Elevated insulin sensitivity and β-cell function during pregnancy in mothers of growth-restricted newborns

The “Barker hypothesis” suggests that low birth weight might predict future risk of developing obesity, cardiovascular disease, and type 2 diabetes. Identification of the causes of fetal growth restriction (FGR) is critical for preventive and management strategies. Some studies indicate that maternal carbohydrate metabolism might be involved in FGR development. We aimed to evaluate, in a large number of normotensive pregnant women with normal glucose tolerance, the effect of insulin sensitivity and β-cell function on unexplained fetal growth. A total of 1,814 Caucasian pregnant women with normal prepregnancy body mass index were tested with a 75-g, 2-h glucose load (24–28 gestation wk). Insulin sensitivity was evaluated with fasting (QUICKI) and dynamic index (OGIS) and β-cell function with a modified insulinogenic index as ΔAUCinsulin/ΔAUCglucose and disposition index. FGR was a birth weight below the 5th percentile for gestational age. FGR developed in 99 (5.5%) pregnant women that showed significantly higher QUICKI, OGIS, insulinogenic, and disposition index with respect to women with normal-weight babies ( P < 0.0001). By using multiple regression analysis in the FRG group, QUICKI and OGIS appeared as significant independent variables ( P < 0.0001 and P < 0.0366, respectively). We conclude that elevated insulin sensitivity seems to be one of the factors involved in determining unexplained fetal growth retardation; its assessment, even only in the fasting state, could be useful to guide any possible monitoring and therapeutic strategies to reduce fetal complications.

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Circulating Spexin Decreased and Negatively Correlated with Systemic Insulin Sensitivity and Pancreatic β Cell Function in Obese Children

Annals of Nutrition and Metabolism ◽

10.1159/000496459 ◽

2019 ◽

Vol 74 (2) ◽

pp. 125-131 ◽

Cited By ~ 7

Author(s):

Ting Chen ◽

Fengyun Wang ◽

Zhenyu Chu ◽

Ling Sun ◽

Haitao Lv ◽

...

Keyword(s):

Blood Pressure ◽

Insulin Sensitivity ◽

Cell Function ◽

Insulinogenic Index ◽

Model Assessment ◽

Pancreatic Β Cell ◽

Obese Children ◽

Β Cell ◽

Β Cell Function ◽

Obese Subjects

Objectives: Spexin (SPX) is a novel peptide that has recently emerged as an important regulatory adipokine of obesity and related metabolic disease. Little is known about its role in children. The aim of the current study was to determine the potential role of SPX in obese children and explore its relationships with obesity-related markers, insulin sensitivity and pancreatic β cell function. Method: We studied the levels of serum SPX in 40 obese and 32 normal weight pre-puberty children (mean age was 8.59 ± 1.82 and 8.15 ± 2.03 years in obesity and control groups respectively). We investigated the levels of body mass index, blood pressure, lipids, glucose, insulin, Homeostasis model assessment for insulin-resistant (HOMA-IR, HOMA for β-cell function [HOMA-β]), insulinogenic index and C-peptide index and analyzed their correlations with SPX levels. Results: SPX levels were significantly decreased in obese children compared to controls. Moreover, serum SPX levels were lower in IR obese subjects in contrast with the non-IR obese subjects. Serum SPX concentrations correlated negatively and significantly with triglycerides, systolic blood pressure, diastolic blood pressure, fasting insulin level, HOMA-IR, insulinogenic index, and HOMA-β levels in obese children. Conclusions: In summary, serum SPX levels significantly decreased in obese children and negatively correlated with insulin resistance and pancreatic β cell function indicators. Therefore, SPX may play a protective role in the process of glucose homeostasis and is closely related to β cell function in obese children.

