Oral GTT Research Articles

Exon 2-mediated deletion of Trem2 does not worsen metabolic function in diet-induced obese mice.

Triggering receptor expressed on myeloid cells 2 (Trem2) is highly expressed on myeloid cells and is involved in cellular lipid homeostasis and inflammatory processes. Trem2 deletion in mice (Trem2-/- ) evokes adipose tissue dysfunction, but its role in worsening obesity-induced metabolic dysfunction has not been resolved. Here we aimed to determine the causal role of Trem2 in regulating glucose homeostasis and insulin sensitivity in mice. Nine-week-old male and female littermate wild-type (WT) and Trem2-/- mice were fed a low- or high-fat diet for 18weeks and phenotyped for metabolic function. Diet-induced weight gain was similar between genotypes, irrespective of sex. Consistent with previous reports, we find that loss of Trem2 causes massive adipocyte hypertrophy and an attenuation in the lipid-associated macrophage transcriptional response to obesity. In contrast to published data, we find that loss of Trem2 does not worsen metabolic function in obese mice. No differences in intraperitoneal glucose tolerance (ipGTT), oral GTT or mixed meal substrate control, including postprandial glucose, non-esterified fatty acids, insulin or triglycerides, were found between WT and Trem2-/- animals. Similarly, no phenotypic differences existed when animals were challenged with stressors on metabolic demand (i.e. acute exercise or environmental temperature modulation). Collectively, we report a disassociation between adipose tissue remodelling caused by loss of Trem2 and whole-body metabolic homeostasis in obese mice. The complementary nature of experiments conducted gives credence to the conclusion that loss of Trem2 is unlikely to worsen glucose homeostasis in mice.

Halophila beccarii extract ameliorate glucose uptake in 3T3-L1 adipocyte cells and improves glucose homeostasis in streptozotocin-induced diabetic rats

The regulation of carbohydrate metabolizing enzymes is an effective way of reducing blood glucose levels and improving glycogen synthesis during the management of type 2 diabetes. The present investigation was conducted to explain the detailed mechanism with which a Seagrass, Halophila beccarii extract (HBE) enhances the glucose uptake in the 3T3-L1 adipocyte cell culture system in invitro. HBE stimulates the glucose uptake by the translocation of glucose transporter 4 (GLUT4) on to plasma cell membrane through induction of insulin receptor substrate 1 (IRS-1)/protein kinase B (Akt) signaling pathways. To assess the effect of HBE on T2DM, we used invivo experimental diabetes rat models induced with streptozotocin (STZ) to perform oral GTT and ITT. Furthermore, we assessed the enzymatic profile of Glycolysis, Pentose phosphate pathway, and gluconeogenesis from liver tissue homogenate. After long-term exposure with HBE, our results confirmed, that HBE improves the glucose uptake in 3T3-L1 cell lines by up-regulation of glucose transporter type 4 (GLUT4) through uptake of glucose by the adipocytes. The resulting data indicated that HBE had a great potentiality in preventing diabetes and maintaining glucose homeostasis through improving glucose uptake. The present data also showed that HBE with its insulin mimetic activity activates glycogen synthesis and enhances glucose utilization by regulating the carbohydrate metabolic enzymes. The similarity between HBE and insulin indicates that the HBE follows the mechanisms same as the insulin signaling pathway to show the antidiabetic activity.

Prevalence of Impaired Oral Glucose Tolerance in Patients with Polycystic Ovarian Syndrome

Objectives: To find the prevalence of PCOS in patients with menstrual irregularities and then to find the prevalence of impaired glucose tolerance among patients with PCOS. Study design: Descriptive cross sectional Place and Duration of Study: Department of Obstetrics and Gynecology, District Headquarter Hospital, Gujranwala from 1st November 2017 to 2nd May 2018. Methodology: Two hundred and twenty threepatients with menstrual irregularities were included In the study. Rotterdam classification criteria were used for proper identification of polycystic ovarian syndrome facilitated by clinical investigation. These patients were called for the oral GTT as explained in operational definitions. All blood samples were sent to our hospital laboratory. Results: Mean age of women was 32.54±7.54 years. Among women, 120 (53.8%) had family history of diabetes. Impaired glucose tolerance was confirmed in 55(24.7%) patients. Women who were diagnosed with PCOS among them impaired glucose tolerance was confirmed in 20(18.2%) patients. Conclusion: Glucose tolerance frequency was not significantly higher. However elderly and obese women had higher frequency of impaired glucose tolerance. Key words: PCOS, Menstrual irregularities, Impaired, Glucose, Tolerance

