Journal of diabetes and its complications最新文献

Aims: Early-onset type 2 diabetes (T2DM) (18-45 years) is rising globally, yet complication incidence in this group remains unclear. We investigated the incidence of early-onset T2DM, the incidence of micro- and macrovascular complications, and how comorbidities (e.g., severe mental illness) and sociodemographic factors (e.g., education level) influence complication risk and timing in Denmark.

Methods: Using nationwide registers, we followed 8,129,005 individuals from 1996 to 2020 to estimate the incidence rate (IR) of early-onset T2DM. 49,850 individuals with early-onset T2DM were followed to calculate IRs for microvascular (nephropathy, retinopathy) and macrovascular (cardiovascular disease, amputation) complications. Incidence rate ratios (IRRs) assessed associations between comorbidities, sociodemographic factors, and complications. Poisson regression models calculated IRs and IRRs.

Results: From 1996 to 2020, the IR of early-onset T2DM more than doubled in men and tripled in women, with women dominating younger age groups. During follow-up (7.9-9.8 years), 37.6 % developed complications. Higher complication IRs were observed in men, those with sociodemographic disadvantages, and individuals with comorbidities. Early complications (≤5 years) were more common among the unemployed, single individuals, and those with comorbidities.

Conclusions: The rising IR of early-onset T2DM in younger women, and complications disproportionately affecting men and those with comorbidities or sociodemographic disadvantages, highlight the need for targeted interventions.

Type 2 diabetes is a chronic disease requiring comprehensive pharmacological and non-pharmacological interventions to slow its progression and prevent or delay its micro- and macrovascular complications. Oxidative stress contributes to the development and progression of type 2 diabetes as well as to the development of its complications through several mechanisms. Therefore, therapeutic targeting of oxidative stress could aid in managing this disease and its complications. In our study, we have collected information on the most frequently used antidiabetic drugs (metformin, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors) in the EU and the USA based on their antioxidant effects. Based on our results, we can conclude that the antioxidant effects of the investigated antidiabetics may contribute significantly to the management of the disease and its complications and may open new therapeutic perspectives in their prevention.

Background: Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) were often coexistent conditions driven by insulin resistance and systemic inflammation. Effective management strategies that address both metabolic disorders were urgently needed. This study investigates the effect of combining semaglutide, a glucagon-like peptide-1 receptor agonist, with metformin on liver inflammation and pancreatic beta-cell function in patients with T2DM and NAFLD.

Methods: This retrospective study analyzed 261 patients with T2DM and NAFLD treated at our institution from January 2021 to December 2023. Patients were divided into two groups: 127 received metformin alone (M group), and 134 received a combination of semaglutide and metformin (SAM group). Liver inflammation and fibrosis were assessed using alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GTP), and the FIB-4 index. Pancreatic beta-cell function and insulin sensitivity were evaluated using the Matsuda index, HbA1c, fasting glucose, and the oral disposition index (DIo).

Results: Post-treatment, the SAM group showed significantly greater improvements in liver inflammation markers (ALT: 23.59 ± 5.67 U/L in SAM vs. 25.56 ± 5.46 U/L in M; AST: 18.97 ± 3.94 U/L in SAM vs. 20.15 ± 3.95 U/L in M), reduced fibrosis (FIB-4 index: 1.05 ± 0.44 in SAM vs. 1.16 ± 0.51 in M), and enhanced beta-cell function (Matsuda index: 5.18 ± 1.09 in SAM vs. 4.84 ± 1.15 in M; DIo: 0.18 ± 0.06 in SAM vs. 0.16 ± 0.05 in M). Glycemic control, as indicated by reduced HbA1c, was also superior in the SAM group.

