scholarly journals Pregnancy Serum DLK1 Concentrations are associated with Indices of Insulin Resistance and Secretion

2021 ◽  
Author(s):  
Clive J Petry ◽  
Keith A Burling ◽  
Peter Barker ◽  
Ieuan A Hughes ◽  
Ken K Ong ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Transmembrane Protein ◽  
Protein A ◽  
Maternal Serum ◽  
Offspring Size ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Glucose Tolerance Tests ◽  
Epidermal Growth ◽  
Size At Birth

Abstract Context DLK1 (delta like non-canonical notch ligand 1) is a paternally-expressed imprinted gene that encodes an epidermal growth factor repeat-containing transmembrane protein. A bioactive, truncated DLK1 protein is present in the circulation, and has roles in development and metabolism. Objective We sought to investigate links between maternal pregnancy circulating DLK1 concentrations and: (1) maternal and fetal DLK1 genotypes, (2) maternal insulin resistance and secretion and (3) offspring size at birth. Patients, design and setting We measured third trimester maternal serum DLK1 concentrations and examined their associations with parentally-transmitted fetal and maternal DLK1 genotypes, indices of maternal insulin resistance and secretion derived from 75g oral glucose tolerance tests performed around week 28 of pregnancy, and offspring size at birth in 613 pregnancies from the Cambridge Baby Growth Study. Results Maternal DLK1 concentrations were associated with the paternally-transmitted fetal DLK1 rs12147008 allele (p=7.8x10 -3) but not with maternal rs12147008 genotype (p=0.4). Maternal DLK1 concentrations were positively associated with maternal pre-pregnancy BMI (p=3.5x10 6), and (after adjustment for maternal BMI) with both maternal fasting insulin resistance (HOMA IR: p=0.01) and measures of maternal insulin secretion in response to oral glucose (insulinogenic index: p=1.2x10 -3; insulin disposition index: p=0.049). Further positive associations were found with offspring weight (p=0.02) and head circumference at birth (p=0.04). Conclusion These results are consistent with a partial paternal or placental origin for the maternal circulating DLK1 which may lead to increased maternal circulating DLK1 concentrations, stimulation of maternal insulin resistance and compensatory hyperinsulinemia during pregnancy, and the promotion of fetal growth.

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 Multiple Micronutrient Supplementation during Pregnancy and Increased Birth Weight and Skinfold Thicknesses in the Offspring: The Cambridge Baby Growth Study

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3466
Author(s):  
Clive J. Petry ◽  
Ken K. Ong ◽  
Ieuan A. Hughes ◽  
David B. Dunger
Keyword(s):  
Glucose Tolerance ◽  
Offspring Size ◽  
Oral Glucose ◽  
Micronutrient Supplementation ◽  
Oral Glucose Tolerance ◽  
Growth Study ◽  
Positive Effects ◽  
Increased Risk ◽  
Multiple Micronutrient ◽  
Size At Birth

Multiple micronutrient supplementation (MMS) in pregnancy has previously been associated with positive effects on fetal growth, but its value in high-income countries remains controversial. In this study, we investigated effects of pregnancy MMS on offspring size at birth and adiposity, along with risks of various maternal outcomes of pregnancy, using the prospective Cambridge Baby Growth Study. Maternal MMS was reported in 528 out of 970 women who completed pregnancy questionnaires. Gestational diabetes (GDM) was assessed using results from 75 g oral glucose tolerance tests at week 28 of pregnancy. Offspring size at birth was assessed using standard anthropometric measurements and adiposity using skinfold calipers. MMS was associated with increased risk of developing GDM (risk ratio = 1.86 (1.13–3.08), p = 0.02), as well as increased offspring size at birth in terms of weight (p = 0.03), head circumference (p = 0.04), and flank, and subscapular and triceps skinfold thicknesses (p = 0.04, 0.03, and 0.003, respectively). There was no association with quadriceps skinfold thickness (p = 0.2), suggesting that the increased adiposity was partially regionalized. In women who underwent oral glucose tolerance testing, nearly all of these associations were attenuated by adjusting for GDM. These results suggest that the increased offspring size at birth, including (regionalized) adiposity associated with pregnancy, and MMS may be partially related to the development of GDM.

scholarly journals Fasting insulin reflects heterogeneous physiological processes: role of insulin clearance

2011 ◽  
Vol 301 (2) ◽  
pp. E402-E408 ◽  
Author(s):  
Mark O. Goodarzi ◽  
Jinrui Cui ◽  
Yii-Der I. Chen ◽  
Willa A. Hsueh ◽  
Xiuqing Guo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Waist Circumference ◽  
Mexican Americans ◽  
Fasting Glucose ◽  
Insulin Clearance ◽  
Oral Glucose ◽  
Metabolic Clearance ◽  
Insulinogenic Index ◽  
Fasting Insulin

