Subsequent Oral Glucose Tolerance Test Research Articles

Insulin-Dendrimer Nanocomplex for Multi-Day Glucose-Responsive Insulin Therapy in Ossabaw Miniature Swine with Type 1 Diabetes

Background: Therapy for type 1 diabetes resulting from immunogenic destruction of the insulin-producing pancreatic beta cells has been a challenge for over 100 years. Delivering exogenous insulin to maintain euglycemia is a delicate balance between plasma glucose transport to insulin-responsive tissues, glucose absorption in the gut, and the pharmacodynamics of insulin. The synthesis of short- and long-acting insulins and use of insulin pumps have made great strides in the standard of diabetes care. Despite advances, hypoglycemia is a major limitation. There is no approved therapy that offers glucose-responsive insulin function. Toward this end we engineered a nanoscale complex combining both electrostatic and dynamic-covalent interactions between a synthetic dendrimer carrier and an insulin analogue modified with a high-affnity glucose-binding motif. Hypothesis: This insulin nanocomplex will yield an injectable insulin depot providing both glucose-sensitive and long-lasting insulin availability in a translation preclinical model. Methods: Ossabaw minature swine (41-59 kg; N=6) were made diabetic with alloxan, which was confirmed by stable hyperglycemia (228±43 mg/dL). Oral glucose tolerance tests (OGTT) were conducted at the diabetic baseline and each of the following 6 days after one subcutaneous injection of the insulin nanocomplex. Results: The basline OGTT elicted blood glucose of 350-450 mg/dL for 90 min of the 150 min OGTT, while serum insulin remained at ~5 μU/mL, nearly the detection limit. In contrast, 3 h after injection of insulin nanocomplex (~0.8-0.9 mg/kg) blood glucose decreased to 71±12 mg/dL. Subsequent OGTTs on days 1-6 increased blood glucose from normoglycemia to ~200 mg/dL and serum insulin increased to ~60-220 μU/mL, followed by return to nearly normolgycemia hours after the OGTT. Hypoglycemia was avoided in all pigs. Conclusions: The subcutaneous nanocomplex of a modified insulin and a synthetic dendrimer carrier produced a glucose-responsive insulin depot for week-long glycemic control following a single routine injection. These findings offer great promise for overcoming the hypoglycemia risk of intensive glucose control. Future studies should include additional physiological challenges of exercise and nutritional states. Support: Juvenile Diabetes Research Foundation 5-CDA-2020-947-A-N, Helmsley Charitable Trust 2019PG-T1D016 and 2102-04994, American Diabetes Association Pathway 1-19-ACE-31, National Science Foundation BMAT1944875, European Union-Next Generation EU LX22NPO5104, Czech Academy of Sciences RVO 6138963. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Metformin and exercise effects on postprandial insulin sensitivity and glucose kinetics in pre-and-diabetic adults.

The potential interaction between metformin and exercise on glucose-lowering effects remains controversial. We studied the separated and combined effects of metformin and/or exercise on fasting and postprandial insulin sensitivity in individuals with pre- and - type 2 diabetes (T2D). Eight T2D adults (60±4 years) with overweight/obesity (32±4 kg·m-2) under chronic metformin treatment (9±6 years; 1281±524 mg·day-1) underwent four trials; a) taking their habitual metformin treatment (MET), b) substituting during 96 h their metformin medication by placebo (PLAC), c) placebo combined with 50 min bout of high-intensity interval exercise (PLAC+EX), and d) metformin combined with exercise (MET+EX). Plasma glucose kinetics using stable isotopes (6,6-2H2 and [U-13C] glucose), and glucose oxidation by indirect calorimetry, were assessed at rest, during exercise, and in a subsequent oral glucose tolerance test (i.e., OGTT). Postprandial glucose and insulin concentrations were analyzed as mean and incremental area under the curve (iAUC), and insulin sensitivity was calculated (i.e., MATSUDAindex and OGISindex). During OGTT, metformin reduced glucose iAUC (i.e., MET and MET+EX lower than PLAC and PLAC+EX, respectively; P=0.023). MET+EX increased MATSUDAindex above PLAC (4.8±1.4 vs 3.3±1.0, respectively; P=0.018) and OGISindex above PLAC (358±52 vs 306±46 mL·min-1·m-2, respectively; P=0.006). Metformin decreased plasma appearance of the ingested glucose (Ra OGTT; MET vs PLAC, -3.5; 95% CI -0.1 to -6.8 µmol·kg-1·min-1; P=0.043). Metformin combined with exercise potentiates insulin sensitivity during an OGTT in individuals with pre- and - type 2 diabetes. Metformin's blood glucose-lowering effect seems mediated by decreased oral glucose entering the circulation (gut-liver effect) an effect partially blunted after exercise.

