Glycated hemoglobin measurements at three, 12 and 24 months postpartum after gestational diabetes.

PURPOSE: To determine the associations between glycated hemoglobin (A1C) values at three, 12 and 24 months postpartum taken during the Families Defeating Diabetes trial. METHODS: The Families Defeating Diabetes trial was a randomized 12 month lifestyle intervention delivered in the first year postpartum. Women were reviewed at three, 6 12 and 24 months for body habitus, diet and lifestyle choices. Glycated hemoglobin levels were measured at three, 12 and 24 months. RESULTS: There were 170 randomization participants: 89 interventional (INT); and 81 control (CON). Of these 170 participants, 50 INT and 47 CON completed 12-month follow-up and 26 INT and 24 CON completed 24-month follow-up. Study outcomes did not differ between the cohorts. Combined intraclass correlation coefficients for reliability of repeated results showed substantial reliability: 0.74 (95% CI 0.63, 0.83) between three and 12 month A1C; and 0.72 (95% CI 0.51, 0.85) for three and 24 month A1C. Pearson correlations for three month vs 12 month A1C were r=0.745 (p.

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research.

Restoration and loss after disaster: Applying the dual-process model of coping in bereavement.

The article asks whether disasters that destroy life but leave the material infrastructure relatively intact tend to prompt communal coping focusing on loss, while disasters that destroy significant material infrastructure tend to prompt coping through restoration/rebuilding. After comparing memorials to New Zealand's Christchurch earthquake and Pike River mine disasters, we outline circumstances in which collective restorative endeavor may be grassroots, organized from above, or manipulated, along with limits to effective restoration. We conclude that bereavement literature may need to take restoration more seriously, while disaster literature may need to take loss more seriously.

CONCEPTT: Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: A multi-center, multi-national, randomized controlled trial - Study protocol.

BACKGROUND: Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy. METHODS/DESIGN: A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes. DISCUSSION: This will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012.

Maternal, umbilical arterial and umbilical venous 25-hydroxyvitamin D and adipocytokine concentrations in pregnancies with and without gestational diabetes.

OBJECTIVE: Gestational diabetes mellitus (GDM) has been associated with inflammation as well as Vitamin D insufficiency. While Vitamin D has anti-inflammatory properties, relationships between Vitamin D and inflammatory markers remain unexplored in GDM. Therefore, this case--control study investigated adipocytokine and Vitamin D [25(OH)D] concentrations and correlations in GDM and control women, as well as their neonates. DESIGN/PARTICIPANTS/MEASUREMENTS: seventy-three women participated: 36 GDM and 37 controls. Maternal samples were drawn at 31 weeks. Umbilical arterial and venous samples were collected at birth. 25(OH)D and adipocytokine concentrations were compared for GDM vs control maternal, umbilical arterial and venous samples. Correlations were explored between biochemical results, maternal and neonatal demographics. RESULTS: Compared with age- and weight-matched control participants, GDM women had significantly lower concentrations of 25(OH)D (77·3 ± 24·3 vs 93·2 ± 19·2 nm/l; P = 0·009); adiponectin (17·5 ± 11·8 vs 34·1 ± 20·3 µg/ml, P < 0·001); resistin (25·4 ± 9·1 vs 31·9 ± 12·1 ng/ml, P = 0·045); and plasminogen activator inhibitor-1 (PAI-1) 13·9 ± 10·0 vs 21·0 ± 12·6 ng/ml, P = 0·038), while delivering 1 week earlier (38·2 ± 1·2 vs 39·5 ± 0·9 weeks, P < 0·001). GDM maternal 25(OH)D concentrations positively correlated with PAI-1, IL-8 and TNF-α concentrations. Umbilical 25(OH)D concentrations were not significantly different in GDM vs control offspring, whereas adiponectin, resistin and PAI-1 concentrations were significantly lower in GDM offspring. CONCLUSIONS: GDM women had lower 25(OH)D concentrations than controls, while neonatal umbilical concentrations of 25(OH)D did not differ. GDM maternal and GDM offspring had lower adiponectin, resistin and PAI-1 concentrations compared with controls. Results suggest that both GDM women and their offspring demonstrate abnormal adipocytokine patterns.

Effect of Lifestyle on Reducing Risk Factors for Type 2 Diabetes among Arab Canadian Muslim Women: A Randomized Control Trial.

