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991.
Melissa M. Kallas-Koeman Jason M. Kong Jennifer A. Klinke Sonia Butalia Abhay K. Lodha Ken I. Lim Qiuli M. Duan Lois E. Donovan 《Diabetologia》2014,57(4):681-689
Aims/hypothesis
The aim of this study was to compare glycaemic control and maternal–fetal outcomes in women with type 1 diabetes managed on insulin pumps compared with multiple daily injections of insulin (MDI).Methods
In a retrospective study, glycaemic control and outcomes of 387 consecutive pregnancies in women with type 1 diabetes who attended specialised clinics at three centres 2006–2010 were assessed.Results
Women using insulin pumps (129/387) were older and had a longer duration of diabetes, more retinopathy, smoked less in pregnancy, and had more preconception care (p?<?0.01 for each). Among 113 pregnancies >20 weeks’ gestation in women on insulin pumps and 218 in women on MDI, there was a significant difference in HbA1c in the first trimester (mean HbA1c 6.90?±?0.71% (52?±?7.8 mmol/mol) vs 7.60?±?1.38% (60?±?15.1 mmol/mol), p?<?0.001), which persisted until the third trimester (mean HbA1c 6.49?±?0.52% (47?±?5.7 mmol/mol) vs 6.81?±?0.85% (51?±?9.3 mmol/mol), p?=?0.002). Rates of diabetic ketoacidosis were similar in women on insulin pumps vs MDI (1.8% vs 3.0%, p?=?0.72). Despite lower HbA1c, women on insulin pumps did not have an increased incidence of severe hypoglycaemia (8.0% vs 7.6%, p?=?0.90) or more weight gain (16.3?±?8.7 vs 15.2?±?6.2 kg, p?=?0.18). More large-for-gestational-age infants in the pump group (55.0% vs 39.2%, p?=?0.007) may have resulted from confounding by parity.Conclusions/interpretation
In this large multicentre study, women using insulin pumps in pregnancy had lower HbA1c without increased risk of severe hypoglycaemia or diabetic ketoacidosis but no improvement in other pregnancy outcomes. This information can help inform care providers and patients about the glycaemic effectiveness and safety of insulin pumps in pregnancy. 相似文献992.
993.
994.
Felicity Payne Koini Lim Amandine Girousse Rebecca J. Brown Nora Kory Ann Robbins Yali Xue Alison Sleigh Elaine Cochran Claire Adams Arundhati Dev Borman David Russel-Jones Phillip Gorden Robert K. Semple Vladimir Saudek Stephen O’Rahilly Tobias C. Walther Inês Barroso David B. Savage 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(24):8901-8906
Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this pathway. The mutations lead to a marked reduction in PCYT1A expression and PC synthesis. The phenotypic consequences include some features, such as severe fatty liver and low HDL cholesterol levels, that are predicted by the results of previously reported liver-specific deletion of murine Pcyt1a. Both patients also had lipodystrophy, severe insulin resistance, and diabetes, providing evidence for an additional and essential role for PCYT1A-generated PC in the normal function of white adipose tissue and insulin action.All living cells are surrounded by a lipid membrane. Eukaryotic cells also contain several internal membrane-bound organelles, which enable them to compartmentalize related biological functions and thereby to enhance the efficiency of these processes. Phospholipids are the predominant component of these membranes. Their hydrophilic head groups interact with the cytosol, whereas their hydrophobic side chains are either buried within the hydrophobic interior of a typical membrane bilayer or interact with the hydrophobic neutral lipid core of lipoproteins and lipid droplets (LDs). Phospholipids are generally defined by their organic head group with phosphatidylcholine (PC) constituting over 50% of all membrane phospholipids. PC was first isolated in the 19th century and the major enzymatic pathway involved in its synthesis was revealed by Kennedy and Weiss (1) in the 1950s. Cells synthesize PC in three consecutive steps (Fig. 1A): choline kinase phosphorylates choline before choline phosphate cytidylyltransferase 1 α (encoded by the PCYT1A gene) generates the high-energy donor CDP-choline in the rate-limiting step of the pathway. In the last step, DAG:CDP-choline cholinephosphotransferase (CPT) uses CDP-choline and diacylglycerol (DAG) to form PC (2, 3).Open in a separate windowFig. 1.Cosegregation of biallelic PCYT1A mutations with fatty liver, low HDL cholesterol levels, lipodystrophy, insulin-resistant diabetes, and short stature. (A) Schematic illustration of the Kennedy PC synthesis pathway. CK, choline kinase; CPT, CDP-choline:1,2-diacylglycerol cholinephosphotransferase; PCYT1A, choline-phosphate cytidylyltransferase A, CTP:phosphocholine-cytidylyltransferase. (B) Family pedigrees of both probands demonstrating that only compound heterozygous carriers of PCYT1A mutations manifest fatty liver (red), low HDL cholesterol (blue), lipodystrophy (yellow), and insulin resistance/type 2 diabetes (T2DM) (green). PCYT1A mutation status, height (Ht.), and body mass index (BMI) are indicated below each individual’s symbol. ND, not determined; WT, wild type. (C) The location of PCYT1A mutations E280del, V142M, and 333fs in relation to known functional domains of PCYT1A. Domain M, membrane binding domain; domain P, phosphorylated region. (D) Conservation around the V142(red*) and E280(red*) mutation sites. Sequence alignment of representative metazoan sequences in the region surrounding the mutated residues. Hydrophobic (blue) and polar (green) residues interacting with V142 are highlighted. Only residues different from the human sequence are shown. Sequence IDs: human (Homo sapiens) , zebrafish (Danio rerio) F1QEN6, sea squirt (Ciona intestinalis) P49585, sea urchin (Strongylocentrotus purpuratus) H3I3V9, water flee (Daphnia pulex) E9G1P5, Drosophila (D. melanogaster) Q9W0D9, Caenorhabditis (C. elegans) XP_002130773.1, Trichoplax (T. adherens) B3RI62. (E and F) Structure of the catalytic domain of PCYT1A highlighting the role of V142M in the core packing. The two chains in the dimer are shown in yellow and gray; the residues and the secondary structure units are highlighted in color in the yellow monomer A: loop L3 with V142, red; α-helix, green; and the interacting β-sheet, blue. The residues packing with V142 are shown in ball-and-stick and space-filling representations, the dimer stabilizing R140 is shown in ball-and-stick colored according to the atom type. E is a global view, and F is a zoomed-in view of the catalytic core.Membrane phospholipids are a defining feature of advanced life-forms so it is perhaps not surprising that the pathways involved in their synthesis are ancient, and mutations affecting them are rarely tolerated in evolution. Here, we describe the identification and characterization of pathogenic human loss-of-function mutations affecting the eponymous Kennedy pathway. P49583相似文献
995.
