Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: a randomised double-blind placebo-controlled study.

Abstract:

AIMS/HYPOTHESIS:Pharmacological augmentation of glucagon-like peptide 1 receptor signalling by dipeptidyl peptidase 4 (DPP-4) inhibition reduced intestinal lipoprotein secretion in experimental studies, suggesting that DPP-4 inhibitors may ameliorate dyslipidaemia and thus reduce cardiovascular risk in patients with type 2 diabetes. We assessed the effects of alogliptin (Alo) and Alo co-administered with pioglitazone (Pio) vs placebo (Pbo) on triacylglycerol (TG)-rich lipoproteins in type 2 diabetes before and following a high-fat meal. METHODS:Seventy-one patients (age 18-70 years), who did not reach HbA(1c) 6.5% (48 mmol/mol) with lifestyle and/or metformin, sulfonylurea or glinide therapy, participated in this 16 week, double-centre (university hospitals) Pbo-controlled parallel-group study. All participants, people doing measurements or examinations, and people assessing the outcomes were blinded to group assignment. Fasting TG 1.7-5.0 mmol/l was among the entry criteria. Patients received a high-fat mixed meal before and 4 and 16 weeks after randomisation (allocation by central office) to Alo (n = 25), Alo/Pio (n = 22) or Pbo (n = 24). Blood was sampled at pre-specified intervals, starting at 15 min before and ending 8 h after meal ingestion. RESULTS:At week 16, Alo (n = 25) and Alo/Pio (n = 21) vs Pbo (n = 24) produced similar significant reductions in total postprandial TG response (incremental AUC [iAUC]; p < 0.001), as well as in chylomicron TG (p < 0.001) and VLDL1 TG iAUCs (p < 0.001 and p = 0.012, respectively). Postprandial chylomicron apolipoprotein B-48 iAUC showed a significant decrease after Alo treatment (p = 0.028), and a non-significant trend towards a decrease with Alo/Pio (p = 0.213). The incidence of adverse events was low and consistent with previous studies. CONCLUSIONS/INTERPRETATION:Treatment with Alo and Alo/Pio produced significant reductions in postprandial TG and TG-rich lipoproteins, contributing to an improved overall cardiometabolic risk profile in type 2 diabetes. The data support the concept that incretins not only modulate glucose metabolism but also influence chylomicron metabolism in intestinal cells. TRIAL REGISTRATION:ClinicalTrials.gov number NCT00655863.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Eliasson B,Möller-Goede D,Eeg-Olofsson K,Wilson C,Cederholm J,Fleck P,Diamant M,Taskinen MR,Smith U

doi

10.1007/s00125-011-2447-3

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

915-25

issue

4

eissn

0012-186X

issn

1432-0428

journal_volume

55

pub_type

杂志文章,多中心研究,随机对照试验
  • Marine lipids normalize cholesteryl ester transfer in IDDM.

    abstract::Patients with insulin-dependent diabetes mellitus (IDDM) have a pathological increase in cholesteryl ester transfer (CET) that enriches the apolipoprotein B-containing lipoproteins with cholesteryl ester and increases their atherogenicity. Since we have shown earlier that omega-3 (n-3) fatty acids present in marine li...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00400682

    authors: Bagdade JD,Ritter M,Subbaiah PV

    更新日期:1996-04-01 00:00:00

  • Effect of glucagon antibodies on plasma glucose, insulin and somatostatin in the fasting and fed rat.

    abstract::A potent high-titre glucagon antibody pool was used to induce a state of acute glucagon deficiency in order to investigate the importance of glucagon in maintaining euglycaemia in the fed and fasted anaesthetised rat. Binding characteristics of the antiserum and evidence of its neutralisation of the biological effects...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00280887

    authors: Tan K,Tsiolakis D,Marks V

    更新日期:1985-07-01 00:00:00

  • Accumulation of autoreactive effector T cells and allo-specific regulatory T cells in the pancreas allograft of a type 1 diabetic recipient.

