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1.
BMJ. 2019 Apr 3;365:l1226. doi: 10.1136/bmj.l1226.

Continuous subcutaneous insulin infusion versus multiple daily injection regimens in children and young people at diagnosis of type 1 diabetes: pragmatic randomised controlled trial and economic evaluation.

Author information

1
Department of Endocrinology, Alder Hey Children's NHS Foundation Trust, Liverpool L12 2AP, UK jo.blair@alderhey.nhs.uk.
2
Clinical Trials Research Centre, University of Liverpool, Liverpool, UK.
3
Centre for Health Economics and Medicines Evaluation, Bangor University, Bangor, UK.
4
Department of Diabetes, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
5
Department of Research, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
6
Department of Endocrinology, Alder Hey Children's NHS Foundation Trust, Liverpool L12 2AP, UK.
7
Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, UK.

Abstract

OBJECTIVE:

To compare the efficacy, safety, and cost utility of continuous subcutaneous insulin infusion (CSII) with multiple daily injection (MDI) regimens during the first year following diagnosis of type 1 diabetes in children and young people.

DESIGN:

Pragmatic, multicentre, open label, parallel group, randomised controlled trial and economic evaluation.

SETTING:

15 paediatric National Health Service (NHS) diabetes services in England and Wales. The study opened to recruitment in May 2011 and closed in January 2017.

PARTICIPANTS:

Patients aged between 7 months and 15 years, with a new diagnosis of type 1 diabetes were eligible to participate. Patients who had a sibling with the disease, and those who took drug treatments or had additional diagnoses that could have affected glycaemic control were ineligible.

INTERVENTIONS:

Participants were randomised, stratified by age and treating centre, to start treatment with CSII or MDI within 14 days of diagnosis. Starting doses of aspart (CSII and MDI) and glargine or detemir (MDI) were calculated according to weight and age, and titrated according to blood glucose measurements and according to local clinical practice.

MAIN OUTCOME MEASURES:

Primary outcome was glycaemic control (as measured by glycated haemoglobin; HbA1c) at 12 months. Secondary outcomes were percentage of patients in each treatment arm with HbA1c within the national target range, incidence of severe hypoglycaemia and diabetic ketoacidosis, change in height and body mass index (as measured by standard deviation scores), insulin requirements (units/kg/day), partial remission rate (insulin dose adjusted HbA1c <9), paediatric quality of life inventory score, and cost utility based on the incremental cost per quality adjusted life year (QALY) gained from an NHS costing perspective.

RESULTS:

294 participants were randomised and 293 included in intention to treat analyses (CSI, n=144; MDI, n=149). At 12 months, mean HbA1c was comparable with clinically unimportant differences between CSII and MDI participants (60.9 mmol/mol v 58.5 mmol/mol, mean difference 2.4 mmol/mol (95% confidence interval -0.4 to 5.3), P=0.09). Achievement of HbA1c lower than 58 mmol/mol was low among the two groups (66/143 (46%) CSII participants v 78/142 (55%) MDI participants; relative risk 0.84 (95% confidence interval 0.67 to 1.06)). Incidence of severe hypoglycaemia and diabetic ketoacidosis were low in both groups. Fifty four non-serious and 14 serious adverse events were reported during CSII treatment, and 17 non-serious and eight serious adverse events during MDI treatment. Parents (but not children) reported superior PedsQL scores for those patients treated with CSII compared to those treated with MDI. CSII was more expensive than MDI by £1863 (€2179; $2474; 95% confidence interval £1620 to £2137) per patient, with no additional QALY gains (difference -0.006 (95% confidence interval -0.031 to 0.018)).

CONCLUSION:

During the first year following type 1 diabetes diagnosis, no clinical benefit of CSII over MDI was identified in children and young people in the UK setting, and treatment with either regimen was suboptimal in achieving HbA1c thresholds. CSII was not cost effective.

