|Determinants of insulin resistance in infants at age 1 year: impact of gestational diabetes mellitus.|
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|PMID: 22699283 Owner: NLM Status: MEDLINE|
|OBJECTIVE: The offspring of women with gestational diabetes mellitus (GDM) display a propensity for the early accrual of cardiometabolic risk factors, including insulin resistance, in childhood and adolescence. Thus, we sought to identify early life determinants of insulin resistance in infants of women with and without GDM.
RESEARCH DESIGN AND METHODS: In total, 104 full-term, singleton infants born to women with (n = 36) and without (n = 68) GDM were evaluated at age 1 year, with insulin resistance assessed by homeostasis model (HOMA-IR).
RESULTS: HOMA-IR at 1 year did not differ between infants born to mothers with and without GDM (P = 0.74). The sole independent predictor of infant HOMA-IR in the non-GDM group was birth weight (t = 3.33, P = 0.002). In contrast, weight gain in the 1st year was the only independent predictor of HOMA-IR in infants of women with GDM (t = 2.19, P = 0.039).
CONCLUSIONS: In the 1st year of life, weight gain in infants born to women with GDM is associated with insulin resistance, unlike in their peers.
|Carla A Borgoño; Jill K Hamilton; Chang Ye; Anthony J Hanley; Philip W Connelly; Mathew Sermer; Bernard Zinman; Ravi Retnakaran|
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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-06-14|
|Title: Diabetes care Volume: 35 ISSN: 1935-5548 ISO Abbreviation: Diabetes Care Publication Date: 2012 Aug|
|Created Date: 2012-07-24 Completed Date: 2012-12-05 Revised Date: 2013-08-13|
Medline Journal Info:
|Nlm Unique ID: 7805975 Medline TA: Diabetes Care Country: United States|
|Languages: eng Pagination: 1795-7 Citation Subset: IM|
|Division of General Internal Medicine, University of Toronto, Toronto, Ontario, Canada.|
|APA/MLA Format Download EndNote Download BibTex|
Diabetes, Gestational / physiopathology*
Insulin Resistance / physiology*
|MOP-84206//Canadian Institutes of Health Research; MOP-89831//Canadian Institutes of Health Research|
Journal ID (nlm-ta): Diabetes Care
Journal ID (iso-abbrev): Diabetes Care
Journal ID (hwp): diacare
Journal ID (pmc): dcare
Journal ID (publisher-id): Diabetes Care
Publisher: American Diabetes Association
© 2012 by the American Diabetes Association.
Received Day: 26 Month: 1 Year: 2012
Accepted Day: 17 Month: 3 Year: 2012
Print publication date: Month: 8 Year: 2012
Electronic publication date: Day: 14 Month: 7 Year: 2012
Volume: 35 Issue: 8
First Page: 1795 Last Page: 1797
PubMed Id: 22699283
Publisher Id: 0173
|Determinants of Insulin Resistance in Infants at Age 1 Year : Impact of gestational diabetes mellitus|
|Carla A. Borgoño, MD, PHD1|
|Jill K. Hamilton, MD2|
|Chang Ye, MSC3|
|Anthony J. Hanley, PHD345|
|Philip W. Connelly, PHD46|
|Mathew Sermer, MD7|
|Bernard Zinman, MD348|
|Ravi Retnakaran, MD34|
1Division of General Internal Medicine, University of Toronto, Toronto, Ontario, Canada
2Hospital for Sick Children, Department of Pediatrics, Toronto, Ontario, Canada
3Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada
4Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada
5Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada
6Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada
7Division of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada
8Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
|Correspondence: Corresponding author: Ravi Retnakaran, firstname.lastname@example.org.
C.A.B. and J.K.H. share co-first authorship on this study.
The offspring of women with gestational diabetes mellitus (GDM) exhibit a propensity for the early accrual of cardiometabolic risk factors in childhood and adolescence (1). Indeed, compared with their peers, offspring exposed to GDM in utero are more likely to develop insulin resistance in childhood and by as early as age 5 years (2,3). However, little is known about perinatal and early life risk factors associated with infant insulin resistance after exposure to maternal GDM. Thus, we sought to evaluate insulin resistance and its determinants in the offspring of women with and without GDM at age 1 year.
This analysis was performed within an ongoing prospective observational study in which the infants of women with or without GDM are undergoing serial assessment in the early years of life. The study protocol has been previously described (4). In brief, pregnant women are recruited in late second trimester and undergo a 3-h, 100-g oral glucose tolerance test (OGTT) for diagnosis of GDM (National Diabetes Data Group criteria) (5). The offspring are then evaluated in the 1st year of life. The protocol has been approved by institutional research ethics boards, and all mothers provided written informed consent for their infant’s participation. The current analysis was restricted to the first 104 singleton, full-term infants whose mothers had consented to infant blood work at age 1 year as of July 2011.
As previously described (6,7), the antepartum OGTT enabled assessment of maternal insulin sensitivity (Matsuda index) and lipids. All women diagnosed with GDM on the OGTT received treatment with diet/exercise counseling, and six women also received insulin. Data on obstetrical outcomes were obtained from an institutional database tracking labor and delivery. At age 12 months, participating infants attended the clinical investigation unit after requested overnight fast (or at least 4–5 h, if they required feeding). Fasting blood samples were drawn from the infants for the measurement of glucose and insulin. Specific insulin was measured by electrochemiluminescence immunoassay kit and Elecsys 1010 immunoassay analyzer (Roche, Laval, Canada). Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR) (8), an established measure that has been used in young children (9).
