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1.
BMJ. 2019 Mar 20;364:l1232. doi: 10.1136/bmj.l1232.

The BMJ Awards 2019: Diabetes Team of the Year.

Author information

1
London, UK.
PMID:
30894350
DOI:
10.1136/bmj.l1232
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2.
BMJ. 2018 Nov 14;363:k4365. doi: 10.1136/bmj.k4365.

Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study.

Author information

1
Clinical Epidemiology Division, Department of Medicine, Solna, Eugeniahemmet, T2, Karolinska University Hospital, 17176 Stockholm, Sweden peter.ueda@ki.se.
2
Clinical Epidemiology Division, Department of Medicine, Solna, Eugeniahemmet, T2, Karolinska University Hospital, 17176 Stockholm, Sweden.
3
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
4
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
5
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
6
Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
7
The Swedish National Diabetes Register, Västra Götalandsregionen, Gothenburg, Sweden.
8
KG Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway.
9
HUNT Research Center, Faculty of Medicine, Norwegian University of Science and Technology, Levanger, Norway.

Abstract

OBJECTIVE:

To assess the association between the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and seven serious adverse events of current concern.

DESIGN:

Register based cohort study.

SETTING:

Sweden and Denmark from July 2013 to December 2016.

PARTICIPANTS:

A propensity score matched cohort of 17 213 new users of SGLT2 inhibitors (dapagliflozin, 61%; empagliflozin, 38%; canagliflozin, 1%) and 17 213 new users of the active comparator, glucagon-like peptide 1 (GLP1) receptor agonists.

MAIN OUTCOME MEASURES:

The primary outcomes were lower limb amputation, bone fracture, diabetic ketoacidosis, acute kidney injury, serious urinary tract infection, venous thromboembolism, and acute pancreatitis, as identified from hospital records. Hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazards models.

RESULTS:

Use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation (incidence rate 2.7 v 1.1 events per 1000 person years, hazard ratio 2.32, 95% confidence interval 1.37 to 3.91) and diabetic ketoacidosis (1.3 v 0.6, 2.14, 1.01 to 4.52) but not with bone fracture (15.4 v 13.9, 1.11, 0.93 to 1.33), acute kidney injury (2.3 v 3.2, 0.69, 0.45 to 1.05), serious urinary tract infection (5.4 v 6.0, 0.89, 0.67 to 1.19), venous thromboembolism (4.2 v 4.1, 0.99, 0.71 to 1.38) or acute pancreatitis (1.3 v 1.2, 1.16, 0.64 to 2.12).

CONCLUSIONS:

In this analysis of nationwide registers from two countries, use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation and diabetic ketoacidosis, but not with other serious adverse events of current concern.

PMID:
30429124
PMCID:
PMC6233755
DOI:
10.1136/bmj.k4365
[Indexed for MEDLINE]
Free PMC Article
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Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and have the following declarations: CJ reports personal fees from Pfizer and Bayer outside the submitted work; BE reports personal fees from Amgen, AstraZeneca, Boerhringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Mundipharma, Navamedic, Novo Nordisk, and RLS Global outside the submitted work, and grants from Sanofi outside the submitted work; and SG reports personal fees and research grants from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Novo Nordisk, and Sanofi outside of the submitted work. The other authors did not have any potential conflicts to report.

3.
Diabet Med. 2019 Mar 21. doi: 10.1111/dme.13952. [Epub ahead of print]

Relationship between corneal confocal microscopy and markers of peripheral nerve structure and function in Type 2 diabetes.

Author information

1
Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.
2
School of Optometry and Vision Science, University of New South Wales, Sydney, NSW, Australia.
3
School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
4
Department of Endocrinology, Prince of Wales Hospital, Sydney, NSW, Australia.

Abstract

AIMS:

To investigate changes in corneal nerve morphology in Type 2 diabetes and to establish relationships between in vivo corneal confocal microscopy and markers of peripheral nerve structure and function.

PARTICIPANTS AND METHODS:

We recruited 57 participants with Type 2 diabetes and 26 healthy controls of similar age and sex distribution. We also recruited a disease control group of 54 participants with Type 1 diabetes. All participants were assessed for distal symmetrical polyneuropathy using the Total Neuropathy Score. In vivo corneal confocal microscopy was used to assess corneal nerve fibre length, corneal nerve fibre density, corneal nerve branch density and inferior whorl length. Peripheral nerve structure was assessed using median nerve ultrasonography. Large fibre function was assessed according to median nerve axonal excitability. Small fibre function was assessed using SudoscanTM and the Survey of Autonomic Symptoms.

