Journal of Diabetes Investigation最新文献

This review highlights the significance of the Japan Diabetes Complications Study (JDCS), one of the earliest large-scale studies of people with type 2 diabetes outside Europe and the United States, in understanding type 2 diabetes mellitus among East Asian populations, particularly in Japan. Historically, large-scale clinical studies on type 2 diabetes mellitus have predominantly focused on Western populations, despite East Asians comprising the largest proportion of diabetic patients globally. The JDCS, which was initiated in 1996, enrolled 2,033 Japanese type 2 diabetes mellitus patients. It aimed to evaluate the effects of intensive lifestyle interventions on diabetic complications. The study demonstrated that lifestyle-focused interventions significantly reduced the risk of stroke and other complications compared to conventional treatment. Key findings of its sub-analyses include the unique characteristics of Japanese patients with type 2 diabetes mellitus, such as their lower body mass index (BMI) compared to Western counterparts and a stronger association between even modest BMI increases and beta cell dysfunction. Additionally, the JDCS provided insights into the risk factors for nephropathy, retinopathy, and macrovascular complications, emphasizing the importance of controlling blood pressure, glycemia, and lifestyle factors. The study also explored the impact of diet, exercise, and mental health on diabetic outcomes, revealing the protective effects of physical activity and a balanced diet, while highlighting the risks associated with high salt intake and depression. A risk prediction model tailored to Japanese patients was also developed. Overall, this study made a significant contribution to the evidence-based management of type 2 diabetes mellitus in East Asia.

Background: The relationship between the systemic immune-inflammatory index (SII) and the prognosis of cardiovascular disease (CVD) patients with diabetes or prediabetes remains uncertain. This study investigated the association between baseline SII and all-cause and cardiovascular mortality in American adults with CVD and diabetes or prediabetes.

Methods: Our survey included 4,060 adults with cardiovascular disease and diabetes or prediabetes from the National Health and Nutrition Examination Survey (1998-2020). Using restricted cubic splines (RCS) based on Cox regression models and a two-piecewise Cox proportional hazards model for both sides of the inflection point, we elucidated the nonlinear relationship between baseline SII and mortality. Mediation analysis was used to explore the indirect impact of SII on mortality through eGFR.

Results: In the median 129 months of follow-up, 620 people died from cardiovascular causes and 1,800 from all causes. In the CVD population with diabetes or prediabetes, SII showed a U-shaped relationship with all-cause mortality. The association between SII and CVD mortality was nonlinear and J-shaped. Stratified and interaction analysis confirmed the stability of the core results. Notably, eGFR partially mediated the association between SII and both all-cause and cardiovascular mortality by 9.4% and 6.9%, respectively.

Conclusions: SII revealed a U-shaped relationship with all-cause mortality (inflection point: lnSII = 6) and a J-shaped association with CVD mortality (inflection point: lnSII = 5.73) in CVD patients with diabetes or prediabetes among American patients. Thus, assessing the SII index may offer valuable insights into risk assessment and prognosis in patients with CVD who are diabetic or prediabetic.

Background: Constipation is a common complication in type 2 diabetes mellitus (T2DM), yet its impact on mortality remains unclear. This study aimed to investigate the association between constipation and all-cause mortality in patients with T2DM.

Methods: We conducted a retrospective cohort study using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2010. Mortality outcomes were ascertained through linkage to National Death Index records until December 31, 2019. The association between constipation and all-cause mortality was assessed using weighted Cox proportional hazards regression models. Kaplan-Meier curves were then employed to visualize survival probabilities. Effect modification was explored through stratified analyses and interaction tests.

Results: Of 1,339 participants with T2DM, 146 (10.90%) reported constipation. During a median follow-up of 10.75 years, 411 deaths occurred (57 in the constipation group, 354 in the non-constipation group). Fully adjusted weighted Cox regression analysis revealed that constipation was associated with increased all-cause mortality (HR 1.50, 95% CI 1.01-2.22, P = 0.04). Kaplan-Meier analysis demonstrated a significantly lower survival probability in patients with constipation (log-rank P < 0.05). Stratified analyses and interaction tests corroborated these findings across various subgroups.

Conclusions: Constipation is associated with elevated all-cause mortality risk in T2DM patients. These findings suggest that constipation management may be an important consideration in improving long-term outcomes for individuals with T2DM.

Aims: Diabetic chorea refers to sudden involuntary movements developing in people with diabetes mellitus and is known to occur mainly in those with severe hyperglycemia. We conducted a questionnaire survey of case-reporting facilities in Japan to elucidate their clinical characteristics.

Methods: We searched the PubMed and Ichushi databases for case reports published from January 1, 2012, to December 31, 2017, using "diabetes" and "chorea" as keywords, and sent a questionnaire to the reporting institutions.

