Age-Dependent Nongenetic Influences of Birth Weight and Adult Body Fat on Insulin Sensitivity in Twins

AbstractBackgroundHigher birth weight is associated with higher adult body mass index (BMI). If genetic variants can be identified with alleles that predispose to both greater fetal growth and to greater adult adiposity, such shared genetic effects might indicate biological processes important in the early patterning of adiposity. However, variants identified in genome-wide association studies of adult BMI have overall been only weakly associated with birth weight. Genetic variants have recently been identified where one allele is associated with higher adult body fat percentage, but lower risk of metabolic disease, likely due to a favourable body fat distribution. The effect of these adult metabolically favourable adiposity alleles on an individual’s own birth weight is unknown.AimWe aimed to test the effect on birth weight of a fetal genetic predisposition to higher metabolically favourable adult adiposity and to compare this with the effects of a fetal genetic predisposition to higher adult BMI. We also aimed to examine the effects of a genetic predisposition to higher metabolically favourable adult adiposity or BMI on other birth anthropometric traits (length, ponderal index, head circumference and skinfold thickness) and on cord-blood insulin, leptin and adiponectin.MethodsWe used published GWAS data from up to 406,063 individuals to estimate the fetal effects on birth weight of alleles that are robustly associated with higher metabolically favourable adult adiposity or BMI. We additionally used 9,350 mother-child pairs from four cohorts to test the effects of the same alleles on other birth anthropometric traits and cord-blood markers. In all analyses, we adjusted for potential confounding due to the maternal genotype. We used inverse-variance weighted meta-analyses to combine summary data across SNPs.ResultsFetal genetic predisposition to higher metabolically favourable adult adiposity was associated with higher birth weight (10 grams (95% CI: 7 to 13) higher mean birth weight per 1 SD pooled “genetic score”). Fetal genetic predisposition to higher adult BMI was also associated with higher birth weight, but with a smaller magnitude of effect (4 grams (95% CI: 0 to 8) higher mean birth weight per 1 SD pooled “genetic score”) and with higher heterogeneity across SNPs. Effects on other birth anthropometric outcomes were consistent with the effect on birth weight but with wider confidence intervals. There was no strong evidence for an effect on cord-blood markers.ConclusionsSome genetic variants previously linked to adult adiposity influence birth weight. Alleles that predispose to higher metabolically favourable adult adiposity collectively have a stronger effect on birth weight than those predisposing to higher BMI. This suggests that the early accumulation of a metabolically favourable fat distribution might underlie part of the observed association between higher birth weight and higher adult BMI. Larger samples are needed to clarify the effects on other birth anthropometric measures and cord-blood markers.

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Relationship between Insulin Sensitivity and Body Fat Composition, and Leptin Sensitivity in Non-Obese and Overweight/Obese Adults

Myanmar Health Sciences Research Journal ◽

10.34299/mhsrj.00950 ◽

2019 ◽

Vol 31 (3) ◽

pp. 212-218

Keyword(s):

