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Peter Holmberg Jørgensen, Troels Torp Andreassen and Karin Damm Jørgensen

Abstract. The influence of biosynthetic human growth hormone on biomechanical properties (strain at maximum load, maximum load, relative failure energy, maximum stiffness) and collagen content of intact rat skin was measured after injection of biosynthetic human growth hormone for 90 days at doses of 0.16, 1.10 and 8.33 mg· kg−1 · day−1. The mechanical test showed that strain at maximum load, maximum load and relative failure energy increased with increasing doses of biosynthetic hGH. In the group receiving 8.33 mg · kg−1 · day−1, skin collagen content per surface area and skin collagen concentration in per cent of dry weight were increased, whereas the fat concentration in per cent of dry weight was decreased. Also when correcting the mechanical data for cross-sectional area, a positive correlation between dose and relative failure energy was found. When dividing the mechanical data by collagen content per surface area of the skin, the maximum stress and relative failure energy reached the highest value at a dose of 1.10 mg · kg−1 · day−1. The study shows that biosynthetic hGH can induce an increase in collagen content and mechanical strength of intact rat skin which is dependent on the dose of biosynthetic hGH, and that the increase in mechanical strength cannot be explained only by an increased collagen content.

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Freja B Kampmann, Anne Cathrine B Thuesen, Line Hjort, Anne A Bjerregaard, Jorge E Chavarro, Jan Frystyk, Mette Bjerre, Inge Tetens, Sjurdur F Olsen, Allan A Vaag, Peter Damm and Louise G Grunnet

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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Lilian C Mendoza, Jürgen Harreiter, David Simmons, Gernot Desoye, J M Adelantado, Fabiola Juarez, Ana Chico, Roland Devlieger, Andre van Assche, Sander Galjaard, Peter Damm, Elisabeth R Mathiesen, Dorte M Jensen, Lise Lotte T Andersen, Mette Tanvig, Annunziata Lapolla, Maria G Dalfra, Alessandra Bertolotto, Urszula Mantaj, Ewa Wender-Ozegowska, Agnieszka Zawiejska, David Hill, Judith G Jelsma, Frank J Snoek, Mireille N M van Poppel, Christof Worda, Dagmar Bancher-Todesca, Alexandra Kautzky-Willer, Fidelma P Dunne, Rosa Corcoy and the DALI Core Investigator Group

Objective

Risk factors are widely used to identify women at risk for gestational diabetes mellitus (GDM) without clear distinction by pregnancy period or oral glucose tolerance test (OGTT) time points. We aimed to assess the clinical risk factors for Hyperglycemia in pregnancy (HiP) differentiating by these two aspects.

Design and methods

Nine hundred seventy-one overweight/obese pregnant women, enrolled in the DALI study for preventing GDM. OGTTs were performed at ≤19 + 6, 24–28 and 35–37 weeks (IADPSG/WHO2013 criteria). Women with GDM or overt diabetes at one time point did not proceed to further OGTTs. Potential independent variables included baseline maternal and current pregnancy characteristics. Statistical analysis: Multivariate logistic regression.

Results

Clinical characteristics independently associated with GDM/overt diabetes were at ≤19 + 6 weeks, previous abnormal glucose tolerance (odds ratio (OR): 3.11; 95% CI: 1.41–6.85), previous GDM (OR: 2.22; 95% CI: 1.20–4.11), neck circumference (NC) (OR: 1.58; 95% CI: 1.06–2.36 for the upper tertile), resting heart rate (RHR, OR: 1.99; 95% CI: 1.31–3.00 for the upper tertile) and recruitment site; at 24–28 weeks, previous stillbirth (OR: 2.92; 95% CI: 1.18-7.22), RHR (OR: 3.32; 95% CI: 1.70-6.49 for the upper tertile) and recruitment site; at 35–37 weeks, maternal height (OR: 0.41; 95% CI: 0.20–0.87 for upper tertile). Clinical characteristics independently associated with GDM/overt diabetes differed by OGTT time point (e.g. at ≤19 + 6 weeks, NC was associated with abnormal fasting but not postchallenge glucose).

Conclusion

In this population, most clinical characteristics associated with GDM/overt diabetes were non-modifiable and differed by pregnancy period and OGTT time point. The identified risk factors can help define the target population for future intervention trials.