Diabetology International最新文献

Metabolic-dysfunction-associated fatty liver disease (MAFLD) or metabolic-dysfunction-associated steatotic liver disease (MASLD) has been recognised as one of the most important aetiologies of chronic liver disease and also a marker of high risk for atherosclerotic cardiovascular disease (ASCVD) in patients with or without diabetes. The presence of diabetes accelerates the progression of MASLD. The pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH) is complex and the diagnostic procedures to assess histologic endpoints in clinical trials are challenging. This poses significant difficulties in the discovery of newer drugs with meaningful efficacy. A comprehensive literature search using MEDLINE (via PubMed), Scopus and Google Scholar databases was performed to write a narrative evidence-based review on the current status of different pharmacotherapies in MASLD. Despite numerous pharmacotherapies being studied, until recently, there was no approved agent for the treatment of MASH. However, some established and few emerging medications have recently shown promising effects in preventing its progression, as evidenced in preclinical and clinical trials. This narrative review summarises the current status, mechanisms, efficacy and safety of established as well as new and emerging pharmacotherapies for treatment of MASH. It also provides a practical approach to the clinical use of these agents.

We encountered a 19-year-old woman who was found to have glucosuria (3+) on urinalysis at school at the age of 11 years and 10 months. She had a three-generation family history of diabetes. She was 150.6 cm tall (+ 0.28 standard deviations (SD)), weighed 50.8 kg (+ 1.0 SD), and did not have obesity or deafness. She had a glycated hemoglobin (HbA1c) of 10.9%, blood glucose of 334 mg/dL, negativity for urine ketones, serum C-peptide concentration of 1.63 ng/mL, and negativity for anti-glutamic acid decarboxylase (GAD) and tyrosine phosphatase-like protein IA-2 (IA-2) autoantibodies. The patient was initially diagnosed with childhood-onset type 2 diabetes mellitus without obesity because she could be weaned off insulin treatment within 1 month. Her HbA1c level was maintained at 6% using diet and metformin for 3 years after, but deteriorated to 9.9% in the 4th year. Subsequently, the oral hypoglycemic regimen was strengthened, but her HbA1c rose even higher. She stopped attending hospital for 19 months, but at the age of 19 years and 11 months, she was urgently admitted to our hospital with diabetic ketoacidosis, when her fasting serum C-peptide concentration had decreased to 0.49 ng/mL. No mutations in maturity-onset diabetes of the young-related genes were identified. She was negative for anti-GAD, IA-2, and zinc transporter 8 antibodies, but positive for islet cell antibody, confirming a diagnosis of slowly progressive type 1 diabetes. Therefore, the type of diabetes present in children and adolescents should be diagnosed with great care and reconsidered according to the clinical course.

Aims: Once-weekly novel insulin preparations such as Icodec and basal insulin Fc (BIF)/insulin Efsitora Alfa have raised hope among clinicians and patients when they were developed and evaluated in a series of clinical trials. However, there were conflicting results regarding their efficacy and safety. This meta-analysis was carried out to evaluate the efficacy and safety of once-weekly insulin in patients with Type 2 diabetes mellitus (T2DM).

Methods: PubMed/MEDLINE, Cochrane database, Scopus, and WHO International Clinical Trials Registry Platform (ICTRP) were searched till November 2024 for randomized controlled trials (RCTs). Our literature search found 2759 articles, out of which 11 studies with 11 reports were included in the meta-analysis as per eligibility criteria.

Results: 5799 participants from 11 RCTs were included. Once-weekly insulin showed significant reduction of HbA1c, and pooled mean difference of once-weekly insulin vs once-daily insulin was - 0.09 (95% CI - 0.16 to - 0.02). Subgroup analysis revealed that Icodec - 0.12 (95% CI - 0.20 to - 0.04) was found to be superior, whereas BIF was found to be non-inferior 0.01 (95% CI - 0.11 to 0.13) compared to once-daily insulin regimen in reduction of HbA1c in T2DM. No significant differences were observed between once-weekly and once-daily insulin for other safety outcomes.

