression of metformin transporters, were associated with changes in treatment HbA1c (P < 0.01) and metformin secretory clearance (P < 0.05). Population pharmacokinetic modeling further confirmed a 24% reduction in apparent clearance in homozygous carriers of one such variant, rs784888. Genetic variants in other transcription factors, peroxisome proliferator-activated receptor-α and hepatocyte nuclear factor 4-α, were significantly associated with HbA1c change only. Overall, our study highlights the importance of genetic variants in transcription factors as modulators of metformin PK and response.

Post-partum weight loss and glucose metabolism in women with gestational diabetes: the DEBI Study.

AIMS: Women with gestational diabetes are at high risk for developing diabetes; post-partum weight loss may reduce the risk of diabetes. We evaluated the association of post-partum weight change with changes in glucose, insulin and homeostasis model assessment of insulin resistance in a subsample (n = 72) of participants from Diet Exercise and Breastfeeding Intervention (DEBI), a randomized pilot trial of lifestyle intervention for women with gestational diabetes. METHODS: Glucose and insulin were measured fasting and 2 h after an oral glucose tolerance test at 6 weeks and 12 months post-partum. Women were categorized by weight change (lost > 2 kg vs. maintained/gained) between 6 weeks and 12 months post-partum. RESULTS: Compared with women who maintained or gained weight, women who lost > 2 kg experienced significantly lower increases in fasting glucose [age-adjusted means: 0.1 mmol/l (95% CI -0.03 to 0.3) vs. 0.4 mmol/l (95% CI 0.3-0.6); P < 0.01] and 2-h insulin [10.0 pmol/l (95% CI -56.9 to 76.9) vs. 181.2 pmol/l (95% CI 108.3-506.9); P < 0.01] and a significant reduction in 2-h glucose [-0.9 mmol/l (95% CI -1.4 to -0.3) vs. 0.3 mmol/l (95% CI -0.3 to 0.9); P < 0.01]. In multiple linear regression models adjusted for age, Hispanic ethnicity, medication use, meeting the Institute of Medicine's recommendations for gestational weight gain, breastfeeding and randomized group, a 1-kg increase in weight was significantly associated with increases in fasting and 2-h glucose (P < 0.05), but was not associated with insulin or homeostasis model assessment of insulin resistance. CONCLUSIONS: In women with gestational diabetes, modest post-partum weight loss may be associated with improvements in glucose metabolism.

Sex ratio variations among the offspring of women with diabetes in pregnancy.

AIMS: It has long been hypothesized that natural selection would favour a reproductive strategy biased towards females under adverse circumstances in order to maximize the number of surviving grandchildren. An excess of daughters in women with Type 1 diabetes and a greater likelihood of gestational diabetes in women carrying male fetuses have also been reported. This study aims to compare the sex ratio across categories of maternal glycaemia. METHODS: Among 288,009 mother-infant pairs delivering at Kaiser Permanente Northern California in 1996-2008, sex ratios were calculated for the following categories: pregravid diabetes, gestational diabetes, mild pregnancy hyperglycaemia (defined as an abnormal screening but normal diagnostic test for gestational diabetes) and normoglycaemia. Odds ratios for delivering a male were estimated with logistic regression; normoglycaemic pregnancies comprised the reference. RESULTS: Women with pregravid diabetes delivered the fewest males (ratio male/female = 1.01), followed by women with normoglycaemic pregnancies and those with an abnormal screening only (both sex ratios = 1.05); women with gestational diabetes delivered the most males (sex ratio = 1.07). Odds ratio estimates suggested the same pattern, but none attained statistical significance. CONCLUSIONS: The crude sex ratios in this cohort suggest a possible gradient by category of maternal glycaemia. Women with gestational diabetes, a condition characterized by excessive fuel substrates, appear to deliver more males. Women with pregravid diabetes delivered the fewest males, possibly reflecting the unfavourable state of chronic disease.

Pregnancy plasma glucose levels exceeding the American Diabetes Association thresholds, but below the National Diabetes Data Group thresholds for gestational diabetes mellitus, are related to the risk of neonatal macrosomia, hypoglycaemia and hyperbilirubinaemia.