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Association of Baseline Characteristics With Insulin Sensitivity and β-Cell Function in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study Cohort

10.2337/figshare.13247033 ◽

2020 ◽

Author(s):

Neda Rasouli ◽

Naji Younes ◽

Kristina M. Utzschneider ◽

Silvio E. Inzucchi ◽

Ashok Balasubramanyam ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Sensitivity ◽

African Americans ◽

Cell Function ◽

Insulinogenic Index ◽

Model Assessment ◽

Β Cell ◽

Black African ◽

Β Cell Function

Objective: We investigated sex and racial differences in insulin sensitivity, β-cell function and HbA1c, and the associations with selected phenotypic characteristics. Research Design and Methods: This is a cross-sectional analysis of baseline data from 3,108 GRADE participants. All had type 2 diabetes diagnosed <10 years and were on metformin monotherapy. Insulin sensitivity and β-cell function were evaluated using the homeostasis model assessment of insulin sensitivity (HOMA2-S) and estimates from oral glucose tolerance tests including the Matsuda index, insulinogenic index (IGI), C-peptide index (CPI) and oral disposition index (DI). Results: The cohort was 56.6±10 years of age (mean±SD), 63.8% male, with BMI 34.2±6.7 kg/m2, HbA1c 7.5±0.5% and type 2 diabetes duration 4.0±2.8 years. Women had higher DI than men but similar insulin sensitivity. DI was the highest in Black/African Americans, followed by American Indians/Alaska Natives, Asians and Whites in descending order. Compared to white, American Indian/Alaska Native had significantly higher HbA1c but Black/African Americans and Asians had lower HbA1c. However, when adjusted for glucose levels, Black/African Americans had higher HbA1c than whites. Insulin sensitivity correlated inversely with BMI, waist to hip ratio, triglyceride to HDL cholesterol ratio (TG/HDL- C) and the presence of metabolic syndrome; whereas DI was associated directly with age and inversely with BMI, HbA1c and TG/HDL-C. Conclusion: In the GRADE cohort, β-cell function differed by sex and race and was associated with the concurrent level of HbA1c. HbA1c also differed among the races, but not sex. Age, BMI and TG/HDL-C were associated with multiple measures of β-cell function and insulin sensitivity.

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The increase in serum 25-hydroxyvitamin D following weight loss does not contribute to the improvement in insulin sensitivity, insulin secretion and β-cell function

British Journal Of Nutrition ◽

10.1017/s0007114515001610 ◽

2015 ◽

Vol 114 (2) ◽

pp. 161-168 ◽

Cited By ~ 3

Author(s):

Véronique Thibault ◽

Anne-Sophie Morisset ◽

Christine Brown ◽

André C. Carpentier ◽

Jean-Patrice Baillargeon ◽

...

Keyword(s):

Weight Loss ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Cell Function ◽

Disposition Index ◽

Model Assessment ◽

Β Cell ◽

Hydroxyvitamin D ◽

Β Cell Function ◽

25 Hydroxyvitamin D

Serum 25-hydroxyvitamin D (25(OH)D) concentrations have been reported to increase following weight loss. Moreover, both weight loss and higher serum 25(OH)D concentrations have been associated with a lower risk of developing type 2 diabetes. The objective of the present study was to determine whether the increase in serum 25(OH)D concentration following weight loss is associated with improved insulin sensitivity, insulin secretion and disposition index (β-cell function). Data from two prospective lifestyle modification studies had been combined. Following a lifestyle-modifying weight loss intervention for 1 year, eighty-four men and women with prediabetes and a BMI ≥ 27 kg/m2 were divided based on weight loss at 1 year: < 5 % (non-responders, n 56) and ≥ 5 % (responders, n 28). The association between the change in serum 25(OH)D concentration and changes in insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA%S) and Matsuda), insulin secretion (AUC of C-peptide) and disposition index after adjustment for weight loss was examined. Participants in the responders' group lost on average 9·5 % of their weight when compared with non-responders who lost only 0·8 % of weight. Weight loss in responders resulted in improved insulin sensitivity (HOMA%S, P= 0·0003) and disposition index (P= 0·02); however, insulin secretion remained unchanged. The rise in serum 25(OH)D concentration following weight loss in responders was significantly higher than that in non-responders (8·9 (sd 12·5) v. 3·6 (sd 10·7) nmol/l, P= 0·05). However, it had not been associated with amelioration of insulin sensitivity and β-cell function, even after adjustment for weight loss and several confounders. In conclusion, the increase in serum 25(OH)D concentration following weight loss does not contribute to the improvement in insulin sensitivity or β-cell function.

