1.Clinical, metabolic, and autoimmune characteristics of newly diagnosed young Filipino adults with diabetes mellitus.
Elizabeth Paz-Pacheco ; Angelique Bea C. Uy ; Angelique Love Tiglao-Gica ; Anna Elvira S. Arcellana ; Aura Bree Dayo-Lacdao ; Cynthia P. Cordero ; Cecilia A. Jimeno ; Ma. Cecille Añ ; onuevo-Cruz ; Noel R. Juban
Acta Medica Philippina 2026;60(2):41-49
OBJECTIVES
In Asia, younger individuals (below age 45) are diagnosed to have type 2 diabetes with increased rates of obesity defined by lower BMI yet with greater visceral adiposity (waist circumference and waisthip ratios). The prevalence data on type 1 diabetes is not well established, considered to be low, but is seen to be increasing as well. This changing phenotype therefore, presents a clinical dilemma in terms of correctly classifying diabetes and deciding on the consequent appropriate treatment. Distinguishing type 1 from type 2 diabetes has become more difficult with type 2 diabetes dramatically increasing in young adults and children. This study aims to define the characteristics of diabetes among young adults in the Philippines to provide a basis for appropriate management amidst changes in diabetes phenotypes seen globally.
METHODSIn this cross-sectional analytic study, we characterized the demographic, metabolic, and autoimmune features of diabetes among young adult Filipinos aged 18 to 45 years old consulting at a tertiary referral center in Manila, Philippines. Baseline serum A1c, FBS, 75-g oral glucose tolerance test, insulin, serum C-peptide, insulin autoantibodies, leptin, adiponectin, lipid profile, and thyroid function tests were obtained from the participants and analyzed. The homeostasis model assessment (HOMA) was used to estimate the insulin sensitivity.
RESULTSA total of 348 patients with diabetes were included, with females comprising two-thirds of the participants. The mean age at diagnosis of diabetes was 35.9±7.22 years. The mean BMI was 28.12 kg/m2, with median waist to hip ratio (WHR) of 0·93. Metabolic syndrome was found in 60% of participants and 67.82% were obese by body mass index. The mean A1c was 9.07±2.52%. Good glucose control (A1c less than 7.0%) was seen in 23% of participants while nearly half (48%) had HbA1c which was >9.0%. The median levels of fasting insulin and C-peptide were 12.62 (range 1.33–90.42) mIU/L and 0.78 ng/mL (range 0–16.2), respectively.
Included participants were diagnosed with diabetes within a year and as such, majority did not have any micro- or macrovascular complications. The most common diabetes complication was sensory neuropathy detected by monofilament testing, which was found in 28% of participants, followed by non-proliferative diabetic retinopathy in 13%. A history of previous diabetic ketoacidosis was found in 10 patients (2.87%). Glutamic acid decarboxylase (GAD) and insulin auto-antibodies were found in 3.2% and 19.3% of participants, respectively. Approximately half (51.73%) of the participants were insulin resistant by HOMA-IR.
CONCLUSIONIn contrast with Caucasians and other Asians, diabetes among young Filipino adults is associated with lower BMI but with a similarly high visceral adiposity as shown by an elevated WHR. Metabolic syndrome with insulin resistance as defined by a variety of indices is predominant. Type 1 diabetes with autoantibodies occur in only a small fraction of this population. Data derived from this work can provide a framework for cluster analysis towards personalized management specific to this population.