Conclusion: The combination of semaglutide and metformin significantly improves liver inflammation, fibrosis, and beta-cell function in patients with T2DM and NAFLD compared to metformin alone.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, commonly utilized for diabetic nephropathy, have demonstrated benefits beyond glucose control, including organ protection. This study investigated the protective effects of the SGLT2 inhibitor, dapagliflozin (DAPA), on palmitate-induced renal tubular epithelial cell (HK-2) injury, particularly concentrating on mitochondrial function and oxidative stress. HK-2 cells were treated with 150 μmol/L palmitate to induce mitochondrial dysfunction and oxidative stress, and they were co-treated with 2 μmol/L DAPA for 24 h. DAPA significantly increased cell viability (P < 0.05), reduced reactive oxygen species (ROS) levels (P < 0.001), and restored mitochondrial membrane potential (P < 0.05). It also lowered malondialdehyde (MDA) level (P < 0.001) and increased superoxide dismutase (SOD) expression level (P < 0.001). Western blot analysis revealed that DAPA reversed palmitate-induced upregulation of apoptosis-related proteins, including Bax and Cytochrome C. DAPA also mitigated the overactivation of autophagy-related proteins, such as LC3 and Beclin-1, indicating its role in modulating autophagy under diabetic nephropathy. Electron microscopy confirmed improvements in mitochondrial morphology, accompanying by reduced swelling and restored cristae structure. These findings highlight the potential of DAPA, as an SGLT2 inhibitor, to mitigate renal injury by enhancing mitochondrial function and reducing oxidative stress, providing novel insights into its therapeutic value for diabetic nephropathy management.

Aim: To explore the association between bone disorder and the risk for progression of diabetic kidney disease (DKD) in persons with type 1 diabetes mellitus (T1DM).

Methods: In this prospective cohort study the association between bone mineral density (BMD), bone-derived factors (sclerostin, Dickkopf-1, and osteoprotegerin (OPG)), and four outcomes were investigated: 1) progression of albuminuria; 2) decline in estimated glomerular filtration rate (eGFR) ≥30 %; 3) kidney failure (KF); and 4) a composite kidney outcome consisting of at least one of the outcomes.

Results: In 318 participants (median follow-up time 5.5 years) patients with osteoporosis (BMD with T-score < -2.5) had increased risk of eGFR decline: hazard ratio (HR) 2.56 (95 % CI 1.06-6.19, p = 0.04), KF: HR 9.92 (95 % CI 1.16-84.95, p = 0.04), and the composite kidney outcome: HR 2.42 (95 % CI 1.18-4.96, p = 0.02). Patients with high OPG had increased risk of eGFR decline, KF, and the composite outcome, compared to patients with low OPG in unadjusted analysis. No bone-derived factor was associated with any outcome in adjusted analyses.

Conclusions: In patients with T1DM low BMD was associated with progression of DKD, suggesting an interaction between bone and kidney.

Aims: To examine if healthcare access modifies the association between age at diagnosis of diabetes and the prevalence of retinopathy.

Methods: BRFSS 2020 survey data was obtained from 12,198 adults. Participants with missing information in the variables "retinopathy" (N = 569) and "insurance-cost barrier" (N = 75) were excluded. The final sample included 11,556 participants. Age at diagnosis of diabetes was the main exposure and retinopathy was the main outcome. We tested if the main association was different among the insurance-cost barrier variable. Binary logistic regression models were used to calculate odds ratios (OR) and 95 % confidence intervals (CI).

Results: The odds of retinopathy decreased by 22 % in patients 46-64 years-of-age (OR 0.78; 95 CI 0.6-1.0) and 57 % in those 65+ (OR 0.43; 95 CI 0.28-0.65). The odds decreased by 39 % if female (OR 0.61; 95 CI 0.48-0.77). An increase in odds by 86 % (OR 1.86; 95 CI 1.07-3.21) occurred in other non-Hispanics, 50 % (OR 1.50; 95 CI 1.13-1.99) in black non-Hispanics and 70 % (OR 1.70; 95 CI 1.17-2.46) in Hispanics. There was no evidence that age at diagnosis of diabetes and presence of retinopathy varied by insurance cost (p > 0.05).

Conclusion: Health professionals may utilize these results to advocate for early disease intervention.

