An early pregnancy HbA1c ≥5.9% (41 mmol/mol) is optimal for detecting diabetes and identifies women at increased risk of adverse pregnancy outcomes.

OBJECTIVE: Pregnant women with undiagnosed diabetes are a high-risk group that may benefit from early intervention. Extrapolating from nonpregnancy data, HbA1c ≥6.5% (48 mmol/mol) is recommended to define diabetes in pregnancy. Our aims were to determine the optimal HbA1c threshold for detecting diabetes in early pregnancy as defined by an early oral glucose tolerance test (OGTT) at <20 weeks' gestation and to examine pregnancy outcomes relating to this threshold. RESEARCH DESIGN AND METHODS: During 2008-2010 in Christchurch, New Zealand, women were offered an HbA1c measurement with their first antenatal bloods. Pregnancy outcome data were collected. A subset completed an early OGTT, and HbA1c performance was assessed using World Health Organization criteria. RESULTS: HbA1c was measured at a median 47 days' gestation in 16,122 women. Of those invited, 974/4,201 (23%) undertook an early OGTT. In this subset, HbA1c ≥5.9% (41 mmol/mol) captured all 15 cases of diabetes, 7 with HbA1c <6.5% (<48 mmol/mol). This HbA1c threshold was also 98.4% (95% CI 97-99.9%) specific for gestational diabetes mellitus (GDM) before 20 weeks (positive predictive value = 52.9%). In the total cohort, excluding women referred for GDM management, women with HbA1c of 5.9-6.4% (41-46 mmol/mol; n = 200) had poorer pregnancy outcomes than those with HbA1c <5.9% (<41 mmol/mol; n = 8,174): relative risk (95% CI) of major congenital anomaly was 2.67 (1.28-5.53), preeclampsia was 2.42 (1.34-4.38), shoulder dystocia was 2.47 (1.05-5.85), and perinatal death was 3.96 (1.54-10.16). CONCLUSIONS: HbA1c measurements were readily performed in contrast to the low uptake of early OGTTs. HbA1c ≥5.9% (≥41 mmol/mol) identified all women with diabetes and a group at significantly increased risk of adverse pregnancy outcomes.

Medically facilitated discharge of adult diabetic ketoacidosis admissions: precipitants and average length of stay.

AIMS: To assess the impact of medically facilitated discharge by a specialist registrar on diabetic ketoacidosis (DKA) length of stay (LOS) and to collect data from these DKA admissions for a descriptive summary of their clinical and biochemical characteristics. METHOD: DKA admissions were identified through the electronic patient management system, Monday to Friday over a 9 month period. The admitting team was then offered assistance with discharge planning ('study intervention'). The registrar also collected clinical information for all identified DKA admissions. RESULTS: There were 71 DKA admissions; 92% had type 1 diabetes and 56% were overnight admissions. Following exclusion of four admissions with prolonged LOS secondary to major comorbidities, mean LOS fell from 3.7 (± 1.0) to 2.8 (± 0.3) days. Facilitated discharge had no major impact on LOS. The commonest precipitant for admission was insulin omission, accounting for 65% of admissions. Local practice was to discharge patients following resolution of acidosis, but prior to complete abolition of ketosis. CONCLUSIONS: The majority of DKA admissions were of short duration. Achieving further reduction in LOS is therefore difficult. Insulin omission was the commonest DKA precipitant. Diabetes clinical resources may be best allocated on preventing DKA admissions, rather than facilitating early discharge.

Assessment of glucose meter performance at the antenatal diabetes clinic: exploration of patient-related and pre-analytical factors.

BACKGROUND: To assess glucose meter performance in a diabetes antenatal clinic, focussing on clinical and pre-analytical factors that might impact on the quantification of meter accuracy and precision. METHODS: The Freestyle Lite and the Performa glucose meters were assessed by trained researchers. Finger stick glucose was measured and compared with plasma venous glucose, obtained from a concomitantly collected antecubital fossa sample. Venous plasma was separated on-site then sent to the laboratory for measurement of glucose using the hexokinase method (comparative method). Additional data collected included: (i) timing of and also (ii) quantity of last carbohydrate intake; (iii) time periods between collection, preparation and analysis of the venous sample; (iv) the haemolysis index of the plasma sample and (v) haematocrit. RESULTS: There were 104 participants. Both meters fulfilled ISO 15197 standards, with 99% and 97% of Freestyle Lite and Performa results, respectively, falling within acceptable limits for this standard. Both meters showed minor proportional bias, reading low at higher glucose values. Consensus error grid analysis showed 100% of results from the Freestyle Lite and 99% from the Performa falling within Zone A, thus the observed differences in measured capillary and venous plasma glucose were sufficiently minor that they would have little effect on clinical action. No association was observed between [capillary-plasma] glucose difference and the five variables outlined above. CONCLUSIONS: The two glucose meters tested showed a reassuringly acceptable level of performance, when assessed by a research team in the setting of a diabetes antenatal clinic.

Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model.

BACKGROUND: Pre-eclampsia is a leading cause of maternal deaths. These deaths mainly result from eclampsia, uncontrolled hypertension, or systemic inflammation. We developed and validated the fullPIERS model with the aim of identifying the risk of fatal or life-threatening complications in women with pre-eclampsia within 48 h of hospital admission for the disorder. METHODS: We developed and internally validated the fullPIERS model in a prospective, multicentre study in women who were admitted to tertiary obstetric centres with pre-eclampsia or who developed pre-eclampsia after admission. The outcome of interest was maternal mortality or other serious complications of pre-eclampsia. Routinely reported and informative variables were included in a stepwise backward elimination regression model to predict the adverse maternal outcome. We assessed performance using the area under the curve (AUC) of the receiver operating characteristic (ROC). Standard bootstrapping techniques were used to assess potential overfitting. FINDINGS: 261 of 2023 women with pre-eclampsia had adverse outcomes at any time after hospital admission (106 [5%] within 48 h of admission). Predictors of adverse maternal outcome included gestational age, chest pain or dyspnoea, oxygen saturation, platelet count, and creatinine and aspartate transaminase concentrations. The fullPIERS model predicted adverse maternal outcomes within 48 h of study eligibility (AUC ROC 0·88, 95% CI 0·84-0·92). There was no significant overfitting. fullPIERS performed well (AUC ROC >0·7) up to 7 days after eligibility. INTERPRETATION: The fullPIERS model identifies women at increased risk of adverse outcomes up to 7 days before complications arise and can thereby modify direct patient care (eg, timing of delivery, place of care), improve the design of clinical trials, and inform biomedical investigations related to pre-eclampsia. FUNDING: Canadian Institutes of Health Research; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction; Preeclampsia Foundation; International Federation of Obstetricians and Gynecologists; Michael Smith Foundation for Health Research; and Child and Family Research Institute.

Metformin increases plasma ghrelin in Type 2 diabetes.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Metformin, unlike the other major antihyperglycaemic drugs, is not associated with weight gain. * Ghrelin is an appetite-stimulating hormone whose concentrations vary in relation to food, obesity and diabetes control. * Reports are conflicting about how metformin affects ghrelin concentrations, and this study was aimed at resolving this issue in patients with Type 2 diabetes. WHAT THIS STUDY ADDS: * In this study an increase in ghrelin concentrations was seen in response to metformin treatment in patients with Type 2 diabetes. * This effect was opposite to what might be expected if the effect of metformin on weight control was mediated via suppression of ghrelin. * It is likely that the ghrelin response was secondary to improved glycaemic control. * Meal time changes in appetite and satiety did not correlate with changes in ghrelin, which suggests ghrelin may not be important in meal initiation. AIMS: Metformin treatment of Type 2 diabetes is not usually associated with weight gain, and may assist with weight reduction. Plasma ghrelin concentrations are inversely associated with obesity and food intake. Metformin might therefore affect ghrelin concentrations, although previous studies have shown variable results in this regard. The primary aim of this study was to determine the effect of metformin on plasma ghrelin, appetite and satiety in patients with Type 2 diabetes. METHODS: Eighteen patients with Type 2 diabetes were studied before and after 6 weeks of metformin treatment, which was titrated to 1 g b.d. On the study days patients were fed standard meals of 390 kcal at 08.00 and 12.30 h, plasma samples were collected at 15- and 30-min intervals, and appetite and satiety were measured on visual analogue scales. Changes in the area under the concentration-time curves (AUCs) of plasma ghrelin, insulin, glucose, appetite and satiety were assessed and examined for correlations with metformin AUCs. Changes in fasting adiponectin and leptin were also measured. RESULTS: Treatment with metformin increased the mean AUC (07.30-16.30 h) of plasma ghrelin by 24% (P= 0.003), while decreasing those of glucose by 19% (P < 0.001) and insulin by 19% (P= 0.001). No changes were detected in hunger and satiety, or in fasting adiponectin or leptin concentrations. There were no clear correlations between metformin plasma concentrations (AUC) and changes in plasma glucose, insulin or ghrelin. CONCLUSIONS: Treatment of Type 2 diabetes with metformin was associated with increased plasma ghrelin concentrations, without associated changes in hunger and satiety.