Human ; Acids ; Adiponectin ; Adiposity ; Adult ; Aged ; Antibodies ; Asia ; Asian ; Asian Continental Ancestry Group ; Autoantibodies ; Body Mass Index ; C-peptide ; Carboxy-lyases ; Child ; Cluster Analysis ; Demography ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Diabetic Ketoacidosis ; Diabetic Retinopathy ; Diagnosis ; Fasting ; Female ; Glucose ; Glucose Tolerance Test ; Glutamate Decarboxylase ; Glutamic Acid ; Insulin ; Insulin Resistance ; Ketosis ; Leptin ; Lipids ; Metabolic Syndrome ; Obesity ; Patients ; Peptides ; Phenotype ; Philippines ; Population ; Prevalence ; Serum ; Therapeutics ; Thyroid Gland ; Thyroid Function Tests ; Young Adult
2.One-hour OGTT reveals what conventional screening misses: A hidden prediabetes burden in Malaysia
Gerard Jason Mathews ; Seetha Devi Subramanian ; Nor Shaffinaz Yusoff Azmi Merican ; Shartiyah Ismail ; Joel Mathews ; Leng Ean Charis Kong ; Chong Hui Khaw ; Shubash Shander Ganapathy ; Arvinder-Singh HS
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):1-
Introduction:
Prediabetes or intermediate hyperglycemia (IH) represents a critical phase in the trajectory toward type 2 diabetes mellitus
(T2DM). Recent evidence from the International Diabetes Federation (IDF) suggests that 1-hour OGTT (1HOGTT) ≥8.6
mmol/L is a more sensitive biomarker for early beta-cell dysfunction, with enhanced detection of IH and future T2DM
risk. Conventional screening using hemoglobin A1c (HbA1c) or 2-Hour OGTT (2HOGTT) may delay identification
of prediabetes, narrowing the window for early intervention. This study evaluates 1HOGTT as a screening tool for
prediabetes among Malaysians.
Methodology:
This cross-sectional study enrolled adults without prior T2DM or prediabetes. Participants underwent 1HOGTT, 2HOGTT,
and HbA1c, classified as per the Malaysian Clinical Practice Guideline for T2DM (6th Edition) and IDF 2024 criteria.
Agreement between tests was assessed using McNemar’s test and Cohen’s kappa. Diagnostic accuracy was evaluated
via receiver operating characteristic (ROC) curve analysis. Cost-effectiveness was determined using reagent cost only.
Results:
The majority of the 310 participants were female (71.6%), Malay (87.1%), with average age of 40. The 1HOGTT identified
prediabetes in 21.6% (n = 67) compared to 17.1% (n = 53) by HbA1c and 2.6% (n = 8) by 2HOGTT. McNemar’s test confirmed
statistically significant discordance between 1HOGTT and 2HOGTT (chi-square = 53.397, p <0.001): 61 participants were
prediabetic by 1HOGTT but normal by 2HOGTT, versus only 2 in the reverse direction. No significant discordance was
found between 1HOGTT and HbA1c (chi-square = 2.817, p = 0.093). 1HOGTT demonstrated excellent discriminatory
ability against 2HOGTT (AUC = 0.908; 95% CI: 0.837–0.978), significantly outperforming HbA1c (AUC = 0.664; CI: 0.462–
0.867; DeLong p = 0.012). In a population-level cost analysis, 1HOGTT achieved lowest cost per prediabetes case detected
(RM 5.79) – approximately 8.3 times and 8.1 times more cost-effective than 2HOGTT (RM 48.08) and HbA1c (RM 46.78)
respectively.
Conclusion
1HOGTT identifies a significant proportion of individuals with prediabetes missed by 2HOGTT and HbA1c. Incorporating 1HOGTT enhances the detection of prediabetes, is cost-effective, and enables timely preventive measures in our
population with high diabetes burden.
Glucose Tolerance Test
;
Glycated Hemoglobin
;
Prediabetic State
3.Efficacy and Safety of SGLT2 Inhibitors in Elderly (≥75 Years) With Type 2 Diabetes: A Real-World Study
Siew Wai Shuit ; Shamharini Nagaratnam ; Fei Bing Yong ; Norisha Nandini Passkaren ; Keen Tien Boey ; Nur Syahirah Asarapoo ; Sathya Rajagopal ; Vikganesa Mahalingam ; Zanariah Hussein
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):36-
Introduction:
Sodium-glucose-linked-transporter inhibitors (SGLT2-i)
have demonstrated cardiovascular and renal benefits in
type 2 diabetes mellitus (T2DM), but patients aged ≥75
years remain underrepresented in major trials, creating
uncertainty regarding their risk–benefit profile. Real-world
data show mixed safety signals. In Malaysia, local evidence
is limited despite a growing elderly diabetic population.