PURPOSE: This study aimed to investigate whether modifiable risk factors for type 2 diabetes (T2D) can be reduced by an intensive healthy lifestyle intervention designed for Arab Muslim women of Middle Eastern descent (AWMD) who are at high risk for this disease. We hypothesized that among Canadian AWMD, the intervention would (a) reduce the identified health risk factors for T2D (body mass index [BMI], ≥30 kg·m-2; fasting blood glucose [FBG], ≥5.6 mmol·L-1; and waist circumference [WC], ≥80 cm); (b) improve anthropometric measurements; (c) improve lifestyle factors (physical activity level [steps per day] and dietary habits); and (d) improve cardiovascular fitness and reduce blood pressure. METHODS: After informed consent, 60 participants were randomized to either an exercise and nutrition group (ENG; n = 30) or a control group (CON; n = 30). ENG attended a women-only supervised exercise program that presented Arabic music and traditional Lebanese Dabka three times a week in a Mosque gym for 12 wk. A nutritionist was available 1 h·wk-1 for nutrition education. The CON followed their typical day. RESULTS: ENG and CON had similar increased risk profiles for diabetes at baseline. Large significant pre/posttreatment interaction effects were found for BMI, FBG, and WC with a reduced diabetes risk for ENG compared with CON for BMI (1,58) = 1184.8, P < 0.001), FBG (1,58) = 187.7, P < 0.001), and WC (1,58) = 326.4, P < 0.001). The ENG had significantly more participants reach postintervention target values (BMI: χ2(1) = 16.48, P = 0.001; FBG: χ2(1) = 52.26, P < 0.001; WC: χ2(1) = 4.29, P = 0.038) compared with the CON. Adherence to the program was 100%. CONCLUSIONS: Modifiable risk factors for T2D were reduced by using a culturally sensitive intervention program with high adherence through weight loss, regular exercise, and nutrition education.

SEVERE HYPERANDROGENISM IN A PREMENOPAUSAL WOMAN WITH AN IMAGING-NEGATIVE LEYDIG CELL TUMOR.

OBJECTIVE: Hirsutism and hyperandrogenism in premenopausal women are most often associated with polycystic ovarian syndrome. We present a case of progressive, severe hyperandrogenism with negative imaging identified on surgical histopathology as being due to a Leydig cell tumor (LCT), thus illustrating localization challenges associated with these small tumors. METHODS: Laboratory investigations included testosterone, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, 24-hour urine cortisol, and prolactin. Imaging included pelvic ultrasound, adrenal magnetic resonance imaging, and computed tomography. Ovarian vein sampling was not available. RESULTS: A 42-year-old woman presented with frontal alopecia, voice deepening, coarse facial hair, and amenorrhea on a background of lifelong oligomenorrhea. Peak testosterone was 30.2 nmol/L (female normal range is <2.0 nmol/L) with normal dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, prolactin, 24-hour urine cortisol, and thyroid-stimulating hormone. Transvaginal ultrasound, adrenal magnetic resonance imaging, and computed tomography of the thorax and abdomen revealed no androgen source. Testosterone failed to suppress with gonadotropin-releasing hormone agonist. Although no abnormality was seen during oophorectomy, surgical pathology documented a 1.8-cm, well-circumscribed hilar LCT. Postoperative testosterone was <0.5 nmol/L. CONCLUSION: Although this patient had testosterone levels well into the masculine range, multiple imaging results were negative with a LCT found only after oophorectomy. LCTs are rare ovarian stromal tumors and while 50 to 70% of these tumors produce androgen, size and clinical severity may not be well correlated. This case report illustrates that despite an association with substantially elevated androgen levels, the small size of LCTs can result in localization challenges.

Dynamic response of cerebral blood flow to insulin-induced hypoglycemia.

The dynamics of cerebral blood flow (CBF) at the onset of hypoglycemia may play a key role in hypoglycemia unawareness; however, there is currently a paucity of techniques that can monitor adult CBF with high temporal resolution. Herein, we investigated the use of diffuse correlation spectroscopy (DCS) to monitor the dynamics of CBF during insulin-induced hypoglycemia in adults. Plasma glucose concentrations, cortisol levels, and changes in CBF were measured before and during hypoglycemia in 8 healthy subjects. Cerebral blood flow increased by 42% following insulin injection with a delay of 17 ± 10 min, while the onset of hypoglycemia symptoms was delayed by 24 ± 11 min. The findings suggest that the onset of CBF increments precedes the appearance of hypoglycemia symptoms in nondiabetic subjects with normal awareness to hypoglycemia, and DCS could be a valuable tool for investigating the role of CBF in hypoglycemia unawareness.

