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1.
Diabet Med. 2019 Jan 30. doi: 10.1111/dme.13914. [Epub ahead of print]

Effect of combining pre-exercise carbohydrate intake and repeated short sprints on the blood glucose response to moderate-intensity exercise in young individuals with Type 1 diabetes.

Author information

1
Division of Paediatrics, School of Medicine, The University of Western Australia, Perth.
2
School of Human Sciences, The University of Western Australia, Perth.
3
Telethon Kids Institute, The University of Western Australia, Perth.
4
Department of Endocrinology and Diabetes, Perth Children's Hospital, Nedlands, Western Australia, Australia.

Abstract

AIMS:

To determine whether pre-exercise ingestion of carbohydrates to maintain stable glycaemia during moderate-intensity exercise results in excessive hyperglycaemia if combined with repeated sprints in individuals with Type 1 diabetes.

METHODS:

Eight overnight-fasted people with Type 1 diabetes completed the following four 40-min exercise sessions on separate days in a randomized counterbalanced order under basal insulinaemic conditions: continuous moderate-intensity exercise at 50% V ˙ O 2 peak; intermittent high-intensity exercise (moderate-intensity exercise interspersed with 4-s sprints every 2 min and a final 10-s sprint); continuous moderate-intensity exercise with prior carbohydrate intake (~10 g per person); and intermittent high-intensity exercise with prior carbohydrate intake. Venous blood was sampled during and 2 h after exercise to measure glucose and lactate levels.

RESULTS:

The difference in marginal mean time-averaged area under the blood glucose curve between continuous moderate-intensity exercise + prior carbohydrate and intermittent high-intensity exercise + prior carbohydrate during exercise and recovery was not significant [0.2 mmol/l (95% CI -0.7, 1.1); P = 0.635], nor was the difference in peak blood glucose level after adjusting for baseline level [0.2 mmol/l (95% CI -0.7, 1.1); P = 0.695]. The difference in marginal mean time-averaged area under the blood glucose curve between continuous moderate-intensity and intermittent high-intensity exercise during exercise and recovery was also not significant [-0.2 mmol/l (95% CI -1.2, 0.8); P = 0.651].

CONCLUSIONS:

When carbohydrates are ingested prior to moderate-intensity exercise, adding repeated sprints is not significantly detrimental to glycaemic management in overnight fasted people with Type 1 diabetes under basal insulin conditions.

PMID:
30701617
DOI:
10.1111/dme.13914
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2.
Diabet Med. 2019 Jan 30. doi: 10.1111/dme.13915. [Epub ahead of print]

Heart failure among people with Type 2 diabetes mellitus: real-world data of 289 954 people from a diabetes database.

Author information

1
Herz- und Diabeteszentrum NRW, Diabeteszentrum, Bad Oeynhausen, Universität Ulm, Ulm.
2
Institut für Epidemiologie und medizinische Biometrie, ZIBMT, Universität Ulm, Ulm.
3
Deutsches Zentrum für Diabetesforschung DZD, München-Neuherberg, Geislingen.
4
ALB FILS KLINIKEN, Helfenstein Klinik Geislingen, Medizinische Klinik, Geislingen.
5
Klinikum Bayreuth GmbH, Medizinische Klinik 1, Klinik für Gastroenterologie, Bayreuth.
6
MVZ Schwerin West GmbH, Schwerin, Bad Aibling, Germany.
7
Diabeteszentrum Praxis Zimmermann, Bad Aibling, Germany.

Abstract

AIM:

Comparing people with Type 2 diabetes mellitus with and without heart failure in terms of metabolic control, therapeutic regimen and comorbidities.

METHODS:

The Prospective Diabetes Registry (DPV) is a longitudinal documentation system for demographics, medical care and outcome in people with diabetes mellitus. It consists of follow-up data from people with diabetes mellitus who have agreed to be recorded in the registry. Clinical data are submitted by general practitioners, specialists and clinics throughout Germany and Austria. Some 289 954 people with Type 2 diabetes mellitus (years 2000 to 2015) were analysed using demographic statistics and adjustment for confounders based on linear and logistic regression analysis.

RESULTS:

People with Type 2 diabetes mellitus (ICD code: E11) and heart failure (ICD code: I50) (N = 14 723) were older, more often women and presented with longer diabetes duration compared with those without heart failure. After adjustment for age, gender and diabetes duration, people with heart failure showed lower HbA1c , higher BMI and more intense insulin therapy. Analysis revealed that people with heart failure were more often treated with insulin, and more frequently received anti-hypertensives and lipid-lowering medication. They presented with lower systolic and diastolic BP. People with heart failure more frequently showed a history of comorbidities.

CONCLUSION:

Heart failure is common in diabetes mellitus, but the prevalence in the DPV is lower frequent than expected. The reason for improved metabolic control in heart failure may be intensified therapy with insulin, lipid-lowering medication and anti-hypertensives in this cohort. This article is protected by copyright. All rights reserved.