TRIAL REGISTRATION:

Current Controlled Trials ISRCTN29255275; European Clinical Trials Database 2010-023792-25.

PMID:
30944112
PMCID:
PMC6446076
DOI:
10.1136/bmj.l1226
[Indexed for MEDLINE]
Free PMC Article
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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the UK NIHR Health Technology Assessment Programme for the submitted work; JCB undertakes paid advisory work, and has received funding for research, to attend academic meetings and to support a nursing salary from Novo Nordisk, a pharmaceutical company that manufactures some of the insulins used in the SCIPI study (work for this company relates to growth hormone therapy and not diabetes); MD has received payment for advisory work, funding to attend academic meetings and to support a nursing salary from Novo Nordisk, a pharmaceutical company that manufactures some of the insulins used in the SCIPI study (work for this company relates to growth hormone therapy and not diabetes), and has received expenses from Merk Serono to attend educational meetings; JWG is chairman of the NovoNordisk UK Foundation, receives funding from NovoNordisk, Ipsen, Serono, and Pfizer to part support attendance at annual scientific meetings of the European Society for Paediatric Endocrinology, and receives speaker’s fees to talk on communication skills from Pfizer and Lilly; no other relationships or activities that could appear to have influenced the submitted work.

2.
BMJ. 2019 Feb 6;364:k5258. doi: 10.1136/bmj.k5258.

#TalkAboutComplications.

PMID:
30728129
DOI:
10.1136/bmj.k5258
[Indexed for MEDLINE]
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Conflict of interest statement

Competing interests The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: Both authors have received funding from diabetes device and drug companies to attend events. Renza Scibilia was involved in the development of the Diabetes Australia Language Position Statement. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests Provenance and peer review: Commissioned, based on an idea from the author; not externally peer reviewed.

3.
BMJ. 2019 Jan 16;364:k5222. doi: 10.1136/bmj.k5222.

Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank.

Author information

1
Epidemiology and Public Health Group, University of Exeter Medical School, RD&E Wonford, Exeter EX2 5DW, UK.
2
Genetics of Complex Traits Group, University of Exeter Medical School, Exeter, UK.
3
Biostatistics Center, CT Institute for Clinical & Translational Science, University of Connecticut Health Center, Farmington, CT, USA.
4
Center on Aging, University of Connecticut Health Center, Farmington, CT, USA.
5
National Institute on Aging, Baltimore, MD, USA.
6
Epidemiology and Public Health Group, University of Exeter Medical School, RD&E Wonford, Exeter EX2 5DW, UK D.Melzer@exeter.ac.uk.

Abstract

OBJECTIVE:

To compare prevalent and incident morbidity and mortality between those with the HFE p.C282Y genetic variant (responsible for most hereditary haemochromatosis type 1) and those with no p.C282Y mutations, in a large UK community sample of European descent.

DESIGN:

Cohort study.

SETTING:

22 centres across England, Scotland, and Wales in UK Biobank (2006-10).

PARTICIPANTS:

451 243 volunteers of European descent aged 40 to 70 years, with a mean follow-up of seven years (maximum 9.4 years) through hospital inpatient diagnoses and death certification.

MAIN OUTCOME MEASURE:

Odds ratios and Cox hazard ratios of disease rates between participants with and without the haemochromatosis mutations, adjusted for age, genotyping array type, and genetic principal components. The sexes were analysed separately as morbidity due to iron excess occurs later in women.

