Diabetologia最新文献

Aims/hypothesis

Existing evidence on the relationship between intake of monounsaturated fatty acids (MUFAs) and type 2 diabetes is conflicting. Few studies have examined whether MUFAs from plant or animal sources (MUFA-Ps and MUFA-As, respectively) exhibit differential associations with type 2 diabetes. We examined associations of intakes of total MUFAs, MUFA-Ps and MUFA-As with type 2 diabetes risk.

Methods

We used data from 51,290 women in the Nurses’ Health Study (1990–2016), 61,703 women in the Nurses’ Health Study II (1991–2017) and 29,497 men in the Health Professionals Follow-up Study (1990–2016). Using food frequency questionnaires and food composition tables, we calculated MUFA-P and MUFA-A intakes every 4 years and modelled their associations with type 2 diabetes using Cox regression models.

Results

During 3,268,512 person-years of follow-up, we documented 13,211 incident type 2 diabetes cases. After multivariate adjustment, total MUFA intake was associated with higher type 2 diabetes risk, with HR for Q5 vs Q1 of 1.10 (95% CI 1.01, 1.22). MUFA-Ps and MUFA-As demonstrated divergent associations, with HRs of 0.87 (95% CI 0.81, 0.94) and 1.34 (1.23, 1.45), respectively. In substitution analyses, HRs were 0.92 (95% CI 0.86, 0.99) for replacing 2% of energy from trans fatty acids or 0.72 (0.66, 0.78) and 0.82 (0.77, 0.88) for replacing 5% from MUFA-As and 5% from the sum of saturated fatty acids and MUFA-As with MUFA-Ps, respectively. Substituting MUFA-As for saturated fatty acids and refined carbohydrates was associated with a 43% and 33% higher risk, respectively.

Conclusions/interpretation

Higher intake of MUFA-Ps was associated with lower type 2 diabetes risk, whereas increased intake of MUFA-As was associated with higher risk. Replacing saturated fatty acids, trans fatty acids and MUFA-As with MUFA-Ps may be beneficial for type 2 diabetes prevention.

Graphical Abstract

Aims/hypothesis

Eating disorders are over-represented in type 1 diabetes and are associated with an increased risk of complications, but it is unclear whether type 1 diabetes affects the treatment of eating disorders. We assessed incidence and treatment of eating disorders in a nationwide sample of individuals with type 1 diabetes and diabetes-free control individuals.

Methods

Our study comprised 11,055 individuals aged <30 who had been diagnosed with type 1 diabetes in 1998–2010, and 11,055 diabetes-free control individuals matched for age, sex and hospital district. We ascertained incidence of eating disorders from hospital records using Poisson regression. Eating disorder treatment was assessed by new prescriptions for psychotropic medications and hospital treatment for eating disorders.

Results

During a mean follow-up of 13.1 years, there were 175 incident cases of eating disorders among individuals with type 1 diabetes and 75 among the control individuals (adjusted incidence rate ratio 2.35; 95% CI 1.80, 3.09). The prescription of psychotropic medications was similar among eating disorder patients with and without type 1 diabetes. However, those with type 1 diabetes received outpatient hospital treatment for their eating disorder less often than those without diabetes (mean 3.32 vs 5.33 outpatient care visits per year [adjusted difference 1.24; 95% CI 0.39, 2.08]).

Conclusions/interpretation

People with type 1 diabetes are more likely to be diagnosed with eating disorders than their diabetes-free peers. However, they receive less outpatient hospital treatment for their eating disorders despite their greater risk for major adverse health outcomes. These findings emphasise the need for targeted eating disorder treatment for people with type 1 diabetes.

Graphical Abstract

Aims/hypothesis: Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, shows some promise in alleviating beta cell stress and preserving beta cell function in preclinical studies of type 1 diabetes. The aim of this phase 2, placebo-controlled, double-blinded, randomised clinical trial was to investigate the efficacy and safety of fenofibrate in adults and adolescents with newly diagnosed type 1 diabetes.

Methods: We enrolled 58 individuals (aged 16 to 40 years old) with newly diagnosed type 1 diabetes and randomised them to daily oral treatment with fenofibrate 160 mg or placebo for 52 weeks (in a block design with a block size of 4, assigned in a 1:1 ratio). Our primary outcome was change in beta cell function after 52 weeks of treatment, assessed by AUC for C-peptide levels following a 2 h mixed-meal tolerance test. Secondary outcomes included glycaemic control (assessed by HbA_1c and continuous glucose monitoring), daily insulin use, and proinsulin/C-peptide (PI/C) ratio as a marker of beta cell stress. We assessed outcome measures before and after 4, 12, 26 and 52 weeks of treatment. Blinding was maintained for participants, their healthcare providers and all staff involved in handling outcome samples and assessment.

Results: The statistical analyses for the primary outcome included 56 participants (n=27 in the fenofibrate group, after two withdrawals, and n=29 in the placebo group). We found no significant differences between the groups in either 2 h C-peptide levels (mean difference of 0.08 nmol/l [95% CI -0.05, 0.23]), insulin use or glycaemic control after 52 weeks of treatment. On the contrary, the fenofibrate group showed a higher PI/C ratio at week 52 compared with placebo (mean difference of 0.024 [95% CI 0.000, 0.048], p<0.05). Blood lipidome analysis revealed that fenofibrate repressed pathways involved in sphingolipid metabolism and signalling at week 52 compared with placebo. The 52 week intervention evoked few adverse events and no serious adverse events. Follow-up in vitro experiments in human pancreatic islets demonstrated a stress-inducing effect of fenofibrate.

