Maternal C-Peptide and Insulin Sensitivity, but Not BMI, Associate with Fatty Acids in the First Trimester of Pregnancy

Maternal obesity in pregnancy is a pro-inflammatory condition exposing the fetus to an adverse environment. Here, we tested associations of maternal obesity (primary exposures: BMI, leptin) and metabolic parameters (secondary exposures: glucose, C-peptide, and insulin sensitivity) with total serum concentrations of fatty acids in the first trimester of human pregnancy. This cross-sectional study included 123 non-smoking women with singleton pregnancy. In maternal serum, cotinine, leptin, and C-peptide (ELISA), glucose (hexokinase-based test) and fatty acids (gas chromatography) were quantified, and the insulin sensitivity index (ISHOMA) was calculated. Concentrations of fatty acid classes and total fatty acids did not differ between BMI or leptin categories. However, n-3 polyunsaturated fatty acids (PUFA) were decreased in the category with the highest C-peptide concentration (n-3 PUFA: CI −35.82–−6.28, p < 0.006) and in the lowest ISHOMA category (n-3 PUFA: CI −36.48–−5.61, p < 0.008). In a subcohort, in which fetal sex was determined (RT-qPCR of placental tissue), C-peptide was significantly associated with docosahexaenoic acid (DHA) in mothers bearing a female (n = 46), but not male (n = 37) fetus. In conclusion, pregnant women with high fasting C-peptide and low ISHOMA had decreased n-3 PUFA, and DHA was lower with higher C-peptide only in mothers bearing a female fetus.

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Abstract 1924: Carriers of Loss-of-Function Mutations in ABCA1 Display Pancreatic Beta Cell Dysfunction

Circulation ◽

10.1161/circ.118.suppl_18.s_406 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Menno Vergeer ◽

Liam R Brunham ◽

Joris Koetsveld ◽

Janine K Kruit ◽

C B Verchere ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Plasma Glucose ◽

Sensitivity Index ◽

Loss Of Function ◽

Β Cell ◽

C Peptide ◽

Cell Dysfunction ◽

Time Interaction

Background The ATP Binding Cassette transporter A1 (ABCA1) transports free cholesterol to nascent high-density lipoproteins (HDL) and maintains plasma HDL levels. In mice, ABCA1 is essential in regulating intracellular cholesterol homeostasis and insulin secretion in the β cell. The role of ABCA1 in human glucose metabolism is unclear. Objective and methods To assess the effects of ABCA1 dysfunction on glucose homeostasis in humans , we matched heterozygous carriers of disruptive mutations in ABCA1 and non-carriers for age, gender and BMI and performed oral glucose tolerance tests (OGTT; 9 vs. 8 respectively) and hyperglycemic clamping experiments (6 vs. 6). Results Carriers had lower HDL-C levels than non-carriers (0.58 ± 0.3 vs. 1.46 ± 0.4 mmol/L, p=0.001) but LDL-C did not differ (3.4 ± 1.0 vs. 2.8 ± 0.8 mmol/L, p=0.21). Fasting plasma glucose was not different (5.2 ± 1.5 vs. 5.0 ± 0.4 mmol/L). Glucose curves after OGTT were significantly higher in carriers than in non-carriers (genotype * time interaction, p=0.005; plasma glucose at t=60 min 9.0 ± 3.0 mmol/L vs. 6.0 ± 1.4 mmol/L respectively, p=0.02). During hyperglycemic clamps, carriers showed a lower first phase insulin and C-peptide response than non-carriers (genotype * time interaction, p<0.05 and p<0.01 respectively; insulin at t=5 min 164±118 vs. 352 ±141 pmol/L, p<0.05; C-peptide at t=5 min 1033 ± 628 vs. 1942 ± 723 pmol/L, p<0.05) but no difference in insulin sensitivity index (0.0216 ± 0.012 mg kg −1 . min −1 . pM −1 for carriers and 0.0197 ± 0.005 mg kg −1 . min −1 . pM −1 for non-carriers; p=0.73). Disposition index - a measure of β cell function, adjusted for insulin sensitivity - was lower in carriers than in non-carriers (1037 ± 610 vs. 2718 ± 1524; p<0.05). Non-carriers responded to an arginine stimulus with an increase in C-peptide levels (from 3558 ± 1240 pM to 6817 ± 1665 pM; p<0.005), whereas in carriers this increase did not reach statistical significance (from 3727 ± 1843 pM to 5480 ± 1757 pM; p=0.12). Conclusion Carriers of loss-of-function mutations in ABCA1 show impaired insulin secretion without insulin resistance, resulting in glucose intolerance. Our data confirm previous studies in mice and provide evidence for a role of ABCA1 in β cell dysfunction and the pathophysiology of diabetes mellitus in man.

