Diabetes, Obesity & Metabolism最新文献

Aim: Digital health interventions and economic incentives have shown promise in facilitating diabetes self-management, though evidence is limited. Therefore, this study aimed to evaluate the effectiveness and cost-effectiveness of a comprehensive app-based diabetes self-management programme with rewards for healthy behaviours and health outcomes.

Materials and methods: The TRIal to slow the Progression Of Diabetes (TRIPOD) study was an open-label, parallel-group, randomised controlled trial conducted at Duke-NUS Medical School, Singapore. Adults with Type 2 Diabetes (diabetes), HbA_1c of 7.5%-11.0% (inclusive) and taking at least one oral diabetes medication were eligible. In total, 269 participants were randomised across three arms [Usual care (UC): 117, diabetes management programme (DMP) (intervention without rewards): 36, DMP+ (intervention with rewards): 116]. Data were analysed using intention-to-treat analysis with change in HbA_1c at month 12 between DMP+ and UC as the primary outcome. Cost-effectiveness of DMP+ relative to UC was also calculated.

Results: Mean HbA_1c improved by 0.1% in UC and by 0.5% in DMP+ at 12 months, revealing a mean difference of 0.4% (95% confidence interval (CI): -0.70, -0.08, p = 0.015). The odds ratio of HbA_1c improvements of >0.5% was 2.12 (95% CI: 1.17, 3.85, p = 0.013) for DMP+ relative to UC. The incremental cost-effectiveness ratio of DMP+ relative to UC was SGD8,516 (USD6,531) per quality-adjusted life year gained if effectiveness could be maintained with a single year of intervention.

Conclusions: A comprehensive app-based diabetes self-management programme with rewards for healthy behaviours and health outcomes (DMP+) cost-effectively improved glycaemic control in Type 2 diabetes patients. Organizations focusing on value-based healthcare should consider subsidising similar interventions.

Background: Previous studies indicated that metabolic heterogeneity of obesity would affect the risk of cardiovascular disease (CVD). However, the alterations in CVD risk associated with transitions between various metabolic health statuses influenced by obesity status remain unclear.

Methods: We utilized data from the China Health and Retirement Longitudinal Study (CHARLS), a longitudinal cohort study involving Chinese residents aged 45 years and older. Baseline data were collected in 2011-2012, with follow-up surveys conducted up to 2020. Participants in the study were categorized into four body mass index-metabolic phenotypes: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obesity (MHOO), metabolically unhealthy normal weight (MUNW) and metabolically unhealthy overweight/obesity (MUOO). Transitions in these phenotypes over 4 years were analysed. Cox regression models were used to assess the associations of these phenotypes and their transitions with CVD incidence.

Results: Among 7721 participants, 1353 (17.5%) developed CVD during the follow-up period. Both overweight/obese and metabolically unhealthy statuses were associated with increased CVD risk. The highest risk was observed in the MUOO group (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.50-2.09, p < 0.0001), followed by the MUNW (HR 1.35, 95% CI: 1.13-1.66, p < 0.001) and MHOO (HR: 1.29, 95% CI: 1.08-1.56, p = 0.002) groups compared to the MHNW group. The deteriorations of obesity and metabolic health status elevated the incidence of CVD, whereas improvements in these statuses reduced the risk of CVD. Additionally, alterations in metabolic health status conferred greater benefits in overweight/obese individuals compared to those with normal weight.

Conclusion: The study highlights the importance of maintaining and promoting metabolic health, particularly in overweight/obese individuals, to reduce CVD risk. Metabolic health status plays a more crucial role than obesity status in predicting CVD incidence.

Aims: Dyslipidemia is a risk factor for cardiovascular diseases. Some patients are resistant to conventional treatment. In these patients, there is the possibility of using PCSK9 inhibitors. The objective of this systematic review was to compare alirocumab with inclisiran in improving the lipid profile.

Materials and methods: This study was carried out in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols Statement (PRISMA) and registered with PROSPERO (CRD42024563261). The following databases were accessed on 2 July 2024: PubMed, Scopus and Web of Science. Clinical trials that evaluated the lipid profile were included. With these data, meta-analyses were carried out seeking to evaluate the difference between the baseline and the 12- and 24-week endpoints.

Results: Initially, 1157 studies were found, of which 32 were included. In total, 30 718 patients participated in the included studies. There was a statistically significant difference, favouring alirocumab 75 mg (-51.54%, 95% confidence interval [CI] -53.43%; -49.66%), in relation to inclisiran 300 mg (-41.34%, 95% CI -50.30%; -31.34%) in reducing low-density lipoprotein cholesterol (LDL-C) (p = 0.05), in relation to inclisiran 200 and 300 mg in reducing total cholesterol (p < 0.01) (p < 0.01) and triglycerides (p = 0.02) (p = 0.04) in 24 weeks. Furthermore, alirocumab 150 mg was superior to both doses of inclisiran in reducing total cholesterol (p < 0.01) (p < 0.01). There was no statistically significant difference in the reduction of lipoprotein(a) by alirocumab 75 mg (-22.35%, 95% CI -24.67; -20.03) and 150 mg (-25.17%, 95% CI -30.94; -19.41) compared to inclisiran 300 mg (-13.37, 95% CI -28.66; 1.93) (p = 0.26) (p = 0.16).

