1.Risk factors of presence and severity of diabetic retinopathy in a Tertiary Hospital.
Gertrude Camille Crisostomo REYES ; Mark Henry JOVEN
Philippine Journal of Internal Medicine 2026;64(1):43-55
BACKGROUND
Diabetic retinopathy (DR) remains to be the leading cause of blindness worldwide. Traditionally, risk factors such as diabetes duration, HbA1c levels, hypertension and dyslipidemia have been closely linked to the development of this condition. However, recent research suggests that these factors account for only a portion of DR cases. Emerging studies highlight additional potential risk factors including diabetic nephropathy, insulin use, and body mass index -though data on these factors remain limited and at times contradictory. While there have been a few local studies exploring some of these variables, none have comprehensively examined how these factors collectively influence the occurrence and severity of diabetic retinopathy. This study aims to asses both the factors associated with presence and occurrence of diabetic retinopathy.
METHODOLOGYThis analytical cross-sectional study included patients with diabetes (n=201, aged 18 years and older) who underwent fundus photography at The Medical City Ortigas between January 1, 2022, and December 31, 2022. Data collection involved a thorough review of patient records, which provided demographic information and details on potential risk factors. The presence and severity of diabetic retinopathy (DR) were assessed based on fundus photography results, as interpreted by ophthalmologists. To evaluate the statistical significance of the association between risk factors and DR status, logistic regression analysis was done
RESULTSDuration of diabetes (odds ratio [OR] 1.07; 95% CI, 1.01-1.13 per year increase), HBA1c (OR 1.4; 95% CI, 1.1-1.86),
fasting blood sugar (OR 1.4; 95% CI, 0.977-0.998), hypercholesterolemia (OR 5.02; 95% CI 1.67-16.44) and presence of
nephropathy (OR 3.39; 95% CI 1.49-8) were correlated with diabetic retinopathy.
The presence of diabetic retinopathy was significantly associated with several clinical factors. Each additional year of diabetes mellitus duration was associated with a 1.07-fold increase in the likelihood of DR. Additionally, each 1% increase in HbA1c was linked to a 1.40-fold increase in DR risk. The presence of diabetic nephropathy and hypercholesterolemia were also strong predictors, associated with a 3.39-fold and 5-fold increase in the likelihood of DR, respectively. Glycemic control, dyslipidemia and nephropathy appear to be associated with more severe forms of diabetic retinopathy. Clinicians handling diabetes patients with this patient profile should be wary of this diabetes complication.
Human ; Male ; Female ; Adolescent: 13-18 Yrs Old ; Young Adult: 19-24 Yrs Old ; Adult: 25-44 Yrs Old ; Diabetic Retinopathy ; Hospitals ; Risk ; Risk Factors ; Tertiary Care Centers
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.Filipino translation and cross-cultural adaptation of the diabetic foot knowledge subscale (DFKS) and foot self-care behavior scale (FSCBS) and its content validation and reliability testing.
Aaron Patrick S. MANALO ; Aliyah Renee P. QUIZON ; Jocel M. REGINO ; Lia Katrina L. LOPEZ ; Mary Margaret Louise C. QUIMSON ; Justine Ann Marie V. DE LARA ; Christian Rey D. RIMANDO ; David Benjamin L. ANG
Acta Medica Philippina 2025;59(16):7-20
BACKGROUND
Type 2 diabetes is the most common type of diabetes in the Philippines. Diabetic foot complications represent a prevalent and significant chronic concern for individuals with type 2 diabetes. This poses an immediate community health concern, as diabetic complications may threaten an individual's well-being.
OBJECTIVEThis study intends to cross-culturally adapt the Diabetic Foot Knowledge Subscale (DFKS) and Foot Self-Care Behavior Scale (FSCBS) questionnaires into the Filipino language as an assessment tool among Filipinos with diabetes.
METHODSThe study employed a psychometric research design, where it entailed Phase A and Phase B. Phase A involved the forward translation of the DFKS and FSCBS questionnaires, followed by the synthesis of the translations and backward translation. Subsequently, an expert committee reviewed the translations and concluded the final version. The final translated versions of the questionnaires ensured that it can be understood by an individual who has a Grade 6 level of reading proficiency. Phase B entailed the validity testing with the evaluation of the expert committee, and reliability testing of the said questionnaires with a sample size of 30 participants. A wash-out period of 24 hours was given for the test-retest reliability, followed by data analysis. The validity and reliability of the questionnaires were measured using the item and scale content validity indices and the internal consistency and test-retest reliability, respectively, to ensure their accuracy and appropriateness. The content validity of the questionnaires was evaluated individually by the experts using a Likert scale from 1-4, with 4 being the highest meaning the item was very relevant and succinct. Scores per item were between 3 and 4, which indicate that the translated version of the items were relevant and succinct or were relevant but needed minor revisions.
