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1.
BMJ. 2018 Dec 5;363:k4880. doi: 10.1136/bmj.k4880.

Incretin based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: population based cohort study.

Author information

1
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine Road, H425.1, Montreal, QC, H3T 1E2, Canada.
2
Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada.
3
Institute of Clinical Pharmacology and Toxicology, Charité University Medicine Berlin, Berlin, Germany.
4
Division of Endocrinology, Jewish General Hospital, Montreal, QC, Canada.
5
Department of Medical Pharmacology and Toxicology, CHU Montpellier; Laboratory of Biostatistics, Epidemiology and Public Health, University of Montpellier, Montpellier, France.
6
Department of Medical and Clinical Pharmacology, Centre of PharmacoVigilance and Pharmacoepidemiology, INSERM UMR 1027, CIC 1426, Toulouse University Hospital, Faculty of Medicine, University of Toulouse, France.
7
Department of Oncology, McGill University Health Centre, Montreal, QC, Canada.
8
Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada.
9
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine Road, H425.1, Montreal, QC, H3T 1E2, Canada laurent.azoulay@mcgill.ca.

Abstract

OBJECTIVE:

To determine whether use of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes.

DESIGN:

Population based cohort study.

SETTING:

General practices contributing data to the UK Clinical Practice Research Datalink.

PARTICIPANTS:

154 162 adults newly treated with antidiabetic drugs between 1 January 2007 and 31 March 2017, followed until 31 March 2018.

MAIN OUTCOME MEASURES:

Use of DPP-4 inhibitors and GLP-1 receptor agonists was modelled as a time varying variable and compared with use of other second or third line antidiabetic drugs. All exposures were lagged by one year to account for cancer latency and to minimise reverse causality. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals of incident cholangiocarcinoma associated with use of DPP-4 inhibitors and GLP-1 receptor agonists, separately. A post hoc pharmacovigilance analysis was conducted using the World Health Organization's global individual case safety report database, VigiBase, to estimate reporting odds ratios of cholangiocarcinoma.

RESULTS:

During 614 274 person years of follow-up, 105 incident cholangiocarcinoma events occurred (rate 17.1 per 100 000 person years). Use of DPP-4 inhibitors was associated with a 77% increased hazard of cholangiocarcinoma (hazard ratio 1.77, 95% confidence interval 1.04 to 3.01). Use of GLP-1 receptor agonists was associated with an increased hazard with a wide confidence interval (hazard ratio 1.97, 0.83 to 4.66). In the pharmacovigilance analysis, the use of DPP-4 inhibitors and GLP-1 receptor agonists were both associated with increased reporting odds ratios for cholangiocarcinoma, compared with use of sulfonylureas or thiazolidinediones (1.63, 1.00 to 2.66, 4.73, 2.95 to 7.58, respectively).

CONCLUSION:

Compared with use of other second or third line antidiabetic drugs, use of DPP-4 inhibitors, and possibly GLP-1 receptor agonists, might be associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: this study was funded by the Canadian Institutes of Health Research. RWP received consulting fees for work unrelated to this project from Amgen, Eli Lilly, Merck, and Pfizer. All other authors have no conflicts to disclose, and have no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

2.
3.
Diabet Med. 2018 Dec 4. doi: 10.1111/dme.13873. [Epub ahead of print]

Prospective memory slips are associated with forgetting to take glucose-lowering therapies among adults with diabetes: results from the second Diabetes MILES - Australia (MILES-2) survey.

Trawley S1,2,3, Baptista S2,3,4, Pouwer F2,5, Speight J2,3,6,7.

Author information

1
The Cairnmillar Institute, Melbourne, Victoria, Australia.
2
School of Psychology, Deakin University, Geelong, Victoria, Australia.
3
The Australian Centre for Behavioural Research in Diabetes, Diabetes Victoria, Melbourne, Victoria, Australia.
4
Non Communicable Disease Unit, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
5
STENO Diabeter Center Odense, Odense University Hospital, Odense, Denmark.
6
Department of Psychology, University of Southern Denmark, Odense, Denmark.
7
AHP Research, Hornchurch, UK.

Abstract

AIMS:

Prospective memory has been long considered a fundamental cognitive ability for optimal medication taking, but the role of prospective memory errors (termed 'slips') in diabetes self-care is unclear. Our aim was to examine associations between prospective memory and medication taking in adults with Type 1 and Type 2 diabetes mellitus.