Uric acid (UA) is mainly synthesized in the liver, intestine, and vascular endothelium and excreted by the kidney (70 %) and intestine (30 %). Hyperuricemia (HUA) occurs when UA production exceeds excretion. Many studies have found that elevated UA is associated with diabetic microvascular complications (DMC), including diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic peripheral neuropathy (DPN). In addition, too high or too low UA levels will promote the occurrence and development of chronic diseases, but the relationship between UA and diabetic microvascular complications (DMC) is not clear. Therefore, the rational treatment of UA in patients with diabetes is essential. In this review, we summarize and discuss the mechanism and treatment of UA and DMC and may provide potential advice for rational drug selection.

Background and hypothesis: The kidneys may be susceptible to ectopic fat and its lipotoxic effects, disposing them to chronic kidney disease (CKD) in type 2 diabetes (T2D). We investigated whether the kidney parenchyma fat content and kidney sinus fat volume would be higher in persons with T2D and CKD.

Methods: Cross-sectional study including 29 controls, 27 persons with T2D and no CKD, and 48 persons with T2D and early CKD (urine albumin creatinine ratio (UACR) ≥ 30 mg/g). Kidney parenchyma fat content and kidney sinus fat volume were assessed using magnetic resonance spectroscopy and Dixon scans respectively.

Results: In the control, T2D without CKD and T2D with CKD groups, respectively, median [1st - 3rd quartile] UACR was 5 [4 - 6], 6 [5 - 10] and 95 [43 - 278] mg/g. and mean ± standard deviation estimated glomerular filtration rate was 89 ± 11, 94 ± 11 and 77 ± 22 ml/min/1.73m². Kidney parenchyma fat content was, respectively, 1.0 [0.5-2.4], 0.7 [0.2-1.2], 1.0 [0.3-2.0] % (p = 0.26). Kidney sinus fat volume was 2.8 [1.6-7.6], 8.0 [4.7-11.3], 10.3 [5.7-14.0] ml (p < 0.01). Around 90 % of T2D participants received a sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonist.

Conclusions: In a setting of modern, multifactorial T2D management, kidney parenchyma fat content, evaluated with magnetic resonance spectroscopy, was similar among healthy controls and persons with T2D irrespective of CKD status. Still, kidney sinus fat volume was higher in the presence of T2D and higher still with CKD.

Background: This study aimed to examine the association between mean cumulative glycemic burden (MCGB) and variability cumulative glycemic burden (VCGB) with diabetic foot ulcers (DFUs).

Methods: Participants were followed up at least 4 times with 4 recorded glycosylated hemoglobin (HbA1c) measurements. Glycemic burden during follow-up period was defined as the trapezoidal areas enclosed by the HbA1c measurements taken during two consecutive visits and the responding time interval. MCGB was calculated by dividing sum of total trapezoidal areas by the period of follow-up. VCGB was defined as the standard deviation of the trapezoidal areas divided to the mean of trapezoidal areas. To identify the association between MCGB and VCGB with DFUs, a Cox regression analysis was conducted.

Results: Among 1876 diabetic patients, 138 (7.4 %) developed foot ulcers. As MCGB increased across quartiles, DFUs incidence also rose significantly (3.2 % to 16.0 %, P < 0.001). Similarly, the prevalence of DFUs increases with increasing quartiles of mean HbA1c level (3.2 % to 16.2 %; P < 0.001). When assessing VCGB, ulcer incidence gradually increased with the quartiles increased (P = 0.040), but HbA1c variability did not follow a similar trend (P = 0.133). Multivariable Cox regression analysis indicates that compared to the first quartile, both MCGB and VCGB in the fourth quartile significantly increase the risk of DFUs (HR = 2.99 and 5.29, respectively).

Conclusions: Elevated MCGB and VCGB correlate positively with DFUs. In clinical practice, lowering blood glucose levels and reducing glycemic variability are both crucial for reducing the occurrence of diabetic foot ulcers.