scholarly journals Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity

2008 ◽  
Vol 159 (5) ◽  
pp. 577-583 ◽  
Author(s):  
Lovisa E Johansson ◽  
Ulf Lindblad ◽  
Charlotte A Larsson ◽  
Lennart Råstam ◽  
Martin Ridderstråle
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Cell Function ◽  
Leisure Time Physical Activity ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Β Cell ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Β Cell Function

ObjectiveThe insulin responsive adiponutrin or patatin-like phospholipase 3 (PNPLA3, previously ADPN) gene shows association with obesity and in vitro adipocyte lipolysis. This study aimed to replicate the association between PNPLA3 variants and obesity, and to investigate their effect on insulin resistance and β-cell function.Methodsrs738409 (Met148Ile) and rs2072907 (C to G) were genotyped using TaqMan allelic discrimination assay in a Swedish population-based sample (n=1811). Oral glucose tolerance test (OGTT) with data from three time points (0, 30, and 120 min) were available from individuals under the age of 50 years (n=973).ResultsBoth variant alleles were associated with decreased prevalence of obesity (P<0.05); odds ratio 0.75 (0.61–0.93) per carried Ile-allele for rs738409 and 0.80 (0.64–1.00) per carried G-allele for rs2072907. For obesity as a quantitative trait, there was no association in the whole population, but in obese subjects body mass index (BMI; P=0.023) and waist (P=0.0098) were higher in carriers of the Ile-allele. The Ile-carriers also displayed decreased insulin secretion in response to OGTT (30 min insulin; P=0.007, insulinogenic index; P=0.0051) with no significant differences in fasting plasma glucose (P=0.31), β-cell function (disposition index; P=0.17) or homeostasis model of assessment insulin resistance (HOMA-IR; P=0.063). The correlation between BMI and HOMA-IR differed (Met/X versus Ile/Ile, P=0.028), Met-allele carriers were seemingly more insulin resistant at a lower BMI. The rs2072907 variant shows similar results for insulin secretion. The significance of this finding remained after adjusting for age, gender, and level of self-reported leisure-time physical activity.ConclusionWe confirm the association between PNPLA3 and obesity. In addition, the rs738409 variant was associated with insulin secretion. There seems to be a differential effect of the Ile-allele depending on the degree of obesity, possibly as a consequence of insulin resistance.

scholarly journals The shape of the glucose response curve during an OGTT heralds β−cell function in a large Chinese population

2019 ◽  
Author(s):  
Xinqi Cheng ◽  
Na Yang ◽  
Yuxiu Li ◽  
Qi Sun ◽  
Ling Qiu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Chinese Population ◽  
Response Curve ◽  
Cell Function ◽  
Serum Insulin ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Β Cell ◽  
Glucose Response ◽  
Β Cell Function

Abstract Background The shape of the glucose response during an oral glucose tolerance test can detect β-cell function and insulin resistance. But there were few studies in Chinese, so we aimed to verify the utility of these connections in a large Chinese population. Methods A total of 11,866 times of 3-h OGTT were categorized to either a monophasic or a multiphasic group based on the shape of the glucose response. Homeostasis model assessments of fasting insulin resistance, Matsuda index, insulinogenic index and the disposition index were assessed by plasma glucose and serum insulin concentration obtained at fasting or during an OGTT. Results Individuals with a monophasic shape had significantly higher glucose, insulin, and had significantly lower insulin sensitivity and impaired β-cell function than multiphasic group. In addition, Individuals were younger with a multiphasic shape compared to those with a monophasic shape. Conclusion The monophasic OGTT glucose response curve could reflect impaired β-cell function in a large Chinese population.

scholarly journals The shape of the glucose response curve during an OGTT heralds β−cell function in a large Chinese population

