1.A cross-sectional study on the degree of awareness of Type 2 Diabetes Mellitus complication-related risk factors among Filipinos.
Francis PASAPORTE ; Marsha TOLENTINO
Philippine Journal of Internal Medicine 2026;64(1):1-6
OBJECTIVES
In the past decade, the prevalence of diabetes in the Philippines has been increasing. The prevalence of diabetes is 7.1% and it is the sixth leading cause of death among adults. Preventive measures to address the incidence of diabetes, as well as diabetes-related complications, have been in place. However, knowledge of the risk factors for developing cardiovascular or renal-related Type 2 Diabetes Mellitus (T2DM) complications has numerous benefits for T2DM patients. This study aimed to describe common risk factors among Filipino T2D patients which increase their risk of developing cardiorenal complications including Heart Failure and CKD. Furthermore, the study aimed to assess the
awareness of T2DM patients regarding these risk factors
A clinic-based cross-sectional survey among Filipinos with T2DM Philippines was conducted in the different regions in the Philippines from April 2021 to January 2022. The study participants were 16,268 patients of various ages and sex, however, only 11,578 of them answered the form completely. The patients and their corresponding physicians answered a validated self-assessment form on whether they had 8 identified risk factors for T2DM.
RESULTSThis survey identified Hypertension as the most common risk factor present in 96.49% of T2DM patients followed by Dyslipidemia (82.56%), Family History of CVD (77.11%), Obesity (59.66%), Kidney Disease (38.08%), Personal History of CVD (36.22%), Smoking (35.49%) and Family History of Kidney Disease (33.05%). Most patients were aware of the presence of these risk factors. However, there were some identified by the physician but unknown to the patient. In decreasing order of frequency, these were personal history of heart and blood vessel diseases (7.19%), followed by family history of kidney disease (5.44%) and smoking (5.1%).
CONCLUSIONThis survey was able to identify crucial risk factors in developing T2DM complications that are most common among T2DM patients in the Philippines. Furthermore, for the first time, the study was able to show the level of awareness of T2DM patients regarding the risk factors that they have in developing these complications. These data show the importance of determining and addressing the common risk factors in preventing T2DM complications. Moreover, identification of these risk factors is an important step in prevention of cardiorenal complications.
Identification (psychology) ; Cross-sectional Studies ; Diabetes Mellitus, Type 2 ; Diabetes Complications ; Kidney Diseases
2.Approximation of serum bicarbonate concentration using serum carbon dioxide combining power in patients with diabetic ketoacidosis.
Meghan Marie ALIÑO ; Gorgonia PANILAGAO
Philippine Journal of Internal Medicine 2026;64(1):56-62
BACKGROUND
Determination of serum bicarbonate (HCO3 - ) using arterial blood gas analysis in patients with diabetic ketoacidosis allows for the evaluation of the severity of the condition, determines whether HCO3 - therapy is required, and tracks the progression and resolution of the disease. Serum carbon dioxide combining power (CO2CP) from venous chemistry analysis has often been used as an indicator of metabolic acidosis. This study investigated the relationship between HCO3 - and CO2CP and developed an approximation formula for serum bicarbonate concentration using its predictor variables, as this may lessen the need to repeat arterial blood gas analysis or be used in settings in which blood gas analyzers are unavailable.
METHODOLOGYThis single-center, retrospective, cross-sectional study investigated a total of 77 patients diagnosed with diabetic ketoacidosis. Assessment of the bivariate correlations between serum HCO3 - and serum CO2CP as well as other potential predictor variables was done via Pearson’s correlation coefficient. Predictor variables that were significantly correlated with serum HCO3 - were identified and an approximation formula was developed by regression analysis. Evaluation of the correlation between the approximated HCO3 - value and the actual serum HCO3 - concentration was performed using correlation coefficient and residual statistics to assess agreement.
