Metformin and insulin treatment of gestational diabetes: effects on inflammatory markers and IGF-binding protein-1 – secondary analysis of a randomized controlled trial

Abstract Background Gestational diabetes mellitus (GDM) is characterized by disturbed glucose metabolism and activation of low-grade inflammation. We studied whether metformin treatment has favorable or unfavorable effects on inflammatory markers and insulin-like growth factor-binding protein 1 (IGFBP-1) in GDM patients compared with insulin, and whether these markers associate with major maternal or fetal clinical outcomes. Methods This is a secondary analysis of a previous randomized controlled trial comparing metformin (n = 110) and insulin (n = 107) treatment of GDM. Fasting serum samples were collected at the time of diagnosis (baseline, mean 30 gestational weeks [gw]) and at 36 gw. Inflammatory markers serum high-sensitivity CRP (hsCRP), interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8) and glycoprotein acetylation (GlycA) as well as three IGFBP-1 phosphoisoform concentrations were determined. Results In the metformin and insulin groups combined, hsCRP decreased (p = 0.01), whereas IL-6 (p = 0.002), GlycA (p < 0.0001) and all IGFBP-1 phosphoisoforms (p < 0.0001) increased from baseline to 36 gw. GlycA (p = 0.02) and non-phosphorylated IGFBP-1 (p = 0.008) increased more in patients treated with metformin than those treated with insulin. Inflammatory markers did not clearly associate with pregnancy outcomes but non-phosphorylated IGFBP-1 was inversely associated with gestational weight gain. Conclusions Metformin had beneficial effects on maternal serum IGFBP-1 concentrations compared to insulin, as increased IGFBP-1 related to lower total and late pregnancy maternal weight gain. GlycA increased more during metformin treatment compared to insulin. The significance of this observation needs to be more profoundly examined in further studies. There were no evident clinically relevant relations between inflammatory markers and pregnancy outcome measures. Trial registration The trial comparing metformin and insulin treatment was registered in ClinicalTrials.gov ( NCT01240785 ) November 3, 2010. Retrospectively registered

Metformin and insulin treatment of gestational diabetes : effects on inflammatory markers and IGF-binding protein-1-secondary analysis of a randomized controlled trial

Background: Gestational diabetes mellitus (GDM) is characterized by disturbed glucose metabolism and activation of low-grade inflammation. We studied whether metformin treatment has favorable or unfavorable effects on inflammatory markers and insulin-like growth factor-binding protein 1 (IGFBP-1) in GDM patients compared with insulin, and whether these markers associate with major maternal or fetal clinical outcomes. Methods: This is a secondary analysis of a previous randomized controlled trial comparing metformin (n = 110) and insulin (n = 107) treatment of GDM. Fasting serum samples were collected at the time of diagnosis (baseline, mean 30 gestational weeks [gw]) and at 36 gw. Inflammatory markers serum high-sensitivity CRP (hsCRP), interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8) and glycoprotein acetylation (GlycA) as well as three IGFBP-1 phosphoisoform concentrations were determined. Results: In the metformin and insulin groups combined, hsCRP decreased (p = 0.01), whereas IL-6 (p = 0.002), GlycA (p <0.0001) and all IGFBP-1 phosphoisoforms (p <0.0001) increased from baseline to 36 gw. GlycA (p = 0.02) and non-phosphorylated IGFBP-1 (p = 0.008) increased more in patients treated with metformin than those treated with insulin. Inflammatory markers did not clearly associate with pregnancy outcomes but non-phosphorylated IGFBP-1 was inversely associated with gestational weight gain. Conclusions: Metformin had beneficial effects on maternal serum IGFBP-1 concentrations compared to insulin, as increased IGFBP-1 related to lower total and late pregnancy maternal weight gain. GlycA increased more during metformin treatment compared to insulin. The significance of this observation needs to be more profoundly examined in further studies. There were no evident clinically relevant relations between inflammatory markers and pregnancy outcome measures.Peer reviewe

Intraoperative Complications and Mid-Term Follow-Up of Large-Diameter Head Metal-on-Metal Total Hip Arthroplasty and Hip Resurfacing Arthroplasty