Conclusions/interpretation: Contrary to the beneficial effects of fenofibrate found in preclinical studies, this longitudinal, randomised, placebo-controlled trial does not support the use of fenofibrate for preserving beta cell function in individuals with newly diagnosed type 1 diabetes.

Trial registration: EudraCT number: 2019-004434-41 FUNDING: This study was funded by the Sehested Hansens Foundation.

Aims/hypothesis: Glycaemic control and clinical outcomes in diabetes are improved by continuous subcutaneous insulin infusion (CSII). Atmospheric pressure changes during flights may affect insulin delivery from pumps and cause unintended metabolic consequences, including hypoglycaemia, in people with type 1 diabetes. The present report evaluates both hypobaric flight simulation and real-world data in pilots using insulin pumps while flying.

Methods: In the flight simulation part of this study, an in vitro study of insulin pumps was conducted in a hypobaric chamber, de-pressurised to 550 mmHg to mimic the atmospheric pressure changes in airliner cabins during commercial flights. Insulin delivery rates and bubble formation were recorded for standard flight protocol. Insulin infusion sets, without pumps, were tested in a simulated rapid decompression scenario. The real-world observational study was a 7.5-year retrospective cohort study in which pre- and in-flight self-monitored blood glucose (SMBG) values were monitored in pilots with insulin-treated diabetes. Commercial and private pilots granted a medical certificate to fly within the European Union Aviation Safety Agency approved protocol and receiving insulin either by pump or multiple daily injections (MDI) were included.

Results: In the flight simulation study, full cartridges over-delivered 0.60 U of insulin during a 20 min ascent and under-delivered by 0.51 U during descent compared with ground-level performance. During emergency rapid decompression, 5.6 U of excess insulin was delivered. In the real-world study, seven pilots using CSII recorded 4656 SMBG values during 2345 h of flying across 1081 flights. Only 33 (0.7%) values were outside an acceptable safe range (5.0-15.0 mmol/l [90-270 mg/dl]). No clinically significant fall in the median SMBG concentration was observed after aircraft ascent and no in-flight SMBG values were within the hypoglycaemic range (<4.0 mmol/l [<72 mg/dl]). Compared with pilots receiving MDI therapy, pilots using CSII recorded more SMBG values within the acceptable range (99.3% vs 97.5%), fewer values in the low red range (0.02% vs 0.1%), fewer in-flight out-of-range values (0.2% vs 1.3%) and maintained stricter glycaemic control during flight.

Conclusions/interpretation: Ambient pressure reduction during simulated flights results in bubble formation and expansion within insulin cartridges. This causes unintended delivery of small insulin doses independent of pre-determined delivery rates and represents the maximum amount of insulin that could be delivered and retracted. However, in vivo, pilots using CSII in-flight did not experience a fall in blood glucose or episodes of hypoglycaemia during these atmospheric pressure changes and the use of insulin pumps can be endorsed in view of their clinical benefits.

A panel of primary care and diabetes specialists conducted focused literature searches on the current role of glycaemic control in the management of type 2 diabetes and revisited the evolution of evidence supporting the importance of early and intensive blood glucose control as a central strategy to reduce the risk of adverse long-term outcomes. The optimal approach to type 2 diabetes management has evolved over time as the evidence base has expanded from data from trials that established the role of optimising glycaemic control to recent data from cardiovascular outcomes trials (CVOTs) demonstrating organ-protective effects of newer glucose-lowering drugs (GLDs). The results from these CVOTs were derived mainly from people with type 2 diabetes and prior cardiovascular and kidney disease or multiple risk factors. In more recent years, earlier diagnosis in high-risk individuals has contributed to the large proportion of people with type 2 diabetes who do not have complications. In these individuals, a legacy effect of early and optimal control of blood glucose and cardiometabolic risk factors has been proven to reduce cardiovascular and kidney disease events and all-cause mortality. As there is a lack of RCTs investigating the potential synergistic effects of intensive glucose control and organ-protective effects of newer GLDs, this article re-evaluates the evolution of the scientific evidence and highlights the importance of integrating glycaemic control as a pivotal early therapeutic goal in most people with type 2 diabetes, while targeting existing cardiovascular and kidney disease. We also emphasise the importance of implementing multifactorial management using a multidisciplinary approach to facilitate regular review, patient empowerment and the possibility of tailoring interventions to account for the heterogeneity of type 2 diabetes.

Human molecular genetics has brought incredible insights into the variants that confer risk for the development of tissue-specific autoimmune diseases, including type 1 diabetes. The hallmark cell-mediated immune destruction that is characteristic of type 1 diabetes is closely linked with risk conferred by the HLA class II gene locus, in combination with a broad array of additional candidate genes influencing islet-resident beta cells within the pancreas, as well as function, phenotype and trafficking of immune cells to tissues. In addition to the well-studied germline SNP variants, there are critical contributions conferred by T cell receptor (TCR) and B cell receptor (BCR) genes that undergo somatic recombination to yield the Adaptive Immune Receptor Repertoire (AIRR) responsible for autoimmunity in type 1 diabetes. We therefore created the T1D TCR/BCR Repository (The Type 1 Diabetes T Cell Receptor and B Cell Receptor Repository) to study these highly variable and dynamic gene rearrangements. In addition to processed TCR and BCR sequences, the T1D TCR/BCR Repository includes detailed metadata (e.g. participant demographics, disease-associated parameters and tissue type). We introduce the Type 1 Diabetes AIRR Consortium goals and outline methods to use and deposit data to this comprehensive repository. Our ultimate goal is to facilitate research community access to rich, carefully annotated immune AIRR datasets to enable new scientific inquiry and insight into the natural history and pathogenesis of type 1 diabetes.