Guidelines for the management of hypertensive disorders of pregnancy 2008.

This is the Executive Summary of updated guidelines developed by the Society of Obstetric Medicine of Australia and New Zealand for the management of hypertensive diseases of pregnancy. They address a number of challenging areas including the definition of severe hypertension, the use of automated blood pressure monitors, the definition of non-proteinuric pre-eclampsia and measuring proteinuria. Controversial management issues are addressed such as the treatment of severe hypertension and other significant manifestations of pre-eclampsia, the role of expectant management in pre-eclampsia remote from term, thromboprophylaxis, appropriate fluid therapy, the role of prophylactic magnesium sulfate and anaesthetic issues for women with pre-eclampsia. The guidelines stress the need for experienced team management for women with pre-eclampsia and mandatory hospital protocols for treatment of hypertension and eclampsia. New areas addressed in the guidelines include recommended protocols for maternal and fetal investigation of women with hypertension, preconception management for women at risk of pre-eclampsia, auditing outcomes in women with hypertensive diseases of pregnancy and long-term screening for women with previous pre-eclampsia.

Comparison of blood glucose meters in a New Zealand diabetes centre.

BACKGROUND: To assess the accuracy and precision of the Roche Performa and Medisense Optium Xceed (5 and 10 s reading) blood glucose meters. METHODS: Capillary blood samples were taken from 100 patients attending a diabetes centre and blood glucose measured on Roche Performa (n = 4) and Medisense Optium Xceed 5 s (n = 2) and 10 s reading (n = 2) meters. Venous plasma glucose from samples taken simultaneously was measured by the laboratory hexokinase method as reference standard. Imprecision was determined on the meters by replicate analysis (n = 20) of control solutions provided by the manufacturers and also patient venous whole-blood samples. Accuracy was assessed relative to the reference method by Bland-Altman plots, Passing and Bablok regression analysis, and both Clarke and consensus error grid analysis. Coefficients of variation (CVs) were calculated to determine imprecision. RESULTS: Bland-Altman and Passing-Bablok analysis confirmed significant systematic bias for all meters, with relative under-reading of higher glucose concentrations. Error grid analysis showed that <5% readings exceeded +/-20% (or +/-0.83 mmol/L for readings <4 mmol/L) deviation from the reference method (1%, 2% and 4% for the Roche, Optium 5 and 10 s meters, respectively). CVs were all <4% for the control solutions and <6% for patient samples. CONCLUSIONS: Both Roche Performa and Medisense Optium glucose meters (5 and 10 s readings) perform satisfactorily and are acceptable for operational use.

Metformin versus insulin for the treatment of gestational diabetes.

BACKGROUND: Metformin is a logical treatment for women with gestational diabetes mellitus, but randomized trials to assess the efficacy and safety of its use for this condition are lacking. METHODS: We randomly assigned 751 women with gestational diabetes mellitus at 20 to 33 weeks of gestation to open treatment with metformin (with supplemental insulin if required) or insulin. The primary outcome was a composite of neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma, 5-minute Apgar score less than 7, or prematurity. The trial was designed to rule out a 33% increase (from 30% to 40%) in this composite outcome in infants of women treated with metformin as compared with those treated with insulin. Secondary outcomes included neonatal anthropometric measurements, maternal glycemic control, maternal hypertensive complications, postpartum glucose tolerance, and acceptability of treatment. RESULTS: Of the 363 women assigned to metformin, 92.6% continued to receive metformin until delivery and 46.3% received supplemental insulin. The rate of the primary composite outcome was 32.0% in the group assigned to metformin and 32.2% in the insulin group (relative risk, 0.99 [corrected]; 95% confidence interval, 0.80 [corrected] to 1.23 [corrected]). More women in the metformin group than in the insulin group stated that they would choose to receive their assigned treatment again (76.6% vs. 27.2%, P<0.001). The rates of other secondary outcomes did not differ significantly between the groups. There were no serious adverse events associated with the use of metformin. CONCLUSIONS: In women with gestational diabetes mellitus, metformin (alone or with supplemental insulin) is not associated with increased perinatal complications as compared with insulin. The women preferred metformin to insulin treatment. (Australian New Zealand Clinical Trials Registry number, 12605000311651.).