RESULTS:

Of 2890 participants homozygous for p.C282Y (0.6%, or 1 in 156), haemochromatosis was diagnosed in 21.7% (95% confidence interval 19.5% to 24.1%, 281/1294) of men and 9.8% (8.4% to 11.2%, 156/1596) of women by end of follow-up. p.C282Y homozygous men aged 40 to 70 had a higher prevalence of diagnosed haemochromatosis (odds ratio 411.1, 95% confidence interval 299.0 to 565.3, P<0.001), liver disease (4.30, 2.97 to 6.18, P<0.001), rheumatoid arthritis (2.23, 1.51 to 3.31, P<0.001), osteoarthritis (2.01, 1.71 to 2.36, P<0.001), and diabetes mellitus (1.53, 1.16 to 1.98, P=0.002), versus no p.C282Y mutations (n=175 539). During the seven year follow-up, 15.7% of homozygous men developed at least one incident associated condition versus 5.0% (P<0.001) with no p.C282Y mutations (women 10.1% v 3.4%, P<0.001). Haemochromatosis diagnoses were more common in p.C282Y/p.H63D heterozygotes, but excess morbidity was modest.

CONCLUSIONS:

In a large community sample, HFE p.C282Y homozygosity was associated with substantial prevalent and incident clinically diagnosed morbidity in both men and women. As p.C282Y associated iron overload is preventable and treatable if intervention starts early, these findings justify re-examination of options for expanded early case ascertainment and screening.

PMID:
30651232
PMCID:
PMC6334179
DOI:
10.1136/bmj.k5222
[Indexed for MEDLINE]
Free PMC Article
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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form (at www.icmje.org/coi_disclosure.pdf) and declare: no support from any organisation for the submitted work; 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

4.
BMJ. 2019 Jan 9;364:l54. doi: 10.1136/bmj.l54.

Helen Salisbury: When policy doesn't match evidence.

PMID:
30626583
DOI:
10.1136/bmj.l54
[Indexed for MEDLINE]
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Conflict of interest statement

Competing interests: I am a GP partner, I teach medical students at Oxford University and St Anne’s College, Oxford, and I answer readers’ medical problems for Take A Break magazine. I am also a member of the National Health Action Party and serve on its national executive committee.

6.
Diabetes. 2019 Apr 1. pii: db181362. doi: 10.2337/db18-1362. [Epub ahead of print]

T Cell-Specific PTPN2-Deficiency in NOD Mice Accelerates the Development of Type 1 Diabetes and Autoimmune Co-Morbidities.

Wiede F1,2,3, Brodnicki T4,5, Goh PK6,2,3, Leong YA2, Jones GW7,8,9, Yu D2, Baxter AG10, Jones SA7,8, Kay T4,5, Tiganis T1,2,3.

Author information

1
Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia, Tony.Tiganis@monash.edu Florian.Wiede@petermac.org.
2
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800.
3
Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.
4
St. Vincent's Institute, Fitzroy, Victoria 3065, Australia.
5
Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria 3065, Australia.
6
Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
7
Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, Wales, UK.
8
Systems Immunity University Research Institute, Cardiff University, Cardiff, Wales, UK.
9
School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
10
Comparative Genomics Centre, James Cook University, Townsville, QLD, Australia.

Abstract

Genome-wide association studies have identified PTPN2 as an important non-major histocompatibility complex gene for autoimmunity. Single nucleotide polymorphisms that reduce PTPN2 expression have been linked with the development of varied autoimmune disorders, including type 1 diabetes. The tyrosine-phosphatase PTPN2 attenuates T cell receptor and cytokine signalling in T cells to maintain peripheral tolerance, but the extent to which PTPN2-deficiency in T cells might influence type 1 diabetes onset remains unclear. Non-Obese Diabetic (NOD) mice develop spontaneous autoimmune type 1 diabetes, similar to that seen in humans. T cell PTPN2-deficiency in NOD mice markedly accelerated the onset and increased the incidence of type 1 diabetes, as well as that of other disorders, including colitis and Sjogren's syndrome. Although PTPN2-deficiency in CD8+ T cells alone was able to drive the destruction of pancreatic β cells and onset of diabetes, T cell-specific PTPN2-deficiency was also accompanied by increased CD4+ T-helper type 1 differentiation and T follicular helper cell polarisation and an increased abundance of B cells in pancreatic islets as seen in human type 1 diabetes. These findings causally link PTPN2-deficiency in T cells with the development of type 1 diabetes and associated autoimmune co-morbidities.