Several processes contribute to variation in fasting insulin concentration, including fasting glucose, insulin resistance, insulin secretion, and insulin clearance. Our goal was to determine the relative contribution of each of these insulin-related traits, plus anthropometric parameters, to fasting insulin among 470 Mexican Americans. The euglycemic hyperinsulinemic clamp yielded insulin sensitivity (M value) and metabolic clearance rate of insulin (MCRI). Acute insulin secretion was estimated by the insulinogenic index (IGI30) from the oral glucose tolerance test. Regression (univariate) and generalized estimating equations (multivariate) were used to describe the relationship of insulin-related traits to fasting insulin. Univarate analyses were used to select which traits to include in the multivariate model. In multivariate analysis, MCRI, M, BMI, waist circumference, and fasting glucose were independently associated with fasting insulin. Decreasing M and MCRI were associated with increasing fasting insulin, whereas increasing BMI, waist circumference, and fasting glucose were associated with increasing fasting insulin. Standardized coefficients allowed determination of the relative strength of each trait's association with fasting insulin in the entire cohort (strongest to weakest): MCRI (−0.35, P < 0.0001), M (−0.24, P < 0.0001), BMI (0.20, P = 0.0011), waist circumference (0.16, P = 0.021), and fasting glucose (0.11, P = 0.014). Fasting insulin is a complex phenotype influenced by several independent processes, each of which might have its own environmental and genetic determinants. One of the most associated traits was insulin clearance, which has implications for studies that have used fasting insulin as a surrogate for 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.

Association between insulin resistance and cardinal rheological parameters in young healthy Japanese individuals during 75 g oral glucose tolerance test

2021 ◽  
Vol 21 ◽  
Author(s):  
Larasati Martha ◽  
Takao Kimura ◽  
Akihiro Yoshida ◽  
Katsuhiko Tsunekawa ◽  
Tomoyuki Aoki ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Platelet Count ◽  
Density Lipoprotein ◽  
Tolerance Test ◽  
Rheological Parameters ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Model Assessment ◽  
Matsuda Index ◽  
Wbc Count

Background: Insulin resistance is a well-known predictor and risk factor for Type 2 Diabetes Mellitus (T2DM). Higher hematocrit induced by higher insulin resistance affects blood rheology. Objective: This study intended to reveal the association between indices of insulin resistance and hemorheological parameters during a 75 g oral glucose tolerance test (75-g OGTT). Methods: A total of 575 healthy young Japanese participants took 75-g OGTT. We then analyzed the association between insulin resistance indices and hematological parameters. Results: The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was significantly correlated with hematocrit (Ht), hemoglobin (Hb), Red Blood Cell (RBC), White Blood Cell (WBC), platelet count, lipid parameters, and Body Mass Index (BMI). The Matsuda index was negatively correlated with RBC count, WBC count, platelet count, Total Cholesterol (TC), Low-Density Lipoprotein-Cholesterol (LDL-C), triglyceride (TG), and positively correlated with High-Density Lipoprotein-Cholesterol (HDL-C). The disposition index was negatively correlated with Hb, RBC count, LDL-C, and BMI, while remaining positively correlated with HDL-C. The Homeostasis Model Assessment of beta cell (HOMA- IR ) was positively correlated with WBC count, platelet count, TC, LDL-C, and TG. The insulinogenic index was positively correlated with WBC count, platelet count, and TC. Multiple regression analysis revealed that HOMA-IR was independently associated with TG, and the Matsuda index was independently associated with TG, WBC count, and platelet count. The insulinogenic index was independently associated with WBC count. Conclusion: Cardinal rheological parameters reflected insulin resistance and were released even in the young, healthy Japanese individuals within the physiological range of glycemic control.

scholarly journals Absence of an Acute Insulin Response Predicts Onset of Type 2 Diabetes in a Caucasian Population with Impaired Glucose Tolerance

2008 ◽  
Vol 93 (7) ◽  
pp. 2633-2638 ◽  
Author(s):  
G. Nijpels ◽  
W. Boorsma ◽  
J. M. Dekker ◽  
F. Hoeksema ◽  
P. J. Kostense ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Hyperglycemic Clamp ◽  
Impaired Insulin ◽  
Oral Glucose Tolerance Tests ◽  
Glucose Tolerance Tests

