Diabetologia最新文献

Aims/hypothesis: The aim of this study was to clarify the impact of autoimmune disease (AD) comorbidity on the risk and prognosis of latent autoimmune diabetes in adults (LADA).

Methods: We used data from a Swedish study comprising newly diagnosed cases of LADA (n=586, stratified into LADA^low and LADA^high by autoantibody levels), type 2 diabetes (n=2003) and matched control participants (n=2355). Information on 33 ADs and diabetic retinopathy was obtained by linkage to regional and national registers. We estimated the ORs for LADA and type 2 diabetes in relation to ADs before diabetes diagnosis, and the HRs for diabetic retinopathy after diabetes diagnosis. We performed functional pathway analyses to explore biological mechanisms driving the associations.

Results: Individuals with ADs exhibit an increased susceptibility to LADA (OR 1.70; 95% CI 1.36, 2.13), particularly those with thyroid dysfunction (OR 1.88; 95% CI 1.38, 2.56), inflammatory bowel disease (OR 1.78; 95% CI 1.00, 3.16) or vitiligo (OR 3.91; 95% CI 1.93, 7.94), with stronger associations being observed for the LADA^high phenotype. Only psoriasis was linked to type 2 diabetes (OR 1.47; 95% CI 1.08, 1.99). The biological pathways shared by LADA and ADs revolved around immune responses, including innate and adaptive immune pathways. The HRs for diabetic retinopathy in LADA patients with and without AD vs those with type 2 diabetes were 2.11 (95% CI 1.34, 3.32) and 1.68 (95% CI 1.15, 2.45), respectively.

Conclusions/interpretation: We confirm that several common ADs confer an excess risk of LADA, especially LADA with higher GADA levels, but having such a comorbidity does not appear to affect the risk of diabetic retinopathy.

Aims/hypothesis: Postprandial hypoglycaemia (PPHG) is a frequent late complication of Roux-en-Y gastric bypass (RYGB) in people without diabetes. We aimed to examine the pathogenetic mechanisms of PPHG and its clinical consequences in people with a history of type 2 diabetes.

Methods: In this case-control study, 24 participants with type 2 diabetes treated with RYGB (14 women; median [IQR] age 53.5 [13.8] years, BMI 29.3 [6.3] kg/m², HbA_1c 36.0 [6.2] mmol/mol [5.4% (0.6%)]) underwent a dual-tracer, frequently sampled, 300 min, 75 g OGTT for the diagnosis of PPHG (glucose nadir <3.0 mmol/l, or <3.3 mmol/l with symptoms). Plasma glucose, glucose tracers, insulin, C-peptide, glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon, adrenaline (epinephrine), noradrenaline (norepinephrine), cortisol and NEFAs were measured. Mathematical models were implemented to estimate glucose metabolic fluxes and beta cell function. ECG recordings, cognitive testing and hypoglycaemia awareness assessments were repeated during the OGTT. Glycaemic levels and dietary habits were assessed under free-living conditions.

Results: PPHG occurred in 12 (50%) participants, mostly without symptoms, due to excessive tracer-derived glucose clearance (mean group difference ± SE in AUC_{0-180 min} +261±72 ml min^-1 kg^-1 × min) driven by higher whole-body insulin sensitivity and early glucose-stimulated hyperinsulinaemia, the latter depending on lower insulin clearance and enhanced beta cell function, regardless of incretin hormones. PPHG participants also had defective counterregulatory hormone responses to hypoglycaemia, preventing a physiological increase in endogenous glucose production and the appearance of symptoms and signs of sympathetic cardiovascular activation and neuroglycopenia. PPHG was associated with more frequent and prolonged hypoglycaemia on 14 day continuous glucose monitoring and alterations in free-living dietary habits.

Conclusions: Our results demonstrate that post-bypass PPHG occurs frequently in individuals with a history of type 2 diabetes, often without warning symptoms, and expose its complex pathogenetic mechanisms, revealing potential therapeutic targets.

Aims/hypothesis: Diabetes mellitus is a significant global health concern that is projected to affect 7.7% of the global population by 2030. Understanding factors that influence diabetes knowledge and management adherence is crucial for effective diabetes mellitus management and prevention. This study investigates the relationships between demographic and clinical factors and their impact on diabetes knowledge and behaviour, as well as the potential influence of diabetes knowledge on management behaviours.

Methods: The study comprised a cross-sectional survey of 1050 adults, collecting data on age, sex, marital status, education, employment, hypertension, dyslipidaemia (any lipid imbalance, such as high cholesterol, high LDL-cholesterol or low HDL-cholesterol), smoking and diabetes status. Two multiple linear regression models were used to identify factors associated with diabetes knowledge and behaviour, and a simple linear regression model was used to assess the relationship between knowledge and behaviour.