Coadministration of sitagliptin or metformin has no major impact on the adverse metabolic outcomes induced by dexamethasone treatment in rats

AimsGlucocorticoids (GC) in excess cause glucose intolerance and dyslipidemia due to their diabetogenic actions. Conceptually, antidiabetic drugs should attenuate these side effects. Thus, we evaluated whether the coadministration of metformin or sitagliptin (or both) with dexamethasone could attenuate GC-induced adverse effects on metabolism. Materials and methodsAdult male rats were treated for 5 consecutive days with dexamethasone (1 mg/kg, body mass (bm), intraperitoneally). Additional groups were coadministered with metformin (300 mg/kg, bm, by oral gavage (og)) or sitagliptin (20 mg/kg, bm, og) or with both compounds in combination. The day after the last treatments, rats were submitted to glucose tolerance tests, pyruvate tolerance test, and euthanized for biometric, biochemical, morphologic, and molecular analyses. Key findingsDexamethasone treatment resulted in reduced body mass and food intake, increased blood glucose and plasma insulin, dyslipidemia, glucose intolerance, pyruvate intolerance, and increased hepatic content of glycogen and fat. Sitagliptin coadministration improved glucose tolerance compared with the control group, an effect paralleled with higher levels of active GLP-1 during an oral GTT. Overall, sitagliptin or metformin coadministration did not prevent any of the dexamethasone-induced metabolic disturbances. SignificanceCoadministration of sitagliptin or metformin result in no major improvement of glucose and lipid metabolism altered by dexamethasone treatment in male adult rats.

Increased individual glucose tolerance test values in women with gestational diabetes.

Individual oral glucose tolerance test (OGTT) values may be of interest to clinicians. We evaluate factors associated with these values. This retrospective study included 225 pregnant women diagnosed with gestational diabetes by abnormal 100-gram oral GTT. Predictor variables were maternal age, race/ethnicity, gravida, parity, pre-pregnancy Body Mass Index (BMI), weight gain in current pregnancy, family history of diabetes, personal history of gestational diabetes, and neonate gender. Outcome variables were continuous OGTT and categorical elevated OGTT for fasting, 1-hour postprandial, 2-hour postprandial, and 3-hour postprandial. Obese BMI was associated with increased odds for higher fasting level in the continuous OGTT and elevated categorical OGTT; for 1-hour postprandial this significant obese association only occurred for the continuous OGTT. Higher weight gain in pregnancy was associated with a higher fasting level continuous OGTT and elevated categorical OGTT. Higher maternal age at time of delivery was associated with higher 2-hour continuous OGTT and an elevated 1-hour categorical OGTT. Female neonate gender was associated with decreased odds for elevated 2-hour categorical OGTT. Hispanic and Black race/ethnicities were each associated with higher 3-hour continuous OGTT. These findings can help clinicians identify the women potentially at risk for having abnormal GTT values diagnostic of GDM to provide preemptive early intervention. Clinicians have the goals to identify these women early so that women can be properly educated and counseled in terms of their nutrition status and as to what negative clinical outcomes may occur should their glucose levels remain poorly controlled in the pregnancy.

OR16-03 Metabolic Effects Of Hypothalamic Pomc Neurons Generated Postnatally From Tanycytes On A Pomc Null Genetic Background