PMID:
30936146
DOI:
10.2337/db18-1362
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7.
Diabetes. 2019 Apr 1. pii: db190080. doi: 10.2337/db19-0080. [Epub ahead of print]

Diabetes-Associated Myelopoiesis Drives Stem Cell Mobilopathy Through an OSM-p66Shc Signaling Pathway.

Author information

1
Veneto Institute of Molecular Medicine (VIMM), 35129 Padova, Italy.
2
Department of Medicine - DIMED, University of Padova, 35128 Padova, Italy.
3
Department of Surgery, Oncology and Gastroenterology, University of Padova, 35129 Padova, Italy.
4
Istituto Oncologico Veneto IOV-IRCCS, 35128 Padova, Italy.
5
European Institute of Oncology (IEO), 20139 Milan, Italy.
6
Department of Biomedical Sciences, 35131 Padova, Italy.
7
Veneto Institute of Molecular Medicine (VIMM), 35129 Padova, Italy gianpaolofadini@hotmail.com.

Abstract

Diabetes impairs the mobilization of hematopoietic stem/progenitor cells (HSPCs) from the bone marrow (BM), which can worsen the outcomes of HSPC transplantation and of diabetic complications. In this study, we examined the oncostatin M (OSM) - p66Shc pathway as a mechanistic link between HSPC mobilopathy and excessive myelopoiesis. We found that streptozotocin (STZ)-induced diabetes in mice skewed hematopoiesis towards the myeloid lineage, via hematopoietic-intrinsic p66Shc. The overexpression of Osm resulting from myelopoiesis prevented HSPC mobilization after G-CSF. The intimate link between myelopoiesis and impaired HSPC mobilization after G-CSF was confirmed in human diabetes. Using cross-transplantation experiments, we found that deletion of p66Shc in the hematopoietic or non-hematopoietic system partially rescued defective HSPC mobilization in diabetes. Additionally, p66Shc mediated the diabetes-induced BM microvasculature remodeling. Ubiquitous or hematopoietic restricted Osm deletion phenocopied p66Shc deletion in preventing diabetes-associated myelopoiesis and mobilopathy. Mechanistically, we discovered that OSM couples myelopoiesis to mobilopathy by inducing Cxcl12 in BM stromal cells via non-mitochondrial p66Shc. Altogether, these data indicate that cell-autonomous activation of the OSM-p66Shc pathway leads to diabetes-associated myelopoiesis, whereas its transcellular hemato-stromal activation links myelopoiesis to mobilopathy. Targeting the OSM-p66Shc pathway is a novel strategy to disconnect mobilopathy from myelopoiesis and restore normal HSPC mobilization.

PMID:
30936144
DOI:
10.2337/db19-0080
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8.
Diabetes Care. 2019 Apr 2. pii: dc181838. doi: 10.2337/dc18-1838. [Epub ahead of print]

Heart Rate, Autonomic Function, and Future Changes in Glucose Metabolism in Individuals Without Diabetes: The Whitehall II Cohort Study.

Author information

1
Steno Diabetes Center Copenhagen, Gentofte, Denmark christian.stevns.hansen@regionh.dk.
2
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
3
National Institute of Public Health, Southern Denmark University, Odense, Denmark.
4
National Heart and Lung Institute, Imperial College, London, U.K.
5
Department of Public Health, Aarhus University, Aarhus, Denmark.
6
Danish Diabetes Academy, Odense, Denmark.
7
Department of Epidemiology and Public Health, University College London, London, U.K.
8
Faculty of Medicine, Semmelweis University, Budapest, Hungary.

Abstract

OBJECTIVE:

Autonomic nervous system dysfunction is associated with impaired glucose metabolism, but the temporality of this association remains unclear in individuals without diabetes. We investigated the association of autonomic function with 5-year changes in glucose metabolism in individuals without diabetes.

