scholarly journals Impaired β-cell function and decreased insulin sensitivity in subjects with normal oral glucose tolerance but isolated high glycosylated hemoglobin

2018 ◽  
Vol 65 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Qi Fu ◽  
Min Sun ◽  
Zhixiao Wang ◽  
Wei He ◽  
Yu Duan ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Glycosylated Hemoglobin ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cell ◽  
Β Cell Function

Identifying glucose thresholds for incident diabetes by physiological analysis: a mathematical solution

2015 ◽  
Vol 308 (7) ◽  
pp. R590-R596 ◽  
Author(s):  
Ele Ferrannini ◽  
Maria Laura Manca
Keyword(s):  
Insulin Sensitivity ◽  
Confidence Interval ◽  
Glucose Tolerance ◽  
Odds Ratio ◽  
Cell Function ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cell ◽  
Glucose Levels ◽  
Β Cell Function

Plasma glucose thresholds for diagnosis of type 2 diabetes are currently based on outcome data (risk of retinopathy), an inherently ill-conditioned approach. A radically different approach is to consider the mechanisms that control plasma glucose, rather than its relation to an outcome. We developed a constraint optimization algorithm to find the minimal glucose levels associated with the maximized combination of insulin sensitivity and β-cell function, the two main mechanisms of glucose homeostasis. We used a training cohort of 1,474 subjects (22% prediabetic, 7.7% diabetic) in whom insulin sensitivity was measured by the clamp technique and β-cell function was determined by mathematical modeling of an oral glucose tolerance test. Optimized fasting glucose levels were ≤87 and ≤89 mg/dl in ≤45-yr-old women and men, respectively, and ≤92 and ≤95 mg/dl in >45-yr-old women and men, respectively; the corresponding optimized 2-h glucose levels were ≤96, ≤98, ≤103, and ≤105 mg/dl. These thresholds were validated in three prospective cohorts of nondiabetic subjects (Relationship Between Insulin Sensitivity and Cardiovascular Disease Study, Botnia Study, and Mexico City Diabetes Study) with baseline and follow-up oral glucose tolerance tests. Of 5,593 participants, 452 progressed to diabetes. Similarly, in the three cohorts, subjects with glucose levels above the estimated thresholds had an odds ratio of 3.74 (95% confidence interval = 2.64–5.48) of progressing, substantially higher than the risk carried by baseline conventionally defined prediabetes [odds ratio = 2.32 (95% confidence interval = 1.91–2.81)]. The concept that optimization of glucose concentrations by direct measures of insulin sensitivity and β-cell function identifies gender- and age-specific thresholds that bear on disease progression is proven in a physiologically sound, quantifiable manner.

scholarly journals Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients

2011 ◽  
Vol 165 (1) ◽  
pp. 69-76 ◽  
Author(s):  
A Battezzati ◽  
A Mari ◽  
L Zazzeron ◽  
G Alicandro ◽  
L Claut ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Cell Function ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cell ◽  
Β Cell Function

BackgroundCystic fibrosis (CF)-related diabetes is a leading complication of CF and is associated with pulmonary and nutritional deterioration, years before an evident hyperglycemia, possibly because of insulin deficiency and resistance.AimTo evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population.MethodsA total of 165 CF subjects (80 females) aged 17±5 years and 18 age- and sex-matched healthy controls (CON) received an oral glucose tolerance test with glucose, insulin and C-peptide determinations. Insulin sensitivity was defined on the basis of glucose and insulin concentrations using the oral glucose insulin sensitivity index, whereas β-cell function was determined on the basis of a model relating insulin secretion (C-peptide profile) to glucose concentration.ResultsFifteen percent of CF patients had glucose intolerance and 6% had diabetes without fasting hyperglycemia and 3% had diabetes with fasting hyperglycemia. β-cell function was reduced in CF patients compared with CON (70.0±4.1 vs 117.9±11.6 pmol/min per m2 per mM, P<0.001) and decreased significantly with age by −2.7 pmol/min per m2 per mM per year (confidence interval (CI) −4.5 to −0.82), i.e. almost 4% yearly. The early insulin secretion index was also reduced. Insulin sensitivity was similar to CON. CF patients who attained glucose tolerance comparable to CON had lower β-cell function and higher insulin sensitivity.ConclusionThe major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining β-cell function, consisting of delayed and reduced responsiveness to hyperglycemia, that in CF patients with normal glucose tolerance may be compensated by an increased insulin sensitivity.

scholarly journals Effects of Sucralose Ingestion versus Sucralose Taste on Metabolic Responses to an Oral Glucose Tolerance Test in Participants with Normal Weight and Obesity: A Randomized Crossover Trial

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 29 ◽  
Author(s):  
Alexander D. Nichol ◽  
Clara Salame ◽  
Kristina I. Rother ◽  
M. Yanina Pepino
Keyword(s):  
Glucose Tolerance ◽  
Cell Function ◽  
Normal Weight ◽  
Taste Perception ◽  
Metabolic Responses ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cell ◽  
Β Cell Function ◽  
Weight Groups