Background and Aims: Large-diameter head total hip arthroplasty and hip resurfacing arthroplasty were popular in Finland from 2000 to 2012 for the treatment of hip osteoarthritis. The aim of this retrospective study was to investigate the mid-term survival of large-diameter head total hip arthroplasty patients operated on in three university hospitals and to compare these results to the survival of hip resurfacing arthroplasty patients. Material and Methods: A total of 3860 hip arthroplasties (3029 large-diameter head total hip arthroplasties in 2734 patients and 831 hip resurfacing arthroplasties in 757 patients) were operated on between January 2004 and December 2009. The mean follow-up was 4.3years (range: 0.3-8.0years) in the total hip arthroplasty group and 5.1years (range: 1.7-7.9years) in the hip resurfacing arthroplasty group. Cox multiple regression model and Kaplan-Meier survival analysis were used to study the survival of the total hip arthroplasties and the hip resurfacing arthroplasties. Intraoperative complications and reasons for revisions were also evaluated. Results: In Cox regression analysis, the hazard ratio for revision of hip resurfacing arthroplasty was 1.5 compared with large-diameter head total hip arthroplasty (95% confidence interval: 1.0-2.2) (p=0.029). The cumulative Kaplan-Meier survival rate was 90.7% at 7.7years for the large-diameter head total hip arthroplasty (95% confidence interval: 86.8-94.6) and 92.2% at 7.6years for hip resurfacing arthroplasty (95% confidence interval: 89.9-94.6). There were a total of 166/3029 (5.5%) intraoperative complications in the large-diameter head total hip arthroplasty group and 20/831 (2.4%) in the hip resurfacing arthroplasty group (p=0.001). Revision for any reason was performed on 137/3029 (4.5%) of the arthroplasties in the large-diameter head total hip arthroplasty group and 52/831 (6.3%) in the hip resurfacing arthroplasty group (p=0.04). Conclusion: The mid-term survival of both of these devices was poor, and revisions due to adverse reactions to metal debris will most likely rise at longer follow-up. There were more intraoperative complications in the large-diameter head total hip arthroplasty group than in the hip resurfacing arthroplasty group.Peer reviewe

Serum lipids and their association with birth weight in metformin and insulin treated patients with gestational diabetes

AimsTo compare the effects of metformin and insulin treatment on maternal serum lipids in patients with gestational diabetes (GDM), and to analyse the associations between individual lipids and birth weight (BW).MethodsThis is a secondary analysis of a randomized trial comparing metformin (n = 110) and insulin (n = 107) treatment of GDM. Fasting serum lipidome was measured at baseline (the time of diagnosis, mean 30 gestational weeks, gw) and at 36 gw using nuclear magnetic resonance spectroscopy.ResultsTotal and VLDL triglycerides, and VLDL cholesterol increased from baseline to 36 gw in both treatment groups. The rise in triglycerides was greater in the metformin treated patients (p ConclusionCompared to insulin, metformin treatment of GDM led to higher maternal serum concentrations of triglyceride-rich lipoproteins. Especially triglycerides and cholesterol in VLDL were positively associated with BW. Women with high VLDL cholesterol or high apoB/apoA-1 may benefit from insulin treatment over metformin with respect to offspring BW.</p

Treatment of keloid scars with intralesional triamcinolone and 5-fluorouracil injections - a randomized controlled trial

Keloids have high recurrence rates. Current first-line therapy is triamcinolone (TAC) injection, but it has been suggested that approximately 50% of keloids are steroid resistant. We compared the efficacy of intralesional 5-fluorouracil (5-FU) and triamcinalone injections in a double-blind randomized controlled trial. Forty-three patients with 50 keloid scars were treated with either intralesional TAC or 5-FU-injections over 6 months. There was no statistically significant difference in the remission rate at 6 months between the 5-FU and TAC groups (46% vs 60%, respectively). Local adverse effects were higher in the TAC group compared to the 5-FU group. Occurrence of skin atrophy in TAC group was 44% and in the 5-FU group 8% (p <0.05). Also the occurrence of telangiectasia in the TAC group was 50% and in the 5-FU 21% (p <0.05). Vascularity of the keloids, assessed by spectral imaging and immunohistochemical staining for blood vessels, after treatment decreased in the TAC group, but not in the 5-FU group (p <0.05). Fibroblast proliferation evaluated by Ki-67 staining significantly decreased in the TAC group (p <0.05) but increased in the 5-FU group (p <0.05). TAC and 5-FU injections did not differ in their clinical effectivity in this randomized study, but 5-FU injections lead to increased proliferation rate and did not affect vascular density in histological assessment. Due to the greater number of adverse effects observed after TAC treatment, 5-FU injections may be preferable for cosmetically sensitive skin areas. (C) 2018 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Generalized Painleve-Gullstrand descriptions of Kerr-Newman black holes

