Diabetes, Obesity & Metabolism最新文献

Aim: This real-world, retrospective cohort study aimed to assess the efficacy, safety and tolerability of oral semaglutide-the first GLP-1 receptor agonist available in oral form-in patients aged 65 years and older with type 2 diabetes mellitus (T2DM).

Materials and methods: The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline (V1) to six months (V3). Secondary endpoints included change in body weight, proportion of patients achieving HbA1c <7%, proportion of patients achieving both an HbA1c reduction of ≥1% and a body weight reduction of ≥5%. Exploratory endpoints were also assessed, including evaluations at three months (V2).

Results: One hundred and one patients (mean age 74.7 ± 6.1 years) started oral semaglutide treatment. Mean HbA1c decreased significantly from V1 to V3 (change: -0.44%, p < 0.001), with reductions already evident at V2. The proportion of patients achieving an HbA1c ≤7% increased from 36.6% at V1 to 61.7% at V3. At V3, 9.6% of patients achieved an HbA1c reduction of ≥1% and a weight loss of ≥5%. Body weight decreased from a baseline mean of 76.8-73.7 kg at V3 (p < 0.001). Body mass index, waist circumference, total cholesterol, low-density lipoprotein cholesterol and systolic blood pressure decreased significantly from V1 to V3, with changes already evident at V2. Eleven patients (10.9%) reported adverse events. Seven patients (6.9%) discontinued treatment.

Conclusion: Oral semaglutide effectively improves glycaemic control and weight management in elderly patients with T2DM while improving lipid and cardiovascular parameters and proving to be safe and well tolerated.

Aims: To date, bariatric surgery (BS) is the most effective long-term treatment for obesity, but weight regain (WR) is common. The very low-calorie ketogenic diet (VLCKD) is effective for weight loss and may influence gut microbiota (GM) composition, but it has been scarcely evaluated in post-bariatric patients. This study compared the efficacy and safety of a VLCKD in patients with WR post-bariatric surgery (BS+) and in bariatric surgery-naïve patients (BS-).

Methods: In this prospective, case-control study, 33 patients (15 BS+, 18 BS-) underwent an 8-week-long VLCKD. Outcomes included weight loss, metabolic profile, safety and GM composition.

Results: Both groups achieved significant weight loss (BS+: -6.9%, BS-: -8.3%), but the BS+ group showed slightly less metabolic improvement, particularly in insulin resistance and triglycerides. GM composition differed at baseline, reflecting the lasting effects of BS, and VLCKD led to significant changes in both groups. Microbial diversity and specific taxonomic shifts were more pronounced in BS- patients. Mild renal function changes were noted in BS+ patients, though these remained within clinically acceptable ranges.

Conclusion: VLCKD is effective in both BS+ and BS- patients, though metabolic and microbial responses may be less robust post-surgery, possibly due to anatomical and physiological changes. Tailored approaches may be therefore needed to optimize outcomes in post-bariatric patients.

Aims: This analysis evaluated whether gastrointestinal (GI) adverse events (AEs) including nausea, vomiting, diarrhoea (N/V/D) and dyspepsia were associated with weight reduction with tirzepatide across the SURMOUNT-1 to -4 trials.

Materials and methods: SURMOUNT-1 to -4 were global Phase 3 clinical trials evaluating the safety and efficacy of tirzepatide among participants with obesity or overweight with or without type 2 diabetes (T2D). Participants were randomly assigned to receive once weekly subcutaneous tirzepatide or placebo. This post hoc analysis investigated weight change at the primary endpoint from baseline among participants who self-reported no N/V/D, any N/V/D or nausea alone. Mediation analyses evaluated the contribution of N/V/D and dyspepsia on weight reduction. Time to first use of antidiarrheal and antiemetic usage was reported by time intervals.

Results: Baseline characteristics were similar between participants who reported N/V/D and those who did not. More participants reported GI AEs in the tirzepatide treatment arms (27.8%-72.8%) than with placebo (12.2%-32.5%). Most GI AEs were non-serious and occurred during dose escalation. Between 1.0% and 10.5% of tirzepatide-treated participants discontinued treatment due to GI AEs. Weight reduction with tirzepatide was similar among participants reporting no nausea, nausea alone, or any N/V/D. Mediation analyses suggested that N/V/D and dyspepsia were associated with up to 3.1% of total weight reduction. When required, first use of antidiarrheal and antiemetic medication was most commonly reported during dose escalation.

Conclusions: In this post hoc analysis, GI AEs appeared to contribute slightly to the weight reduction seen with tirzepatide in participants with obesity or overweight with or without T2D.

Background: Fatty liver disease may be associated with increased risks of intrahepatic and extrahepatic cancers. Our objective was to investigate associations between new subcategories of steatotic liver disease (SLD) recently proposed by nomenclature consensus group and cancer risk.

