Risk Factors for Spontaneously Self-Reported Postprandial Hypoglycemia After Bariatric Surgery

Context: Postprandial hypoglycemia (PPHG) is a recognized complication of Roux-en-Y gastric bypass (RYGB) surgery. Data on PPHG after laparoscopic sleeve gastrectomy (LSG) are scant. Objective: The objective of the study was to identify preoperative predictors of PPHG in subjects spontaneously self-reporting PPHG after RYGB or LSG. Patients, Setting, and Intervention: Nondiabetic patients spontaneously self-reporting symptoms/signs of PPHG (PPHG group, 21 RYGB and 11 LSG) were compared in a case-control design with subjects who never experienced spontaneous or oral glucose tolerance test (OGTT)-induced hypoglycemia over 24 months after surgery (No-PPHG group, 13 RYGB and 40 LSG). Paired pre- and postoperative 3-hour OGTTs were analyzed in all participants. Main Outcome Measures: Insulin sensitivity was assessed by the oral glucose insulin sensitivity index and β-cell function by mathematical modeling of the C-peptide response to glucose. Results: Before surgery, the body mass index was lower in PPHG than No-PPHG patients in the RYGB (P = .002) and trended similarly in the LSG group (P = .08). Fasting glycemia and the glucose-OGTT nadir were lower in the PPHG than the No-PPHG subjects in both surgery groups. Before surgery, insulin sensitivity was higher in PPHG than No-PPHG in the RYGB (393 ± 55 vs 325 ± 44 mL/min−1 · m−2, P = .001) and LSG groups (380 ± 48 vs 339 ± 60 mL/min−1 · m−2, P = .05) and improved to a similar extent in all groups after surgery. Before surgery, β-cell glucose sensitivity was higher in PPHG than No-PPHG in both RYGB (118 ± 67 vs 65 ± 24 pmol/min−1 · m2 · mM−1) and LSG patients (114 ± 32 vs 86 ± 33) (both P = .02) and improved in all subjects after surgery. Conclusions: In subjects self-reporting PPHG after surgery, lower presurgery plasma glucose concentrations, higher insulin sensitivity, and better β-cell glucose sensitivity are significant predictors of PPHG after both RYGB and LSG.

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00341.2006 ◽

2007 ◽

Vol 292 (6) ◽

pp. E1575-E1580 ◽

Cited By ~ 9

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.

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Measurement of bioactive osteocalcin in humans using a novel immunoassay reveals association with glucose metabolism and β-cell function

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00321.2019 ◽

2020 ◽

Vol 318 (3) ◽

pp. E381-E391 ◽

Cited By ~ 7

Author(s):

Julie Lacombe ◽

Omar Al Rifai ◽

Lorraine Loter ◽

Thomas Moran ◽

Anne-Frédérique Turcotte ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Glucose Metabolism ◽

Cell Function ◽

Fasting Glucose ◽

Tolerance Test ◽

Oral Glucose ◽

Sensitivity Index ◽

Model Assessment ◽

Β Cell

Osteocalcin (OCN) is a bone-derived hormone involved in the regulation of glucose metabolism. In serum, OCN exists in carboxylated and uncarboxylated forms (ucOCN), and studies in rodents suggest that ucOCN is the bioactive form of this hormone. Whether this is also the case in humans is unclear, because a reliable assay to measure ucOCN is not available. Here, we established and validated a new immunoassay (ELISA) measuring human ucOCN and used it to determine the level of bioactive OCN in two cohorts of overweight or obese subjects, with or without type 2 diabetes (T2D). The ELISA could specifically detect ucOCN concentrations ranging from 0.037 to 1.8 ng/mL. In a first cohort of overweight or obese postmenopausal women without diabetes ( n = 132), ucOCN correlated negatively with fasting glucose (r = −0.18, P = 0.042) and insulin resistance assessed by the homeostatic model assessment of insulin resistance (r = −0.18, P = 0.038) and positively with insulin sensitivity assessed by a hyperinsulinemic-euglycemic clamp (r = 0.18, P = 0.043) or insulin sensitivity index derived from an oral glucose tolerance test (r = 0.26, P = 0.003). In a second cohort of subjects with severe obesity ( n = 16), ucOCN was found to be lower in subjects with T2D compared with those without T2D (2.76 ± 0.38 versus 4.52 ± 0.06 ng/mL, P = 0.009) and to negatively correlate with fasting glucose (r = −0.50, P = 0.046) and glycated hemoglobin (r = −0.57, P = 0.021). Moreover, the subjects with ucOCN levels below 3 ng/mL had a reduced insulin secretion rate during a hyperglycemic clamp ( P = 0.03). In conclusion, ucOCN measured with this novel and specific assay is inversely associated with insulin resistance and β-cell dysfunction in humans.