RESULTSSerum CO2CP had significant correlation with serum HCO3 - (r = 0.768, p < 0.05). By multiple regression analysis, the following approximation formula was therefore expressed: HCO3 - = 12.682 + (0.612 x CO2CP) – [ketones] + (0.085 x BUN) - (0.026 x SGPT) – (1.23 x Creatinine) - (0.067 x Chloride). Examination of residuals revealed a mean of zero (0), indicating no significant difference between the actual and approximated levels of serum HCO3 -
CONCLUSIONThe predictor variables included in the formula collectively contribute significantly to the approximation of serum HCO3 - . The approximated serum HCO3 - values also showed significant correlation with actual serum HCO3 - concentration; thus, the formula may be utilized to derive an approximation of serum bicarbonate concentration in patients with diabetic ketoacidosis.
Human ; Male ; Female ; Adolescent: 13-18 Yrs Old ; Young Adult: 19-24 Yrs Old ; Adult: 25-44 Yrs Old ; Attention ; Bicarbonates ; Carbon Dioxide ; Diabetic Ketoacidosis ; Ketosis ; Patients ; Carbon ; Power (psychology) ; Power, Psychological ; Serum
3.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
4.Prevalence of Diabetic Peripheral Neuropathy and Its Association With Serum Neuron-Specific Enolase Among Type 2 Diabetes Mellitus Patients
Siti Kaamilah Mohd Zin ; Fatimah Zaherah Mohamed Shah ; Nor Amelia Mohd Fauzi ; Rohana Abdul Ghani ; Nur &lsquo ; Aini Eddy Warman
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):33-
Introduction:
Diabetic peripheral neuropathy (DPN) is a common
complication of type 2 diabetes mellitus (T2DM), with
nerve conduction studies recognized as the diagnostic
gold standard. Serum neuron-specific enolase (NSE) has
been linked with DPN. This study aims to determine the
prevalence of DPN among T2DM patients, evaluate clinical
characteristics, and explore the relationship between NSE
and DPN.
Methodology:
A cross-sectional study was conducted at Universiti
Teknologi MARA Specialist Centre Sungai Buloh and
Hospital Al-Sultan Abdullah, involving patients aged 18–60
years, diagnosed with T2DM for more than 5 years (n = 132).
All participants underwent anthropometric measurement,
completed the Michigan Neuropathy Screening Instrument
evaluation, and biochemical parameters, including lipid
profile, hemoglobin A1c, and serum creatine and NSE.
The diagnosis of DPN was made based on positive NCS
findings. Logistic regression was used to identify factors
associated with DPN.
Results:
The study population had a mean age of 60.16 ± 10.28 years
and a mean duration of diabetes of 14.82 ± 6.66 years. The
prevalence of DPN was 51.5% (n = 68). Serum NSE levels
were significantly higher (p = 0.003) and independently
associated with the presence of DPN (adjusted odds ratio
[OR] 1.033, 95% confidence interval [CI] 1.009–1.058, p =
0.006). Participants with DPN were also more likely to be
on insulin therapy (p = 0.040). In addition, retinopathy
(adjusted OR 3.567, 95% CI 1.528–8.329, p = 0.013) and
elevated Urine Albumin-to-Creatinine Ratio levels
indicating albuminuria (adjusted OR 1.031, 95% CI 1.002–
1.061, p = 0.037) were significantly associated with DPN.
Conclusion
More than half of the study population had DPN, which
was significantly associated with both retinopathy and
nephropathy, as well as with elevated serum NSE.
This emphasizes the importance of early screening and
highlights the role of NSE as a surrogate marker for
neuropathy in diabetes.