Results: Significant associations were found between diabetes knowledge and the following factors: age (44.32 ± 9.53 for ≥50 years vs 39.73 ± 9.95 for 18 to <25 years; p<0.0001), sex (49.00 ± 12.35 for women vs 45.09 ± 13.27 for men; p<0.0001), marital status (50.92 ± 11.69 for married vs 45.39 ± 13.10 for single; p<0.0001), smoking status (45.78 ± 13.22 for smokers vs 48.22 ± 12.15 for non-smokers; p=0.003), hypertension (46.46 ± 13.11 for present vs 47.31 ± 12.87 for absent; p=0.007) and diabetes status (69.49 ± 17.35 for present vs 62.76 ± 16.88 for absent; p<0.001). Behaviour scores correlated similarly with these factors except for diabetes and smoking status. The adjusted simple linear regression model revealed that diabetes knowledge was significantly associated with better management behaviours (coefficient=0.0794, p<0.001) after adjusting for demographic and clinical factors.

Conclusions/interpretation: This study highlights the importance of demographic and clinical factors in the context of diabetes knowledge and behaviours, underscoring the need for targeted educational and preventive programmes to improve diabetes management, especially in vulnerable populations. Additionally, the strong association between diabetes knowledge and management behaviours supports a knowledge-attitude-behaviour (KAB) model of diabetes management.

Aims/hypothesis: The majority of hybrid closed-loop systems still require carbohydrate counting (CC) but the evidence for its justification remains limited. Here, we evaluated glucose control with simplified meal announcement (SMA) vs CC in youth and young adults with type 1 diabetes using the mylife CamAPS FX system.

Methods: We conducted a two-centre, randomised crossover, non-inferiority trial in two University Hospitals in Switzerland in 46 participants (aged 12-20 years) with type 1 diabetes using multiple daily injections (n=35), sensor-augmented pump (n=4) or hybrid closed-loop (n=7) therapy before enrolment. Participants underwent two 3 month periods with the mylife CamAPS FX system (YpsoPump, Dexcom G6) to compare SMA (individualised carbohydrate meal sizes) with CC, in a randomly assigned order using computer-generated sequences. The primary endpoint was the proportion of time glucose was in target range (3.9-10.0 mmol/l) with a non-inferiority margin of 5 percentage points. Secondary endpoints were other sensor glucose and insulin metrics, usability and safety endpoints.

Results: Forty-three participants (18 women and girls) completed the trial. In the intention-to-treat analysis, time in range (mean±SD) was 69.9±12.4% with SMA and 70.7±13.0% with CC (estimated mean difference -0.6 percentage points [95% CI -2.4, 1.1], demonstrating non-inferiority). Time <3.9 mmol/l (median [IQR] 1.8 [1.2-2.2]% vs 1.9 [1.6-2.5]%) and >10.0 mmol/l (28.2±12.6% vs 27.2±13.4%) was similar between periods. Total daily insulin dose was higher with SMA (54.0±14.7 U vs 51.7±12.1 U, p=0.037). Three participants experienced serious adverse events, none of which were intervention-related.

Conclusions/interpretation: Glucose control using the CamAPS FX algorithm with SMA was non-inferior to its use with CC in youth and young adults with type 1 diabetes.

Trial registration: ClinicalTrials.gov NCT05481034.

Funding: The study was supported by the Swiss Diabetes Foundation and by a YTCR grant from the Bangerter-Rhyner Foundation and the Swiss Academy of Medical Sciences. Dexcom and Ypsomed provided product support.

Aims/hypothesis: We aimed to: (1) externally validate the five-item Hypoglycaemia Awareness Questionnaire (HypoA-Q) impaired awareness subscale (HypoA-Q IA); (2) examine how impaired awareness of hypoglycaemia (IAH) relates to the risk of severe hypoglycaemia and level 2 hypoglycaemia; and (3) identify factors associated with IAH.

Methods: Nationwide survey of T1D Exchange registrants was conducted to collect data on demographics, 6 month severe-hypoglycaemia history, hypoglycaemia awareness status (via HypoA-Q IA, the Gold instrument and the Clarke instrument) and continuous glucose monitor (CGM) measures. The Clarke hypoglycaemia awareness factor (Clarke-HAF) was calculated to exclude severe-hypoglycaemia history items. Analyses included Cronbach's α, Spearman correlations and logistic regression.

Results: Valid survey responses were collected from N=1580 adults with type 1 diabetes (median age, 44 years; 52% female participants; median HbA_1c, 48 mmol/mol [6.5%]). Of these, 94% of participants were using CGMs and 69% were using hybrid closed-loop (HCL) systems; 30% had at least one severe-hypoglycaemia episode in the past 6 months. The HypoA-Q IA had satisfactory internal reliability (α=0.79) and construct validity. Higher HypoA-Q IA scores were independently associated with greater risk of severe hypoglycaemia (p<0.001), performing comparably to the Gold instrument and the Clarke-HAF instrument. HypoA-Q IA-determined IAH was independently associated with 88% higher odds of developing severe hypoglycaemia (p<0.001) and twofold higher odds for spending ≥1% of time in level 2 hypoglycaemia (p=0.011). Higher age and longer diabetes duration were associated with higher IAH risk (p<0.001). CGM and HCL use was associated with lower IAH risk (p<0.001).

Conclusions/interpretation: The HypoA-Q IA is a brief, valid and reliable tool for assessing IAH in today's technology-oriented era. IAH was independently associated with severe hypoglycaemia and level 2 hypoglycaemia in a cohort with high prevalence of advanced diabetes technology use and HbA_1c within the recommended range. CGM and HCL use was related to lower IAH risk.

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