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The Macrophage Activation Marker Soluble CD163 is Longitudinally Associated With Insulin Sensitivity and β-cell Function

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz166 ◽

2019 ◽

Vol 105 (3) ◽

pp. e285-e294 ◽

Cited By ~ 1

Author(s):

Zhila Semnani-Azad ◽

Philip W Connelly ◽

Luke W Johnston ◽

Ravi Retnakaran ◽

Stewart B Harris ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Sensitivity ◽

Cell Function ◽

Sensitivity Index ◽

Insulinogenic Index ◽

Β Cell ◽

Soluble Cd163 ◽

Β Cell Function ◽

Longitudinal Associations

Abstract Context Chronic inflammation arising from adipose tissue macrophage (ATM) activation may be central in type 2 diabetes etiology. Our objective was to assess the longitudinal associations of soluble CD163 (sCD163), a novel biomarker of ATM activation, with insulin sensitivity, β-cell function, and dysglycemia in high-risk subjects. Methods Adults at risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 408). Levels of sCD163 were measured using fasting serum. Insulin sensitivity was assessed by HOMA2-%S and the Matsuda index (ISI). β-cell function was determined by insulinogenic index (IGI) over HOMA-IR and insulin secretion-sensitivity index-2 (ISSI-2). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes. Generalized estimating equations (GEE) evaluated longitudinal associations of sCD163 with insulin sensitivity, β-cell function, and incident dysglycemia adjusting for demographic and lifestyle covariates. Areas under receiver-operating-characteristic curve (AROC) tested whether sCD163 improved dysglycemia prediction in a clinical model. Results Longitudinal analyses showed significant inverse associations between sCD163 and insulin sensitivity (% difference per standard deviation increase of sCD163 for HOMA2-%S (β = −7.01; 95% CI, −12.26 to −1.44) and ISI (β = −7.60; 95% CI, −11.09 to −3.97) and β-cell function (ISSI-2 (β = −4.67; 95 %CI, −8.59 to −0.58) and IGI/HOMA-IR (β = −8.75; 95% CI, −15.42 to −1.56)). Increased sCD163 was associated with greater risk for incident dysglycemia (odds ratio = 1.04; 95% CI, 1.02-1.06; P < 0.001). Adding sCD163 data to a model with clinical variables improved prediction of incident dysglycemia (AROC=0.6731 vs 0.638; P < 0.05). Conclusions sCD163 was longitudinally associated with core disorders that precede the onset of type 2 diabetes.

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Parental History of Type 2 Diabetes Abrogates Ethnic Disparities in Key Glucoregulatory Indices

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-01895 ◽

2017 ◽

Vol 103 (2) ◽

pp. 514-522 ◽

Cited By ~ 2

Author(s):

Ebenezer Nyenwe ◽

Ibiye Owei ◽

Jim Wan ◽

Sam Dagogo-Jack

Keyword(s):