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Effect of Iron Chelation Therapy on Glucose Metabolism in Non-Transfusion-Dependent Thalassaemia

Acta Haematologica ◽

10.1159/000450673 ◽

2016 ◽

Vol 137 (1) ◽

pp. 20-26 ◽

Cited By ~ 4

Author(s):

Ampaiwan Chuansumrit ◽

Pimprae Pengpis ◽

Pat Mahachoklertwattana ◽

Nongnuch Sirachainan ◽

Preamrudee Poomthavorn ◽

...

Keyword(s):

Insulin Sensitivity ◽

Serum Ferritin ◽

Cell Function ◽

Iron Status ◽

Iron Chelation ◽

Tolerance Test ◽

Oral Glucose ◽

Β Cell ◽

Iron Load ◽

Β Cell Function

Aims: To compare insulin sensitivity, β-cell function and iron status biomarkers in non-transfusion-dependent thalassaemia (NTDT) with iron excess during pre- and post-iron chelation. Methods: Subjects with NTDT, aged older than 10 years, with serum ferritin >300 ng/ml, were included. Iron chelation with deferasirox (10 mg/kg/day) was prescribed daily for 6 months. Results: Ten patients with a median age of 17.4 years were enrolled. The comparison between pre- and post-chelation demonstrated significantly lower iron load: median serum ferritin (551.4 vs. 486.2 ng/ml, p = 0.047), median TIBC (211.5 vs. 233.5 µg/dl, p = 0.009) and median non-transferrin binding iron (5.5 vs. 1.4 µM, p = 0.005). All patients had a normal oral glucose tolerance test (OGTT) both pre- and post-chelation. However, fasting plasma glucose was significantly reduced after iron chelation (85.0 vs.79.5 mg/dl, p = 0.047). MRI revealed no significant changes of iron accumulation in the heart and liver after chelation, but there was a significantly lower iron load in the pancreas, assessed by higher T2* at post-chelation compared with pre-chelation (41.9 vs. 36.7 ms, p = 0.047). No adverse events were detected. Conclusions: A trend towards improving insulin sensitivity and β-cell function as well as a reduced pancreatic iron load was observed following 6 months of iron chelation (TCTR20160523003).

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Vigorous Physical Activity may be Important for the Insulin Sensitivity in Immigrants From the Middle East and Native Swedes

Journal of Physical Activity and Health ◽

10.1123/jpah.2013-0222 ◽

2015 ◽

Vol 12 (2) ◽

pp. 273-281 ◽

Cited By ~ 1

Author(s):

Daniel Arvidsson ◽

Ulf Lindblad ◽

Jan Sundquist ◽

Kristina Sundquist ◽

Leif Groop ◽

...

Keyword(s):

Physical Activity ◽

Insulin Sensitivity ◽

Sedentary Time ◽

Cell Function ◽

Vigorous Physical Activity ◽

Oral Glucose ◽

Sensitivity Index ◽

Β Cell ◽

Β Cell Function ◽

Activity Measures

Purpose:To compare physical activity measures and their associations with insulin sensitivity, β-cell function and body mass index (BMI) between Iraqi immigrants and native Swedes.Methods:A cross-sectional study of 493 Iraqis (58% men) and 469 Swedes (54% men) aged 30 to 75 years living in the city of Malmö, Sweden. Accelerometry was used for physical activity measures (sedentary time, breaks in sedentary time, moderate and vigorous physical activity, total counts). Insulin sensitivity index and oral disposal index were determined from an oral glucose tolerance test and BMI by body weight and height.Results:Iraqi men were less physically active than Swedish men, while the physical activity was more similar in the women. BMI was a strong predictor of insulin sensitivity and β-cell function and frequently associated with the physical activity measures. BMI modified the associations of insulin sensitivity and β-cell function with the physical activity measures to such extent that only VPA and total counts show direct associations with insulin sensitivity in addition to the indirect associations via BMI. Iraqi women demonstrated weaker associations compared with Swedish women.Conclusions:Physical activity and performed at vigorous intensity may be important mainly for the insulin sensitivity in Iraqi immigrants and native Swedes.