Generalized Painleve-Gullstrand metrics are explicitly constructed for the Kerr-Newman family of charged rotating black holes. These descriptions are free of all coordinate singularities; moreover, unlike the Doran and other proposed metrics, an extra tunable function is introduced to ensure all variables in the metrics remain real for all values of the mass M, charge Q, angular momentum aM, and cosmological constant \Lambda > - 3/(a^2). To describe fermions in Kerr-Newman spacetimes, the stronger requirement of non-singular vierbein one-forms at the horizon(s) is imposed and coordinate singularities are eliminated by local Lorentz boosts. Other known vierbein fields of Kerr-Newman black holes are analysed and discussed; and it is revealed that some of these descriptions are actually not related by physical Lorentz transformations to the original Kerr-Newman expression in Boyer-Lindquist coordinates - which is the reason complex components appear (for certain ranges of the radial coordinate) in these metrics. As an application of our constructions the correct effective Hawking temperature for Kerr black holes is derived with the method of Parikh and Wilczek.Comment: 5 pages; extended to include application to derivation of Hawking radiation for Kerr black holes with Parikh-Wilczek metho

Amino acid profile in women with gestational diabetes mellitus treated with metformin or insulin

Aims: We compared the effects of metformin and insulin treatments of gestational diabetes mellitus (GDM) on amino acid metabolism.Methods: 217 pregnant women diagnosed with GDM were randomized to receive either metformin or insulin. 1H nuclear magnetic spectroscopy was used to determine serum concentrations of alanine, glutamine, glycine, isoleucine, leucine, valine, histidine, phenylalanine, tyrosine, glucose and lactate at the time of diagnosis and at 36 gestational weeks (gw).Results: Majority of the amino acid concentrations increased from 30 to 36 gw. The rise in alanine (16% vs. 8%, p Conclusions: Compared to insulin metformin caused a greater increase in serum alanine, isoleucine and lactate concentrations. Although the observed differences in the metabolic variables were relatively small and not outright concerning, additional studies and follow-up data are required to ensure the safety of metformin use in pregnancy.</p

Cord serum metabolome and birth weight in patients with gestational diabetes treated with metformin, insulin, or diet alone

AbstractIntroductionRecent research has demonstrated the benefits of metformin treatment in gestational diabetes (GDM) on short-term pregnancy outcomes (including excessive fetal growth and pre-eclampsia), but its effects on fetal metabolism remain mostly unknown. Our aim was to study the effects of metformin treatment compared with insulin or diet on the cord serum metabolome and also to assess how these metabolites are related to birth weight (BW) in pregnancies complicated by GDM.Research design and methodsCord serum samples were available from 113, 97, and 98 patients with GDM treated with diet, insulin, and metformin, respectively. A targeted metabolome was measured using nuclear magnetic resonance spectroscopy. The patients in the metformin and insulin groups had participated in a previous randomized trial (NCT01240785).ResultsCord serum alanine was elevated in the metformin group (0.53 mmol/L) compared with the insulin (0.45 mmol/L, pConclusionsMetformin treatment in GDM leads to an increase in cord serum alanine. The possible long-term implications of elevated neonatal alanine in this context need to be evaluated in future studies. Although previous studies have shown that metformin increased maternal TG levels, the cord serum TG levels were not affected. Cord serum HDL cholesterol and several FA variables are related to the regulation of fetal growth in GDM. Moreover, these associations seem to be independent of maternal confounding factors.Trial registration number NCT01240785.</p

Factors associated with decision-making on prophylactic hysterectomy and attitudes towards gynecological surveillance among women with Lynch syndrome (LS) : a descriptive study

To prevent endometrial carcinoma in Lynch syndrome (LS), regular gynecological surveillance visits and prophylactic surgery are recommended. Previous data have shown that prophylactic hysterectomy is an effective means of cancer prevention, while the advantages and disadvantages of surveillance are somewhat unclear. We aimed to evaluate female LS carriers' attitudes towards regular gynecological surveillance and factors influencing their decision-making on prophylactic surgery that have not been well documented. Pain experienced during endometrial biopsies was also evaluated. Postal questionnaires were sent to LS carriers undergoing regular gynecological surveillance. Questionnaires were sent to 112 women with LS, of whom 76 responded (68%). Forty-two (55%) had undergone prophylactic hysterectomy by the time of the study. The majority of responders (64/76; 84.2%) considered surveillance appointments beneficial. Pain level during endometrial biopsy was not associated with the decision to undergo prophylactic surgery. The level of satisfaction the women had with the information and advice provided during surveillance was significantly associated with the history of prophylactic hysterectomy (satisfaction rate of 73.2% versus 31.8% of nonoperated women, p = 0.003). The women who had undergone prophylactic surgery were older than the nonoperated women both at mutation testing (median of 42.3 years versus 31.6 years, p <0.001) and at the time of the study (median of 56.9 years versus 46.0 years, respectively, p <0.001). Women with LS pathogenic variants have positive experiences with gynecological surveillance visits, and their perception of the quality of the information and advice obtained plays an important role in their decision-making concerning prophylactic surgery.Peer reviewe