Evaluating the glucose tolerance test in mice Andrikopoulos, Sofianos; Blair, Amy R; Deluca, Nadia ...
American journal of physiology: endocrinology and metabolism,
12/2008, Letnik:
295, Številka:
6
Journal Article
Recenzirano
University of Melbourne Department of Medicine (Austin Health/Northern Health), Heidelberg Repatriation Hospital, Heidelberg Heights, Victoria, Australia
Submitted 21 July 2008
; accepted in final ...form 18 September 2008
The objective of this study was to determine the optimal conditions under which to assess glucose tolerance in chow- and high-fat-fed C57BL/6J mice. Mice were fed either chow or high-fat diet for 8 wk. Variables tested were fasting duration (0-, 3-, 6-, and 24-h and overnight fasting), route of administration (intraperitoneal vs. oral) load of glucose given (2, 1, or 0.5 g/kg and fixed 50-mg dose), and state of consciousness. Basal glucose concentrations were increased in high-fat- compared with chow-fed mice following 6 h of fasting (9.1 ± 0.3 vs. 7.9 ± 0.4 mmol/l P = 0.01). Glucose tolerance was most different and therefore significant ( P = 0.001) in high-fat-fed mice after 6 h of fasting (1,973 ± 96 vs. 1,248 ± 83 mmol·l –1 ·120 min –1 ). The difference in glucose tolerance was greater following an OGTT (142%), in contrast to an IPGTT, with a 127% difference between high fat and chow. We also found that administering 2 g/kg of glucose resulted in a greater level of significance ( P = 0.0008) in glucose intolerance in high-fat- compared with chow-fed mice. A fixed dose of 50 mg glucose regardless of body weight was enough to show glucose intolerance in high-fat- vs. chow-fed mice. Finally, high-fat-fed mice showed glucose intolerance compared with their chow-fed counterparts whether they were tested under conscious or anesthetized conditions. We conclude that 2 g/kg glucose administered orally following 6 h of fasting is best to assess glucose tolerance in mice under these conditions.
intraperitoneal glucose tolerance test; oral glucose tolerance test; fasting; high-fat feeding; C57BL/6J
Address for reprint requests and other correspondence: S. Andrikopoulos, Univ. of Melbourne, Dept. of Medicine (AH/NH), Heidelberg Repatriation Hospital, 300 Waterdale Road, Heidelberg Heights, Victoria, Australia (e-mail: sof{at}unimelb.edu.au )
Recently, the absence of metabolic effects from nonnutritive sweeteners has been questioned.
The aim of this study was to evaluate the effects of sucralose consumption on glucose metabolism ...variables.
We performed a randomized controlled trial involving healthy subjects without comorbidities and with a low habitual consumption of nonnutritive sweeteners (n = 33/group).
The intervention consisted of sucralose consumption as 15% of Acceptable Daily Intake every day for 14 d using commercial sachets. The control group followed the same procedures without any intervention. The glucose metabolism variables (insulin sensitivity, acute insulin response to glucose, disposition index, and glucose effectiveness) were evaluated by using a 3-h modified intravenous-glucose-tolerance test before and after the intervention period.
Individuals assigned to sucralose consumption showed a significant decrease in insulin sensitivity with a median (IQR) percentage change of −17.7% (−29.3% to −1.0%) in comparison to −2.8% (−30.7% to 40.6%) in the control group (P= 0.04). An increased acute insulin response to glucose from 577 mU · L-1· min (350–1040 mU · L-1· min) to 671 mU · L-1· min (376–1010 mU · L-1· min) (P = 0.04) was observed in the sucralose group for participants with adequate adherence.
Sucralose may have effects on glucose metabolism, and our study complements findings previously reported in other trials. Further studies are needed to confirm the decrease in insulin sensitivity and to explore the mechanisms for these metabolic alterations. This trial was registered at www.clinicaltrials.gov as NCT02589002.