Hypothalamic proopiomelanocortin (POMC) neurons are an integral part of the central melanocortin system and regulate feeding and energy balance in vertebrates. Tanycytes are radial glial-like cells lining the third ventricle that contain a subpopulation of adult stem cells, which can differentiate under specific circumstances into glia and neurons, including POMC neurons. However, the capacity of these stem cell-derived neurons to fully mature and integrate into existing neural circuits of physiological relevance is unknown. This study systematically tested whether Pomc mRNA-positive cells newly generated from tanycyte precursors can differentiate into melanocortin-secreting POMC neurons, integrate into the normal anatomical projection pathways of these cells and rescue the obesity phenotype caused by the loss of Pomc expression in ArcPomcfneo/fneo mice. We generated an inducible compound genetic mouse model by crossing RaxCreERT2 with the Cre-dependent ArcPomcfneo/fneo and LSL-syp-tdTomato alleles. Rax is expressed exclusively in postnatal tanycytes, thereby limiting tamoxifen-induced recombination of the two floxed alleles by CreERT2 to tanycytes. As expected, tamoxifen treatment of the mice at age 4–5 wk recapitulated endogenous Rax expression 16 wk later as observed by red fluorescent tdTomato expression in all tanycytes. In addition, Cre recombinase-mediated deletion of the floxed-neomycin cassette from the neuronal enhancer region of the ArcPomcfneo alleles relieved their constitutive transcriptional silencing. Consequently, tamoxifen treatment consistently generated a significant number of newly generated POMC neurons from tanycytes (~10% of the POMC neurons in a WT mouse), identified by Pomc FISH and POMC/α-MSH immunofluorescence in the soma and established terminal projections to hypothalamic nuclei including the PVH and DMH involved in energy homeostasis. A subpopulation of these neurons also expressed the synaptophysin-tDTomato reporter. We performed serial body weight, food intake, body composition, oral GTT and insulin measurements with the RaxCreERT2/+, ArcPomcfneo/fneo mice and found no significant differences in any of these metabolic variables compared to untreated obese ArcPomcfneo/fneo mice. These data are consistent with previous studies from our lab suggesting that Pomc expression has to be at least ~30% of normal to mitigate the obesity phenotype in Pomc-null mice. In conclusion, we demonstrated that tanycytes are capable of generating mature Pomc-expressing neurons in the hypothalamus of adult mice. However, we propose that determining the underlying mechanisms involved in the generation of hypothalamic POMC neurons from tanycytes and interventions to increase their number, might lead to a novel approach to treat obesity. Nothing to Disclose: SG, GW, RML, MJL

SUN-926 Malignant Transformation of a Benign Glucagonoma After 13 Years

Glucagonoma are rare neuroendocrine tumors arising solely in the pancreas and approximately 25 % of glucagonoma cases start in a benign form. We hereby report a 76 -year-old male who was initially diagnosed with asymptomatic benign glucagonoma. Follow-up surveillance 13 years later shows that the tumor has undergone differentiation into a malignant form. Case Report: A 63-year-old man was referred for evaluation of an enhancing lesion (2.7 cm) at the pancreatic tail. He was completely asymptomatic with normal physical exam. Initial labs: normal except for elevated serum glucagon level (206 pg/mL, ref 0–60). A 2-hour oral GTT confirmed the autonomy of glucagon secretion by the tumor. Somatostatin and other tumor markers were normal. PET scan showed abnormal uptake at the distal pancreatic tail, correlating with the CT scan findings. The patient underwent laparoscopic distal pancreatectomy, with removal of a 2.8cm mass which predominantly expressed glucagon. Plasma glucagon level in the peripheral venous blood and intraoperative splenic vein dropped to <50 pg/mL immediately after the surgical resection. Following surgery patient remained completely asymptomatic for the next 13 years with normal blood glucose, glucagon, insulin, chromogranin levels, complete blood count and liver functions. Additionally patient continued to have normal surveillance MRIs of the abdomen. 13 years following removal of pancreatic mass, an elevated glucagon serum level (230 pg/mL) was noted on routine surveillance screening. At this time patient also remained asymptomatic. Abdominal MRI and PET scan revealed a 4-cm pancreatic mass with hepatic metastases. Biopsy of the hepatic lesion confirmed glucagonoma. Patient was treated with Lanreotide which has normalized the serum glucagon levels and the tumor size remained stable for the 12 months of follow up. Discussion: In our patient the glucagon secreting tumor without any classic presenting symptoms was found incidentally and the asymptomatic glucagonoma treated surgically presumably at an earlier stage. It is known that some glucagonomas are associated with serum levels of the peptide in the “physiologically elevated” range, even in the presence of necrolytic migratory erythema. The complete remission without any treatment lasting for more than 13 years confirmed the benign nature of the tumor. It is also reported that gluconomas less than 2 cm in size has less potential for metastasis. The usual recommendation is to monitor these patients post-resection to a maximum of 10 years although in our patient the malignant nature of the tumor was expressed 13 years after initial resection. The reason for malignant transformation after this prolonged period remains unknown. This case highlights the importance of continuous monitoring neuroendocrine tumors even beyond 10 years after surgery.

