This study was designed to investigate postprandial responses to a mixed meal in simulated shift work conditions. Nine normal healthy subjects (six males and three females) were studied on two occasions at the same clock time (1330 h) after consuming test meals, first in their normal environment and secondly after a 9 h phase advance (body clock time 2230 h). Plasma glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), triacylglycerol (TAG) and non-esterified fatty acids (NEFAs) were determined at intervals for 6 h after each test meal. Postprandial plasma glucose, insulin, GIP and GLP-1 profiles were evaluated by calculating areas under the curve (AUC) for the first 2 h and the last 4 h of the sampling together with total AUC. Significantly higher postprandial glucose responses (total AUC) were observed after the phase shift than before (AUC 0-360 min, 2.01 (1.51-2.19) vs 1.79 (1.56-2.04) mmol/l.min; P < 0.02; mean (range)). No significant difference was observed when the first 2 h of each response was compared, but significantly higher glucose levels were observed in the last 4 h of the study after the phase shift than before (AUC 120-360 min, 1.32 (1.08-1.42) vs 1.16 (1.00-1.28) mmol/l.min; P < 0.05). Similar results were obtained for insulin (AUC 0-360 min, 81.72 (30.75-124.97) vs 58.98 (28.03-92.57) pmol/l.min; P < 0.01; AUC 120-360 min, 40.73 (16.20-65.25) vs 25.71 (14.25-37.33) pmol/l.min; P < 0.02). No differences were observed in postprandial plasma GIP and GLP-1 responses before and after the phase shift. Postprandial circulating lipid levels were affected by phase shifting. Peak plasma TAG levels occurred 5 h postprandially before the phase shift. Postprandial rises in plasma TAG were significantly delayed after the phase shift and TAG levels continued to rise throughout the study. Plasma postprandial NEFA levels fell during the first 3 h both before and after the phase shift. Their rate of return to basal levels was significantly delayed after the phase shift compared with before. This study demonstrates that a simulated phase shift can significantly alter pancreatic B-cell responses and postprandial glucose and lipid metabolism.

European normoglycaemic women with previous GDM display both glucoregulatory and antilipolytic insulin resistance, reduced beta-cell function and dyslipidaemia. These metabolic abnormalities are likely to contribute to their increased risk of future type 2 diabetes.

Aims/hypothesis: We assessed the impact of ethnic origin on metabolism in women following gestational diabetes mellitus (GDM). Materials and methods: Glucose regulation and other features of the metabolic syndrome were studied at 20.0 (18.2-22.1) months (geometric mean [95% CI]) post-partum in women with previous GDM (185 European, 103 Asian-Indian, 80 African-Caribbean). They were compared with the same features in 482 normal control subjects who had normal glucose regulation during and following pregnancy. Results: Impaired glucose regulation or diabetes by WHO criteria were present in 37% of women with previous GDM (diabetes in 17%), especially in those of African-Caribbean and Asian-Indian origin (50 and 44%, respectively vs 28% in European, p=0.009). BMI, waist circumference, diastolic blood pressure, fasting triglyceride and insulin levels, and insulin resistance by homeostatic model assessment (HOMA), were increased following GDM (p<0.001 for all, vs control subjects).Where glucose regulation was normal following GDM, basal insulin secretion (by HOMA) was high (p<0.001 vs control subjects). Irrespective of glucose regulation in pregnancy, Asian-Indian origin was associated with high triglyceride and low HDL cholesterol levels, and AfricanCaribbean with increased waist circumference, blood pressure, and insulin levels, together with insulin resistance and low triglyceride concentrations. Nonetheless, the GDMassociated features were consistent within each ethnic group. The metabolic syndrome by International Diabetes Federation criteria was present in 37% of women with previous GDM, especially in non-Europeans (Asian-Indian 49%, African-Caribbean 43%, European 28%, p=0.001), and in 10% of controls. Conclusions/interpretation: Following GDM, abnormal glucose regulation and the metabolic syndrome are common, especially in non-European women, indicating a need for diabetes and cardiovascular disease prevention strategies.

Rats were injected with monosodium 1-glutamate (MSG) daily for the 1st 5 days of life and allowed to mature. This is known to cause selective destruction of neurons in the retina and in the arcuate nucleus of the hypothalamus. The adult animals had a significant increase in body fat without an increase in weight, a marked reduction in pituitary, thyroid, adrenal, gonadal and prostate weights. Pituitary, hypothalamic and serum thyrotropin (TSH) were significantly reduced in the males. Serum growth hormone (GH) was markedly reduced in both sexes and the serum prolactin (Prl) was increased significantly in females. FSH did not appear to be abnormal and the LH may have been increased in the males. Serum T₄ was significantly reduced in females. The fertility of the females was normal, but treated males mated with normal females showed a marked reduction in fertility and, although the litter sizes of the offspring were normal, the birth weights of the pups of both sexes were significantly reduced. These persistent alterations in neuroendocrine function indicate that lesions produced by neonatal MSG treatment provide a convenient model for studying hypothalamic function.