PMID:
30701607
DOI:
10.1111/dme.13915
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3.
Diabet Med. 2019 Jan 30. doi: 10.1111/dme.13913. [Epub ahead of print]

Understanding adolescent and parent acceptability and feasibility experience in a large Type 1 diabetes mellitus behavioural trial.

Author information

1
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.
2
Divisions of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
3
Divisions of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
4
Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
5
Division of Pediatric Endocrinology, Stanford University, Stanford, CA.
6
Department of Pediatrics, Barbara Davis Center for Childhood Diabetes, The Children's Hospital of Colorado, Aurora, CO.
7
James M. Anderson Center for Healthy System Excellence, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Abstract

AIMS:

Using an 18-month, multisite randomized control trial as an exemplar, the aim of this study was to identify themes related to adolescent and parental feasibility and acceptability for participation in large behavioural trials designed to improve adolescents' Type 1 diabetes self-management.

METHODS:

Thematic analysis methodology was used to develop themes describing factors related to acceptability and feasibility.

RESULTS:

Based on a sample of interviews (N = 72), factors contributing to intervention acceptability and feasibility were identified. Aspects of acceptability included: a framework for goal-setting, the coach as a non-judgemental listener, perception of an ongoing benefit to participation and the delivery mode. Aspects of feasibility included: participants' altruism to help adolescents with Type 1 diabetes; pre-enrolment preparation for intervention content and duration; and the option of remote intervention delivery via telephone or video, which minimized travel time and costs. In addition, participants described positive outcomes including improvements in behaviour, Type 1 diabetes self-management behaviours and parent-adolescent communication, and emotion-attitude changes. Participants also described potential revisions that may inform future trials.

CONCLUSIONS:

Acceptability and feasibility of behavioural interventions with adolescents with chronic illness have multifactorial dimensions. While empowering adolescent self-management, parental support is also an under-appreciated aspect to consider. Potential revisions were identified for subsequent behavioural trials.

PMID:
30701596
DOI:
10.1111/dme.13913
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4.
Diabet Med. 2019 Feb;36(2):139-141. doi: 10.1111/dme.13849.

Assessing the outcomes of pregnancies of women with diabetes.

Author information

1
Diabetic Medicine, Auckland, New Zealand.
2
Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
3
Diabetic Medicine, Southampton, UK.
4
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
PMID:
30698865
DOI:
10.1111/dme.13849
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5.
Diabet Med. 2019 Feb;36(2):151-157. doi: 10.1111/dme.13843.

Gestational diabetes and adiposity are independent risk factors for perinatal outcomes: a population based cohort study in Sweden.

Author information

1
Department of Obstetrics & Gynaecology, School of Medical Sciences, Örebro University, Örebro, Sweden.
2
School of Medical Sciences, Örebro University, Örebro, Sweden.
3
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
4
Department of Medicine, Clinical Epidemiology Unit, Karolinska Universitetssjukhuset, Solna, Sweden.
5
Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.
6
School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.

Abstract

AIMS:

To evaluate the interaction effects of gestational diabetes (GDM) with obesity on perinatal outcomes.

METHODS:

A population-based cohort study in Sweden excluding women without pre-gestational diabetes with a singleton birth between 1998 and 2012. Logistic regression was performed to evaluate the potential independent associations of GDM and BMI with adverse perinatal outcomes as well as their interactions. Main outcome measures were malformations, stillbirths, perinatal mortality, low Apgar score, fetal distress, prematurity and Erb's palsy.

RESULTS:

Some 1,294,006 women were included, with a GDM prevalence of 1% (n = 14,833). The rate of overweight/obesity was 67.7% in the GDM-group and 36.1% in the non-GDM-group. No significant interaction existed. Offspring of women with GDM had significantly increased risk of malformations, adjusted odds ratio (aOR) 1.16 (95% confidence intervals 1.06-1.26), prematurity, aOR 1.86 (1.76-1. 98), low Apgar score, aOR 1.36 (1.10-1.70), fetal distress, aOR 1.09 (1.02-1.16) and Erb's palsy aOR 2.26 (1.79-2.86). No risk for stillbirth or perinatal mortality was seen. Offspring of overweight (BMI 25-29.9 kg/m2 ), obese (BMI 30-34.9 kg/m2 ) and severely obese women (BMI ≥ 35.0 kg/m2 ) had significantly increased risks of all outcomes including stillbirth 1.51 (1.40-1.62) to 2.85 (2.52-3.22) and perinatal mortality 1.49 (1.40-1.59) to 2.83 (2.54-3.15).

CONCLUSIONS:

There is no interaction effect between GDM and BMI for the studied outcomes. Higher BMI and GDM are major independent risk factors for most serious adverse perinatal outcomes. More effective pre-pregnancy and antenatal interventions are required to prevent serious adverse pregnancy outcomes among women with either GDM or high BMI.

PMID:
30698864
DOI:
10.1111/dme.13843
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6.
Diabet Med. 2019 Feb;36(2):158-166. doi: 10.1111/dme.13861.