RESULTS:

Corneal nerve fibre length, fibre density and branch density and inferior whorl length were significantly lower in individuals with Type 2 diabetes compared to controls (P<0.001 for all). In the Type 2 diabetes cohort, correlations were observed between neuropathy severity and corneal nerve fibre density (P=0.004), corneal nerve branch density (P=0.003), corneal nerve fibre length (P=0.002) and inferior whorl length (P=0.01). Significant correlations were observed between corneal confocal outcomes and axonal excitability measurements. No association was found between corneal confocal microscopy and median nerve cross-sectional area, Sudoscan measurements or the Survey of Autonomic Symptoms.

CONCLUSIONS:

This study demonstrated significant changes in corneal nerves in individuals with Type 2 diabetes. Reductions in corneal nerve measures correlated with increasing neuropathy severity. Associations were found between corneal confocal microscopy and markers of voltage-gated potassium channel function.

PMID:
30897245
DOI:
10.1111/dme.13952
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4.
Diabet Med. 2019 Mar 21. doi: 10.1111/dme.13950. [Epub ahead of print]

Foot deformity in a man with Type 2 diabetes.

Author information

1
Abertawe Bro Morgannwg University Health Board, Singleton Hospital, Swansea, UK.
PMID:
30897242
DOI:
10.1111/dme.13950
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5.
Diabet Med. 2019 Mar 21. doi: 10.1111/dme.13951. [Epub ahead of print]

Prospective association between late evening food consumption and risk of prediabetes and diabetes: the Whitehall II cohort study.

Author information

1
Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark.
2
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
3
Department of Public Health, Aarhus University, Aarhus, Denmark.
4
Danish Diabetes Academy, Odense, Denmark.
5
1st Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
6
Department of Epidemiology & Public Health, University College London, London, UK.
7
National Institute of Public Health, Southern Denmark University, Copenhagen, Denmark.
8
Salk Institute for Biological Studies, La Jolla, CA, USA.

Abstract

AIMS:

We examined whether late evening food consumption was prospectively associated with the risk of developing prediabetes or diabetes in a large observational study of individuals with normoglycaemia.

METHODS:

Participants were 2642 men and women with normoglycaemia (HbA1c < 39 mmol/mol; < 5.7%) from the Whitehall II study. Time of last eating episode (TLEE) before the examination day was assessed at baseline. We studied the associations of TLEE with 5-year changes in HbA1c and risk of developing prediabetes or diabetes (HbA1c ≥ 39 mmol/mol; ≥ 5.7%). Potential heterogeneity in the association between TLEE and prediabetes or diabetes was examined using recursive partitioning modelling for time-to-event outcomes.

RESULTS:

There was a tendency of an overall association of TLEE with change in HbA1c but with little effect size [β per 1-h increase in TLEE = 0.2 mmol/mol, 95% CI -0.0 to 0.3 (0.01%, -0.00 to 0.03); P = 0.055] and no association with the risk of developing prediabetes/diabetes (risk ratio per 1-h increase in TLEE = 1.03, 95% CI 0.94 to 1.13; P = 0.511). According to the recursive partitioning modelling, women with HbA1c ≤ 36 mmol/mol and TLEE after 21:00 had a 1.51 times (95% CI 1.16 to 1.93) higher 5-year risk of developing prediabetes or diabetes than those having their TLEE between 16:00 and 21:00 (35.4% vs. 23.5%; P = 0.003).

CONCLUSIONS:

There was no overall association of TLEE with the development of prediabetes or diabetes in the Whitehall II population. However, explorative analyses suggested that eating late in the evening was associated with increased risk of developing prediabetes/diabetes among women with good glycaemic control. Whether restricting late evening food consumption is effective and feasible for the prevention of Type 2 diabetes needs testing in randomized controlled trials.

PMID:
30897241
DOI:
10.1111/dme.13951
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6.
Diabet Med. 2019 Mar 19. doi: 10.1111/dme.13949. [Epub ahead of print]

Prevalence of diabetes in Poland: a combined analysis of national databases.