    abstract:AIMS/HYPOTHESIS:Simultaneous kidney-pancreas transplantation is an established treatment for patients with type 1 diabetes and end-stage renal failure, even though restored beta cell function may become affected by recurrent islet autoimmunity or graft rejection. We characterised infiltrating lymphocytes isolated from ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-008-1237-z

    authors: Velthuis JH,Unger WW,van der Slik AR,Duinkerken G,Engelse M,Schaapherder AF,Ringers J,van Kooten C,de Koning EJ,Roep BO

    更新日期:2009-03-01 00:00:00

  • Coping with Type II diabetes: the patient's perspective.

    abstract:AIMS/HYPOTHESIS:The Cost of Diabetes in Europe-Type II study is the first coordinated attempt to assess the total costs of Type II (non-insulin-dependent) diabetes mellitus in Europe. Although gaining a clearer understanding of the economics of diabetes was the goal of the study, a secondary objective was to consider t...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-002-0861-2

    authors: Koopmanschap M

    更新日期:2002-07-01 00:00:00

  • Gene expression profiling of diabetic and galactosaemic cataractous rat lens by microarray analysis.

    abstract:AIMS/HYPOTHESIS:Osmotic and oxidative stress is associated with the progression and advancement of diabetic cataract. In the present study, we used a cDNA microarray method to analyse gene expression patterns in streptozotocin-induced diabetic rats and galactose-fed cataractous lenses. In addition, we investigated the ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-005-1687-5

    authors: Kubo E,Singh DP,Akagi Y

    更新日期:2005-04-01 00:00:00

  • Pathophysiology of postprandial hyperglycaemia in women with type 1 diabetes during pregnancy.

    abstract:AIMS/HYPOTHESIS:Although maternal hyperglycaemia is associated with increased risk of adverse pregnancy outcome, the mechanisms of postprandial hyperglycaemia during pregnancy are poorly understood. We aimed to describe glucose turnover in pregnant women with type 1 diabetes, according to stage of gestation (early vs l...

    journal_title:Diabetologia

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00125-011-2363-6

    authors: Murphy HR,Elleri D,Allen JM,Harris J,Simmons D,Rayman G,Temple RC,Umpleby AM,Dunger DB,Haidar A,Nodale M,Wilinska ME,Hovorka R

    更新日期:2012-02-01 00:00:00

  • The impact of ethnicity and sex on subclinical cardiovascular disease: the Diabetes Heart Study.

    abstract:AIMS/HYPOTHESIS:African-Americans with type 2 diabetes and access to adequate healthcare are at lower risk of clinical coronary artery disease than are white diabetic patients. We evaluated whether ethnic differences in subclinical cardiovascular disease, coronary and carotid artery calcified plaque and carotid artery ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-005-0017-2

    authors: Freedman BI,Hsu FC,Langefeld CD,Rich SS,Herrington DM,Carr JJ,Xu J,Bowden DW,Wagenknecht LE

    更新日期:2005-12-01 00:00:00

  • MAFA controls genes implicated in insulin biosynthesis and secretion.

    abstract:AIMS/HYPOTHESIS:Effects of the transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MAFA) on the regulation of beta cell gene expression and function were investigated. MATERIALS AND METHODS:INS-1 stable cell lines permitting inducible up- or downregulation of this transcription factor were...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-006-0490-2

    authors: Wang H,Brun T,Kataoka K,Sharma AJ,Wollheim CB

    更新日期:2007-02-01 00:00:00

  • The nucleotide exchange factor SIL1 is required for glucose-stimulated insulin secretion from mouse pancreatic beta cells in vivo.

    abstract:AIMS/HYPOTHESIS:Regulation of insulin secretion along the secretory pathway is incompletely understood. We addressed the expression of SIL1, a nucleotide exchange factor for the endoplasmic reticulum (ER) chaperone glucose-regulated protein 78 kD (GRP78), in pancreatic beta cells and investigated whether or not SIL1 is...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-014-3230-z

    authors: Ittner AA,Bertz J,Chan TY,van Eersel J,Polly P,Ittner LM

    更新日期:2014-07-01 00:00:00

  • Proteinuria in the acutely diabetic rat and its response to insulin treatment.