This study evaluates the glycemic efficacy and safety of
SGLT2-i in advanced elderly patients in a real-world public
hospital setting.
Methodology:
We conducted a retrospective observational cohort study
of patients aged ≥75 years with T2DM initiated on SGLT2-i
in Hospital Putrajaya (2020–2024). Electronic records were
reviewed for demographics, comorbidities, medications,
and biochemical parameters. Outcomes at 6–12 months
assessed glycemic control and safety. Adverse events
and discontinuation rates were recorded. Patients with
incomplete data, type 1 diabetes, active malignancy, or
severe renal impairment were excluded.
Results:
A total of 104 patients (mean age 78.2 years; 54% female)
were included with a high proportion (76.9%) classified as at
high cardiovascular risk due to established macrovascular
disease (57.7%) or nephropathy (53.8%). Indications for
SGLT2-i initiation were glycemic control alone (69.2%) and
together with cardiorenal protection (58.7%). Glycemic
control remained stable (hemoglobin A1c: 7.66–7.45%; p =
0.076), with preserved renal function (estimated glomerular
filtration rate: 58.65–58.11 mL/min/1.73 m²; p = 0.575).
Overall safety was favorable, with 90.4% experiencing no
adverse events. Minor adverse events included urinary
tract infections (2.9%) and polyuria (1.9%). ASCVD-related
hospitalizations occurred in 4.8% of patients, with a low
discontinuation rate (7.7%). A statistically significant
weight reduction was observed (baseline 66.67 kg, −1.01
kg; p = 0.005) but was not clinically significant. Proteinuria
improvement was noted in 15.7% of patients.
Conclusion
SGLT2-i are safe and well-tolerated in elderly T2DM
patients (≥75 years), with stable glycemic control, preserved
renal function, and minimal adverse events, supporting
their use in very elderly Asian populations.
Aged
;
Diabetes Mellitus, Type 2
;
Sodium-Glucose Transporter 2 Inhibitors
4.Real-World Continuous Glucose Monitoring Patterns in Malaysian Adults With Type 2 Diabetes: A Single-Centre Study
Ryan Jia Xian Koh ; Siti Nabilah Atiqah Othman ; Maszariffah Mashor ; Azni Abdul Latif ; Ooi Chuan Ng
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):45-46
Introduction:
Malaysia has one of the highest diabetes prevalence rates
in Asia (1 in 5), with >50% fail to achieve optimal glycemic
control. Continuous glucose monitoring (CGM) provides
detailed insights beyond hemoglobin A1c (HbA1c),
capturing daily glucose fluctuations and variability. Realworld data describing CGM patterns and their clinical
associations in Malaysian adults with type 2 diabetes
mellitus (T2DM) are limited.
Methodology:
This cross-sectional study analyzed CGM data from 25
Malaysian adults with T2DM, standardized over 14 days.
CGM metrics included time in range (TIR), time above
range (TAR), time below range (TBR), mean glucose,
and coefficient of variation (CV). Weekday–weekend
comparisons were performed, and correlations with
age, diabetes duration, HbA1c, body mass index (BMI),
treatment regimen, and complications were assessed.