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Sex-dependent nutritional programming: fish oil intake during early pregnancy in rats reduces age-dependent insulin resistance in male, but not female, offspring

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00392.2012 ◽

2013 ◽

Vol 304 (4) ◽

pp. R313-R320 ◽

Cited By ~ 27

Author(s):

Fatima L. C. Sardinha ◽

Flavia S. Fernandes ◽

Maria G. Tavares do Carmo ◽

Emilio Herrera

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

Insulin Sensitivity ◽

Early Pregnancy ◽

Adult Life ◽

Male Offspring ◽

Oral Glucose ◽

Sensitivity Index ◽

Standard Diet ◽

Model Assessment

Prenatal and early postnatal nutritional status may predispose offspring to impaired glucose tolerance and changes in insulin sensitivity in adult life. The long-term consequences of changes in maternal dietary fatty acid composition were determined in rats. From day 1 until day 12 of pregnancy, rats were given isocaloric diets containing 9% nonvitamin fat based on soybean, olive, fish (FO), linseed, or palm oil. Thereafter, they were maintained on the standard diet; offspring were studied at different ages. Body weight at 4, 8, and 12 mo and lumbar adipose tissue and liver weights at 12 mo did not differ between females on the different diets, whereas in males the corresponding values were all lower in the offspring from the FO group compared with the other dietary groups. Plasma glucose concentrations (both basal and after an oral glucose load) did not change with sex or dietary group, but plasma insulin concentrations were lower in females than in males and, in males, were lowest in the FO group. Similar relations were found with both the homeostasis model assessment of insulin resistance and insulin sensitivity index. In conclusion, the intake of more n–3 fatty acids (FO diet) during early pregnancy reduced both fat accretion and age-related decline in insulin sensitivity in male offspring but not in females. It is proposed that the lower adiposity caused by the increased n–3 fatty acids during the intrauterine life was responsible of the lower insulin resistance in male offspring.

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Influence of Tacrolimus on Glucose Metabolism before and after Renal Transplantation: A Prospective Study

Journal of the American Society of Nephrology ◽

10.1681/asn.v123583 ◽

2001 ◽

Vol 12 (3) ◽

pp. 583-588 ◽

Cited By ~ 1

Author(s):

ELLY M. VAN DUIJNHOVEN ◽

JOHANNES M. M. BOOTS ◽

MAARTEN H. L. CHRISTIAANS ◽

BRUCE H. R. WOLFFENBUTTEL ◽

JOHANNES P. VAN HOOFF

Keyword(s):

Insulin Resistance ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Glucose Metabolism ◽