English

CONTEXT: Patients with impaired glucose tolerance are diagnosed with difficulty in the clinical setting because of the absence of classical symptoms of the disease. Due to recent introduction of this class of glucose intolerance, and relative lack of knowledge of its clinical significance impaired glucose tolerance is still the subject of research to determine its course and prognostic implications. AIMS: To study the prevalence of impaired glucose tolerance in first degree relatives of type II diabetic patients, above 30 years of age. SETTINGS AND DESIGN: Inclusion of persons above the age of 30 years who are first degree relatives of type II diabetic, admitted in indoor or attending as outpatients in Department of Medicine, Sanjay Gandhi Memorial Hospital, Rewa, Madhya Pradesh. METHODS AND MATERIAL: A complete general and systemic examination and Oral GTT to be carried out on selected subjects. RESULTS: More than one-fourth of the subjects were found to have an impaired Oral Glucose tolerance test. None of them previously knew their oral glucose tolerance state. Total prevalence of impaired glucose tolerance found in this study was 27.27%. CONCLUSION: Testing for impaired glucose tolerance should be considered in all individuals at age 45 years and above and if normal it should be repeated at three year interval. Keeping in mind the results of this study, this testing should be carried out at an earlier age group, especially for the 'at

Glp2r is required for postprandial glycemic control (1114.3)

Glucagon‐like peptide 2 (GLP‐2) is secreted from enteroendocrine L cells and proposed as a key promoter of intestinal metabolic reprogramming and tissue regeneration, contributing to improving glucose homeostasis and insulin sensitivity after RYGB. Through the gut‐brain‐liver axis, GLP‐2 plays crucial roles in the control of food intake and hepatic glucose production. We showed in Cell Metab (2013) that GLP‐2 receptor (Glp2r) in POMC neurons is required for GLP‐2 to promote glucose homeostasis at the postabsorptive status. However, little is known about the physiological relevance of GLP‐2 in the glycemic control at the postprandial status when GLP‐2 is physiologically secreted. In this study, we first developed an innovative stable isotopic tracer approach to quantify non‐steady postprandial glucose kinetics in mice, which were assessed by the appearance rate of ingested glucose (Ra,ingested) after intragastric feeding U‐13C6‐D‐glucose‐enriched elementary diet; and the appearance rate of endogenous glucose (Ra,endogenous) by iv infusion of 6,6‐2H2‐D‐glucose. We then generated mice with Glp2r deletion in the intestinal epithelium by crossing Glp2r‐floxed mice with villin‐Cre mice. Finally, we show that Glp2r global KO mice display glucose intolerance after an oral GTT and postprandial hyperglycemia after the elementary meal as a result of increased hepatic production of endogenous glucose (Ra,endogenous, attributed to the increased rate of gluconeogenesis) and decreased splanchnic sequestration of ingested glucose (Ra,ingested), pointing to a physiological role of GLP‐2 in postprandial glycemic control. Moreover, villin‐Glp2r KO mice display postprandial glucose intolerance, suggesting that the gut epithelium is a key site for GLP‐2 action to promote postprandial glycemic control. We conclude that Glp2r activation is required for postprandial glycemic control and GLP‐2 secretion augmentation may contribute to improving postprandial hyperglycemia in diabetes.Grant Funding Source: Supported by the USDA CRIS 6250‐51000‐055

Association of Diabetes Mellitus and Insulin Resistant in Polycystic Ovarian Syndrome (PCOS) Women in Kerala