Results:
Participants had a mean age of 56.2 ± 13.2 years (52%
male), mean HbA1c 9.4 ± 2.7%, diabetes duration 10.7 ±
9.0 years, and BMI 29.8 ± 9.4 kg/m². Mean TIR, TAR, TBR,
mean glucose, and CV were similar between weekdays
and weekends (p >0.34 for all). TIR >70% was achieved by
52% of participants on weekdays and 48% on weekends,
with no statistically significant difference (p = 0.75). Longer
diabetes duration correlated with lower TIR (r = −0.62, p <0.001), higher mean glucose (r = 0.58, p = 0.002), and greater
variability (r = 0.54, p = 0.004). Older age was associated with
lower TIR (r = −0.48, p = 0.014) and higher mean glucose (r
= 0.44, p = 0.025). Higher HbA1c correlated with lower TIR
(r = −0.36, p = 0.04), higher TAR (r = 0.35, p = 0.05), greater
variability (r = 0.51, p = 0.006), and increased target organ
damage (ρ = 0.55, p = 0.004). BMI was not associated with
TIR (r = −0.18, p = 0.38). Participants with ≥2 complications
had lower TIR (55.8 ± 28.4% vs 76.7 ± 19.2%, p = 0.073), while
insulin the
Conclusion
In Malaysian adults with T2DM, CGM metrics were similar
between weekdays and weekends, indicating lifestyle
differences had minimal impact on glycemic control. Longer
diabetes duration, older age, higher HbA1c, multiple
complications, and insulin therapy identified patients at
highest risk for poor glycemic control, greater variability,
and hypoglycemia. These findings support the use of
CGM for risk stratification, individualized monitoring,
and therapy optimization to reduce complications and
hypoglycemia risk.
Adult
;
Blood Glucose
;
Blood Glucose Self-Monitoring
;
Continuous Glucose Monitoring
;
Diabetes Mellitus, Type 2
5.The Hidden Risk of a First-Line Therapy: Renal Abscess With SGLT2 Inhibitor Use
Wei Ton Wong ; Khairi Syazwan Rashid ; Afiq Hazim Ab Rahim
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):52-53
Introduction:
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are
cornerstone therapies for heart failure and diabetes,
offering proven cardiorenal benefits. However, expanded
use necessitates vigilance regarding adverse effects,
particularly genitourinary infections. While mild cystitis is
common, serious upper urinary tract infections remain rare
and potentially life-threatening. We describe a case of renal
abscess presenting as recurrent urinary tract infections
(UTI) following SGLT2 inhibitor initiation, emphasizing
the need for clinical vigilance.
Case:
A 69-year-old male with a significant cardiovascular
history, including heart failure with reduced ejection
fraction (HFrEF), hypertrophic cardiomyopathy with an
implantable cardioverter-defibrillator for non-sustained
ventricular tachycardia, diabetes mellitus, hypertension,
and hyperlipidemia, presented with a 1-week history of
right flank pain, dysuria, urinary frequency, and fever.
Initial labs confirmed infection: leukocytosis (22.6 × 10³/ µL),
markedly elevated CRP (200 mg/L), and bacteriuria. He was
diagnosed with a UTI and started on IV Cefuroxime. This
marked his third UTI admission in 5 months, following
discharge just 3 weeks prior for septic shock secondary
to UTI, establishing a relapsing pattern. Subsequent urine
and blood cultures were unremarkable. Medication review
revealed Dapagliflozin had been initiated for HFrEF
8 months ago. Following clinical improvement from each prior UTI episode, Dapagliflozin was consistently
restarted. Despite an initial antibiotic response, symptoms
recurred after discharge each time. The recurrent nature
of his infections prompted a renal ultrasound revealing a
large (5.3 × 7.5 × 7.4 cm), non-drainable, heterogeneously
hypoechoic collection at the left kidney’s mid-lower pole,
diagnostic of an early renal abscess.
Conclusion
This report highlights renal abscess as a rare and severe
complication of SGLT2 inhibitor therapy. It serves as a
critical reminder that recurrent or relapsing UTIs in patients
on these agents should prompt immediate investigation
with renal imaging to rule out deep-seated pathology
rather than simple cystitis. While these drugs offer proven
cardiorenal benefits, their role in promoting urological
infections necessitates a cautious approach.
Abscess
;
Sodium-Glucose Transporter 2 Inhibitors
6.Blood collection tubes utilized for fasting blood sugar measurement.
Philippine Journal of Pathology 2026;11(1):30-36
BACKGROUND
Diabetes mellitus (DM) remains a major global health burden, with increasing prevalence in developing countries such as the Philippines. Accuracy of glucose measurement is vital for diagnosis and management; however, preanalytical variables, particularly glycolysis from varying collection tubes, temperature and time interval can significantly affect test results. Despite guideline recommendations favoring plasma, serum is still commonly used in local clinical practice.