Humans
;
Diabetes Mellitus, Type 2
;
Diabetic Neuropathies
;
Prevalence
;
Phosphopyruvate Hydratase
5.Recurrent Diabetic Ketoacidosis: Predictors and Clinical Outcomes in a 24-Year Retrospective Cohort
Liang Wei Wong ; Lisa Mohamed Nor ; Raja Nurazni binti Raja Azwan ; Adilah Zulaikha binti Abd Latib ; Hidayatil Alimi bin Keya Nordin ; Qin Zhi Lee ; Kean Heng Lim ; Jia Ling Low ; Mohd Fyzal bin Bahrudin ; Syaza binti Izhar Hisham ; Jia Whey Jacelyn Ong ; Chin Voon Tong
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):33-34
Introduction:
Diabetic ketoacidosis (DKA) is a life-threatening complication associated with significant morbidity and healthcare
burden. Despite advances in diabetes care, recurrent
DKA remains common, often reflecting gaps in treatment
adherence and patient education. Identifying predictors
of recurrence is crucial for risk stratification and targeted
intervention.
Methodology:
We conducted a retrospective observational study of all
adult DKA admissions to a tertiary centre between 2001
and 2025. Electronic medical records were reviewed for
demographic data, biochemical parameters, precipitating
factors, and clinical outcomes. DKA was defined using standard biochemical criteria. Recurrent DKA was defined as ≥2 admissions during the study period. Factors associated
with recurrent DKA admissions were analyzed. Patients
under the age of 18 years and those with missing vital
information were excluded.
Results:
A total of 667 DKA admissions, comprising 566 patients,
were identified, of which 101 admissions (15.1%) were
recurrent, involving 65 patients. Among recurrent DKA
episodes, the most common precipitating factors were
infection (64.4%) and insulin omission (62.4%). After
multivariate analyses, patients with type 1 diabetes
mellitus (T1DM) were more likely to develop recurrent
DKA compared to those with type 2 diabetes mellitus
(aOR 4.16; 95% confidence interval [CI] 2.58–6.70; p <0.001).
Insulin omission was strongly associated with recurrent
DKA (aOR 2.29; 95% CI 1.46–3.60; p <0.001). In contrast,
baseline glycated hemoglobin and chronic kidney disease
were not significantly associated with recurrence. Diabetic
counseling during the first DKA admission did not reduce
recurrent DKA. There were no significant differences in
mortality (3.9% vs 6.2%, p = 0.524) or critical care admission
rates (40.6% vs 38.7%, p = 0.718) between recurrent and first
DKA episodes.
Conclusion
Recurrent DKA accounts for a substantial proportion of
DKA admissions and is strongly associated with insulin
omission and T1DM. Our findings suggest that recurrent
DKA is driven predominantly by behavioral and adherencerelated factors, indicating the need for multidisciplinary
interventions beyond standard inpatient counseling.
Diabetic Ketoacidosis
;
Retrospective Studies
6.Clinical and Biochemical Characteristics of Adult Diabetic Ketoacidosis: T1DM vs. T2DM
Mohd Fyzal Bahrudin ; Chin Voon Tong ; Raja Nurazni Raja Azwan ; Adilah Zulaikha Abd Latib ; idayatil Alimi Keya Nordin ; Qin Zhi Lee ; Kean Heng Lim ; Jia Ling Low ; Syaza Izhar Hisham ; Liang Wei Wong ; Jia Whey Jacelyn Ong ; Lisa Mohamed Nor ; Zanariah Hussein
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):39-40
Introduction:
The rising incidence of diabetic ketoacidosis (DKA) in type 2
diabetes mellitus (T2DM) represents a paradigm shift from
its traditional recognition as a hallmark complication of
type 1 diabetes mellitus (T1DM). However, contemporary
data comparing clinical presentation, precipitating factors,
and outcomes between these two populations remain
limited.
Methodology:
In this retrospective observational study, all adult DKA
admissions with T1DM or T2DM at a tertiary centre between
2001 and 2025 were studied. DKA was defined according
to standard biochemical criteria. Electronic medical records were reviewed to extract demographic data, biochemical
parameters, precipitating factors, management details, and
clinical outcomes of all adult DKA admission in T1DM and
T2DM. Patients aged <18 years or those with incomplete
data were excluded.
