Journal of Diabetes Investigation最新文献

Aims/introduction: Diabetic retinopathy (DR) is a common complication of diabetes that can lead to poor vision and blindness. This study aimed to explore the mechanism of action of miR-130a-3p in DR progression.

Materials and methods: In this study, we administered a single intraperitoneal injection of 100 mg/kg streptozotocin (STZ) to construct a DR mouse model, and induced a human monocyte cell line (THP-1) to differentiate into M0 macrophages, after which the M0 macrophages were cultured with 30 mM high glucose (HG) as a model of inflammation. The relative gene and protein levels were validated by RT-qPCR and western blotting. Macrophage polarization and retinal damage in the mice were tested using ELISA, MDC staining, immunofluorescence staining, and HE staining.

Results: The results revealed that the expression of miR-130a-3p was low in M1 macrophages, whereas the expression of miR-130a-3p was high in M2 macrophages, and the level of miR-130a-3p was reduced after HG treatment of macrophages. The overexpression of miR-130a-3p attenuated HG- or STZ-induced inflammation, promoted macrophage autophagy, inhibited M1 polarization of macrophages, and attenuated the progression of DR. In addition, YY1 was the downstream target gene of miR-130a-3p, and overexpression of miR-130a-3p inhibited YY1 expression. However, overexpression of YY1 weakened the effect of miR-130a-3p mimic. After further treatment with the PI3K/Akt/mTOR pathway activator 740 Y-P, the effect of YY1 knockdown was weakened, macrophage autophagy was inhibited, and M1 polarization and inflammation were promoted.

Conclusion: miR-130a-3p inhibited the activation of the PI3K/Akt/mTOR pathway by downregulating YY1 expression, thus facilitating macrophage autophagy, inhibiting M1 polarization and the inflammatory response of macrophages, and finally attenuating the progression of DR. The results of this study provide theoretical support for the use of miR-130a-3p as a new target for the treatment of DR.

Introduction: Insulin icodec is a basal insulin designed for once-weekly administration. This study assessed the pharmacological properties of icodec in Japanese individuals with type 1 diabetes (T1D).

Materials and methods: In a randomized, open-label, crossover study, 24 Japanese individuals with T1D (20-64 years; glycated hemoglobin ≤9.0%) received once-weekly icodec for 8 weeks and once-daily insulin glargine U100 for 14 days at individual constant equimolar doses per week together with bolus insulin aspart. Individual doses were determined during run-in with glargine U100 titrated to prebreakfast self-measured plasma glucose (SMPG) of 4.4-7.2 mmol/L. Blood samples for icodec pharmacokinetics were taken from the first icodec dose until 35 days after last dose. The steady-state glucose-lowering effect was measured in glucose clamps (target 6.7 mmol/L) during 24-48 h and 150-168 h after last icodec dose and 0-24 h after last glargine U100 dose. One-week glucose-lowering effect of icodec was simulated using a pharmacokinetic/pharmacodynamic model. Hypoglycemia was identified from SMPG during the treatment periods.

Results: Icodec pharmacokinetic steady state was achieved on average after 2-3 weeks of treatment. Model-derived daily glucose-lowering effect during the weekly dosing interval averaged 14.6%, 18.0%, 16.6%, 14.9%, 13.3%, 11.9%, and 10.7%, respectively. Rates of level 2 hypoglycemia (PG <3.0 mmol/L) were 37.3 vs 30.6 episodes per patient-year of exposure for icodec vs glargine U100.

Discussion: Icodec pharmacological properties in Japanese individuals with T1D in this study support the potential of icodec to provide basal insulin coverage with once-weekly dosing in Japanese individuals with diabetes.

With the rapid advancement of diabetes technology, the number of patients with type 1 diabetes (T1D) using automated insulin delivery (AID) systems is increasing, making the presence of such patients in the perioperative period more common. This study presents two cases of T1D patients who underwent thyroidectomy while using AID, following a protocol designed in collaboration with the diabetology, anesthesiology, and surgical teams. Two female patients, aged 12 and 33 years, both using AID systems, were admitted for elective thyroidectomy. Glycemic metrics prior to surgery indicated good glycemic control, leading to the decision to continue AID during the procedures. The use of AID enabled safe surgical performance with satisfactory glycemic control. In one case, a continuous glucose monitoring (CGM) sensor disruption likely resulted from acetaminophen distribution and/or sensor's proximity to the surgical field. This report highlights the need for standardized guidelines regarding the use of AID in the perioperative period.

We briefly summarizes the mechanism of GLP-1RA therapy in HO both in rodents and in humans. We also summarized the clinical trials and case reports of GLP-1RA therapy in HO, especially the more and more often used semaglutide. We are hoping the therapy of GLP-1RA in HO will arouse more attention from clinicians in the future.