Type 2 Diabetes ◽

Insulin Sensitivity ◽

African Americans ◽

Cell Function ◽

Ethnic Disparities ◽

Disposition Index ◽

Β Cell ◽

Β Cell Function ◽

Parental Diabetes

Abstract Context There are ethnic differences in glucoregulation and prevalence of type 2 diabetes, but studies on the role of genetics in modifying ethnic effects in normoglycemic African-Americans and Caucasians are limited. Therefore, we investigated glucoregulation in normoglycemic African-Americans and Caucasians with or without parental diabetes. Design Fifty subjects with parental diabetes (from the Pathobiology of Prediabetes in a Biracial Cohort Study) and 50 subjects without parental diabetes were matched in age, sex, ethnicity, and body mass index (BMI). Subjects underwent a 75-g oral glucose tolerance test (OGTT), physical examination, anthropometry, biochemistries, indirect calorimetry and assessment of body composition, insulin sensitivity by euglycemic clamp (Si-clamp), and β-cell function by Disposition index. Results The mean age was 40.5 ± 11.6 years, BMI 28.7 ± 5.9 kg/m2, fasting plasma glucose 90.2 ± 5.9 mg/dL, and 2-hour postglucose 120.0 ± 26.8 mg/dL. Offspring with parental diabetes showed higher glycemic excursion during OGTT–area under the curve–glucose (16,005.6 ± 2324.7 vs 14,973.8 ± 1819.9, P < 0.005), lower Si-clamp (0.132 ± 0.068 vs 0.162 ± 0.081 µmol/kg fat-free mass/min/pmol/L, P < 0.05), and lower Disposition index (8.74 ± 5.72 vs 11.83 ± 7.49, P < 0.05). Compared with lean subjects without parental diabetes, β cell function was lower by ∼30% in lean subjects with parental diabetes, ∼40% in obese subjects without parental diabetes, and ∼50% in obese individuals with parental diabetes (P < 0.0001). African-Americans without parental diabetes had ∼40% lower insulin sensitivity (P < 0.001), twofold higher acute insulin secretion (P < 0.001), but ∼30% lower Disposition index (P < 0.01) compared with Caucasians without parental diabetes. Remarkably, there were no significant differences by ethnicity in these glucoregulatory measures among subjects with parental diabetes. Conclusion Offspring with parental diabetes harbor substantial impairments in glucoregulation compared with individuals without parental diabetes. Ethnic disparities in glucoregulation were abrogated by parental diabetes.

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Vitamin D affects insulin sensitivity and β-cell function in obese non-diabetic youths

Acta Endocrinologica ◽

10.1530/eje-19-0369 ◽

2019 ◽

Vol 181 (4) ◽

pp. 439-450 ◽

Cited By ~ 1

Author(s):

Domenico Corica ◽

Chiara Zusi ◽

Francesca Olivieri ◽

Marco Marigliano ◽

Claudia Piona ◽

...

Keyword(s):

Vitamin D ◽

Insulin Sensitivity ◽

Cell Function ◽

Hypovitaminosis D ◽

Insulinogenic Index ◽

Β Cell ◽

Total Vitamin ◽

Proportional Control ◽

Matsuda Index ◽

Β Cell Function

Objective Vitamin D may potentially play a central role in glucose homeostasis and β-cell function (BCF), although studies are not consistent. Aim of our study was to test the hypotheses of a direct relationship between vitamin D, insulin sensitivity (IS) and BCF in overweight and obese non-diabetic children. Design and methods Cross-sectional study carried out at the Childhood Obesity Outpatient Clinic, University Hospital of Verona. One hundred twenty-two Caucasian overweight and obese children (age: 12.8 ± 0.2 years) were enrolled. Exclusion criteria: genetic or endocrine causes of obesity, chronic diseases or therapies. Patients underwent oral glucose tolerance test. HOMA-IR, Matsuda index and insulinogenic index were calculated. BCF was reconstructed by mathematical modeling and described by Derivative and Proportional Control. Total 25-hydroxyvitamin D and vitamin D-binding protein (VDBP) were measured. Two SNPs (rs4588 and rs7041) in the VDBP gene were studied, and bioavailable vitamin D (BVD) was calculated. Results Hypovitaminosis D was documented in 90% of patients. Forty-seven subjects were homozygous for both SNPs. Total vitamin D was positively correlated with Matsuda index (P = 0.002), VDBP (P = 0.045), and negatively with BMI SDS (P = 0.043), HOMA-IR (P = 0.008), HOMA-B (P = 0.001), IGI (P = 0.007), derivative control (P = 0.036) and proportional control (P = 0.018). Total vitamin D, adjusted for age, gender, BMI SDS, puberty and seasonality of vitamin D measurement, was a predictor of Matsuda index, HOMA-IR, HOMA-B, IGI, proportional control (all P < 0.05). BVD was positively correlated with total vitamin D (P < 0.001) and negatively with BMI SDS (P = 0.041). Conclusions Hypovitaminosis D negatively influences BCF and IS, suggesting that vitamin D levels might be implicated in glucose metabolism impairment in overweight and obese individuals.