RESEARCH DESIGN AND METHODS:

Analyses were based on 9,000 person-examinations for 3,631 participants without diabetes in the Whitehall II cohort. Measures of autonomic function included 5-min resting heart rate and six heart rate variability (HRV) indices. Associations between baseline autonomic function measures and 5-year changes in fasting and 2-h plasma glucose, serum insulin concentrations, insulin sensitivity (insulin sensitivity index [ISI0-120] and HOMA of insulin sensitivity), and β-cell function (HOMA of β-cell function) were estimated in models adjusting for age, sex, ethnicity, metabolic factors, and medication.

RESULTS:

A 10-bpm higher resting heart rate was associated with 5-year changes in fasting and 2-h insulin and ISI0-120 of 3.3% change (95% CI 1.8; 4.8)%, P < 0.001; 3.3% change (1.3; 5.3), P = 0.001; and -1.4 (-2.4; -0.3), P = 0.009, respectively. In models adjusted for age, sex, and ethnicity, higher baseline values of several HRV indices were associated with a 5-year decrease in fasting and 2-h insulin and ISI0-120. However, significance was lost by full adjustment. A majority of HRV indices exhibited a trend toward higher values being associated with lower insulin levels and higher insulin sensitivity.

CONCLUSIONS:

Higher resting heart rate in individuals without diabetes is associated with future unfavorable changes in insulin levels and insulin sensitivity. Associations may be mediated via autonomic function; however, results are inconclusive. Resting heart rate may be a risk marker for future pathophysiological changes in glucose metabolism.

PMID:
30940642
DOI:
10.2337/dc18-1838
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9.
Diabetes Care. 2019 Apr 2. pii: dc181226. doi: 10.2337/dc18-1226. [Epub ahead of print]

The Economic Burden of Elevated Blood Glucose Levels in 2017: Diagnosed and Undiagnosed Diabetes, Gestational Diabetes, and Prediabetes.

Author information

1
IHS Markit, Washington, DC tim.dall@ihsmarkit.com.
2
Lewin Group, Falls Church, VA.
3
Novo Nordisk, Plainsboro, NJ.
4
IHS Markit, Washington, DC.

Abstract

OBJECTIVE:

This study was conducted to update national estimates of the economic burden of undiagnosed diabetes, prediabetes, and gestational diabetes in the United States for year 2017 and provide state-level estimates. Combined with published estimates for diagnosed diabetes, these updated statistics provide a detailed picture of the economic costs associated with elevated blood glucose levels.

RESEARCH DESIGN AND METHODS:

This study estimated medical expenditures exceeding levels occurring in the absence of diabetes or prediabetes and the indirect economic burden associated with reduced labor force participation and productivity. Data sources analyzed included Optum medical claims for ∼5.8 million commercially insured patients continuously enrolled from 2013 to 2015, Medicare Standard Analytical Files containing medical claims for ∼2.8 million Medicare patients in 2014, and the 2014 Nationwide Inpatient Sample containing ∼7.1 million discharge records. Other data sources were the U.S. Census Bureau, Centers for Disease Control and Prevention, and Centers for Medicare and Medicaid Services.

RESULTS:

The economic burden associated with diagnosed diabetes (all ages), undiagnosed diabetes and prediabetes (adults), and gestational diabetes (mothers and newborns) reached nearly $404 billion in 2017, consisting of $327.2 billion for diagnosed diabetes, $31.7 billion for undiagnosed diabetes, $43.4 billion for prediabetes, and nearly $1.6 billion for gestational diabetes. Combined, this amounted to an economic burden of $1,240 for each American in 2017. Annual burden per case averaged $13,240 for diagnosed diabetes, $5,800 for gestational diabetes, $4,250 for undiagnosed diabetes, and $500 for prediabetes.