Author information

1
Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow.
2
National Institute of Public Health - National Institute of Hygiene, Warsaw.
3
Department of Internal Diseases, Diabetology and Cardiometabolic Diseases, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice.
4
National Health Fund, Warsaw.
5
PEX PharmaSequence LLC.
6
Department of Preventive Medicine and Medical Education, Medical University of Gdansk, Gdansk.
7
Department of Children's Diabetology, Medical University of Silesia.
8
Medical University in Warsaw, Warsaw.
9
Jaspers, Warsaw.
10
Department of Cardiology, Clinical Center of Cardiology, Medical University of Gdansk, Gdansk.
11
Chair of Pediatrics, Diabetology and Endocrinology, Medical University of Gdansk, Gdansk, Poland.
12
Data Mining Group, Silesian University of Technology, Gliwice.

Abstract

AIMS:

To assess the number of people with diabetes in Poland using combined national sources and to evaluate the usefulness of data from an insurance system for epidemiological purposes.

METHODS:

The data were collected from four sources: 1) 2013 all-billing records of the national insurance system comprising people of all age groups undergoing procedures or receiving services in primary healthcare, specialist practices and hospitals and also those receiving drugs; 2) an epidemiological study, NATPOL, that involved the assessment of people with undiagnosed diabetes; 3) the RECEPTOmetr Sequence study on prescriptions; and 4) regional child diabetes registries.

RESULTS:

In 2013, 1.76 million people (0.98 million women and 0.79 million men) had medical consultations (coded E10-E14) and 2.13 million people (1.19 million women and 0.94 million men) purchased drugs or strip tests for diabetes. A total of 0.04 million people who used medical services did not buy drugs. In total, the number of people with diabetes in the insurance system was 2.16 million (1.21 million women and 0.95 million men), which corresponds to 6.1% (95% CI 6.11-6.14) of women and 5.1% (95% CI 5.12-5.14) of men. Including undiagnosed cases, the total number of people with diabetes in Poland was 2.68 million in 2013.

CONCLUSION:

The estimated prevalence of diabetes (diagnosed and undiagnosed cases) in Poland is 6.97%. Data from the national insurance system with full coverage of the population can be treated as a reliable source of information on diseases with well-defined diagnosis and treatment methods, combined with an assessment of the number of undiagnosed individuals. This article is protected by copyright. All rights reserved.

PMID:
30889281
DOI:
10.1111/dme.13949
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7.
Diabetes. 2019 Apr;68(4):679-680. doi: 10.2337/db19-ti04.

In This Issue of Diabetes.

[No authors listed]
PMID:
30894392
DOI:
10.2337/db19-ti04
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8.
Diabetes. 2019 Mar 18. pii: db180933. doi: 10.2337/db18-0933. [Epub ahead of print]

Ameliorating Methylglyoxal-Induced Progenitor Cell Dysfunction for Tissue Repair in Diabetes.

Author information

1
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences.
2
Center for Molecular Medicine and Genetics.
3
Department of Immunology and Microbiology.
4
Division of Endocrinology, School of Medicine.
5
Integrated Biosciences.
6
Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA.
7
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences; jiemei.wang@wayne.edu.
8
Cardiovascular Research Institute; Wayne State University, Detroit, MI.

Abstract

Patient-derived progenitor cell (PC) dysfunction is severely impaired in diabetes, but the molecular triggers that contribute to mechanisms of PC dysfunction are not fully understood. Methylglyoxal (MGO) is one of the highly reactive dicarbonyl species formed during hyperglycemia. We hypothesize that the MGO scavenger glyoxalase 1 (GLO1) reverses bone marrow-derived progenitor cell (BMPCs) dysfunction through augmenting the activity of an important endoplasmic reticulum (ER) stress sensor, inositol-requiring enzyme 1α (IRE1α), resulting in improved diabetic wound healing. BMPCs were isolated from adult male db/db type-2 diabetic mice and their healthy corresponding control db/+ mice. MGO at the concentration of 10µM induced immediate and severe BMPC dysfunction, including impaired network formation, migration, proliferation, and increased apoptosis, which were rescued by adenovirus-mediated GLO1 overexpression. IRE1α expression and activation in BMPCs were significantly attenuated by MGO exposure but rescued by GLO1 overexpression. MGO can diminish IRE1α RNase activity by directly binding to IRE1α in vitro In a diabetic mouse cutaneous wound model in vivo, cell therapies using diabetic cells with GLO1 overexpression remarkably accelerated wound closure by enhancing angiogenesis, compared with diabetic control cell therapy. Augmenting tissue GLO1 expression by adenovirus-mediated gene transfer or with the small-molecule inducer trans-resveratrol and hesperetin formulation also improved wound closure and angiogenesis in diabetic mice. In conclusion, our data suggest that GLO1 rescues BMPC dysfunction and facilitates wound healing in diabetic animals, at least partly through preventing MGO-induced impairment of IRE1α expression and activity. Our results provide important knowledge for the development of novel therapeutic approaches targeting MGO to improve PC-mediated angiogenesis and tissue repair in diabetes.