OBJECTIVEThis study evaluated the effectiveness of different commercially available blood collection tubes in preserving glucose stability by minimizing pre-analytical glycolysis.
METHODOLOGYA cross-sectional observational and quasi-experimental study was conducted among 40 healthy adult participants (18–59 years) from a tertiary institution in Quezon City, Philippines. A total of 160 samples were collected using four tube types (one plasma and three serum tubes). Samples were analyzed at varying time intervals (0–180 minutes) and storage conditions (room temperature and 4°C). Glucose levels were measured using the glucose oxidase method. Statistical analysis included Shapiro–Wilk, Kruskal–Wallis H-test, Welch’s t-test, and Dwass–Steel–Critchlow–Fligner post hoc comparisons at a 1% significance level.
RESULTSGlucose concentrations differed significantly across tube types (pCONCLUSION
Blood collection tube type and delayed processing significantly influence glucose measurements. While acceptable within analytical limits, systematic biases may affect clinical interpretation. Standardization of blood collection practices and stricter pre-analytical protocols are essential to improve diagnostic accuracy for diabetes in the Philippines.
Medical Laboratory Science ; Diabetes Mellitus ; Blood Glucose ; Fasting
7.Bridging the Gap: Adoption and Barriers to Continuous Glucose Monitoring in Paediatric Type 1 Diabetes
Sok Bee Lim ; Siti Sarah Ahmad Dardiri ; Nalini M. Selveindran ; Arini Nuran Md Idris ; Janet Yeow Hua Hong
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):123-
Introduction:
ISPAD guidelines recommend continuous glucose monitoring (CGM) as the standard of care for paediatric type 1 diabetes
(T1DM). However, a “real-world” adoption gap persists, particularly in resource-limited settings. The Introductions of
the study were to evaluate CGM adoption prevalence, identify documented barriers, and compare glycemic outcomes
between active and non-active users.
Methodology:
This retrospective review analyzed electronic medical records (EMR) of 125 paediatric T1DM patients at Hospital Putrajaya
(2025). Data included CGM status, insulin delivery method, and documented barriers. Independent T-tests compared
mean hemoglobin A1c (HbA1c) between groups, and multivariable logistic regression identified independent predictors
of adoption.
Results:
Cohort mean age was 11.8 ± 3.8 years. Active CGM users were 32.8% (n = 41), of whom 29.3% (n = 12) utilized predominantly
automated insulin delivery (AID) systems. The remaining 67.2% (n = 84) were classified as non-active users, comprising
both never-users and ex-users (discontinued use). Active users achieved significantly lower mean HbA1c than non-active
users (8.73% vs 9.86%; p <0.001), with no significant difference in rates of DKA (p = 0.564) or severe hypoglycemia (p =
0.250). Among never-users, 42.9% lacked documented technology counselling (p = 0.001). Multivariable analysis identified
funding source as the sole independent predictor of CGM adoption (adjusted OR = 7.76, p <0.001). While the primary
documented barrier was financial (31.0%), a lack of documented barriers was noted in 61.9% of non-active users.
Conclusion
A substantial technology gap exists, primarily driven by financial access rather than clinical demographics. The difference
of 1.13% in HbA1c between groups underscores the need to address financial setbacks to improve technology access in
Malaysia and prevent diabetes complications.
Child
;
Blood Glucose
;
Blood Glucose Self-Monitoring
;
Continuous Glucose Monitoring
;
Diabetes Mellitus, Type 1
8.Moxibustion at different temperatures for cognitive impairment in type 2 diabetes mellitus: a randomized controlled trial.
Yan WEI ; Yuhao QU ; Aihong YUAN ; Lele ZHANG ; Min YE ; Qunwei LI ; Hongyu XIE
Chinese Acupuncture & Moxibustion 2025;45(9):1233-1240
OBJECTIVE:
To observe the effects of moxibustion at different temperatures on cognitive function and blood glucose levels in patients with cognitive impairment associated with type 2 diabetes mellitus (T2DM).
