Journal of diabetes and its complications最新文献

Aims

Type 1 diabetes has been associated with mitochondrial dysfunction. However, the mechanism of this dysfunction in adults remains unclear.

Methods

A secondary analysis was conducted using data from several clinical trials measuring in-vivo and ex-vivo mitochondrial function in adults with type 1 diabetes (n = 34, age 38.8 ± 14.6 years) and similarly aged controls (n = 59, age 44.6 ± 13.9 years). In-vivo mitochondrial function was assessed before, during, and after isometric exercise with ³¹phosphorous magnetic resonance spectroscopy. High resolution respirometry of vastus lateralis muscle tissue was used to assess ex-vivo measures.

Results

In-vivo data showed higher rates of anaerobic glycolysis (p = 0.013), and a lower maximal mitochondrial oxidative capacity (p = 0.012) and mitochondrial efficiency (p = 0.024) in adults with type 1 diabetes. After adjustment for age and percent body fat maximal mitochondrial capacity (p = 0.014) continued to be lower and anaerobic glycolysis higher (p = 0.040) in adults with type 1 diabetes. Ex-vivo data did not demonstrate significant differences between the two groups.

Conclusions

The in-vivo analysis demonstrates that adults with type 1 diabetes have mitochondrial dysfunction. This builds on previous research showing in-vivo mitochondrial dysfunction in youths with type 1 diabetes and suggests that defects in substrate or oxygen delivery may play a role in in-vivo dysfunction.

Aim

The efficacy of hybrid closed-loop systems (HCLs) in managing glycemic control in pregnant women with type 1 diabetes remains inadequately characterized. We evaluated the use of the Medtronic Minimed 780G HCLs.

Methods

The retrospective observational study analyzed the glycemic and perinatal outcomes of pregnant women using the HCLs, followed at our tertiary centre. Independent t-tests were employed to compare data among trimesters based on pre-pregnancy HbA_1c. The associations between glycemic parameters and perinatal outcomes were explored using Spearman rho.

Results

Among the 21 women (age: 33.5 ± 4.2 years, diabetes duration: 21.2 ± 7.6 years, pre-pregnancy HbA_1c 7.0 ± 1.1 % (52.9 ± 11.9 mmol/mol)) time in range (pTIR, 63–140 mg/dl; 3.5–7.8 mmol/l) increased progressively throughout pregnancy (trimesters: first: 64.0 ± 9.0 %; second:71.3 ± 11.8 %; third: 75.7 ± 8.1 %). Simultaneously, mean sensor glucose decreased (trimesters: first: 130 ± 10.4 mg/dl (7.2 ± 0.6 mmol/l); second: 120.9 ± 13.4 mg/dl (6.7 ± 0.7 mmol/l); third: 117.3 ± 9.1 mg/dl (6.5 ± 0.5 mmol/l)). Although a majority of women achieved the target pTIR until the third trimester, this did not consistently prevent the delivery of a large-for-gestational-age baby. Notably, one ketoacidosis event occurred, and there were no reported instances of severe hypoglycemia.

Conclusion

Use of the Minimed 780G HCLs enabled the attainment of recommended pregnancy glycemic targets for most women with type 1 diabetes in a real-world setting.

Aims

Conduct a secondary analysis of the TIME (Telehealth-supported, Integrated Community Health Workers (CHWs), Medication access, diabetes Education) made simple trial (SIMPLE) to evaluate healthcare utilization and explore variables that may have influenced HbA1c.

Methods

Participants (N = 134 [67/group]) were low-income, uninsured Hispanics with or at risk for type 2 diabetes mellitus. We included in-person and telehealth clinician visits, other visits, missed visits, orders placed, and guideline-adherence (e.g., vaccinations, quarterly HbA1c for uncontrolled diabetes). Using multivariable models, we explored for associations between HbA1c changes and these measures.

Results

The control arm had higher missed visits rates (intervention: 45 %; control: 56 %; p = 0.007) and missed telehealth appointments (intervention: 10 %; control: 27.4 %; p = 0.04). The intervention group received more COVID vaccinations than the control (p = 0.005). Other health measures were non-significant between groups. Intervention individuals' HbA1c improved with more missed visits (−0.60 %; p < 0.01) and worsened with improved guideline-adherent HbA1c measurements (HbA1c: 1.2 %; p = 0.057). The control group had non-significant HbA1c associations.