Conclusion: Alirocumab was superior to inclisiran in improving the lipid profile, especially in reducing LDL-C, total cholesterol and triglycerides.

Aims: Define the relationship between N-terminal atrial natriuretic peptide (NT-ANP) levels and incident metabolic syndrome and type 2 diabetes mellitus ('metabolic disease') in healthy adults and develop a risk prediction score.

Materials and methods: Retrospective cohort study of Olmsted County Heart Function Study participants, a random sampling of county residents aged 45 years and older (n = 2042). Clinical data were collected during enrolment between 1997 and 2000 and upon follow-up 4 years later. Outcomes were followed for 8 years. We studied 715 subjects without metabolic disease at enrolment who completed follow-up, assessing incident metabolic disease as the primary outcome. Youden's index was used to identify optimal cut-points and develop the risk score.

Results: Upon multivariate analysis adjusting for age gender, HDL and triglycerides, higher baseline serum NT-ANP levels were associated with a lower risk of metabolic disease (OR: 0.65, CI 0.49-0.85, p = 0.002). Higher baseline serum insulin and aldosterone levels were associated with higher risk of incident metabolic disease (OR: 2.04, CI 1.57-2.65, p < 0.001; OR: 1.43, CI 1.14-1.81, p = 0.002, respectively). Baseline serum NT-ANP < 3337 pg/mL was 96.6% sensitive for future development of metabolic disease. A weighted score including all three biomarkers was 78.6% sensitive and 77.3% specific.

Conclusions: In healthy adults aged 45 years or older, higher baseline NT-ANP levels are associated with a lower four-year risk of developing metabolic disease. Serum NT-ANP levels are a sensitive biomarker of future risk of metabolic disease and have screening utility when combined with insulin and aldosterone levels into a composite score.

Aims: Current evidence of the impact of acute exercise on insulin levels in individuals with type 1 diabetes remains controversial. Therefore, we conducted a systematic review and meta-analysis to explore exercise-induced changes in insulin levels.

Materials and methods: We conducted a systematic review (until 05 November 2023) and meta-analysis exploring the effect of exercise on insulin concentration in individuals with type 1 diabetes. We included randomised cross-over studies for rapid-acting insulin and pre- and post-studies for long-acting insulin in individuals with type 1 diabetes performing any type of acute exercise and had a control condition. The exercise-induced change in insulin levels was the outcome of interest. When possible, the mean differences (MDs) in insulin levels were pooled using the DerSimonian and Laird random effect method. Risk of bias was assessed for each included study.

Results: Seventeen trials, encompassing 186 participants with type 1 diabetes, were included in the systematic review. Twelve out of 17 studies included participants on rapid-acting insulin regimens and used a cross-over design, whereas five out of 17 single-arm studies included participants on (ultra)long-acting insulin. Seven out of 12 studies on rapid-acting insulins and all the single-arm studies were at high risk of bias. Results suggest a statistically significant, small-to-moderate increase of rapid-acting insulin after 30 min of exercise (MD of 18.44 [95% CI 0.02; 36.86; I² 0%] pmol/L); meanwhile, findings on (ultra)long-acting insulin were inconclusive.

Conclusions: A small-to-moderate increase of insulin levels in studies including rapid-acting insulin was found after a bout of physical exercise in individuals with type 1 diabetes. However, current gaps in high-quality evidence challenge our understanding of insulin kinetics around exercise.

Objective: The associations of lean mass distribution with mortality risk are not fully elucidated. We aimed to evaluate the effects of a new lean mass distribution indicator-android/gynoid lean mass ratio (AGLR) evaluated by dual-energy x-ray absorptiometry (DXA) on the risk of all-cause and specific-cause mortality in a NHANES cohort.

Methods: This was a population-based cohort study, which included 18 542 subjects aged 20 years and older from the US National Health and Nutrition Examination Survey (US NHANES, 2003-2006 and 2011-2018). The primary outcomes of our study were all-cause mortality, cardiovascular (CVD) mortality and cancer mortality, which were obtained from the linkage to registries. Cox proportional hazard regression models were used to investigate the association between lean mass distribution and mortality risk among the US NHANES general population. Restricted cubic spline nested in Cox regression was also used to test whether there was a non-linear association of AGLR as a continuous variable with the risk of mortality.

Results: During a median follow-up of 6.9 years, 1412 participants died, of whom 435 were due to CVD and 340 were due to cancer. The multivariable-adjusted (Model 4) hazard ratios (HRs) for each SD increase in AGLR were 1.53 (95% confidence interval [CI] 1.40-1.67) for all-cause mortality, 1.56 (95% CI 1.30-1.87) for cancer mortality and 1.64 (95% CI 1.47-1.84) for CVD mortality. The associations were robust in sensitivity analyses and present in most subgroups.

Conclusions: AGLR evaluated by DXA was associated with a higher risk of all-cause and specific-cause mortality among the general population from the US NHANES cohort.

