Glucose Tolerance Test

Background A previous study has demonstrated that symptoms suggestive of dumping syndrome appear after a provocation test early after laparoscopic sleeve gastrectomy (LSG) in 45 % of patients, and these are mainly related to early dumping. The aim of this study is to evaluate the evolution of dumping symptoms during the first postoperative year. Methods Twenty-five non-diabetic morbidly obese patients (6 male, 19 female) were evaluated with an oral glucose tolerance test (OGTT) preoperatively, at 6 weeks and at 6 months postoperatively. In addition, 12 of them repeated the OGTT at 12 months after LSG. Sigstad score was used to separate dumpers from non-dumpers and Arts' questionnaire to differentiate between early and late dumping. Insulin and glucose levels were also measured. Results Sigstad score remained significantly elevated at 6 and 12 months postoperatively compared to preoperative values. Symptoms suggestive of dumping syndrome were recorded in 40 % of patients at 6 months and in 33 % at 12 months postoperatively. Arts' questionnaire demonstrated that early dumping score remained higher compared to baseline at 6 and 12 months postoperatively. Late dumping scores increased gradually during the time and that difference was statistically significant at 12 months after LSG. Hypoglycaemia occurred at 33 % of patients both at 6 and 12 months postoperatively.

Leptin resistance is a hallmark of obesity, but its etiology is unknown, and its clinical measurement is elusive. Leptin-sensitive subjects have normal resting energy expenditure (REE) at a low leptin concentration, while leptin-resistant subjects have a normal REE at a higher leptin concentration; thus, the ratio of REE:Leptin may provide a surrogate index of leptin sensitivity. We examined changes in REE and leptin in a cohort of 17 obese subjects during experimental weight loss therapy with the insulin-suppressive agent octreotide-LAR, 40 mg i.m. q28d for 6 months. Six subjects lost significant weight (>10%) and BMI (>-3 kg/m(2)) with a 34% decline in leptin and a 46% decrease in insulin area under the curve (IAUC) to oral glucose tolerance testing. These subjects maintained their pretreatment REE, and thus exhibited a rise in REE:Leptin, while the other 11 showed minimal changes in each of these parameters. For the entire cohort, the change in IAUC correlated negatively wi...

The prevalence and associated factors of diabetes mellitus (DM) and impaired glucose tolerance (IGT) were studied in a tribal community with an apparently high diabetes prevalence. A sample of 724 subjects aged Ն 25 years was selected using a multi-stage cluster method and underwent a 75 g oral glucose tolerance test. The crude prevalence of DM and IGT were 8.3 % (men 9.9 %; women 7.5 %) and 7.9 % (men 4.1 %; women 9.7 %), respectively. Age-adjusted prevalence rates, according to the standard population of Segi, were 10.4 % (95 % CI 7.7-13.2) and 9.8 % (95% CI 7.2-12.5) for DM and IGT, respectively. No urban/rural differences were found in the prevalence rates of DM and IGT. New cases (5.1%) were almost twice as common as previously known cases (3.2 %). Family history of diabetes, obesity, and advanced age were associated with higher rates of diabetes. The results confirmed that diabetes is common in the Danagla community compared to other communities of northern Sudan. Varying environmental, nutritional, and genetic factors may contribute to this high prevalence. These findings will have profound impact on the health services for this community and the Sudan as a whole.

OBJECTIVE To study the effects of long-term growth hormone (GH) treatment on lipid metabolism and carbohydrate tolerance in GH-deficient adults. DESIGN Open trial of GH treatment for 4 years. GH dose was (median, range) 0·025 (0·010-0·050) IU/kg daily. PATIENTS Thirteen GH-deficient hypopituitary adults (seven men, six women), aged (median, range) 47 (24-65) years were followed for 4 years. MEASUREMENTS Fasting lipids, lipoproteins, apolipoproteins, glucose and insulin concentrations were measured at yearly intervals during GH therapy. A 75-g oral glucose tolerance test (OGTT) was also performed yearly, during which circulating glucose and insulin were measured at 30-minute intervals for 3 h. RESULTS Fasting total and low density lipoprotein (LDL) cholesterol concentrations decreased on GH therapy, but no change was observed in fasting triglyceride or high density lipoprotein (HDL) concentrations. Compared to pretreatment values, total and LDL cholesterol levels were significantly lower at 1 year (mean Ϯ SEM) (6·39 Ϯ 0·46 vs. 5·71 Ϯ 0·38 mmol/l, P < 0·05; 4·46 Ϯ 0·36 vs. 3·24 Ϯ 0·20 mmol/l, P < 0·01, respectively) and the reductions were maintained for

Volume 152 Number 8 14. Winer BJ. Statistical principles in experimental design. 2d ed. New York: McGraw-Hill, 1971:545. 15. Caritis SN, ToigG, Heddinger LA, Ashmead G. A doubleblind study comparing ritodrine and terbutaline in the treatment of preterm labor. AM J OBSTET GvNECOL 1984;150:7. Evaluation of ritodrine as loading dose 16. Caritis SN, Wong LK, Lin LS. Differences in pharmacokinetic behavior of ritodrine in pregnant and nonpregnant rhesus monkeys [Abstract 349]. San Francisco: Society for Gynecologic Investigation, thirty-first annual meeting, March 21-24, 1984.

