for Journals by Title or ISSN
for Articles by Keywords
Followed Journals
Journal you Follow: 0
Sign Up to follow journals, search in your chosen journals and, optionally, receive Email Alerts when new issues of your Followed Journals are published.
Already have an account? Sign In to see the journals you follow.
Journal Cover Diabetologia
  [SJR: 3.528]   [H-I: 182]   [248 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1432-0428 - ISSN (Online) 0012-186X
   Published by Springer-Verlag Homepage  [2354 journals]
  • Up Front
    • Pages: 1 - 2
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4507-9
      Issue No: Vol. 61, No. 1 (2018)
  • Gian Franco Bottazzo, 1946–2017
    • Authors: Ezio Bonifacio; Emanuele Bosi; R. David Leslie
      Pages: 3 - 5
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4486-x
      Issue No: Vol. 61, No. 1 (2018)
  • Diabetic cardiomyopathy: a hyperglycaemia- and insulin-resistance-induced
           heart disease
    • Authors: Guanghong Jia; Adam Whaley-Connell; James R. Sowers
      Pages: 21 - 28
      Abstract: Diabetic cardiomyopathy is characterised in its early stages by diastolic relaxation abnormalities and later by clinical heart failure in the absence of dyslipidaemia, hypertension and coronary artery disease. Insulin resistance, hyperinsulinaemia and hyperglycaemia are each independent risk factors for the development of diabetic cardiomyopathy. The pathophysiological factors in diabetes that drive the development of cardiomyopathy include systemic metabolic disorders, inappropriate activation of the renin–angiotensin–aldosterone system, subcellular component abnormalities, oxidative stress, inflammation and dysfunctional immune modulation. These abnormalities collectively promote cardiac tissue interstitial fibrosis, cardiac stiffness/diastolic dysfunction and, later, systolic dysfunction, precipitating the syndrome of clinical heart failure. Recent evidence has revealed that dysregulation of coronary endothelial cells and exosomes also contributes to the pathology behind diabetic cardiomyopathy. Herein, we review the relationships among insulin resistance/hyperinsulinaemia, hyperglycaemia and the development of cardiac dysfunction. We summarise the current understanding of the pathophysiological mechanisms in diabetic cardiomyopathy and explore potential preventative and therapeutic strategies.
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4390-4
      Issue No: Vol. 61, No. 1 (2018)
  • Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond
    • Authors: Hans-Peter Hammes
      Pages: 29 - 38
      Abstract: Diabetic retinopathy remains a relevant clinical problem. In parallel with diagnostic and therapeutic improvements, the role of glycaemia and reactive metabolites causing cell stress and biochemical abnormalities as treatment targets needs continuous re-evaluation. Furthermore, the basic mechanisms of physiological angiogenesis, remodelling and pruning give important clues about the origins of vasoregression during the very early stages of diabetic retinopathy and can be modelled in animals. This review summarises evidence supporting a role for the neurovascular unit—composed of neuronal, glial and vascular cells—as a responder to the biochemical changes imposed by reactive metabolites and high glucose. Normoglycaemic animal models developing retinal degeneration, provide valuable information about common pathways downstream of progressive neuronal damage that induce vasoregression, as in diabetic models. These models can serve to assess novel treatments addressing the entire neurovascular unit for the benefit of early diabetic retinopathy.