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Overweight is associated with impaired β-cell function during pregnancy: a longitudinal study of 553 normal pregnancies

Acta Endocrinologica ◽

10.1530/eje-09-0416 ◽

2010 ◽

Vol 162 (1) ◽

pp. 67-73 ◽

Cited By ~ 9

Author(s):

E Qvigstad ◽

N Voldner ◽

K Godang ◽

T Henriksen ◽

J Bollerslev

Keyword(s):

Insulin Sensitivity ◽

Gestational Diabetes ◽

Glucose Tolerance ◽

Cell Function ◽

Normal Weight ◽

Oral Glucose ◽

Β Cell ◽

Overweight Women ◽

Glucose Tolerant ◽

Β Cell Function

ObjectiveTo monitor β-cell function and insulin sensitivity longitudinally in a large cohort of pregnant women to elucidate mechanisms that influence glycemic control in pregnancy.Design and methodsFive hundred and fifty-three pregnant Scandinavian women underwent 75 g oral glucose tolerance test (OGTT) at weeks 14–16 and 30–32. Insulin sensitivity (Matsuda index) and β-cell function (ratio of AUCinsulin to AUCglucose, AUCins/glc) were calculated from 520 complete tests, and subsequently β-cell function was adjusted for insulin sensitivity, rendering an oral disposition index (DIo).ResultsEleven women (2.1%) had gestational diabetes mellitus (GDM1) at weeks 14–16, and 49 (9.4%) at weeks 30–32 (GDM2), which is higher than that previously reported in this region. In the subdivision of OGTT, more overweight (body mass index>25) was found in glucose-intolerant groups (glucose-tolerant women (normal glucose tolerance, NGT) 38 versus GDM2 women 58 and GDM1 women 82%, P<0.005). In early pregnancy, insulin sensitivity was lowest in GDM1, intermediate in GDM2, and highest in NGT. In late pregnancy, insulin sensitivity decreased in all groups, most in gestational diabetes. β-cell function demonstrated minor shifts during pregnancy, but when adjusted for decreasing insulin sensitivity, DIo levels fell by 40% (P<0.001). DIo was significantly attenuated relative to glucose intolerance (GDM1 25% and GDM2 53%) during pregnancy. In overweight women, DIo levels were lower throughout pregnancy (P<0.001 versus normal weight women), this reduction was significant (P<0.01) in both NGT (21–25%) and GDM2 subjects (26–49%).Conclusionβ-cell function adjusted for insulin sensitivity (DIo) deteriorated during pregnancy in both glucose-tolerant and glucose-intolerant women. The failure to compensate the decrease in insulin sensitivity was accentuated in overweight women.

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Association of Baseline Characteristics With Insulin Sensitivity and β-Cell Function in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study Cohort

10.2337/figshare.13247033.v1 ◽

2020 ◽

Author(s):

Neda Rasouli ◽

Naji Younes ◽

Kristina M. Utzschneider ◽

Silvio E. Inzucchi ◽

Ashok Balasubramanyam ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Sensitivity ◽

African Americans ◽

Cell Function ◽

Insulinogenic Index ◽

Model Assessment ◽

Β Cell ◽

Black African ◽

Β Cell Function

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Impact of a High Intake of Dairy Product on Insulin Sensitivity in Hyperinsulinemic Adults: A Crossover Randomized Controlled Trial

Current Developments in Nutrition ◽

10.1093/cdn/nzz083 ◽

2019 ◽

Vol 3 (8) ◽

Cited By ~ 5

Author(s):

Sarah O'Connor ◽

Pierre Julien ◽

Stanley John Weisnagel ◽

Claudia Gagnon ◽

Iwona Rudkowska

Keyword(s):

Risk Factors ◽

Clinical Trial ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Cell Function ◽