CONCLUSIONS:

Updated statistics underscore the importance of reducing the burden of prediabetes and diabetes through better detection, prevention, and treatment.

PMID:
30940641
DOI:
10.2337/dc18-1226
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12.
Diabetes Care. 2019 Apr 1. pii: dc182158. doi: 10.2337/dc18-2158. [Epub ahead of print]

Association Between Topical Corticosteroid Use and Type 2 Diabetes in Two European Population-Based Adult Cohorts.

Author information

1
Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark yuki.maria.fukuda.andersen.01@regionh.dk.
2
Copenhagen Research Group for Inflammatory Skin (CORGIS), Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
3
Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
4
Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
5
Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, U.K.
6
NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, U.K.
7
Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, U.K.
8
Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
9
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
10
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

OBJECTIVE:

Topical corticosteroids (CSs) are commonly used to treat inflammatory skin conditions including eczema and psoriasis. Although topical CS package inserts describe hyperglycemia and glycosuria as adverse drug reactions, it is unclear whether topical CS use in real life is also associated with an increased risk of type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS:

Two matched case-control studies and one cohort study were conducted using routinely collected health care data from Denmark and the U.K. A total of 115,218 and 54,944 adults were identified as case subjects with new-onset T2D in the Danish and U.K. case-control study, respectively. For the Danish cohort study, 2,689,473 adults were included. The main exposure was topical CSs, and the outcome was incident T2D.

RESULTS:

Topical CS was significantly associated with T2D in the Danish (adjusted odds ratio [OR] 1.35 [95% CI 1.33-1.38]) and U.K. (adjusted OR 1.23 [95% CI 1.19-1.27]) case-control studies. Individuals who were exposed to topical CSs had significantly increased risk of incident T2D (adjusted hazard ratio 1.27 [95% CI 1.26-1.29]). We observed significant dose-response relationships between T2D and increasing potency of topical CSs in the two Danish studies. The results were consistent across all sensitivity analyses.

CONCLUSIONS:

We found a positive association between topical CS prescribing and incident T2D in Danish and U.K. adult populations. Clinicians should be cognizant of possible diabetogenic effects of potent topical CSs.

PMID:
30936111
DOI:
10.2337/dc18-2158
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13.
J Clin Endocrinol Metab. 2019 Apr 4. pii: jc.2018-02502. doi: 10.1210/jc.2018-02502. [Epub ahead of print]

Effects of Diabetes on Motor Recovery after Cerebral Infarct: A Diffusion Tensor Imaging Study.

Author information

1
Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Yeungnam University.
2
Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University.

Abstract

PURPOSE:

Little is known about the effects of diabetes on motor recovery after cerebral infarct. To address this, we recruited patients with corona radiata infarct and controlled for the integrity of the corticospinal tract (CST) determined using diffusion tensor tractography (DTT).

METHODS:

One hundred patients were recruited, and DTT was performed within 7-30 days of infarct onset. Based on the DTT findings (DTT+: CST was preserved around the infarct, DTT-: CST was interrupted by the infarct) and the presence (DM+) or absence (DM-) of diabetes, patients were divided into, DTT+/DM- (36 patients), DTT+/DM+ (19 patients), DTT-/DM- (32 patients), and DTT-/DM+ (13 patients) groups. Six months after cerebral infarct, motor function on the affected side was evaluated for each patient using the upper Motricity Index (MI), lower MI, modified Brunnstrom classification (MBC), and the functional ambulation category (FAC).

RESULTS:

In the patients with a DTT+ finding, no motor function scores were significantly different between the DTT+/DM- and DTT+/DM+ groups at six-month evaluation. However, in patients with DTT- finding, all motor function scores at the six-month evaluation were significantly higher in the DTT-/DM- group than in the DTT-/DM+ group.

CONCLUSION:

When the CST is interrupted by a corona radiata infarct, recovery of motor function in patients with diabetes is more impaired than those without diabetes.

