Journal of Diabetes Investigation最新文献

Aims/introduction: We aimed to explore the short-term effects of tofogliflozin on the insulin secretory capacity of people with type 2 diabetes.

Materials and methods: We performed a multicenter, prospective, randomized, active-controlled, open-label, parallel-group comparison study of people with type 2 diabetes aged 20-89 years, with hemoglobin A1c (HbA1c) 6.5%-9.0%, not previously treated with antihyperglycemic agents. The participants were randomly assigned to a group that received 20 mg tofogliflozin per day or a group that received 500 mg metformin per day for 4 weeks. Fasting blood samples were obtained and oral glucose tolerance testing was performed before and after treatment. The changes from baseline to week 4 in glucose tolerance and insulin secretory capacity were compared.

Results: Thirty participants in the metformin group and 35 in the tofogliflozin group completed the study. After 4 weeks, the HbA1c, glycated albumin, and fasting plasma glucose concentrations had significantly decreased in both groups, with no significant differences between the two groups. The fatty liver index improved significantly more in the tofogliflozin group. The disposition index (DI) did not significantly increase in either group, and there was no difference between the groups. However, in the tofogliflozin group, the DI improved in participants with poorer glucose tolerance at baseline or larger improvements after treatment, but not in the metformin group.

Conclusion: Short-term tofogliflozin therapy did not improve the insulin secretory capacity of treatment-naïve people with type 2 diabetes. However, tofogliflozin may facilitate the early recovery of insulin secretory capacity in individuals with poor glucose tolerance.

Aims: To investigate the dynamic changes of soluble receptor for advanced glycation end products (sRAGE) and its relationship with β-cell function and glycemic remission in newly diagnosed type 2 diabetes mellitus (T2DM) after short-term intensive insulin therapy (SIIT).

Methods: A total of 98 drug-naive patients with newly diagnosed T2DM underwent a two-week SIIT and were followed for 16 weeks. Serum sRAGE was measured at baseline, after SIIT, and at the 1-month follow-up. HOMA-β and HOMA-IR were used to reflect β-cell function and insulin resistance, respectively. Pearson or Spearman correlation coefficients were used to assess the correlations, and logistic regression was applied to evaluate associations between changes in sRAGE (ΔsRAGE) and 16-week glycemic remission, adjusting for potential confounders.

Results: sRAGE levels increased significantly after SIIT (P < 0.001) and remained higher at 1 month. The increase in sRAGE after SIIT was positively correlated with the changes in HOMA-β and negatively correlated with changes in HOMA-IR. Participants who achieved glycemic remission had greater ΔsRAGE after SIIT than those who did not (273.9 ± 268.2 vs 76.7 ± 257.7 pg/mL, P = 0.001). In multivariate analysis, ΔsRAGE was independently associated with remission (OR = 1.228 per 100 pg/mL, 95% CI 1.006-1.500, P = 0.044), and the AUC of this model was 0.783 (95% CI 0.690-0.876).

Conclusions: Elevation of sRAGE after SIIT is independently associated with short-term glycemic remission in newly diagnosed T2DM. The increase in sRAGE accompanied by an improvement in β-cell function, suggests that increased sRAGE may reflect a compensatory response during metabolic recovery.

Aims/introduction: Diabetic retinopathy (DR) is a prevalent chronic complication of type 2 diabetes mellitus (T2DM), contributing significantly to vision impairment. Circular RNAs (circRNAs) have emerged as key regulators in the pathogenesis of DR. This study aimed to investigate the differential expression profiles and potential functions of circRNAs in patients with DR compared to those without DR.

Materials and methods: In this single-center, prospective study, serum samples from 20 T2DM patients with DR and 20 without DR were analyzed using the Arraystar Human circRNA Expression Profile V2.0 microarray. An additional cohort of 40 patients (20 DR and 20 without DR) was used to validate selected circRNAs via quantitative reverse transcription PCR (qRT-PCR). Enriched signaling pathways were identified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. CircRNA-miRNA-mRNA interaction networks were constructed using bioinformatics tools.

Results: A total of 376 circRNAs were differentially expressed, including 169 upregulated and 207 downregulated circRNAs. qRT-PCR validation confirmed five downregulated circRNAs and three upregulated circRNAs, which were selected for competing endogenous RNA analysis. The circRNA-miRNA-mRNA network analysis revealed that hsa_circRNA_407262 (also known as circRNA LOC389906) may act as a miRNA sponge regulating key signaling pathways, including wingless/integrated, gonadotropin-releasing hormone, tumor necrosis factor, and rat sarcoma pathways.