We propose that deletion of pro-melanin-concentrating hormone (pMCH) would increase energy expenditure and further improve glucose tolerance in mice lacking stearoyl-coA desaturase-1 (SCD1). To test our hypothesis, we bred and metabolically challenged Pmch-/-; Scd1-/- double-knockout mice, with comparison to Pmch-/- mice; Scd1-/- mice and C57Bl/6J controls. Deletion of both Pmch and Scd1 increased both food intake and energy expenditure relative to control mice. Pmch-/-; Scd1-/- double-knockout mice had improved glucose tolerance relative to control mice. The majority of the metabolic effects were contributed by inactivation of the Scd1 gene. We conclude that the increased food intake and increased energy expenditure of Scd1-/- mice are independent of the neuropeptide melanin-concentrating hormone.

We compared the increases in the prevalence of gestational diabetes mellitus (GDM) based on the 1999 World Health Organization (WHO) criteria and its risk factors in Tianjin, China, over a 12-year period. We also examined the changes in the prevalence using the criteria of International Association of Diabetes and Pregnancy Study Group (IADPSG).

Aims/hypothesis: Preferential visceral adipose tissue (VAT) accumulation has been clearly associated with insulin resistance. In contrast, the impact of visceral obesity on beta cell function is controversial. Methods: In 62 non-diabetic women and men (age 24-69 years, BMI 21-39 kg/m 2 ), we measured VAT and subcutaneous adipose tissue (SAT) fat mass by magnetic resonance imaging. We also measured insulin secretion and beta cell function by C-peptide deconvolution and physiological modelling of data from a frequently sampled, 75-g, 3-h OGTT, respectively. Results: VAT (range 0.1-3.1 kg) was strongly related to sex, age and BMI; SAT was related to sex and BMI. Controlling for sex, age, BMI and SAT by multivariate analysis, excess VAT was associated with a clinical phenotype comprising higher plasma glucose levels, BP, heart rate and serum transaminases. The corresponding metabolic phenotype consisted of insulin resistance (partial r=−0.38) and hyperinsulinaemia (partial r=0.29). The latter, however, was appropriate for the degree of insulin resistance regardless of obesity and abdominal fat distribution. Moreover, none of the model-derived parameters describing beta cell function (glucose sensitivity, rate sensitivity and potentiation) was independently associated with excess VAT. Conclusions/interpretation: In non-diabetic Caucasian adults of either sex, preferential visceral fat deposition in itself is part of an insulin-resistant phenotype. The insulin secretory response to a physiological challenge is increased to fully compensate for the insulin resistance, but the dynamics of beta cell function (glucose sensitivity, rate sensitivity and potentiation) are largely preserved.

The purpose of this study was to investigate the effect of endurance training (10 weeks) on previously reported alterations of lactate exchange in obese Zucker fa/fa rats. We used sarcolemmal vesicles to measure lactate transport capacity in control sedentary rats, Zucker (fa/fa), and endurance trained Zucker (fa/fa) rats. Monocarboxylate transporter (MCT) 1 and 4 content was measured in sarcolemmal vesicles and skeletal muscle. Training increased citrate synthase activity in soleus and in red tibialis anterior, and improved insulin sensitivity measured by intraperitoneal glucose tolerance test. Endurance training increased lactate influx in sarcolemmal vesicles at 1 mM of external lactate concentration and increased MCT1 expression on sarcolemmal vesicles. Furthermore, muscular lactate level was significantly decreased after training in red tibialis anterior and extensor digitorum longus. This study shows that endurance training improves impairment of lactate transport capacity that is found in insulin resistance state like obesity and type 2 diabetes.

We studied the impact of a training program on glucose tolerance in gestational diabetes mellitus. Women with gestational diabetes mellitus (N = 19) were randomized into either group I, a 6-week diet alone group (24 to 30 kcal/kg/24 hours; 20% protein, 40% carbohydrate, 40% fat), or group II, which followed the same diet plus exercise (20 minutes three times a week for 6 weeks). An arm ergometer was used to maintain heart rate in the training range. Glycemic response was monitored by glycosylated hemoglobin, a 50 gm oral glucose challenge with a fasting and 1-hour plasma glucose, and blood glucose selfmonitoring, fasting and 1 hour after meals. Week 1 glycemic parameters were the same for both groups.