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4435-8
      Issue No: Vol. 61, No. 1 (2018)
  • When beta cells talk back
    • Authors: Heather C. Denroche; Dominika Nackiewicz; C. Bruce Verchere
      Pages: 39 - 42
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4443-8
      Issue No: Vol. 61, No. 1 (2018)
  • Devoting attention to glucose variability and hypoglycaemia in type 2
    • Authors: Martin K. Rutter
      Pages: 43 - 47
      Abstract: In the Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE), insulin degludec was non-inferior to insulin glargine in terms of cardiovascular events and mortality. However, there were lower rates of severe hypoglycaemia with insulin degludec. DEVOTE investigators now extend these findings by presenting the results of two observational epidemiological analyses based on trial data. In the first of these analyses (DEVOTE 2), Zinman et al (Diabetologia
      DOI : 10.1007/s00125-017-4423-z) demonstrate that, compared with individuals with lower day-to-day fasting glycaemic variability, those with higher day-to-day fasting glycaemic variability had a similar risk of major adverse cardiovascular events (MACE) but a higher risk of severe hypoglycaemia and all-cause mortality. In the second analysis (DEVOTE 3), Pieber et al (Diabetologia
      DOI : 10.1007/s00125-017-4422-0) found that individuals who experienced severe hypoglycaemia had a similar risk of MACE compared with those who never experienced severe hypoglycaemia, but had a more than twofold higher risk of subsequent total mortality and cardiovascular disease (CVD) mortality. The strengths of these studies relate to the availability of high-quality prospective data on adjudicated severe hypoglycaemia, MACE and mortality events in a large number of high-risk insulin-treated individuals with type 2 diabetes. Limitations include the observational nature of the data and thus residual confounding remains possible. Furthermore, the short duration of the trial resulted in limited statistical power for some analyses. Therefore, whilst DEVOTE 2 and DEVOTE 3 raise awareness of the mortality risks associated with glucose variability and severe hypoglycaemia in high-risk, insulin-treated patients with type 2 diabetes, they cannot clarify causal relationships. Preventing severe hypoglycaemia in those with type 2 diabetes should already be a priority in clinical practice. However, findings from future clinical trials are needed to guide physicians on whether it is beneficial to target glucose variability, and risk for severe hypoglycaemia, to reduce the risks for CVD events and mortality in these individuals.
      PubDate: 2018-01-01
      Issue No: Vol. 61, No. 1 (2018)
  • DEVOTE 3: temporal relationships between severe hypoglycaemia,
           cardiovascular outcomes and mortality
    • Authors: Thomas R. Pieber; on behalf of the DEVOTE Study Group; Steven P. Marso; Darren K. McGuire; Bernard Zinman; Neil R. Poulter; Scott S. Emerson; Richard E. Pratley; Vincent Woo; Simon Heller; Martin Lange; Kirstine Brown-Frandsen; Alan Moses; Jesper Barner Lekdorf; Lucine Lehmann; Kajsa Kvist; John B. Buse
      Pages: 58 - 65
      Abstract: Aims/hypothesis The double-blind Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) assessed the cardiovascular safety of insulin degludec. The incidence and rates of adjudicated severe hypoglycaemia, and all-cause mortality were also determined. This paper reports a secondary analysis investigating associations of severe hypoglycaemia with cardiovascular outcomes and mortality. Methods In DEVOTE, patients with type 2 diabetes were randomised to receive either insulin degludec or insulin glargine U100 (100 units/ml) once daily (between dinner and bedtime) in an event-driven, double-blind, treat-to-target cardiovascular outcomes trial. The primary outcome was the first occurrence of an adjudicated major adverse cardiovascular event (MACE; cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Adjudicated severe hypoglycaemia was the pre-specified secondary outcome. In the present analysis, the associations of severe hypoglycaemia with both MACE and all-cause mortality was evaluated in the pooled trial population using time-to-event analyses, with severe hypoglycaemia as a time-dependent variable and randomised treatment as a fixed factor. An investigation with interaction terms indicated that the effect of severe hypoglycaemia on the risk of MACE and all-cause mortality were the same for both treatment arms, and so the temporal association for severe hypoglycaemia with subsequent MACE and all-cause mortality is reported for the pooled population. Results There was a non-significant difference in the risk of MACE for individuals who had vs those who had not experienced severe hypoglycaemia during the trial (HR 1.38, 95% CI 0.96, 1.96; p = 0.080) and therefore there was no temporal relationship between severe hypoglycaemia and MACE. There was a significantly higher risk of all-cause mortality for patients who had vs those who had not experienced severe hypoglycaemia during the trial (HR 2.51, 95% CI 1.79, 3.50; p < 0.001). There was a higher risk of all-cause mortality 15, 30, 60, 90, 180 and 365 days after experiencing severe hypoglycaemia compared with not experiencing severe hypoglycaemia in the same time interval. The association between severe hypoglycaemia and all-cause mortality was maintained after adjustment for the following baseline characteristics: age, sex, HbA1c, BMI, diabetes duration, insulin regimen, hepatic impairment, renal status and cardiovascular risk group. Conclusions/interpretation The results from these analyses demonstrate an association between severe hypoglycaemia and all-cause mortality. Furthermore, they indicate that patients who experienced severe hypoglycaemia were particularly at greater risk of death in the short term after the hypoglycaemic episode. These findings indicate that severe hypoglycaemia is associated with higher subsequent mortality; however, they cannot answer the question as to whether severe hypoglycaemia serves as a risk marker for adverse outcomes or whether there is a direct causal effect. Trial registration NCT01959529
