Journal of Diabetes Investigation最新文献

Introduction: Developing a more effective treatment for the global impact of diabetic kidney disease is crucial. This study examined the renoprotective effects of combining glucagon-like peptide-1 receptor agonists (GLP-1 RA) with sodium-glucose cotransporter 2 inhibitors (SGLT2i) compared to SGLT2is alone in type 2 diabetes (DM).

Materials and methods: This retrospective cohort study used data from the TriNetX Global Collaborative Network. Type 2 DM patients with estimated glomerular filtration rates ≥60 mL/min/1.73 m² who used GLP-1 RA or SGLT2i between January 1, 2013, and December 31, 2023. Propensity score matching balanced baseline characteristics, resulting in 71,186 patients in each group (combined GLP-1 RA and SGLT2i therapy vs SGLT2i alone). Cox regression model was adopted to compare outcomes over a 5-year period, including major adverse kidney events (MAKE), acute kidney injury (AKI), end-stage kidney disease (ESKD), and all-cause mortality.

Results: After matching, the average age was 57.1 ± 10.8 years for the GLP-1 RA plus SGLT2i group and 57.2 ± 11.7 years for the SGLT2i-only group. The GLP-1 RA plus SGLT2i group had significantly lower risk of MAKE (hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.69-0.77), AKI (HR: 0.82, 95% C0I: 0.77-0.87), ESKD (HR: 0.61, 95% CI: 0.47-0.78), and all-cause mortality (HR: 0.54, 95% CI: 0.50-0.58) compared to the SGLT2i-only group. Moreover, subgroup analyses showed consistent benefits across different subgroups.

Conclusions: Dual therapy with GLP-1 RA and SGLT2i is supported to enhance renal outcomes and address the growing burden of diabetic kidney disease.

Aims/introduction: Diabetic kidney disease (DKD) is a major cause of kidney failure. FOS-like antigen 2 (FOSL2) has been revealed to be increased in kidney biopsies of patients with lupus nephritis, while its association with DKD remains unsolved. This study aimed to characterize the role of FOSL2 in DKD and its mechanism.

Method: The kidney tissues of DKD mice induced by STZ and a high-fat diet were subjected to PAS and Masson's staining. Glomerular mesangial cells (MCs) were treated with high glucose (HG) or normal glucose (NG). CCK-8 and EdU assays were performed to detect cell proliferation, and immunoblotting was conducted to analyze ECM deposition. ChIP-qPCR was performed on MCs to detect the binding of FOSL2 on the TGF-β1 promoter and a dual-luciferase assay to detect the impact of FOSL2 on the transcription of the TGF-β1 promoter.

Results: FOSL2 was elevated in the kidney tissues of DKD mice. Knockdown of FOSL2 reduced the mRNA expression of TGF-β1 to decrease the protein expression of GLUT1 and mTOR in the kidney tissues of DKD mice, and TGF-β1 reversed the effects caused by knockdown of FOSL2. The mTOR inhibitor Rapamycin alleviated kidney injury in the presence of FOSL2. Knockdown of FOSL2 inhibited the proliferation and improved ECM deposition of MCs, which were reversed by TGF-β1. Rapamycin and GLUT1 inhibitor BAY-876 reversed the promotion effect of FOSL2 on the proliferation of NG-MCs/HG-MCs and improved ECM deposition of MCs.

Conclusions: Our data demonstrated that FOSL2 accentuates DKD in mice by increasing TGF-β1-induced GLUT1/mTOR signaling.

Objective: We here investigated whether lactation during puerperium could help to reverse the diabetogenic effect of gestation and further explored the lipid profiling changes upon breastfeeding.

Methods: Thirty-five women diagnosed with GDM were recruited, and fasting plasma samples were collected at ~6 weeks postpartum. Maternal metabolic parameters were determined, and an untargeted lipidomic analysis was performed. The relationship between underlying lipidomic responses and lactation was explored.

Results: Improved glucose homeostasis and insulin sensitivity were observed in GDM women who adopted breastfeeding during the puerperium. Further lipidomics analysis revealed prominent correlations between lipid constitution changes and breastfeeding in women with GDM. A total of 766 lipid species were identified, 33 of which were found to be significantly altered in response to lactation. Significant associations between dysregulated lipids and maternal metabolic parameters were also shown. Subsequently, we identified a panel of three lipids that were strongly associated with breastfeeding, from which we constructed a predictive model with higher discriminating power.