Effect of different levels of acute hypoxia on subsequent oral glucose tolerance in males with overweight: A balanced cross-over pilot feasibility study.

Previous research has shown that ≤60 min hypoxic exposure improves subsequent glycaemic control, but the optimal level of hypoxia is unknown and data are lacking from individuals with overweight. We undertook a cross-over pilot feasibility study investigating the effect of 60-min prior resting exposure to different inspired oxygen fractions (CON FI O2 =0.209; HIGH FI O2 =0.155; VHIGH FI O2 =0.125) on glycaemic control, insulin sensitivity, and oxidative stress during a subsequent oral glucose tolerance test (OGTT) in males with overweight (mean (SD) BMI=27.6 (1.3) kg/m2 ; n=12). Feasibility was defined by exceeding predefined withdrawal criteria for peripheral blood oxygen saturation (SpO2 ), partial pressure of end-tidal oxygen or carbon dioxide and acute mountain sickness (AMS), and dyspnoea symptomology. Hypoxia reduced SpO2 in a stepwise manner (CON=97(1)%; HIGH=91(1)%; VHIGH=81(3)%, p < 0.001), but did not affect peak plasma glucose concentration (CON=7.5(1.8) mmol∙L-1 ; HIGH=7.7(1.1) mmol∙L-1 ; VHIGH=7.7(1.1) mmol∙L-1 ; p=0.777; η2 =0.013), plasma glucose area under the curve, insulin sensitivity, or metabolic clearance rate of glucose (p > 0.05). We observed no between-conditions differences in oxidative stress (p > 0.05), but dyspnoea and AMS symptoms increased in VHIGH (p < 0.05), with one participant meeting the withdrawal criteria. Acute HIGH or VHIGH exposure prior to an OGTT does not influence glucose homeostasis in males with overweight, but VHIGH is associated with adverse symptomology and reduced feasibility.

Preference of Women for Gestational Diabetes Screening Method According to Tolerance of Tests and Population Characteristics.

AimsTo determine the preferred method of screening for gestational diabetes mellitus (GDM).Methods1804 women from a prospective study (NCT02036619) received a glucose challenge test (GCT) and 75g oral glucose tolerance test (OGTT) between 24-28 weeks. Tolerance of screening tests and preference for screening strategy (two-step screening strategy with GCT compared to one-step screening strategy with OGTT) were evaluated by a self-designed questionnaire at the time of the GCT and OGTT.ResultsCompared to women who preferred one-step screening [26.2% (472)], women who preferred two-step screening [46.3% (834)] were less often from a minor ethnic background [6.0% (50) vs. 10.7% (50), p=0.003], had less often a previous history of GDM [7.3% (29) vs. 13.8% (32), p=0.008], were less often overweight or obese [respectively 23.1% (50) vs. 24.8% (116), p<0.001 and 7.9% (66) vs. 18.2% (85), p<0.001], were less insulin resistant in early pregnancy (HOMA-IR 8.9 (6.4-12.3) vs. 9.9 (7.2-14.2), p<0.001], and pregnancy outcomes were similar except for fewer labor inductions and emergency cesarean sections [respectively 26.6% (198) vs. 32.5% (137), p=0.031 and 8.2% (68) vs. 13.0% (61), p=0.005]. Women who preferred two-step screening had more often complaints of the OGTT compared to women who preferred one-step screening [50.4% (420) vs. 40.3% (190), p<0.001].ConclusionsA two-step GDM screening involving a GCT and subsequent OGTT is the preferred GDM screening strategy. Women with a more adverse metabolic profile preferred one-step screening with OGTT while women preferring two-step screening had a better metabolic profile and more discomfort of the OGTT. The preference for the GDM screening method is in line with the recommended Flemish modified two-step screening method, in which women at higher risk for GDM are recommended a one-step screening strategy with an OGTT, while women without these risk factors, are offered a two-step screening strategy with GCT.Clinical Trial RegistrationNCT02036619 https://clinicaltrials.gov/ct2/show/NCT02036619

A rare challenging case of co-existent craniopharyngioma, acromegaly and squamous cell lung cancer.

