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AIMS: To evaluate the completeness of insulin resuspension by users of neutral Hagedorn (NPH) insulin pens and premixed insulin pens and to relate this to how patients mix insulin before injecting. METHODS: Patients (n = 180) administering a medium duration or premixed insulin in cartridges in disposable pens were asked questions about mixing insulin, injection technique and storing insulin. They were also asked to demonstrate how they mixed their insulin and to send in a half-used pen. The cloudy component equates to the complexed insulin, while the clear component is the diluting fluid or soluble insulin, depending on the type of insulin used. The optical density, a simple way of measuring cloudiness, was measured in each cartridge or disposable pen and was compared with the range obtained from a series of unused control pens. The results for 146 pens containing the most commonly used insulin were included. The 21 patients whose residual pen insulins showed optical densities > 5 SD from the mean were re-interviewed and their medical records were examined in detail. Insulin in the pens was also measured by immunoassay to confirm the utility of optical density measurements. RESULTS: Only one patient mixed the insulin as the manufacturers recommended. In 58 out of 146 pens or cartridges (40%) the opacity of the insulin varied significantly from the expected value. CONCLUSIONS: Most patients in Kirkcaldy do not mix insulin adequately. This may result in their giving different incorrect doses of insulin during the use of each pen. More emphasis should be given to teaching patients to mix correctly.

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OBJECTIVE: To identify factors independently affecting fetal weight in women with type I diabetes. DESIGN: Prospectively recorded data in consecutive women with type I diabetes, between 1975-1992. SETTING: Simpson Memorial Maternity Hospital, Edinburgh. Population Three hundred and two pregnancies with type I diabetes identified before pregnancy, with antenatal care and delivery in the Simpson Memorial Maternity Hospital, a singleton pregnancy, and the same diabetic physician. METHODS: Normal ranges for birthweight were established for the total hospital population. All cases and the total population had pregnancy dating by ultrasound. The relation between standardised birthweight and explanatory variables was investigated using correlation analysis, t tests and chi2 tests as appropriate, and subsequently using multiple linear regression. RESULTS: Standardised birthweight in cases, compared with the reference population, showed a unimodal, approximately normal distribution, markedly shifted to the right (mean + 1.26 SD). The most predictive variable was glycated haemoglobin concentration at 27-33 weeks, which explained 6.3% of the birthweight variance, while smoking explained 2.7% and maternal weight 2.0%. There was a trend towards a negative relationship with glycated haemoglobin concentration at 6-12 weeks. Smoking and glycated haemoglobin concentration were strongly intercorrelated. CONCLUSIONS: Most of the variance in standardised birthweight remains unexplained, but glycated haemoglobin concentration at 27-33 weeks is the most powerful explanatory variable. Possible reasons why there is not a stronger relationship between markers of maternal glycaemia and birthweight are discussed.

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In a screen designed to identify genes expressed preferentially in retina, we identified a cDNA encoding the human ortholog of rat STXBP1 (n-Sec1, Munc-18-1, rbSec1), a protein implicated in vesicle trafficking and neurotransmitter release. This protein also has similarity to Drosophila Rop (65% aa identity) and Caenorhabditis elegans UNC-18 (58% aa identity). The major human cDNA encodes a protein of 594 amino acids which has 100 % amino acid identity with its rat and murine counterparts. Additionally, there is an alternative splice form in humans, arising from the inclusion of an additional exon, which encodes a protein of 603 amino acids and is also 100% identical to the corresponding rat isoform. We found expression of the shorter cDNA in all tissues and cell lines we examined with highest levels in retina and cerebellum. By RT-PCR analysis, we found expression of the longer cDNA in neural tissues only. We mapped the structural gene to 9q34.1, a region without obvious candidate phenotypes. However, due to its evolutionary conservation and abundant expression in retina and brain, STXBP1 should be considered a candidate gene for retinal and/or neural disorders mapping to 9q34.1.

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Identification of genes expressed preferentially or exclusively in photoreceptors will facilitate the understanding of photoreceptor biology as well as provide candidate genes for inherited retinal degenerations. To achieve this goal we performed a differential hybridization screen of 3717 well-isolated phage clones from a human retinal cDNA library. Clones were selected for further study if they hybridized exclusively or strongly preferentially to a probe derived from RNA isolated from the cone-predominant retina of 13-line ground squirrels as compared to a probe derived from human fibroblast RNA. Twenty percent of clones (9/45) identified by this screen were derived from photoreceptor-specific genes and an additional 24.4% (11/45) were from neural-specific genes, demonstrating the utility of this strategy in identifying genes important for retinal biology.