PMID:
30885990
DOI:
10.2337/db18-0933
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9.
Diabetes Care. 2019 Apr;42(4):e69. doi: 10.2337/dci18-0065.

Response to Comment on Lacy et al. Long-term Glycemic Control and Dementia Risk in Type 1 Diabetes. Diabetes Care 2018;41:2339-2345.

Author information

1
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA mary.lacy2@ucsf.edu.
2
Division of Research, Kaiser Permanente, Oakland, CA.
3
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA.
4
Division of Epidemiology, Public Health Sciences, University of California Davis School of Medicine, Davis, CA.
PMID:
30894391
PMCID:
PMC6429631
[Available on 2020-04-01]
DOI:
10.2337/dci18-0065
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10.
Diabetes Care. 2019 Apr;42(4):e68. doi: 10.2337/dc18-2467.

Comment on Lacy et al. Long-term Glycemic Control and Dementia Risk in Type 1 Diabetes. Diabetes Care 2018;41:2339-2345.

Author information

1
Endocrinology Division, Department of Internal Medicine, University Hospital "Dr. José E. González," Universidad Autónoma de Nuevo León, Monterrey, Mexico.
2
Endocrinology Division, Department of Internal Medicine, University Hospital "Dr. José E. González," Universidad Autónoma de Nuevo León, Monterrey, Mexico drfernandolavalle@hotmail.com.
PMID:
30894390
DOI:
10.2337/dc18-2467
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11.
Diabetes Care. 2019 Apr;42(4):e66-e67. doi: 10.2337/dci18-0066.

Response to Comment on Umpierrez and Klonoff. Diabetes Technology Update: Use of Insulin Pumps and Continuous Glucose Monitoring in the Hospital. Diabetes Care 2018;41:1579-1589.

Author information

1
Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA geumpie@emory.edu.
2
Diabetes Research Institute, Mills-Peninsula Medical Center, San Mateo, CA.

Publication type

Publication type

12.
Diabetes Care. 2019 Apr;42(4):e64-e65. doi: 10.2337/dc18-2455.

Comment on Umpierrez and Klonoff. Diabetes Technology Update: Use of Insulin Pumps and Continuous Glucose Monitoring in the Hospital. Diabetes Care 2018;41:1579-1589.

Author information

1
Health Psychology, Johannes Gutenberg University, Mainz, Germany jegramme@uni-mainz.de.
2
Diabetes Technology Working Group, German Diabetes Association, Ulm, Germany.
3
Science-Consulting in Diabetes GmbH, Neuss, Germany.
4
Health Psychology, Johannes Gutenberg University, Mainz, Germany.
PMID:
30894388
DOI:
10.2337/dc18-2455
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13.
Diabetes Care. 2019 Apr;42(4):e63. doi: 10.2337/dci18-0057.

Response to Comment on Cheng et al. Trends and Disparities in Cardiovascular Mortality Among U.S. Adults With and Without Self-Reported Diabetes, 1988-2015. Diabetes Care 2018;41:2306-2315.

Author information

1
Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA ycheng@cdc.gov.
2
Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA.

Publication type

Publication type

14.
Diabetes Care. 2019 Apr;42(4):e62. doi: 10.2337/dc18-2175.

Comment on Cheng et al. Trends and Disparities in Cardiovascular Mortality Among U.S. Adults With and Without Self-Reported Diabetes, 1988-2015. Diabetes Care 2018;41:2306-2315.

Author information

1
Diabetes Registry, Azienda Unità Sanitaria Locale - IRCCS Reggio Emilia, Reggio Emilia, Italy.
2
Epidemiology Unit, Azienda Unità Sanitaria Locale - IRCCS Reggio Emilia, Reggio Emilia, Italy massimo.vicentini@ausl.re.it.
3
Osservatorio Epidemiologico, ATS Val Padana, Mantua, Italy.
4
Epidemiology Unit, Azienda Unità Sanitaria Locale - IRCCS Reggio Emilia, Reggio Emilia, Italy.
5
Specialization School of Hygiene and Preventive Medicine, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
6
Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy.
PMID:
30894386
DOI:
10.2337/dc18-2175
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16.
Diabetes Care. 2019 Apr;42(4):497-498. doi: 10.2337/dc19-ti04.

