The relation of insulin, leptin and IGF‐1 to birthweight in offspring of women with type 1 diabetes

Lindsay, Robert; Hamilton, B; Calder, Andrew A.; Johnstone, Frank D.; Walker, James

doi:10.1111/j.1365-2265.2004.02104.x

Cited by 36 publications

(27 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Fetal hormonal and lipid profiles in OT1DM and control subjects. As previously reported for this cohort (9,12,13), maternal type 1 diabetes was associated with marked increases in absolute values of cord insulin, proinsulin, 32-33 split proinsulin, and leptin in both sexes ( Table 2). Male OT1DM demonstrated a small decrease in fetal adiponectin compared with male control subjects and female OT1DM.…”

Section: Resultssupporting

confidence: 84%

“…A comprehensive description of recruitment and exclusion criteria are available in the online appendix (available at http://dx.doi.org/10.2337/db07-0585) and previous publications (9,12,13). Subjects and maternal and cord blood assays.…”

Section: Methodsmentioning

confidence: 99%

“…Oversupply of lipids, particularly nonesterified fatty acids (NEFAs), to the fetus have been proposed as a factor in promoting fetal adiposity (7,8). Maternal diabetes during pregnancy is associated with characteristic overgrowth of the fetus as well as marked hyperinsulinemia and hyperleptinemia, which is easily detectable in cord samples at birth (9). Offspring of mothers with type 2 diabetes are subject to in utero programming effects with increased risk of type 2 diabetes and obesity in childhood and early adulthood (10).…”

mentioning

confidence: 99%

See 2 more Smart Citations

IGF-1 and Leptin Associate With Fetal HDL Cholesterol at Birth

Nelson

Freeman²,

Sattar³

et al. 2007

Diabetes

View full text Add to dashboard Cite

OBJECTIVE-Offspring of mothers with type 1 diabetes (OT1DM) demonstrate increased fat deposition, hyperinsulinemia, and hyperleptinemia in utero. We examined the influence of maternal diabetes on cord lipids at birth and relationship to body composition, cord insulin, leptin, and other hormonal measures. RESEARCH DESIGN AND METHODS-We performed an observational study measuring fetal, HDL, and LDL cholesterol; triglycerides; and nonesterified fatty acids (NEFAs) in a total of 139 OT1DM and 48 control subjects at birth and assessed cross-sectional relationships with birth weight, fetal insulin, leptin, adiponectin, and IGF-1. RESULTS-Concentrations of total cholesterol (male OT1DM[mean Ϯ SD] 1.49 Ϯ 0.45 mmol/l and male control subjects 1.74 Ϯ 0.33 mmol/l; P Ͻ 0.001), HDL cholesterol (0.53 Ϯ 0.21 and 0.74 Ϯ 0.19 mmol/l, respectively; P Ͻ 0.001), and NEFA (median 0.17 [interquartile range 2.30Ϫ2.95] and 0.21 [0.18 -0.36], respectively; P Ͻ 0.001) were significantly lower in male OT1DM, with no significant differences in female subjects. Differences in male subjects were independent of mode of delivery. Cord lipids were unrelated to birth weight in OT1DM and did not show consistent relationships with fetal insulin. Unexpectedly, IGF-1 was a strong correlate of HDL cholesterol in control subjects (r ϭ 0.40, P ϭ 0.002) and OT1DM (r ϭ 0.32, P Ͻ 0.001) but a negative correlate of triglycerides in control subjects (r ϭ Ϫ0.48, P Ͻ 0.001) and OT1DM (r ϭ Ϫ0.21, P ϭ 0.004), with these relationships present in both sexes. In OT1DM, leptin was also independently correlated (negatively, P Ͻ 0.001) with HDL cholesterol in male and female subjects.CONCLUSIONS-Maternal diabetes is associated with significant alterations in lipid levels in male fetuses. IGF-1, leptin, and male sex rather than insulin may be the major determinants of HDL cholesterol and triglycerides in utero. Diabetes 56:2705-2709, 2007 T here is increasing interest in how the intrauterine environment might influence cardiovascular and metabolic disease throughout life. In nondiabetic pregnancies, lower birth weight (1,2) (and smaller fetal abdominal circumference [3]) is associated with higher cord triglycerides and less consistently with lower HDL cholesterol (1,4) in addition to the welldescribed associations with increased risk of cardiovascular disease in adult life (5). Notably, much is still not known about the control or function of circulating fetal lipoproteins in utero. While free fatty acids cross the placenta, lipoproteins do not, and transfer of cholesterol is extremely limited (6). Oversupply of lipids, particularly nonesterified fatty acids (NEFAs), to the fetus have been proposed as a factor in promoting fetal adiposity (7,8). Maternal diabetes during pregnancy is associated with characteristic overgrowth of the fetus as well as marked hyperinsulinemia and hyperleptinemia, which is easily detectable in cord samples at birth (9). Offspring of mothers with type 2 diabetes are subject to in utero programming effects with increased risk of type 2 diabet...