European and South Asian women with previous GDM are shorter than control women from the same ethnic groups. The data demonstrate that this is unlikely to be an artefact resulting from the use of an fixed 75 g load in women of differing sizes, and suggest that there are likely to be common pathophysiological mechanisms underlying GDM and the determination of final adult height.

All criteria produced similar estimates of diabetes prevalence. However, analyses based on a single fasting glucose screen (and a threshold of 6.1 mmol/l) failed to identify 60% of women with abnormal 2-h glucose levels. Screening women with previous GDM (and by analogy, other groups at high risk of diabetes) with a single fasting glucose has low sensitivity for the detection of abnormal glucose tolerance. Recent guidelines recommending this approach require reevaluation.

OBJECTIVE Women with a history of gestational diabetes mellitus (GDM) and women with polycystic ovary syndrome (PCOS) both demonstrate abnormalities in insulin action and secretion, and both are at increased risk of developing type 2 diabetes. To determine whether these similarities re¯ect a common pathophysiological basis, we examined the prevalence of ultrasound-based polycystic ovarian morphology in a large multiethnic group of women with a history of GDM and a group of women who had normal glucose tolerance during pregnancy. PATIENTS AND DESIGN We studied 91 women with previous GDM (48 European, 20 South Asian, 10 Afro-Caribbean and 13 of other or mixed ethnicity) and 73 normoglycaemic control women (56 European, one South Asian, 14 Afro-Caribbean and two of other or mixed ethnicity), a median (interquartile range) of 20 (11±36) and 29 (17±49) months postpartum, respectively. A detailed history was taken, and the prevalence of PCO morphology on ultrasound scan was assessed. Fasting lipids, insulin, glucose status, gonadotrophins and testosterone were measured. Estimates of b-cell function (%B) and insulin sensitivity (%S) were derived using the HOMA algorithm. RESULTS Women with previous GDM had higher fasting glucose (5´4 (4´8±6´0) vs. 4´7 (4´4±5´0) mmol/l, P < 0´0001) and features reminiscent of syndrome X: higher BMI (26´4 (22´8±31´4) vs. 23´8 (21´0±27´5) kg/m 2 , P 0´002), waist/hip ratio (0´82 (0´79±0´88) vs. 0´77 (0´73±0´81), P < 0´0001), fasting insulin (165 (68±299) vs. 54 (24±156) pmol/l, P < 0´0001), triglycerides (1´1 (0´8±1´6) vs. 0´8 (0´6±1´1) mmol/l, P < 0´0001) and lower insulin sensitivity (%S) (27 (16±62) vs. 86 (34±139)%, P < 0´0001) compared to control women. The prevalence of PCO was higher in the previous GDM group than in the control subjects (47/91 (52%) vs. 20/73 (27%), x 2 9´86, P 0´002 overall, odds ratio 2´7, P 0´007 by logistic regression allowing for ethnicity). There was no difference in any metabolic parameter between the post-GDM PCO group and the post-GDM normal ovaries group, but irregular cycles were more prevalent in the PCO group (22/47 (47%) vs. 9/44 (21%), x 2 7´03, P 0´008). CONCLUSIONS We found a higher prevalence of polycystic ovarian morphology in women with a history of gestational diabetes. Among the women with previous gestational diabetes, irregular cycles were more prevalent in the PCO group than in the women with normal ovarian morphology, but no other differences in endocrine or metabolic parameters were detected. These ®ndings con®rm an association between PCO and gestational diabetes and suggest that women with gestational diabetes display metabolic abnormalities irrespective of ovarian morphology.

Objective To assess the prevalence and characteristics of islet cell autoimmunity amongst women with gestational diabetes selected from South Asian and Afro-Caribbean as well as European populations. Design Cross-sectional retrospective survey of subject cohort.Population Three hundred and twenty-one women with a recent history of gestational diabetes (173 European, 86 South Asian and 62 Afro-Caribbean), a median (range) of 22 (1-150) months postpartum.Results Antibodies to Glutamic acid decarboxylase were found in 13 (4%) of these women. There was no difference in the prevalence of anti-glutamic acid decarboxylase positivity between the three ethnic groups (European 4.6%, South Asian 3.5%, Afro-Caribbean 3.2%). Anti-glutamic acid decarboxylase positive women were leaner than anti-glutamic acid decarboxylase negative women (body mass index, median (upper-lower quartile) 23.9 (22.5±26.7) vs 26.6 (23.4-30.5)kg/m 2 , P 0.03, P 0.049 allowing for ethnicity). There was no difference between glutamic acid decarboxylase-positive and glutamic acid decarboxylase-negative women for age, family history of diabetes, waist/hip ratio, prevalence of insulin treatment during pregnancy, postpartum glucose status, lipid pro®le and indices of insulin action and beta-cell function.Conclusions Markers of islet cell autoimmunity are found as frequently in gestational diabetes women of South Asian and Afro-Caribbean origin, as they are in European subjects. Identi®cation of future risk of type 1 diabetes is relevant to the planning of clinical management and intervention strategies in women with gestational diabetes of all major ethnic groups.