In This Issue of Diabetes Care.

[No authors listed]
PMID:
30894380
DOI:
10.2337/dc19-ti04
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17.
Diabetes Care. 2019 Mar 20. pii: dc181613. doi: 10.2337/dc18-1613. [Epub ahead of print]

Mediation of the Effect of Glycemia on the Risk of CVD Outcomes in Type 1 Diabetes: The DCCT/EDIC Study.

Author information

1
Biostatistics Center, The George Washington University, Rockville, MD ibebu@bsc.gwu.edu.
2
Biostatistics Center, The George Washington University, Rockville, MD.
3
University of Pittsburgh, Pittsburgh, PA.
4
University of California, San Diego, San Diego, CA.

Abstract

OBJECTIVE:

The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study has demonstrated the major role of hyperglycemia as a risk factor for clinical cardiovascular outcomes in type 1 diabetes (T1D). We assessed whether and to what extent the effect of glycemia is mediated by other established cardiovascular disease (CVD) risk factors.

RESEARCH DESIGN AND METHODS:

In the DCCT, 1,441 participants were randomized to receive either intensive or conventional diabetes therapy. The EDIC observational follow-up study enrolled 96% of the surviving DCCT cohort with 94% of the survivors still actively participating after more than 27 years of follow-up. Mediation of the effect of glycemia, as captured by HbA1c, on the subsequent CVD risk was quantified using the relative change in the CVD risk associated with HbA1c between models without and with the potential mediator.

RESULTS:

Adjusted for age, only a few factors (e.g., pulse, triglycerides, albumin excretion rate) explained more than 10% of the effect of glycemia on CVD risk when considered individually. In multivariable models, these traditional risk factors together mediated up to ∼50% of the effect of glycemia on the risk of CVD. However, the association between HbA1c and the risk of CVD remained highly significant even after adjustment for these risk factors.

CONCLUSIONS:

While HbA1c is associated with many traditional CVD risk factors, its association with these factors alone cannot explain its effects on risk of CVD. Consequently, aggressive management of traditional nonglycemic CVD risk factors, coupled with aggressive glycemic management, is indicated for individuals with type 1 diabetes.

PMID:
30894365
DOI:
10.2337/dc18-1613
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18.
Diabetes Care. 2019 Mar 18. pii: dc181569. doi: 10.2337/dc18-1569. [Epub ahead of print]

The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity: A Randomized, Double-Blind, Placebo Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients.

Author information

1
Turku PET Centre, University of Turku, Turku, Finland.
2
Antaros Medical AB, Mölndal, Sweden.
3
Section of Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
4
Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
5
Central Finland Central Hospital, Jyväskylä, Finland, and Terveystalo, Jyväskylä, Finland.
6
Institute of Clinical Physiology, National Research Council (IFC-CNR), Pisa, Italy.
7
AstraZeneca Gothenburg, Mölndal, Sweden.
8
Turku PET Centre, University of Turku, Turku, Finland pirjo.nuutila@utu.fi.
9
Department of Endocrinology, Turku University hospital, Turku, Finland.

Abstract

OBJECTIVE:

The aim of this study was to investigate tissue-specific effects of dapagliflozin on insulin sensitivity and liver and body fat in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS:

This randomized, double-blind, parallel group, placebo-controlled study recruited 32 patients with type 2 diabetes. Enrolled patients were to have HbA1c 6.5-10.5% (48-91 mmol/mol) and ≥3 months of stable treatment with metformin, dipeptidyl peptidase 4 inhibitor, or their combination. Patients were randomized 1:1 to receive 10 mg dapagliflozin or placebo daily for 8 weeks. Before and after the intervention, tissue insulin sensitivity was measured using [18F]-fluorodeoxyglucose and positron emission tomography (PET) during hyperinsulinemic-euglycemic clamp. Liver proton density fat fraction (PDFF) and adipose tissue volumes were assessed using MRI, and blood biomarkers were analyzed.