14.
J Clin Endocrinol Metab. 2019 Apr 2. pii: jc.2019-00129. doi: 10.1210/jc.2019-00129. [Epub ahead of print]

Metformin Improves Peripheral Insulin Sensitivity in Youth with Type 1 Diabetes.

Author information

1
Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO.
2
Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO.
3
Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, CO.
4
Yale School of Medicine University.
5
Nemours Children's Specialty Care, Jacksonville, FL.
6
Indiana University School of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology & Diabetology.
7
Jaeb Center for Health Research, Tampa, FL.
8
University of Minnesota.
9
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO.
10
Department of Biostatistics and Informatics, Colorado School of Public Health, University of Anschutz Medical Campus, Aurora, CO.
11
University of Iowa, Stead Family Department of Pediatrics, Endocrinology and Diabetes,.Children's Hospital of Pittsburgh at University of Pittsburgh Medical Center.
12
Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO.

Abstract

CONTEXT:

Type 1 diabetes in adolescence is characterized by insulin deficiency and resistance (IR), both thought to increase cardiovascular disease risk. We previously demonstrated adolescents with type 1 diabetes have adipose, hepatic and muscle IR, and that metformin lowers daily insulin dose, suggesting improved IR. However, whether metformin improves IR in muscle, hepatic or adipose tissues in type 1 diabetes was unknown.

OBJECTIVE:

Measure peripheral, hepatic and adipose insulin sensitivity before and after metformin or placebo therapy in obese youth with type 1 diabetes.

DESIGN:

Double-blind placebo controlled clinical trial.

SETTING:

Multi-Center at 8 sites of the type 1 diabetes Exchange Clinic Network.

PATIENTS OR OTHER PARTICIPANTS:

A subset of 12-19 year-olds with type 1 diabetes (inclusion criteria: BMI ≥85th percentile, HbA1c 7.5-9.9%, insulin dosing ≥0.8 units/kg/day) from a larger trial (NCT02045290) were enrolled.

INTERVENTION:

Participants were randomized to 3 months of metformin (N=19) or placebo (N=18), underwent three-phase hyperinsulinemic euglycemic clamp with glucose and glycerol isotope tracers to assess tissue-specific IR before and after treatment.

MAIN OUTCOME MEASURES:

Peripheral insulin sensitivity, endogenous glucose release, rate of lipolysis.

RESULTS:

Between-group differences in change in insulin sensitivity favored metformin regarding whole-body IR (∆glucose infusion rate 1.3 [0.1, 2.4] mg/kg/min, p=0.03) and peripheral IR (∆ metabolic clearance rate 0.923 [-0.002, 1.867] dL/kg/min, p=0.05). Metformin did not impact insulin suppression of endogenous glucose release (p=0.12). Adipose IR was not assessable with traditional methods in this highly-IR population.

CONCLUSIONS:

Metformin appears to improve whole-body and peripheral IR in overweight/obese youth with type 1 diabetes.

15.
J Clin Endocrinol Metab. 2019 Apr 2. pii: jc.2018-02685. doi: 10.1210/jc.2018-02685. [Epub ahead of print]

Reductions in insulin resistance are mediated primarily via weight loss in subjects with type 2 diabetes on semaglutide.

Author information

1
Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
2
Rotherham Institute for Obesity, Clifton Medical Centre, Rotherham, UK.
3
University of Colorado Denver, Denver, Colorado, USA.
4
Hospital Universitario Quirón Salud Madrid, Universidad Europea de Madrid, Madrid, Spain.
5
Novo Nordisk A/S, Søborg, Denmark.
6
University of Freiburg Medical Center, Medical Faculty, University of Freiburg, Freiburg, Germany.

Abstract

CONTEXT:

Semaglutide, a once-weekly glucagon-like peptide 1 (GLP-1) analog approved for use in patients with type 2 diabetes (T2D), demonstrated superior body weight (BW) reductions and decreased insulin resistance (IR) vs comparators across the SUSTAIN 1-3 clinical trials.