SummaryCo-existence of craniopharyngioma and acromegaly has been very rarely reported. A 65-year-old man presented with visual deterioration, fatigue and frontal headaches. Magnetic resonance imaging revealed a suprasellar heterogeneous, mainly cystic, 1.9 × 2 × 1.9 cm mass compressing the optic chiasm and expanding to the third ventricle; the findings were consistent with a craniopharyngioma. Pituitary hormone profile showed hypogonadotropic hypogonadism, mildly elevated prolactin, increased insulin-like growth factor 1 (IGF-1) and normal thyroid function and cortisol reserve. The patient had transsphenoidal surgery and pathology of the specimen was diagnostic of adamantinomatous craniopharyngioma. Post-operatively, he had diabetes insipidus, hypogonadotropic hypogonadism and adrenocorticotropic hormone and thyroid-stimulating hormone deficiency. Despite the hypopituitarism, his IGF-1 levels remained elevated and subsequent oral glucose tolerance test did not show complete growth hormone (GH) suppression. Further review of the pre-operative imaging revealed a 12 × 4 mm pituitary adenoma close to the right carotid artery and no signs of pituitary hyperplasia. At that time, he was also diagnosed with squamous cell carcinoma of the left upper lung lobe finally managed with radical radiotherapy. Treatment with long-acting somatostatin analogue was initiated leading to biochemical control of the acromegaly. Latest imaging has shown no evidence of craniopharyngioma regrowth and stable adenoma. This is a unique case report of co-existence of craniopharyngioma, acromegaly and squamous lung cell carcinoma that highlights diagnostic and management challenges. Potential effects of the GH hypersecretion on the co-existent tumours of this patient are also briefly discussed.Learning points:Although an extremely rare clinical scenario, craniopharyngioma and acromegaly can co-exist; aetiopathogenic link between these two conditions is unlikely.Meticulous review of unexpected biochemical findings is vital for correct diagnosis of dual pituitary pathology.The potential adverse impact of GH excess due to acromegaly in a patient with craniopharyngioma (and other neoplasm) mandates adequate biochemical control of the GH hypersecretion.

Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test.

Impaired glucose tolerance (IGT) is diagnosed by a standardized oral glucose tolerance test (OGTT). However, the OGTT is laborious, and when not performed, glucose tolerance cannot be determined from fasting samples retrospectively. We tested if glucose tolerance status is reasonably predictable from a combination of demographic, anthropometric, and laboratory data assessed at one time point in a fasting state. Given a set of 22 variables selected upon clinical feasibility such as sex, age, height, weight, waist circumference, blood pressure, fasting glucose, HbA1c, hemoglobin, mean corpuscular volume, serum potassium, fasting levels of insulin, C-peptide, triglyceride, non-esterified fatty acids (NEFA), proinsulin, prolactin, cholesterol, low-density lipoprotein, HDL, uric acid, liver transaminases, and ferritin, we used supervised machine learning to estimate glucose tolerance status in 2,337 participants of the TUEF study who were recruited before 2012. We tested the performance of 10 different machine learning classifiers on data from 929 participants in the test set who were recruited after 2012. In addition, reproducibility of IGT was analyzed in 78 participants who had 2 repeated OGTTs within 1 year. The most accurate prediction of IGT was reached with the recursive partitioning method (accuracy = 0.78). For all classifiers, mean accuracy was 0.73 ± 0.04. The most important model variable was fasting glucose in all models. Using mean variable importance across all models, fasting glucose was followed by NEFA, triglycerides, HbA1c, and C-peptide. The accuracy of predicting IGT from a previous OGTT was 0.77. Machine learning methods yield moderate accuracy in predicting glucose tolerance from a wide set of clinical and laboratory variables. A substitution of OGTT does not currently seem to be feasible. An important constraint could be the limited reproducibility of glucose tolerance status during a subsequent OGTT.

Plasma Glycated CD59, a Novel Biomarker for Detection of Pregnancy-Induced Glucose Intolerance.

OBJECTIVEPlasma glycated CD59 (pGCD59) is an emerging biomarker in diabetes. We assessed whether pGCD59 could predict the following: the results of the glucose challenge test (GCT) for screening of gestational diabetes mellitus (GDM) (primary analysis); and the diagnosis of GDM and prevalence of large for gestational age (LGA) newborns (secondary analyses).RESEARCH DESIGN AND METHODSCase-control study of 1,000 plasma samples from women receiving standard prenatal care, 500 women having a normal GCT (control subjects) and 500 women with a failed GCT and a subsequent oral glucose tolerance test (case patients).RESULTSCompared with control subjects, the median (interquartile range) pGCD59 value was 8.5-fold higher in case patients and 10-fold higher in GDM patients, as follows: control subjects 0.33 (0.19); case patients 2.79 (1.4); GDM patients 3.23 (1.43) (P < 0.001); area under the receiver operating characteristic curve 0.92. LGA prevalence was 4.3% in the lowest quartile and 13.5% in the highest quartile of pGCD59.CONCLUSIONSOne pGCD59 measurement during weeks 24–28 identifies pregnancy-induced glucose intolerance with high sensitivity and specificity and can potentially identify the risk for LGA.