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4422-0
      Issue No: Vol. 61, No. 1 (2018)
  • Random non-fasting C-peptide testing can identify patients with
           insulin-treated type 2 diabetes at high risk of hypoglycaemia
    • Authors: Suzy V. Hope; Bridget A. Knight; Beverley M. Shields; Anita V. Hill; Pratik Choudhary; W. David Strain; Timothy J. McDonald; Angus G. Jones
      Pages: 66 - 74
      Abstract: Aims/hypothesis The aim of this study was to determine whether random non-fasting C-peptide (rCP) measurement can be used to assess hypoglycaemia risk in insulin-treated type 2 diabetes. Methods We compared continuous glucose monitoring-assessed SD of blood glucose and hypoglycaemia duration in 17 patients with insulin-treated type 2 diabetes and severe insulin deficiency (rCP < 200 pmol/l) and 17 matched insulin-treated control patients with type 2 diabetes but who had preserved endogenous insulin (rCP > 600 pmol/l). We then assessed the relationship between rCP and questionnaire-based measures of hypoglycaemia in 256 patients with insulin-treated type 2 diabetes and a comparison group of 209 individuals with type 1 diabetes. Results Continuous glucose monitoring (CGM)-assessed glucose variability and hypoglycaemia was greater in individuals with rCP < 200 pmol/l despite similar mean glucose. In those with low vs high C-peptide, SD of glucose was 4.2 (95% CI 3.7, 4.6) vs 3.0 (2.6, 3.4) mmol/l (p < 0.001). In the low-C-peptide vs high-C-peptide group, the proportion of individuals experiencing sustained hypoglycaemia ≤ 4 mmol/l was 94% vs 41% (p < 0.001), the mean rate of hypoglycaemia was 5.5 (4.4, 6.7) vs 2.1 (1.4, 2.9) episodes per person per week (p = 0.004) and the mean duration was 630 (619, 643) vs 223 (216, 230) min per person per week (p = 0.01). Hypoglycaemia ≤ 3 mmol/l was infrequent in individuals with preserved C-peptide (1.8 [1.2, 2.6] episodes per person per week vs 0.4 [0.1, 0.8] episodes per person per week for low vs high C-peptide, p = 0.04) and only occurred at night. In a population-based cohort with insulin-treated type 2 diabetes, self-reported hypoglycaemia was twice as frequent in those with rCP < 200 pmol/l (OR 2.0, p < 0.001) and the rate of episodes resulting in loss of consciousness or seizure was five times higher (OR 5.0, p = 0.001). The relationship between self-reported hypoglycaemia and C-peptide was similar in individuals with type 1 and type 2 diabetes. Conclusions/interpretation Low rCP is associated with increased glucose variability and hypoglycaemia in patients with insulin-treated type 2 diabetes and represents a practical, stable and inexpensive biomarker for assessment of hypoglycaemia risk.
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4449-2
      Issue No: Vol. 61, No. 1 (2018)
  • The shape of the glucose concentration curve during an oral glucose
           tolerance test predicts risk for type 1 diabetes
    • Authors: Heba M. Ismail; Type 1 Diabetes TrialNet Study Group; Ping Xu; Ingrid M. Libman; Dorothy J. Becker; Jennifer B. Marks; Jay S. Skyler; Jerry P. Palmer; Jay M. Sosenko
      Pages: 84 - 92
      Abstract: Aims/hypothesis We aimed to examine: (1) whether specific glucose-response curve shapes during OGTTs are predictive of type 1 diabetes development; and (2) the extent to which the glucose-response curve is influenced by insulin secretion. Methods Autoantibody-positive relatives of people with type 1 diabetes whose baseline OGTT met the definition of a monophasic or biphasic glucose-response curve were followed for the development of type 1 diabetes (n = 2627). A monophasic curve was defined as an increase in OGTT glucose between 30 and 90 min followed by a decline of ≥ 0.25 mmol/l between 90 and 120 min. A biphasic response curve was defined as a decrease in glucose after an initial increase, followed by a second increase of ≥ 0.25 mmol/l. Associations of type 1 diabetes risk with glucose curve shapes were examined using cumulative incidence curve comparisons and proportional hazards regression. C-peptide responses were compared with and without adjustments for potential confounders. Results The majority of participants had a monophasic curve at baseline (n = 1732 [66%] vs n = 895 [34%]). The biphasic group had a lower cumulative incidence of type 1 diabetes (p < 0.001), which persisted after adjustments for age, sex, BMI z score and number of autoantibodies (p < 0.001). Among the monophasic group, the risk of type 1 diabetes was greater for those with a glucose peak at 90 min than for those with a peak at 30 min; the difference persisted after adjustments (p < 0.001). Compared with the biphasic group, the monophasic group had a lower early C-peptide (30–0 min) response, a lower C-peptide index (30–0 min C-peptide/30–0 min glucose), as well as a greater 2 h C-peptide level (p < 0.001 for all). Conclusions/interpretation Those with biphasic glucose curves have a lower risk of progression to type 1 diabetes than those with monophasic curves, and the risk among the monophasic group is increased when the glucose peak occurs at 90 min than at 30 min. Differences in glucose curve shapes between the monophasic and biphasic groups appear to be related to C-peptide responses.
