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.Qishen Granules Modulate Metabolism Flexibility Against Myocardial Infarction via HIF-1 α-Dependent Mechanisms in Rats.
Xiao-Qian SUN ; Xuan LI ; Yan-Qin LI ; Xiang-Yu LU ; Xiang-Ning LIU ; Ling-Wen CUI ; Gang WANG ; Man ZHANG ; Chun LI ; Wei WANG
Chinese journal of integrative medicine 2025;31(3):215-227
OBJECTIVE:
To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation.
METHODS:
In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions.
RESULTS:
QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism.
CONCLUSIONS
QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals
;
Myocardial Infarction/physiopathology*
;
Male
;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
;
Rats, Sprague-Dawley
;
Glucose/metabolism*
;
Drugs, Chinese Herbal/therapeutic use*
;
Energy Metabolism/drug effects*
;
Rats
;
Fatty Acids/metabolism*
;
Myocardium/pathology*
9.Huanglian-Renshen-Decoction Maintains Islet β-Cell Identity in T2DM Mice through Regulating GLP-1 and GLP-1R in Both Islet and Intestine.
Wen-Bin WU ; Fan GAO ; Yue-Heng TANG ; Hong-Zhan WANG ; Hui DONG ; Fu-Er LU ; Fen YUAN
Chinese journal of integrative medicine 2025;31(1):39-48
OBJECTIVE:
To elucidate the effect of Huanglian-Renshen-Decoction (HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β -cell identity through regulating paracrine and endocrine glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) in both islet and intestine.
METHODS:
The db/db mice were divided into the model (distilled water), low-dose HRD (LHRD, 3 g/kg), high-dose HRD (HHRD, 6 g/kg), and liraglutide (400 µ g/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group (n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Then, GLP-1, GLP-1R, prohormone convertase 1/3 (PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA), and pancreatic and duodenal homeobox 1 (PDX1) were detected by Western blot, IHC, IF, and real-time quantitative polymerase chain reaction, respectively.
RESULTS:
HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time (P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon (P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass (P<0.01). After HRD treatment, the levels of GLP-1, GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased (P<0.05 or P<0.01).
CONCLUSION
HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.
Animals
;
Glucagon-Like Peptide 1/metabolism*
;
Diabetes Mellitus, Type 2/metabolism*
;
Glucagon-Like Peptide-1 Receptor/metabolism*
;
Insulin-Secreting Cells/pathology*
;
Drugs, Chinese Herbal/pharmacology*
;
Male
;
Blood Glucose/metabolism*
;
Insulin/blood*
;
Mice
;
Intestinal Mucosa/pathology*
;
Apoptosis/drug effects*
;
Cell Proliferation/drug effects*
;
Islets of Langerhans/pathology*
10.Hesperidin Suppressed Colorectal Cancer through Inhibition of Glycolysis.
Ke-Xiang SUN ; Wei-Shan TAN ; Hao-Yue WANG ; Jia-Min GAO ; Shu-Yun WANG ; Man-Li XIE ; Wan-Li DENG
Chinese journal of integrative medicine 2025;31(6):529-540
OBJECTIVE:
To explore the role of the natural compound hesperidin in glycolysis, the key ratelimiting enzyme, in colorectal cancer (CRC) cell lines.
METHODS:
In vitro, HCT116 and SW620 were treated with different doses of hesperidin (0-500 µmol/L), cell counting kit-8 and colone formation assays were utilized to detected inhibition effect of hesperidin on CRC cell lines. Transwell and wound healing assays were performed to detect the ability of hesperidin (0, 25, 50 and 75 µmol/L) to migrate CRC cells. To confirm the apoptotic-inducing effect of hesperidin, apoptosis and cycle assays were employed. Western blot, glucose uptake, and lactate production determination measurements were applied to determine inhibitory effects of hesperidin (0, 25 and 50 µmol/L) on glycolysis. In vivo, according to the random number table method, nude mice with successful tumor loading were randomly divided into vehicle, low-dose hesperidin (20 mg/kg) and high-dose hesperidin (60 mg/kg) groups, with 6 mice in each group. The body weights and tumor volumes of mice were recorded during 4-week treatment. The expression of key glycolysis rate-limiting enzymes was determined using Western blot, and glucose uptake and lactate production were assessed. Finally, protein interactions were probed with DirectDIA Quantitative Proteomics, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.
RESULTS:
Hesperidin could inhibit CRC cell line growth (P<0.05 or P<0.01). Moreover, hesperidin presented an inhibitory effect on the migrating abilities of CRC cells. Hesperidin also promoted apoptosis and cell cycle alterations (P<0.05). The immunoblotting results manifested that hesperidin decreased the levels of hexokinase 2, glucose transporter protein 1 (GLUT1), GLUT3, L-lactate dehydrogenase A, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), PFKFB3, and pyruvate kinase isozymes M2 (P<0.01). It remarkably suppressed tumor xenograft growth in nude mice. GO and KEGG analyses showed that hesperidin treatment altered metabolic function.
CONCLUSION
Hesperidin inhibits glycolysis and is a potential therapeutic choice for CRC treatment.
Hesperidin/therapeutic use*
;
Colorectal Neoplasms/metabolism*
;
Glycolysis/drug effects*
;
Animals
;
Humans
;
Apoptosis/drug effects*
;
Mice, Nude
;
Cell Movement/drug effects*
;
Cell Line, Tumor
;
Cell Proliferation/drug effects*
;
Glucose/metabolism*
;
Cell Cycle/drug effects*
;
Mice, Inbred BALB C
;
Mice
;
HCT116 Cells
;
Lactic Acid


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