RESULTSThe validity scores for the translated DFKS and FSCBS questionnaires were obtained using the Scale Content Validity Index (S-CVI) with a score of 0.96 and 0.92, respectively. Moreover, all items in the questionnaires obtained an Item Content Validity Index (I-CVI) of 0.88-1.00. The DFKS also has an acceptable internal consistency with a Cronbach’s alpha of 0.72, while the FSCBS has a good internal consistency with a Cronbach’s alpha of 0.85. The test-retest reliability shows an acceptable Spearman’s correlation at 0.76 for the DFKS and a strong positive Pearson correlation coefficient at 0.73 for the FSCBS.
CONCLUSIONThe validity of the two questionnaires was acceptable and the test-retest reliability showed a strong positive correlation among the items thereby making the cross-cultural adaptation of the questionnaires successful. The Filipino versions of the DFKS and FSCBS questionnaires accurately measure the knowledge and behavior of individuals with type 2 diabetes, respectively.
Human ; Diabetes Mellitus, Type 2 ; Diabetic Foot ; Public Health ; Cross-cultural Comparison
6.SUN Yuanzheng's experience with yuan-primary and luo-connecting meridian-regulating acupuncture for diabetic retinopathy.
Hongju YOU ; Yuanzheng SUN ; Jiaohui LI ; Yuan ZHANG
Chinese Acupuncture & Moxibustion 2025;45(4):516-520
This paper summarizes Professor SUN Yuanzheng's academic thought and clinical experience in treating diabetic retinopathy (DR) with yuan-primary and luo-connecting meridian-regulating acupuncture. Professor SUN considers that the fundamental cause of DR lies in visceral dysfunction, with stagnation in the ocular collateral vessels and impairment of the mysterious orifices being the core pathogenesis. He proposes the treatment model of "regulating viscera, unblocking ocular collaterals, and opening mysterious orifices" based on yuan-primary and luo-connecting meridian-regulating acupuncture. Yuan-primary and luo-connecting points are used to balance qi, blood, yin, and yang of the viscera. Baihui (GV20) is stimulated with transcranial repetitive acupuncture to activate the yang qi of the governor vessel and invigorate qi in the twelve meridians, improving systemic microcirculation. Combining this with stimulation of ocular areas, Fengchi (GB20), and periocular points, the stasis in the ocular collaterals are cleared and the mysterious orifices are unblocked, addressing both the root and manifestations of DR.
Humans
;
Diabetic Retinopathy/physiopathology*
;
Acupuncture Therapy/history*
;
Meridians
;
Acupuncture Points
;
Qi
7.Effect mechanism of electroacupuncture on diabetic peripheral neuropathy in rats based on gut microbiota and metabolomics.
Shanshan AI ; Dongrui GAO ; Ziting ZHAI ; Suyong WANG ; Yawen XUE ; Zhihan LIU ; Xiao YAN
Chinese Acupuncture & Moxibustion 2025;45(7):945-956
OBJECTIVE:
To explore the effect mechanism of electroacupuncture (EA) for ameliorating diabetic peripheral neuropathy (DPN) based on the analysis of gut microbiota and metabolomics.
METHODS:
Thirty SPF-grade male SD rats were randomly divided into a normal group, a model group, and an EA group, with 10 rats in each one. Except in the normal group, the intraperitoneally injection with streptozotocin was used to induce diabetes mellitus model in the rest groups. In the EA group, acupuncture was delivered at bilateral "Zusanli" (ST36), "Sanyinjiao" (SP6), "Pishu" (BL20) and "Shenshu" (BL23), and electric stimulation was attached to "Zusanli" (ST36)-"Sanyinjiao" (SP6) and "Pishu" (BL20)-"Shenshu" (BL23), on the same side, with continuous wave and a frequency of 2 Hz, for 10 min in each intervention. The intervention measure of each group was delivered once every 2 days, 3 times a week, for 8 consecutive weeks. Body weight, random blood glucose (RBG), thermal withdrawal latency (TWL), and mechanical withdrawal threshold (MWT) before intervention, and in 4 and 8 weeks of intervention, separately, as well as sensory nerve conduction velocity (SCV) and motor nerve conduction velocity (MCV) of the sciatic nerve after intervention were measured. Metagenomic sequencing (MS) was used to analyze gut microbiota and screen for differential species. Liquid chromatography-mass spectrometry (LC-MS) was employed to detect the differential metabolites in plasma, and the metabolic pathway enrichment analysis was performed on the differential metabolites. Spearman correlation analysis was adopted to assess the relationship between gut microbiota and metabolomics.