Lack of predictive power of plasma lipids or lipoproteins for gestational diabetes mellitus in Japanese women.

Aims/IntroductionTo determine the diagnostic potential of plasma lipids and apolipoproteins in gestational diabetes mellitus (GDM), we carried out a retrospective cohort study of 1,161 Japanese women at 20–28 weeks of gestation who underwent a glucose challenge test (GCT).Materials and MethodsA total of 1,161 Japanese women at 20–28 weeks of gestation underwent a GCT. Participants with a positive test (GCT[+]) underwent a subsequent oral glucose tolerance test. Clinical and biochemical parameters were determined and quantification of apolipoproteins (Apo), including ApoB, ApoB48, ApoA-I and ApoC-III, was carried out.ResultsThe prevalence of GCT(+; with a 130 mg/dL glucose cut-off) and GDM was 20% and 4%, respectively. There was a trend for increased triglycerides and ApoC-III in GDM(+) participants. However, the difference in plasma triglycerides, ApoC-III or ApoB48 did not reach statistical significance between GDM(+) and GDM(−) women. Values of 1-h glucose (P < 0.001) and fasting glucose (P = 0.002) were significant risk factors for GDM.ConclusionsPrediction of GDM using only the ApoC-III value is not easy, although triglycerides and ApoC-III were higher in the GDM(+) group. The present findings show no significant difference in plasma lipid levels between women diagnosed with GDM and those with normal glucose tolerance.

A Chinese risk score model for identifying postprandial hyperglycemia without oral glucose tolerance test

The aim of the study is to develop a risk score model for identifying postprandial hyperglycemia without oral glucose tolerance tests (OGTT) in Chinese population, and minimize the number of subjects needing further OGTT. Multivariable stepwise logistic regression was used to develop risk score models in a derivation cohort (7953 participants without known diabetes). The developed models were verified in a validation cohort (another 1455 subjects without known diabetes). All subjects had completed questionnaires, physical examination and OGTT. Performances of the risk score models were estimated using receiver operating characteristic curves. Two risk score models for screening postprandial hyperglycemia were developed. The simple model used non-invasive risk factors (age, height, weight, waist, systolic blood pressure, pulse, hypertension, dyslipidemia and family history of diabetes mellitus), and the full model contained additional variables [fasting blood glucose (FBG), triglyceride/high density lipoprotein cholesterol] obtainable by invasive laboratory tests. The area under receiver operating characteristic curve (AUC) of simple model was similar to FBG and glycated haemoglobin. The full model has the largest AUC [0.799 (0.789-0.809) and 0.730 (0.702-0.758)] in both derivation and validation cohorts (p < 0.001 compared with simple model, FBG, and glycated haemoglobin). At a cutoff point of 80, the sensitivity, specificity and percentage that needed subsequent OGTT were 75.97, 67.56 and 48.38%, respectively. We developed a risk score model for screening postprandial hyperglycemia based on routine clinical information. It could effectively identify patients at high-risk for postprandial hyperglycemia and remarkably reduce the number of subjects requiring OGTT.

Lifestyle interventions for diabetes mellitus type 2 prevention

Background and aims Transferring the results from clinical trials on type 2 diabetes prevention is the objective of the Diabetes in Europe-Prevention using Lifestyle, Physical Activity and Nutritional intervention (DE-PLAN) project in Catalonia, whose cost-effectiveness analysis is now presented. Patients and methods A prospective cohort study was performed in primary care involving individuals without diagnosed diabetes aged 45–75 years (n = 2054) screened using the questionnaire Finnish Diabetes Risk Score (FINDRISC) and a subsequent oral glucose tolerance test. Where feasible, high-risk individuals who were identified (n = 552) were allocated sequentially to standard care (n = 219), a group-based (n = 230) or an individual-level (n = 103) intensive (structured programme of 6 h using specific teaching techniques) lifestyle intervention (n = 333). The primary outcome was the development of diabetes (WHO). We evaluated the cost of resources used with comparison of standard care and the intervention groups in terms of effectiveness and quality of life (15D questionnaire). Results After 4.2-year median follow-up, the cumulative incidences were 18.3% (14.3–22.9%) in the intensive intervention group and 28.8% (22.9–35.3%) in the standard care group (36.5% relative-risk-reduction). The corresponding 4-year HR was 0.64 (0.47–0.87; P < .004). The incremental cost induced by intensive intervention compared with the standard was 106€ per participant in the individual level and 10€ in the group-based intervention representing 746€ and 108€ per averted case of diabetes, respectively. The estimated incremental cost-utility ratio was 3243€ per quality-adjusted life-years gained. Conclusion The intensive lifestyle intervention delayed the development of diabetes and was efficient in economic analysis.