Results:
A total of 601 DKA episodes were analyzed, comprising
130 (21.6%) in patients with T1DM and 471 (78.4%) in those
with T2DM. Mean age was 26.9 ± 0.71 years for T1DM and
52.1 ± 0.7 years for T2DM. Gender distribution was balanced
(male 48.3%, female 51.7%). Mean hemoglobin A1c (HbA1c)
was 11.3 ± 0.3% in T1DM and 12.1 ± 0.2% in T2DM. Infection
was the most common precipitating factor overall (69.0%),
occurring more frequently in T2DM than in T1DM (74.7%
vs. 56.2%), followed by medication non-adherence (62.4%
vs. 43.8%). Significant differences were observed between
groups in admission pH, bicarbonate (both p <0.001), blood
ketones (p = 0.028), and HbA1c (p = 0.010), whereas anion
gap (p = 0.056) and blood glucose levels (p = 0.755) did not
differ significantly. Clinical outcomes were comparable
with respect to intensive care unit (ICU) admission rates
(40.0% in T1DM vs. 39.0% in T2DM, p = 0.779) and median
resolution time (p = 0.462). However, the median length of
hospital stay was significantly longer in T2DM (8.2 ± 0.32
vs. 5.4 ± 0.4 days; p <0.001). Overall mortality was 6.0%,
with substantially higher mortality in T2DM compared to
T1DM (7.4% vs. 0.8%, p = 0.013).
Conclusion
In this large regional series of adult DKA, most episodes
occurred in T2DM. Despite similar ICU admission rates
and time to resolution, T2DM was associated with more
frequent infection-related precipitants, longer hospital
stays, and higher mortality, underscoring the need for
targeted preventive strategies in this population.
Adult
;
Diabetes Mellitus, Type 1
;
Diabetic Ketoacidosis
;
Diabetes Mellitus, Type 2
7.Euglycemic Diabetic Ketoacidosis: Clinical Insights From a Tertiary-Centre Cohort
Jia Ling Loh ; Chin Voon Tong ; Lisa Mohamed Nor
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):46-
Introduction:
Euglycemic diabetic ketoacidosis (EDKA) is an uncommon
but potentially life-threatening complication of diabetes,
characterized by significant ketoacidosis in the absence
of marked hyperglycemia. The increasing use of sodiumglucose co-transporter-2 inhibitors (SGLT2i) has contributed
to its rising incidence; however, data describing its clinical
spectrum remain limited.
Methodology:
We conducted a retrospective observational study of 19
patients admitted for EDKA between 2002 and 2025. EDKA
was defined as metabolic acidosis with ketosis in the presence
of blood glucose <11 mmol/L. Demographic characteristics, comorbidities, biochemical parameters, triggers,
and clinical outcomes were analyzed. Continuous variables
were reported as mean (SD) or median (interquartile
range [IQR]), and categorical variables as frequencies and
percentages.
Results:
The cohort displayed a mean age of 52 (SD 22.2) years,
with a slight female predominance (52.6%). The majority
had underlying type 2 diabetes mellitus (89.5%). Other
comorbidities include hypertension (63.2%) and chronic
kidney disease (31.6%). Despite severe metabolic
derangement, the mean blood glucose at presentation
was modest at 9.3 (SD 3.38) mmol/L. Median pH was 7.1
(IQR 0.35) and bicarbonate 9.1 mmol/L, with a markedly
elevated median anion gap of 25.3 mmol/L. SGLT2i exposure was identified in 47.4% of patients,
predominantly empagliflozin, with most initiated within
6 months. Nevertheless, infection was still the leading
precipitant (68.4%), while 31.6% were adjudicated as having
SGLT2i as the primary precipitating factor, probably due
to underreporting during the diagnosis. Nearly half of the
patients required intensive care (47.4%). The mean time to
DKA resolution was 19 (SD 10.1) hours. Overall outcomes
were favorable, with 89.5% of patients discharged and a
mortality rate of 10.5%.