Sarah Tan Lin Xie Robert Anderson Andrew Hammond Angelina Y. Fong Seok Lim Andrew M. Allen Stephen B. Harrap 《Internal medicine journal》2020,50(1):114-117
Whether part of the blood pressure lowering effects of glyceryl trinitrate (GTN) is the result of centrally mediated reduction in sympathetic activity is debated. In humans, baroreflex activity potentially obscures the central sympatholytic effects of GTN. We examined this in a routine clinical tilt test in a patient with baroreflex failure secondary to previous neck radiotherapy. With reduced baroreflex function we observed an exaggerated fall in blood pressure and reduced sympathetic activity with GTN, supporting a peripheral vasodilation and central sympatholytic effect. 相似文献
996.
997.
998.
Shweta Urva PhD Tamer Coskun MD Corina Loghin MD Xuewei Cui PhD Emily Beebe BS Libbey O'Farrell BS Daniel A. Briere MS Charles Benson MD Michael A. Nauck MD Axel Haupt MD 《Diabetes, obesity & metabolism》2020,22(10):1886-1891
The effect of dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide on gastric emptying (GE) was compared to that of GLP-1RAs in non-clinical and clinical studies. GE was assessed following acute and chronic treatment with tirzepatide in diet-induced obese mice versus semaglutide or long-acting GIP analogue alone. Participants [with and without type 2 diabetes (T2DM)] from a phase 1, 4-week multiple dose study received tirzepatide, dulaglutide or placebo. GE was assessed by acetaminophen absorption. In mice, tirzepatide delayed GE to a similar degree to that achieved with semaglutide; however, these acute inhibitory effects were abolished after 2 weeks of treatment. GIP analogue alone had no effect on GE or on GLP-1's effect on GE. In participants with and without T2DM, once-weekly tirzepatide (≥5 and ≥4.5 mg, respectively) delayed GE after a single dose. This effect diminished after multiple doses of tirzepatide or dulaglutide in healthy participants. In participants with T2DM treated with an escalation schedule of tirzepatide 5/5/10/10 or 5/5/10/15 mg, a residual GE delay was still observed after multiple doses. These data suggest that tirzepatide's activity on GE is comparable to that of selective GLP-1RAs. 相似文献
999.
Elizabeth T. Jensen PhD Alain G. Bertoni MD Osa L. Crago BS Kristi L. Hoffman PhD Alexis C. Wood PhD Zorayr Arzumanyan BS Lok-Sze Kelvin Lam BSc Kathryn Roll RN Kevin Sandow BS Martin Wu PhD Stephen S. Rich PhD Jerome I. Rotter MD Yii-Der I. Chen PhD Joseph F. Petrosino PhD Mark O. Goodarzi MD 《Diabetes, obesity & metabolism》2020,22(11):1976-1984
1000.
Lisa J. Moran Eliza C. Tassone Jacqueline Boyle Leah Brennan Cheryce L. Harrison Angelica Lindn Hirschberg Siew Lim Kate Marsh Marie L. Misso Leanne Redman Mala Thondan Chandrika Wijeyaratne Rhonda Garad Nigel K. Stepto Helena J. Teede 《Obesity reviews》2020,21(10)
Lifestyle is fundamental in chronic disease prevention and management, and it has been recommended as a first‐line treatment in the Australian polycystic ovary syndrome (PCOS) guideline 2011. The first international evidence‐based guideline on PCOS was developed in 2018, which expanded the scope and evidence in the Australian guideline. This paper summarizes the lifestyle recommendations and evidence summaries from the guideline. International multidisciplinary guideline development groups delivered the International Evidence‐based Guideline for the Assessment and Management of Polycystic Ovary Syndrome 2018. The process followed the Appraisal of Guidelines for Research and Evaluation II and The Grading of Recommendations, Assessment, Development and Evaluation framework. Extensive communication and meetings addressed six prioritized clinical questions through five reviews. Evidence‐based recommendations were formulated before consensus voting within the panel. Evidence shows the benefits of multicomponent lifestyle intervention, efficacy of exercise and weight gain prevention with no specific diet recommended. Lifestyle management is the first‐line management in the intervention hierarchy in PCOS. Multicomponent lifestyle intervention including diet, exercise and behavioural strategies is central to PCOS management with a focus on weight and healthy lifestyle behaviours. The translation programme optimizes reach and dissemination for health professionals and consumers. 相似文献