Coste-efectividad de la intervención sobre el estilo de vida para prevenir la diabetes tipo 2

Background and aimsTransferring the results from clinical trials on type 2 diabetes prevention is the objective of the Diabetes in Europe-Prevention using Lifestyle, Physical Activity and Nutritional intervention (DE-PLAN) project in Catalonia, whose cost-effectiveness analysis is now presented. Patients and methodsA prospective cohort study was performed in primary care involving individuals without diagnosed diabetes aged 45-75 years (n=2054) screened using the questionnaire Finnish Diabetes Risk Score (FINDRISC) and a subsequent oral glucose tolerance test. Where feasible, high-risk individuals who were identified (n=552) were allocated sequentially to standard care (n=219), a group-based (n=230) or an individual-level (n=103) intensive (structured programme of six hours using specific teaching techniques) lifestyle intervention (n=333). The primary outcome was the development of diabetes (WHO). We evaluated the cost of resources used with comparison of standard care and the intervention groups in terms of effectiveness and quality of life (15D questionnaire). ResultsAfter 4.2-year median follow-up, the cumulative incidences were 18.3% (14.3-22.9%) in the intensive intervention group and 28.8% (22.9-35.3%) in the standard care group (36.5% relative-risk-reduction). The corresponding 4-year HR was 0.64 (0.47-0.87; P<.004). The incremental cost induced by intensive intervention compared with the standard was 106€ per participant in the individual level and 10€ in the group-based intervention representing 746€ and 108€ per averted case of diabetes, respectively. The estimated incremental cost-utility ratio was 3243€ per quality-adjusted life-years gained. ConclusionThe intensive lifestyle intervention delayed the development of diabetes and was efficient in economic analysis.

Predictors and Clinical Implications of a False Negative Glucose Challenge Test in Pregnancy

ObjectiveA common approach to screening for glucose intolerance in pregnant women is the use of a 50g glucose challenge test (GCT) in the late second trimester, followed by a diagnostic oral glucose tolerance test (OGTT) when the GCT is positive (1-hour post-challenge blood glucose ≥ 7.8mmol/L). As women with a negative GCT do not undergo the diagnostic OGTT, it is possible that they could have undiagnosed gestational diabetes (GDM) or gestational impaired glucose tolerance (GIGT). Thus, we sought to characterize predictors of a false negative GCT and its clinical implications. MethodsTwo hundred two women with a negative GCT screening test underwent subsequent OGTT, which enabled their stratification into two groups: (1) those with normal glucose tolerance on OGTT (n = 166) and (2) those with either GDM (n = 8) or GIGT (n = 28). ResultsThe 36 women found to have GDM or GIGT at the time of OGTT had higher GCT glucose values than those with normal glucose tolerance (mean 6.6mmol/L vs. 5.9mmol/L, P < 0.001), as well as poorer insulin sensitivity (P = 0.004) and pancreatic beta-cell function (P < 0.001). On logistic regression analysis, the only significant independent predictor of GDM/GIGT was the GCT glucose value (OR 2.19; 95% CI 1.40 to 3.41, P < 0.001). However, there was no clear GCT glucose threshold for identifying GDM/GIGT, consistent with its modest area under the receiver operating characteristic curve (0.71). Importantly, there were also no differences between the two groups in median length of gestation, median birth weight, prevalence of macrosomia, or proportion of low Apgar scores. ConclusionFalse negative GCTs cannot be readily predicted by risk factors. However, their clinical implications at delivery may be benign.

Is abnormal 50-g glucose-challenge testing an independent predictor of adverse pregnancy outcome?