Glucose tolerance tests are used frequently in nonclinical research with laboratory animals, for example during characterization of obese phenotypes. Despite published standard operating procedures ...for glucose tolerance tests in rodents, how glucose doses should be calculated when obese
and lean animals are compared is not well documented. Typically the glucose dose is calculated as 2 g/kg body weight, regardless of body composition. With this approach, obese mice receive larger glucose doses than do lean animals, potentially leading to overestimation of glucose intolerance
in obese animals. In this study, we performed intraperitoneal glucose tolerance tests in mice with diet-induced obesity and their lean controls, with glucose doses based on either the total body weight or the lean body mass of the animals. To determine glucose tolerance, we determined the
blood glucose AUC during the glucose tolerance test. We found that the blood glucose AUC was increased significantly in obese mice compared with lean mice by 75% on average when glucose was dosed according to the lean body mass and by 87% when the glucose dose was calculated according to total
body weight. Therefore, mice with diet-induced obesity were approximately equally glucose intolerant between the 2 dose-calculation protocols. However, we recommend calculating the glucose dose according to the lean body mass of the mice, because doing so eliminates the concern regarding overdosing of obese animals.
We aimed to determine the upper and lower cutoff values to simplify the diagnosis of gestational diabetes mellitus (GDM). We investigated the 50-g oral glucose tolerance test (OGTT) results from 1441 ...pregnancies and identified 423 gravidas who underwent the 100-g OGTT from 2011 to 2019. We collected the results of 50- and 100-g OGTTs. Moreover, we obtained the sum of the 50-g OGTT and 0-hour values, and the sum of those levels and 1-hour values. We determined the upper cutoff at 50-g OGTT, 0-, 1-hour, sum of 50-g OGTT and 0-hour results, and sum of those levels and 1-hour results for the confirmation of GDM. Also, we determined the lower cutoff at these tests for the exclusion of GDM. The upper cutoffs in 50-g OGTT, 0-, 1-hour, the sum of 50-g OGTT and 0-hour were 222, 115, 212, and 315 mg/dL, respectively. The lower cutoffs in 50-g OGTT, 0-, 1-hour, the sum of 50-g OGTT and 0-hour were 131, 65, 151, and 208 mg/dL, respectively. In addition, we discovered that the upper and lower cutoffs in the sum of 50-g OGTT, 0- and 1-hour values were >516 and <373 mg/dL, respectively. We implemented these cutoffs to our study group at 50-g OGTT and 0-, 1-hour of 100-g OGTT. It could omit 2- and 3-hour sampling in 216 gravidas (51.1%). Our approach was able to simplify GDM diagnostic steps in half of our study group.
An ideal screening test for gestational diabetes should be capable of identifying not only women with the disease but also the women with a high risk of developing gestational diabetes mellitus ...(GDM). Screening and diagnosis are the main steps leading to the way of management. There is a lack of consensus among healthcare professionals regarding the screening methods worldwide. Different study groups advocate a variety of screening methods with the support of evidence-based comprehensive data. Some of the organizations suggest screening for high risk or all pregnant women, while others prefer to offer definitive testing without screening. Glycemic thresholds are also not standardized to decide GDM among different guidelines. Prevalence rates of GDM vary between populations and with the choice of glucose thresholds for both screening and definitive tests. One-step or two-step methods have been used for GDM diagnosis. However, screening includes selecting patients with historical risk factors, 50 g 1-h glucose challenge test, fasting plasma glucose, random plasma glucose, and hemoglobin A1c with different cutoffs. In this chapter, screening and diagnosis methods of GDM accepted by different study groups will be discussed which will be followed by the evaluation of different glycemic thresholds. Then the advantages and disadvantages of used methods will be explained and the chapter will finish with an evaluation of the current international guidelines.