Objective Numerous genes have been associated with the risk for type 2 diabetes mellitus (DM2). In an attempt to understand how specific variants of different genes interact and intervene in the molecular and physiological mechanisms of disorders such as diabetes or insulin resistance, the search for gene-gene interactions is constantly growing. We searched for a possible interaction between two polymorphisms (Trp64Arg of ADRB3 gene and-75G/A of APOA1 gene) and the risk for DM2 in a population from southern Spain. Design and methods A cross-sectional study in southern Spain of 1020 people, aged 18-65 years. All persons underwent a clinical, anthropometrical and biochemical evaluation, including an oral glucose tolerance test (OGTT). Insulin resistance was measured by homeostasis model of assessment (HOMA). The polymorphisms-75G/A of APOA1 and Trp64Arg of ADRB3 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR, respectively. Results The genotype frequencies of the-75G/A polymorphism of the APOA1 gene were 62•7% GG, 25•7% GA and 11•6% AA, whereas for the Trp64Arg polymorphism of the ADRB3 gene, they were 87•5% Trp/Trp, 11•7% Trp/Arg and 0•8% Arg/Arg. Subjects with both gene variants had a greater odds ratio (OR) of having DM2 [OR = 5•5; 95% confidence interval (CI) = 1•2-23•5] than persons with one or none of the variants, after adjusting for age, sex, body mass index (BMI) and homeostasis model assessment of insulin resistance (HOMA-IR). Conclusions Joint association of allele-75A (APOA1) and allele Arg64 (ADRB3) increase the risk of DM2 in a population from southern Spain.

A high fasting glucose level may be a marker not only for microvascular complications, but also for macrovascular complications. We evaluated the clinical significance of a high fasting glucose level (Ն110 mg/dL), detected either at baseline or during follow-up, in the Bezafibrate Infarction Prevention (BIP) study.

Introduction Patients with history of gestational diabetes (GDM) are at high risk for developing diabetes mellitus (DM) after pregnancy. This study investigates the rate of GDM patients who received screening and the prevalence of DM in the early post-partum period. Materials and methods This study included 78 patients diagnosed and treated for GDM between January 2005 and December 2007. They were evaluated whether or not they were screened with 75 g oral glucose tolerance test (OGTT) or fasting blood glucose measurement at post-partum 6–12-week period. The rates of DM and impaired glucose tolerance (IGT) were determined. Results Of 78 GDM patients only 10 (12.8%) patients were screened with OGTT and 27 (34.6%) patients were screened with fasting blood glucose (FBG) measurement. 41 (52.6%) patients did not receive any post-partum screening. Insulin treated patients during pregnancy underwent OGTT more frequently (p = 0.008). We found that 61% of the patients who did not receive any screening test were seen by a doctor for any reason during this period. DM was diagnosed in 50% of patients who underwent OGTT and 7.4% of patients who underwent FBG measurement during early post-partum period (p = 0.013). Conclusion Despite the fact that GDM is generally strictly and carefully monitored during pregnancy, it is usually neglected in the post-partum period. Insulin treated patients during pregnancy should be informed better for post-partum screening with OGTT. OGTT appears to be a better way of screening to diagnose DM.

To evaluate the effectiveness of an ambulatory program for glycemic control of women with gestational diabetes mellitus (GDM). A total of 33 women with GDM whose FBS from OGTT &gt; or = 105 mg/dl were scheduled to attend weekly ambulatory care for dietary therapy with their family. FBS and 2-hour postprandial blood glucose were monitored every visit for a few weeks. At the end of this program, those with poor glycemic control were admitted for further tight dietary control by conventional 3-day course after which insulin was finally started for the women whose glycemic control remained poor. After the ambulatory program, 14 of 33 cases (42.4%) achieved good glycemic control without hospitalization. Another 6 cases (18.2%) did not need insulin therapy after admission for 3-day intensive dietary therapy. Altogether, 20 out of 33 cases (60.6%) of GDM whose FBS from OGTT &gt; or = 105 mg/dl could avoid insulin therapy after attending the ambulatory program alone or with additional 3-day...

As there have been few studies in North India of the prevalence of diabetes within the past decade, this study aimed to assess the prevalence and risk factors associated with diabetes in the North Indian city of Chandigarh. This cross-sectional survey of 2227 subjects (response rate: 94%), aged ≥20 years and representative of the urban Chandigarh population, was conducted from April 2008 to June 2009. Fasting plasma glucose (FPG) and 2-h plasma glucose (2hPG) following ingestion of 75 g of an anhydrous glucose equivalent were estimated by glucometer in all subjects except those with known diabetes, in whom only FPG was measured. Diagnosis of diabetes was based on 1999 WHO criteria. The collected prevalence data was age-standardized for the Chandigarh population, and multivariate logistic-regression analysis was used to correlate risk factors with the presence of diabetes. A total of 349 subjects (15.7%, 95% CI: 13.9-16.9) were diabetic, comprising 210 (9.4%) with known diabetes and 139 (6.2%) with newly diagnosed diabetes, and 344 (15.4%, 95% CI: 14.3-17.1) subjects were prediabetic. The age-standardized prevalence of diabetes and prediabetes were 11.1% (95% CI: 9.7-12.4) and 13.2% (95% CI: 11.8-14.6), respectively. Age ≥50 years, a family history of diabetes, BMI ≥23 kg/m(2), abdominal obesity and hypertension were significantly and positively associated with the presence of diabetes, whereas educational status was negatively associated with diabetes (P&amp;lt;0.001 for all). The age-standardized prevalence of diabetes and prediabetes were 11.1% and 13.2%, respectively. Older age, family history of diabetes, obesity and hypertension were positively related, while educational status was negatively related, to the presence of diabetes.