Objective: To determine whether an abnormal 50-g glucose-challenge test (GCT) is independently associated with adverse pregnancy outcome. Methods: A retrospective study of women with abnormal GCT (>140 mg/dL) but normal subsequent 100-g oral glucose-tolerance test (OGTT). Pregnancy outcome was compared with that of women with normal GCT (<140 mg/dL). Results: Of the 79,153 women delivered during the study period, the results of the GCT were available for 14,268. Of these, 809 (5.7%) had an abnormal GCT and normal OGTT and were eligible for the study group. An abnormal GCT was independently associated with an increased risk for macrosomia (odds ratio [OR] = 2.0, 95% CI: 1.5–2.7), large for gestational age (OR = 1.6, 95% CI: 1.3–2.0), cesarean section (OR = 1.3, 95% CI: 1.1–1.6), respiratory morbidity (OR = 1.6, 95% CI: 1.1–2.7) and neonatal hypoglycemia (OR = 1.8, 95% CI: 1.1–3.2). In contrast, an abnormal GCT was associated with decreased risk for preterm delivery at less than 37 weeks (OR = 0.7, 95% CI: 0.5–0.9) and 34 weeks (OR = 0.3, 95% CI: 0.1–0.6). The association between abnormal GCT and adverse pregnancy outcome was unrelated to the degree of GCT abnormality except for cases in which the GCT was extremely high (≥180 mg/dL). Conclusion: Women with abnormal-GCT result are at increased risk for adverse pregnancy outcome even in the presence of a normal subsequent OGTT.

Circadian variation in the response to the glucose challenge test in pregnancy: implications for screening for gestational diabetes mellitus.

OBJECTIVEA common approach to screening for gestational diabetes mellitus (GDM) is the universal testing of all pregnant women with a 1-h, 50-g glucose challenge test (GCT), followed by a diagnostic oral glucose tolerance test (OGTT) in those in whom the GCT is positive (≥7.8 mmol/L). More important, the GCT is performed at any time of day, but there has been limited study of the effect of time of day on test performance. Thus, using their subsequent OGTT (performed in the morning), we sought to characterize the metabolic function of women with positive GCTs in relation to the timing of their test.RESEARCH DESIGN AND METHODSA total of 927 women with positive GCTs underwent a 3-h 100-g OGTT. They were stratified into four groups by time of day (hours) of their GCT: <0900 (n = 171), 0900–1059 (n = 288), 1100–1259 (n = 189), and ≥1300 (n = 279).RESULTSOn the OGTT, the prevalence of GDM progressively decreased across the GCT groups from <0900 h (26.9%) to 0900–1059 h (25.0%) to 1100–1259 h (21.7%) to ≥1300 h (21.5%; P = 0.0022). After adjustment for GDM risk factors, mean adjusted glucose area under the curve (AUCgluc) similarly decreased across the groups, while insulin sensitivity (Matsuda index) and β-cell function (Insulin Secretion-Sensitivity Index-2) progressively increased (all P < 0.0001). In particular, compared with the <0900- and 0900–1059-h groups, women whose positive GCT occurred after 1300 h had superior metabolic function, as evidenced by lower AUCgluc, higher insulin sensitivity, and better β-cell function (all P ≤ 0.0097).CONCLUSIONSAmong women with a positive GCT, those tested in the afternoon have better metabolic function and a lower risk of GDM on subsequent OGTT.

Screening for gestational diabetes mellitus: A prospective study in a tertiary care institution of North India

The aim of this study was to determine the relevance of universal screening for gestational diabetes mellitus (GDM) in the patients attending the antenatal clinic of a tertiary institute of North India. This was a prospective study conducted on 700 pregnant women attending the antenatal clinic of Lok Nayak Hospital, New Delhi at or before 24 weeks of gestation. All patients underwent screening with a 50-g 1-h glucose challenge test at 24-28 weeks of gestation. The women with an abnormal glucose challenge test subsequently underwent a diagnostic 3-h oral glucose tolerance test. All the patients were followed up till delivery. Out of 700, thirteen patients were lost to follow up and hence the final outcomes were measured on 687 patients. Out of 687, 613 patients (89.2%) had a normal glucose challenge test value, that is, <140 mg%, and 74 (10.8%) had a glucose challenge test value ≥140 mg%. On the subsequent oral glucose tolerance test, 64 (9.3%) had normal values and only 10 (1.5%) had an abnormal oral glucose tolerance test, that is, GDM. With such a low prevalence rate it appears to be unjustified to recommend universal screening for GDM. These findings may be considered as a basis for conducting larger, multicentric studies to establish the prevalence rate of GDM before deciding on a policy for screening.