Higher rates of large-for-gestational-age newborns mediated by excess maternal weight gain in pregnancies with Type 1 diabetes and use of continuous subcutaneous insulin infusion vs multiple dose insulin injection.

Author information

1
Berlin Centre for Diabetes and Pregnancy, Department of Obstetrics and Gynaecology, St Joseph Hospital, Berlin, Germany.
2
Department of Obstetrics, Campus Rudolf-Virchow, Charité Medical Faculty, Humboldt University, Berlin, Germany.
3
Vivantes Neukoelln Hospital, Berlin, Germany.

Abstract

AIMS:

To compare glycaemic control, maternal and neonatal outcomes in pregnancies with Type 1 diabetes, managed either by continuous subcutaneous insulin infusion, multiple daily insulin injection or switch from multiple daily insulin injection (MDI) to continuous subcutaneous insulin infusion (CSII) in early pregnancy.

RESEARCH DESIGN AND METHODS:

Data from 339 singleton pregnancies were retrospectively reviewed. HbA1c values were measured preconception and in each trimester. In a secondary analysis, use of CSII pre-pregnancy was compared with initiation of CSII during pregnancy.

RESULTS:

MDI was used in 140 pregnancies (41.3%) and CSII was used in 199 (58.7%), including 34 pregnancies (10.0%) during which the women switched to CSII. In pregnancies during which CSII was used duration of diabetes [median (interquartile range) 16.0 (8.0-23.0) years vs 11.0 (5.5-17.5) years; P<0.001] was longer, and the Institute of Medicine recommendations for appropriate weight gain were exceeded more often (64.8% vs. 50.8%; P=0.01). CSII use and pre-pregnancy BMI were independent predictors of excess weight gain. There was no difference in glucose control, but CSII was associated with higher birth weight [median (interquartile range) 3720 (3365-4100) g vs 3360 (3365-4100) g; P<0.001] and higher large-for-gestational-age (LGA) rate (44.7% vs. 33.6%; P=0.04) than MDI. HbA1c concentration in the third trimester and excess weight gain were predictive of LGA infants [odds ratio 2.33 (95% CI 1.54-3.51); P<0.001 and 1.89 (95% CI 1.02-3.51); P=0.04]. In pregnancies where CSII therapy was initiated in the first trimester and in those with pre-pregnancy use, similar glucose control and outcome was achieved.

CONCLUSIONS:

There was no advantage of CSII with respect to glycaemic control and neonatal outcomes. The rate of LGA neonates was higher in the CSII group, possibly mediated by excess maternal weight gain, which was more frequent than in women treated with MDI.

PMID:
30698863
DOI:
10.1111/dme.13861
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7.
Diabet Med. 2019 Jan 30. doi: 10.1111/dme.13912. [Epub ahead of print]

Association between HbA1c and the development of cystic fibrosis-related diabetes.

Author information

1
All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough, Cardiff, UK.
2
Diabetes Research Group, Division of Infection and Immunity, Cardiff, UK.
3
Thyroid Research Group, Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK.
4
Cardiff Business School, Cardiff University, Cardiff, UK.

Abstract

AIMS:

To examine HbA1c as a predictor of risk for future development of cystic fibrosis-related diabetes and to assess the association with the development of retinopathy in people with cystic fibrosis-related diabetes.

METHODS:

A 7-year retrospective longitudinal study was conducted in 50 adults with cystic fibrosis, comparing oral glucose tolerance test results with HbA1c values in predicting the development of cystic fibrosis-related diabetes. Retinal screening data were also compared with HbA1c measurements to assess microvascular outcome.

RESULTS:

An HbA1c value ≥37 mmol/mol (5.5%; hazard ratio 3.49, CI 1.5-8.1) was significantly associated with the development of dysglycaemia, as defined by the oral glucose tolerance test over a 7-year period. Severity of diabetic retinopathy was associated with a higher HbA1c and longer duration of cystic fibrosis-related diabetes.

CONCLUSION:

There is a link between HbA1c level and the future development of dysglycaemia in cystic fibrosis based on oral glucose tolerance test, as well as microvascular outcomes. Although current guidance does not advocate the use of HbA1c as a diagnostic tool in cystic fibrosis-related diabetes, it may be of clinical use in determining individuals at risk of future development of cystic fibrosis-related diabetes.

PMID:
30697808
DOI:
10.1111/dme.13912
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8.
Diabet Med. 2019 Jan 30. doi: 10.1111/dme.13911. [Epub ahead of print]

How tightly controlled do fluctuations in blood glucose levels need to be to reduce the risk of developing complications in people with Type 1 diabetes?

Author information

1
Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, Glasgow, UK.
2
School of Medicine, University of Glasgow, Glasgow, UK.
3
Glasgow Royal Infirmary, Glasgow, UK.