Screening and diagnostic criteria for gestational diabetes (GDM) are inconsistent across Europe, and the development of a uniform GDM screening strategy is necessary. Such a strategy would create opportunities for more women to receive timely treatment for GDM. Developing a consensus on screening for GDM in Europe is challenging, as populations are diverse and healthcare delivery systems also differ. The European Board & College of Obstetrics and Gynaecology (EBCOG) has responded to this challenge by appointing a steering committee, including members of the EBCOG and the Diabetic Pregnancy Study Group (DPSG) associated with the EASD, to develop a proposal for the use of uniform diagnostic criteria for GDM in Europe. A proposal has been developed and has now been approved by the Council of the EBCOG. The current proposal is to screen for overt diabetes at the first prenatal contact using cutoff values for diabetes outside pregnancy, with particular efforts made to screen high-risk groups. When screening for GDM is performed at 24 weeks' gestation or later, the proposal is now to use the 75 g OGTT with the new WHO diagnostic criteria for GDM. However, more research is necessary to evaluate the best GDM screening strategy for different populations in Europe. Therefore, no clear recommendation has been made on whether a universal one-step, two-step or a risk-factorbased screening approach should be used. The use of the same WHO diagnostic GDM criteria across Europe will be an important step towards uniformity.

Insulin resistance has been suggested to increase the risk of certain diseases, including osteochondrosis and laminitis. Our objective was to evaluate the effect of adaptation to high-glycemic meals on glucose-insulin regulation in healthy Thoroughbred weanlings. Twelve Thoroughbred foals were raised on pasture and supplemented twice daily with a feed high in either sugar and starch (SS; 49% nonstructural carbohydrates, 21% NDF, 3% crude fat on a DM basis) or fat and fiber (FF; 12% nonstructural carbohydrates, 44% NDF, 10% crude fat on a DM basis). As weanlings (age 199 +/- 5 d; BW 274 +/- 5 kg) the subjects underwent a modified frequently sampled i.v. glucose tolerance test. A series of 39 blood samples was collected from -60 to 360 min, with a glucose bolus of 300 mg/kg BW injected at 0 min and an insulin bolus of 1.5 mIU/kg BW at 20 min. All samples were analyzed for glucose and insulin, and basal samples also were analyzed for plasma cortisol, triglyceride, and IGF-I. The minima...

We have separated the effect of insulin on glucose distribution/transport, glucose disposal, and endogenous production (EGP) during an intravenous glucose tolerance test (IVGTT) by use of a dual-tracer dilution methodology. Six healthy lean male subjects (age 33 +/- 3 yr, body mass index 22.7 +/- 0.6 kg/m(2)) underwent a 4-h IVGTT (0.3 g/kg glucose enriched with 3-6% D-[U-(13)C]glucose and 5-10% 3-O-methyl-D-glucose) preceded by a 2-h investigation under basal conditions (5 mg/kg of D-[U-(13)C]glucose and 8 mg/kg of 3-O-methyl-D-glucose). A new model described the kinetics of the two glucose tracers and native glucose with the use of a two-compartment structure for glucose and a one-compartment structure for insulin effects. Insulin sensitivities of distribution/transport, disposal, and EGP were similar (11.5 +/- 3.8 vs. 10.4 +/- 3.9 vs. 11.1 +/- 2.7 x 10(-2) ml small middle dot kg(-1) small middle dot min(-1) per mU/l; P = nonsignificant, ANOVA). When expressed in terms of ability ...

Objective: We investigated whether a reduced iso-a acid derived from an extract of Humulus lupulus L., META060, had an effect on weight gain, body composition, and metabolism in a high-fat-diet (HFD) fed mouse model. Methods: Weight gain was monitored for up to 20 wk in mice receiving a low-fat diet, an HFD, or an HFD supplemented with META060 or rosiglitazone. Body composition was determined using dualenergy x-ray absorptiometric analysis. Indirect calorimetric measurements were performed to investigate the energy balance in the mice, and oral glucose tolerance tests were administered to examine the effect of META060 on the glycemic response. Results: The HFD-fed mice administered META060 for 14 wk had a significantly lower mean weight than HFD-fed mice (30.58 AE 0.5 versus 37.88 AE 0.7 g, P < 0.05). Indirect calorimetric measurements showed an increased metabolic flexibility in mice supplemented with META060. In addition, glucose tolerance was improved, comparable to the effects of rosiglitazone treatment. Conclusions: META060 has potential therapeutic value for managing obesity and insulin resistance, and further research into the mechanism of action is warranted.