Insulin Sensitivity ◽

Body Fat ◽

Negative Relationship ◽

The Body ◽

Sensitivity Index ◽

Moderate Degree ◽

Model Assessment ◽

Obese Adults ◽

Leptin Sensitivity ◽

Fat Composition

Both insulin and leptin are major contributors for the body energy balance. Obesity is a state of energy imbalance and is also associated with changes in both insulin sensitivity and leptin sensitivity. The aim of this study was to find out the relationship between insulin sensitivity and body fat composition, and leptin sensitivity in non-obese and obese adults. A total of 86 adults participated: 42 non-obese and 44 over-weight/obese. Body fat (BF) percent was determined by skinfold method. Fasting plasma glucose was analyzed by glucose oxidase-phenol and 4 aminophenazone (GOD-PAP) method using spectro-photometer, fasting serum insulin and leptin concentrations by direct sandwich ELISA method and resting energy expenditure (REE) by indirect calorimetry. Leptin sensitivity index and insulin sensitivity were expressed as REE : Leptin ratio and homeostatic model assessment-insulin resistance (HOMA-IR), respectively. It was found that median value of HOMA-IR was significantly higher [2.93 vs 1.72, p<0.01] and leptin sensitivity was significantly lower [116.76 vs 265.66, p<0.001] in the overweight/obese adults than the non-obese adults, indicating that insulin sensitivity and leptin sensitivity were markedly reduced in overweight/obese adults in compare to non-obese adults. There was a moderate degree of positive relationship between HOMA-IR and BF only in the overweight/obese (ρ=0.509, n=44, p<0.001) and all adults (ρ=0.39, n=86, p<0.001). Similarly, a weak negative relationship between leptin sensitivity index and HOMA-IR was found in the overweight/obese (ρ=-0.328, n=44, p<0.05) and all adults (ρ=-0.35, n=86, p<0.01). It can be concluded that the insulin sensitivity was adiposity dependent, but, it did not depend on leptin sensitivity.

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Maternal diabetes alters birth weight in glucokinase-deficient (MODY2) kindred but has no influence on adult weight, height, insulin secretion or insulin sensitivity

Diabetologia ◽

10.1007/s001250051490 ◽

2000 ◽

Vol 43 (8) ◽

pp. 1060-1063 ◽

Cited By ~ 45

Author(s):

G. Velho ◽

A. T. Hattersley ◽

P. Froguel

Keyword(s):

Insulin Secretion ◽

Birth Weight ◽

Insulin Sensitivity ◽

Maternal Diabetes ◽

Adult Weight

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Beneficial Effect of Diazoxide in Obese Hyperinsulinemic Adults1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.6.4852 ◽

1998 ◽

Vol 83 (6) ◽

pp. 1911-1915 ◽

Cited By ~ 3

Author(s):

Ramin Alemzadeh ◽

Gina Langley ◽

Lori Upchurch ◽

Pam Smith ◽

Alfred E. Slonim

Keyword(s):

Insulin Sensitivity ◽

Glucose Tolerance ◽

Body Fat ◽

Therapeutic Potential ◽

Controlled Trial ◽

Insulin Response ◽

Tolerance Test ◽

Fat Free Mass ◽

Zucker Rats ◽

Significant Difference

Hyperinsulinemia, insulin resistance, and increased adipose tissue are hallmarks of the obesity state in both humans and experimental animals. The role of hyperinsulinemia as a possible preceding event in the development of obesity has been proposed. We previously demonstrated that administration of diazoxide (DZ), an inhibitor of insulin secretion, to obese hyperinsulinemic Zucker rats resulted in less weight gain, enhanced insulin sensitivity, and improved glucose tolerance. Assuming that hyperinsulinemia plays a major role in the development of human obesity, then its reversal should have therapeutic potential. To test this hypothesis, we conducted a randomized placebo-controlled trial in 24 hyperinsulinemic adults [body mass index (BMI) > 30 kg/m2]. All subjects were placed on a low-calorie (1260 for females and 1570 for males) Optifast (Sandoz, Minneapolis, MN) diet. After an initial 1-week lead-in period, 12 subjects (mean ± se for age and BMI, 31 ± 1 and 40 ± 2, respectively) received DZ (2 mg/kg BW·day; maximum, 200 mg/day, divided into 3 doses) for 8 weeks; and 12 subjects (mean± se for age and BMI, 28 ± 1 and 43 ± 1, respectively) received placebo. Compared with the placebo group, DZ subjects had greater weight loss (9.5 ± 0.69% vs. 4.6 ± 0.61%, P < 0.001), greater decrease in body fat (P < 0.01), greater increase in fat-free mass to body fat ratio (P < 0.01), and greater attenuation of acute insulin response to glucose (P < 0.01). However, there was no significant difference in insulin sensitivity and glucose effectiveness, as determined by the insulin-modified iv glucose tolerance test (Bergman’s minimal model) and no significant difference in glycohemoglobin values. Conclusion: 8 weeks treatment with DZ had a significant antiobesity effect in hyperinsulinemic obese adults without inducing hyperglycemia.