Abstract

In 2011, the James Lind Alliance published a 'top 10' list of priorities for Type 1 diabetes research based on a structured consultation process. Whether reducing fluctuations in blood glucose can prevent long-term microvascular and macrovascular complications was one of these. In this narrative review, 8 years on, we have assessed the updated evidence for the assertion that increased glucose variability plays an independent and clinically important role in the complications of Type 1 diabetes, over and above mean blood glucose and the effects of hypoglycaemia: the 'glucose variability hypothesis'. Although studies in cultured cells and ex vivo vessels have been suggestive, most studies in Type 1 diabetes have been small and/or cross-sectional, and based on 'finger-prick' glucose measurements that capture glucose variability only in waking hours and are affected by missing data. A recent analysis of the Diabetes Control and Complications Trial that formally imputed missing data found no independent effect of short-term glucose variability on long-term complications. Few other high-quality longitudinal studies have directly addressed the glucose variability hypothesis in Type 1 diabetes. We conclude that there is little substantial evidence to date to support this hypothesis in Type 1 diabetes, although increasing use of continuous glucose monitoring provides an opportunity to test it more definitively. In the meantime, we recommend that control of glycaemia in Type 1 diabetes should continue to focus on the sustained achievement of target HbA1c and avoidance of hypoglycaemia.

PMID:
30697804
DOI:
10.1111/dme.13911
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Publication type

Publication type

9.
Diabet Med. 2019 Jan 28. doi: 10.1111/dme.13910. [Epub ahead of print]

Prevalence of diabetes among children treated with growth hormone in Israel.

Author information

1
Israel Centre for Disease Control, Israel Ministry of Health, Ramat Gan.
2
Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv.
3
Paediatric Endocrinology Unit, Kaplan Medical Centre, Rehovot.
4
Endocrinology and Diabetes Research Unit, Schneider Children's Medical Centre, Petah Tikva, Israel.

Abstract

AIMS:

To determine the long-term risk of diabetes in a cohort of children treated with recombinant human growth hormone in Israel, using data from the Israeli National Diabetes Register.

METHODS:

Between 1988 and 2009, 2513 children were approved for growth hormone treatment. They were assigned to one of two groups. The first group included children treated for isolated growth hormone deficiency and who were small for gestational age and the second included those treated for multiple pituitary hormone deficiency, chronic renal failure, Turner syndrome or Prader-Willi syndrome. The cohort was cross-linked with the Israeli National Diabetes Register for 2014 (mean follow-up duration 12.1±5.3 years), and prevalent cases of diabetes were identified. Standardized prevalence ratios for diabetes were calculated for people aged 10-29 years.

RESULTS:

In 2014, a total of 23 individuals were identified with diabetes (four with pre-existing diabetes, seven developed diabetes before age 17 years and 12 developed it at a later age). In the isolated growth hormone deficiency and small-for-gestational-age group there was no difference in the prevalence of diabetes compared with the general population (standardized prevalence ratio 2.05, 95% CI 0.94-3.89). In the group that included people with multiple pituitary hormone deficiency, chronic renal failure, Turner syndrome and Prader-Willi syndrome there was a significantly higher diabetes prevalence (standardized prevalence ratio 11.94, 95% CI 6.53-20.00) compared with the general population.

CONCLUSIONS:

No difference in diabetes prevalence was found in the isolated growth hormone deficiency and small-for-gestational-age group, compared with the general population. Children treated with growth hormone with pre-existing risk factors had an increased prevalence of diabetes. It is advisable to monitor blood glucose levels closely during and after growth hormone treatment, especially in such children.

PMID:
30690790
DOI:
10.1111/dme.13910
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10.
Diabetes. 2019 Jan 29. pii: db181151. doi: 10.2337/db18-1151. [Epub ahead of print]

Insulin Therapy of Gestational Diabetes Does Not Fully Protect Offspring from Diet-Induced Metabolic Disorders.

Author information

1
The Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Zhejiang university school of medicine, Hangzhou, Zhejiang, China.
2
Department of Pathology and Pathophysiology, Zhejiang University school of medicine, Hangzhou, Zhejiang, China.
3
Department of Obstetrics, Women's Hospital, Zhejiang University school of medicine, Hangzhou, China.
4
The International Peace Maternity and Child Health Hospital, Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China hhf57@zju.edu.cn.
5
Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.
6
The Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Zhejiang university school of medicine, Hangzhou, Zhejiang, China hhf57@zju.edu.cn.
7
The International Peace Maternity and Child Health Hospital, Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Gestational diabetes mellitus (GDM) is associated with increased risk of metabolic disorders in offspring in later life. Although mounting evidence suggests that therapy for GDM could improve neonatal health, it is not known whether the therapy confers long-term metabolic benefits to offspring in their later adult lives. Here, using a mouse model of diabetes in the latter half of pregnancy to mimic human GDM, we find that the efficient insulin therapy of GDM confers significant protection against glucose intolerance and obesity in offspring fed on normal chow diet. However, the therapy fails to protect offspring when challenged with a high fat diet, especially for male offspring. Genome-wide DNA methylation profiling of pancreatic islets from male offspring identified hypermethylated regions in several genes that regulate insulin secretion, including Abcc8, Cav1.2 and Cav2.3 that encode KATP or Ca2+ channels, which is associated with reduced gene expression and impaired insulin secretion. This finding suggests a methylation-mediated epigenetic mechanism for GDM-induced intergenerational glucose intolerance. It highlights that even efficient insulin therapy of GDM is insufficient to fully protect adult offspring from diet-induced metabolic disorders.