OBJECTIVE:

To investigate the relationship between IR and BW across the SUSTAIN 1-3 trials.

DESIGN:

Post hoc analysis of the SUSTAIN 1-3 trials.

SETTING:

311 sites in 30 countries. Patients or Other Participants: 2,432 subjects with T2D.

INTERVENTIONS:

Semaglutide 0.5 or 1.0 mg, placebo or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg).

MAIN OUTCOME MEASURE:

To assess the extent of the effect on IR that is mediated (indirect effect) and not mediated (direct effect) by the effect on BW.

RESULTS:

Across SUSTAIN 1-3, mean BW was significantly reduced with semaglutide 0.5 mg (3.7-4.3 kg; p<0.0001) and semaglutide 1.0 mg (4.5-6.1 kg; p<0.0001) vs comparators (1.0-1.9 kg). There were significantly greater reductions in IR with semaglutide 0.5 mg (27-36%) and semaglutide 1.0 mg (32-46%) vs comparators (17-28%). Greater reductions in BW were generally associated with greater decreases in IR. The effect on IR was primarily mediated by weight loss (70-80% and 34-94%, respectively, for semaglutide 0.5 mg and 1.0 mg vs comparator).

CONCLUSIONS:

Semaglutide consistently reduced BW and IR in subjects with T2D in SUSTAIN 1-3. In this analysis, IR improvement was positively associated with, and primarily mediated by, the effect of semaglutide on BW.

16.
J Clin Endocrinol Metab. 2019 Apr 1. pii: jc.2018-02736. doi: 10.1210/jc.2018-02736. [Epub ahead of print]

Gastric emptying in patients with well-controlled type 2 diabetes compared to non-diabetic young and older controls.

Author information

1
Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia.
2
Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China.
3
Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia.

Abstract

CONTEXT:

Gastric emptying is a major determinant of postprandial glycaemia, and is often delayed in longstanding, complicated type 2 diabetes (T2DM). There is, however, little information about gastric emptying in well-controlled T2DM.

OBJECTIVE:

To evaluate the rate of gastric emptying in community-based patients with relatively well-controlled T2DM, compared to non-diabetic young and older controls.

PARTICIPANTS AND DESIGN:

111 patients with T2DM managed by diet (n=52) or metformin monotherapy (n=59) (HbA1c 6.6±0.1%/49.0±0.9mmol/mol), 18 age- and BMI-matched older non-diabetic subjects, and 15 young healthy subjects consumed a standardised mashed potato meal (368.5kcal) containing 100uL 13C-octanoic acid. Gastric emptying (by breath test) and blood glucose were evaluated over 240min.

RESULTS:

Gastric emptying was slower in the non-diabetic older than young subjects (2.3±0.1 vs. 3.0±0.1kcal/min, P=0.0008). However, relative to the age-/BMI-matched non-diabetic subjects, gastric emptying (2.8±0.1kcal/min) was faster in T2DM patients (P=0.0005). Furthermore, gastric emptying was faster in the metformin-treated (3.0±0.1kcal/min) than diet-controlled (2.7±0.1kcal/min) T2DM patients (P=0.011), although there were no differences in age, BMI, HbA1c or the duration of known diabetes. The increments in blood glucose (at t=30 and 60 and the incremental area under the curve during t=0-120min) after the meal were related directly to the rate of gastric emptying in the T2DM subjects, regardless of treatment with or without metformin (P<0.05 each).

CONCLUSIONS:

Gastric emptying is slowed with aging, but otherwise is relatively more rapid in patients with well-controlled T2DM. This provides a strong rationale for slowing gastric emptying to improve postprandial glycaemic control in these patients.

17.
Lancet. 2019 Mar 30;393(10178):1262. doi: 10.1016/S0140-6736(19)30741-X.

Gestational diabetes in England: cause for concern.

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