Targeting glycosphingolipid synthesis has emerged as a novel approach for treating metabolic diseases. 32 (EXEL-0346) represents a new class of glucosylceramide synthase (GCS) inhibitors. This report details the elaboration of hit 8 with the goal of achieving and maintaining maximum GCS inhibition in vivo. 32 inhibited GCS with an IC 50 of 2 nM and achieved maximum hepatic GCS inhibition after four or five daily doses in rodents. Robust improvements in glucose tolerance in DIO mice and ZDF rats were observed after 2 weeks of q.d. dosing. Four weeks of dosing resulted in decreased plasma triglycerides and reduced hepatic fat deposition. Thus, 32 provides insight into the amount of metabolic regulation that can be restored following achievement of maximal target knockdown.

Purpose: We tested the feasibility and preliminary efficacy of a lifestyle intervention for middle-aged and older patients with schizophrenia and type-2 diabetes mellitus, using a randomized pre-test, post-test control group design. Method: Individuals with a diagnosis of schizophrenia or schizoaffective disorder over the age of 40 were randomly assigned to 24week Diabetes Awareness and Rehabilitation Training (DART; n = 32) groups or Usual Care plus Information (UCI; n = 32) comparison groups. Participants were recruited from board-and-care facilities and day treatment programs. Fifty-seven patients completed baseline and 6-month assessments consisting of an interview, measures of body mass index, blood pressure, fasting blood chemistry, and accelerometry. A mixed-model analysis of variance was used to analyze the data. Results: A significant group × time interaction was found for body weight, with patients in the DART group losing a mean of 5 lb and those in the UCI gaining a mean 6 lb. Significant group × time interactions were also found for triglycerides, diabetes knowledge, diabetes self-efficacy, and self-reported physical activity, but not for fasting plasma glucose or glycosylated hemoglobin. Conclusions: Group-based lifestyle interventions are feasible and produce positive health changes in middle-aged and older patients with schizophrenia and diabetes mellitus.

Nutritional management of animals during pregnancy can affect glucose and insulin dynamics in the resulting offspring through influences on fetal development. Additionally, high starch feeding in mature horses is associated with reduced insulin sensitivity and an increased risk for diseases such as obesity and laminitis. However, no study has yet evaluated the effect of feeding a high starch diet to pregnant mares on glucose and insulin dynamics in their offspring. Twenty late-gestation mares maintained on pasture were provided two-thirds of digestible energy requirements from isocaloric, isonitrogenous low starch (LS, n = 10) or high starch (HS, n = 10) feed. Their foals were assessed with an insulin-modified frequently sampled intravenous glucose tolerance test at 5, 40, 80, and 160 d of age. Baseline glucose concentrations, insulin sensitivity, and insulin-independent glucose clearance in 5-d foals were all greater than values observed in mature horses and declined towards mature values as foals reached 160 d of age. Baseline glucose concentrations were all within normal range, but higher in foals born from HS mares through 80 d of age. Insulin sensitivity was not different between dietary groups until a trend for lower insulin sensitivity in HS foals emerged at 160 d of age. These data are the first to characterize decreasing insulin sensitivity and glucose tolerance in Thoroughbred foals from 5 to 160 d of age. This study also presents the first data examining glucose and insulin dynamics in developing foals in response to maternal high starch diet.

The Sirt1/AMPK signaling pathway is a key sensor of energy status and regulates glucose and lipid metabolism. Leucine (Leu) activates Sirt1 by lowering its Km for NAD(+) and potentiates other sirtuin/AMPK-activators, resulting in improvement of insulin sensitivity. Since metformin (Met) converges on this pathway, we hypothesized that leucine would amplify its gluco-regulatory effects. The effects of Leu (24g/kg diet)+Met (0.05-0.5g/kg diet) combinations were compared to standard therapeutic Met (1.5g/kg diet; ~300mg/kg BW) on glycemic control in high fat diet induced insulin resistant mice for 6weeks. The effects of Leu on Met stimulation of Sirt1 and AMPK activities were further evaluated in adipocytes. Sub-therapeutic levels of Met combined with Leu resulted in increases in Sirt1 activity and in tissue P-AMPK/AMPK ratio and corresponding dose-responsive improvements in fasting and post-prandial glucose, in glucose response to an insulin tolerance test and in the area under the cur...

Background: Many volatile organic compounds are present in exhaled breath and may represent by-products of endogenous biological processes. Ethanol is produced via alcoholic fermentation of glucose by gut bacteria and yeast, while acetone derives from oxidations of free fatty acids, influenced by glucose metabolism. We hypothesized that the integrated analysis of breath ethanol and acetone would provide a good approximation of the blood glucose profile during a glucose load.