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4453-6
      Issue No: Vol. 61, No. 1 (2018)
  • Size and shape of the associations of glucose, HbA 1c , insulin and
           HOMA-IR with incident type 2 diabetes: the Hoorn Study
    • Authors: Carolien Ruijgrok; Jacqueline M. Dekker; Joline W. Beulens; Ingeborg A. Brouwer; Veerle M. H. Coupé; Martijn W. Heymans; Femke P. C. Sijtsma; David J. Mela; Peter L. Zock; Margreet R. Olthof; Marjan Alssema
      Pages: 93 - 100
      Abstract: Aims/hypothesis Glycaemic markers and fasting insulin are frequently measured outcomes of intervention studies. To extrapolate accurately the impact of interventions on the risk of diabetes incidence, we investigated the size and shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose (2hPG), HbA1c, fasting insulin and HOMA-IR with incident type 2 diabetes mellitus. Methods The study population included 1349 participants aged 50–75 years without diabetes at baseline (1989) from a population-based cohort in Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011 criteria or known diabetes at follow-up. Logistic regression models were used to determine the associations of the glycaemic markers, fasting insulin and HOMA-IR with incident type 2 diabetes. Restricted cubic spline logistic regressions were conducted to investigate the shape of the associations. Results After a mean follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes (11.3%); the majority were screen detected by high FPG. In multivariate adjusted models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7) for 2hPG, 3.8 (2.0, 7.2) for HbA1c, 1.9 (0.9, 3.6) for fasting insulin and 2.8 (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA1c with incident diabetes were non-linear, rising more steeply at higher values. Conclusions/interpretation FPG was most strongly associated with incident diabetes, followed by 2hPG, HbA1c, HOMA-IR and fasting insulin. The strong association with FPG is probably because FPG is the most frequent marker for diabetes diagnosis. Non-linearity of associations between glycaemic markers and incident type 2 diabetes should be taken into account when estimating future risk of type 2 diabetes based on glycaemic markers.
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4452-7
      Issue No: Vol. 61, No. 1 (2018)
  • Glucose patterns during an oral glucose tolerance test and associations
    • Authors: Adam Hulman; Dorte Vistisen; Charlotte Glümer; Michael Bergman; Daniel R. Witte; Kristine Færch
      Pages: 101 - 107
      Abstract: Aims/hypothesis In addition to blood glucose concentrations measured in the fasting state and 2 h after an OGTT, intermediate measures during an OGTT may provide additional information regarding a person’s risk of future diabetes and cardiovascular disease (CVD). First, we aimed to characterise heterogeneity of glycaemic patterns based on three time points during an OGTT. Second, we compared the incidences of diabetes and CVD and all-cause mortality rates among those with different patterns. Methods Our cohort study included 5861 participants without diabetes at baseline from the Danish Inter99 study. At baseline, all participants underwent an OGTT with measurements of plasma glucose levels at 0, 30 and 120 min. Latent class mixed-effects models were fitted to identify distinct patterns of glycaemic response during the OGTT. Information regarding incident diabetes, CVD and all-cause mortality rates during a median follow-up time of 11, 12 and 13 years, respectively, was extracted from national registers. Cox proportional hazard models with adjustment for several cardiometabolic risk factors were used to compare the risk of diabetes, CVD and all-cause mortality among individuals in the different latent classes. Results Four distinct glucose patterns during the OGTT were identified. One pattern was characterised by high 30 min but low 2 h glucose values. Participants with this pattern had an increased risk of developing diabetes compared with participants with lower 30 min and 2 h glucose levels (HR 4.1 [95% CI 2.2, 7.6]) and participants with higher 2 h but lower 30 min glucose levels (HR 1.5 [95% CI 1.0, 2.2]). Furthermore, the all-cause mortality rate differed between the groups with significantly higher rates in the two groups with elevated 30 min glucose. Only small non-significant differences in risk of future CVD were observed across latent classes after confounder adjustment. Conclusions/interpretation Elevated 30 min glucose is associated with increased risk of diabetes and all-cause mortality rate independent of fasting and 2 h glucose levels. Therefore, subgroups at high risk may not be revealed when considering only fasting and 2 h glucose levels during an OGTT.