Objective: To determine the association of Insulin Resistance (IR) characteristics; as a predictor of diabetes mellitus and hormonal disturbance in patients with PCOS. Material and methods: Design: Prospective study Setting: Kerala Medical college and Hospital, Mangode, Cherpulassery, Palakkad Dist,, Kerala Subjects: 51 females with PCOS diagnosed by Rotterdam criteria were enrolled. Methods: Patients with PCOS were examined in detail for anthropometry, blood pressure, hirsutism and acanthosis nigricans and other markers of insulin resistance. Biochemical estimation such as fasting glucose and fasting lipid profile with an oral GTT were done. Analysis of TSH, FSH, LH, DHEA-S, Testosterone, cortisol were done by radioimmunoassay. Results: 51 females with PCOS were enrolled for the study of which (78.4%) 40 were having IR and among those (72.5%) 29 had diabetes. P<0.001, which is statistically very high significant Conclusions: IR characteristics could emerge as a marker of diabetes mellitus in PCOS subjects in Kerala state population

Delta insulin-like growth factor binding protein-1 (ΔIGFBP-1): a marker of hepatic insulin resistance?

Insulin-like growth factor binding protein-1 (IGFBP-1) is a hepatically synthesised protein which can be used as a marker of insulin resistance. We hypothesised that the fall in serum IGFBP-1 at 2 h following a glucose load (ΔIGFBP-10-2h) would be a more robust measure of hepatic insulin resistance than a fasting level alone. All subjects had a standard 75 g oral GTT including IGFBP-1 and insulin measurement to enable calculation of ΔIGFBP-10-2h, ΔInsulin0-2h, and insulin sensitivity indices. At a second visit, subjects had a frequently sampled intravenous glucose tolerance test (FSIVGTT) in order to determine the insulin sensitivity index, Si. Twenty-two individuals had normal glucose tolerance (NGT) and 9 impaired fasting glucose (IFG). ΔIGFBP-10-2h correlated with Si in total subjects (r = 0.49, p = 0.005) and NGT subjects (r = 0.50, p = 0.02) but not in IFG subjects (r = 0.43, p = 0.24). ΔInsulin0-2h/ΔIGFBP-10-2h correlated significantly with Si in total subjects (r = -0.68, p < 0.001) and in NGT subjects (r = -0.57, p = 0.005). Multivariate analysis was fitted using different models while keeping other explanatory variables constant. The fasting IGFBP-1 model was a better predictor of Si (β = 0.431, p < 0.0001) than the ΔInsulin0-2h/ΔIGFBP10-2h model (β = -0.185, p = 0.004). The dynamic indices ΔIGFBP-10-2h and ΔInsulin0-2h/ΔIGFBP-10-2h appear suitable markers of (hepatic) insulin resistance with potential clinical utility.

Prevalence of the Metabolic Syndrome in Kidney Transplantation

Objectives We investigated the prevalence of the metabolic syndrome (MS) in kidney transplantation patients and assessed its development based on plasma adiponectin levels and the results of an oral glucose tolerance test (OGTT). Methods We performed a cross-sectional study of 94 recipients with stable graft function who underwent kidney transplantation between January 1999 and October 2008. The presence of MS was determined using National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria with body mass index (BMI) used in place of waist circumference. In addition, we measured plasma adiponectin level and performed a 75-g oral GTT. Results Fourteen (14.9 %) recipients suffered from MS for a mean period of 46.7 months (range, 1–106) after transplantation. BMI at the time of transplantation was significantly greater in the MS group (23.4 ± 3.24 vs 20.1 ± 2.50; P < .0001), whereas plasma adiponectin level was significantly lower (11.95 ± 5.13 vs 17.71 ± 8.47; P = .0158). The insulinogenic index values were similar, whereas the homeostatic model assessment of insulin resistance was greater in the MS group (2.598 ± 1.918 vs 1.340 ± 0.934; P = .0002). Conclusion The level of adiponectin, which was lower in kidney transplant recipients who developed MS, was negatively correlated with insulin sensitivity. We concluded that a low adiponectin level may correlate with the prevalence of MS in kidney transplantation in association with impaired insulin sensitivity.