Conclusions: This study identified five downregulated and three upregulated circRNAs associated with DR. Among them, hsa_circRNA_407262 may play a crucial role in the pathological process of DR and holds potential as a candidate biomarker for early diagnosis.

Aims/introduction: Our study explores interconnections between the occurrence of gastrointestinal (GI) symptoms with immunohistochemical analysis of colon biopsies, markers of intestinal permeability, and inflammation in individuals with type 1 diabetes.

Material and methods: Twenty subjects with type 1 diabetes and seven healthy controls underwent colonoscopy. Colon biopsy materials were analyzed immunohistochemically for CD3+, CD20+, CD4+, CD8+, CD138+, and CD68+ cell counts. The levels of lipopolysaccharide (LPS), LPS-binding protein (LBP), and endogenous anti-endotoxin core antibodies (EndoCAb IgG and IgM) were measured in serum. Fecal calprotectin, immunoglobulin A (IgA), albumin, protein, and intestinal alkaline phosphatase (IAP) activity were analyzed in patient subgroups.

Results: Immune cell infiltration in lamina propria did not differ between type 1 diabetes and control subjects. In type 1 diabetes, the number of CD20+, CD8+, CD138+, and CD68+ cells correlated with several GI symptoms and usage of medications for diarrhea. Fecal calprotectin correlated positively with the number of CD20+ B cells, CD3+ T cells, and CD138+ plasma cells. A negative correlation was found between CD20+ B-cell number and fecal IgA, while CD68+ macrophage number correlated positively with fecal albumin. Serum EndoCAb IgM correlated negatively with CD138+ plasma cells and CD4+ T cells, and positively with CD68+ macrophages. Serum LBP correlated negatively with CD4+ T cells, demonstrating links between gut mucosal inflammation and the systemic response to endotoxin.

Conclusions: In type 1 diabetes, CD immune cell infiltration in the colon mucosa tended to correlate with fecal and systemic markers of inflammation and gastrointestinal symptoms. A key direction for future studies will be to elucidate the underlying pathogenic mechanisms.

Background: Remnant cholesterol to high-density lipoprotein cholesterol ratio (RHR) has been identified as a reliable predictor for metabolic disease risk. Nevertheless, its relevance in the context of diabetic kidney disease (DKD) remains unexplored. Therefore, this study seeks to explore the association between the risk of DKD and RHR in individuals with T2DM.

Methods: In this cross-sectional study, 2,958 patients diagnosed, as T2DM admitted to the hospital from 2018 to 2023 were assessed. The analysis was conducted through restricted cubic spline (RCS) and logistic regression methodologies, complemented by additional stratified and interaction analyses.

Results: As the quartiles of RHR increase, there is a notable increase in the prevalence of DKD, with the rates of 39.6%, 44.5%, 55.1%, and 60.7%, respectively. Logistic regression analysis showed a positive association between RHR and DKD (OR = 1.14, 95% CI: 1.04-12.25), with this effect being more pronounced in patients over 60 years old. RCS analysis identified an inverted L-shaped association, with an inflection point at 1.31. Mediation analyses identified SBP and FPG as partial mediators of the association between DKD and RHR, accounting for 10.4% and 3.3% of the mediation, respectively. Additionally, AUC for RHR (AUC = 0.654, 95% CI: 0.633-0.676) was significantly higher compared to those of RC, HDL, and TG.

Conclusions: RHR exhibits a positive association with the risk of DKD, underscoring its potential utility as a cost-effective biomarker for stratifying the risk of DKD.

The patient was a 73-year-old man with diabetes who developed marked hyperglycemia after several years of insulin therapy. Investigations showed marked hyperinsulinemia, positive insulin antibodies with low affinity/high binding capacity, insulin-specific IgE and eosinophil infiltration on skin biopsy, confirming insulin allergy. Positivity for insulin receptor autoantibodies (IRAb) initially led to a diagnosis of type B insulin resistance syndrome. However, a relatively low C-peptide level (1.57 ng/mL) despite severe hyperinsulinemia (1231.9 μU/mL) was key for differentiation. After cessation of insulin and initiating a multi-drug anti-diabetes regimen, the patient's glycemic control improved markedly, with a decrease in HbA_1c from 12.3 to 6.7%. His serum insulin level decreased, and his IRAb test turned negative. This case highlights the fact that a high insulin antibody titer can cause a false-positive IRAb result. A disproportionately low C-peptide level in the presence of hyperinsulinemia may aid differentiation between insulin allergy and type B insulin resistance syndrome.

