Journal of Diabetes Investigation最新文献

Neonatal diabetes mellitus (NDM) is a monogenic condition diagnosed <6 months of age with >40 genetic causes. International guidelines recommend referral for genetic testing immediately after diagnosis since the genetic result guides clinical management. We used next-generation sequencing to identify a homozygous pathogenic variant, p.(Arg244*), in COQ9 in 2 individuals referred for NDM testing. Both had insulin-treated hyperglycemia, severe structural brain defects, dysmorphic features, and lactic acidosis. Recessive loss-of-function variants in COQ9 cause Coenzyme Q10 deficiency-5, a multi-system mitochondrial disease, with 7 cases reported. Neonatal hyperglycemia has not been reported in any of these cases but has been described for two other Coenzyme Q10 disorders caused by variants in COQ2 and COQ4. Our report shows that individuals with COQ9-related disease can present with neonatal hyperglycemia, expanding the clinical spectrum of this disorder. We recommend the inclusion of COQ9, as well as COQ2 and COQ4, to gene panels used for NDM testing.

Aims: Recent advancements in plasma lipidomes genome-wide association studies data have enhanced our understanding of lipid categories, significantly improving risk assessments for metabolic dysfunction-associated fatty liver disease (MAFLD) beyond traditional lipid biomarkers.

Materials and methods: This study utilized Mendelian randomization (MR) to assess the causal relationships between 179 lipid species across 13 subclasses and MAFLD, primarily using the Wald ratio and IVW methods. Corrections were made using false discovery rate (FDR), supplemented by Bayesian colocalization analysis.

Results: Elevated levels of genetically predicted phosphatidylcholine (16:0_16:1) [OR_{Wald ratio} = 2.638, 95% CI 1.557-4.469, P = 3.11 × 10^-4], phosphatidylcholine (16:1_18:0) (OR_{Wald ratio} = 2.644, 95% CI 1.559-4.486, P = 3.11 × 10^-4), triacylglycerol (46:2) (OR_{Wald ratio} = 2.515, 95% CI 1.524-4.153, P = 3.11 × 10^-4), and triacylglycerol (48:2) (OR_IVW = 1.863, 95% CI 1.300-2.669, P = 6.95 × 10^-4) were significantly associated with increased MAFLD risk, with rs1260326 within the GCKR gene playing a crucial role. Colocalization analysis indicated that in significant evidences, the posterior probability for hypothesis 4 was over 80%, identifying rs780093 as a shared causal variant. Additionally, 16 suggestive evidences were identified.

Conclusion: The study confirmed the significant role of specific lipid molecules in influencing MAFLD risk, providing new scientific bases and potential therapeutic targets for future treatment strategies.

Aims: In Japan, type 1 diabetes (T1D) is classified into three subtypes based on its onset patterns; however, the proportion of each subtype remains unexplored. To elucidate the heterogeneity in adult-onset type 1 diabetes, we compared the frequencies of subtypes and clinical features by age at onset.

Materials and methods: This cross-sectional, observational, single-institution study included 482 individuals (161 male) with T1D. The clinical and laboratory data, including glutamic acid decarboxylase autoantibodies, were extracted from the medical records.

Results: The number of adults who developed T1D decreased with age. Among all patients, 62% (n = 299) had acute-onset T1D, 27% (n = 131) had slowly progressive T1D (SPIDDM), and 11% (n = 52) had fulminant T1D. The proportion of patients with fulminant T1D was approximately equivalent in all age groups; however, the percentage of patients with acute-onset T1D decreased from 78% in the 20-29 age group to 27% in the 70-79 age group. The proportion of patients with SPIDDM significantly increased with age, ranging from 16% in the 20-29 age group to 60% in the 70-79 age group. Among patients with SPIDDM, the prevalence of definite SPIDDM was 89%, and this prevalence did not differ based on the age at onset. Body mass index and C-peptide levels among patients with probable SPIDDM were significantly higher than those among patients with definite SPIDDM.