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OBJECTIVE: To study prospectively the prediction power, at different gestations, of clinical and ultrasound measurements for fetal size in diabetic pregnancy. SETTING: A large combined obstetric diabetic clinic in a teaching hospital. PARTICIPANTS: One hundred and eighty-one pregnancies in which women had scans at least two of three specific time points and who were delivered of singletons after 34 weeks: 73% were pre-gestational insulin-dependent diabetics, the others were pre-gestational White class A or gestational diabetics. INTERVENTIONS: Clinical estimates of fundal height and fetal size and ultrasound estimates of abdominal circumference and head circumference were routinely carried out at gestational ages of 28, 34 and 38 weeks or before delivery. MAIN OUTCOME MEASURES: Standardised birthweight, corrected for gestation and parity. The relation with clinical and ultrasound measurements was investigated using multiple linear regression and the capability of the measurements to predict macrosomic births (> 95th centile of normals) using receiver-operator characteristic curves. RESULTS: All measurements are poor predictors of eventual standardised birthweight. Prediction improves with closeness to delivery. Prediction is significantly improved by adding ultrasound to clinical information, but at 34 weeks or later this only contributes 8% of the variance. There is no difference in the prediction power for macrosomia between clinical and ultrasound measurements. CONCLUSIONS: Even regular serial scanning and clinical examination will not always diagnose the macrosomic fetus in diabetic pregnancy. In our hands, clinical examination is as predictive as ultrasound measurements. Ultrasound does add to clinical prediction power but only to a small extent. Ultrasound should be used in a selected way, as defined by clinical findings, and with recognition and understanding of the errors and biases involved.

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The infant of an insulin-dependent diabetic mother is at increased risk of perinatal death, neonatal problems and major congenital malformations: Many of these problems are preventable. All young women with diabetes should receive contraceptive advice and information about pregnancy. The objects of pre-pregnancy care are to assess suit-ability for pregnancy, to optimise control in early pregnancy and to improve pregnancy outcome through the provision of individualised education and information. Pre-pregnancy care can reduce the congenital malformation rate to approximately that of the nondiabetic. In each area there should be one designated diabetologist and one designated obstetrician who, together with their team, should see all pregnant women in a combined clinic in a hospital with an intensive care baby unit. All pregnant women with diabetes should have 24-hour access to the specialist team. Tight glycaemic control during pregnancy can reduce complications of pregnancy greatly, improving infant mortality and morbidity. Insulin requirements usually change during pregnancy. Education about hypoglycaemia and avoidance of ketoacidosis is essential. Women should have regular examination of the fundi and renal function. They should have ultrasound scanning to assess gestation, to look for abnormalities and to assess fetal growth. Fetal monitoring should be used, particularly for those at high risk. Women with good diabetic control and no complications of diabetes or pregnancy may be delivered at 39 to 40 weeks but those at high risk earlier. During labour or caesarean section blood glucose should be normalised using intravenous glucose and insulin supervised by a specialist team. An experienced paediatrician should be available. Breast feeding should be encouraged.

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Eating disorders in diabetes mellitus may be associated with serious diabetic complications. This study examines the prevalence of complications and the usefulness of the Eating Attitudes Test (EAT) in screening for eating disorders in a group of insulin-dependent diabetic women. Coping strategies for dealing with diabetes are also investigated. Increased rates of diabetic complications and insulin manipulation were confirmed among subjects with eating disorders. The EAT alone had a poor predictive value for identifying eating disorders, but the presence of raised EAT score or insulin manipulation proved effective in identifying almost all cases of eating disorder. Subjects with high EAT scores showed coping styles characterised by acceptance-resignation.

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OBJECTIVE: To identify the date of ovulation in pregnant women with Type 1 diabetes in order to assess the validity of the concept of early growth delay. DESIGN: Identification of ovulation by measurement of urinary luteinising hormone and assessment of fetal growth using ultrasound scan. SETTING: Diabetic pre-pregnancy and antenatal clinic in a teaching hospital. SUBJECTS: Twenty women with Type 1 diabetes who had attended a pre-pregnancy clinic. MEASURES: Urinary LH, by laboratory and kit methods, during conception cycles. Human chorionic gonadotrophin measured in early pregnancy. Early ultrasound scans by a single observer blind to menstrual and ovulation dates. OUTCOME: Gestation calculated from ovulation date and gestation estimated from menstrual dates, compared with gestation at age indicated by early ultrasound scan. RESULTS: When the date of ovulation was identified in 20 women with Type 1 diabetes there was no evidence of growth delay in any pregnancy. When gestation was estimated from menstrual dates there was apparent early growth delay in six pregnancies. CONCLUSION: This study, together with others discussed, indicates that early growth delay is probably an artefact of incorrectly estimated ovulation date.