Conclusions: We generally revealed that lactation during puerperium appears to have favorable effects on diabetogenic risk factors for GDM women. We also discovered that lipidomic changes related to lactation could elucidate the mother's recovery from GDM pregnancy.

We report case details of a morbidly obese patient with type 2 diabetes mellitus (T2DM) who became a failure of diabetes remission after laparoscopic sleeve gastrectomy (LSG). He had a marked improvement of hyperglycemia after the revision surgery using Roux-en-Y gastric bypass (RYGB), where passage failure of a solid food intake at the gastric angle portion disappeared after the revision surgery. Interestingly, he showed improvements of insulin and a marked glicentin secretions with minor changes in glucagon related peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) secretions in the oral glucose tolerance test OGTT after the RYGB surgery compared with post-LSG. Although a marked increase in glucose-induced glicentin secretion after RYGB surgery with increased insulin secretion, further studies are needed to confirm if the increased glicentin secretion after RYGB surgery is linked to stimulation of insulin secretion.

Background: This study investigates the gender-specific genetic influence of the single nucleotide polymorphism (SNP) rs1111875 on diabetes risk within the Taiwanese population using data from the Taiwan Biobank. Diabetes mellitus, particularly type 2 diabetes (T2D), is influenced by genetic factors, and the rs1111875 SNP near the hematopoietically expressed homeobox (HHEX) gene has been linked to T2D susceptibility.

Methods: The study included 69,272 participants after excluding those from arsenic-polluted areas and those with incomplete data. Logistic regression models were used for analyses.

Results: The analyses revealed that the CT genotype of rs1111875 was associated with an increased risk of diabetes (OR = 1.092, 95% CI = 1.030-1.157, P = 0.003), as was the TT genotype (OR = 1.280, 95% CI = 1.165-1.407, P < 0.001). The effect was more pronounced in women (CT: OR = 1.118, 95% CI = 1.036-1.207, P = 0.004; TT: OR = 1.404, 95% CI = 1.243-1.585, P < 0.001). Men exhibited a higher overall risk of diabetes (OR = 1.565, 95% CI = 1.445-1.694, P < 0.001) and had a higher prevalence (12.71% vs 7.80%, P < 0.001) compared to women.

Conclusions: The findings underscore the importance of considering gender differences in genetic studies of diabetes and suggest that personalized diabetes management strategies should account for both genetic and gender-specific risk factors. This research contributes to the broader understanding of genetic determinants of diabetes and their interaction with gender, aiming to enhance personalized healthcare strategies for diabetes prevention and treatment.

Aims/introduction: To determine the association of irregular dietary habits with HbA1c and body mass index (BMI) in people with diabetes.

Materials and methods: We included 4,421 people with diabetes aged 20-74 years (type 1 diabetes (T1D), 19.1%) who answered a questionnaire at mealtime. Adjusted least square means in HbA1c and BMI in patients with irregular dietary habits: "irregular mealtimes (irregular)," "skipping breakfast (SB)," and "late dinner (LD)" were compared to those with "regular dietary habits (regular)." Multivariable logistic regression analyses were performed to examine the association of irregular dietary habits with HbA1c ≥ 7% and BMI ≥25 kg/m².

Results: HbA1c was significantly higher for "irregular" in both sexes and for "LD" in women than those of "regular" in people with T1D. HbA1c was significantly higher for "LD," and BMI was higher for almost all irregular dietary habits than those of "regular" in people with type 2 diabetes (T2D). Odds ratios (ORs) for HbA1c ≥7% were 3.20 (95% confidence interval (CI), 1.30-7.89) for T1D women with "irregular" and 1.73 (1.20-2.49) and 2.20 (1.14-3.65) for T2D men and women with "LD," respectively. ORs for BMI ≥25 kg/m² were 1.60 (95% CI, 1.15-2.22) for T2D men with "irregular" and 1.43 (1.02-2.01) and 2.11 (1.21-3.65) for T2D women and men with "LD," respectively.

Conclusions: Irregular mealtimes are associated with poor glycemic control in T1D women and are associated with obesity in T2D men. Furthermore, a late dinner was associated with high HbA1c levels and BMI in people with T2D.

Aims: This study aimed to identify metabolic markers for diabetic peripheral neuropathic pain (DPNP) in patients with type 2 diabetes mellitus (T2DM).

Materials and methods: Blood metabolite levels in the amino acid, biogenic amine, sphingomyelin, phosphatidylcholine (PC), carnitines, and hexose classes were analyzed in nondiabetic control (n = 27), T2DM without DPNP (n = 58), and T2DM with DPNP (n = 29) using liquid chromatography tandem mass spectrometry. Variable importance projection (VIP) evaluation by partial least squares discriminant analysis was performed on clinical parameters and metabolites.