Dairy Product ◽

Insulinogenic Index ◽

Β Cell ◽

Related Risk ◽

Β Cell Function

ABSTRACT Background Dairy product intake has been associated with decreased risk of type 2 diabetes (T2D) in cohort studies. However, results from clinical trials on T2D-related risk factors remain inconclusive. Objective The aim of this clinical trial was to evaluate the impact of high dairy product intake (HD) (≥4 servings/d) for 6 wk, compared with an adequate dairy product intake (AD) (≤2 servings/d), on glycemic and insulinemic parameters, insulin sensitivity, insulin secretion, and β-cell function in hyperinsulinemic adults. Methods In this crossover clinical trial, hyperinsulinemic adults were randomly assigned to HD or AD for 6 wk, then crossed over after a 6-wk washout period. Serum glucose, insulin, C-peptide, HOMA-IR, Matsuda index, insulinogenic index, and disposition index were measured and analyzed using a repeated-measures mixed model adjusted for age, sex, and BMI. Anthropometric measures were collected and food intake was evaluated using a validated FFQ. Results Nineteen men and 8 women completed the study (mean ± SD age: 55 ± 14 y; BMI: 31.3 ± 3.3 kg/m2. Dairy product intake was 5.8 servings/d in the HD condition and 2.3 servings/d in the AD condition after 6 wk. No difference was observed between HD and AD after 6 wk for all outcomes. Conclusions HD does not affect glycemic and insulinemic parameters, insulin sensitivity, insulin secretion, and β-cell function over AD in hyperinsulinemic adults. Additional larger and longer studies assessing T2D-related risk factors are required. This trial was registered at clinicaltrials.gov as NCT02961179.

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Large-for-Gestational-Age May Be Associated With Lower Fetal Insulin Sensitivity and β-Cell Function Linked to Leptin

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-00917 ◽

2018 ◽

Vol 103 (10) ◽

pp. 3837-3844 ◽

Cited By ~ 2

Author(s):

Yu Dong ◽

Zhong-Cheng Luo ◽

Anne Monique Nuyt ◽

Francois Audibert ◽

Shu-Qin Wei ◽

...

Keyword(s):

Birth Weight ◽

Insulin Sensitivity ◽

Cord Blood ◽

Gestational Age ◽

Cell Function ◽

Large For Gestational Age ◽

Β Cell ◽

Cord Plasma ◽

Increased Risk ◽

Β Cell Function

AbstractContextFetal overgrowth is associated with increased risk for type 2 diabetes in adulthood. It is unclear whether there are alterations in insulin sensitivity and β-cell function in early life.ObjectiveTo determine whether large-for-gestational-age (LGA) (birth weight > 90th percentile), an indicator of fetal overgrowth, is associated with altered fetal insulin sensitivity and β-cell function.Study Design, Population, and OutcomesIn the Design, Development, and Discover birth cohort in Canada, we studied 106 pairs of LGA and optimal-for-gestational-age (OGA; birth weight, 25th to 75th percentiles) infants matched by maternal ethnicity, smoking status, and gestational age. Cord plasma glucose-to-insulin ratio was used as an indicator of fetal insulin sensitivity, and proinsulin-to-insulin ratio was used as an indicator of β-cell function. Cord plasma leptin and high-molecular-weight (HMW) adiponectin concentrations were measured.ResultsComparisons of infants who were born LGA vs OGA, adjusted for maternal and newborn characteristics, showed that cord blood insulin, proinsulin, and leptin concentrations were significantly higher, whereas HWM adiponectin concentrations were similar. Glucose-to-insulin ratios were significantly lower (15.4 ± 28.1 vs 22.0 ± 24.9; P = 0.004), and proinsulin-to-insulin ratios significantly higher (0.73 ± 0.82 vs 0.60 ± 0.78; P = 0.005) in LGA vs OGA newborns, indicating lower insulin sensitivity and β-cell function in LGA newborns. These significant differences were almost unchanged after further adjustment for cord blood adiponectin levels but disappeared upon additional adjustment for cord blood leptin levels.ConclusionsThis study demonstrates that LGA may be associated with decreases in both fetal insulin sensitivity and β-cell function. The alterations appear to be linked to elevated leptin levels.

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