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Impact of incretin hormones on β-cell function in subjects with normal or impaired glucose tolerance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00571.2005 ◽

2006 ◽

Vol 291 (6) ◽

pp. E1144-E1150 ◽

Cited By ~ 60

Author(s):

Elza Muscelli ◽

Andrea Mari ◽

Andrea Natali ◽

Brenno D. Astiarraga ◽

Stefania Camastra ◽

...

Keyword(s):

Insulin Secretion ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Cell Function ◽

Oral Glucose ◽

Incretin Effect ◽

Β Cell ◽

Β Cell Function ◽

Glucose Sensitivity ◽

Cell Glucose

The mechanisms by which the enteroinsular axis influences β-cell function have not been investigated in detail. We performed oral and isoglycemic intravenous (IV) glucose administration in subjects with normal (NGT; n = 11) or impaired glucose tolerance (IGT; n = 10), using C-peptide deconvolution to calculate insulin secretion rates and mathematical modeling to quantitate β-cell function. The incretin effect was taken to be the ratio of oral to IV responses. In NGT, incretin-mediated insulin release [oral glucose tolerance test (OGTT)/IV ratio = 1.59 ± 0.18, P = 0.004] amounted to 18 ± 2 nmol/m2 (32 ± 4% of oral response), and its time course matched that of total insulin secretion. The β-cell glucose sensitivity (OGTT/IV ratio = 1.52 ± 0.26, P = 0.02), rate sensitivity (response to glucose rate of change, OGTT/IV ratio = 2.22 ± 0.37, P = 0.06), and glucose-independent potentiation were markedly higher with oral than IV glucose. In IGT, β-cell glucose sensitivity (75 ± 14 vs. 156 ± 28 pmol·min−1·m−2·mM−1 of NGT, P = 0.01) and potentiation were impaired on the OGTT. The incretin effect was not significantly different from NGT in terms of plasma glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide responses, total insulin secretion, and enhancement of β-cell glucose sensitivity (OGTT/IV ratio = 1.73 ± 0.24, P = NS vs. NGT). However, the time courses of incretin-mediated insulin secretion and potentiation were altered, with a predominance of glucose-induced vs. incretin-mediated stimulation. We conclude that, under physiological circumstances, incretin-mediated stimulation of insulin secretion results from an enhancement of all dynamic aspects of β-cell function, particularly β-cell glucose sensitivity. In IGT, β-cell function is inherently impaired, whereas the incretin effect is only partially affected.

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Agreement and Reliability of Fasted and Oral Glucose Tolerance Test-Derived Indices of Insulin Sensitivity and Beta Cell Function in Boys

International Journal of Sports Medicine ◽

10.1055/s-0043-104932 ◽

2017 ◽

Vol 38 (06) ◽

pp. 411-417 ◽

Cited By ~ 3

Author(s):

Emma Cockcroft ◽

Craig Williams ◽

Sarah Jackman ◽

Neil Armstrong ◽

Alan Barker

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Glucose Tolerance Test ◽

Cell Function ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Β Cell ◽

Β Cell Function ◽

Method Agreement

AbstractAssessment of plasma insulin and glucose outcomes is important in paediatric studies aimed at reducing future risk of type 2 diabetes and cardiovascular disease. The aims of this study are to determine the between-method agreement and the day-to-day reliability of fasting and oral glucose tolerance test (OGTT)-derived estimates of insulin sensitivity and β-cell function in healthy boys. Fasting and OGTT assesments of insulin resistance and β-cell function were performed on 28 boys (12.3±2.9 years). Measurements were repeated after 1 week (fasting, n=28) and 1 day (OGTT, n=8). Agreement between estimates of insulin resistance and β-cell function was examined using Pearson’s correlation coefficient. Reliability was assessed using change in the mean, Pearson’s correlation coefficient, and typical error expressed as a coefficient of variation (CV). The Matsuda index was positively related with QUICKI (r=0.88, P<0.001) and negatively related to HOMA-IR (r=−0.76, P<0.001). The Cederholm index was not significantly related with fasting estimates of insulin resistance (all r<0.40, P>0.05). For reliability, QUICKI had the lowest CV% for the fasting (4.7%) and the Cederholm index for the OGTT (6.4%) estimates. The largest CV% was observed in fasting insulin (30.8%) and insulinogenic index 30’ (62.5%). This study highlights differences in between-method agreement and day-to-day reliability for estimates of insulin resistance in youth. The low CV supports the use of the FGIR (fasting) and Cederholm (OGTT) indices in this population.