METHODS:
A total of 66 T2DM patients with cognitive impairment were randomly assigned to a high-temperature group (22 cases, 1 case dropped out, 1 case was eliminated), a medium-temperature group (22 cases, 2 cases were eliminated), and a low-temperature group (22 cases, 2 cases were eliminated). All groups received moxibustion at Baihui (GV20), Dazhui (GV14), and Shenting (GV24) based on their existing glycemic control treatment. Moxibustion temperatures were maintained at 44-46 ℃ (high-temperature group), 41-43 ℃ (medium-temperature group), and 38-40 ℃ (low-temperature group), respectively, for 20 min per session, every other day, 3 times a week for 3 months. The Montreal cognitive assessment (MoCA) score, mini-mental state examination (MMSE) score, short-term memory (STM) accuracy and average reaction time, Rey-Osterrieth complex figure (ROCF) score, fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were assessed before and after treatment. Clinical efficacy was evaluated after treatment.
RESULTS:
After treatment, MMSE scores in all three groups were higher than those before treatment (P<0.05). In the high-temperature group, the total MoCA score and the scores of visuospatial and executive function, memory and delayed recall, attention, naming, language, and abstraction were higher than those before treatment (P<0.05); the scores of ROCF copy, immediate recall, and delayed recall were higher than those before treatment (P<0.05); the HbA1c level was lower than that before treatment (P<0.05). In the medium-temperature group, the total MoCA score and the scores of memory and delayed recall, attention, and language were higher than those before treatment (P<0.05). STM accuracy was higher than before treatment (P<0.05), and STM average reaction time was shorter than before treatment (P<0.05) in both the high-temperature and medium-temperature groups. After treatment, the total MoCA score and the scores of visuospatial and executive function, memory and delayed recall, attention, and language in the high-temperature group were higher than those in the medium- and low-temperature groups (P<0.05); MMSE score, STM accuracy, and ROCF immediate recall and delayed recall scores were higher than those in the medium- and low-temperature groups (P<0.05); STM average reaction time was shorter than that in the medium- and low-temperature groups (P<0.05); HbA1c level was lower than that in the low-temperature group (P<0.05). The total MoCA score, attention score, and MMSE score in the medium-temperature group were higher than those in the low-temperature group (P<0.05), and STM average reaction time was shorter than that in the low-temperature group (P<0.05). There were no statistically significant differences in FPG within or between the three groups before and after treatment (P>0.05). The total effective rates were 75.0% (15/20) in the high-temperature group, 50.0% (10/20) in the medium-temperature group, and 15.0% (3/20) in the low-temperature group; the total effective rate in the high-temperature group was significantly higher than that in the low-temperature group (P<0.05).
CONCLUSION
Moxibustion at different temperatures has a dose-effect relationship in treating cognitive impairment in T2DM patients. A temperature range of 44-46 ℃ is more effective in improving cognitive function and stabilizing average blood glucose levels over 2-3 months.
Humans
;
Diabetes Mellitus, Type 2/therapy*
;
Male
;
Female
;
Moxibustion
;
Middle Aged
;
Aged
;
Cognitive Dysfunction/psychology*
;
Cognition
;
Temperature
;
Blood Glucose/metabolism*
;
Adult
;
Acupuncture Points
9.Pharmacotherapy in patients with heart failure with reduced ejection fraction: A systematic review and meta-analysis.
Jia TANG ; Ping WANG ; Chenxi LIU ; Jia PENG ; Yubo LIU ; Qilin MA
Chinese Medical Journal 2025;138(8):925-933
BACKGROUND:
Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated.
METHODS:
PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI).
