Diabetic Medicine最新文献

Background and aims: Impaired glucose intolerance (IGT) and impaired fasting glucose (IFG) are totally different. Lifestyle modification is effective in moving from prediabetes to normoglycaemia. There is a lack of information showing the effect of lifestyle modification according to each prediabetes and assessing its effect on the degree of reversibility to normoglycaemia and on cardiometabolic markers.

Methods and results: We searched for randomized controlled trials (RCT) that enrolled individuals with IGT or IFG. Meta-analysis was performed to compare the proportion of subjects progressing to type 2 diabetes mellitus (T2DM); proportion reversing to normoglycaemia and mean differences in glucose level and cardiometabolic parameters. Thirty-six RCTs were included. The proportion of subjects progressing from impaired glycaemia to T2DM was higher among those with IGT (16.3% vs. 10.9%), whereas reversion to normoglycaemia was higher in subjects with IFG (27.2% vs. 24.8%). The effect of lifestyle modification on glucose level was significant on those with IFG (mean difference [MD] = -1.56 mg/dL, 95% CI: -2.71, -0.40), but not on those with IGT of (MD = 1.47 mg/dL, 95% CI: -1.33, 4.28).

Conclusion: Diverse lifestyle modification interventions improved glucose levels in people with IFG, but not in those with IGT. Our findings imply that different non-pharmacological interventions are warranted for IGT and IFG.

Suggested mechanisms for an association between early life adversity and worse glycaemic control.

Aim: Several wordings of the definition of severe hypoglycaemia (SH) exist. This study aims to evaluate how different SH definition wordings affect SH history assessment.

Methods: In this cross-sectional study, surveys were emailed to registrants of the T1D Exchange, a U.S. national type 1 diabetes patient registry. Participants' demographic information was collected. Six-month SH history was evaluated with questionnaires including SH definition wordings from either (1) professional societies, (2) a diabetes community website, or (3) a hypoglycaemia research questionnaire. Analyses included the McNemar test, pairwise Wilcoxon signed-rank test, logistic regression analysis, Kappa statistics, and Spearman correlation.

Results: A total of 1580 valid responses were obtained from participants (52% female; mean ± SD age: 46 ± 15 years; 95% White; mean ± SD diabetes duration: 25 ± 16 years). Questionnaires with four different SH definition wordings yielded significant variations in the prevalence of SH (i.e., having developed at least one episode of SH) and the number of SH episodes: the ADA/ENDO 2013 definition wording yielded the highest results on both metrics, whereas HypoA-Q and ADA 2023 yielded the lowest. Among participants reporting at least one SH episode, the number of episodes identified with the different SH definition wordings was poorly correlated (R_s: 0.09-0.37; p < 0.001). Race, education level, and household income were associated with higher odds of discrepancies in SH history (p < 0.05).

Conclusion: This U.S. national survey with individuals living with type 1 diabetes demonstrated significant discrepancies in SH history when assessed with different SH definition wordings. Race and socioeconomic status were associated with these discrepancies.

Type 2 diabetes (T2D) is a complex condition characterised by the interaction between insulin resistance and beta cell dysfunction. C-peptide, a key biomarker of endogenous insulin secretion, has a role in diagnosing type 1 diabetes (T1D). However, its utility in T2D has not been extensively studied. This review provides an overview of the progression of C-peptide levels over time in T2D and discuss its interpretation in clinical settings. We reviewed current evidence on the relationship between C-peptide levels and response to antidiabetic drugs, as well as the utility of C-peptide testing in T2D treatment strategies. We also reviewed available evidence for C-peptide in predicting future outcomes in T2D. In this review, we hoped to clarify the value of C-peptide testing in understanding and managing T2D and to highlight areas where further research is needed.

Aim: Time-restricted eating (TRE) limits the time for food intake to typically 6-10 h/day without other dietary restrictions. The aim of the RESET2 (the REStricted Eating Time in the treatment of type 2 diabetes) trial is to investigate the effects on glycaemic control (HbA_1c) and the feasibility of a 1-year TRE intervention in individuals with overweight/obesity and type 2 diabetes. The aim of the present paper is to describe the protocol for the RESET2 trial.

