Abnormal levels of adipokines in adolescent offspring of women with type 1 diabetes – Results from the EPICOM study

Lohse, Zuzana; Bytoft, Birgitte; Knorr, Sine; Clausen, Tine D.; Jensen, Rikke Beck; Beck‐Nielsen, Henning; Hermann, Anne Pernille; Oturai, Peter; Frystyk, Jan; Damm, Peter; Gravholt, Claus Højbjerg; Højlund, Kurt; Jensen, Dorte Møller

doi:10.1016/j.metabol.2017.04.002

Cited by 7 publications

(20 citation statements)

References 34 publications

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“…In the present study adiponectin concentrations were lower among GDM offspring, who also were more insulin resistant. Our results were in line with previous studies, also reporting lower adiponectin concentrations in GDM offspring at infancy (38), as well as in offspring of mothers with GDM or type 1 diabetes aged 6-13 (11) and 13-20 years (13). Offspring BMI had a substantial influence on the decreased adiponectin concentrations in exposed offspring in these studies as also observed in our study.…”

Section: Decreased Adiponectin Concentrations In Gdm Offspringsupporting

confidence: 93%

“…Dysregulation of leptin is assumed to play a mediating role on future metabolic disease in offspring exposed to a hyperglycemic environment in utero. Our findings of a 38% elevated leptin concentration among GDM offspring are in line with previously reported effect estimates in offspring aged 6-20 years, who were born to mothers with type 1 diabetes or GDM (11,12,13). Other studies have reported no difference in leptin concentrations between GDM and control offspring in infancy (32) and in young adulthood (14).…”

Section: Elevated Leptin Concentration In Gdm Offspringsupporting

confidence: 92%

“…Offspring BMI had a substantial influence on the decreased adiponectin concentrations in exposed offspring in these studies as also observed in our study. In the latter study, which exclusively examined type 1 diabetes exposed offspring, a decreased adiponectin concentration was only evident among females (13). Sexual dimorphism of adipokines related to an adverse exposure in utero has previously been reported (39), but is not fully understood.…”

Section: Decreased Adiponectin Concentrations In Gdm Offspringmentioning

confidence: 83%

“…While increased leptin and/or decreases adiponectin concentrations have been observed in cord blood from GDM pregnancies in the majority of studies (6,7,8), other studies did not find any difference in either leptin or adiponectin between GDM and control offspring at birth (9,10). Studies examine the impact of GDM on leptin and adiponectin levels in childhood and onward have showed conflicting results with some studies reporting increased leptin and/or decreased adiponectin concentrations in offspring of women with GDM or type 1 diabetes (11,12,13) and others no associations (14,15). Importantly, previous studies were mainly of small sample size and very few examined adiponectin and leptin concentrations in adolescence, which is a highly interesting time period where both changes in body composition and metabolism occur.…”

Section: Introductionmentioning

confidence: 99%

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Increased leptin, decreased adiponectin and FGF21 concentrations in adolescent offspring of women with gestational diabetes

Kampmann

Thuesen

Hjort

et al. 2019

European Journal of Endocrinology

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Objective Fetal exposure to gestational diabetes mellitus (GDM) increases the risk of metabolic diseases in the offspring. Leptin, adiponectin, and fibroblast growth factor 21 (FGF21) may play potential roles in the underlying disease mechanisms. We investigated the impact of fetal exposure to GDM on leptin, adiponectin, and FGF21 concentrations and their associations with measures of adiposity and metabolic traits during childhood/adolescence. Design and methods The follow-up study included 504 GDM and 540 control offspring aged 9–16 from the Danish National Birth Cohort. Anthropometric measurements, fasting blood samples, puberty status and fat percentages by dual-energy X-ray absorptiometry were examined. Serum concentrations of leptin, adiponectin, and FGF21 were measured by validated immune assays. Results GDM offspring had 38% (95% CI: 22–55%) higher leptin, 0.6 mg/L (95% CI: −1.2, −0.04 mg/L) lower adiponectin, and 32% (95% CI: −47%, −12%) lower FGF21 concentrations than control offspring (P < 0.05). After adjustment for confounders including maternal pre-pregnancy BMI, GDM offspring had borderline higher leptin (P = 0.06) and significantly lower FGF21 concentrations (P = 0.006). When accounting for offspring BMI z-score, GDM exposure had no significant independent effect on leptin or adiponectin concentrations, whereas FGF21 was still significant. In univariate analyses, leptin and adiponectin were associated with fasting insulin, HOMA-IR, and adiposity, and FGF21 with total fat percentage. Conclusions GDM offspring had higher leptin, lower adiponectin and FGF21 concentrations than control offspring. Elevated leptin and decreased adiponectin concentrations associated with adverse metabolic traits and were most likely driven by higher obesity prevalence among GDM offspring. The functional implications of decreased FGF21 concentrations among GDM offspring need to be further explored.