Conclusions: The proportion of adult-onset T1D subtypes differed according to the age at onset. In adult-onset T1D, some etiological differences may be based on age at onset.

Aims: This study conducts a comprehensive analysis of the relative impact of risk factors for diabetic nephropathy (DN) during disease progression, with a particular emphasis on the role of gut microbiota. We developed multiple predictive models trying to enhance the early identification of high-risk patients in clinical practice.

Materials and methods: We collected data from type 2 diabetes mellitus patients, categorizing them by renal function for comparison. Logistic regression identified risk factors for DN, and we developed nomogram and random forest risk prediction models. Finally, we analyzed the correlations among these factors.

Results: Compared to patients with diabetes alone, those with DN have a longer disease duration, characterized by abdominal obesity, hypertension, chronic inflammation, activation of the complement system, and declining renal function, along with a significant reduction in Bifidobacterium and Enterobacterium. Patients with macroalbuminuria exhibit a higher male prevalence, as well as elevated blood pressure and lipid levels, and poorer renal function. Increased waist-to-hip ratio, systolic blood pressure, urea, neutrophil-to-lymphocyte ratio, and complement C3, along with decreased Enterobacterium and albumin, have been identified as significant risk factors for DN. The nomogram model developed based on these findings demonstrates good predictive capacity. And the establishment of the random forest model further underscores the importance of the aforementioned indicators. Additionally, significant correlations were observed among obesity, inflammation, blood pressure, lipid levels, and gut microbiota.

Conclusions: Dysbiosis, metabolic disorders, and chronic inflammation play key roles in the progression of DN and may serve as new targets for future prevention and treatment strategies.

Aims/introduction: Ginsenoside Rg1 is an active ingredient found mainly in ginseng that has a variety of pharmacological effects, such as hypoglycemic, antioxidant, and anti-inflammatory effects, and it inhibits vascular formation. In this study, we explored the effect of ginsenoside Rg1 on angiogenesis in diabetic retinopathy (DR) on the basis of its ability to inhibit angiogenesis and the specific molecular mechanism involved.

Materials and methods: We induced an in vivo model of diabetes by injection of 55 mg/kg streptozotocin (STZ) into the abdominal cavity of SD rats daily for 3 days. Moreover, human retinal microvascular endothelial cells (HRMECs) were treated with 30 mmol/L glucose for 24 h to construct a high-glucose (HG) cell model in vitro. The expression of related genes and proteins was detected by RT-qPCR and Western blotting. HRMECs and retinal damage were evaluated by CCK-8, scratch, tube formation assays, and HE staining.

Results: In this study, Rg1 inhibited HG-induced angiogenesis of HRMECs and inhibited STZ-induced vascular leakage and capillary degeneration in vivo, alleviating the progression of DR. Mechanistically, Rg1 upregulated the expression of FBXW7 by inhibiting miR-100-3p, thereby promoting the ubiquitination and degradation of c-MYC, inhibiting HG-induced HRMECs proliferation, migration, invasion, and angiogenesis, and improving the development of DR.

Conclusions: Overall, our study demonstrates that ginsenoside Rg1 can inhibit DR angiogenesis via the miR-100-3p/FBXW7/c-MYC molecular axis. These findings provide a novel idea for the treatment of DR and provide an experimental basis for further research on the application of Rg1 in the treatment of DR.

Aims/introduction: To investigate the predictive value of the biliverdin reductase-A (BVR-A) and the homeostasis model assessment for insulin resistance (HOMA-IR) on mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus, and to establish a nomogram model.

Materials and methods: This study included 140 patients with type 2 diabetes mellitus. Based on Montreal Cognitive Assessment (MoCA) scores, participants were categorized into the normal cognitive function (T2DM-NCF) group (65 cases) and the mild cognitive impairment (T2DM-MCI) group (75 cases). Multivariate logistic regression analysis was performed to identify the factors associated with MCI in patients with type 2 diabetes mellitus. A nomogram prediction model was developed using R software for the selected factors, and its predictability and accuracy were verified.