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4468-z
      Issue No: Vol. 61, No. 1 (2018)
  • Type 2 diabetes, socioeconomic status and life expectancy in Scotland
           (2012–2014): a population-based observational study
    • Authors: Jeremy Walker; on behalf of the Scottish Diabetes Research Network Epidemiology Group; Helen Colhoun; Shona Livingstone; Rory McCrimmon; John Petrie; Naveed Sattar; Sarah Wild
      Pages: 108 - 116
      Abstract: Aims/hypothesis The aim of this study was to assess the role of socioeconomic status (SES) in the associations between type 2 diabetes and life expectancy in a complete national population. Methods An observational population-based cohort study was performed using the Scottish Care Information – Diabetes database. Age-specific life expectancy (stratified by SES) was calculated for all individuals with type 2 diabetes in the age range 40–89 during the period 2012–2014, and for the remaining population of Scotland aged 40–89 without type 2 diabetes. Differences in life expectancy between the two groups were calculated. Results Results were based on 272,597 individuals with type 2 diabetes and 2.75 million people without type 2 diabetes (total for 2013, the middle calendar year of the study period). With the exception of deprived men aged 80–89, life expectancy in people with type 2 diabetes was significantly reduced (relative to the type 2 diabetes-free population) at all ages and levels of SES. Differences in life expectancy ranged from −5.5 years (95% CI −6.2, −4.8) for women aged 40–44 in the second most-deprived quintile of SES, to 0.1 years (95% CI −0.2, 0.4) for men aged 85–89 in the most-deprived quintile of SES. Observed life-expectancy deficits in those with type 2 diabetes were generally greater in women than in men. Conclusions/interpretation Type 2 diabetes is associated with reduced life expectancy at almost all ages and levels of SES. Elimination of life-expectancy deficits in individuals with type 2 diabetes will require prevention and management strategies targeted at all social strata (not just deprived groups).
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4478-x
      Issue No: Vol. 61, No. 1 (2018)
  • Maternal obesity as a risk factor for early childhood type 1 diabetes: a
           nationwide, prospective, population-based case–control study
    • Authors: Nina Lindell; Annelie Carlsson; Ann Josefsson; Ulf Samuelsson
      Pages: 130 - 137
      Abstract: Aims/hypothesis Genetic and environmental factors are believed to cause type 1 diabetes. The aim of this study was to investigate the influence of maternal BMI and gestational weight gain on the subsequent risk of childhood type 1 diabetes. Methods Children in the Swedish National Quality Register for Diabetes in Children were matched with control children from the Swedish Medical Birth Register. Children were included whose mothers had data available on BMI in early pregnancy and gestational weight gain, giving a total of 16,179 individuals: 3231 children with type 1 diabetes and 12,948 control children. Results Mothers of children with type 1 diabetes were more likely to be obese (9% [n = 292/3231] vs 7.7% [n = 991/12,948]; p = 0.02) and/or have diabetes themselves (2.8% [n = 90/3231] vs 0.8% [n = 108/12,948]; p < 0.001) compared with mothers of control children. Gestational weight gain did not differ significantly between the two groups of mothers. In mothers without diabetes, maternal obesity was a significant risk factor for type 1 diabetes in the offspring (p = 0.04). A child had an increased risk of developing type 1 diabetes if the mother had been obese in early pregnancy (crude OR 1.20; 95% CI 1.05, 1.38; adjusted OR 1.18; 95% CI 1.02, 1.36). Among children with type 1 diabetes (n = 3231) there was a difference (p < 0.001) in age at onset in relation to the mother’s BMI. Among children in the oldest age group (15–19 years), there were more mothers who had been underweight during pregnancy, while in the youngest age group (0–4 years) the pattern was reversed. Conclusions/interpretation Maternal obesity, in the absence of maternal diabetes, is a risk factor for type 1 diabetes in the offspring, and influences the age of onset of type 1 diabetes. This emphasises the importance of a normal maternal BMI to potentially decrease the incidence of type 1 diabetes.