Volume do stent à ultra-sonografia intracoronária como preditor de reestenose angiográfica: estudo em pacientes com alto risco de reestenose

INTRODUÇÃO: Em populações não selecionadas, obstruções em vasos de fino calibre são mais susceptíveis à reestenose após intervenção coronária percutânea (ICP). Por isso, entre as características angiográficas preditoras do fenômeno, o diâmetro luminal de referência (D.L.R.) é particularmente relevante. Tais resultados são corroborados por ultra-sonografia intracoronária (USIC), evidenciando a influência das dimensões vasculares sobre a resposta clínica no processo da reestenose, independente da presença de outros preditores, nessas populações não selecionadas. O objetivo deste trabalho foi avaliar os preditores angiográficos e ultra-sonográficos intracoronários de reestenose, em pacientes em que o alto risco de reestenose foi especialmente caracterizado por busca ativa de diabete melito (DM) e de disglicidemia. MÉTODO: Setenta pacientes portadores de 77 lesões obstrutivas ateroscleróticas coronarianas foram submetidos a ICP com stent, com sucesso. Realizou-se controle angiográfico e com USIC do resultado do implante, imediatamente após o término do procedimento e 6 meses após. Procedeu-se à busca ativa de alterações do metabolismo da glicose mediante a realização de GTTo, em todos os casos sem diagnóstico prévio de DM. RESULTADOS: Foram identificados 23 (32,86%) indivíduos com DM e 16 (22,85%) com intolerância à glicose. Pela análise bivariada, os parâmetros considerados preditores de reestenose angiográfica pelo critério binário foram: D.L.R. > 2,82 mensurado na condição controle 6 meses após ICP - RR=0,60 (0,15-0,81) IC 95% (p=0,014), volume de stent < 119,8 mm³ ao USIC - RR=0,74 (0,38- 0,89) IC 95% (p=0,0005) e área de stent < 8,91 mm² ao USIC - RR=0,66 (0,24-0,85) IC 95% (p=0,006). A análise multivariada evidenciou que o único parâmetro preditor de reestenose foi volume de stent < 119,8 mm³ (p=0,01). CONCLUSÃO: Com base nestes resultados, conclui-se que, em população de pacientes com alto risco para desenvolvimento de reestenose, o calibre do vaso esteve relacionado de forma inversa à taxa de reestenose, sendo o volume de stent pelo USIC < 119,8 mm³ considerado preditor independente de reestenose.

Leptin Is Associated with Insulin Resistance in Japanese Migrants

Leptin and insulin are both influenced by body adiposity. Insulin plays an important role in the context of the metabolic syndrome (MS). We evaluated whether leptin was associated with insulin resistance and MS after adjusting for confounders in Japanese-Brazilian women. A total of 717 Japanese-Brazilian women aged >/=30 years were investigated for the presence of MS. They were submitted to clinical examination and laboratory measurements, including oral GTT, lipid profile, uric acid, C-reactive protein (CRP), insulin, and leptin levels. Insulin sensitivity was assessed by HOMA. Diagnosis of MS was based on the National Cholesterol Education Program criteria modified for Asians. Pearson correlation coefficient and logistic regression analysis were used. MS was diagnosed in 56% (95% CI 52-59); these subjects were older and had higher body mass index (BMI) and fat mass, and worse metabolic profile. Leptin and CRP levels were statistically greater in women with MS when compared to those without the syndrome (8.6 +/- 8.0 vs. 7.2 +/- 5.9 ng/mL and 0.219 +/- 0.848 vs. 0.360 +/- 0.852 mg/dL, p < 0.05). Leptin was significantly correlated to BMI, fat mass, waist circumference, HOMA-IR, and insulin but not to other components of MS, such as fasting plasma glucose, blood pressure, HDL-cholesterol, triglyceride, and CRP levels. Correlation between leptin and HOMA-IR or fasting insulinemia was maintained after adjustments for body adiposity. However, in logistic regression model, age, BMI, 2-h glucose, and uric acid were independently associated with MS, but not leptin. Adiposity-adjusted correlation of leptin with HOMA-IR and fasting insulinemia suggested that the former is associated with insulin resistance, despite the lack of independent association with the definition of the MS according to NCEP-ATP III. These findings in such Japanese-Brazilian population of high prevalence of MS need to be confirmed in other populations.