    abstract::The development of proteinuria and its response to insulin therapy in acute experimental diabetes was examined in 11 female rats by sequentially measuring 24 h excretion of glucose and total protein before diabetes, during 5-37 days of acute streptozotocin diabetes, during and after 7-14 days of continuous subcutaneou...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF03216225

    authors: Pennell JP,Millard MM,Ashby MH

    更新日期:1981-07-01 00:00:00

  • The effects of a specific growth hormone antagonist on overnight insulin requirements and insulin sensitivity in young adults with Type 1 diabetes mellitus.

    abstract:AIMS/HYPOTHESIS:Growth hormone hypersecretion in Type 1 diabetes could exacerbate insulin resistance and contribute to declining glycaemic control. Our aim was to determine the effects of specific growth hormone blockade on insulin sensitivity and lipolysis in young adults with Type 1 diabetes. METHODS:We studied the ...

    journal_title:Diabetologia

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/s00125-003-1175-8

    authors: Williams RM,Amin R,Shojaee-Moradie F,Umpleby AM,Acerini CL,Dunger DB

    更新日期:2003-09-01 00:00:00

  • Islet-intrinsic effects of CFTR mutation.

    abstract::Cystic fibrosis-related diabetes (CFRD) is the most significant extra-pulmonary comorbidity in cystic fibrosis (CF) patients, and accelerates lung decline. In addition to the traditional view that CFRD is a consequence of fibrotic destruction of the pancreas as a whole, emerging evidence may implicate a role for cysti...

    journal_title:Diabetologia

    pub_type: 杂志文章,评审

    doi:10.1007/s00125-016-3936-1

    authors: Koivula FNM,McClenaghan NH,Harper AGS,Kelly C

    更新日期:2016-07-01 00:00:00

  • Effects of streptozotocin-induced diabetes and noradrenaline infusion on cardiac output and its regional distribution in pithed rats.

    abstract::46Sc-and 99mTc-labelled microspheres were used to measure the effects of noradrenaline infusion on cardiac output and its regional distribution in 10 control and 10 streptozotocin-diabetic pithed rats. Plasma noradrenaline concentrations during the infusion were similar in both groups. Pressor responses were significa...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00279926

    authors: Lucas PD

    更新日期:1985-02-01 00:00:00

  • Improved survival in patients with diabetic nephropathy.

    abstract::The effect of early antihypertensive treatment on survival of patients with diabetic nephropathy was evaluated by studying two cohorts of Type 1 (insulin-dependent) diabetic patients developing persistent proteinuria in I: 1957-1973 (late treatment group n = 49) and II: 1979-1983 (early treatment group n = 71). At ons...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00297455

    authors: Mathiesen ER,Borch-Johnsen K,Jensen DV,Deckert T

    更新日期:1989-12-01 00:00:00

  • Underestimation of D-glucose utilisation as judged from the conversion of D-[3-(3)H]glucose to (3)HOH.

    abstract:AIMS/HYPOTHESIS:The conversion of D-[3-(3)H]glucose to (3) HOH is currently measured to assess D-glucose utilisation. The validity of such a procedure was re-evaluated. METHODS:The conversion of D-[3-(3)H]glucose and D-[5-(3)H]glucose to (3) HOH was measured in rat pancreatic islets, parotid cells and erythrocytes. Th...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-002-0907-5

    authors: Sener A,Giroix MH,Malaisse WJ

    更新日期:2002-09-01 00:00:00

  • Oesophageal dysmotility, delayed gastric emptying and autonomic neuropathy correlate to disturbed glucose homeostasis.

    abstract:AIMS/HYPOTHESIS:Among diabetic patients, glucose homeostasis may be affected by abnormal gastrointestinal motility and autonomic neuropathy. This study analysed whether oesophageal dysmotility, delayed gastric emptying or autonomic neuropathy affect glucose homeostasis. MATERIALS AND METHODS:Oesophageal manometry and ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-006-0354-9

    authors: Ohlsson B,Melander O,Thorsson O,Olsson R,Ekberg O,Sundkvist G

    更新日期:2006-09-01 00:00:00

  • Pentamidine, a new diabetogenic drug in laboratory rodents.