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4481-2
      Issue No: Vol. 61, No. 1 (2018)
  • The chromosome 6q22.33 region is associated with age at diagnosis of type
           1 diabetes and disease risk in those diagnosed under 5 years of age
    • Authors: Jamie R. J. Inshaw; Neil M. Walker; Chris Wallace; Leonardo Bottolo; John A. Todd
      Pages: 147 - 157
      Abstract: Aims/hypothesis The genetic risk of type 1 diabetes has been extensively studied. However, the genetic determinants of age at diagnosis (AAD) of type 1 diabetes remain relatively unexplained. Identification of AAD genes and pathways could provide insight into the earliest events in the disease process. Methods Using ImmunoChip data from 15,696 cases, we aimed to identify regions in the genome associated with AAD. Results Two regions were convincingly associated with AAD (p < 5 × 10−8): the MHC on 6p21, and 6q22.33. Fine-mapping of 6q22.33 identified two AAD-associated haplotypes in the region nearest to the genes encoding protein tyrosine phosphatase receptor kappa (PTPRK) and thymocyte-expressed molecule involved in selection (THEMIS). We examined the susceptibility to type 1 diabetes at these SNPs by performing a meta-analysis including 19,510 control participants. Although these SNPs were not associated with type 1 diabetes overall (p > 0.001), the SNP most associated with AAD, rs72975913, was associated with susceptibility to type 1 diabetes in those individuals diagnosed at less than 5 years old (p = 2.3 × 10−9). Conclusion/interpretation PTPRK and its neighbour THEMIS are required for early development of the thymus, which we can assume influences the initiation of autoimmunity. Non-HLA genes may only be detectable as risk factors for the disease in individuals diagnosed under the age 5 years because, after that period of immune development, their role in disease susceptibility has become redundant.
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4440-y
      Issue No: Vol. 61, No. 1 (2018)
  • Pancreatic neuro-insular network in young mice revealed by 3D panoramic
    • Authors: Shiue-Cheng Tang; Chia-Ning Shen; Pei-Yu Lin; Shih-Jung Peng; Hung-Jen Chien; Ya-Hsien Chou; Chester E. Chamberlain; Pankaj J. Pasricha
      Pages: 158 - 167
      Abstract: Aims/hypothesis It has been proposed that the neuro-insular network enables rapid, synchronised insulin secretion. However, to date, acquiring the pancreatic tissue map to study the neural network remains a challenging task as there is a lack of feasible approaches for large-scale tissue analysis at the organ level. Here, we have developed 3-dimensional (3D) panoramic histology to characterise the pancreatic neuro-insular network in young mice. Methods Pancreases harvested from young wild-type B6 mice (3 and 8 weeks old) and db/db mice (3 weeks old; db/db vs db/+) were used to develop 3D panoramic histology. Transparent pancreases were prepared by optical clearing to enable deep-tissue, tile-scanning microscopy for qualitative and quantitative analyses of islets and the pancreatic tissue network in space. Results 3D panoramic histology reveals the pancreatic neurovascular network and the coupling of ganglionic and islet populations via the network. This integration is identified in both 3- and 8-week-old mice, featuring the peri-arteriolar neuro-insular network and islet–ganglionic aggregation. In weaning hyperphagic db/db mice, the 3D image data identifies the associated increases in weight, adipose tissue attached to the pancreas, density of large islets (major axis > 150 μm) and pancreatic sympathetic innervation compared with db/+ mice. Conclusions/interpretation Our work provides insight into the neuro-insular integration at the organ level and demonstrates a new approach for investigating previously unknown details of the pancreatic tissue network in health and disease.