2019 ◽  
Author(s):  
Xinqi Cheng ◽  
Na Yang ◽  
Yuxiu Li ◽  
Qi Sun ◽  
Ling Qiu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Chinese Population ◽  
Response Curve ◽  
Cell Function ◽  
Serum Insulin ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Β Cell ◽  
Glucose Response ◽  
Β Cell Function

Abstract Background The shape of the glucose response during an oral glucose tolerance test can detect β-cell function and insulin resistance. But there were few studies in Chinese, so we aimed to verify the utility of these connections in a large Chinese population. Methods A total of 11,866 times of 3-h OGTT were categorized to either a monophasic or a multiphasic group based on the shape of the glucose response. Homeostasis model assessments of fasting insulin resistance, Matsuda index, insulinogenic index and the disposition index were assessed by plasma glucose and serum insulin concentration obtained at fasting or during an OGTT. Results Individuals with a monophasic shape had significantly higher glucose, insulin, and had significantly lower insulin sensitivity and impaired β-cell function than multiphasic group. In addition, Individuals were younger with a multiphasic shape compared to those with a monophasic shape. Conclusion The monophasic OGTT glucose response curve could reflect impaired β-cell function in a large Chinese population.

scholarly journals The shape of the glucose response curve during an OGTT heralds β−cell function in a large Chinese population

2019 ◽  
Author(s):  
Xinqi Cheng ◽  
Na Yang ◽  
Yuxiu Li ◽  
Qi Sun ◽  
Ling Qiu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Chinese Population ◽  
Response Curve ◽  
Cell Function ◽  
Serum Insulin ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Β Cell ◽  
Glucose Response ◽  
Β Cell Function

Abstract Background The shape of the glucose response during an oral glucose tolerance test can detect β-cell function and insulin resistance. But there were few studies in Chinese, so we aimed to verify the utility of these connections in a large Chinese population. Methods A total of 11,866 times of 3-h OGTT were categorized to either a monophasic or a multiphasic group based on the shape of the glucose response. Homeostasis model assessments of fasting insulin resistance, Matsuda index, insulinogenic index and the disposition index were assessed by plasma glucose and serum insulin concentration obtained at fasting or during an OGTT. Results Individuals with a monophasic shape had significantly higher glucose, insulin, and had significantly lower insulin sensitivity and impaired β-cell function than multiphasic group. In addition, Individuals were younger with a multiphasic shape compared to those with a monophasic shape. Conclusion The monophasic OGTT glucose response curve could reflect impaired β-cell function in a large Chinese population.

scholarly journals Estimates of Insulin Secretory Function in Apparently Healthy Volunteers Vary as a Function of How the Relevant Variables Are Quantified

2011 ◽  
Vol 57 (4) ◽  
pp. 627-632 ◽  
Author(s):  
Barry R Johns ◽  
Fahim Abbasi ◽  
Gerald M Reaven
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Plasma Glucose ◽  
Insulin Action ◽  
Cell Function ◽  
Model Assessment ◽  
Pancreatic Β Cell ◽  
Homeostasis Model Assessment ◽  
Β Cell ◽  
Β Cell Function

BACKGROUND Several surrogate estimates have been used to define relationships between insulin action and pancreatic β-cell function in healthy individuals. Because it is unclear how conclusions about insulin secretory function depend on specific estimates used, we evaluated the effect of different approaches to measurement of insulin action and secretion on observations of pancreatic β-cell function in individuals whose fasting plasma glucose (FPG) was &lt;7.0 mmol/L (126 mg/dL). METHODS We determined 2 indices of insulin secretion [homeostasis model assessment of β-cell function (HOMA-β) and daylong insulin response to mixed meals], insulin action [homeostasis model assessment of insulin resistance (HOMA-IR) and steady-state plasma glucose (SSPG) concentration during the insulin suppression test], and degree of glycemia [fasting plasma glucose (FPG) and daylong glucose response to mixed meals] in 285 individuals with FPG &lt;7.0 mmol/L. We compared the relationship between the 2 measures of insulin secretion as a function of the measures of insulin action and degree of glycemia. RESULTS Assessment of insulin secretion varied dramatically as a function of which of the 2 methods was used and which measure of insulin resistance or glycemia served as the independent variable. For example, the correlation between insulin secretion (HOMA-β) and insulin resistance varied from an r value of 0.74 (when HOMA-IR was used) to 0.22 (when SSPG concentration was used). CONCLUSIONS Conclusions about β-cell function in nondiabetic individuals depend on the measurements used to assess insulin action and insulin secretion. Viewing estimates of insulin secretion in relationship to measures of insulin resistance and/or degree of glycemia does not mean that an unequivocal measure of pancreatic β-cell function has been obtained.