PMID:
30696708
DOI:
10.2337/db18-1151
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11.
Diabetes. 2019 Jan 24. pii: db181172. doi: 10.2337/db18-1172. [Epub ahead of print]

Opposing Effects of Neuropilin-1 and -2 on Sensory Nerve Regeneration in Wounded Corneas: Role of Sema3C in Ameliorating Diabetic Neurotrophic Keratopathy.

Author information

1
Departments of Ophthalmology and Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
2
Qingdao Eye Hospital, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
3
Departments of Ophthalmology and Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA av3899@wayne.edu.

Abstract

The diabetic cornea exhibits pathological alterations such as delayed epithelial wound healing and nerve regeneration. We sought to investigate the role of Semaphorin (SEMA) 3C in corneal wound healing and re-innervation in normal and diabetic B6 mice. Wounding induced the expression of SEMA3A, 3C and their receptor Neuropilin (NRP) 2, but not NRP1 in normal corneal epithelial cells (CECs); this upregulation was suppressed for SEMA3C and NRP2 in diabetic corneas. Injections of Sema3C-specific siRNA and NRP2 neutralizing antibodies in wounded mice resulted in a decrease in the rate of wound healing and regenerating nerve fibers, while exogenous SEMA3C had opposing effects in diabetic corneas. NRP1 neutralization, on the other hand, decreased epithelial wound closure but increased sensory nerve regeneration in diabetic corneas, suggesting a detrimental role in nerve regeneration. Taken together, epithelium-expressed SEMA3C plays a role in corneal epithelial wound closure and sensory nerve regeneration. The hyperglycemia-suppressed SEMA3C/NRP2 signaling may contribute to the pathogenesis of diabetic neurotrophic keratopathy, and SEMA3C might be used as an adjunctive therapeutic for treating the disease.

PMID:
30679185
DOI:
10.2337/db18-1172
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12.
Diabetes. 2019 Jan 24. pii: db180694. doi: 10.2337/db18-0694. [Epub ahead of print]

Neurovascular Response to Pressure in Patients with Diabetic Foot Ulcer.

Author information

1
Hospices Civils de Lyon, Diabetes department, Centre Hospitalier Lyon-Sud, Pierre Bénite, France. julien.vouillarmet@chu-lyon.fr.
2
UMR CNRS 5305, Laboratoire de Biologie Tissulaire et Ingénierie thérapeutique, Lyon, France.
3
Claude Bernard Lyon 1 University, Lyon, France.
4
Hospices Civils de Lyon, Diabetes department, Centre Hospitalier Lyon-Sud, Pierre Bénite, France.
5
Vascular medecine department, CHU d'Angers, Angers, France.
6
Department of Medicine, Würzburg University Clinic, Würzburg, Germany.

Abstract

Diabetic foot ulcer (DFU) is a problem worldwide and prevention is crucial. We hypothesized that the inability of the skin to respond to pressure is involved in DFU pathogenesis and could be an important predictive factor to take into account.We included 29 patients with DFU and 30 patients with type 2 diabetes without DFU. Neuropathy and skin blood flow at rest were assessed in response to acetylcholine, sodium nitroprusside, local heating (42°C), and to non-noxious locally applied pressure. Results were compared to those obtained from 10 healthy age-matched control subjects.Vasodilatation in response to pressure was significantly impaired in both diabetic groups compared to healthy subjects. The vasodilator capacity to pressure was significantly lower in patients with DFU compared to those without DFU, despite the absence of significant difference in cutaneous pressure perception threshold and vascular reactivity to acetylcholine, sodium nitroprusside, and heat.This pronounced alteration of neurovascular response to pressure in patients with DFU is a good marker of skin vulnerability and could be used to better predict individuals at risk.

PMID:
30679184
DOI:
10.2337/db18-0694
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13.
Diabetes. 2019 Jan 24. pii: db180699. doi: 10.2337/db18-0699. [Epub ahead of print]

Potential of Allogeneic Adipose-Derived Stem Cell - Hydrogel Complex for Treating Diabetic Foot Ulcers.

Author information

1
Department of Plastic Surgery, Korea University Guro Hospital, Seoul, South Korea.
2
Department of Plastic Surgery, Asan Medical Center, Seoul, South Korea.
3
Department of Plastic Surgery, Korea University Guro Hospital, Seoul, South Korea pshan@kumc.or.kr.
4
Department of Foot and Ankle Surgery, Eulji Medical Center, Seoul, South Korea.
5
Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, South Korea.