Diabetes mellitus is increasing worldwide and reliable animal models are important for progression of the research field. The pig is a commonly used large animal model in diabetes research and the ...present study aimed to refine a model for oral glucose tolerance test (OGTT) in young growing pigs, as well as describing intravenous glucose tolerance test (IVGTT) in the same age group. The refined porcine OGTT will reflect that used in children and adolescents. Eighteen pigs were obtained one week after weaning and trained for two weeks to bottle-feed glucose solution, mimicking the human OGTT. The pigs subsequently underwent OGTT (1.75 g/kg BW) and IVGTT (0.5 g/kg BW). Blood samples were collected from indwelling vein catheters for measurements of glucose and the diabetes related hormones insulin, glucagon and active glucagon-like peptide-1. The study confirmed that pigs can be trained to bottle-feed glucose dissolved in water and thereby undergo an OGTT more similar to the human standard OGTT than previously described methods in pigs. With the refined method for OGTT, oral intake only consists of glucose and water, which is an advantage over previously described methods in pigs where glucose is given together with feed which will affect glucose absorption. Patterns of hormonal secretion in response to oral and intravenous glucose were similar to those in humans; however, the pigs were more glucose tolerant with lower insulin levels than humans. In translational medicine, this refined OGTT and IVGTT methods provide important tools in diabetes research when pigs are used as models for children and adolescents in diabetes research.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims
This study was designed to investigate the association between pancreatic fat content (PFC) and insulin secretory capacity as well as glucose tolerance in Korean adults.
Materials
A total of 39 ...participants (mean age 49.9 years, 53% males) without a previous history of diabetes, or those previously diagnosed as having diabetes but with less than 10 years of disease duration and no medication history were included. They were stratified according to the results of the oral glucose tolerance test (OGTT): normal glucose tolerance, prediabetes, and diabetes.
Methods
All participants underwent the proton magnetic resonance spectroscopy (1H‐MRS) to assess PFC. Insulin sensitivity and β‐cell function were measured by the frequently sampled intravenous glucose tolerance tests (FSIVGTT) and OGTT‐derived indices.
Results
As glucose tolerance deteriorated, parameters such as Stumvoll index, oral glucose insulin sensitivity index, homeostatic model assessment (HOMA)‐β, insulinogenic index and oral disposition index from the OGTT, and acute insulin response to glucose (AIR) and disposition index (DI) from the FSIVGTT were decreased. PFC increased with deterioration in glucose tolerance (NGT: 12.0%, prediabetes: 23.7%, and diabetes: 31.9%). Correlation analysis indicated that glucose levels at 60 and 120 min during the OGTT were positively correlated with PFC. Also, there was a significant negative correlation between PFC and DI as well as AIR derived from the FSIVGTT.
Conclusions
PFC evaluated by 1H‐MRS in Korean adults was higher in those diagnosed with diabetes than those with normal glucose tolerance status. PFC also showed a significant negative correlation with indices reflecting beta cell function.
Decreased first-phase insulin response (FPIR) during intravenous glucose tolerance testing (IVGTT) is an early indicator of β-cell dysfunction and predictor of type 1 diabetes (T1D).
Assess whether ...oral glucose tolerance test (OGTT) measures could serve as FPIR alternatives in their ability to predict T1D in autoantibody positive (Aab+) subjects.
OGTT and IVGTT were performed within 30 days of each other. Eleven OGTT variables were evaluated for (1) correlation with FPIR and (2) T1D prediction.
Type 1 Diabetes TrialNet "Oral Insulin for Prevention of Diabetes in Relatives at Risk for T1D" (TN-07) and Diabetes Prevention Trial-Type 1 Diabetes (DPT-1) studies clinical sites.
TN-07 (n = 292; age 9.4 ± 6.1 years) and DPT-1 (n = 194; age 15.1 ± 10.0 years) Aab + relatives of T1D individuals.
(1) Correlation coefficients of OGTT measures with FPIR and (2) T1D prediction at 2 years using area under receiver operating characteristic (ROCAUC) curves.
Index60 showed the strongest correlation in DPT-1 (r = -0.562) but was weaker in TN-07 (r = -0.378). C-peptide index consistently showed good correlation with FPIR across studies (TN-07, r = 0.583; DPT-1, r = 0.544; P < 0.0001). Index60 and C-peptide index had the highest ROCAUCs for T1D prediction (0.778 vs 0.717 in TN-07 and 0.763 vs 0.721 in DPT-1, respectively; P = NS), followed by FPIR (0.707 in TN-07; 0.628 in DPT-1).
C-peptide index was the strongest measure to correlate with FPIR in both studies. Index60 and C-peptide index had the highest predictive accuracy for T1D and were comparable. OGTTs could be considered instead of IVGTTs for subject stratification in T1D prevention trials.
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