Methods: A total of 283 238 participants from the UK Biobank were included. Based on information on cardiometabolic factors, alcohol consumption and the specific aetiology of SLD, individuals were categorized into four groups: no SLD (n = 170 885), metabolic dysfunction-associated steatotic liver disease (MASLD, n = 74 510), MASLD with increased alcohol intake (MetALD, n = 23 320) and other SLD (n = 6718). Outcomes were overall incident cancer (n = 39 352) and 21 site-specific cancers. The Cox proportional hazards model was used to estimate relationships between subcategories of SLD and cardiometabolic factors in MASLD with cancer risk. Population attributable risk (PAR) of cancer associated with SLD was estimated.

Results: MASLD was the most prevalent SLD in the general population. All SLD subcategories were associated with elevated risks of overall cancer, digestive system cancers (except gastric cancer) and breast cancer (HRs 1.079-4.663). Additionally, MASLD was associated with increased risks of renal cancer, endometrial cancer and Hodgkin lymphoma. Compared to MetALD and other SLDs, MASLD has a higher PAR% for the majority of aforementioned cancers. This could be largely explained by its common metabolic abnormalities, dominantly characterized by overweight/obesity and elevated blood pressure, concomitant with hyperglycaemia and hyperlipidaemia.

Conclusions: All subcategories of SLD, particularly MASLD with multiple metabolic abnormalities, were associated with increased risks of multiple cancers, providing a new perspective for cancer prevention.

Aim: To assess the efficacy of the combined administration of myo-inositol and zinc, a mineral involved in the insulin pathway, in paediatric obesity with insulin resistance on HOMA-IR, glucose-insulin metabolism, and lipid profile.

Materials and methods: Double-blind, randomized, placebo-controlled study conducted in North Italy. Fifty-six patients (10-18 years, Tanner stage ≥3) with obesity and insulin resistance were randomized to myo-inositol (2000 mg), zinc gluconate (5 mg), and galactooligosaccharides (GOS) from plant-based origin (1000 mg) (TRT) or placebo (PLC) containing only GOS from plant-based origin (1000 mg). All patients received an isocaloric diet following the Mediterranean diet style. Data were collected at baseline (V0) and after 3 months (V1). The primary outcome was the insulin resistance index (HOMA-IR).

Results: Fifty out of 56 recruited subjects completed the study. TRT improved HDL cholesterol level compared to PLC (p = 0.05) but not insulin resistance. A stratified post hoc analysis was performed by sex, BMI, and subgroups of adherence to the Mediterranean diet. Subjects were divided for obesity grade, fasting insulin (p = 0.0137) and HOMA-IR (p = 0.0273) were lower in TRT than in PLC patients, with a greater effect on severe obesity. No adverse events were detected.

Conclusion: Three months of supplementation with myo-inositol and zinc were beneficial on lipid profile and in managing obesity complications at least in subjects with severe phenotype. Thus, myo-inositol and zinc could be used as non-pharmacological agents. This work suggests a long-term study with a larger sample size to enrich the findings.

Background: The body weight following bariatric surgery is a primary concern for both healthcare professionals and surgical candidates. However, it remains unclear whether variations in preoperative fat distribution influence weight loss outcomes.

Objective: The aim of this study was to evaluate the effect of abdominal fat distribution on postoperative weight loss and body mass index (BMI) reduction, and to clarify the role of different fat depots in weight loss outcomes.

Methods: Preoperative data from patients with overweight or obesity, along with their weight records at 1, 2 and 5 years following surgery, were retrospectively collected. Multiple levels of abdominal fat areas were measured using computerized tomography imaging. Statistical analyses included Pearson's correlation coefficients, multiple linear regressions, ridge regressions, decision tree regressions and paired t tests to evaluate the associations and influences.

Results: A total of 139 patients were initially included. The statistical analysis results indicated that umbilical subcutaneous adipose tissue (SAT) was an independent factor influencing weight and BMI loss at the 1-year follow-up (n = 67, p < 0.01). Furthermore, umbilical SAT demonstrated significant correlations with sustained BMI reduction over the long term.

Conclusion: Umbilical SAT is a significant factor in postoperative weight and BMI loss. Patients with greater SAT may experience more substantial weight and BMI reductions following surgery, offering new insights into personalized weight loss strategies and alternative approaches for assisted weight loss.

Aim: SGLT2 inhibitors may be underused in older adults with type 2 diabetes due to concerns about safety and tolerability. This pooled analysis of the CANVAS Program and CREDENCE trial examined the efficacy and safety of canagliflozin according to age.

Methods: Pooled individual participant data from the CANVAS Program (n = 10 142) and CREDENCE trial (n = 4401) were analysed by baseline age (<65 years, 65 to <75 years, and ≥75 years). A range of adjudicated clinical outcomes were assessed, including major adverse cardiovascular events and CKD progression, as well as safety outcomes. Cox proportional hazards models and Fine and Gray competing risk analysis were used.

Results: Among the 14 543 participants, 7927 (54.5%) were <65 years, 5281 (36.3%) were 65 to <75 years and 1335 (9.2%) were ≥75 years. Older participants had higher rates of atherosclerotic cardiovascular disease and heart failure, longer diabetes duration and lower mean eGFR. Reductions in cardiovascular and kidney outcomes with canagliflozin were consistent across age categories (all p trend >0.10), although there was some evidence that effects on cardiovascular death and all-cause death were attenuated with older age (p trend = 0.02 and 0.03, respectively). Although the incidence of adverse events increased with age, effects of canagliflozin on safety outcomes including acute kidney injury, volume depletion, urinary tract infections and hypoglycaemia, were not modified by age (all p trend >0.10).