Sensitivity Index ◽

Intravenous Glucose ◽

Prospective Longitudinal Study ◽

C Peptide ◽

Before And After ◽

Prospective Longitudinal

Abstract. Most studies concerning the influence of tacrolimus on glucose metabolism have been performed either in animals or after organ transplantation. These clinical studies have largely been transversal with patients who were using steroids. Therefore, this prospective, longitudinal study investigated the influence of tacrolimus on glucose metabolism before and after transplantation. Eighteen Caucasian dialysis patients underwent an intravenous glucose tolerance test before and 5 d after the start of tacrolimus. Insulin sensitivity index (kG), insulin resistance (insulin/glucose ratio and homeostasis model assessment), and C-peptide and insulin secretion were calculated. Trough levels of tacrolimus were measured. After transplantation, the occurrence of posttransplantation diabetes mellitus (PTDM) was prospectively monitored. Statistical analysis was performed using the Wilcoxon signed ranks test and Spearman's rho for correlation. Before tacrolimus, kG was indeterminate in three patients. During tacrolimus, kG decreased in 16 of 18 patients, from a median of 1.74 mmol/L per min to 1.08 mmol/L per min (P < 0.0001). The correlation between C-peptide and insulin data was excellent. Insulin secretion decreased from 851.0 mU × min/L to 558.0 mU × min/L (P = 0.014), whereas insulin resistance did not change. Insulin sensitivity correlated negatively with tacrolimus trough level. After transplantation, three patients developed PTDM; before tacrolimus, two had an indeterminate and one a low normal kG. During tacrolimus administration, kG decreased in almost all patients as a result of a diminished insulin secretion response to a glucose load, whereas insulin resistance did not change. Patients with an abnormal or indeterminate kG seem to be at risk of developing PTDM while on tacrolimus.

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Relationship of maternal obesity and vitamin D concentrations with fetal growth in early pregnancy

European Journal of Nutrition ◽

10.1007/s00394-021-02695-w ◽

2021 ◽

Author(s):

Qianqian Zhang ◽

Chen Zhang ◽

Yi Wang ◽

Jiuru Zhao ◽

Haiyuan Li ◽

...

Keyword(s):

Vitamin D ◽

Fetal Growth ◽

Protective Factor ◽

Maternal Obesity ◽

First Trimester ◽

Normal Weight ◽

Maternal Serum ◽

Clinical Trial Registry ◽

Singleton Pregnancy ◽

Crown Rump Length

Abstract Purpose To evaluate the effects of the association between first trimester vitamin D (VitD) concentrations and increased prepregnancy body mass index (BMI) on early fetal growth restriction (FGR). Methods This retrospective cohort study included 15,651 women with singleton pregnancy who delivered at the International Peace Maternity and Child Health Hospital between January 2015 and November 2016. Women were classified in two groups based on their serum 25(OH)D vitamin levels status: VitD sufficient (SUFF) group and VitD insufficient or deficient (INSUFF/DEF). The cut-off point for vit D concentration was 50.00 nmol/L. Comparisons were made between women with normal prepregnancy body weight (BMI 18.5–23.9 kg/m2) and overweight and obese (OWO) women (BMI > 24.0 kg/m2). Early FGR was defined as first-trimester gestational age-adjusted crown-rump length (CRL) in the lowest 20th centile of the population. Multivariate logistic regression was used to evaluate the association between maternal serum 25(OH)D levels and prepregnancy BMI with first trimester CRL and early FGR. Results In VitD INSUFF/DEF group, the first trimester CRL was decreased (P = 0.005), and the risk of early FGR was increased by 13% (95% CI 1.04–1.24, P = 0.004) compared to the VitD SUFF group. In OWO group, the first trimester CRL was also significantly decreased (P < 0.0001), and the risk of early FGR was significantly increased by 58% (95% CI 1.40–1.78, P < 0.001) compared with normal weight group. Furthermore, there was a significant combined effect of maternal VitD concentrations and OWO on CRL (P for interaction = 0.02) and the risk of early FGR (P for interaction = 0.07). Conclusion Sufficient first trimester serum 25(OH)D concentration was a protective factor for early fetal growth, especially among OWO mothers. Chinese Clinical Trial Registry (Registration number: ChiCTR1900027447 with date of registration on November 13, 2019-retrospectively registered).

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Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2005.121 ◽

2005 ◽

Vol 43 (7) ◽

Cited By ~ 48

Author(s):

Soňa Stanická ◽

Karel Vondra ◽

Terezie Pelikánová ◽

Petr Vlček ◽

Martin Hill ◽

...