An Oral Lipid Challenge and Acute Intake of Caffeinated Coffee Additively Decrease Glucose Tolerance in Healthy Men1–3

Lipid-induced insulin resistance has been investigated primarily with i.v. infusions, and caffeine-induced insulin resistance, with alkaloid caffeine. The effects of orally consumed lipids and coffee have not been established and to our knowledge have never been simultaneously investigated. The goals of this study were to determine whether an oral lipid challenge and caffeinated coffee would disrupt glucose homeostasis and to characterize their respective incretin responses. It was hypothesized that oral ingestion of saturated lipids would impair glucose tolerance and that caffeinated coffee would further hinder glucose management. Ten young, healthy males participated in 5 trials in a randomized, cross-over design. At time 0 h, they underwent an oral fat tolerance test (OFTT: 1 g lipid/kg body weight) or consumed water, followed 5 h later by caffeinated (5 mg/kg) coffee, decaffeinated coffee, or water. At 6 h, volunteers underwent an oral glucose tolerance test (OGTT). Consumption of the OFTT increased glucose concentrations (P < 0.05) after a subsequent OGTT. At 7 h, caffeinated coffee produced the highest glucose concentrations (P < 0.05). Glucagon-like peptide-1 active (GLP-1a) and glucose-dependent insulinotropic polypeptide (GIP) were both increased for up to 6 h in all OFTT trials (P < 0.05). Compared to all other treatments, caffeinated and decaffeinated coffee produced higher GLP-1a response at 6.25 h (P < 0.05), whereas only caffeinated coffee increased GIP secretion (P < 0.05). These results show that oral consumption of lipids and caffeinated coffee can independently and additively decrease glucose tolerance. Incretin hormones could explain at least in part this impaired glucose homeostasis.

264: Cost-effectiveness analysis of screening for GDM

Treatment of gestational diabetes mellitus (GDM) reduces the risk of perinatal and maternal complications associated with GDM, but data on the effectiveness of treatment have not been integrated with data on the accuracy of screening for GDM. The aim of this study was to assess the cost-effectiveness of screening for GDM. We developed a decision model to evaluate costs and effects of six screening strategies for GDM at several moments during pregnancy: random glucose measurement, fasting glucose measurement, 50 g glucose challenge test, risk factor assessment, risk factor assessment combined with a 50 g glucose challenge test (all followed by an oral glucose tolerance test (OGTT) if indicated) and universal screening with an OGTT. Costs and effects of the screening strategies were compared to a strategy without testing. Data on costs, accuracy measures and probabilities were extracted from the literature. The outcome measure of effect was a composite outcome of neonatal death, shoulderdystocia, and birth trauma. We calculated the costs to prevent one serious neonatal complication. Analyses were performed from the perspective of the healthcare system. All screening strategies reduced the risk of serious perinatal complications. At 24 weeks of pregnancy the most effective strategy was screening all women with an OGTT, however at the highest costs. Use of risk factor assessment combined with a 50 g glucose challenge test, and subsequent OGTT if indicated was the most cost-effective strategy. The incremental cost-effectiveness ratio ranged from ϵ23, 479 per prevented neonatal complication with risk factor assessment combined with the 50 g glucose challenge test to ϵ37, 037 per prevented neonatal complication for use of the 50 g glucose challenge test in all women. Screening for GDM with risk factor assessment combined with a 50 g glucose challenge test and an OGTT if indicated is the most cost-effective strategy.

Consumption of caffeinated coffee and a high carbohydrate meal affects postprandial metabolism of a subsequent oral glucose tolerance test in young, healthy males

Caffeine and caffeinated coffee (CC) elicit acute insulin insensitivity when ingested before a carbohydrate load. The effects of CC on glucose tolerance and insulin sensitivity when co-ingested with a high carbohydrate meal and on postprandial metabolism of a subsequent (second) carbohydrate load have not been studied. In a randomised, crossover design, ten healthy males ingested either CC (5 mg caffeine/kg body weight), decaffeinated coffee (DC) or water (W; equal volume) co-ingested with a high glycaemic index cereal followed 3 h later by a 75 g oral glucose tolerance test. After the initial meal, insulin area under the curve (AUC) and insulin sensitivity index did not differ between treatments, although glucose AUC for CC (107 (sem 18) mmol/l x 3 h) and DC (74 (sem 15) mmol/l x 3 h) was greater than W ( - 0.2 (sem 29) mmol/l x 3 h, P < 0.05). After the second carbohydrate load, insulin AUC for CC was 49 % and 57 % greater (P < 0.01) than for DC and W, respectively. Despite the greater insulin response, glucose AUC for CC (217 (sem 24) mmol/l x 2 h) was greater than both DC (126 (sem 11) mmol/l x 2 h, P = 0.01) and W (55 (sem 34) mmol/l x 2 h, P < 0.001). Insulin sensitivity index after the second meal was lower after CC (8.2 (sem 0.9)) compared with both DC (12.4 (sem 1.2), P < 0.01) and W (13.4 (sem 1.4), P < 0.001). Co-ingestion of CC with one meal resulted in insulin insensitivity during the postprandial phase of a second meal in the absence of further CC ingestion. Thus, CC may play a role in daily glycaemic management.