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is a risk factor for perinatal complications. In several countries, the criteria for the diagnosis of GDM have been in flux, the American Diabetes Association (ADA) thresholds recommended in 2000 being lower than those of the National Diabetes Data Group (NDDG) that have been in use since 1979. We sought to determine the extent to which infants of women meeting only the ADA criteria for GDM are at increased risk of neonatal complications. MATERIALS AND METHODS: In a multiethnic cohort of 45,245 women who did not meet the NDDG criteria and were not treated for GDM, we conducted nested case-control studies of three complications of GDM that occurred in their infants: macrosomia (birthweight >4,500 g, n = 494); hypoglycaemia (plasma glucose <2.2 mmo/l, n = 488); and hyperbilirubinaemia (serum bilirubin > or =342 micromol/l (20 mg/dl), n = 578). We compared prenatal glucose levels of the mothers of these infants and mothers of 884 control infants. RESULTS: Women with GDM by ADA criteria only (two or more glucose values exceeding the threshold) had an increased risk of having an infant with macrosomia (odds ratio OR = 3.40, 95% CI = 1.55-7.43), hypoglycaemia (OR = 2.61, 95% CI = 0.99-6.92) or hyperbilirubinaemia (OR = 2.22, 95% CI = 0.98-5.04). Glucose levels 1 h after the 100-g glucose challenge that exceeded the ADA threshold were particularly strongly associated with each complication. CONCLUSIONS/INTERPRETATION: These results lend support to the ADA recommendations and highlight the importance of the 1-h glucose measurement in a diagnostic test for GDM.

Use of alternative medicine by children with cancer in Washington state.

BACKGROUND: Use of alternative medicine is widespread among adult cancer patients, but considerably less is known about the use of these therapies by pediatric cancer patients. Our objective was to investigate the distribution and patterns of alternative medicine use by children diagnosed with cancer in Washington State. METHODS: Pediatric cancer patients (< or =18 years) with first primary neoplasms were identified from the Cancer Surveillance System of western Washington. Telephone interviews were conducted with parents of 75 patients to obtain data on the prevalence and types of alternative medicine used, satisfaction with conventional and alternative medicine, motivations for use of alternative medicine, adverse effects, and costs. RESULTS: Seventy-three percent of patients used at least one alternative treatment or therapy. Twenty-one percent of patients consulted an alternative provider (e.g., acupuncturist, naturopathic doctor), and insurance companies covered 75% of these costs. Twenty-eight percent used high-dose dietary supplements such as vitamins C or E, and 35% used herbal preparations. Although use of alternative medicine was associated with parental dissatisfaction with their child's physician (P = 0.02), no patient used alternative medicine as a substitute for standard medical care. Most patients used alternative medicine to cope with disease symptoms or the side effects of the medical treatments. CONCLUSIONS: Pediatric oncology patients use alternative treatments as adjuncts to conventional care. Both researchers and health care providers should remain informed about the benefits and adverse effects of alternative therapies in order to discuss treatment options with patients and their families and to monitor treatment efficacy.

Predictors of self-initiated, healthful dietary change.

OBJECTIVE: To examine demographic and psychosocial factors that predict healthful dietary change. DESIGN: A cohort study, examining how factors assessed at baseline predicted change in fat-related dietary habits and fruit and vegetable intakes 2 years later. PARTICIPANTS: Participants were recruited in 1995 and 1996 by random-digit dialing (response rate 0.63), and followed-up in 1997 and 1998 (follow-up rate 0.82). The final sample included 336 men and 502 women. MAIN OUTCOME MEASURES: Fruit and vegetable intake and fat-related dietary patterns, measured by telephone-administered surveys. STATISTICAL ANALYSES: Chi2 tests and linear regression were used to test associations of baseline characteristics with dietary change. RESULTS: Fat intake (energy from fat) decreased by approximately 2 percentage points and fruits and vegetables intake increased by 0.17 servings per day (both P<.001). Changes were significantly larger among women and persons who were well educated. Persons in the maintenance stage of change and persons who believed there was a strong relationship between diet and cancer made the largest dietary changes. Use of food labels was strongly associated with fat reduction, but not with increases in fruits and vegetables. APPLICATIONS: These results suggest that food labels are useful for helping people reduce fat intake, that interventions should target persons at all stages of dietary change, and that new efforts are needed to reach men and persons who are less well educated.