Abstract Context: In persons with impaired glucose tolerance (IGT), both impaired insulin secretion and insulin resistance contribute to the conversion to type 2 diabetes mellitus (T2DM). However, few studies have used criterion standard measures to asses the predictive value of impaired insulin secretion and insulin resistance for the conversion to T2DM in a Caucasian IGT population. Objectives: The objective of the study was to determine the predictive value of measures of insulin secretion and insulin resistance derived from a hyperglycemic clamp, including the disposition index, for the development of T2DM in a Caucasian IGT population. Design, Setting, and Participants: The population-based Hoorn IGT study consisted of 101 Dutch IGT subjects (aged &lt; 75 yr), with mean 2-h plasma glucose values, of two separate oral glucose tolerance tests, between 8.6 and 11.1 mmol/liter. A hyperglycemic clamp at baseline was performed to assess first-phase and second-phase insulin secretion and insulin sensitivity. During follow-up, conversion to T2DM was assessed by means of 6-monthly fasting glucose levels and yearly oral glucose tolerance tests. Results: The cumulative incidence of T2DM was 34.7%. Hazard ratio for T2DM development adjusted for age, sex, and body mass index was 5.74 [95% confidence interval (CI) 2.60–12.67] for absence of first insulin peak, 1.58 (95% CI 0.60–4.17) for lowest vs. highest tertile of insulin sensitivity, and 1.78 (95% CI 0.65–4.88) for lowest vs. highest tertile of the disposition index. Conclusions: In these Caucasian persons with IGT, the absence of the first insulin peak was the strongest predictor of T2DM.

scholarly journals Maternal testosterone levels during pregnancy are associated with offspring size at birth

2006 ◽  
Vol 155 (2) ◽  
pp. 365-370 ◽  
Author(s):  
S M Carlsen ◽  
G Jacobsen ◽  
P Romundstad
Keyword(s):  
Birth Weight ◽  
Animal Studies ◽  
Maternal Serum ◽  
Sex Hormone Binding Globulin ◽  
Offspring Size ◽  
Testosterone Levels ◽  
Environment And Development ◽  
Maternal Testosterone ◽  
Size At Birth ◽  
Androgen Levels

Objective: Animal studies have indicated that maternal androgen levels influence the intrauterine environment and development of the offspring. Human data are missing. We therefore investigated the possible association between maternal androgens and offspring size at birth in humans. Design: A random sample of parous Caucasian women (n = 147) was followed prospectively through pregnancy. Methods: Maternal serum levels of dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone and sex hormone-binding globulin (SHBG) were measured at gestational weeks 17 and 33. The main outcome measures were weight and length at birth. Associations between maternal androgen levels and offspring birth weight and length were investigated using multiple linear regression modeling adjusted for potential confounding by maternal height, pre-pregnancy body mass index, smoking, parity, offspring gender and gestational age at birth. Results: Elevated maternal testosterone levels at week 17 and 33 were both associated with lower birth weights and lengths. Accordingly, at week 17, an increase in maternal testosterone levels from the 25th to the 75th percentile was associated with a decrease in birth weight by 160 g (95% confidence interval (CI); 29–290 g), while at week 33 that estimate was 115 g (95% CI; 21–207 g). No similar associations were observed for DHEAS, androstenedione or SHBG. Conclusions: Elevated maternal testosterone levels during human pregnancy are associated with growth restriction in utero. Our results support animal studies, which have indicated that maternal androgen levels influence intrauterine offspring environment and development.

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.

Female rats are protected against fructose-induced changes in metabolism and blood pressure

2002 ◽  
Vol 283 (6) ◽  
pp. H2478-H2484 ◽  
Author(s):  
Denise Galipeau ◽  
Subodh Verma ◽  
John H. McNeill
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Female Rats ◽  
Male Rats ◽  
Oral Glucose ◽  
Metabolic Parameter ◽  
Female Sex Hormones ◽  
Glucose Tolerance Tests ◽  
Induced Changes ◽  
And Control

The objective of this study was to determine whether the effects of a fructose diet, which causes hyperinsulinemia, insulin resistance, and hypertension in male rats, are dependent on sex. Blood pressure was measured via the tail-cuff method, and oral glucose tolerance tests were performed to assess insulin sensitivity. Blood pressure in female rats did not differ between fructose-fed and control rats at any time point (126 ± 5 and 125 ± 3 mmHg at week 9 for fructose-fed and control rats, respectively) nor was there a difference in any metabolic parameter measured. Furthermore, the vascular insulin resistance that is present in male fructose-fed rats was not observed. After ovariectomy, fructose caused a significant change in systolic blood pressure from baseline compared with fructose-fed ovary-intact rats (change of 21 ± 5 vs. −2 ± 4 mmHg). The results demonstrate that females do not develop hypertension or hyperinsulinemia upon fructose feeding except after ovariectomy, suggesting that female sex hormones may confer protection against the effects of a fructose diet.

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