Methods: RESET2 is a randomised, controlled, parallel-group, open-label trial. One hundred and sixty individuals with type 2 diabetes (HbA_1c >53 mmol/mol (>7.0%)), and Body Mass Index ≥25 kg/m² will be randomised to standard care plus TRE, or to standard care and habitual living. Both the intervention and control group will follow standard diabetes care including regular clinical visits 3-4 times/year. The intervention is divided into two periods: (1) a 3-month TRE period with a fixed eating window with a self-selected timing to obtain data from the participants' experiences with TRE and (2) a 9-month individually adjusted TRE period. Participants in the TRE group will be instructed to reduce their eating window by a minimum of 3 h/day compared to the habitual eating window and with an eating window of 8-10 h/day. Test days will be scheduled at baseline, after 3 months and after 1 year. The primary outcome is HbA_1c (evaluated 3 months and 1 year after randomisation) and secondary outcomes are body weight, fat mass, continuous glucose monitoring derived time-in-range and use of antidiabetic medicine (evaluated 1 year after randomisation). Additionally, we will conduct a process evaluation to assess whether the TRE intervention functioned as hypothesised.

Maturity onset diabetes of the young (MODY) is a highly heterogeneous monogenic disease that occurs due to β-cell dysfunction. It is divided into different types depending on the gene mutated, and a total of 16 genes have been found to be associated with MODY. However, due to the current lack of understanding of monogenic diabetes, 90% of MODY is currently misdiagnosed and ignored in clinical practice. In this paper, we report the clinical data of a patient diagnosed with diabetes. Genetic testing revealed a novel BLK heterozygous mutation (c.363G>A) in the patient and in his father and son. He had no islet-specific autoantibodies and showed a reduced meal-induced response of insulin. Precise diagnosis of MODY individuals is important to the treatment.

Aims: Diabetes distress (DD) is prevalent among people with diabetes. While automated insulin delivery systems (AIDs) improve glycaemic control, their impact on DD is unclear. We aimed to investigate the effect of AIDs on DD in people with diabetes and their caregivers.

Methods: We focused on people with diabetes using AIDs versus other insulin delivery systems, with DD as the outcome. We included randomised controlled trials (RCTs), before-after studies (BAS) and observational studies until 4 April 2024. After screening, 40 studies were included in the systematic review, comprising 5426 participants (3210 adults, 1131 paediatric and 1085 caregivers). Twenty-seven studies were selected for the meta-analysis (focusing solely on type 1 diabetes). We used random effects models by population and study design. We also conducted a subgroup analysis by age group (children vs. teenagers).

Results: In adults, eight BAS and five RCTs indicated a significant small DD reduction post-AID initiation (standardised mean difference [95% confidence intervals] -0.32 [95% CI: -0.40, -0.24] and [-0.19 (-0.27, -0.11)]). No significant changes were observed in the paediatric population. In caregivers, eleven BAS and five RCTs indicated a significant moderate DD reduction (-0.48 [95% CI: -0.78, -0.18] and (-0.22 [-0.38, -0.06])). Subgroup analysis revealed an increased benefit in parents of children compared to parents of teenagers.

Conclusions: This work suggests that AIDs is associated with a DD reduction in adults and caregivers but not in children/teenagers with type 1 diabetes. More longitudinal studies and better systematic DD assessments are needed.

Aims: Acute hypoglycaemia promotes pro-inflammatory cytokine production, increasing the risk for cardiovascular events in diabetes. AMP-activated protein kinase (AMPK) is regulated by and influences the production of pro-inflammatory cytokines. We sought to examine the mechanistic role of AMPK in low glucose-induced changes in the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF), which is elevated in people with diabetes.

Methods: Macrophage cell line Raw264.7 cells, primary macrophage bone marrow-derived macrophages obtained from wild-type mice or AMPK γ1 gain-of-function mice, were used, as were AMPKα1/α2 knockout mouse embryonic fibroblasts (MEFs). Allosteric AMPK activators PF-06409577 and BI-9774 were used in conjunction with inhibitor SBI-0206965. We examined changes in protein phosphorylation/expression using western blotting and protein localisation using immunofluorescence. Metabolic function was assessed using extracellular flux analyses and luciferase-based ATP assay. Cytokine release was quantified by enzyme-linked immunosorbent assay (ELISA). Oxidative stress was detected using a fluorescence-based reactive oxygen species (ROS) assay, and cell viability was examined using flow cytometry.

Results: Macrophages exposed to low glucose showed a transient and modest activation of AMPK and a metabolic shift towards increased oxidative phosphorylation. Moreover, low glucose increased oxidative stress and augmented the release of macrophage MIF. However, pharmacological activation of AMPK by PF-06409577 and BI-9774 attenuated low glucose-induced MIF release, with a similar trend noted with genetic activation using AMPKγ1 gain-of-function (D316A) mice, which produced a mild effect on low glucose-induced MIF release. Inhibition of NFĸB signalling diminished MIF release and AMPK activation modestly but significantly reduced low glucose-induced nuclear translocation of NFĸB.

Conclusions: Taken together, these data indicate that pharmacological AMPK activation suppresses the release of MIF from macrophages caused by energy stress, suggesting that AMPK activation could be a useful strategy for mitigating hypoglycaemia-induced inflammation.