Compared to glycated haemoglobin A1c (HbA1c), the rapidly developing continuous glucose monitoring (CGM) technology provides more detailed information about glycemic control. Amongst the new glucose metrics derived from CGM, time in target range of 3.9-10.0 mmol/L (time in range, TIR) has been widely used for the assessment of glucose control. In recent years, the rise of new technologies and therapies including advanced hybrid closed-loop automated insulin delivery systems and new hypoglycemic drugs has made it possible to achieve better glycemic control. In this context, the concept of time in tight range (TITR), defined as the percentage of time spent in target glucose range of 3.9-7.8 mmol/L, has gained increasing attention. Whilst TITR is highly correlated with TIR, there are still differences between the two metrics. These differences make TITR a more appropriate indicator in certain situations, such as when glucose levels are close to normal or when tighter glycemic control is required. This review summarizes recent studies related to TITR.

Background: Diabetic nephropathy (DN) is one of the main causes of end-stage renal disease (ESRD), but its mechanism has not been clearly studied. We utilized integrative transcriptome analysis to explore the pathogenesis of DN.

Methods: We conducted an analysis by combining bulk dataset and single-cell transcriptome dataset. Through this approach, we identified that Serpine2 may regulate the 'collagen-containing extracellular matrix' pathway involved in DN. Subsequently, we established DN animal and cell models using db/db mice and mesangial cells (MCs) to validate the role of Serpine2 in DN. In the animal model, we detected the expression level of Serpine2 in DN using western blotting (WB) and immunofluorescence (IF) assays. To further clarify the molecular mechanism of Serpine2 in DN, we knocked down Serpine2 and observed its effects on MCs proliferation and extracellular matrix (ECM) accumulation.

Results: Our single-cell analysis of DN models highlighted a pivotal role for MCs in the disease's initiation. Next, through Cytoscape analysis of differentially expressed genes (DEGs) in MCs, we identified the following 10 hub genes: Acta2, Angpt2, Ccn1, Col4a1, Col4a2, Col8a1, Kdr, Thbs1, Tpm4 and Serpine2. Subsequently, we identified that Serpine2 and Kdr were also significantly DEGs in the bulk analysis of glomeruli. Additionally, our integrated gene set enrichment analysis of bulk dataset and single-cell RNA dataset revealed that the 'collagen-containing extracellular matrix' was a key pathway in DN progression. Serpine2 was one of the crucial genes involved in regulating this pathway. Therefore, we speculated that the regulation of the 'collagen-containing extracellular matrix' pathway by Serpine2 was an important mechanism. Importantly, WB and IF staining confirmed that Serpine2 expression was upregulated in the MCs of diabetic mice. Knockdown of Serpine2 in cultured MCs alleviated high-glucose-induced excessive MCs proliferation and ECM accumulation. Finally, we found that ERK agonist Ro 67-7476 eliminated the effect of Serpine2 siRNA.

Conclusions: In summary, Serpine2 regulates MCs proliferation and ECM synthesis through activation of the ERK1/2 pathway, which is an important pathogenesis mechanism of DN. These findings offer fresh perspectives on the mechanisms of glomerulosclerosis in DN pathogenesis and may provide new targets for treating DN.

Aim: Intraindividual body weight variability (BWV), that is, the degree of weight fluctuations over time, is associated with an increased risk of cardiovascular diseases (CVDs) in multiple settings. The impact of BWV on cardiovascular risk in type 1 diabetes (T1D) remains unclear, despite the issues relative to weight management in individuals with this condition.

Materials and methods: Using data from the Swedish National Diabetes Register, we identified individuals with T1D and without CVD at baseline with at least three measurements of body weight taken over three consecutive years. We estimated BWV as quartiles of the standard deviation of weight measures and explored its longitudinal association with the incidence of CVD during a 12.7 ± 4.6 year follow-up through adjusted Cox regression models. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke and all-cause mortality. We modelled the function of risk in relation to the magnitude of BWV, testing also whether weight trends, that is, increasing, stable or decreasing, age, sex and glycaemic control modified the association between BWV and the outcome.

Results: Among the 36 333 individuals with T1D in the register, we identified 19 373 individuals with at least three measures of body weight and without CVD at baseline. Participants with the highest BWV had a 42% increased risk of reaching the primary endpoint compared to those with the lowest BWV (hazard ratio [HR] = 1.42, 95% confidence interval [CI]: 1.24-1.62). In addition, high BWV was significantly associated with a 51% increased risk of all-cause mortality (HR = 1.51, 95% CI: 1.28-1.78), a 37% increased risk of peripheral artery disease (HR = 1.37, 95% CI: 1.06-1.77) and a 55% increased risk of hospitalization for heart failure (HR = 1.55, 95% CI: 1.20-2.01). BWV showed a quasi-linear association with the primary endpoint. No interaction was observed when comparing subgroups for weight trends, sex or degree of glycaemic control. In the subgroup of elderly individuals, the association of BWV with the primary endpoint was no longer significant.

Conclusions: High BWV is associated with an increased risk of CVD and all-cause mortality in individuals with T1D, independently of canonical risk factors. Weight trends, sex and glycaemic control do not modify such association while older age attenuates it.