Keyword(s):

Hormone Replacement Therapy ◽

Insulin Sensitivity ◽

Hormone Replacement ◽

Glucose Disposal ◽

Sensitivity Index ◽

Insulin Sensitivity Index ◽

Thyroid Hormone Replacement ◽

C Peptide ◽

Glucoregulatory Hormones ◽

Thyroid Hormone Replacement Therapy

AbstractWe examined insulin sensitivity and secretion, together with the levels of selected glucoregulatory hormones, in 15 female patients with severe hypothyroidism (H) and during subsequent thyroid hormone replacement therapy (HRT) using the euglycaemic hyperinsulinaemic clamp technique. Insulin action, as evaluated by glucose disposal, the insulin sensitivity index, and fasting post-hepatic insulin delivery rate were established. The basal levels of insulin, C-peptide and counter-regulatory hormones were measured in basal condition. In H, glucose disposal (p<0.01), the insulin sensitivity index (p<0.01) and post-hepatic insulin delivery rate (p<0.05) were significantly lower than during HRT. No significant changes in the levels of fasting insulin and C-peptide were observed. The levels of counter-regulatory hormones in patients with H were significantly higher than during HRT (glucagon, p<0.05; epinephrine, p<0.01; cortisol, p<0.05; growth hormone, p<0.05). In H, an inverse correlation between insulin sensitivity and insulin secretion was observed (p<0.05). Cortisol was the most important factor affecting the variability of insulin sensitivity values, regardless of thyroid function (p=0.0012). In conclusion, H altered both insulin sensitivity and the levels of selected counter-regulatory hormones. The situation was restored by HRT, as manifested not only by normalisation of insulin sensitivity, secretion and levels of glucoregulatory hormones, but also by improvement of their relationships.

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Caffeine ingestion impairs insulin sensitivity in a dose-dependent manner in both men and women

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2012-0201 ◽

2013 ◽

Vol 38 (2) ◽

pp. 140-147 ◽

Cited By ~ 15

Author(s):

Marie-Soleil Beaudoin ◽

Brian Allen ◽

Gillian Mazzetti ◽

Peter J. Sullivan ◽

Terry E. Graham

Keyword(s):

Insulin Sensitivity ◽

Glucose Homeostasis ◽

Insulin Response ◽

Oral Glucose ◽

Sensitivity Index ◽

Dependent Manner ◽

Caffeine Ingestion ◽

Men And Women ◽

C Peptide ◽

Dose Dependent

The effects of alkaloid caffeine on insulin sensitivity have been investigated primarily in men, and with a single caffeine dose most commonly of 5–6 mg·kg−1 of body weight (BW). It is unknown if the effects of caffeine on glucose homeostasis are sex-specific and (or) dose-dependent. This study examined whether caffeine ingestion would disrupt glucose homeostasis in a dose-dependent or threshold manner. It also examined whether sex-specific responses to caffeine exist. It was hypothesized that women would have an exaggerated response to caffeine, and that caffeine would only impair glucose metabolism once a threshold was reached. Twenty-four healthy volunteers (12 males, 12 females) participated in 4 trials, in a crossover, randomized, and double-blind fashion. They ingested caffeine (1, 3, or 5 mg·kg−1 of BW) or placebo followed, 1 h later, by a 2-h oral glucose tolerance test. Glucose, insulin, C-peptide area under the curve (AUC), and insulin sensitivity index data were fitted to a segmented linear model to determine dose–responses. There were no differences between sexes for any endpoints. Regression slopes were significantly different from zero (p < 0.05) for glucose, insulin, and C-peptide AUCs, with thresholds being no different from zero. Increasing caffeine consumption by 1 mg·kg−1 of BW increased insulin and C-peptide AUCs by 5.8% and 8.7%, respectively. Despite this exaggerated insulin response, glucose AUC increased by 11.2 mmol per 120 min·L–1 for each mg·kg−1 BW consumed. These results showed that caffeine ingestion disrupted insulin sensitivity in a dose-dependent fashion beginning at very low doses (0–1 mg·kg−1 BW) in both healthy men and women.