Treatment satisfaction after commencement of insulin in Type 2 diabetes.

Fifty patients with Type 2 diabetes were recruited for a study assessing treatment satisfaction and well-being, following commencement on insulin during routine clinical care. A month after starting insulin, participants completed a Diabetes Treatment Satisfaction Questionnaire (DTSQ) and a Well-being Questionnaire. At seven months, the same questionnaires and clinical measurements were repeated and, in addition, patients completed a Diabetes Treatment Satisfaction Questionnaire (change) (DTSQc). Mean HbA1c decreased from 9.69 to 8.26% (P < 0.001), and the lipid profile showed a corresponding improvement. BMI increased from 30.9 to 32.0 kgm(-2) (P < 0.001). Perceived frequency of hyperglycaemia decreased (P = 0.021), correlating with the change in HbA1c (r = 0.399, P = 0.006). The DTSQc showed improvements at seven months in scores for treatment satisfaction, convenience, flexibility, understanding of diabetes, willingness to recommend the treatment to others, and satisfaction to continue current treatment (all P < 0.001). There was no relationship between weight gain, HbA1c and total or subscale scores. In summary, after seven months of insulin treatment, patients reported positive changes in their perception of treatment satisfaction. These findings, in conjunction with the known health benefits of improved glycaemic control, should encourage practitioners to consider insulin early in the management of Type 2 diabetes.

Transfer of metformin into human milk.

OBJECTIVES: Our objectives were to determine the milk-to-plasma ratio of metformin in lactating mothers and to estimate infant exposure. METHODS: Two studies were performed. In study 1, 3 nursing mothers taking metformin were studied throughout a dosing interval at steady state. Blood samples were obtained from 2 suckling infants. In study 2, 5 healthy lactating women who volunteered to express milk after weaning were given metformin, 500 mg, at weaning and were studied for up to 72 hours. In both studies, areas under the plasma and milk concentration-time curves were estimated, and the milk-to-plasma concentration ratio based on area under the concentration-time curve analysis was derived. The infant dose was calculated by standard methods. RESULTS: In study 1 the milk-to-plasma concentration ratios based on area under the concentration-time curve analysis were 0.37, 0.50, and 0.71. The estimated "doses" of metformin that would be ingested by the breast-fed infants were 0.18%, 0.20%, and 0.21% of the maternal doses, adjusted for weight. In the breast-fed infants, no metformin was detected (n = 2) or adverse effects noted (n = 3). In study 2, the milk-to-plasma concentration ratio based on area under the concentration-time curve analysis was unable to be calculated for 3 subjects because of the unexpected persistence of metformin in milk beyond the study period. For the 2 subjects studied for 72 hours, the milk-to-plasma concentration ratios based on area under the concentration-time curve analysis were 0.27 and 0.47 and the infant doses were 0.11% and 0.25%. The concentration-time profile for metformin in milk in all subjects was unexpectedly flat. CONCLUSIONS: Metformin appears to be "safe" during lactation because of low infant exposure. The unusual concentration-time profile for metformin in milk suggests that the transfer of metformin into milk is not solely dependent on passive diffusion.

Incidence of type 1 diabetes mellitus diagnosed before age 20 years in Canterbury, New Zealand over the last 30 years.

This study examined the epidemiological characteristics of type 1 diabetes mellitus (DM) presenting in Canterbury, New Zealand, between 1970 and 1999. All patients with type 1 DM aged 0-19 years at diagnosis within the Canterbury geographical region were either admitted to the regional hospital or seen acutely as outpatients in clinics at the same institution. Primary ascertainment of incident cases, through notification by the attending physician or paediatrician, began prospectively in 1982. Incident cases between 1970 and 1982 were ascertained retrospectively from clinic and hospital records. For the years 1970-99, there were 474 incident cases (256 males, 218 females). Incidence rates determined from 5-yearly census population denominators ranged from 2.40 to 26.59 patients/100,000 person years. The mean for 5-year periods, starting from 1970, increased from 6.79 to 22.79 patients/100,000 person years, i.e. a 3.4-fold increase over 30 years. The increase in incidence based on linear regression of these data is 0.59 patients/100,000 per year, or an annual increase of 5% derived from regression of the natural logarithms of the incidence data. These observations are consistent with the increasing attack rates for type 1 DM reported worldwide.