The association between glucose challenge test, obesity and pregnancy outcome in 6390 non-diabetic women

Objective: To evaluate the association between obesity, glucose challenge test (GCT) and pregnancy outcome.Methods: A prospective cohort study of 6854 consecutive gravid patients screened for gestational diabetes (GDM) using 50-gram GCT, at 24–28 weeks' gestation was performed. A screening value ⩾ 130 mg/dl was followed by 100 gr oral GTT. Patients who were diagnosed with GDM were excluded. For purpose of analysis patients were categorized by prepregnancy BMI and by different GCT thresholds. Maternal outcome was defined by rate of preeclampsia, gestational age at delivery, cesarean section (CS) rate and the need for labor induction. Neonatal outcome was defined by fetal size (macrosomia/LGA), arterial cord pH, respiratory complications and neonatal intensive care unit (NICU) admission.Results: Overall, a positive GCT result (GCT ⩾ 130 mg/dl) was identified in 2541/6854 (37%) women. GDM was further diagnosed in 464/6854 (6.8%) of subjects. In both groups of screening results ( > 130 mg/dl and < 130 mg/dl), the obese women were significantly older, gained more weight during pregnancy and had a lower rate of nulliparity in comparison to the non obese women. The obese women had higher rates of macrosomia, LGA and induction of labor. No difference was found in mean birth weight, the total rate of cesarean section, preterm delivery, 5 minute Apgar score ⩽ 7, mean arterial cord pH, NICU admission and a need for respiratory support in comparison to non obese women in both groups of screening results. A gradual increase in the rate of macrosomia, LGA and cesarean section was identified in both obese and non-obese women in relation to increasing GCT severity categories.Conclusion: Fetal size and cesarean section rate are associated with the degree of carbohydrate intolerance (screening results). Furthermore, obesity remains the main contributor impacting fetal size.

The association between preeclampsia and the severity of gestational diabetes: The impact of glycemic control

Objectives We sought to determine if the rate of preeclampsia is related to the severity of gestational diabetes mellitus (GDM), and if it can be decreased by optimizing glycemic control. Study design A retrospective analysis of prospectively collective data of 1813 patients with GDM was performed to determine the rate of preeclampsia. Patients were stratified after treatment was begun by level of glycemic control (well controlled was defined as mean blood glucose <95 mg/dL). The extent of hyperglycemia was analyzed by the level of the abnormality in the oral GTT and by the degree of abnormality of daily glucose control after treatment has begun. Severity of GDM was categorized using fasting plasma glucose (FPG) on a 3-hour oral GTT by 10 mg/dL increments. Results Overall, preeclampsia was diagnosed in 9.6% (174/1813) of diabetic patients. The GDM subjects who developed preeclampsia were significantly younger, had a higher nulliparity rate, were more obese, and gained significantly more weight during pregnancy. However, no difference was found in glycemic profile characteristics between the 2 groups. A comparison between patients with FPG <105 and FPG >105 revealed that the rate of preeclampsia increased significantly, 7.8% vs 13.8%, (O.R 1.81, 95%CI 1.3-2.51). For GDM patients with only mild hyperglycemia (FPG <105 mg/dL), no significant difference was found in the rate of preeclampsia. Preeclampsia rate was further evaluated in relation to level of glycemic control; for the well-controlled patients (mean blood glucose [MBG] <95 mg/dL, n = 994), similar rates of preeclampsia were found between each category of FPG severity. In contrast, in poorly controlled patients (MBG >95 mg/dL, n = 819), a comparison between severity threshold of FPG <115 and FPG >115 revealed that the preeclampsia rate was 9.8% vs 18% (O.R 2.56, 95%C.I. 1.5-4.3). In a logistic regression model, only prepregnancy BMI (O.R 2.3, 95%CI 1.16-2.30) and severity of GDM (O.R 1.7, 95%CI 1.21-2.38) were independently and significantly associated with an increased risk of preeclampsia. Conclusion The rate of preeclampsia is influenced by the severity of GDM and prepregnancy BMI. Optimizing glucose control during pregnancy may decrease the rate of preeclampsia, even in those with a greater severity of GDM.