Conclusions

Findings suggest that the SIMPLE trial's improved HbA1c levels stemmed from a CHW-driven intervention and not additional healthcare contact. Exploratory outcomes resulted in seemingly counterintuitive HbA1c associations with missed visits and guideline-adherent measurements; these may suggest that an intervention that enhances communication provides support to reduce the amount of follow-up needed by participants without sacrificing clinical improvements.

Gastric emptying of a glucose drink was measured in people with type 2 diabetes given lixisenatide (20 μg/day or placebo) for 8 weeks. Intragastric retention at 240 min (2 (0−11)% vs 48 (3–97)%; P < 0.0001) was much greater with lixisenatide than placebo. Accordingly, lixisenatide may delay liquid gastric emptying markedly.

Aim

To demonstrate cardiovascular safety of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and sodium/glucose cotransporter 2 inhibitors (SGLT-2i) across age-groups.

Methods

PubMed, Embase and Cochrane were searched for cardiovascular outcome trials (CVOTs) testing newer agents until August 31, 2022 (PROSPERO ID CRD42021260167). Studies with ≥1000 T2D participants enrolled for ≥12 months were included. Random effect models were used to report relative-risk (RR) for three-point major adverse cardiovascular events (3P-MACE) and its components by age subgroups (65 years; 75 years).

Results

For SGLT-2is, five CVOTs (46,969 patients, 45–50 % ≥65 years) were included. SGLT-2is reduced risk of MACE (RR; 0.91 [CI, 0.85–0.98]); cardiovascular death (CV-death) (RR; 0.84 [CI, 0.73–0.96]); and all-cause mortality (ACM) (RR; 0.86 [CI, 0.79–0.93]) with no difference in subgroups <65 or ≥65 years.

For GLP-1RAs, nine CVOTs (n = 64,236, 34–75 % ≥65 years) were included. GLP-1RAs reduced risk of MACE (RR; 0.89 [CI, 0.83–0.95]), stroke (RR; 0.86 [CI, 0.76–0.97]) and ACM (RR; 0.90 [CI, 0.83–0.97]) with no significant difference in subgroups <65 or ≥65 years. Additionally, GLP-1RAs reduced risk of MACE (10 %), ACM (12 %) and CV-death (12 %) with no significant difference in subgroups <75 or ≥75 years.

Four CVOTs (n = 33,063; 35–58 % ≥65 years) with DPP-4is were included. There were no significant differences in risk for CV outcomes with DPP-4is compared to placebo in any of the age subgroups.

Conclusion

The overall cardiovascular safety profile of newer anti-hyperglycemic agents is consistent in older and younger individuals.

Background-aim

Non-alcoholic fatty liver disease (NAFLD¹) is the most frequent chronic liver disorder worldwide. Currently, no pharmacological treatment has been approved for NAFLD. Probiotics have been suggested as a potential therapy for NAFLD. The aim of this systematic review and meta-analysis was to assess the impact of probiotic intake on liver tests, lipids, glycemic parameters and inflammatory markers in NAFLD patients.

Methods

We searched electronic databases using related terms. Meta-analysis was performed using random-effects models. Clinical outcomes were presented as standard mean difference (SMD²) with a 95 % confidence interval (CI³). Publication bias and heterogeneity were evaluated in eligible studies.

Results

Fifteen randomized clinical trials comprising 899 participants were included in our meta-analysis. Probiotic supplementation improved alanine transaminase [SMD -0.796; 95 % CI (−1.419, −0.172); p = 0.012], Homeostatic Model Assessment for Insulin Resistance (HOMA-IR⁴) [SMD -0.596; 95 % CI (−1.071, −0.121); p = 0.01] and insulin levels [SMD -1.10; 95 % CI (−2.121, −0.087); p = 0.03]. No significant effects were observed on fasting glucose, hemoglobin A1c, aspartate transaminase, lipid profile, interleukin-6 and tumor necrosis factor-α.

Conclusions

Probiotic intake may improve insulin sensitivity and alanine transaminase in NAFLD patients.