Aims: This study aimed to determine the maximum daily insulin dose (MDI) and associated factors in critically ill patients with coronavirus disease 2019 (COVID-19) receiving insulin therapy, under ventilator and/or extracorporeal membrane oxygenation (ECMO) management.

Materials and methods: This cross-sectional analysis used the Cross ICU Searchable Information System data from a Japanese multicenter retrospective observational cohort study of critically ill patients with COVID-19 receiving ventilation and/or ECMO, from February 2020 to March 2022. Maximum daily insulin dose was determined, and factors associated with it and maximum daily insulin dose per body weight were assessed using linear regression analysis.

Results: The analysis included 788 patients. Their mean age, glycated hemoglobin level, maximum daily insulin dose, and time from admission to the maximum daily insulin dose were 65.2 ± 13.0 years, 7.0 ± 1.5% (53.0 ± 7.1 mmol/mol), 46.0 ± 43.6 U/day, and 7.3 ± 7.0 days, respectively. Male sex (β = 6.902, P = 0.034), body mass index (β = 1.020, P = 0.001), glycated hemoglobin (β = 12.272, P < 0.001), and having renal failure (β = 20.637, P = 0.003) were independent determinants of maximum daily insulin dose. Age (β = 0.004, P = 0.035), glycated hemoglobin (β = 0.154, P < 0.001), and having renal failure (β = 0.282, P = 0.004) were independent determinants of maximum daily insulin dose per body weight.

Conclusions: In patients with COVID-19 on ventilator and/or ECMO management, the maximum daily insulin dose reached after about 1 week of hospitalization was approximately 46.0 U/day. Glycated hemoglobin and renal failure were both associated with the maximum daily insulin dose and maximum daily insulin dose per body weight.

Background: Polyethylene glycol loxenatide (PEG-Loxe) is applied in treating type 2 diabetes mellitus. Nevertheless, the effect and mechanism of PEG-Loxe on lipid metabolism disorder and insulin resistance in type 2 diabetes mellitus are not fully understood.

Methods: Type 2 diabetes mellitus rats developed by high-fat diet/streptozotocin injection were treated with PEG-Loxe (0.3 or 1 mg/kg). Insulin resistance was evaluated by fasting blood glucose (FBG), oral glucose tolerance test, fasting insulin, homeostasis model of assessment for insulin resistance and for insulin sensitivity. Immunohistochemistry, hematoxylin and eosin staining, and biochemistry measurements were performed to assess lipid metabolism. Inflammatory response and oxidative stress were assessed by inflammatory cytokines and reactive oxygen species. Genes' expressions were tested using RT-qPCR, western blot, and in situ hybridization. Relationships of molecules were validated by pull-down assay and RNA immunoprecipitation. mRNA stability was examined by actinomycin D assay.

Results: High-PEG-Loxe decreased FBG and ameliorated glucose tolerance, hyperinsulinemia, and insulin resistance. Low-PEG-Loxe partly while high-PEG-Loxe apparently relieved hepatocyte injury, reduced lipase I, triglyceride, total cholesterol and leptin, and increased adiponectin in type 2 diabetes mellitus rats. PEG-Loxe mitigated inflammatory response and oxidative stress. High-PEG-Loxe reduced RhoA and Rho-associated coiled-coil kinase 2 (ROCK2) in liver tissues of type 2 diabetes mellitus rats, while both doses of PEG-Loxe decreased steroid receptor RNA activator (SRA). SRA overexpression reversed the protective functions of high-PEG-Loxe. SRA cooperated with cellular nucleic acid binding protein (CNBP) to enhance ROCK2 mRNA stability.

Conclusion: High-PEG-Loxe relieves insulin resistance and lipid metabolism disorder in type 2 diabetes mellitus through SRA/CNBP/ROCK2 axis. This research provides a molecular mechanism of PEG-Loxe for treating type 2 diabetes mellitus.

Aims/introduction: Placental glucose transport is regulated by glucose transporter proteins (GLUTs). The study aimed to examine placental expression of GLUT-1, GLUT-3, and GLUT-4 mRNA in patients with type 1 diabetes, early gestational diabetes (eGDM), and healthy controls, and to investigate correlations between GLUTs expression and clinical parameters. Additionally, we compared placental transcriptome profiles in recruited subgroups.

Materials and methods: We recruited 59 pregnant women: 23 with type 1 diabetes, 17 with eGDM, and 19 controls. Patients with diabetes attended follow-up visits at each trimester. Transcriptome studies were performed in 4 patients per subgroup.

Results: The mean age was similar across all subgroups. eGDM patients had significantly higher BMI and were predominantly obese. We observed a significant 2-fold (P = 0.009) decrease in placental GLUT-3 mRNA expression in the type 1 diabetes and eGDM groups. GLUT-4 mRNA expression was significantly lower in the eGDM group compared to type 1 diabetes (3-fold) and controls (6-fold) (P = 0.007). There was a significant negative correlation between GLUT-3 (R = -0.29) and GLUT-4 (R = -0.27) mRNA expression and neonatal birth weight. GLUT-4 expression was negatively correlated with 1st trimester HbA1c (R = -0.72) and OGTT 120' (R = -0.82) results in eGDM patients, and 3rd trimester glycemic variability (R = -0.49) in type 1 diabetes. Microarray analysis revealed significant transcriptomic changes, with 45 down-regulated and 365 up-regulated genes in type 1 diabetes, and 21 significant changes in eGDM.