Results: Sixteen variables with VIP > 1.0 (P < 0.05) were identified across all patient groups, and 5 variables were identified to discriminate between the two T2DM groups. DPNP patients showed elevated fasting blood glucose, glutamate, PC aa C36:1, lysoPC a C18:1, and lysoPC a C18:2, while low-density lipoprotein cholesterol, phenylalanine, and tryptophan were reduced. Glutamate, lysoPC a C18:1, and lysoPC a C18:2 discriminated T2DM with DPNP from those without DPNP with an AUC of 0.671. The AUC was improved to 0.765 when ratios of metabolite pairs were considered.

Interpretation: Blood metabolites include glutamate, and phospholipid-related metabolites implicated in neuropathic pain may have the potential as biomarkers for DPNP. Further investigation is required to understand the mechanism of action of these altered metabolites in DPNP.

Aims/introduction: The relationship between economic disadvantages and the risk of developing gestational diabetes mellitus (GDM), as well as its impact on birth outcomes, remains uncertain.

Materials and methods: From the Taiwan Maternal and Child Health Database, we identified 984,712 pregnant women between 1 January 2007 and 31 December 2018. Using propensity score matching, we selected 5,068 pairs of women across four income levels: very low, low, middle and high. We used a multivariable Cox regression model to assess the risk of GDM in these pregnant women and analyzed the birth outcomes.

Results: The mean age of the pregnant women was 30.89 years. We found no significant difference in GDM risk among pregnant women with different family income. However, newborns of women with GDM and very low-income were at higher risk for several adverse conditions, such as small for gestational age (adjusted odds ratio (aOR) 1.17, 95% confidence interval (CI) 1.04-1.31), large for gestational age (aOR 1.27, 95% CI 1.08-1.51), hypoxic-ischemic encephalopathy (aOR 3.19, 95% CI 1.15-8.86), respiratory distress (aOR 1.58, 95% CI 1.14-2. 19), congenital anomalies (aOR 1.32, 95% CI 1.08-1.62), jaundice requiring phototherapy or exchange transfusion (aOR 1.14, 95% CI 1.05-1.24) and so on.

Conclusions: This study found that low family income alone was not associated with GDM development. However, for a GDM pregnancy, pregnant women with lower income had worse birth outcomes. Improving maternal health and nutrition among low-income pregnant women with GDM might be critical to improving birth outcomes.

Objective: To explore the relationship between adipose tissue deposition and triglyceride-glucose (TyG) index, an indicator clinically used to assess insulin resistance (IR), in middle-aged and elderly women using quantitative computed tomography (QCT) and MRI mDIXON-Quant sequence.

Methods: All participants underwent quantitative computed tomography (QCT) and MRI mDIXON-Quant examination and calculated the TyG index based on the fasting blood glucose and triacylglycerol. Bounded by the median TyG index, all participants were divided into low TyG group and high TyG group. Visceral fat mass (VFM) and subcutaneous fat mass (SFM) were measured on QCT images. Hepatic proton density fat fraction (H-PDFF), pancreatic proton density fat fraction (P-PDFF), and lumbar bone marrow fat fraction (L-BMFF) were measured on MRI mDIXON-Quant images.

Results: Adjusting for age and body mass index (BMI), TyG was moderately positively correlated with H-PDFF, and r/P was 0.416/<0.001, TyG index was weakly positively correlated with VFM and P-PDFF, and r/P were 0.385/<0.001 and 0.221/0.030. There was a difference of VFM, H-PDFF, and P-PDFF between low TyG group and high TyG group (P < 0.05). Adjusting for age and BMI, VFM, and H-PDFF were the risk factors of high TyG, and H-PDFF was the independent risk factor of high TyG.

Conclusions: VFM and H-PDFF were the risk factors of IR, and H-PDFF was the independent risk factor. Early identification and active treatment of adipose tissue deposition, especially hepatic fat deposition, may reserve and delay the progression of IR and even metabolic syndrome.

GIP is a multifaceted hormone whose role in metabolism is highly context-dependent. Pharmacological GIP receptor activation promotes weight loss and improves insulin sensitivity, contrasting sharply with the lipogenic and insulin-resistant effects of endogenous GIP. However, it remains unclear whether these effects simply amplify endogenous GIP's actions or represent distinct mechanisms.