Conclusion
EDKA presents with severe metabolic acidosis despite
deceptively normal glucose levels, increasing the risk of
delayed recognition. Early assessment of ketones and acid–
base status is essential in patients with diabetes presenting
with unexplained metabolic acidosis, particularly among
those receiving SGLT2 inhibitors, to facilitate timely
diagnosis and management.
Diabetic Ketoacidosis
8.Diabetic Ketoacidosis in Pregnancy: Clinical Triggers, Outcomes, and Missed Opportunities—A Case Series
Jia Whey Jacelyn Ong ; Chin Voon Tong ; Raja Nurazni binti Raja Azwan ; Adilah Zulaikha binti Abd Latib ; Hidayatil Alimi bin Keya Nordin ; Qin Zhi Lee ; Kean Heng Lim ; Jia Ling Low ; Mohd Fyzal bin Bahrudin ; Syaza binti Izhar Hisham ; Liang Wei Wong ; Lisa Mohamed Nor ; Nurain Mohd Noorr
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):48-49
Introduction:
Diabetic ketoacidosis (DKA) in pregnancy is an uncommon
yet life-threatening emergency, with disproportionate risks
to both mother and fetus. Pregnancy-specific physiological changes predispose patients to rapid metabolic decompensation, often with atypical presentations. Despite
this, local data remain limited. We describe the clinical
profile, precipitating factors, and outcomes of DKA in
pregnancy in a tertiary centre, with emphasis on potentially
preventable triggers.
Cases:
Nine pregnant patients with DKA were identified from a
retrospective review of all cases admitted for DKA from
2002 to 2025. Mean age was 31.67 ± 5.20 years; all were
Malay. The majority had type 2 diabetes mellitus (55.6%),
followed by type 1 diabetes (33.3%) and latent autoimmune
diabetes in adults (11.1%). The mean period of amenorrhea
was 19.67 ± 12.62 weeks.
Infection was the leading precipitant (44.4%), with
additional triggers including insulin omission (22.2%),
hyperemesis gravidarum, preterm labor, steroid exposure,
and perioperative fasting. Most diagnoses were made in
the emergency department (55.6%).
Biochemical parameters reflected significant severity (mean
bicarbonate 7.89 ± 2.98 mmol/L; anion gap 25.00 ± 5.81),
with 88.9% classified as severe DKA. Intensive Care Unit
(ICU) care was required in 77.8% of cases. The majority
(77.8%) were admitted to the ICU unit, with a median time
to resolution of 13.00 ± 12.00 hours (interquartile range
[IQR]), and the median hospital length of stay was 7.00 ±
5.00 days (IQR).
Complications during treatment included hypokalemia
(33.3%), acute kidney injury (22.2%), and hypoglycemia
(11.1%). Rebound DKA occurred in one-third of patients.
All patients were discharged clinically stable. Outcome
data demonstrated pregnancy loss in three cases and one
preterm birth.
Conclusion
DKA in pregnancy remains a severe and resource-intensive
condition. This series highlights missed opportunities in
prevention, with modifiable precipitants such as infection
and insulin omission commonly identified. The high
severity at presentation suggests delays in recognition.
Early detection, optimized metabolic care, and targeted
preventive strategies are crucial to improving maternal
and fetal outcomes.
Female
;
Pregnancy
;
Diabetic Ketoacidosis
9.Treatment progress and clinical strategies for ankle fractures combined with diabetes mellitus.
Fu-Qiang MA ; Yu-Chen LIU ; Xiang-Yu WANG
China Journal of Orthopaedics and Traumatology 2025;38(9):976-980
Ankle fractures are common traumatic injuries, especially among diabetic patients, and their treatment faces many challenges. Diabetic patients, due to factors such as long-term high blood sugar, osteoporosis, microvascular lesions and neuropathy, are prone to problems such as delayed fracture healing, increased risk of infection, non-union of fractures and postoperative complications, which affect their treatment effect and recovery process. Diabetes significantly affects the treatment of ankle fractures, mainly through factors such as high blood sugar, osteoporosis, microvascular lesions, and hypercoagulable state of the blood. In recent years, advancements in strong fixation techniques, blood glucose control and postoperative rehabilitation have achieved remarkable results in the treatment of ankle fractures for diabetic patients. However, at present, there are many studies on the treatment of ankle fractures in patients with diabetes, but there is still a lack of large-scale data reports. With the continuous advancement of medical technology, through precise admission assessment, perfect perioperative management, advanced fixation techniques and the latest treatment concepts, postoperative complications could be significantly reduced, and the fracture healing and prognosis of patients with ankle fractures combined with diabetes could be improved.