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Insulin Sensitivity, Glucose Effectiveness, and Body Fat Distribution Pattern in Nondiabetic Offspring of Patients With NIDDM

Diabetes Care ◽

10.2337/diacare.14.10.890 ◽

1991 ◽

Vol 14 (10) ◽

pp. 890-896 ◽

Cited By ~ 59

Author(s):

K. Osei ◽

D. A. Cottrell ◽

M. M. Orabella

Keyword(s):

Insulin Sensitivity ◽

Distribution Pattern ◽

Body Fat ◽

Fat Distribution ◽

Body Fat Distribution ◽

Glucose Effectiveness

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Abstract P250: Insulin Resistance During Pregnancy is Inversely Associated With Gynoid Fat Distribution Postpartum

Circulation ◽

10.1161/circ.137.suppl_1.p250 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Katherine H Ingram ◽

Roxanna Lopez

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Insulin Sensitivity ◽

Gestational Weight Gain ◽

Body Fat ◽

Visceral Fat ◽

Post Partum ◽

Lower Body ◽

Negatively Associated ◽

Gestational Weight

An association between abdominal adiposity and insulin resistance is well-established. Recent research indicates that subcutaneous fat accumulation in the lower body may be associated with higher levels of insulin sensitivity. Hypothesis: This pilot study tested the hypothesis that the distribution of body fat in the lower body after pregnancy is negatively associated with gestational insulin resistance. Methods: In 32 nulliparous pregnant women (age 27±4.5, BMI 29.5±7.9, 69% non-hispanic white), the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was computed from fasting glucose and insulin at 24-28 weeks gestation. Body composition was assessed at mid-gestation (18-20 weeks) and at four weeks post-partum. Total body fat was estimated via bioelectrical impedance (InBody 720) and skinfold thicknesses were measured at seven sites. Dual-energy xray absorptiometry (DXA) measures of regional fat (gynoid, visceral, and leg) were obtained post-partum only. Gestational weight gain was monitored by medical records. Partial correlation analyses were controlled for age and race and then analyses were repeated controlling for baseline (mid-gestation) body fat percent. HOMA-IR was log-transformed for normality. Results: HOMA-IR was associated with post-partum body fat ( r =0.45, p < .05) and adiposity in the trunk region ( r =0.58, 0.57 and 0.52 for DXA visceral fat, suprailiac skinfold, and abdominal skinfold, respectively, p < .01), but not with gestational weight gain ( r =.07, p = ns), DXA gynoid region ( r = 0.26, p = ns), or any other leg measure. When analyses were further controlled for baseline body fat, post-partum measures of lower-body adiposity were strongly and negatively correlated with HOMA-IR ( r = -0.66, -0.48, and -0.48 for thigh skinfold, DXA gynoid, and DXA leg, respectively, p < .05 for all). Neither DXA visceral fat ( r = .23; p = ns) nor any other post-partum fat measures were associated with HOMA-IR when controlling for baseline body fat. Conclusions: Gestational insulin resistance was negatively associated with post-partum thigh fat accumulation, independent of overall body fat. These data indicate that insulin sensitivity may be associated with the ability to store fat in the lower body and should warrant further study of subcutaneous leg fat as a metabolically “healthy” storage depot.

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Abstract P098: Maternal Insulin/Glycemic Regulation, Leptin, and Adiposity Levels are Associated with Newborn Adiposity

Circulation ◽

10.1161/circ.129.suppl_1.p098 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Julie Patenaude ◽

Catherine Allard ◽

Marilyn Lacroix ◽

Laeticia Guillemette ◽

Marie-Claude Battista ◽

...