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OBJECTIVES: To document individual variations in the rise in insulin requirements during type I diabetic pregnancies, to relate the degree of increase to maternal characteristics and fetal outcome, and to examine these factors in a subgroup of patients experiencing a large fall in insulin requirement in the third trimester. METHODS: Insulin dose was documented in 237 pregnancies in women with type I diabetes. Multiple regression analysis was performed to identify significant associations with maternal and fetal characteristics. Eighteen pregnancies with a fall in insulin requirement of 30% or more in the third trimester were considered in detail. RESULTS: The mean absolute increase in insulin requirement was 52 units. The degree of rise was significantly related to maternal weight gain between 20-29 weeks and maternal weight at booking, and was inversely related to duration of diabetes. It was not related to the degree of diabetes control, complications of pregnancy, White class, or outcome of pregnancy. In the 18 women experiencing a large fall in insulin requirement, there was no relation with maternal characteristics or fetal outcome. CONCLUSION: There is a wide individual variation in the change in insulin requirements in type I diabetic pregnancy. The degree of increase is related only to maternal weight gain during weeks 20-29 and maternal weight at booking, and is inversely related to duration of diabetes. Large falls in insulin requirement remain unexplained and may not be associated with placental failure.

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This study investigates reports that phosphoglucomutase-1 (PGM1) phenotype is associated with fetal growth and gestation length. A total of 350 women were studied, 234 having uncomplicated pregnancies and 114 with a baby weighing greater than 90th centile, corrected for parity, gestation and fetal sex. All women had gestation confirmed by early ultrasound. Conventional cellulose acetate electrophoresis was used to distinguish the three common PGM1 phenotypes and polyacrylamide gel isoelectric focusing to distinguish the ten PGM1 subtypes. Neither PGM1 phenotype nor subtype were found to be associated with gestation length or standardised birth weight. Logistic regression, where maternal age, parity, fetal sex, maternal weight, gestation and smoking were introduced as explanatory variables in addition to PGM1 phenotype testing against the dependent variables birth weight, standardised birth weight and gestation length, did not show differences related to PGM1 phenotype. Two possible reasons for the discrepancy with previously published data are discussed. We conclude that the study provides no support for the belief that PGM1 phenotype is related to fetal growth or gestation length and that the original observations could have arisen as a result of statistical artefact due to multiple testing.

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Four hundred and six insulin-dependent diabetic women completed a Menstrual Health Questionnaire published in Balance. Sixty-seven percent of women experienced changes in blood glucose levels or glycosuria premenstrually and 70% during the menstrual phase. Changes were more common in women who regarded themselves as suffering from premenstrual syndrome. Those experiencing premenstrual craving for sweet foods tended to have higher blood glucose levels or more glycosuria at those times. This may be a consequence of some women indulging their craving. Premenstrual symptoms were not caused by hypoglycaemia. When compared with age-matched non-diabetic women responding to a similar questionnaire, the diabetic women had a later menarche and, among those not on steroidal contraceptives, were more likely to report very irregular menstrual cycles. Among those regarding themselves as sufferers of premenstrual syndrome, diabetic women had less severe premenstrual symptoms than non-diabetic women. When women from these two self-designated premenstrual [corrected] syndrome suffering groups were matched for severity of premenstrual depression, differences still persisted in the severity of some symptoms perimenstrually, raising the possibility that in some way diabetes may alter women's experience of menstrual cycle-related symptoms.

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OBJECTIVE: To assess the effect of uncomplicated diabetes on umbilical artery flow velocity waveforms (FVWs); to investigate the relation between glycaemic control and FVWs and the predictive value of umbilical artery FVWs for antenatal fetal compromise. DESIGN: Prospective descriptive study. SETTING: A large diabetic pregnancy clinic in a teaching hospital. SUBJECTS: 128 pregnancies complicated by diabetes mellitus. 170 non diabetic women with no pre-existing or pregnancy complications. INTERVENTIONS: In diabetic pregnancies, umbilical artery resistance index (RI) Doppler recordings and glycosylated haemoglobin were measured every 2 weeks from 28 weeks. MAIN OUTCOME MEASURES: Umbilical artery RI and antenatal fetal compromise defined as a non reactive, decelerative cardiotocograph and/or a biophysical profile score persistently less than 6 and leading to immediate caesarean section. RESULTS: Uncomplicated diabetic pregnancies had FVW values similar to those in the non-diabetic range. Glycaemic control was unrelated to umbilical artery FVW values. Abnormal umbilical artery RI was found in nine pregnancies, these were more likely to show evidence of fetal compromise and to be associated with birthweights of less than 50th centile. In seven pregnancies there was evidence of fetal compromise, but only three of these pregnancies had abnormal FVW values. CONCLUSIONS: The non-diabetic range of umbilical artery RI values is appropriate for diabetic pregnancies. Long-term glycaemic control, within the range in this study, does not seem to affect umbilical artery RI. Abnormal umbilical artery RI is a significant predictor of fetal compromise in diabetic pregnancy, but fetal compromise can occur in association with normal RI values. Undue reliance should not be placed on normal FVW values in diabetic pregnancies.

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