    abstract::The antiprotozoal drug, pentamidine, has been reported to induce hypoglycaemia associated with inappropriately high plasma insulin concentrations, followed by insulin-dependent diabetes mellitus. It has been suggested that this drug can be toxic to the islet B cell, inducing early cytolytic release of insulin leading ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00282521

    authors: Saï P,Boillot D,Boitard C,Debray-Sachs M,Reach G,Assan R

    更新日期:1983-11-01 00:00:00

  • Reduced tricarboxylic acid cycle flux in type 2 diabetes mellitus?

    abstract:AIMS/HYPOTHESIS:Mitochondrial dysfunction has been postulated to underlie muscular fat accumulation, leading to muscular insulin sensitivity and ultimately type 2 diabetes mellitus. Here we re-interpret previously published data on [(13)C]acetate recovery in breath gas obtained during exercise in type 2 diabetic patien...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-008-1069-x

    authors: Schrauwen P,Hesselink MK

    更新日期:2008-09-01 00:00:00

  • Localisation and composition of skeletal muscle diacylglycerol predicts insulin resistance in humans.

    abstract:AIMS/HYPOTHESIS:We sought to evaluate if the cellular localisation and molecular species of diacylglycerol (DAG) were related to insulin sensitivity in human skeletal muscle. METHODS:Healthy sedentary obese controls (Ob; n = 6; mean±SEM age 39.5 ± 2.3 years; mean ± SEM BMI 33.3 ± 1.4 kg/m(2)), individuals with type 2 ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-011-2419-7

    authors: Bergman BC,Hunerdosse DM,Kerege A,Playdon MC,Perreault L

    更新日期:2012-04-01 00:00:00

  • Pharmacological reduction of NEFA restores the efficacy of incretin-based therapies through GLP-1 receptor signalling in the beta cell in mouse models of diabetes.

    abstract:AIMS/HYPOTHESIS:Type 2 diabetes mellitus is associated with reduced incretin effects. Although previous studies have shown that hyperglycaemia contributes to impaired incretin responses in beta cells, it is largely unknown how hyperlipidaemia, another feature of type 2 diabetes, contributes to impaired glucagon-like pe...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-012-2776-x

    authors: Kang ZF,Deng Y,Zhou Y,Fan RR,Chan JC,Laybutt DR,Luzuriaga J,Xu G

    更新日期:2013-02-01 00:00:00

  • Electron microscopy of renal and ocular changes in virus-induced diabetes mellitus in mice.

    abstract::The eyes, kidneys and pancreas of mice (SJL/J) infected with encephalomyocarditis virus were examined by light and electron microscopy. Diabetic mice with the longest duration (6 months) of diabetes showed marked renal and ocular alterations. Fasting blood glucose levels were 17.8-21.9 mmol/l and glycosuria was presen...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00282717

    authors: Rodrigues M,Currier C,Yoon J

    更新日期:1983-04-01 00:00:00

  • Type I (insulin dependent) diabetes mellitus. Is there strong evidence for a non-HLA linked gene?

    abstract::A recent investigation of families containing two and three consecutive generations affected with Type I (insulin dependent) diabetes mellitus has led to speculation that there is a second susceptibility gene, not linked to the major histocompatibility complex. These families differ in important respects from families...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00252759

    authors: Suarez BK,Van Eerdewegh P

    更新日期:1981-05-01 00:00:00

  • How common are foot problems among individuals with diabetes? Diabetic foot ulcers in the Dutch population.

    abstract:AIMS/HYPOTHESIS:Contemporary data on diabetic foot ulcer prevalence are scarce. Most studies were conducted in the 1990s, reporting incidence rates of 1.9-2.6%. Since then the prevalence of diabetes has doubled and the organisation of diabetes care has undergone major changes. Up-to-date data that quantify the occurren...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-017-4274-7

    authors: Stoekenbroek RM,Lokin JLC,Nielen MM,Stroes ESG,Koelemay MJW

    更新日期:2017-07-01 00:00:00

  • Risk of cancer in patients on insulin glargine and other insulin analogues in comparison with those on human insulin: results from a large population-based follow-up study.

    abstract:AIMS/HYPOTHESIS:Several publications suggest an association between certain types of insulin and cancer, but with conflicting results. We investigated whether insulin glargine (A21Gly,B31Arg,B32Arg human insulin) is associated with an increased risk of cancer in a large population-based cohort study. METHODS:Data for ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-011-2312-4

    authors: Ruiter R,Visser LE,van Herk-Sukel MP,Coebergh JW,Haak HR,Geelhoed-Duijvestijn PH,Straus SM,Herings RM,Stricker BH