Aims

To investigate early indicators of cardiovascular disease (CVD) in children and adolescents with type 1 diabetes mellitus (T1DM), focusing on pulse wave velocity (PWV) and its associations with various anthropometric and glycemic parameters.

Patients and methods

A total of 124 children and adolescents with T1D (mean age 10.75 ± 3.57 years) were included in this cross-sectional study. Anthropometric data, including height, weight, body mass index (BMI), glycemic parameters, such as HbA1c and time in range (TIR) were assessed. PWV was assessed by oscillometric method using the Mobil-O-Graph PWA device. Univariate and multivariate linear regression were used to explore the association of PWV z-score with anthropometric, demographic, and glycaemic variables.

Results

Significant negative association between PWV and age and height (β = −0.336, 95 % CI -0.44 to −0.25, p < 0.001 and β = −0.491, 95 % CI -0.62 to −0.36, p < 0.001, respectively), while gender showed a significant positive association with PWV, with females displaying higher PWV values compared to males (β = 0.366, 95 % CI 0.17 to 0.56, p < 0.001). TIR was positively associated with PWV (β = 0.092, 95 % CI 0.01 to 0.16, p = 0.017 only for patients having TIR ≤ 50 %. Finally, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were positively associated with PWV (β = 0.086, 95 % CI 0.02 to 0.14, p = 0.007 and β = 0.152, 95 % CI 0.07 to 0.23, p < 0.001, respectively).

Conclusion

Youth with T1DM who spend <50 % of time in range exhibit uniquely increased signs of arterial stiffness, indicating that poor glycemic control may contribute to early vascular damage. Differences related to age, gender and height should be considered.

Background

Pulse wave velocity (PWV) and augmentation index (AIx) are indices used to assess arterial stiffness. We evaluated the effect of sodium glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) on arterial stiffness indices.

Methods

We searched PubMed (up to January 2024) for RCTs assessing the effect of SGLT2i or GLP1-RA on arterial stiffness with reporting outcomes PWV and AIx. Effect sizes of the included studies were expressed as weighted mean difference (WMD) and 95 % confidence interval. Subgroup analyses were performed based on comparator (placebo vs. active comparator), design (RCT vs. crossover), population (diabetic vs. all) and blindness (yes vs. no).

Results

A total of 19 studies (SGLT2i, 12 studies; GLP1-RA, 5 studies; SGLT2i/GLP1-RA combination, 2 studies) assessing 1212 participants were included. We did not find any statistically significant association between GLP1-RA or SGLT2i and PWV or AIx. None of the subgroup analyses showed any statistically significant result.

Conclusion

No evidence of a favorable change in arterial stiffness indices (PWV, AIx) was found following the administration of SGLT2i or GLP1-RA.

Aims

To investigate effects of tirzepatide, a dual receptor agonist for glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1), on eating behaviors.

Methods

Eating behaviors were evaluated by using a validated questionnaire survey in 33 Japanese patients with type 2 diabetes mellitus (T2DM) (mean age: 51.8 years) who were treated with tirzepatide (2.5 mg/week for 4 weeks and then 5.0 mg/week) for 6 months (M).

Results

Treatment with tirzepatide significantly decreased median hemoglobin A1c (HbA1c) (baseline/3 M/6 M: 7.3 %/6.0 %/5.8 %), mean body weight (BW) (baseline/3 M/6 M: 87.7 kg/82.0 kg/79.6 kg) and mean relative score of eating behaviors (baseline/3 M/6 M: 57.0/50.7/45.9). In the GLP-1 receptor agonist (GLP-1RA) naïve group (n = 20, men/women: 13/7), HbA1c and BW were continuously decreased up to 6 M. Changes in eating behaviors were mainly observed in the first 3 M. In the GLP-1RA non-naïve group (n = 13, men/women: 8/5), reductions in HbA1c and BW were predominant in the first 3 M, and changes in eating behaviors were observed up to 6 M. There were no significant correlations of changes in scores of eating behaviors with changes in glycemic control or those in BW.

Conclusions

Tirzepatide ameliorates eating behaviors as well as glycemic management and obesity in Japanese patients with T2DM, and the patterns of improvement are partially dependent on prior exposure to GLP-1RAs.