"Why did you really do it?" A mixed-method analysis of the factors underpinning motivations to register as a body donor.

Individuals who register as body donors do so for various reasons, with aiding medical science a common motivation. Despite awareness of several key reasons for donation, there are few in-depth explorations of these motivations to contextualize persons' reasons for donating. This study undertakes a mixed-method exploration of motivations for body donation to facilitate deeper understanding of the reasons underpinning donor registration. A survey of all newly registered body donors at a New Zealand university was performed over a single year. The survey included basic demographic information, a categorical question on reason for donation, a free-text question on donation motivation, and a free-text question allowing "other" comments on body donation. Basic statistical analysis was performed on demographic and categorical data, and thematic analysis used on free-text responses. From 169 registrants, 126 people (average age 70.5 years; 72 female) returned completed surveys (response rate 75%). Categorical data indicate a primary motivation of aiding medical science (86%). Fifty-one respondents (40%) provided free-text data on motivation, with other comments related to motivation provided by forty-one (33%). Common themes included reference to usefulness, uniqueness (pathophysiology and anatomy), gift-giving, kinship, and impermanence of the physical body. Consistent with previous studies, the primary reason for body donation was aiding medical science, however underpinning this was a complex layer of themes and sub-themes shaping motivations for choices. Findings provide important information that can guide development of robust informed consent processes, aid appropriate thanksgiving service delivery, and further contextualize the importance of medical professionals in body donation culture.

Gene-drug interaction: additive influence of mutant APOA1 and testosterone on plasma HDL-cholesterol.

OBJECTIVES: Factors associated with decreased plasma high-density lipoprotein (HDL) cholesterol concentration, or hypoalphalipoproteinemia, include androgenic steroids and mutations in APOA1, encoding apolipoprotein (apo) A-I, the main structural protein of HDL. However, there is little information regarding the extent of plasma HDL lowering when exogenous testosterone is used in subjects with monogenic low HDL. DESIGN AND METHODS: A man with coronary heart disease (CHD) had been receiving exogenous testosterone post-orchidectomy. He had marked hypoalphalipoproteinemia, which was not responsive to diet or medication. To identify a possible genetic contribution to his biochemical phenotype, we sequenced the LCAT and APOA1 genes. RESULTS: There were no sequence abnormalities in LCAT, but we found that he was a heterozygote for a novel APOA1 mutation in codon 107 (AAG->TGG), which predicted the replacement of lysine by tryptophan (K107W). Serial biochemical measurements over 11 years showed that plasma HDL cholesterol on either intramuscular or oral testosterone was 0.19 +/- 0.06 mmol/L, while plasma HDL cholesterol on transdermal testosterone was significantly higher at 0.52 +/- 0.18 mmol/L (p = 0.015, unpaired t-test). CONCLUSIONS: The findings suggest that the low plasma HDL cholesterol associated with heterozygosity for mutant APOA1 can become extremely depressed during treatment with oral or intramuscular androgens. The findings also suggest that transdermal testosterone may perturb HDL to a lesser extent than other routes of delivery in such patients.

Costs of recalled and recommended diets for pregnant women with type 1, type 2 and gestational diabetes.

OBJECTIVE: The costs associated with nutritious foods may be a barrier to healthy dietary choices and of particular concern to pregnancies complicated by diabetes. Therefore, a survey was conducted in a tertiary care diabetes and pregnancy clinic to compare the associated costs of actual food choices versus the cost of a constructed recommended diet. METHODS: Women with types 1, 2 and gestational diabetes mellitus (GDM) completed 24-hour dietary recalls under the supervision of the research coordinator (Actual Diet). A Recommended Diet for this population was constructed independent of participant responses. Actual and Recommended Diets were standardized per 2000 kcal, priced and compared for content and cost. RESULTS: Seventy-five women participated: 27 with GDM, 29 with type 1 diabetes and 19 with type 2 diabetes. There were no significant cost differences between Recommended and Actual Diets food choices expressed per 2000 kcal: Recommended Diet $10.14±3.72; Actual Diet GDM: $11.30±3.88; Actual Diet type 1 diabetes: $9.00±3.16; Actual Diet type 2 diabetes: $10.24±3.92. Percentage of fibre intake was lower for Actual Diets than Recommended Diet for all groups, while percentage of protein intake was lower in Actual than Recommended Diet for women with type 1 diabetes. CONCLUSION: Clinical recommendations for healthy food choices may not be more expensive than actual choices made by pregnant women with diabetes.