    更新日期:2012-01-01 00:00:00

  • A new mutation (db3J) at the diabetes locus in strain 129/J mice. II. Studies of pancreatic alpha cell function in culture.

    abstract::Monolayer cell cultures from pancreatic islets of aging 129/J strain diabetes (db3J/db3J) and lean littermate control mice were tested for differences in glucagon and insulin secretion in either serum-free Eagle's minimal essential medium (MEM) or Dulbecco's modified minimal essential medium (DMEM). There was a highly...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00258314

    authors: Leiter EH,Strack I,Eisenstein AB

    更新日期:1980-07-01 00:00:00

  • Islet amyloid polypeptide (amylin) and insulin are differentially expressed in chronic diabetes induced by streptozotocin in rats.

    abstract::Islet amyloid polypeptide (IAPP) is overexpressed relative to insulin under several experimental conditions relevant to diabetes mellitus, including the immediate phase (7 days) following induction of streptozotocin diabetes. In the present study, IAPP and insulin gene expression were examined in chronic streptozotoci...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00418536

    authors: Mulder H,Ahrén B,Sundler F

    更新日期:1996-06-01 00:00:00

  • Proinsulin in development: New roles for an ancient prohormone.

    abstract::In postnatal organisms, insulin is well known as an essential anabolic hormone responsible for maintaining glucose homeostasis. Its biosynthesis by the pancreatic beta cell has been considered a model of tissue-specific gene expression. However, proinsulin mRNA and protein have been found in embryonic stages before th...

    journal_title:Diabetologia

    pub_type: 杂志文章,评审

    doi:10.1007/s00125-006-0232-5

    authors: Hernández-Sánchez C,Mansilla A,de la Rosa EJ,de Pablo F

    更新日期:2006-06-01 00:00:00

  • Male-to-female excess in diabetes diagnosed in early adulthood is not specific for the immune-mediated form nor is it HLA-DQ restricted: possible relation to increased body mass index.

    abstract:UNLABELLED:AIMS/HYPOTHESIS. We investigated whether the reported HLA-DQ/DR restricted male-to-female (M:F) excess in Type I (insulin-dependent) diabetes mellitus also exists in Belgian patients, is specific for immune-mediated diabetes, remains genotype-restricted after adjustment for age at diagnosis, and is associate...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s001250051578

    authors: Weets I,Van Autreve J,Van der Auwera BJ,Schuit FC,Du Caju MV,Decochez K,De Leeuw IH,Keymeulen B,Mathieu C,Rottiers R,Dorchy H,Quartier E,Gorus FK,Belgian Diabetes Registry.

    更新日期:2001-01-01 00:00:00

  • Effects of alloxan on glucose-stimulated insulin secretion, glucose metabolism, and cyclic adenosine 3', 5'-monophosphate levels in rat isolated islets of langerhans.

    abstract::Insulin secretion was stimulated and cyclic adenosine 3', 5'-monophosphate (cAMP) levels were elevated in isolated rat islets by 27.5 mmol/l glucose. Alloxan caused a dose-dependent decrease in both variables with complete obliteration of insulin release at a concentration of 1.25 mmol/l. D-glucose, in the presence or...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF01225460

    authors: Zawalich WS,Karl RC,Matschinsky FM

    更新日期:1979-02-01 00:00:00

  • Metabolomics insights into early type 2 diabetes pathogenesis and detection in individuals with normal fasting glucose.

    abstract:AIMS/HYPOTHESIS:Identifying the metabolite profile of individuals with normal fasting glucose (NFG [<5.55 mmol/l]) who progressed to type 2 diabetes may give novel insights into early type 2 diabetes disease interception and detection. METHODS:We conducted a population-based prospective study among 1150 Framingham Hea...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-018-4599-x

    authors: Merino J,Leong A,Liu CT,Porneala B,Walford GA,von Grotthuss M,Wang TJ,Flannick J,Dupuis J,Levy D,Gerszten RE,Florez JC,Meigs JB

    更新日期:2018-06-01 00:00:00