Screening test for Gestational Diabetes

Three hundred pregnant women attending the antenatal out-patient clinic of TU Teaching Hospital between 24-28 weeks of gestation were screened for gestational diabetes using 50 g of oral glucose; venous blood plasma was drawn 1 hour later. Screening test value of &gt;140 mg/dl was taken as cut off for performing the 3-hour diagnostic oral glucose tolerance test, OGTT. Eleven [3.67%] pregnant women had their screening test value of &gt;140 mg/dl and were again subjected to the 3-hour oral GTT, out of which two of the cases (0.66%) were diagnosed as diabetic. Because of low prevalence of diabetes, we recommended only to screen women at high risk for gestational diabetes with 50 g oral glucose and a value of &gt;140 mg/dl taken as cut off for performing the 3-hour oral GTT.

Combining human placental lactogen with routine glucose challenge tests

Objective: To test the hypothesis that among gravidas with abnormal 1 hour glucose challenge tests (GCT), human placental lactogen (HPL) is higher for those found to have gestational diabetes. Study Design: Coincident with the GCT, serum was used to measure HPL by radioimmunoassay technique. Interassay and intraassay coefficients of variance were 6.0% and 1.4%, respectively. All GCT > 130 mg% were followed by a 100 g oral GTT (Carpenter criteria). Results: Two hundred fifty-seven women whose mean age was 29.4 years were studied. Twenty-two percent (57/257) had an elevated GCT. Forty-nine percent (25/57) of those with a positive screen were found to have an abnormal GTT. The mean HPL for this group of 25 women with gestational diabetes was 5.85 ± 2.55 mg/mL and was significantly higher than the 3.38 ± 1.40 mg/mL level in the 32 (32/57) women who had an abnormal GCT but a normal GTT, P = .034. The mean HPL for women who had a normal GCT screen was 4.68 ± 1.64 mg/mL and was not statistically different from the HPL in women with an abnormal GCT but who had a normal GTT, P = .1. However, among the 11 women with a normal GCT but whose infants weighed >4000 g, the mean HPL was 5.83 ± 1.29 mg/mL, which was similar to the mean HPL found in women with gestational diabetes. Conclusion: Our findings suggest that HPL levels are lower in groups of women with positive GCT but a negative GTT when compared to groups with a positive GCT but an abnormal GTT. Adjuvant HPL measurements may improve the positive predictive value of GCT.

Effect of Angiotensin Converting Enzyme Inhibitor (ACEI) on Glucose Intolerance in OLETF Rats

Using three month-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats as a NIDDM model and Long-Evans Tokushima Otsuka (LETO) rats as the control, we examined the effect of ACEI on the onset of diabetes mellitus. Oral administration of captopril (ACEI) was started from the age of 13 to 32 weeks (A group) and from the age of 25 to 32 weeks (B group). Oral GTT (oGTT) was performed at 4-week intervals from 12 weeks to 32 weeks of the age in OLETF and LETO rats. Body weights did not change significantly in either the A or B groups, compared with that in the control group. In oGTT for OLETF rats at 28 and 32 weeks of age, blood glucose levels in the A group were lower at 120 min after glucose administration than those in the B and control groups. In LETO rats, there were no significant changes in blood glucose levels in oGTT in any group. GLUT4 protein concentrations in the skeletal muscle and adipocytes were not significantly changed in any group. These data suggest that ACEI improves the glucose intolerance in NIDDM model rats through some factor other than changes in GLUT4 concentrations.

The hyperglycemia and hyponatremia response of patients during operative hysteroscopy with 5% dextrose in water (D5W)

In 20 patients undergoing operative hysteroscopy using D5W, the rate of hyperglycemia and hyponatremia was examined. All patients exhibited hyperglycemia during and two hours after the procedure as follows: ten patients had hyperglycemia but with less than 100% increase from the normal level of serum glucose, two patients had between a 100% and 300% increase, and eight patients had more than a 300% increase. The rate of hyponatremia was higher in group three than one (7/8 versus 1/10, P=0.0037). The oral GTT was normal in all of the patients. One explanation of these results is that the difference in absorption of glucose is the cause of different hyperglycemic responses. Can we find a test to distinguish these groups prior to hysteroscopic operation?