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

2006 ◽  
Vol 291 (6) ◽  
pp. E1144-E1150 ◽  
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.

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.

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

2017 ◽  
Vol 38 (06) ◽  
pp. 411-417 ◽  
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.

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

2008 ◽  
Vol 93 (3) ◽  
pp. 876-880 ◽  
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.

Determinants of glucose metabolism and the role of NPY in the progression of insulin resistance in chronic migraine

Cephalalgia ◽  
2017 ◽  
Vol 38 (11) ◽  
pp. 1773-1781 ◽  
Author(s):  
Zeynep Oşar Siva ◽  
Derya Uluduz ◽  
Fatma Ela Keskin ◽  
Feyza Erenler ◽  
Huriye Balcı ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Neuropeptide Y ◽  
Chronic Migraine ◽  
Cell Function ◽  
Episodic Migraine ◽  
Oral Glucose ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background Chronic migraine has a well-documented association with increased insulin resistance and metabolic syndrome. The hypothalamus may play a role in the progression of insulin resistance in chronic migraine through the regulation of orexigenic peptides such as neuropeptide Y. Insulin resistance may lead to increased risk of future type 2 diabetes mellitus in patients with chronic migraine, which is more likely to occur if other pathogenetic defects of type 2 diabetes mellitus, such as impaired pancreatic β-cell functions and defects in intestinal glucagon-like peptide-1 secretion after meals. We studied the relationship of fasting neuropeptide Y with insulin resistance, β-cell function, and glucagon-like peptide-1 secretion in non-obese female chronic migraine patients. We also aimed to investigate glucose-stimulated insulin and glucagon-like peptide-1 secretions as early pathogenetic mechanisms responsible for the development of carbohydrate intolerance. Methods In this cross-sectional controlled study, 83 non-obese female migraine patients of reproductive age categorized as having episodic migraine or chronic migraine were included. The control group consisted of 36 healthy females. We studied glucose-stimulated insulin and glucagon-like peptide-1 secretion during a 75 g oral glucose tolerance test. We investigated the relationship of neuropeptide Y levels with insulin resistance and β-cell insulin secretion functions. Results Fasting glucose levels were significantly higher in migraine patients. Plasma glucose and insulin levels during the oral glucose tolerance test were otherwise similar in chronic migraine, episodic migraine and controls. Patients with chronic migraine were more insulin resistant than episodic migraine or controls ( p = 0.048). Glucagon-like peptide-1 levels both at fasting and two hours after glucose intake were similar in chronic migraine, episodic migraine, and controls. Neuropeptide Y levels were higher in migraineurs. In chronic migraine, neuropeptide Y was positively correlated with fasting glucagon-like peptide-1 levels (r = 0.57, p = 0.04), but there was no correlation with insulin resistance (r = 0.49, p = 0.09) or β-cell function (r = 0.50, p = 0.07). Discussion Non-obese premenopausal female patients with chronic migraine have higher insulin resistance, but normal β-cell function is to compensate for the increased insulin demand during fasting and after glucose intake. Increased fasting neuropeptide Y levels in migraine may be a factor leading to increased insulin resistance by specific alterations in energy intake and activation of the sympathoadrenal system.

Sign in / Sign up

Export Citation Format

Share Document