RESULTS:
We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI + BB + MRA + SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI + BB + MRA + SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI + BB + MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle ACEI + BB + MRA in improving LVEF. ACEI + BB + MRA + SGLT-2i was better than ACEI + BB + MRA (-8.05 mL/m 2 , 95% CI: -14.88 to -1.23 mL/m 2 ) and ACEI + BB + SGLT-2i (-18.94 mL/m 2 , 95% CI: -36.97 to -0.61 mL/m 2 ) in improving LVEDVI. ACEI + BB + MRA + SGLT-2i (-3254.21 pg/mL, 95% CI: -6242.19 to -560.47 pg/mL) was superior to ARB + BB + MRA in reducing NT-proBNP.
CONCLUSIONS:
Adding SGLT-2i to ARNI/ACEI + BB + MRA is beneficial for reversing cardiac remodeling. The new quadruple drug "ARNI + BB + MRA + SGLT-2i" is superior to the golden triangle "ACEI + BB + MRA" in improving LVEF.
REGISTRATION
PROSPERO; No. CRD42022354792.
Humans
;
Heart Failure/physiopathology*
;
Stroke Volume/physiology*
;
Angiotensin Receptor Antagonists/therapeutic use*
;
Angiotensin-Converting Enzyme Inhibitors/therapeutic use*
;
Sodium-Glucose Transporter 2 Inhibitors/therapeutic use*
;
Randomized Controlled Trials as Topic
;
Mineralocorticoid Receptor Antagonists/therapeutic use*
;
Adrenergic beta-Antagonists/therapeutic use*
10.Systemic comparison of molecular characteristics in different skin fibroblast senescent models.
Xiaokai FANG ; Shan ZHANG ; Mingyang WU ; Yang LUO ; Xingyu CHEN ; Yuan ZHOU ; Yu ZHANG ; Xiaochun LIU ; Xu YAO
Chinese Medical Journal 2025;138(17):2180-2191
BACKGROUND:
Senescent human skin primary fibroblast (FB) models have been established for studying aging-related, proliferative, and inflammatory skin diseases. The aim of this study was to compare the transcriptome characteristics of human primary dermal FBs from children and the elderly with four senescence models.
METHODS:
Human skin primary FBs were obtained from healthy children (FB-C) and elderly donors (FB-E). Senescence models were generated by ultraviolet B irradiation (FB-UVB), D-galactose stimulation (FB-D-gal), atazanavir treatment (FB-ATV), and replication exhaustion induction (FB-P30). Flow cytometry, immunofluorescence staining, real-time quantitative polymerase chain reaction, co-culturing with immune cells, and bulk RNA sequencing were used for systematic comparisons of the models.
RESULTS:
In comparison with FB-C, FB-E showed elevated expression of senescence-related genes related to the skin barrier and extracellular matrix, proinflammatory factors, chemokines, oxidative stress, and complement factors. In comparison with FB-E, FB-UVB and FB-ATV showed higher levels of senescence and expression of the genes related to the senescence-associated secretory phenotype (SASP), and their shaped immune microenvironment highly facilitated the activation of downstream immune cells, including T cells, macrophages, and natural killer cells. FB-P30 was most similar to FB-E in terms of general transcriptome features, such as FB migration and proliferation, and aging-related characteristics. FB-D-gal showed the lowest expression levels of senescence-related genes. In comparisons with the single-cell RNA sequencing results, FB-E showed almost complete simulation of the transcriptional spectrum of FBs in elderly patients with atopic dermatitis, followed by FB-P30 and FB-UVB. FB-E and FB-P30 showed higher similarity with the FBs in keloids.
CONCLUSIONS
Each senescent FB model exhibited different characteristics. In addition to showing upregulated expression of natural senescence features, FB-UVB and FB-ATV showed high expression levels of senescence-related genes, including those involved in the SASP, and FB-P30 showed the greatest similarity with FB-E. However, D-galactose-stimulated FBs did not clearly present aging characteristics.
Humans
;
Fibroblasts/drug effects*
;
Cellular Senescence/physiology*
;
Skin/metabolism*
;
Child
;
Transcriptome/genetics*
;
Aged
;
Ultraviolet Rays
;
Cells, Cultured
;
Galactose/pharmacology*


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