OBJECTIVE: This study was undertaken to investigate the relationship between pregnancy outcome and prepregnancy overweight or obesity in women with a normal glucose tolerance test. STUDY DESIGN: A historical cohort study of 2459 pregnant women systematically examined for gestational diabetes was performed. Information of oral glucose tolerance test results and clinical outcome were collected from medical records. RESULTS: The risk of hypertensive complications, cesarean section, induction of labor and macrosomia was significantly increased in both overweight women (body mass index [BMI] 25.0-29.9 kg/m 2 ) and obese women (BMI ≥ 30.0 kg/m 2 ) compared with women who were of normal weight (BMI 18.5-24.9 kg/m 2 ). The frequencies of shoulder dystocia, preterm delivery, and infant morbidity other than macrosomia were not significantly associated with maternal BMI. CONCLUSION: Prepregnancy overweight and obesity is associated with adverse pregnancy outcome in glucose-tolerant women. (Am J Obstet Gynecol 2003;189:239-44.) Correction In the article by Hnat et al (Hnat MD, Sibai BM, Caritis S, Hauth J, Lindheimer MD, MacPherson C, et al. Perinatal outcome in women with recurrent preeclampsia compared with women who develop preeclampsia as nulliparas. Am J Obstet Gynecol 2002;186:422-6), an incorrect revision date was listed. The correct date is June 18, 2001.

The acute and the subacute (15 days) hypoglycaemic and antihyperglycaemic effect of the two different doses (250, 500 mg/kg) of the aqueous extract from the leaves of Vitis vinifera L. were evaluated in this study. The aqueous extract was further fractionated through successive solvent extractions and the acute effect of different doses of its subfractions, 25 mg/kg for ethylacetate fraction, 80 mg/kg for n-butanol fraction and 375 mg/kg for remaining aqueous fraction were investigated using normal, glucose-hyperglycaemic and streptozotocin-induced diabetic rats. Blood glucose levels were measured according to the glucose oxidase method. Tolbutamide was used as a reference drug at a dose of 100 mg/kg. The antioxidant activity of the test samples was studied in the liver, kidney and heart tissues of diabetic rats by measuring malondialdehyde (MDA) and glutathion (GSH) levels. All results were compared to the diabetic control groups. The results showed that EtOAc Fr. was rich in polyphenolics and possessed a significant antihyperglycaemic and antioxidant activity equipotent with the reference hypoglycaemic agent (tolbutamide), when evaluated in diabetic rats.

The use of somatostatin analogues for the treatment of acromegaly is now well established. Recently long-acting preparations of octreotide and lanreotide have been introduced. In this study we have assessed the efficacy and tolerability of the long acting somatostatin analogue octreotide LAR in patients with acromegaly, and compared it with lanreotide SR. Five patients with active acromegaly were recruited; they were treated with lanreotide SR for 6 months and then, following a wash-out period, received octreotide LAR for 6 months. They were assessed at baseline, 3- and 6-months, by clinical score, GH and IGF1. Adverse effects were carefully monitored. Both treatments effectively reduced GH and IGF1 levels. Four of five patients achieved a mean GH level of <2.5 ng/ ml with both drugs; with octreotide LAR only, these patients also had GH <1 ng/ml after oral glucose loading. The clinical symptoms score improved significantly with octreotide LAR, as did the ring size; the clinical score correlated significantly with GH. Blood glucose was not adversely affected. All patients experienced minor GI symptoms with lanreotide SR, but less frequently with octreotide LAR. Both drugs caused biliary stasis and had a tendency to form biliary sludge. Octreotide LAR proved effective for the treatment of acromegaly and was well tolerated. Octreotide LAR had some advantages over lanreotide SR, although the differences were not great.

Retrospective clinical reports suggesting that traumatic stress populations display an increased propensity for glucose metabolism disorders were examined in a controlled prospective animal model. Stress-induced behavioural and hypothalamic-pituitary-adrenal (HPA) axis response patterns were correlated to central and peripheral parameters of glucose metabolism and signalling, and to body measurements in Sprague–Dawley rats exposed to predator scent stress. Forty days post-exposure, fasting blood glucose and insulin levels, oral glucose tolerance test, body weight and white adipose tissue mass, systemic corticosterone levels and brain expression of insulin receptor (IR) and insulin-sensitive glucose transporter 4 (GLUT4) protein levels were evaluated. In a second experiment inbred strains with hyper- (Fischer) and hypo- (Lewis) reactive HPA axes were employed to assess the association of metabolic data with behavioural phenomenology versus HPA axis response profile. For data analysis, animals were classified according to their individual behavioural response patterns (assessed at day 7) into extreme, partial and minimal response groups. The exposed Sprague–Dawley rats fulfilling criteria for extreme behavioural response (EBR) (20.55%) also exhibited significant increases in body weight, abdominal circumference and abdominal white adipose tissue mass; a hyperglycaemic oral glucose tolerance test; and fasting hyperglycaemia, hyperinsulinaemia and hypercorticosteronemia, whereas minimal responders (MBR) and control animals displayed no such disturbances. Hippocampal and hypothalamic expression of IR and GLUT4 protein were significantly lower in EBR than in MBR and control rats. The inbred strains showed no metabolic differences at baseline. Exposed Fischer rats displayed hyperglycaemia and hyperinsulinaemia, whereas Lewis rats did not. A significant protracted disorder of glucose metabolism was induced by exposure to a stress paradigm. This metabolic response was associated with the characteristic pattern of HPA axis (corticosterone) response, which underlies the behavioural response to stress.