Results: Compared with the T2DM-NCF group, subjects with MCI were older, had a longer duration of diabetes, higher HOMA-IR, lower BVR-A, lower cognitive scores, and lower education levels (all P < 0.05). Multivariate logistic regression analysis showed that duration of diabetes (OR = 1.407, 95% CI: 1.163-1.701), HOMA-IR (OR = 1.741, 95% CI: 1.197-2.53), and BVR-A (OR = 0.528, 95% CI: 0.392-0.712) were significantly associated with the development of MCI in patients with type 2 diabetes mellitus. The C-index of the nomogram was 0.863 (95% CI: 0.752-0.937).

Conclusions: Our findings suggest that BVR-A and HOMA-IR are significantly associated with the development of MCI in patients with type 2 diabetes mellitus. The nomogram incorporating BVR-A and HOMA-IR aids in predicting the risk of developing MCI in these patients.

Aim: Subclinical diabetic peripheral neuropathy (sDPN) in patients with type 2 diabetes mellitus is insidious, but has been complicated with neurological damage. The aim of this study was to investigate the association between brachial-ankle pulse wave velocity (baPWV) and sDPN in patients with type 2 diabetes mellitus, and to provide reference for clinical prevention and treatment of sDPN.

Materials and methods: From November 2021 to May 2024, a total of 711 type 2 diabetes mellitus patients without symptoms and signs of peripheral nerve damage were recruited. According to whether the nerve conduction velocity (NCV) was abnormal or not, they were divided into the sDPN group and the non-diabetic peripheral neuropathy (non-DPN) group. Logistic regression model, restricted cubic spline (RCS) analysis and subgroup analysis were used to evaluate the correlation between baPWV and sDPN.

Results: A total of 204 (28.69%) of the 711 participants were diagnosed with sDPN. Both amplitude and conduction velocity were negatively correlated with baPWV. In the fully adjusted model, elevated baPWV levels were significantly associated with an increased sDPN risk, with odds ratio (OR) = 1.084, 95% confidence interval (CI): (1.023, 1.148), P = 0.006. RCS showed a linear association between baPWV and sDPN. Subgroup analysis further confirmed that the positive association between baPWV and sDPN was consistent and robust across groups.

Conclusions: Our study indicates a pronounced link between higher baPWV and increased risk of sDPN among type 2 diabetes mellitus patients without symptoms and signs of peripheral nerve damage. These findings underscore the importance of baPWV for early identification of sDPN.

Aims/introduction: As the prevalence of diabetes increases with age, the number of elderly patients with diabetes in Japan, a super-aged society, continues to increase. We conducted a survey to investigate the extent to which outpatients with diabetes recognize dementia as a complication of diabetes.

Materials and methods: A questionnaire was distributed among 777 patients with diabetes to investigate their awareness of dementia and its risk factors. Among these, the Mini-Mental State Examination was also administered to patients over 65 years of age who wished to undergo a cognitive function test among those who participated in the questionnaire survey to examine the factors leading to a decline in cognitive function.

Results: 458 patients selected poor blood glucose control and 176 selected hypoglycemia as the condition that rendered patients susceptible to dementia. Regarding the risk factors for suspected cognitive decline, the risk increased in the following order: old age; lack of knowledge about dementia; and treatment with diet/exercise, oral hypoglycemic agents/Glucagon-like peptide-1, and insulin. Regarding the relationship between cognitive decline and blood glucose control, the risk of suspected cognitive decline increased in the following order: within the standard value, above and below the standard values, in terms of the level of glycated hemoglobin set in "Blood Glucose Control Target for Elderly Diabetes" defined by the Japan Geriatrics Society and the Japan Diabetes Society.

Conclusions: When examining and treating diabetes, it may be pertinent to instruct older adults on target HbA1c levels based on their condition.