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Section: Decreased Adiponectin Concentrations In Gdm Offspringsupporting

confidence: 93%

Section: Elevated Leptin Concentration In Gdm Offspringsupporting

confidence: 92%

Section: Decreased Adiponectin Concentrations In Gdm Offspringmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Increased leptin, decreased adiponectin and FGF21 concentrations in adolescent offspring of women with gestational diabetes

Kampmann

Thuesen

Hjort

et al. 2019

European Journal of Endocrinology

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“…In the EPICOM study, we have previously described reduced insulin sensitivity among the oldest offspring of women with type 1 diabetes (17+ years), and especially among the female participants (31). We also described adiponectin to be significantly lower among the type 1 diabetes-exposed female offspring from the EPICOM cohort, indicating sex differences among the type 1 diabetes-exposed offspring (32).…”

Section: Discussionmentioning

confidence: 63%

Fatty Liver Among Adolescent Offspring of Women With Type 1 Diabetes (the EPICOM Study)

et al. 2019

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Intrauterine exposure to maternal type 1 diabetes is associated with a less favorable metabolic profile later in life. Nonalcoholic fatty liver disease is the hepatic manifestation of a cluster of metabolic abnormalities linked to insulin resistance. This study aimed to evaluate the effect of maternal pregestational type 1 diabetes on the presence of fatty liver in offspring and the association between maternal BMI, glycemic control during pregnancy, offspring metabolic risk factors, and offspring level of soluble CD163 (sCD163) (a marker of macrophage activation) and risk of fatty liver. RESEARCH DESIGN AND METHODS This study was a prospective nationwide follow-up study of offspring (n = 278) of mothers with pregestational type 1 diabetes between 1993 and 1999 and matched control subjects (n = 303). Mean age at the time of follow-up was 16.7 years (range 13.0-20.4 years). We used the fatty liver index (FLI) and waist-to-height ratio (WHtR) to evaluate the presence of fatty liver among the offspring. An FLI ‡60 or WHtR >0.469 were used as cutoff points for fatty liver. RESULTS More type 1 diabetes-exposed offspring had high FLI and WHtR indices compared with unexposed control subjects. We found significant associations between increasing maternal prepregnancy BMI, being born large for gestational age, offspring level of sCD163, as well as offspring metabolic risk factors (decreasing adiponectin and HDL cholesterol and increasing leptin, HOMA of insulin resistance, and HOMA of insulin secretion) and degree of fatty liver. CONCLUSIONS Intrauterine exposure to maternal type 1 diabetes and higher maternal prepregnancy BMI may predispose to fatty liver in the offspring. Offspring metabolic risk factors, including sCD163 levels, are associated with indices of fatty liver. Along with the worldwide increase in obesity, the prevalence of nonalcoholic fatty liver disease (NAFLD) is rising, and in the pediatric population, NAFLD is now considered one of the leading causes of hepatic disease (1). Offspring of women with diabetes have an increased risk of developing type 2 diabetes, prediabetes, and obesity (2). This applies to both offspring of mothers with pregestational diabetes as well as gestational diabetes mellitus, and our research group has previously published data from the EPICOM (Epigenetic, Genetic, and Environmental Effects on Growth, Cognitive Functions, and Metabolism in Offspring of Women

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Management of Preexisting Diabetes in Pregnancy

Alexopoulos

Blair

Peters

2019

JAMA

116

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Importance: The presence of preexisting type 1 or type 2 diabetes in pregnancy increases the risk of adverse maternal and neonatal outcomes, such as preeclampsia, caesarian section, pre-term delivery, macrosomia and congenital defects. Approximately 0.9% of the 4,000,000 births in the United States are complicated by preexisting diabetes. Observations: Women with diabetes have increased risk for adverse maternal and neonatal outcomes and similar risks are present for either type 1 or type 2 diabetes. Both forms of diabetes require similar intensity of diabetes care. Preconception planning is very important to avoid unintended pregnancies, and to minimize risk of congenital defects. Hemoglobin A1c goal at conception is <6.5% and during pregnancy is <6.0%. It is also critical to screen for and optimize comorbid illnesses such as retinopathy and nephropathy. Medications known to be unsafe in pregnancy, such as angiotensin-converting enzyme inhibitors and statins, should be discontinued. Obese women should be screened for obstructive sleep apnea, which is often undiagnosed and can result in poor outcomes. Blood pressure goals must be considered carefully, as lower treatment thresholds may be required for women with nephropathy. During pregnancy, continuous glucose monitor use can improve glycemic control and neonatal outcomes for women with type 1 diabetes. Insulin is first-line therapy for all women with preexisting diabetes; injections and insulin pump therapy are both effective approaches. Rates of severe hypoglycemia are increased during pregnancy; therefore glucagon should be available and close contacts trained in its use. Low-dose aspirin is recommended soon after 12 weeks of gestation to minimize the risk of preeclampsia. The importance of discussing long-acting reversible contraception before and after pregnancy cannot be overstated, to allow for appropriate preconception planning. Conclusions and Relevance: Preexisting diabetes in pregnancy is complex and is associated with significant maternal and neonatal risk, but optimization of glycemic control, medication regimens and careful attention to comorbid conditions can help mitigate these risks, and ensure quality diabetes care before, during and after pregnancy.

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Abnormal levels of adipokines in adolescent offspring of women with type 1 diabetes – Results from the EPICOM study

Cited by 7 publications

References 34 publications

Increased leptin, decreased adiponectin and FGF21 concentrations in adolescent offspring of women with gestational diabetes

Increased leptin, decreased adiponectin and FGF21 concentrations in adolescent offspring of women with gestational diabetes

Fatty Liver Among Adolescent Offspring of Women With Type 1 Diabetes (the EPICOM Study)

Management of Preexisting Diabetes in Pregnancy

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