The relations of dietary habits to insulin sensitivity and postprandial triglyceride metabolism were evaluated in 25 patients with nonalcoholic steatohepatitis (NASH) and 25 age-, body mass index (BMI)-, and gender-matched healthy controls. After a 7-day alimentary record, they underwent a standard oral glucose tolerance test (OGTT), and the insulin sensitivity index (ISI) was calculated from the OGTT; an oral fat load test was also performed in 15 patients and 15 controls. The dietary intake of NASH patients was richer in saturated fat (13.7% ؎ 3.1% vs. 10.0% ؎ 2.1% total kcal, respectively, P ‫؍‬ .0001) and in cholesterol (506 ؎ 108 vs. 405 ؎ 111 mg/d, respectively, P ‫؍‬ .002) and was poorer in polyunsaturated fat (10.0% ؎ 3.5% vs. 14.5% ؎ 4.0% total fat, respectively, P ‫؍‬ .0001), fiber (12.9 ؎ 4.1 vs. 23.2 ؎ 7.8 g/d, respectively, P ‫؍‬ .000), and antioxidant vitamins C (84.3 ؎ 43.1 vs. 144.2 ؎ 63.1 mg/d, respectively, P ‫؍‬ .0001) and E (5.4 ؎ 1.9 vs. 8.7 ؎ 2.9 mg/d, respectively, P ‫؍‬ .0001). The ISI was significantly lower in NASH patients than in controls. Postprandial total and very low density lipoproteins triglyceride at ؉4 hours and ؉6 hours, triglyceride area under the curve, and incremental triglyceride area under the curve were higher in NASH compared with controls. Saturated fat intake correlated with ISI, with the different features of the metabolic syndrome, and with the postprandial rise of triglyceride. Postprandial apolipoprotein (Apo) B48 and ApoB100 responses in NASH were flat and strikingly dissociated from the triglyceride response, suggesting a defect in ApoB secretion. In conclusion, dietary habits may promote steatohepatitis directly by modulating hepatic triglyceride accumulation and antioxidant activity as well as indirectly by affecting insulin sensitivity and postprandial triglyceride metabolism. Our findings provide further rationale for more specific alimentary interventions, particularly in nonobese, nondiabetic normolipidemic NASH patients. (HEPATOLOGY 2003;37:909-916.) Abbreviations: NASH, nonalcoholic steatohepatitis; NAFLD, nonalcoholic fatty liver disease; Tg, triglyceride; BMI, body mass index; OGTT, oral glucose tolerance test; ISI, insulin sensitivity index; VLDL, very low density lipoproteins; Apo, apolipoprotein; ANOVA, analysis of variance; AUC, area under the postprandial curve; IAUC, incremental area under the postprandial curve; SFA, saturated fatty acids; P:S ratio, polyunsaturated to saturated fat ratio. From the

Objective: To investigate the prevalence of type II Diabetes Mellitus (DM) and impaired glucose tolerance (IGT) and identify the metabolic abnormalities and risk factors associated with these conditions in an urban city of Yemen. Research design and methods: Cross-sectional, population-based study investigating 498 adults (245 males and 253 females) aged 25-65 years. The 1999 modified World Health Organization criteria were adopted for the diagnosis of Diabetes Mellitus and IGT. A standard questionnaire was applied and blood lipids, blood pressure, body mass index (BMI) and waist/hip ratio (WHR) were determined. Results: The overall prevalence of type II Diabetes Mellitus was 4.6% (7.4% in males and 2% in females). Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were found in 2% and 2.2% of the study population. Factors independently related to any abnormality in glucose tolerance, using logistic regression analysis, were sex, hyperlipidaemia, hypertriglyceridaemia, and hypertension; whereas sex and age related to DM. More than 80% of the type II diabetics were over the age of 40, 35% being hyperlipidaemic, 22% being hypertensive and 18% obese. Sixty percent of IGT subjects were hyperlipidaemic and 20% were obese. Approximately 78% of obese individuals (≥30 kg/m 2) had normal glucose tolerance. Conclusion: The prevalence of type II DM and its potential increase reflected by the high prevalence of obesity in normal glucose tolerance subjects in the Yemeni population constitutes a major public health problem.

OBJECTIVE-Optimal prevention of young-onset type 2 diabetes requires identification of the early-life modifiable risk factors. We aimed to do this using longitudinal data in 1,604 5-to 19-year-old initially nondiabetic American Indians. RESEARCH DESIGN AND METHODS-For type 2 diabetes prediction, we derived an optimally weighted, continuously distributed, standardized multivariate score (zMS) comprising commonly measured metabolic, anthropometric, and vascular traits (i.e., fasting and 2-h glucose, A1C, BMI, waist circumference, fasting insulin, HDL cholesterol, triglycerides, and blood pressures) and compared the predictive power for each feature against zMS. RESEARCH DESIGN AND METHODS All residents of a geographic area of the Gila River Indian Community in Arizona Ն5 years old were invited to participate in a longitudinal study of diabetes. Participants selected for the present analysis consisted of 1,604 children and adolescents free from diabetes, the majority of whom are Pima or Tohono O'odham Indians (17,18), who had one or more research examination during childhood or adolescence (i.e., Ն5 and Ͻ20 years old) and one or more follow-up examination at which diabetes was assessed. During the time frame of the present study, 2,828 nondiabetic children and adolescents were examined: 300 of these were excluded from the present analyses because data were missing for one of the predictor variables, and 924 were excluded because they did not have a follow-up examination. Those without follow-up tended to have been seen later in the study period than those with follow-up; they were also older and more likely to be male, but, accounting for these factors, there were no significant differences in metabolic variables.