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4408-y
      Issue No: Vol. 61, No. 1 (2018)
  • Live attenuated enterovirus vaccine (OPV) is not associated with islet
           autoimmunity in children with genetic susceptibility to type 1 diabetes:
           prospective cohort study
    • Authors: Hanna Viskari; Sami Oikarinen; Sanna Hoppu; Tytti Vuorinen; Heini Huhtala; Jorma Toppari; Riitta Veijola; Jorma Ilonen; Mikael Knip; Heikki Hyöty
      Pages: 203 - 209
      Abstract: Aims/hypothesis Animal and human studies have implied that enterovirus infections may modulate the risk of islet autoimmunity and type 1 diabetes. We set out to assess whether serial administration of live oral poliovirus vaccine (OPV) in early life can influence the initiation of islet autoimmunity in a cohort of genetically predisposed children. Methods OPV was administered to 64 children and a further 251 children received inactivated poliovirus vaccine (IPV). The emergence of type 1 diabetes-associated autoantibodies in serum (autoantibodies to GAD, insulinoma-associated protein 2, insulin and islet cells) was monitored during prospective follow-up. Stool and serum samples were collected for enterovirus detection by RT-PCR. Results Administration of OPV increased enterovirus detected in stool samples from 11.3% to 38.9% (p < 0.001) during the first year of life. During the follow-up (median 11.0 years), at least one autoantibody was detected in 17.2% of children vaccinated with OPV and 19.1% with IPV (p = 0.723). At least two autoantibodies were observed in 3.1% and 6.8% of children, respectively (p = 0.384). Conclusions/interpretation Replication of attenuated poliovirus strains in gut mucosa is not associated with an increased risk of islet autoimmunity. Trial registration NCT02961595
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4410-4
      Issue No: Vol. 61, No. 1 (2018)
  • Pioglitazone reduces cold-induced brown fat glucose uptake despite
           induction of browning in cultured human adipocytes: a randomised,
           controlled trial in humans
    • Authors: Rebecca K. C. Loh; Melissa F. Formosa; Nina Eikelis; David A. Bertovic; Mitchell J. Anderson; Shane A. Barwood; Shane Nanayakkara; Neale D. Cohen; Andre La Gerche; Anne T. Reutens; Kenneth S. Yap; Thomas W. Barber; Gavin W. Lambert; Martin H. Cherk; Stephen J. Duffy; Bronwyn A. Kingwell; Andrew L. Carey
      Pages: 220 - 230
      Abstract: Aims/hypothesis Increasing brown adipose tissue (BAT) activity is a possible therapeutic strategy to increase energy expenditure and glucose and lipid clearance to ameliorate obesity and associated comorbidities. The thiazolidinedione (TZD) class of glucose-lowering drugs increase BAT browning in preclinical experimental models but whether these actions extend to humans in vivo is unknown. The aim of this study was to determine the effect of pioglitazone treatment on adipocyte browning and adaptive thermogenesis in humans. Methods We first examined whether pioglitazone treatment of cultured human primary subacromioclavicular-derived adipocytes induced browning. Then, in a blinded, placebo-controlled, parallel trial, conducted within the Baker Institute clinical research laboratories, 14 lean male participants who were free of cardiometabolic disease were randomised to receive either placebo (lactose; n = 7, age 22 ± 1 years) or pioglitazone (45 mg/day, n = 7, age 21 ± 1 years) for 28 days. Participants were allocated to treatments by Alfred Hospital staff independent from the study via electronic generation of a random number sequence. Researchers conducting trials and analysing data were blind to treatment allocation. The change in cold-stimulated BAT activity, assessed before and after the intervention by [18F]fluorodeoxyglucose uptake via positron emission tomography/computed tomography in upper thoracic and cervical adipose tissue, was the primary outcome measure. Energy expenditure, cardiovascular responses, core temperature, blood metabolites and hormones were measured in response to acute cold exposure along with body composition before and after the intervention. Results Pioglitazone significantly increased in vitro browning and adipogenesis of adipocytes. In the clinical trial, cold-induced BAT maximum standardised uptake value was significantly reduced after pioglitazone compared with placebo (−57 ± 6% vs −12 ± 18%, respectively; p < 0.05). BAT total glucose uptake followed a similar but non-significant trend (−50 ± 10% vs −6 ± 24%, respectively; p = 0.097). Pioglitazone increased total and lean body mass compared with placebo (p < 0.05). No other changes between groups were detected. Conclusions/interpretation The disparity in the actions of pioglitazone on BAT between preclinical experimental models and our in vivo human trial highlight the imperative to conduct human proof-of-concept studies as early as possible in BAT research programmes aimed at therapeutic development. Our clinical trial findings suggest that reduced BAT activity may contribute to weight gain associated with pioglitazone and other TZDs. Trial registration NCT02236962 Funding This work was supported by the Diabetes Australia Research Program and OIS scheme from the Victorian State Government.
