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- Aydin, Banu K., et al.
(författare)
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High levels of FSH before puberty are associated with increased risk of metabolic syndrome during pubertal transition
- 2022
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Ingår i: Pediatric Obesity. - : John Wiley & Sons. - 2047-6302 .- 2047-6310. ; 17:8
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Tidskriftsartikel (refereegranskat)abstract
- Background During perimenopause, the rise in serum follicle-stimulating hormone (FSH) is associated with increased adiposity, insulin resistance (IR), and metabolic syndrome (MetS). However, data for the pubertal period, which is characterized by increasing FSH levels and changing body composition, are limited. Objectives To investigate the relationships between FSH and anthropometric changes, IR markers, and development of MetS in the peripubertal period. Methods Uppsala Longitudinal Study of Childhood Obesity (ULSCO) is an ongoing study that aims to understand the factors contributing to childhood obesity and the development of obesity-related diseases. We analysed the subset of participants who were prepubertal at the first visit (n = 95, 77 with obesity). Mean follow-up time was 3.0 +/- 1.4 years. Results Higher serum FSH levels at the first visit were associated with an increased likelihood of elevation in body mass index (BMI SDS) (p = 0.025, OR = 16.10) and having MetS (p = 0.044, OR = 4.67) at the follow-up. We observed nonlinear relationships between varying serum FSH levels and markers of adiposity and IR, especially in girls. At the first visit, when girls were prepubertal, FSH was negatively associated with BMI (beta = -0.491, p = 0.005) and positively associated with sex hormone-binding globulin (SHBG) (beta = 0.625, p = 0.002). With the progression of puberty, negative associations between BMI and SHBG disappeared while FSH became positively associated with HOMA-IR (beta = 0.678, p = 0.025) and fasting insulin (beta = 0.668, p = 0.027). Conclusions Higher serum FSH levels in prepubertal children were associated with an increased risk of MetS development during pubertal transition. Along with nonlinear associations between varying serum FSH levels and IR markers, our results might imply a relationship between FSH and IR of puberty.
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| 2. |
- Aydin, Banu K., et al.
(författare)
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Pelvic and breast ultrasound abnormalities and associated metabolic disturbances in girls with premature pubarche due to adrenarche
- 2022
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Ingår i: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265. ; 96:3, s. 339-345
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Tidskriftsartikel (refereegranskat)abstract
- Objective Premature adrenarche (PA) has been suggested as a risk factor for future health problems, such as metabolic syndrome and early menarche. However, not all girls with PA have these features and it is not certain who will develop them. We propose that these abnormalities might be identified earlier, even before they are visible. Design Case-control study. Setting Tertiary care hospital. Participants Forty-eight girls with premature pubarche due to PA and age (mean age 7.6 +/- 1.0 years), weight, body mass index (BMI), birth weight and gestational age-matched 49 girls with no palpable breast tissue. Measurements Early pubertal pelvic and breast ultrasonographic changes and their associations with obesity and metabolic parameters were evaluated. Blood samples were collected, breast and pelvic ultrasound examinations were performed and bone ages were assessed. Results Girls with PA were taller and their bone ages were higher (p = .049 and p = .005). Fasting blood glucose, insulin, triglycerides, high-density lipoprotein and low-density lipoprotein cholesterol were not different between the groups. Luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol were not different either. Ultrasonography revealed breast gland tissue in 30% of girls with PA and 5% of controls (p = .006). Uterine volume and endometrial thickness were higher in girls with PA (p = .03 and p = .04). Endometrial thickness was positively associated with serum insulin levels in the whole study group and after adjusting for age, diagnosis, BMI, mean ovarian volume and LH, FSH, estradiol levels, this association remained with a borderline p-value (R-2 = 0.486, p = .050). Conclusions We found early changes in uterus and breast glands of girls with PA and endometrial thickness was positively associated with insulin levels.
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| 3. |
- Stenlid, Rasmus, et al.