Purpose: To characterize the intercorrelation of changes in intimal-medial thickness (IMT) among carotid artery sites and examine the influence of diabetes and sex on these correlations. Methods: Ultrasonographic IMT measurements from the near and far walls of common and internal segments in the arteries of 1207 participants of the Insulin Resistance Atherosclerosis Study (IRAS) were analyzed to estimate the underlying correlations of IMT changes (average of 5.2 years) among artery sites after correction for measurement error. Results: Differences in IMT progression associated with diabetes and sex were evident at all sites. IMT changes were strongly correlated between left and right arteries (r = 0.32-0.73) and near and far walls (r = 0.42-0.87). Correlations of IMT changes at corresponding sites of internal versus common segments were reduced from r = 0.32 among normal individuals to r = 0.09 among those with diabetes, but were similar for women and men. Conclusions: IMT progression is a diffuse process involving all carotid artery sites. Diabetes does not influence the bilateral and radial nature of progression, but reduces the correlation between distal sites within an artery. Pooling measurements across arteries and walls often yields the most efficient analyses.

Arterial hypertension is an insulin-resistant condition that has been associated with an increased incidence of diabetes. We assessed the prevalence of glucose abnormalities in a population of patients with essential hypertension. METHODS: In this cross-sectional study, 420 consecutively referred essential hypertensive patients were studied at 16 hypertension clinics in university and community hospitals of Spain. Fasting and 2-hour plasma glucose and insulin levels were determined in nondiabetic patients. RESULTS: An abnormal glucose metabolism was diagnosed in 68.5% (95% confidence interval [CI], 63.7%-72.9%) of the patients. Isolated insulin resistance, defined by a homeostasis model assessmentestimated insulin resistance (HOMA-IR) equal to or above 3.8, was shown in 9.3% (95% CI, 6.7%-12.5%); impaired fasting glucose in 11.2% (95% CI, 8.6%-14.7%); impaired glucose tolerance in 22.5% (95% CI, 18.5%-26.9%); silent undiagnosed type 2 diabetes in 11.5% (95% CI, 8.6%-14.5%); and known diabetes mellitus in 13.9% (95% CI, 10.4%-17.2%) of the patients. According to the European Group for the Study of Insulin Resistance and the Adult Treatment Program III criteria, the metabolic syndrome was diagnosed in 41.5% (95% CI, 35.9%-47.3%) and 47.9% (95% CI, 43.1%-52.8%) of the patients, respectively. The prevalence of left ventricular hypertrophy (defined by a left ventricular mass index [LVMI] Ͼ125 g/m 2) was 44.2%. The relation between HOMA-IR and LVMI was statistically nonsignificant, and the LVMI values in the HOMA-IR quartiles were similar. Only 27 patients (6.4%) showed good control of cardiovascular risk factors. In most patients (273, 65%; 95% CI, 60.3%-69.4%) 2 or more cardiovascular risk factors were identified as not being under control. CONCLUSIONS: Two thirds of the patients attending hypertension clinics with essential hypertension show an abnormal glucose metabolism. The metabolic syndrome can be identified in a substantial number of these patients, and 2 or more cardiovascular risk factors are not controlled in the majority of patients.

ISEC (Insulin SECretion) is a computer program which calculates pre-hepatic insulin secretion from plasma C-peptide measurements. The program uses a regression (population) model to derive parameters of C-peptide kinetics from subject's gender, type (normal, obese, non-insulin dependent diabetes mellitus), age, weight, and height. Insulin secretion is calculated as a piece-wise constant (step) function with flexible step length allowing for a fine resolution of the secretion profile between measurements. A constrained regularisation method of deconvolution is employed to carry out the calculations. The calculated profile satisfies three properties: (i) it fits the measurement within t.he given level of the measurement error, (ii) it is non-negative, and (iii) it has a minimum value of a regularisation criterion (norm of second differences) which quantifies the degree of deviation of the secretion profile from a straight line. Both theoretical aspects and specific fealures related to ISEC are considered. To exemplify the use of ISEC, pre-hepatic insulin secretion is calculated during meal tolerance test, frequently sampled intravenous glucose tolerance test, hyperinsulinaemic euglycaemic glucose clamp, and basal conditions with frequent sampling.

The seed powder of Datura metel was tested for its hypoglycemic activity in normal and alloxan-induced diabetic rats. Graded doses (25, 50 and 75 mg/kg, p.o.) of the seed powder when given to both normal and diabetic rats produced significant reduction in blood glucose at the 8 h. The effect was found to be dose dependent with all treatments at the doses administered.