Maternal obesity and familial history of diabetes have opposing effects on infant birth weight in women with mild glucose intolerance in pregnancy

Objective. Pregnant women with an abnormal screening glucose challenge test (GCT) but without gestational diabetes mellitus (GDM) on subsequent oral glucose tolerance test (OGTT) are at increased risk of delivering macrosomic and large for gestational age (LGA) neonates. We thus sought to evaluate the maternal constitutional and biochemical factors that determine infant birth weight in this patient population.Methods. Women with an abnormal GCT were evaluated at the time of their OGTT in late pregnancy. This analysis was restricted to Caucasian women without GDM (N = 86). Maternal demographic and biochemical factors were evaluated in relation to infant birth weight and LGA.Results. After adjustment for length of gestation, birth weight was positively associated with pre-pregnancy body mass index (BMI) (r = 0.31, p = 0.0063) and negatively correlated with maternal serum levels of the insulin-sensitizing protein adiponectin (r = −0.30, p = 0.0084). On multiple linear regression analysis, pre-pregnancy BMI and weight gain in pregnancy were positive independent determinants of infant birth weight, while family history of diabetes emerged as a negative independent correlate. Logistic regression analysis confirmed that pre-pregnancy BMI was a positive predictor of LGA (odds ratio (OR) = 1.25, 95% confidence interval (CI) 1.05–1.49), whereas family history of diabetes was again identified as a negative determinant (OR = 0.10, 95% CI 0.02–0.59). In contrast, neither measures of glycemia nor insulin resistance/sensitivity were independently associated with birth weight or LGA.Conclusion. In pregnant women with an abnormal GCT but without GDM, pre-gravid maternal obesity predicts increased infant birth weight, whereas family history of diabetes is independently associated with decreased infant size.

National survey on the execution of the oral glucose tolerance test (OGTT) in a representative cohort of Italian laboratories

Recently revised diagnostic criteria for diabetes mellitus and the lack of universal agreement on the methodology for the screening and diagnosis of gestational diabetes mellitus (GDM) still generate inconsistency in execution of the oral glucose tolerance test (OGTT). The aim of the present survey was to evaluate the adherence of Italian laboratories to the internationally accepted guidelines in carrying out the OGTT for the diagnosis of diabetes in the general population and for the screening of GDM. A questionnaire was designed to investigate the following issues related to the OGTT: 1) the relationship between laboratories and diabetes centres for the definition of standard protocols; 2) the amount of glucose administered; 3) the number and timing of blood samples; 4) the procedures used for the screening and diagnosis of GDM; and 5) reference to WHO guidelines for the interpretation of the results. The questionnaire was administered to 400 specialists in laboratory medicine working in public or private laboratories nationwide participating in the "Italian External Evaluation of Quality in Laboratory Medicine" Study Group. The survey was completed in the period from June to September 2003. In the observation period, 241 questionnaires were returned by specialists working in laboratories scattered throughout 15 out of the 20 Italian regions. Only 50% of the laboratories performed the OGTT according to protocols defined in agreement with local reference diabetes centres. OGTT using 75 g of glucose in adults and 1.75 g/kg for children as recommended by WHO was performed by 87.1% of the laboratories. WHO indications to collect samples at baseline and at 120 min were followed by 33.2% of the centres. Higher variability was highlighted with respect to the methodology for GDM screening: 49.8% of the laboratories always adopted the two-step procedure consisting of a glucose challenge test (GCT) and subsequent OGTT in positive cases; 4.9% performed the 100-g OGTT with four blood samples; 1.6% the 75-g OGTT with two blood samples; and 2.7% the 75-g OGTT with four blood samples. More than 30% of the centres referred to different diagnostic schemes, 62% of which used individually chosen procedures amongst those reported above, 19% used only the GCT and no subsequent OGTT in positive cases, and 18.4% used a variety of completely different, arbitrarily chosen methods. Finally, only 25.6% of the laboratories referred to the WHO limits for interpretation of the results. For the Italian laboratories investigated, relevant variability was highlighted for performance of the OGTT in general and GDM screening in particular. A variable relationship between laboratories and diabetes centres was also detected, which might represent a relevant indicator for the need for rationalisation or standardisation of the method for performing an OGTT. These data highlight the need for greater collaboration between these different bodies. We suggest that other similar investigations should be carried out in other countries within the framework of the IFCC Global Campaign on Diabetes Mellitus.