show abstract

Section: Resultssupporting

confidence: 84%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

IGF-1 and Leptin Associate With Fetal HDL Cholesterol at Birth

Nelson

Freeman²,

Sattar³

et al. 2007

Diabetes

View full text Add to dashboard Cite

show abstract

“…Maternal and fetal characteristics for this cohort have previously been described and are included in Table 1. Maternal type 1 diabetes was associated with marked increases in absolute values of cord insulin (12) and leptin (13), with reductions in adiponectin (14), HDL cholesterol, and NEFA (Table 1). All these differences remained significant after adjustment for sex and mode of delivery.…”

Section: Resultsmentioning

confidence: 99%

“…Cord blood assays. Plasma insulin, 32-33 split proinsulin, proinsulin, leptin, IGF-1, adiponectin, plasma total cholesterol, triglyceride, nonesterified fatty acid (NEFA), and VLDL, LDL, and HDL cholesterol were assayed as previously described (12)(13)(14)(15). All lipid assays were carried out at the Biochemistry Department of Glasgow Royal Infirmary, which is a Centers for Disease Control and Prevention (Atlanta, GA) reference laboratory and accredited by Clinical Pathology Accreditation U.K. Maternal A1C was measured centrally by one laboratory.…”

mentioning

confidence: 99%

Inflammation and Endothelial Activation Is Evident at Birth in Offspring of Mothers With Type 1 Diabetes

et al. 2007

View full text Add to dashboard Cite

OBJECTIVE-Offspring of mothers with diabetes are at risk of obesity and glucose intolerance in later life. In adults, markers of subclinical inflammation (C-reactive protein [CRP] and interleukin [IL]-6) and endothelial activation (intracellular adhesion molecule [ICAM]-1) are associated with obesity and higher risk for incident type 2 diabetes. We examined whether these biomarkers were elevated at birth in offspring of type 1 diabetic mothers (OT1DM).RESEARCH DESIGN AND METHODS-Umbilical cord plasma CRP, IL-6, and ICAM-1 were measured in 139 OT1DM and 48 control offspring, with analysis relative to fetal lipids and hormonal axes.RESULTS-OT1DM had higher median (interquartile range) CRP (OT1DM 0.17 mg/l [0.13-0.22] vs. control subjects 0.14 mg/l [0.12-0.17], P Ͻ 0.001) and ICAM-1 (OT1DM 180 ng/ml vs. control subjects 166 ng/ml , P ϭ 0.047). IL-6 was not different after necessary adjustment for mode of delivery. Birth weight was unrelated to inflammatory indexes; however, leptin was correlated with CRP (control subjects r ϭ 0.33, P ϭ 0.02; OT1DM r ϭ 0.41, P Ͻ 0.001) and with IL-6 (r ϭ 0.23, P Ͻ 0.01) and ICAM-1 (r ϭ 0.29, P Ͻ 0.001) in OT1DM. In OT1DM, CRP correlated with maternal glycemic control (A1C at 35-40 weeks; r ϭ 0.28, P ϭ 0.01). In multivariate analysis, leptin was a determinant of CRP (P Ͻ 0.001), ICAM-1 (P ϭ 0.003), and IL-6 (P ϭ 0.02) in OT1DM. Inflammatory measures demonstrated positive relationships with triglycerides in OT1DM (CRP, IL-6, and ICAM-1 P Ͻ 0.05) and control subjects (ICAM-1 P ϭ 0.001).CONCLUSIONS-Inflammatory markers are increased in OT1DM and are related to measures of fetal adiposity, particularly leptin, and maternal glycemia. Subclinical inflammation is a novel component of the diabetic intrauterine environment and should be considered a potential etiological mechanism for in utero programming of disease. Diabetes 56:2697-2704, 2007 M aternal diabetes is associated with adverse consequences to mother and baby. Rates of macrosomia and fetal adiposity are higher, resulting in substantive increases in intrapartum complications, independent of increased background risk of perinatal morbidity and mortality. In the longer term, offspring have increased risk of obesity and type 2 diabetes (1,2) in high-risk populations, reflecting potential in utero programming of disease. In adults, inflammatory markers-in particular C-reactive protein (CRP), intracellular adhesion molecule (ICAM)-1, and interleukin (IL)-6 -are associated with adiposity, altered glucose tolerance, and, prospectively, with later risk of development of type 2 diabetes and vascular disease (3-8). In animal models, intrauterine exposure to cytokines, including IL-6, have been associated with increases in fat mass and insulin resistance in later life (9). Changes in inflammatory markers have not been extensively studied in offspring of type 1 diabetic pregnancies at birth; however, gestational diabetes mellitus has been associated with an alteration in the placental transcriptome with a dominance of genes regulating inflam...

show abstract

Roles and Regulation of Leptin in Reproduction

Henson

Castracane

Leptin

View full text Add to dashboard Cite

The relation of insulin, leptin and IGF‐1 to birthweight in offspring of women with type 1 diabetes

Abstract: Maternal diabetes is associated with marked elevation of insulin and leptin in cord blood of their offspring. Hormonal correlates of birthweight differ between ODM and Control with an independent relationship of insulin to birthweight observed only in ODM.

Cited by 36 publications

References 41 publications

IGF-1 and Leptin Associate With Fetal HDL Cholesterol at Birth

IGF-1 and Leptin Associate With Fetal HDL Cholesterol at Birth

Inflammation and Endothelial Activation Is Evident at Birth in Offspring of Mothers With Type 1 Diabetes

Roles and Regulation of Leptin in Reproduction

Contact Info

Product

Resources

About