METHODS:

Some 901 adults with Type 1 diabetes and 927 with Type 2 diabetes completed a cross-sectional survey focused on the psychological and behavioural aspects of living with diabetes. Respondents reported whether they had forgotten to take their diabetes medication over the previous 14 days.

RESULTS:

Twenty-four per cent (n = 220) of adults with Type 1 diabetes and 23% (n = 211) with Type 2 diabetes reported that they had forgotten their medication at least once over the previous 14 days. This was associated with more prospective memory slips in adults with Type 1 diabetes [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.05 to 1.13; P < 0.001] and Type 2 diabetes (OR 1.10, 95% CI 1.05 to 1.15; P < 0.001); and with younger age (both groups), insulin pump use (Type 1 diabetes), insulin treatment (Type 2 diabetes), less frequent blood glucose checks (Type 1 diabetes) and higher HbA1c (Type 1 diabetes).

CONCLUSIONS:

These findings suggest that forgetting medication is relatively common among adults with Type 1 or Type 2 diabetes, and provide preliminary evidence for its relationship with self-reported prospective memory slips.

PMID:
30511764
DOI:
10.1111/dme.13873
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4.
J Clin Endocrinol Metab. 2018 Dec 5. doi: 10.1210/jc.2018-02044. [Epub ahead of print]

Exposure to gestational diabetes is a stronger predictor of dysmetabolic traits in children than size at birth.

Author information

1
Division for Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.
2
Department of Endocrinology, Diabetes and Bone-metabolic Research Unit, Rigshospitalet, Copenhagen Denmark.
3
The Danish Diabetes Academy, Odense, Denmark.
4
Centre for Foetal Programming, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
5
Vitality - Centre for Good Older Lives, Department of Nutrition, Sports & Exercise, University of Copenhagen, Denmark.

Abstract

Context and Objective:

Being born small or large for gestational age and intrauterine exposure to gestational diabetes (GDM) increase the risk of type 2 diabetes (T2D) in the offspring, however, the potential combined deleterious effects of size at birth and GDM exposure remains unknown. We aimed to examine the independent effect of size at birth as well as the influence of GDM exposure in utero on cardio-metabolic traits, body composition, and puberty status in children.

Design, Participants and Methods:

This study is a longitudinal birth cohort study. We used clinical data from 490 offspring of mothers with GDM and 527 control offspring aged 9-16 years, born singleton at term from the Danish National Birth Cohort with available birth weight data.

Results:

We found no evidence of a U-shaped association between size at birth (expressed as birth weight, sex and gestational age adjusted z-score) and cardio-metabolic traits. Body size in childhood and adolescence reflected size at birth, but was not reflected in any metabolic outcome. No synergistic adverse effect of being born small or large for gestational age and being exposed to GDM was shown. However, GDM was associated with an adverse metabolic profile and earlier onset of female puberty in childhood and adolescence independently of size at birth.

Conclusion:

In childhood and adolescence, GDM is a stronger predictor of dysmetabolic traits than size at birth. The combination of being born small or large and being exposed to GDM does not exacerbate the metabolic profile in the offspring.

5.
J Clin Endocrinol Metab. 2018 Dec 4. doi: 10.1210/jc.2018-01339. [Epub ahead of print]

BMI change during puberty is an important determinant of adult type 2 diabetes risk in men.

Author information

1
Centre for Bone and Arthritis Research, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
2
Bioinformatics Core Facility, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
3
Department of Molecular and Clinical Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Abstract

Objective:

The aim of this study was to determine the role of change in body mass index (BMI) during puberty, independent of childhood overweight, for the risk of adult type 2 diabetes in men.

Study design, population and outcome:

We included 36,176 men who had weight and height measured at age 8 (childhood) and 20 (young adult age) available from the BMI Epidemiology Study (BEST) and the Conscription register. Information on type 2 diabetes (n=1,777) was retrieved from the Swedish National Patient Register. Hazard ratios and 95% Confidence Intervals were estimated by Cox regressions including birth year and country of birth as covariates. Because the assumption of proportional hazards was violated for the association between BMI change during puberty and type 2 diabetes, we split the follow-up time into early (≤55.7 years) and late (>55.7 years).

Results:

Both childhood overweight and a high BMI increase during puberty associated with risk of adult type 2 diabetes. Men with childhood overweight that normalized during puberty did not have a significantly increased risk of type 2 diabetes (Early type 2 diabetes 1.28[0.89; 1.82]; Late type 2 diabetes 1.35[0.97; 1.87]). Men who developed overweight during puberty (Early 4.67[3.90; 5.58]; Late 2.85[2.25; 3.61]) and men overweight at both childhood and young adult age (Early 4.82[3.84; 6.05]; Late 3.04[2.27; 4.06]) had substantially increased risk of type 2 diabetes compared with men who were never overweight.