Abstract

Mesenchymal stem cells (MSCs) may hold great promise for treating diabetic wounds. However, it is difficult for a clinician to use MSCs because they have not been commercialized. Meanwhile, a new commercial drug that contains adipose-derived stem cells (ASCs) has been developed. The purpose of this study was to examine the potential of allogeneic ASC sheets for treating diabetic foot ulcers. Fifty-nine patients with diabetic foot ulcers were randomized to either ASC treatment group (n = 30) or control group treated with polyurethane film (n = 29). Either allogeneic ASC sheet or polyurethane film was applied on diabetic wounds weekly. These wounds were evaluated for a maximum of 12 weeks. Complete wound closure was achieved for 73% in the treatment group and 47% in the control group at week 8. Complete wound closure was achieved for 82% in the treatment group and 53% in the control group at week 12. Kaplan-Meier median times to complete closure were 28.5 and 63.0 days for the treatment group and the control group, respectively. There were no serious adverse events related to allogeneic ASC treatment. Thus, allogeneic ASCs might be effective and safe to treat diabetic foot ulcers.

PMID:
30679183
DOI:
10.2337/db18-0699
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14.
Diabetes Care. 2019 Jan 28. pii: dc182176. doi: 10.2337/dc18-2176. [Epub ahead of print]

Maternal and Newborn Vitamin D-Binding Protein, Vitamin D Levels, Vitamin D Receptor Genotype, and Childhood Type 1 Diabetes.

Author information

1
Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway german.tapia@fhi.no.
2
Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway.
3
Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Aker, Oslo, Norway.
4
Barbara Davis Center for Diabetes, University of Colorado, Anschutz Medical Campus, Aurora, CO.
5
Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
6
Department of Immunology, Rikshospitalet, Oslo University Hospital, Oslo, Norway.
7
Department of Medical Genetics, University of Oslo, Oslo, Norway.
8
Department of Pediatric and Adolescent Medicine, Haukeland University Hospital, Bergen, Norway.
9
KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
10
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
11
Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
12
Department of Pediatrics, Østfold Hospital Trust, Grålum, Norway.

Abstract

OBJECTIVE:

Circumstantial evidence links 25-hydroxy vitamin D [25(OH)D], vitamin D-binding protein (DBP), vitamin D-associated genes, and type 1 diabetes (T1D), but no studies have jointly analyzed these. We aimed to investigate whether DBP levels during pregnancy or at birth were associated with offspring T1D and whether vitamin D pathway genetic variants modified associations between DBP, 25(OH)D, and T1D.

RESEARCH DESIGN AND METHODS:

From a cohort of >100,000 mother/child pairs, we analyzed 189 pairs where the child later developed T1D and 576 random control pairs. We measured 25(OH)D using liquid chromatography-tandem mass spectrometry, and DBP using polyclonal radioimmunoassay, in cord blood and maternal plasma samples collected at delivery and midpregnancy. We genotyped mother and child for variants in or near genes involved in vitamin D metabolism (GC, DHCR7, CYP2R1, CYP24A1, CYP27B1, and VDR). Logistic regression was used to estimate odds ratios (ORs) adjusted for potential confounders.

RESULTS:

Higher maternal DBP levels at delivery, but not in other samples, were associated with lower offspring T1D risk (OR 0.86 [95% CI 0.74-0.98] per μmol/L increase). Higher cord blood 25(OH)D levels were associated with lower T1D risk (OR = 0.87 [95% CI 0.77-0.98] per 10 nmol/L increase) in children carrying the VDR rs11568820 G/G genotype (P interaction = 0.01 between 25(OH)D level and rs11568820). We did not detect other gene-environment interactions.

CONCLUSIONS:

Higher maternal DBP level at delivery may decrease offspring T1D risk. Increased 25(OH)D levels at birth may decrease T1D risk, depending on VDR genotype. These findings should be replicated in other studies. Future studies of vitamin D and T1D should include VDR genotype and DBP levels.

PMID:
30692241
DOI:
10.2337/dc18-2176
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15.
Diabetes Care. 2019 Jan 28. pii: dc181965. doi: 10.2337/dc18-1965. [Epub ahead of print]

Frailty and Risk of Fractures in Patients With Type 2 Diabetes.

Author information

1
Center for Clinical Epidemiology and Methodology (CCEM), Guangdong Second Provincial General Hospital, Guangzhou, China lig28@mcmaster.ca.
2
Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.
3
St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
4
Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
5
Departments of Medicine and Radiology, University of Manitoba, Winnipeg, Manitoba, Canada.
6
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
7
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
8
Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
9
Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
10
Department of Medicine, Queen's University, Kingston, Ontario, Canada.
11
Saskatoon Osteoporosis and CaMos Centre, Saskatoon, Saskatchewan, Canada.
12
Department of Medicine, McGill University, Montréal, Québec, Canada.

Abstract

OBJECTIVE:

We aimed to explore whether frailty was associated with fracture risk and whether frailty could modify the propensity of type 2 diabetes toward increased risk of fractures.