Results: Data from a total of 64 cases were included in this study. While most cases had severe hyperglycemia at the onset of diabetic chorea, hypoglycemia/improvement of the plasma glucose served as the trigger for the symptom in 14 cases (21.9%). The Early Remission Group (≤6 months) consisted of 39 cases (60.9%), while the Prolonged Partial Remission Group (>6 months) included 25 cases (39.1%). In the Prolonged Partial Remission Group (>6 months), there were more cases with widespread involuntary movement symptoms, a higher number of cases exhibiting typical imaging findings, and a greater incidence of chorea onset after the initiation of antidiabetic treatment, including hypoglycemia.

Conclusions: Most reported cases of diabetic chorea in Japan were elderly persons with type 2 diabetes mellitus and severe hyperglycemia, although there were also some cases in which the symptom developed in the setting of hypoglycemia. It has been suggested that rapid plasma glucose correction and hypoglycemia might be associated with the risk of development and prognosis of diabetic chorea.

Aims/introduction: Diabetic foot ulcer (DFU) is a prevalent complication of diabetes characterized by heightened inflammation and impaired wound-healing processes. Interleukin-37 (IL-37) is a natural suppressor of innate inflammation. Here, we aim to investigate the potential of IL-37 in enhancing the healing process of diabetic wounds.

Materials and methods: The skin samples of DFU and non-diabetic patients during foot and ankle orthopedic surgery were collected. The IL-37 transgenic mice (IL-37Tg) were created using CRISPR/Cas-mediated genome engineering. Mice were administered streptozotocin (STZ, 150 mg/kg) to induce a diabetic model. After 4 weeks, an equidistant full-thickness excisional wound measuring 8 mm was created on the central back of each mouse and allowed to heal naturally. Body weight and blood glucose levels were measured weekly. The wound area was measured, and skin samples were collected on Day 10 for further Quantitative polymerase chain reaction (qPCR) and WB detection and RNA sequencing analysis.

Results: The proinflammation cytokines such as TNF-α and IL-1β and the MAPK signaling pathway were significantly increased in the wound margin of DFU patients. Compared with diabetic mice, diabetic IL-37Tg mice showed a significantly accelerated healing process. The enriched signaling pathways in RNA sequencing included cytokine-cytokine receptor interaction, TNF signaling pathway, and NOD-like receptor signaling pathway. Through QPCR and WB detection, we found that IL-37 could inhibit the activated MAPK and NOD-like signaling pathway, reducing TNF-α, IL-1β, and NLRP3 expression in the diabetic wound.

Conclusions: IL-37 promotes skin wound healing in diabetic mice, providing a new possible target for treating diabetic wounds.

Aims/introduction: This study aimed to evaluate and compare the effectiveness of oral semaglutide after adding to or switching from incretin-related drugs by assessing the changes in HbA1c and body weight (BW) in participants with type 2 diabetes in clinical settings.

Materials and methods: A total of 368 participants were divided into groups according to antidiabetic medications before oral semaglutide treatment; incretin-related drug-naïve (naïve), switching from dipeptidyl peptide-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonist (GLP-1 RA) groups. Adjusted mean changes in HbA1c and BW at 6 months after oral semaglutide administration were compared among the three groups. Similar analyses were performed in the GLP-1 RAs group between GLP-1RAs before switching.

Results: Mean change of HbA1c in DPP-4i and GLP-1 RA groups was -0.67% (95% confidence interval [CI]: -0.79 to -0.54) and -0.13% (95% CI: -0.40 to 0.15), respectively, which were significantly smaller than incretin-related drug-naïve group; -0.85% (95% CI: -1.08 to -0.62). Mean change in BW between the naïve and DPP-4i groups had no differences; however, these changes were lower in the GLP-1 RA group than in the naïve group. Mean change in HbA1c between pretreatment with GLP-1 RAs had no differences; however, the mean change in BW in the dulaglutide group was significantly higher than that in the injectable semaglutide group.

Conclusion: Oral semaglutide reduced HbA1c levels and BW after adding or switching from other incretin-related drugs in Japanese participants with type 2 diabetes.

Introduction: Obstructive sleep apnea (OSA) is characterized by a complete or partial obstruction of the upper airway, along with hypoxemia, microarousals, and sleep fragmentation. Compelling evidence has clarified a bidirectional correlation between OSA and diabetes mellitus (DM). This paper was to assess the link between OSA and DM via meta-analysis, consisting of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).

Materials and methods: Four databases (PubMed, Cochrane Library, Embase, and CNKI) were screened from inception to March 2024 for observational studies of OSA and DM, including case-control studies and cohort studies. Bidirectional associations between OSA and DM were analyzed, consisting of T1DM and T2DM. Random-effect models were employed to determine the pooled odds ratio (OR) and 95% confidence intervals (CIs) to compare prevalence. Traditional subgroup analyses were implemented. Review Manager 5.3 and Stata 16.0 were utilized for data analyses.

Results: Thirty-five studies were enrolled, including 12 prospective cohort studies, 4 retrospective cohort studies, and 19 case-control studies. DM prevalence was notably higher in OSA patients than in non-OSA patients (OR: 2.29, 95% CI: 1.93-2.72), and OSA prevalence was notably higher in DM patients than in non-DM patients (OR: 2.12, 95% CI: 1.73-2.60). Subgroup analysis uncovered that DM prevalence in the OSA population was more significant in the group <50 years (OR: 3.28, 95% CI: 2.20-4.89) and slightly decreased in the group >50 years (OR: 1.82, 95% CI: 1.38-2.40).