Humans
;
Ankle Fractures/complications*
;
Diabetes Complications/surgery*
;
Diabetes Mellitus
;
Fracture Fixation, Internal
10.Mechanism of Qizhi Jiangtang capsule inhibits podocyte pyroptosis to improve kidney injury in diabetes nephropathy by regulating NLRP3/caspase-1/GSDMD pathway.
Shanshan SU ; Zhaoan GUO ; Huan YANG ; Hui LIU ; Jingnan TANG ; Xiaoyu JIANG
Chinese Journal of Cellular and Molecular Immunology 2025;41(3):204-210
Objective To investigate the impact of Qizhi Jiangtang Capsule (QZJT) on renal damage in diabetic nephropathy (DN) mice via NOD like receptors family pyrin domain containing 3/caspase-1/ Gasdermin D (NLRP3/caspase-1/GSDMD) signaling pathway. Methods Mice were randomly allocated into six experimental groups: a normal control group (NC), a diabetic nephropathy model group (DN), a low-dose QZJT treatment group (L-QZJT), a high-dose QZJT treatment group (H-QZJT), a positive control group administered Shenqi Jiangtang Granules (SQJT), and an ML385 group (treated with an inhibitor of nuclear factor erythroid 2-related factor 2, Nrf2). Upon successful model induction, therapeutic interventions were commenced. Renal function impairment in the mice was evaluated through quantification of fasting blood glucose (FBG), 24-hour urinary albumin (UAlb), serum creatinine (SCr), blood urea nitrogen (BUN), and the kidney-to-body mass ratio (K/B). Renal tissue pathology was evaluated using HE and PAS staining. Serum levels of inflammatory cytokines IL-1β and IL-18 were quantified by ELISA. Levels of podocyte markers and proteins involved in relevant pathways were assessed using Western blot analysis. Results Compared with the NC group, FBG, 24 h UAlb, SCr, and BUN were increased in the DN group, and the K/B mass ratio was also increased. In contrast, compared with the DN group, FBG, 24 h UAlb, SCr, and BUN in both the low-dose (L-QZJT) and high-dose Quanzhou Jintang (H-QZJT) groups were decreased, and the K/B mass ratio was decreased as well. The therapeutic efficacy of H-QZJT was comparable to that of Shenqi Jiangtang Granules. QZJT ameliorated renal histopathological injury in DN mouse, increased the protein levels of Nephrin (a podocyte marker), and decreased the protein levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), pro-caspase-1, and GSDMD-N. After ML385 treatment, renal cells exhibited swelling and morphological changes, the inflammatory infiltrate area was enlarged, the protein levels of NLRP3, ASC, pro-caspase-1, and GSDMD-N were up-regulated, and the levels of IL-1β and IL-18 were increased. Conclusion QZJT may inhibit podocyte pyroptosis by acting on the Nrf2 to regulate the NLRP3/caspase-1/GSDMD pathway, thus improving renal damage in DN mouse.
Animals
;
Diabetic Nephropathies/pathology*
;
Podocytes/pathology*
;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
;
Pyroptosis/drug effects*
;
Drugs, Chinese Herbal/administration & dosage*
;
Caspase 1/genetics*
;
Signal Transduction/drug effects*
;
Mice
;
Phosphate-Binding Proteins/genetics*
;
Male
;
Intracellular Signaling Peptides and Proteins/metabolism*
;
Mice, Inbred C57BL
;
Kidney/pathology*
;
Gasdermins


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