RESEARCH DESIGN AND METHODS:

Data were from a prospective cohort study. Our primary outcome was time to the first incident clinical fragility fracture; secondary outcomes included time to hip fracture and to clinical spine fracture. Frailty status was measured by a Frailty Index (FI) of deficit accumulation. Cox model incorporating an interaction term (frailty × diabetes) was used for analyses.

RESULTS:

The analysis included 3,149 (70% women) participants; 138 (60% women) had diabetes. Higher bone mineral density and FI were observed in participants with diabetes compared with control subjects. A significant relationship between the FI and the risk of incident fragility fractures was found, with a hazard ratio (HR) of 1.02 (95% CI 1.01-1.03) and 1.19 (95% CI 1.10-1.33) for per-0.01 and per-0.10 FI increase, respectively. The interaction was also statistically significant (P = 0.018). The HR for per-0.1 increase in the FI was 1.33 for diabetes and 1.19 for nondiabetes if combining the estimate for the FI itself with the estimate from the interaction term. No evidence of interaction between frailty and diabetes was found for risk of hip and clinical spine fractures.

CONCLUSIONS:

Participants with type 2 diabetes were significantly frailer than individuals without diabetes. Frailty increases the risk of fragility fracture and enhances the effect of diabetes on fragility fractures. Particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.

PMID:
30692240
DOI:
10.2337/dc18-1965
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16.
Diabetes Care. 2019 Jan 28. pii: dc181485. doi: 10.2337/dc18-1485. [Epub ahead of print]

Cumulative Risk of End-Stage Renal Disease Among Patients With Type 2 Diabetes: A Nationwide Inception Cohort Study.

Author information

1
Abdominal Centre Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland patrik.finne@hus.fi.
2
Finnish Registry for Kidney Diseases, Helsinki, Finland.
3
Abdominal Centre Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
4
Folkhälsan Institute of Genetics, Folkhälsan Research Center Biomedicum Helsinki, Helsinki, Finland.
5
Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia.
6
Department of Health and Social Care Systems, National Institute for Health and Welfare (THL), Helsinki, Finland.
7
Centre of Medicine, Kuopio University Hospital, Kuopio, Finland.
8
Department of Social Research, Centre for Research Methods, University of Helsinki, Helsinki, Finland.
9
Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Abstract

OBJECTIVE:

To estimate long-term cumulative risk of end-stage renal disease (ESRD) after diagnosis of type 2 diabetes.

RESEARCH DESIGN AND METHODS:

This nationwide population-based inception cohort study included 421,429 patients with type 2 diabetes diagnosed in 1990-2011; patients were followed until the end of 2013. Data linkage between several national health care registers in Finland, covering 100% of the population, enabled the inclusion of almost all inhabitants who started taking diabetes medication or were hospitalized for diabetes. Cumulative risk of ESRD and hazard ratios [HR] for ESRD and death were estimated according to age, sex, and time period of diabetes diagnosis.

RESULTS:

Among 421,429 patients with type 2 diabetes, 1,516 developed ESRD and 150,524 died during 3,458,797 patient-years of follow-up. Cumulative risk of ESRD was 0.29% at 10 years and 0.74% at 20 years from diagnosis of diabetes. Risk was higher among men than among women (HR 1.93 [95% CI 1.72-2.16]), decreased with older age at diagnosis (HR 0.70 [95% CI 0.60-0.81] for age 60-69 vs. 40-49 years), and was lower for those diagnosed in 2000-2011 than in 1990-1994 (HR 0.72 [95% CI 0.63-0.81]). Patients diagnosed with diabetes in 2000-2011 had lower risk of death during follow-up than those diagnosed in 1990-1994 (HR 0.64 [95% CI 0.63-0.65]).

CONCLUSIONS:

Cumulative risk of ESRD is minimal among patients with type 2 diabetes compared with their risk of death. Patients diagnosed with diabetes at an older age have a lower risk of ESRD due to higher competing mortality.

PMID:
30692239
DOI:
10.2337/dc18-1485
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17.
Diabetes Care. 2019 Jan 28. pii: dc182029. doi: 10.2337/dc18-2029. [Epub ahead of print]

Sex Differences in Cardiovascular Risk Profile From Childhood to Midlife Between Individuals Who Did and Did Not Develop Diabetes at Follow-up: The Bogalusa Heart Study.

Author information

1
Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
2
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA.
3
Section of Endocrinology, Department of Medicine, Tulane University School of Medicine, New Orleans, LA.
4
Southeast Louisiana Veterans Healthcare System Medical Center, New Orleans, LA.
5
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA lbazzano@tulane.edu.

Abstract

OBJECTIVE:

Childhood and young adulthood may represent time periods in which cardiovascular risk factors (CVRFs) and their cumulative exposure lay the foundation for future risk of chronic diseases. We examined the longitudinal burden of CVRFs since childhood in men and women in whom diabetes did and did not develop at follow-up.