Conclusions: In patients with varying degrees of kidney function, canagliflozin reduced cardiovascular and kidney outcomes, regardless of age, with no additional safety concerns identified in older patients.

Aims: TCF7L2 rs7903146 is the most impactful single genetic risk variant for type 2 diabetes. However, its role on disease progression, complications and mortality among people with type 2 diabetes at diagnosis remains unclear.

Materials and methods: We assessed the per allele impact of the rs7903146 T-allele on clinical characteristics and complication risk in 9231 individuals with type 2 diabetes at diagnosis and over a 10-year follow-up period. Log-binomial and robust Poisson regression analyses were used to estimate prevalence ratios for clinical characteristics and macro- and microvascular complications at diabetes onset, while Cox regression was applied to estimate the risk of complications post-diagnosis. Analyses were adjusted for sex, calendar year at birth, age at enrollment and diabetes duration.

Results: The per T-allele impact was associated with 0.6 kg/m² (95% CI: 0.4, 0.8) lower BMI, 1.4 cm (95% CI: 1.0, 1.8) smaller waist circumference, 5.6% (95% CI: 4.2, 7.0) lower insulin secretion and 5.0% (95% CI: 3.3, 6.7) higher insulin sensitivity. Over 10 years, the per T-allele impact was associated with lower risks for major adverse cardiovascular events (0.87 [95% CI 0.79, 0.95]), myocardial infarction (0.82 [95% CI: 0.72, 0.93]) and heart failure (0.85 [95% CI 0.73, 1.00]), with no significant impact on microvascular complications.

Conclusions: The TCF7L2 variant is associated with less obesity, lower insulin secretion and higher insulin action at diabetes onset, and decreased risk of cardiovascular events following type 2 diabetes onset.

Objective: Time in range (TIR) is an important metric to measure variability of blood glucose levels. The aim is to quantify the long-term health benefits and economic return associated with improved TIR for individuals with type 2 diabetes (T2D).

Method: A Markov model with three states (T2D, T2D with cardiovascular disease (CVD) and death) estimated 20-year medical costs, quality-adjusted life-years (QALY) gained and CVD risk under four TIR scenarios: >85%, 71%-85%, 51%-70% and ≤50%. The T2D population was identified using the National Health and Nutrition Examination Survey, and model parameters were sourced from literature. Costs were estimated from a healthcare sector perspective and standardized to 2021 US dollars. Cost ceilings were determined using three willingness-to-pay (WTP) thresholds: $100 000/QALY, $50 000/QALY and $0/QALY (cost-saving).

Results: Compared to TIR <50%, improving TIR to 51%-70% resulted in a 0.79 QALY increase and 4.91% CVD risk reduction; to 71%-85%, a 0.95 QALY increase and 6.24% CVD risk reduction; to >85%, a 1.18 QALY increase and 8.75% CVD risk reduction. To be cost-effective at $100 000/QALY, annual costs for TIR improvements from <50% to 51%-70%, 71%-85% and >85% should be <$1148, $4200 and $7252, respectively. To be cost-saving, these costs should be <$612, $2816 and $5021.

Conclusion: Improving TIR yields significant health benefits. We calculated feasible medical cost allocations for TIR improvements, informing the implementation of interventions like continuous glucose monitoring devices.

Aim: There is ongoing debate concerning the association of metformin with the risk of dementia in type 2 diabetes mellitus (T2DM). This study was conducted to evaluate the impact of metformin therapy on dementia in patients with T2DM.

Materials and methods: PubMed, Embase, Cochrane Library, Web of Science and the ClinicalTrials.gov website were searched until 9 April 2024. Cohort studies investigating the effects of metformin therapy compared with other antidiabetic drugs or no therapy in T2DM were included. The hazard ratio (HR) and the 95% confidence interval (CI) were computed using the random effects model.

Results: Twenty cohort studies (24 individual comparisons) involving 3 463 100 participants were identified. A meta-analysis revealed that people with T2DM who take metformin are linked to a lower incidence of all-cause dementia compared to non-user (n = 17, HR = 0.76, 95% CI = 0.65-0.91, p = 0.002, I² = 98.9%) and sulfonylureas (n = 5, HR = 0.88, 95% CI = 0.85-0.90, p < 0.001, I² = 9.7%), but not to thiazolidinedione (n = 2, HR = 0.53, 95% CI = 0.08-3.41, p = 0.503, I² = 92.7%). Additionally, metformin showed favourable effects in non-specified T2DM (n = 19, HR = 0.75, 95% CI = 0.64-0.89), but not in newly diagnosed T2DM (n = 5, HR = 1.01, 95% CI = 0.81-1.27).

Conclusion: Metformin might correlate with a lower dementia incidence in people with T2DM. However, it is crucial to interpret these results with caution considering the high heterogeneity.