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Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond

Frontiers in Immunology ◽

10.3389/fimmu.2021.752660 ◽

2021 ◽

Vol 12 ◽

Author(s):

Anders Hagen Jarmund ◽

Guro Fanneløb Giskeødegård ◽

Mariell Ryssdal ◽

Bjørg Steinkjer ◽

Live Marie Tobiesen Stokkeland ◽

...

Keyword(s):

Maternal Obesity ◽

Serum Levels ◽

First Trimester ◽

Maternal Serum ◽

Serum Samples ◽

Female Fetus ◽

Reactive Protein ◽

Nulliparous Women ◽

Cytokine Levels ◽

Multiparous Women

Pregnancy implies delicate immunological balance between two individuals, with constant changes and adaptions in response to maternal capacity and fetal demands. We performed cytokine profiling of 1149 longitudinal serum samples from 707 pregnant women to map immunological changes from first trimester to term and beyond. The serum levels of 22 cytokines and C-reactive protein (CRP) followed diverse but characteristic trajectories throughout pregnancy, consistent with staged immunological adaptions. Eotaxin showed a particularly robust decrease throughout pregnancy. A strong surge in cytokine levels developed when pregnancies progressed beyond term and the increase was amplified as labor approached. Maternal obesity, smoking and pregnancies with large fetuses showed sustained increase in distinct cytokines throughout pregnancy. Multiparous women had increased cytokine levels in the first trimester compared to nulliparous women with higher cytokine levels in the third trimester. Fetal sex affected first trimester cytokine levels with increased levels in pregnancies with a female fetus. These findings unravel important immunological dynamics of pregnancy, demonstrate how both maternal and fetal factors influence maternal systemic cytokines, and serve as a comprehensive reference for cytokine profiles in normal pregnancies.

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Islet Function and Insulin Sensitivity in Latent Autoimmune Diabetes in Adults Taking Sitagliptin: A Randomized Trial

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab026 ◽

2021 ◽

Author(s):

Lin Yang ◽

Huiying Liang ◽

Xinyuan Liu ◽

Xia Wang ◽

Ying Cheng ◽

...

Keyword(s):

Insulin Sensitivity ◽

Cell Function ◽

Autoimmune Diabetes ◽

Sensitivity Index ◽

Β Cell ◽

C Peptide ◽

Latent Autoimmune Diabetes ◽

Dipeptidyl Peptidase 4 Inhibitors ◽

Cont Group ◽

Β Cell Function

Abstract Context The long-term effects of dipeptidyl peptidase-4 inhibitors on β-cell function and insulin sensitivity in latent autoimmune diabetes in adults (LADA) are unclear. Objective To investigate the effects of sitagliptin on β-cell function and insulin sensitivity in LADA patients receiving insulin. Design and Setting A randomized controlled trial at the Second Xiangya Hospital. Methods Fifty-one patients with LADA were randomized to sitagliptin + insulin (SITA) group or insulin alone (CONT) group for 24 months. Main Outcome Measures Fasting C-peptide (FCP), 2-hour postprandial C-peptide (2hCP) during mixed-meal tolerance test, △CP (2hCP – FCP), and updated homeostatic model assessment of β-cell function (HOMA2-B) were determined every 6 months. In 12 subjects, hyperglycemic clamp and hyperinsulinemic euglycemic clamp (HEC) tests were further conducted at 12-month intervals. Results During the 24-month follow-up, there were no significant changes in β-cell function in the SITA group, whereas the levels of 2hCP and △CP in the CONT group were reduced at 24 months. Meanwhile, the changes in HOMA2-B from baseline were larger in the SITA group than in the CONT group. At 24 months, first-phase insulin secretion was improved in the SITA group by hyperglycemia clamp, which was higher than in the CONT group (P < .001), while glucose metabolized (M), insulin sensitivity index, and M over logarithmical insulin ratio in HEC were increased in the SITA group (all P < .01 vs baseline), which were higher than in the CONT group. Conclusion Compared with insulin intervention alone, sitagliptin plus insulin treatment appeared to maintain β-cell function and improve insulin sensitivity in LADA to some extent.

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