All analyses were performed using SAS 9.2 (SAS Institute, Cary, NC). The infants of women with and without GDM were compared by Wilcoxon two-sample test (continuous variables) or either χ2 or Fisher exact test (categorical variables) (Table 1). Univariate associations between parental/infant factors and infant HOMA-IR were assessed by Spearman correlation adjusted for infant age (Supplementary Table 1). Multiple linear regression analyses of HOMA-IR were performed in each group with core variables age, sex, race/ethnicity, birth weight, and 1st-year weight gain (Supplementary Table 2). Exploratory multiple linear regression analyses were also performed with single addition of infant feeding, maternal BMI, insulin sensitivity, and lipids (LDL, HDL, and triglycerides), respectively.
Parental and infant characteristics were compared between infants of women with GDM (n = 36) and infants of women without GDM (n = 68) (Table 1). It is notable that there were no significant differences between these groups in birth weight, weight at 1 year, and HOMA-IR at 1 year (both median HOMA-IR = 0.21, P = 0.74). In pregnancy, women with GDM had lower insulin sensitivity (P = 0.003) and higher triglycerides (P = 0.04) than those without GDM. There were no dissimilarities between the groups in infant feeding practices.
On age-adjusted Spearman correlation analysis (Supplementary Table 1), birth weight was associated with HOMA-IR in infants of women without GDM (r = 0.32, P = 0.02) but not in infants of women with GDM (r = −0.18, P = 0.34). Conversely, weight gain in the 1st year was associated with HOMA-IR in infants whose mothers had GDM (r = 0.44, P = 0.02) but not in those whose mothers did not have GDM (r = 0.04, P = 0.78). On multiple linear regression analyses (Supplementary Table 2A), the sole independent predictor of infant HOMA-IR in the non-GDM group was birth weight (t = 3.33, P = 0.002). In contrast, weight gain in the 1st year emerged as the only independent predictor of HOMA-IR in infants of women with GDM (t = 2.19, P = 0.039) (Supplementary Table 2B).
Finally, in each group, we performed exploratory multiple linear regression analyses with single addition to the models of infant feeding, maternal BMI, insulin sensitivity, or lipid variables, respectively. In each case, the sole independent determinant of infant HOMA-IR in the non-GDM group was birth weight. Conversely, 1st-year weight gain was an independent predictor in each model in the GDM group (data not shown).
In this study, there were no differences between the infants of GDM mothers and their peers in birth weight, 1st-year weight gain, or HOMA-IR at age 1 year. However, the early life determinants of insulin resistance differed markedly between these two groups. Indeed, whereas birth weight was the only predictor of infant insulin resistance in the non-GDM group, weight gain in the 1st year was the sole independent determinant in infants of women with GDM.
Unlike their peers, women with GDM received antepartum glucose-lowering treatment. Through its intended effect of limiting excessive fetal growth, it is possible that this treatment may have obscured the relationship between birth weight and infant HOMA-IR that was otherwise readily detectable in the untreated non-GDM group. Alternatively, the relationship between 1st-year weight gain and HOMA-IR in the GDM infants could reflect metabolic programming resulting from fetal exposure to the altered intrauterine environment that antedates the diagnosis of GDM (10,11). Indeed, rapid early postnatal growth has been associated with increased weight gain, adiposity, and insulin resistance in children and adults born small for gestational age (12–15). Our data raise the intriguing possibility that this growth velocity model may similarly apply to the offspring of GDM pregnancies, leading to their early life accrual of insulin resistance and cardiometabolic risk.
A limitation of this study is the lack of assessment of maternal gestational weight gain and neonatal body composition (particularly fat mass) at birth and during the 1st year. In addition, the number of subjects was relatively modest. Nevertheless, as the first study comparing determinants of insulin resistance between infants of GDM pregnancies and their peers at 1 year, this analysis highlights the need for longitudinal evaluation of these groups into early childhood. Ultimately, the insight so derived may inform strategies for breaking the vicious cycle of cardiometabolic disease linking women with GDM and their children.
fn1This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc12-0173/-/DC1.
This study was supported by operating grants from the Canadian Institutes of Health Research (CIHR; MOP-89831 and MOP-84206). A.J.H. holds a Tier-II Canada Research Chair in Diabetes Epidemiology. B.Z. holds the Sam and Judy Pencer Family Chair in Diabetes Research at Mount Sinai Hospital and University of Toronto. R.R. holds a CIHR Clinical Research Initiative New Investigator Award and an Ontario Ministry of Research and Innovation Early Researcher Award, and receives Canadian Diabetes Association Clinician-Scientist incentive funding.
No potential conflicts of interest relevant to this article were reported.
C.A.B. researched data, contributed to analysis, and wrote the manuscript. J.K.H. and R.R. were involved in the design/implementation of the overall study, designed the analysis plan, and supervised the analysis and manuscript. C.Y. performed the statistical analyses. A.J.H., P.W.C., M.S., and B.Z. were involved in the design/implementation of the overall study. All authors contributed to critical revision of the manuscript. R.R. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Parts of this study were presented in abstract form at the 72nd Scientific Sessions of the American Diabetes Association, Philadelphia, Pennsylvania, 8–12 June 2012.
The authors thank the Mount Sinai Hospital Department of Pathology and Laboratory Medicine and Patient Care Services.
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