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Early Detection of Insulin Sensitivity and β-Cell Function with Simple Tests Indicates Future Derangements in Late Pregnancy

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-1363 ◽

2008 ◽

Vol 93 (3) ◽

pp. 876-880 ◽

Cited By ~ 31

Author(s):

A. Lapolla ◽

M. G. Dalfrà ◽

G. Mello ◽

E. Parretti ◽

R. Cioni ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Early Pregnancy ◽

Cell Function ◽

Late Pregnancy ◽

Tolerance Test ◽

Oral Glucose ◽

Β Cell ◽

Β Cell Function

Abstract Objective: Insulin sensitivity and secretion during early and late pregnancy were assessed in women with normal glucose tolerance and gestational diabetes mellitus (GDM). Research Design and Methods: The oral glucose tolerance test (OGTT) was performed in 903 women at 16–20th gestational week, of whom 37 had GDM (GDM1 group), and 859 repeated the OGTT at wk 26–30. At the second test, 55 had GDM (GDM2 group); the others remained normotolerant (ND group). Insulin sensitivity from OGTT (as quantitative insulin sensitivity check index and OGTT insulin sensitivity) and β-cell function (as the ratio of the areas under the insulin and glucose concentration curves, adjusted for insulin sensitivity) were assessed in both tests. Results: In early pregnancy the quantitative insulin sensitivity check index was not different in the three groups, whereas OGTT insulin sensitivity was lowest in GDM2, intermediate in GDM1, and highest in ND. In late pregnancy both indices were reduced in GDM compared with ND and lower than in early pregnancy. In early pregnancy GDM1, but not GDM2, had lower β-cell function than ND. During the late visit, GDM2 also showed impaired β-cell function compared with ND; furthermore, the adaptation to the increase to insulin resistance from early to late pregnancy was defective in GDM2. Conclusions: In early pregnancy insulin sensitivity, as assessed from the OGTT but not from fasting measurements, is impaired in women who developed GDM. β-Cell function impairment is evident only when GDM is manifest and is characterized by inappropriate adaptation to the pregnancy induced increase in insulin resistance.

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Assessment of β-cell function in humans, simultaneously with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00421.2006 ◽

2007 ◽

Vol 293 (1) ◽

pp. E1-E15 ◽

Cited By ~ 207

Author(s):

Claudio Cobelli ◽

Gianna Maria Toffolo ◽

Chiara Dalla Man ◽

Marco Campioni ◽

Paolo Denti ◽

...

Keyword(s):

Insulin Sensitivity ◽

Minimal Model ◽

Glucose Tolerance Test ◽

Cell Function ◽

Tolerance Test ◽

Oral Glucose ◽

Β Cell ◽

Physiological Conditions ◽

Β Cell Function ◽

Hepatic Insulin Extraction

Assessment of insulin secretion in humans under physiological conditions has been a challenge because of its complex interplay with insulin action and hepatic insulin extraction. The possibility of simultaneously assessing β-cell function, insulin sensitivity, and hepatic insulin extraction under physiological conditions using a simple protocol is appealing, since it has the potential to provide novel insights regarding the regulation of fasting and postprandial glucose metabolism in diabetic and nondiabetic humans. In this Perspective, we review data indicating that an oral glucose tolerance test (OGTT) or a meal test is able to accomplish this goal when interpreted with the oral β-cell minimal model. We begin by using the well-established intravenous minimal model to highlight how the oral minimal model was developed and how the oral assessment parallels that of an intravenous glucose tolerance test (IVGTT). We also point out the unique aspects of both approaches in relation to their ability to assess different aspects of the β-cell secretory cascade. We review the ability of the oral model to concurrently measure insulin sensitivity and hepatic insulin extraction, thereby enabling it to quantitatively portray the complex relationship among β-cell function, hepatic insulin extraction, and insulin action. In addition, data from 204 individuals (54 young and 159 elderly) who underwent both IVGTT and meal tolerance tests are used to illustrate how these different approaches provide complementary but differing insights regarding the regulation of β-cell function in humans.