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4479-9
      Issue No: Vol. 61, No. 1 (2018)
  • Biomarkers of inflammation and endothelial dysfunction as predictors of
           pulse pressure and incident hypertension in type 1 diabetes: a 20 year
           life-course study in an inception cohort
    • Authors: Isabel Ferreira; Peter Hovind; Casper G. Schalkwijk; Hans-Henrik Parving; Coen D. A. Stehouwer; Peter Rossing
      Pages: 231 - 241
      Abstract: Aims/hypothesis Vascular inflammation and endothelial dysfunction are thought to contribute to arterial stiffening and hypertension. This study aims to test this hypothesis with longitudinal data in the context of type 1 diabetes. Methods We investigated, in an inception cohort of 277 individuals with type 1 diabetes, the course, tracking and temporal inter-relationships of BP, specifically pulse pressure (a marker of arterial stiffening) and hypertension, and the following biomarkers of systemic and vascular inflammation/endothelial dysfunction: C-reactive protein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cellular adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin). These biomarkers and other risk factors were measured at baseline and repeatedly up to 20 years after the onset of type 1 diabetes. Data were analysed with generalised estimating equations including adjustments for age, sex, smoking status, BMI, HbA1c, serum creatinine, total cholesterol, urinary AER, insulin treatment dose and mean arterial pressure. Results Increases were noted in all biomarkers except sE-selectin, which decreased over time. Levels differed from baseline at 2–4 years and preceded the increase in pulse pressure, which occurred at 8–10 years after the onset of type 1 diabetes. Higher levels of sICAM-1 and sVCAM-1, but not CRP or sE-selectin, at baseline and throughout the 20 year follow-up, were significantly associated with higher (changes in) pulse pressure at subsequent time points. Higher levels of sVCAM-1 at baseline and during follow-up were also significantly associated with the prevalence (OR 3.60 [95% CI 1.36, 9.53] and OR 2.28 [1.03, 5.25], respectively) and incidence (OR 2.89 [1.08, 7.75] and OR 3.06 [1.01, 9.26], respectively) of hypertension. We also investigated the longitudinal associations between BP or hypertension as determinants of subsequent (changes in) levels of CRP, sICAM-1, sVCAM-1 and sE-selectin, but did not find evidence to support a reverse causality hypothesis. Conclusions/interpretation These findings support the involvement of vascular endothelial dysfunction and inflammation in the development of premature arterial stiffening and hypertension in type 1 diabetes.
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4470-5
      Issue No: Vol. 61, No. 1 (2018)
  • Retraction Note to: L-glutamine supplementation induces insulin resistance
           in adipose tissue and improves insulin signalling in liver and muscle of
           rats with diet-induced obesity
    • Authors: P. O. Prada; S. M. Hirabara; C. T. de Souza; A. A. Schenka; H. G. Zecchin; J. Vassallo; L. A. Velloso; E. Carneiro; J. B. C. Carvalheira; R. Curi; M. J. Saad
      Pages: 253 - 253
      Abstract: In light of forensic evidence indicating duplication and/or manipulation of western blot images the Editor-in-Chief is retracting the article cited above.
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4477-y
      Issue No: Vol. 61, No. 1 (2018)
  • Correction to: Respiratory infections are temporally associated with
           initiation of type 1 diabetes autoimmunity: the TEDDY study
    • Authors: Maria Lönnrot; on behalf of the TEDDY Study Group; Kristian F. Lynch; Helena Elding Larsson; Åke Lernmark; Marian J. Rewers; Carina Törn; Brant R. Burkhardt; Thomas Briese; William A. Hagopian; Jin-Xiong She; Olli G. Simell; Jorma Toppari; Anette-G. Ziegler; Beena Akolkar; Jeffrey P. Krischer; Heikki Hyöty
      Pages: 254 - 254
      Abstract: The authors regret that the SNP in SH2B3 was incorrectly referred to as rs3184505 instead of rs3184504 on both mentions in this paper (Methods section and Table 1).
      PubDate: 2018-01-01
      DOI: 10.1007/s00125-017-4487-9
      Issue No: Vol. 61, No. 1 (2018)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
Home (Search)
Subjects A-Z
Publishers A-Z
Your IP address:
About JournalTOCs
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-2016