RESULTS:

After 8 weeks, glycemic control was improved by dapagliflozin (placebo-corrected change in HbA1c -0.39%, P < 0.01), but whole-body glucose uptake was not increased (P = 0.90). Tissue-specific insulin-stimulated glucose uptake did not change in skeletal muscle, liver, myocardium, or white and brown adipose tissue, and endogenous glucose production remained unaffected. However, there were significant placebo-corrected decreases in liver PDFF (-3.74%, P < 0.01), liver volume (-0.10 L, P < 0.05), visceral adipose tissue volume (-0.35 L, P < 0.01), interleukin-6 (-1.87 pg/mL, P < 0.05), and N-terminal prohormone of brain natriuretic peptide (-96 ng/L, P = 0.03).

CONCLUSIONS:

In this study, 8 weeks of treatment with dapagliflozin reduced liver PDFF and the volume of visceral adipose tissue in obese patients with type 2 diabetes. Although glycemic control was improved, no effect on tissue-level insulin sensitivity was observed.

PMID:
30885955
DOI:
10.2337/dc18-1569
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19.
Diabetes Care. 2019 Mar 18. pii: dc181427. doi: 10.2337/dc18-1427. [Epub ahead of print]

Soluble Urokinase Plasminogen Activator Receptor Predicts Cardiovascular Events, Kidney Function Decline, and Mortality in Patients With Type 1 Diabetes.

Author information

1
Steno Diabetes Center Copenhagen, Gentofte, Denmark viktor.rotbain.curovic@regionh.dk.
2
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
3
Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
4
Department of Medicine, Amager Hvidovre Hospital, Glostrup, Denmark.
5
University of Copenhagen, Copenhagen, Denmark.

Abstract

OBJECTIVE:

Soluble urokinase plasminogen activator receptor (suPAR) is an important inflammatory biomarker implicated in endothelial and podocyte dysfunction. However, suPAR's predictive qualities for complications in type 1 diabetes have yet to be determined. We investigated the prognostic value of suPAR for the development of cardiovascular events, decline in renal function, and mortality in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS:

We included 667 patients with type 1 diabetes with various degrees of albuminuria in a prospective study. End points were cardiovascular events (cardiovascular death, nonfatal acute myocardial infarction, nonfatal stroke, or coronary or peripheral arterial interventions), estimated glomerular filtration rate (eGFR) decline ≥30%, progression from lower to higher albuminuric state, development of end-stage renal disease (ESRD), and mortality. Follow-up was 5.2-6.2 years. Results were adjusted for known risk factors. Hazard ratios (HRs) are presented per doubling of suPAR with 95% CI. Relative integrated discrimination (rIDI) was calculated.

RESULTS:

suPAR was available in all participants; median (interquartile range) was 3.4 ng/mL (2.7-4.5). The adjusted HR (95% CI) for cardiovascular events (n = 94), progression in albuminuria (n = 36), eGFR decline (n = 93), ESRD (n = 23), and mortality (n = 58) were 3.13 (1.96-5.45, P < 0.001), 1.27 (0.51-3.19, P = 0.61), 2.93 (1.68-5.11, P < 0.001), 2.82 (0.73-11.9, P = 0.13), and 4.13 (1.96-8.69, P < 0.001), respectively. rIDI was significant for cardiovascular events (22.6%, P < 0.001), eGFR decline (14.4%, P < 0.001), and mortality (23.9%, P < 0.001).

CONCLUSIONS:

In patients with type 1 diabetes and a broad range of albuminuria, a higher level of suPAR is a significant and independent risk factor for cardiovascular events, decline in eGFR ≥30%, and mortality. In addition, suPAR contributes significantly to discrimination for the end points.

PMID:
30885954
DOI:
10.2337/dc18-1427
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20.
Diabetes Care. 2019 Mar 18. pii: dc182542. doi: 10.2337/dc18-2542. [Epub ahead of print]

Sex Differences in Treatment With ACE Inhibitors and Angiotensin Receptor Blockers in Type 1 Diabetes Patients.

Author information

1
Pediatrics, Department of Clinical Sciences, Umeå University, Umeå, Sweden anna.mollsten@umu.se.
2
Pediatrics, Department of Clinical Sciences, Umeå University, Umeå, Sweden.
3
Department of Internal Medicine, Ryhov County Hospital, Jönköping, Sweden.
4
Department of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
PMID:
30885953
DOI:
10.2337/dc18-2542
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