Conclusions: The meta-analysis reveals a bidirectional link between OSA and DM.

Aim and introduction: Diabetes and prediabetes pose significant global public health challenges. Sex steroids, particularly testosterone and estradiol, play crucial roles in various metabolic processes. This study investigates the relationship between sex hormone levels and long-term mortality in adults with prediabetes and diabetes, as well as those without glucose intolerance.

Material and methods: This retrospective cohort study utilized data from the NHANES 2013-2016, including adults aged 50-79 across prediabetic, diabetic, and non-diabetic groups. Serum testosterone, estradiol, and their ratios (T/E) were analyzed. The primary outcomes were all-cause mortality and CVD mortality tracked until December 2019. Cox regression models estimated the associations between hormone levels and mortality risks.

Results: The study included 3,665 participants (male: 2,140; female: 1,775). In males with prediabetes, higher estradiol (adjusted hazard ratio [aHR] = 0.17, 95% confidence interval [CI]: 0.07-0.43) or testosterone (aHR = 0.39, 95% CI: 0.31-0.50) was significantly associated with lower risk of all-cause mortality. Higher estradiol (aHR = 0.12, 95% CI: 0.04-0.32) or testosterone (aHR = 0.36, 95% CI: 0.27-0.48) was significantly associated with lower CVD mortality risk. In females with diabetes, there was a significant association between higher estradiol levels (aHR = 0.22, 95% CI: 0.06-0.83) or T/E ratio (aHR = 0.18, 95% CI: 0.04-0.73) with a reduced all-cause mortality risk.

Conclusions: This study identifies some novel associations between estradiol, testosterone, and their ratios with long-term mortality in men and women across different glycemic statuses. These findings suggest a potential protective role of sex hormones in individuals with altered glucose metabolism, with gender difference, warranting further investigation.

Objective: This ACTION-IO sub-analysis compared attitudes of people with obesity (PwO) and healthcare professionals (HCPs) between South Korea/Japan and global.

Methods: Responses from overall (body mass index [BMI] ≥ 25 kg/m²) and higher BMI (30.0-34.9 kg/m²) groups were compared descriptively; t-and z-tests were used to test for statistical significant difference.

Results: Total responses from South Korea/Japan vs global were as follows: overall (PwO: 3,501 vs 14,502; HCPs: 502 vs 2,785); higher BMI (PwO: 530 vs 7,460) groups. Compared to global, more South Korea/Japan-PwO considered improving existing health condition as top weight loss (WL) goal (overall: 37% vs 28%, higher BMI: 35% vs 26%; P < 0.05) and fear of weight regain as top WL barrier (overall: 52% vs 45%, higher BMI: 65% vs 42%; P < 0.05). Fewer South Korea/Japan-PwO reported discussing weight (overall: 25% vs 51%, higher BMI: 31% vs 54%; P < 0.05). More South Korea/Japan-HCPs felt PwO as themselves responsible for WL (74% vs 55%; P < 0.05). More than two-of-three South Korea/Japan-HCPs (vs four-of-five global) were motivated to help PwO in WL.

Conclusions: South Korea/Japan PwO had differences in their attitudes and behaviors toward obesity care. These findings support the need for increased public awareness of obesity as a disease and for HCPs to play active role initiating weight management dialogue.

Background: The prevalence of type 2 diabetes (T2D) and obesity are increasing in the United States. However, population-level data for mortality trends due to T2D and obesity are limited. This study aims to assess these death trends among adults in the United States categorized by sex, race, and geographical location.

Methods: We queried the CDC-WONDER database for multiple cause of death data of adults aged ≥25 years. The crude mortality rates (CMR), age-adjusted mortality rates (AAMRs), annual percent change (APC), and the average APC (AAPC) along with a 95% confidence interval (CI) were analyzed.

Results: From 1999 to 2022, a total of 88,597 T2DM and obesity-related deaths were recorded in the United States. The AAMR consistently increased from 1999 to 2017 (APC: 7.64; 95% CI: 1.91-9.96), followed by a marked rise from 2017 to 2022 (APC: 20.13; 95% CI: 12.88-38.57). The AAMR was approximately 3.58 times higher during the COVID-19 pandemic compared to the period from 1999 to 2019. The AAMR for males was consistently greater than that for females. The highest AAMR was observed in non-Hispanic (NH) Blacks or African Americans, followed by NH White, Hispanic or Latino, and other NH populations. Rural areas (AAMR: 1.86, 95% CI: 1.83-1.89) exhibited a greater AAMR than urban regions 1.26 (95% CI: 1.25-1.27).

Conclusions: Our results indicate a substantial increasing trend of T2D and obesity-related deaths in the United States especially during the COVID-19 pandemic.