(författare)
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Adolescents with obesity treated with exenatide maintain endogenous GLP-1, reduce DPP-4, and improve glycemic control
- 2023
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: GLP-1 receptor agonists (GLP-1RA) are increasingly used to treat adolescent obesity. However, the effect on endogenous GLP-1 secretory patterns following treatment in adolescents is unknown. The GLP-1RA exenatide was shown to significantly lower BMI and 2-hour glucose in adolescents with obesity, in the placebo-controlled, randomized controlled trial Combat-JUDO. The aim of this study was to evaluate effects of weekly injections of 2 mg exenatide extended release on secretory patterns of endogenous hormones during OGTT.Subjects and Measurements: This study was a pre-planned sub-study of the Combat-JUDO trial, set at the Pediatric clinic at Uppsala University Hospital, Sweden and Paracelsus Medical University, Austria. 44 adolescents with obesity were included and randomized 1:1 to treatment:placebo. 19 patients in the treatment group and 18 in the placebo group completed the trial. Before and after treatment, GLP-1, glucose, insulin, glucagon and glicentin levels were measured during OGTT; DPP-4 and proinsulin were measured at fasting. A per-protocol approach was used in the analyses.Results: Exenatide treatment did not affect GLP-1 levels during OGTT. Treatment significantly lowered DPP-4, proinsulin and the proinsulin-to-insulin ratio at fasting, increased glicentin levels but did not affect insulin, C-peptide or glucagon levels during OGTT.Conclusion: Weekly s.c. injections with 2 mg of exenatide maintains endogenous total GLP-1 levels and lowers circulating DPP-4 levels. This adds an argument in favor of using exenatide in the treatment of pediatric obesity.
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| 4. |
- Stenlid, Rasmus, et al.
(författare)
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Screening for inflammatory markers identifies IL18-Rα as a potential link between exenatide and its anti-inflammatory effect : New results from the Combat-JUDO randomized controlled trial
- 2023
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Ingår i: Annals of Nutrition and Metabolism. - : S. Karger. - 0250-6807 .- 1421-9697. ; 79:6, s. 522-527
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Obesity is associated with chronic inflammation. Chronic inflammation has also been linked to insulin resistance and type 2 diabetes, non-alcoholic fatty liver disease and cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor analogs (GLP-1RA) are clinically used to treat obesity, with known anti-inflammatory properties. How the GLP-1RA exenatide effects inflammation in adolescents with obesity is not fully investigated.Methods: 44 patients were randomized to receive weekly subcutaneous injections with either 2 mg exenatide or placebo for 6 months. Plasma samples were collected at baseline and at the end of the study, and 90 inflammatory proteins were measured.Results: Following treatment with exenatide, 15 out of the 90 proteins were decreased, and one was increased. However, after adjustment for multiple testing, only IL18-R alpha was significantly lowered following treatment.Conclusions: Weekly injections with 2 mg of exenatide lowers circulating IL18-R alpha in adolescents with obesity, which may be a potential link between exenatide and its anti-inflammatory effect in vivo. This contributes to exenatide's pharmaceutical potential as a treatment for obesity beyond weight control and glucose tolerance, and should be further studied mechanistically.
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| 5. |
- Wen, Quan, et al.
(författare)
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Metformin Can Attenuate Beta-Cell Hypersecretion-Implications for Treatment of Children with Obesity
- 2023
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Ingår i: Metabolites. - : MDPI. - 2218-1989 .- 2218-1989. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- In children with obesity, insulin hypersecretion is proposed to precede insulin resistance. We investigated if metformin could be used to attenuate insulin secretion from palmitate-treated isolated islets and its implication for children with obesity. Human islets were exposed to palmitate for 0.5 or 1 day, when metformin was introduced. After culture, glucose-stimulated insulin secretion (GSIS) was measured. Children with obesity, who had received metformin for over six months (n = 21, age 13.9 +/- 1.8), were retrospectively evaluated. Children were classified as either "reducing" or "increasing" based on the difference between AUC(0-120) of insulin during OGTT before and after metformin treatment. In human islets, GSIS increased after culture in palmitate for up to 1 day but declined with continued palmitate exposure. Whereas adding metformin after 1 day of palmitate exposure increased GSIS, adding metformin after 0.5 days reduced GSIS. In children with "reducing" insulin AUC(0-120) (n = 9), 2 h glucose and triglycerides decreased after metformin treatment, which was not observed in patients with "increasing" insulin AUC(0-120) (n = 12). In isolated islets, metformin attenuated insulin hypersecretion if introduced when islet secretory capacity was maintained. In children with obesity, improved glycemic and lipid levels were accompanied by reduced insulin levels during OGTT after metformin treatment.
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