Conclusions: Once-weekly insulin regimen was superior in reducing HbA1c level while maintaining a similar safety profile to the once-daily insulin regimen, thus suggesting that such regimen may potentially be an alternative to the currently established once-daily basal insulin regimen.

Graphical abstract:

Background: Alzheimer's disease (AD) and Type 2 Diabetes Mellitus (T2DM) share overlapping pathophysiological pathways, including metabolic reprogramming, oxidative stress, and impaired cellular homeostasis.

Methods: This review explored the role of metabolism in mediating these processes and its implications for neurodegeneration and metabolic dysfunction in T2DM and AD. A detailed analysis of the current literature was performed using MESH terms on relevant databases (Google Scholar, PubMed, Embase, and Cochrane Library) to systematically observe the causes of cognitive impairment.

Results: Overexpression of Branched Chain Amino Acid (BCAA) is linked to significant disruptions in glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation, leading to reduced acetyl-CoA availability and increased production of reactive oxygen species (ROS). These metabolic disturbances contribute to dysregulated autophagy and the accumulation of amyloid-beta (Aβ) and hyperphosphorylated tau. High glucose levels, characteristic of T2DM, exacerbate Branched Chain Amino T 1-associated dysregulation, amplifying neuronal death and oxidative damage. Interestingly, BCAA supplementation helps counteract certain negative effects by boosting ATP production, indicating a dual role in the progression of the disease. Additionally, the interactions with redox-sensitive enzymes and autophagy pathways further provide evidence of its role in regulating cellular homeostasis.

Conclusion: These findings provide a base for researchers for further research on metabolic pathway modulation, advanced biomarker discovery, precision medicine, targeted antioxidant therapies, and AI-driven predictive modelling. Novel BCAA modulators offer a promising therapeutic direction, potentially bridging the gap between metabolic and neurodegenerative disorders, providing a foundation for innovative interventions in cognitive impairment.

It is well known that the power of low-frequency and high-frequency components of heart rate variability decreases in individuals with diabetes who have diabetic autonomic neuropathy, based on the frequency domain analysis of 24-h electrocardiograph recording. In the present paper, we examined the frequency and power of sinusoidal components within the low-frequency and high-frequency bands using generalized harmonic analysis applied to the R-R interval time series from both individuals with diabetes and healthy controls. In the control group, there were significant differences in frequencies between the first and other components in the low-frequency band. On the other hand, in the individuals with diabetes, there were no significant differences in the component frequencies. In both groups, there were no significant differences in the component frequencies in the high-frequency band. Our present results suggest that diabetes mellitus narrows the frequency band range of the low-frequency component in heart rate variability. This result might help elucidate the mechanism underlying how low-frequency power decreases in individuals with diabetes. Thus, in the spectral analysis of heart rate variability, the use of generalized harmonic analysis enables power calculation differently from traditional methods. We anticipate further diffusion and accumulation of evidence concerning the evaluation of heart rate variability indices using generalized harmonic analysis.

Aims: We investigated changes in eating behavior associated with the administration of tirzepatide and evaluated any changes in diet-related QOL due to tirzepatide.

Methods: The study included 60 outpatients with type 2 diabetes mellitus who had been on tirzepatide for 3 months. The changes in body weight and HbA1c levels of all participants were observed for 3 months following the initiation of tirzepatide treatment. Simultaneously, we conducted a questionnaire survey that included questions on their eating behavior (Eating Behavior Questionnaire) and diet-related quality-of-Life (DDRQOL).