Aims/introduction: To investigate the association between C-reactive protein (CRP) with sensory symptoms and deficits and measures of small fiber damage.

Materials and methods: Adults with and without T2D underwent corneal confocal microscopy (CCM) and assessment of vibration perception threshold (VPT), DN4 symptom questionnaire, and fasting blood tests for CRP and metabolic markers.

Results: Of the 122 participants, 77 had T2D of whom 23 (29.9%) had DPN, and 45 were controls. CRP levels were significantly higher in those with T2D without and with DPN compared to controls (5.6 ± 2.9 and 5.4 ± 4.0 vs 3.8 ± 2.9 mg/L, P = 0.008 and P = 0.046, respectively), with no difference between those with and without DPN (P = 0.894). Higher CRP was independently associated with lower corneal nerve fiber density (CNFD) (β = -5.5 fibers/mm² per 10 mg/L increase, P = 0.036), after adjusting for diabetes duration, BMI, HbA1c, and triglycerides. In the DPN group, those with positive symptoms (burning, painful cold, and electric shocks) had higher CRP levels compared to those with negative symptoms (6.5 ± 4.7 vs 3.8 ± 1.9 mg/L, P = 0.039).

Conclusions: Elevated CRP is associated with small nerve fiber loss and positive neuropathic symptoms in T2D. These findings suggest that CRP may help identify individuals with inflammation-driven DPN who could benefit from targeted interventions.

Aims: Impaired red blood cell (RBC) deformability is a potential contributor to microvascular dysfunction in diabetes. This study aimed to determine the association between erythrocyte deformability and the severity of diabetic retinopathy (DR), focusing on quantitative measures of macular and peripheral ischemia.

Methods: We retrospectively analyzed 79 patients with treatment-naïve DR. RBC deformability was measured using a microfluidic ektacytometer, and the elongation index at 3 pascals (EI@3P) was calculated. Optical coherence tomography angiography (OCTA) and ultra-widefield fluorescein angiography (UWFFA) were performed to quantify macular vessel density, foveal avascular zone (FAZ) area, and peripheral ischemic index. Associations between EI@3P and imaging parameters were assessed across DR severity groups using correlation and regression analyses.

Results: EI@3P significantly decreased with advancing DR stages (P = 0.010). Eyes with lower EI@3P exhibited reduced vessel density and enlarged FAZ in the deep capillary plexus on OCTA (P = 0.042 and P = 0.041, respectively). In severe non-proliferative and proliferative DR, reduced EI@3P was associated with a higher peripheral ischemic index on UWFFA (r = -0.206, P = 0.035). No significant association was observed between EI@3P and glycated hemoglobin or diabetes duration.

Conclusions: Decreased erythrocyte deformability correlates with microvascular ischemia and disease severity in DR, suggesting a hemorheological mechanism linking systemic blood rheology to retinal microcirculatory impairment. EI@3P may serve as a novel biomarker for assessing microvascular complications in diabetes.

Introduction: Recent studies have demonstrated that both oral semaglutide and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have beneficial effects on glycemic and weight management as well as providing renal and cardiovascular protection. However, direct comparisons of the effects of these two drugs in clinical practice remain limited.

Materials and methods: This study is a single-center, retrospective, observational study. Patients with type 2 diabetes who were initiated on oral semaglutide or SGLT2is and continued treatment for 6 months or more were retrospectively analyzed and compared.

Results: The semaglutide group (84 patients) and the SGLT2is group (231 patients) showed similar, significant reductions in glycated hemoglobin (HbA1c) (semaglutide: -0.88 ± 0.14%; P < 0.01, and SGLT2is: -0.86 ± 0.06%; P < 0.01, at 6 months), body weight (semaglutide: -2.58 ± 0.37 kg; P < 0.01, and SGLT2is: -2.30 ± 0.18 kg; P < 0.01, at 6 months), and fat mass (semaglutide: -2.20 ± 0.50 kg; P < 0.01, and SGLT2is: -1.93 ± 0.44 kg; P < 0.01, at 6 months), being decreased similarly and significantly in both groups. On the other hand, there was a significant reduction in skeletal muscle mass only in the SGLT2is group (semaglutide: -0.10 ± 0.30 kg; P = 0.74, and SGLT2is: -0.40 ± 0.14 kg; P < 0.01 at 6 months).

Conclusions: While both drugs elicited comparable effects on glycemic management and body weight reduction in patients with type 2 diabetes, caution is needed when using SGLT2is in patients at potential risk for sarcopenia, as they may lead to less favorable changes in skeletal muscle mass compared to oral semaglutide.