Nutrition and exercise prevent excess weight gain in overweight pregnant women.

PURPOSE: To determine the effect of a Nutrition and Exercise Lifestyle Intervention Program (NELIP) for overweight (OW) and obese (OB) pregnant women on pregnancy weight gain, birth weight, and maternal weight retention at 2 months postpartum. METHODS: This is a single-arm intervention matched by prepregnant body mass index, age, and parity to a historical cohort (4:1). Women with a prepregnancy body mass index of > or = 25.0 kg x m(-2) (N = 65) participated in a NELIP starting at 16-20 wk of pregnancy, continuing until delivery. NELIP consisted of an individualized nutrition plan with total energy intake of approximately 2000 kcal x d(-1) (8360 kJ x d(-1)) and 40%-55% of total energy intake from carbohydrate. Exercise consisted of a walking program (30% HR reserve), three to four times per week, using a pedometer to count steps. Matched historical cohort (MC; N = 260) was from a large local perinatal database. RESULTS: Weight gained by women on the NELIP was 6.8 +/- 4.1 kg (0.38 +/- 0.2 kg x wk(-1)), with a total pregnancy weight gain of 12.0 +/- 5.7 kg. Excessive weight gain occurred before NELIP began at 16 wk of gestation. Eighty percent of the women did not exceed recommended pregnancy weight gain on NELIP. Weight retention at 2 months postpartum was 2.2 +/- 5.6 kg with no difference between the OW and the OB women on NELIP. Mean birth weight was not different between NELIP (3.59 +/- 0.5 kg) and MC (3.56 +/- 0.6 kg, P > 0.05). CONCLUSIONS: NELIP reduces the risk of excessive pregnancy weight gain with minimal weight retention at 2 months postpartum in OW and OB women. This intervention may assist OW and OB women in successful weight control after childbirth.

A walking intervention improves capillary glucose control in women with gestational diabetes mellitus: a pilot study.

Exercise prescriptions that can be translated into clinical recommendations are clearly needed for women with gestational diabetes mellitus (GDM). A pilot project was developed to document the effectiveness of a structured low-intensity walking protocol on capillary glucose control in GDM women. Ten GDM women followed conventional management of diet and insulin therapy, plus a low-intensity walking program (W) from diagnosis to delivery. Capillary glucose concentrations, insulin requirements, and pregnancy outcomes were compared with a matched cohort by body mass index (BMI), age, and insulin usage (20 GDM women who followed conventional management alone (C)). Baseline capillary glucose concentrations were not significantly different between the W and C groups. The W group had an average acute drop in capillary glucose concentration from pre- to post-exercise of 2.0 mmol x L(-1). In addition, the W group had significantly lower mean glucose concentrations in the fasted state and 1 h after meals than the C group in the week prior to delivery. These lower glucose concentrations were achieved while requiring fewer units of insulin per day (C, 0.50 +/- 0.37 U x kg(-1); W, 0.16 +/- 0.13 U x kg(-1); p < 0.05), injected less frequently. These results suggest an effective role in glucose regulation for this structured walking program.

Reduced IFN-alpha secretion by blood dendritic cells in human diabetes.

Characterization of dendritic cells (DC) in human diabetes has been restricted to monocyte-derived DC in type 1 diabetes, whose physiological relevance to endogenous DC is uncertain. Here, we provide the first report characterizing the phenotype and function of endogenous DC subsets in type 1 and type 2 diabetes. We show that DC subsets in each diabetic group exhibit normal properties concerning frequency and activation state, as determined using 4-color flow cytometry of whole blood cells. DC maturation is also intact as confirmed by their efficacious ability to stimulate T cell proliferation in an allogeneic MLR assay. Yet we found that DC are poor producers of IFN-alpha (P < 0.05) in human diabetes. IFN-alpha is a potent antiviral agent and therefore its reduced levels may interfere with T cell-mediated immune responses leading to increased susceptibility and persistence of infections in persons with diabetes.