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Evaluation of different methods for assessment of insulin sensitivity in Göttingen minipigs: introduction of a new, simpler method

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.90851.2008 ◽

2009 ◽

Vol 297 (4) ◽

pp. R1195-R1201 ◽

Cited By ~ 35

Author(s):

Berit Christoffersen ◽

Ulla Ribel ◽

Kirsten Raun ◽

Valeria Golozoubova ◽

Giovanni Pacini

Keyword(s):

Insulin Sensitivity ◽

Cell Function ◽

High Energy ◽

Tolerance Test ◽

Insulin Tolerance Test ◽

Oral Glucose ◽

Β Cell ◽

Simple Index ◽

Insulin Tolerance ◽

Β Cell Function

The use of animal models in diabetes research requires reliable tests for evaluation of insulin sensitivity and β-cell function. Minipigs are being increasingly used in metabolic research, and the aim of this study was to compare different tests and indexes for evaluation of insulin sensitivity and β-cell function in Göttingen minipigs. Hyperinsulinemic, isoglycemic clamp, intravenous (IVGTT) and oral glucose tolerance tests (OGTT), and a modified insulin tolerance test were performed in minipigs fed either low- or high-energy diet. Furthermore, the reproducibility of IVGTT-derived parameters was assessed. Previously described insulin sensitivity indexes [steady-state glucose infusion rate/glucose concentration/insulin concentration from clamp (M/G/I); oral glucose insulin sensitivity (OGIS) and ISIcomp from OGTT; SI from minimal model analysis of IVGTT; and quantitative insulin sensitivity check index from fasting values] were calculated together with an insulin sensitivity index from the modified insulin tolerance test (ISIITT) and a new simple index (S2) derived from the first 30 min of the IVGTT. β-Cell function was assessed from the IVGTT and the OGTT. Reproducibility of the IVGTT-derived parameters was calculated as median intraindividual coefficient of variation (CV%).M/G/I correlated significantly only with S2 ( P < 0.05, r = 0.54). S2 furthermore correlated with SI ( P < 0.001, r = 0.81), ISIITT ( P < 0.001, r = 0.57), and the two indexes from OGTT, ISIcomp ( P < 0.001, r = 0.78) and OGIS ( p < 0.05, r = 0.48). No correlation was found between β-cell function indexes from OGTT and IVGTT. The median CV% of the new S2 index was 13. In conclusion, the new simple index of insulin sensitivity, S2, was revealed to be useful for evaluation of insulin sensitivity in pigs.

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OGTT Glucose Response Curves, Insulin Sensitivity, and β-Cell Function in RISE: Comparison Between Youth and Adults at Randomization and in Response to Interventions to Preserve β-Cell Function

10.2337/figshare.13373708.v1 ◽

2021 ◽

Author(s):

Silva Arslanian ◽

Laure El ghormli ◽

Joon Young Kim ◽

Ashley H. Tjaden ◽

Elena Barengolts ◽

...

Keyword(s):

Insulin Sensitivity ◽

B Cell ◽

Cell Function ◽

Tolerance Test ◽

Oral Glucose ◽

Β Cell ◽

Response Curves ◽

Glucose Response ◽

Cross Sectional ◽

Β Cell Function

Objective: We examined the glucose-response-curves [Biphasic (BPh), Monophasic (MPh), Incessant-Increase (IIn)], during an oral glucose tolerance test (OGTT), and their relationship to insulin sensitivity (IS) and b-cell function (bCF) in youth vs. adults with IGT or recently diagnosed type 2 diabetes. Research Design and Methods: This was both a cross-sectional and longitudinal evaluation of participants in the RISE study randomized to metformin alone for 12 months or glargine for 3 months followed by metformin for 9 months. At baseline/randomization, OGTTs (85 youth, 353 adults) were categorized as BPh, MPh, or IIn. The relationship of the glucose-response-curves to hyperglycemic-clamp-measured IS and bCF at baseline, and the change in glucose-response-curves 12 months after randomization were assessed. Results: At randomization, the prevalence of the BPh-curve was significantly higher in youth than adults (18.8% vs. 8.2%), with no differences in MPh or IIn. IS did not differ across glucose-response-curves in youth or adults. However, irrespective of curve type, youth had lower IS than adults (p<0.05). bCF was lowest in IIn vs. MPh and BPh in youth and adults (p <0.05). Yet, compared with adults, youth had higher bCF in BPh and MPh (p<0.005), but not IIn curves. At month 12, the change in glucose-response-curves did not differ between youth and adults, and there was no treatment effect. Conclusions: Despite a 2-fold higher prevalence of the more-favorable BPh curve in youth at randomization, RISE interventions did not result in beneficial changes in glucose-response-curves in youth compared with adults. Moreover, the typical b-cell hypersecretion in youth was not present in the IIn curve, emphasizing the severity of b-cell dysfunction in youth with this least- favorable glucose-response-curve.

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