RESEARCH DESIGN AND METHODS:

We included 1,530 participants (mean [SD] follow-up time 33.1 years [8.2 years]), who participated in the Bogalusa Heart Study and had been examined at least four times starting in childhood (mean age [SD] at first examination 9.4 years [3.1 years]). The area under the growth curve was used as a measure of cumulative exposure to CVRFs since childhood.

RESULTS:

In childhood, boys and girls in whom diabetes did and did not develop at follow-up had similar CVRFs. Yet, over time, women during the transition from normoglycemia to diabetes experienced greater adverse changes in total cholesterol (TC), LDL cholesterol, and fasting plasma glucose (FPG) (noted as early as 23.5 years old and persisting across adulthood up to the age of the diagnosis of diabetes); a higher burden of exposure to BMI, TC, LDL cholesterol, and FPG from childhood to midlife; and a greater change in rates of BMI, TC, LDL cholesterol, and FPG since childhood than men during the same transition (interaction P values <0.05).

CONCLUSIONS:

The greater exposure of women to and burden of CVRFs associated with diagnosis of diabetes may help to explain the stronger impact of diabetes as a major risk factor for cardiovascular events in women compared with men.

PMID:
30692238
DOI:
10.2337/dc18-2029
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18.
Diabetes Care. 2019 Mar;42(3):e46-e47. doi: 10.2337/dci18-0036. Epub 2019 Jan 24.

Response to Comment on Laiteerapong et al. The Legacy Effect in Type 2 Diabetes: Impact of Early Glycemic Control on Future Complications (The Diabetes & Aging Study). Diabetes Care 2019;42:416-426.

Author information

1
Department of Medicine, The University of Chicago, Chicago, IL nlaiteerapong@uchicago.edu.
2
Center for Health and the Social Sciences, The University of Chicago, Chicago, IL.
3
Department of Medicine, The University of Chicago, Chicago, IL.
4
Division of Research, Kaiser Permanente, Oakland, CA.

Publication type

Publication type

19.
Diabetes Care. 2019 Mar;42(3):e45. doi: 10.2337/dc18-1779. Epub 2019 Jan 24.

Comment on Laiteerapong et al. The Legacy Effect in Type 2 Diabetes: Impact of Early Glycemic Control on Future Complications (The Diabetes & Aging Study). Diabetes Care 2019;42: 416-426.

Author information

1
Aarhus University, Aarhus, Denmark adam.hulman@ph.au.dk.
2
Danish Diabetes Academy, Odense, Denmark.
3
Aarhus University, Aarhus, Denmark.
4
Steno Diabetes Center Copenhagen, Copenhagen, Denmark.
PMID:
30679306
DOI:
10.2337/dc18-1779
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Publication type

Publication type

20.
Diabetes Care. 2019 Jan 24. pii: dc181865. doi: 10.2337/dc18-1865. [Epub ahead of print]

Cardiovascular Risk Factor Burden in U.S. People With Incident Type 2 Diabetes Receiving Antidiabetic and Cardioprotective Therapies.

Author information

1
Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, Australia.
2
Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, Australia sanjoy.paul@unimelb.edu.au.

Abstract

OBJECTIVE:

Individualized treatment of patients with diabetes requires detailed evaluation of risk factor dynamics at the population level. This study evaluated the persistent glycemic and cardiovascular (CV) risk factor burden over 2 years after treatment intensification (TI).

RESEARCH DESIGN AND METHODS:

From U.S. Centricity Electronic Medical Records, 276,884 patients with incident type 2 diabetes who intensified metformin were selected. Systolic blood pressure (SBP) ≥130/140 mmHg and LDL ≥70/100 mg/dL were defined as uncontrolled for those with/without a history of CV disease at TI. Triglycerides ≥150 mg/dL and HbA1c ≥7.5% (58 mmol/mol) were defined as uncontrolled. Longitudinal measures over 2 years after TI were used to define risk factor burden.

RESULTS:

With 3.7 years' mean follow-up, patients were 59 years, 70% obese, 22% had a history of CV disease; 60, 30, 50, and 48% had uncontrolled HbA1c, SBP, LDL, and triglycerides, respectively, at TI; and 81% and 69% were receiving antihypertensive(s) and lipid-modifying therapies, respectively. The proportion of patients with consistently uncontrolled HbA1c increased from 31% in 2005 to 41% in 2014. Among those on lipid-modifying drugs, 41% and 37% had consistently high LDL and triglycerides over 2 years, respectively. Being on antihypertensive therapies, 29% had consistently uncontrolled SBP. Among patients receiving cardioprotective therapies, 63% failed to achieve control in HbA1c + LDL, 57% in HbA1c + SBP, 55% in LDL + SBP, and 63% in HbA1c + triglycerides over 2 years after TI.

CONCLUSIONS:

Among patients on multiple therapies for risk factor control, more than one-third had uncontrolled HbA1c, lipid, and SBP levels, and more than one-half had two CV risk factors that were simultaneously uncontrolled after TI.

PMID:
30679305
DOI:
10.2337/dc18-1865
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