Conclusions: Placental samples from patients with diabetes exhibit changes in GLUTs expression, which correlates with neonatal growth and several glycemic parameters. Additionally, multiple changes in transcriptomic profiles are observed in hyperglycemic patients.

Aims: To compare the prevalence of GDM and pregnancy outcomes between the one-step and two-step methods of universal screening among Thai pregnant women.

Methods: A randomized controlled trial was conducted on singleton Thai pregnant women at a gestational age of 24-28 weeks. They were randomly assigned to either the one-step method group (a universal 75-gm 2-h oral glucose tolerance test: OGTT) or the two-step method group (a universal 50-gm oral glucose challenge test followed by a 100-gm 3-h OGTT). The women received standard antenatal care. The prevalence of GDM and obstetric outcomes were compared.

Results: A total of 143 women meeting the inclusion criteria were randomly allocated into the one-step group (72 cases) and the two-step group (71 cases). The prevalence of GDM was significantly higher in the one-step group than in the two-step group, with rates of 24/73 (33.3%) vs 8/70 (11.3%); P value 0.002; relative risk of 2.96, 95% CI: 1.43-6.14, respectively. Demographic data and maternal and neonatal outcomes were comparable between the two groups.

Conclusions: The one-step method can markedly increase the prevalence of GDM to nearly three times that of the two-step method, leading to a substantial increase in care costs and burdens without clear benefits. Convincingly, the one-step method as a new approach may not be suitable for universal screening in a busy antenatal care setting, especially in low-resource health centers in developing countries or among populations with a high prevalence of GDM.

Aim/introduction: To evaluate the therapeutic efficacy short-term continuous subcutaneous insulin infusion (CSII) intensive therapy combined with a low-carbohydrate diet (LCD) for diabetes remission in patients with newly diagnosed type 2 diabetes mellitus.

Materials and methods: This study included patients newly diagnosed with type 2 diabetes mellitus, who were randomly divided into two groups: conventional (conventional CSII + traditional lifestyle guidance); and intensive (intensive CSII + LCD lifestyle guidance). CSII was used for blood glucose control, with continuous glucose monitoring (CGM) used to monitor blood glucose levels. The primary outcome measure was hemoglobin A1c (HbA1c) level; secondary outcomes included body weight, body mass index (BMI), waist circumference, glycemic control, and biochemical indices.

Results: The time in range (TIR) in the intensive treatment group was greater than that in the conventional treatment group (P < 0.05). There was no significant difference in the incidence of hypoglycemia between the two groups (P > 0.05). Compared with the conventional treatment group, diabetes remission rates were significantly greater in the intensive treatment group (P < 0.05). In the intensive treatment group, fasting plasma glucose (FPG), HbA1c, Homeostasis Model assessment of Insulin Resistance (HOMA-IR), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and changes in body weight, BMI, visceral fat area (VFA), and subcutaneous fat area (SFA) decreased significantly (P < 0.05). FPG, HOMA-IR, TG, LDL-c, and changes in body weight, BMI, waist circumference, and VFA were significantly correlated with HbA1c levels (P < 0.05).

Conclusions: The combination of intensive CSII and LCD lifestyle guidance had been improved the remission rate in patients with newly diagnosed type 2 diabetes mellitus.

Aims: To compare perinatal outcomes and postpartum glucose tolerance between women diagnosed with gestational diabetes mellitus (GDM) before 20 weeks of gestation (EGDM) and those diagnosed at or after 24 weeks of gestation (LGDM) in a Japanese population.

Materials and methods: Data were obtained from a prospective GDM registry. Multivariate analysis was conducted to examine the association between the timing of GDM diagnosis (EGDM vs LGDM) and perinatal outcomes (preterm birth, small for gestational age, large for gestational age, pregnancy-induced hypertension, and neonatal hypoglycemia), as well as postpartum glucose intolerance.

Results: A total of 1,275 mother-infant pairs were analyzed for perinatal outcomes. Of these, 924 women underwent postpartum testing for glucose intolerance. No significant differences in perinatal outcomes were observed between the EGDM and LGDM groups, except that overweight/obese women with EGDM had 2.5-fold higher rate of preterm birth than those with LGDM. Postpartum glucose intolerance was 1.5 times more likely in the EGDM group than in the LGDM group.

Conclusions: Women with EGDM had a significantly higher risk of postpartum glucose intolerance than those with LGDM, despite similar perinatal outcomes between the two groups.