Keyword(s):

Birth Weight ◽

Body Fat ◽

Medical Records ◽

Population Based ◽

Maternal Body Mass Index ◽

Fasting Insulin ◽

Metabolic Characteristics ◽

Neonatal Adiposity ◽

Glycemic Regulation ◽

Maternal Bmi

Introduction: Leptin is a hormone secreted by adipocytes that circulates in proportion to body fat. Placenta also produces leptin suggesting a specific role during pregnancy, maybe contributing to pregnancy-induced insulin resistance. Objective: To determine the associations between maternal levels of leptin, glucose and insulin and weight/adiposity measures in newborns. Methods: A population-based cohort of pregnant women in the region of Sherbrooke, Canada was recruited in early pregnancy (n=1040 at 1 st trimester). Maternal anthropometry was measured and blood samples were collected at the 1 st and 2 nd trimesters to measure glucose (hexokinase), leptin and insulin (ELISA Luminex, Millipore Canada). Birth weights were recorded from the medical records in 783 newborns (full term >36 weeks). We measured skinfolds in 199 newborns within 72h after birth, using a standardized caliper. We measured triceps, biceps, subscapular and supra-iliac skinfolds and the sum of skinfolds was used for analysis representing overall neonatal adiposity. Correlations and linear regression analyses were performed to evaluate the associations between maternal metabolic characteristics and neonatal weight/adiposity measures. Results: Birth weight was associated with maternal body mass index (BMI; r=0.18 and r=0.20 at 1st and 2 nd trimesters respectively; both P <0.001), percent body fat (%bf; r=0.25; P <0.001), weight gain over pregnancy (r=0.14; P <0.001), and fasting leptin (r=0.15, P <0.001). Surprisingly, crude birth weight was not associated with maternal glycemic or insulin levels at 1 st or 2 nd trimesters (all P >0.05). In contrast, sum of skinfolds was associated with maternal fasting glucose (r=0.17, P =0.01) and fasting insulin (r=0.24, P =0.001), in addition to fasting leptin (r=0.18, P =0.01) at 2 nd trimester. Sum of skinfolds was also associated with maternal BMI (r=0.18, P =0.008 at 1 st and r=0.21, P =0.003 at 2 nd trimester) and %bf (r=0.19; P =0.005). After adjustments for maternal BMI or %bf, sum of skinfolds remained significantly associated with maternal fasting insulin (all P <0.05), but not with maternal leptin levels ( P =0.16 to 0.35) Conclusion: These results suggest that maternal insulin/glycemic regulation has a greater impact on neonatal adiposity than overall crude birth weight. Birth weight and neonatal adiposity are both associated with maternal leptin levels, likely representing maternal own adiposity levels that might influence neonatal outcomes directly or indirectly.

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Metabolic Syndrome in Italian Obese Children and Adolescents: Stronger Association with Central Fat Depot than with Insulin Sensitivity and Birth Weight

International Journal of Hypertension ◽

10.4061/2011/257168 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 10

Author(s):

Claudia Brufani ◽

Danilo Fintini ◽

Ugo Giordano ◽

Alberto Enrico Tozzi ◽

Fabrizio Barbetti ◽

...

Keyword(s):

Metabolic Syndrome ◽

Birth Weight ◽

Insulin Sensitivity ◽

Low Birth Weight ◽

Children And Adolescents ◽

Central Obesity ◽

Obese Children ◽

Obesity Index ◽

Central Fat ◽

Fat Depot

Aim. To evaluate whether body fat distribution, birth weight, and family history for diabetes (FHD) were associated with metabolic syndrome (MetS) in children and adolescents.Methods. A total of 439 Italian obese children and adolescents (5–18 years) were enrolled. Subjects were divided into 2 groups: prepubertal and pubertal. MetS was diagnosed according to the adapted National Cholesterol Education Program criteria. Birth weight percentile, central obesity index (measured by dual-energy X-ray absorptiometry), insulin sensitivity (ISI), and disposition index were evaluated. Multivariate logistic regression models were used to determine variables associated with MetS.Results. The prevalence of MetS was 17%, with higher percentage in adolescents than in children (21 versus 12%). In the overall population, central obesity index was a stronger predictor of MetS than insulin sensitivity and low birth weight. When the two groups were considered, central fat depot remained the strongest predictor of MetS, with ISI similarly influencing the probability of MetS in the two groups and birth weight being negatively associated to MetS only in pubertal individuals. Neither FHD nor degree of fatness was a significant predictor of MetS.Conclusion. Simple clinical parameters like increased abdominal adiposity and low birth weight could be useful tools to identify European obese adolescents at risk for metabolic complications.

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