Conclusion:

BMI change during puberty is an important, and childhood BMI a modest, independent determinant of adult type 2 diabetes risk in men.

6.
J Clin Endocrinol Metab. 2018 Dec 3. doi: 10.1210/jc.2018-01599. [Epub ahead of print]

Adipose tissue exosomal proteomic profile reveals a role on placenta glucose metabolism in gestational diabetes mellitus.

Author information

1
Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane QLD, Australia.
2
Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
3
Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.
4
Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia.
5
Mercy Perinatal Research Centre, Mercy Hospital for Women, Victoria, Australia.
6
Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
7
Mater Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.

Abstract

Context:

Molecules produced by adipose tissue (AT) function as an endocrine link between maternal AT and fetal growth by regulating placental function in normal and gestational diabetes mellitus (GDM).

Objective:

We hypothesised that AT-derived exosomes from women with GDM carry a specific set of proteins that influences glucose metabolism in placenta.

Design:

Exosomes were isolated from omental AT-conditioned media from pregnant women with normal glucose tolerance (exo-NGT, n=65) and women with GDM (exo-GDM, n=82). SWATH mass spectrometry (MS) was used to construct a small ion library from AT and exosomal proteins followed by ingenuity pathway analysis (IPA) to determine canonical pathways and biofunctions. The effect of exosomes on human placental cells was determined using a Human Glucose Metabolism RT2 Profiler PCR Array.

Results:

The number of exosomes (vesicles/μg-tissue/24h) was significantly (1.7-fold) higher in GDM compared to NGT, and the number of exosomes positively correlated with birthweight Z score. IPA of the exosomal proteins revealed differential expression of the proteins targeting sirtuin (sirt) signalling pathway, oxidative phosphorylation (OXPHOS) and mechanistic target of rapamycin (mTOR) signalling pathways in GDM compared to NGT. Exo-GDM increased the expression of genes associated with glycolysis and gluconeogenesis in placental cells compared to the effect of exo-NGT.

Conclusions:

Our findings are consistent with the possibility that AT exosomes play an important role in mediating the changes in placental function in GDM, which may be responsible for some of the adverse consequences in this pregnancy complication, such as fetal overgrowth.

7.
J Clin Endocrinol Metab. 2019 Mar 1;104(3):639-646. doi: 10.1210/jc.2018-01239.

Body-Weight Fluctuation and Incident Diabetes Mellitus, Cardiovascular Disease, and Mortality: A 16-Year Prospective Cohort Study.

Oh TJ1,2, Moon JH1,2, Choi SH1,2, Lim S1,2, Park KS2,3, Cho NH4, Jang HC1,2.

Author information

1
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
2
Seoul National University College of Medicine, Seoul, Korea.
3
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
4
Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea.

Abstract

Context:

Body-weight fluctuation (weight cycling) has been found to be associated with higher mortality and cardiovascular events in patients with coronary artery disease. However, there are very limited data regarding the relationship between body-weight fluctuation and health-related outcomes in the general population.

Methods:

We examined whether body-weight fluctuation can associate incident diabetes mellitus and cardiovascular events, and mortality in a Korean population from the Korean Genome and Epidemiology Study. The intraindividual fluctuations of body weight were calculated by average successive variability (ASV); health-related outcomes were collected every 2 years for 16 years in 3,678 participants.

Results:

Participants with a high ASV of body weight were more obese and had higher blood pressure and HbA1c levels at baseline than those with a low ASV of body weight. A 1-unit increase in ASV of body weight was associated with increase in mortality (HR, 1.46; 95% CI, 1.32 to 1.62; P < 0.001). However, the association between the ASV of body weight and incident diabetes mellitus seemed to be influenced by baseline body mass index (BMI): negative effect in subjects with BMI <25 kg/m2 (HR, 1.36; 95% CI, 1.11 to 1.65; P = 0.003) and protective effect in those with BMI ≥25 kg/m2 (HR, 0.76; 95% CI, 0.60 to 0.95; P = 0.014). There was no association between the ASV of body weight and cardiovascular event.

Conclusion:

Body-weight fluctuation was associated with mortality. In addition, the effect of body-weight fluctuation on incident diabetes mellitus depended on the presence of obesity at baseline.

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