Here, we tested the hypothesis that sucralose differentially affects metabolic responses to labeled oral glucose tolerance tests (OGTTs) in participants with normal weight and obesity. Participants (10 with normal weight and 11 with obesity) without diabetes underwent three dual-tracer OGTTs preceded, in a randomized order, by consuming sucralose or water, or by tasting and expectorating sucralose (e.g., sham-fed; sweetness control). Indices of β-cell function and insulin sensitivity (SI) were estimated using oral minimal models of glucose, insulin, and C-peptide kinetics. Compared with water, sucralose ingested (but not sham-fed) resulted in a 30 ± 10% increased glucose area under the curve in both weight groups. In contrast, the insulin response to sucralose ingestion differed depending on the presence of obesity: decreased within 20–40 min of the OGTT in normal-weight participants but increased within 90–120 min in participants with obesity. Sham-fed sucralose similarly decreased insulin concentrations within 60 min of the OGTT in both weight groups. Sucralose ingested (but not sham-fed) increased SI in normal-weight participants by 52 ± 20% but did not affect SI in participants with obesity. Sucralose did not affect glucose rates of appearance or β-cell function in either weight group. Our data underscore a physiological role for taste perception in postprandial glucose responses, suggesting sweeteners should be consumed in moderation.

Detection of Glycemic Abnormalities in Young Adult Patients with Beta Thalassemia Major Using Continuous Glucose Monitoring System (CGMS) and Oral Glucose Tolerance Test (OGTT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2158-2158
Author(s):  
Mohamed A. Yassin ◽  
Ahmed M Elawa ◽  
Ashraf T Soliman
Keyword(s):  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Glucose Tolerance Test ◽  
Cell Function ◽  
Serum Insulin ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cell ◽  
Β Cell Function

Abstract Abstract 2158 Introduction: Both insulin deficiency and insulin resistance are reported in patients with β thalassemia major (BTM). The use of continuous blood glucose monitoring system (CGMS) among the different methods for early detection of glycaemic abnormalities has not been studied thoroughly in these patients. Aims: The aims of this study were: 1. to detect glycaemic abnormalities, if any, in young adults with BTM using fasting blood glucose (FBG), oral glucose tolerance test (OGTT), 72-h continuous glucose concentration by CGMS system, and serum insulin and C-peptide concentrations 2. To compare the results of these two methods in detecting glycaemic abnormalities in these patients and 3. To calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in these patients. In order to evaluate whether glycaemic abnormalities are due to insulin deficiency and/or resistance. Materials and methods: Randomly selected young adults (n = 14) with BTM were the subjects of this study. All patients were investigated using a standard oral glucose tolerance test (OGTT) (using 75 gram of glucose) and 72-h continuous glucose concentration by CGM system (Medtronic system). Fasting serum insulin and C-peptide concentrations were measured and HOMA-B, HOMA-IR were calculated accordingly. Results: Using OGTT, 5 patients had impaired fasting glucose (IFG) (Fasting BG from 5.6 to 6.9 mmol/L). Two of them had impaired glucose tolerance IGT (BG from 7.8 and < 11.1 mmol/L) and one had BG = 16.2 mmol/L after 2-hrs (diabetic). Using CGMS in addition to the glucose data measured by glucometer (3–5 times/ day), 6 patients had IFG. The maximum (postprandial) BG recorded exceeded 11.1 mmol/L in 4 patients (28.5%) (Diabetics) and was > 7.8 but < 11.1 mmol/L in 8 patients (57%) (IGT). The mean values of HOMA and QUICKI in patients with BTM were < 2.6 (1.6± 0.8) and > 0.33 (0.36±0.03) respectively ruling out significant insulin resistance in these adolescents. There was a significant negative correlation between the β-cell function (B %) on the one hand and the fasting and the 2-h BG (r= −0.6, and − 0.48, P< 0.01 respectively) on the other hand. Serum insulin concentrations were not correlated with fasting BG or ferritin levels. The average and maximum BG levels recorded by CGMS were significantly correlated with the fasting BG (r= 0.69 and 0.6 respectively with P < 0.01) and with the BG at 2-hour after oral glucose intake (r= 0.87and 0.86 respectively with P < 0.01). Ferritin concentrations were positively correlated with the fasting BG and the 2-h BG levels in the OGTT (r= 0.69, 0.43 respectively, P < 0.001) as well as with the average and the maximum BG recorded by CGM (r =0.75, and 0.64 respectively with P < 0.01). Ferritin concentrations were negatively correlated with the β-cell function (r= −0.41, P< 0.01). Conclusion: CGMS has proved to be superior to OGTT for the diagnosis of glycaemic abnormalities in young adult patients with BTM. In our patients, defective β-cell function rather than insulin resistance appeared to be the cause for these abnormalities. The significant correlations between serum ferritin concentrations and the beta cell functions suggested the importance of adequate chelation to prevent β-cell dysfunction Disclosures: No relevant conflicts of interest to declare.