Results: HbA1c levels significantly reduced after the first month of administration from 7.40 ± 1.58% at the start to 6.78 ± 0.99% after 3 months (p < 0.001). Body weight also significantly decreased from 80.7 ± 13.2 kg at the start to 78.3 ± 12.9 kg after 3 months (p < 0.001). The total Eating Behavior Questionnaire score significantly reduced from 52.9 ± 10.9 points to 47.7 ± 9.9 points after 3 months (p < 0.001). There was a strong positive correlation only between the variations of the total score of the Eating Behavior Questionnaire and weight variations (r = 0.363, p = 0.005). Regarding the scores by subscales of DDRQOL, "Satisfaction with diet" changed from 75.3 ± 14.5 points at the start to 73.9 ± 14.8 points after 3 months, showing no significant changes (p = 0.335). "Burden of diet therapy" significantly increased from 50.8 ± 14.9 points to 56.1 ± 15.9 points (p = 0.002), as did "Perceived merits of diet therapy" from 57.9 ± 13.9 points to 61.8 ± 11.2 points (p = 0.035).

Conclusions: Administration of tirzepatide improved eating behavior, leading to increased diet-related QOL and decreased HbA1c levels and body weight.

Background: Cost-effective, noninvasive methods to assess glycemic control can aid Diabetes Mellitus (DM) screening and management. We assess the potential of glycated protein in scalp hair as a surrogate marker for glycemic control. Using a Thiobarbituric Acid (TBA) assay, the effects of various cosmetic treatments on the hair and the mass of samples were measured.

Methods: Anthropometrics, demographics, medical history and HbA1c measurements were collected after obtaining informed consent from 192 participants. About 50 strands of hair, 4 cm long, proximal to the scalp, were clipped and stored at - 20 °C. The fructosamine concentration in the samples was determined using the TBA method and a fructose calibration curve. The strength of the correlation between HbA1c and fructosamine for hair samples with and without hair treatments was assessed using Pearson's R.

Results: 56% of participants had a prior DM diagnosis, 61% were female and were predominantly East Indian (73%). Although no significant correlation between fructosamine and HbA1c was observed for the entire population, for the samples with no reported hair treatments, there was a statistically positive association when the sample mass ranged between 40 and 120 mg. The highest correlation, r(28) = 0.647, p = < 0.001 was observed when hair samples greater than 70 mg were used for the assay.

Conclusion: Hair glycation can be a robust, noninvasive indicator of blood glucose control in optimum conditions. However, sample collection limitations, cumbersome processing, lengthy assays, and the influence of cosmetic treatments limit its usefulness as a screening tool for DM.

Background: Hyperglycemic hyperosmolar syndrome (HHS) is a severe complication of diabetes, and is triggered by infection, use of corticosteroids, non-adherence to medications, and acute diseases. Despite advances in diabetes management, the clinical features and outcomes of patients with HHS remain unclear. This study aimed to investigate the clinical characteristics and prognoses of patients with HHS at a university hospital in Japan.

Methods: This retrospective cohort study analyzed 84 consecutive patients diagnosed with HHS between 2018 and 2023. Patients with HHS were classified into "isolated HHS" and "mixed diabetic ketoacidosis (DKA)/HHS" groups based on established criteria. A subgroup analysis further divided the isolated HHS group into those with and without metabolic acidosis. Clinical data were collected from electronic medical records.

Results: The median age of patients with HHS was 75 years, with infections (51.2%) being the most common trigger. Approximately 70% of patients did not receive diabetes medication. The isolated HHS group had a significantly higher 30-day mortality rate (26.0%) than the mixed DKA/HHS group (0%). In the isolated HHS group, those with metabolic acidosis showed markedly worse outcomes, with a 30-day mortality rate of 54.6% versus 20.7% in those without acidosis.

Conclusion: HHS predominantly affects elderly patients and is often associated with poor diabetes management. The isolated HHS group had a worse prognosis than the mixed DKA/HHS group, and the presence of metabolic acidosis other than ketoacidosis significantly increased mortality. Regular blood glucose monitoring and appropriate diabetes medications are crucial for preventing the development of HHS.