scholarly journals Evaluation of Fasting State-/Oral Glucose Tolerance Test-Derived Measures of Insulin Release for the Detection of Genetically Impaired β-Cell Function

PLoS ONE ◽  
2010 ◽  
Vol 5 (12) ◽  
pp. e14194 ◽  
Author(s):  
Silke A. Herzberg-Schäfer ◽  
Harald Staiger ◽  
Martin Heni ◽  
Caroline Ketterer ◽  
Martina Guthoff ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Glucose Tolerance Test ◽  
Cell Function ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Fasting State ◽  
Oral Glucose Tolerance ◽  
Β Cell ◽  
Β Cell Function

Estimation of β-cell function from the data of the oral glucose tolerance test

2007 ◽  
Vol 292 (6) ◽  
pp. E1575-E1580 ◽  
Author(s):  
Shinji Sakaue ◽  
Shinji Ishimaru ◽  
Daisuke Ikeda ◽  
Yoshinori Ohtsuka ◽  
Toshiro Honda ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Cell Function ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Β Cell ◽  
Β Cell Function ◽  
The Relationship

Although a hyperbolic relationship between insulin secretion and insulin sensitivity has been shown, the relationship has been often questioned. We examined the relationship using oral glucose tolerance test (OGTT)-derived indexes. A total of 374 Japanese subjects who had never been given a diagnosis of diabetes underwent a 75-g OGTT. In subjects with normal glucose tolerance (NGT), the ln [insulinogenic index (IGI)] was described by a linear function of ln ( x) ( x, insulin sensitivity index) in regression analysis when the reciprocal of the insulin resistance index in homeostasis model assessment, Matsuda's index, and oral glucose insulin sensitivity index were used as x. Because the 95% confidence interval of the slope of the regression line did not necessarily include −1, the relationships between IGI and x were not always hyperbolic, but power functions IGI × xα = a constant. We thought that IGI × xα was an appropriate β-cell function estimate adjusted by insulin sensitivity and referred to it as β-cell function index (BI). When Matsuda's index was employed as x, the BI values were decreased in subjects without NGT. Log BI had a better correlation with fasting plasma glucose (PG; FPG) and 2-h PG in non-NGT subjects than in NGT subjects. In subjects with any glucose tolerance, log BI was linearly correlated with 1-h PG and glucose spike (the difference between maximum PG and FPG). In conclusion, the relationship between insulin secretion and insulin sensitivity was not always hyperbolic. The BI is a useful tool in the estimation of β-cell function with a mathematical basis.

scholarly journals Glucose metabolic disorder in Klinefelter syndrome: a retrospective analysis in a single Chinese hospital and literature review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shixuan Liu ◽  
Tao Yuan ◽  
Shuoning Song ◽  
Shi Chen ◽  
Linjie Wang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Literature Review ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Klinefelter Syndrome ◽  
Oral Glucose ◽  
Model Assessment ◽  
Β Cell ◽  
Β Cell Function

Abstract Background We aimed to investigate the clinical characteristics and islet β-cell function in patients with Klinefelter syndrome (KS) and hyperglycemia. Methods This is a retrospective study. In total, 22 patients diagnosed with KS were identified from the electronic medical record system, including 9 patients with hyperglycemia (total patients with hyperglycemia, THG-KS group) and 5 hyperglycemic KS patients with oral glucose tolerance test (OGTT) results (HG-KS group). An additional 5 subjects with hyperglycemia and 5 normal glucose tolerance (NGT) subjects matched based on body mass index were included as the HG group and NGT group, respectively. Data from clinical and laboratory examinations were collected. We further performed a literature review of KS and hyperglycemia. Results We found that KS patients developed abnormal glucose metabolism earlier in life than those without KS, and the median age was 17 years, ranging from 10 years to 19 years. Six of 17 (35.3%) patients were diagnosed with diabetes mellitus and 3 of 17 (17.6%) patients were diagnosed with prediabetes. Among 10 patients with both fasting blood glucose and insulin results recorded, there were 8 out of 17 (47.1%) KS patients had insulin resistance. The prevalence of hypertension and dyslipidemia was higher in patients with hyperglycemia and KS than in patients with NGT KS. Compared with the HG group, insulin sensitivity levels were lower in HG-KS group, whereas homeostasis model assessment of β-cell function levels (p = 0.047) were significantly, indicating higher insulin secretion levels in the HG-KS group. Conclusions KS patients develop hyperglycemia earlier in life than those without KS and show lower insulin sensitivity and higher insulin secretion. These patients also have a higher prevalence of other metabolic diseases and may have different frequencies of developing KS-related symptoms.

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