RESULTS:
After 4 and 8 weeks of intervention, when compared with the model group, the EA group showed the increase in body weight, TWL, MWT (P<0.01), and the decrease in RBG (P<0.01). Compared with the normal group, SCV and MCV, as well as Chao1 index were dropped in the model group (P<0.01), and those were elevated in the EA group when compared with those in the model group (P<0.01). The dominant bacterial phyla of each group were Firmicutes (F) and Bacteroidota (B), the ratio of them (F/B) in the model group was lower than that of the normal group (P<0.05), and F/B in the EA group was higher when compared with that in the model group (P<0.05). In comparison with the normal group, the relative abundance increased in Prevotella, Segatella, Prevotella-hominis and Segatella-copri (P<0.05); and it decreased in Ligilactobacillus, Eubacterium, Pseudoflavonifractor, Ligilactobacillus-murinus (P<0.05) in the model group. Compared with the model group, the relevant abundance of the above mentioned gut bacteria was all ameliorated in the EA group (P<0.05, P<0.01). Among the three groups, 120 differential metabolites were identified and enriched in 28 key metabolic pathways, such as glycerophospholipid and linoleic acid, of which, glycerophospholipid was the most significantly affected pathway in EA intervention. Spearman correlation analysis showed that 6 phosphatidylcholine metabolites were significantly positively correlated with Pseudoflavonifractor and were negatively with Prevotella, Segatella, Prevotella-hominis, Segatella-copri; 5 phosphatidylethanolamine metabolites were significantly negatively correlated with Pseudoflavonifractor and positively correlated with Prevotella, Segatella, Prevotella-hominis, Segatella-copri.
CONCLUSION
EA may regulate metabolic pathways such as glycerophospholipid, modulate specific gut microbiota such as Pseudoflavonifractor, Prevotella, and Segatella, and the co-expressed differential metabolites like phosphatidylcholine and phosphatidylethanolamine, thereby reducing blood glucose and protecting nerve function, so as to relieve the symptoms of DPN of rats.
Animals
;
Electroacupuncture
;
Male
;
Gastrointestinal Microbiome
;
Diabetic Neuropathies/microbiology*
;
Rats, Sprague-Dawley
;
Rats
;
Metabolomics
;
Humans
;
Acupuncture Points
8.Effects of acupuncture on podocyte autophagy and the LncRNA SOX2OT/mTORC1/ULK1 pathway in rats with diabetic kidney disease.
Xu WANG ; Yue ZHANG ; Hongwei LI ; Handong LIU ; Jie LI ; Ying FAN ; Zhilong ZHANG
Chinese Acupuncture & Moxibustion 2025;45(10):1450-1458
OBJECTIVE:
To observe the effects of acupuncture on podocyte autophagy and long non-coding RNA SOX2 overlapping transcript (LncRNA SOX2OT)/mammalian target of rapamycin C1 (mTORC1)/Unc-51-like kinase 1 (ULK1) pathway in rats with diabetic kidney disease (DKD), and to explore the mechanism by which acupuncture reduces urinary protein.
METHODS:
A total of 40 SPF-grade male Sprague-Dawley rats were randomly divided into a control group (n=10) and a modeling group (n=30). The DKD model was established by feeding a high-fat, high-sugar diet combined with intraperitoneal injection of streptozotocin (STZ) in the modeling group. Twenty rats with successful DKD model were randomly divided into a model group (n=10) and an acupuncture group (n=10). The acupuncture group received "spleen and stomach-regulating" acupuncture at bilateral "Zusanli" (ST36), "Fenglong" (ST40), "Yinlingquan" (SP9), and "Zhongwan" (CV12), 30 min per session, once daily, five times per week, for four weeks. The general condition, fasting blood glucose (FBG), 2-hour postprandial glucose (2hPG), serum creatinine (SCr), blood urea nitrogen (BUN), 24-hour urinary protein quantification, and urine albumin-to-creatinine ratio (UACR) were compared before and after the intervention. After intervention, urinary podocyte injury marker SPON2 was measured by ELISA. Podocyte autophagosomes and glomerular basement membrane ultrastructure in renal tissue were observed via transmission electron microscopy. Podocyte apoptosis was assessed by TUNEL staining. The protein expression of microtubule-associated protein 1 light chain 3Ⅱ (LC3-Ⅱ), mTORC1, ULK1, Beclin-1, and p62 in renal tissue was detected by Western blot. LncRNA SOX2OT expression in renal tissue was measured by real-time PCR.
RESULTS:
After the intervention, compared with the control group, the model group exhibited increased food and water intake, increased urine output, weight loss, and loose stools; compared with the model group, the food and water intake, urine volume, and loose stools were improved in the acupuncture group. Compared with the control group, FBG, 2hPG, SCr, BUN, 24-hour urinary protein quantification, UACR, and urinary SPON2 were all higher in the model group (P<0.01); compared with the model group, the FBG, 2hPG, SCr, BUN, 24-hour urinary protein quantification, UACR, and urinary SPON2 were all lower in the acupuncture group (P<0.01). Compared with the control group, the model group showed reduced podocyte autophagosomes and thickened glomerular basement membrane; compared with the model group, the acupuncture group had increased podocyte autophagosomes and less thickened basement membrane. Compared with the control group, the podocyte apoptosis index (AI) was higher in the model group (P<0.01); compared with the model group, the AI was lower in the acupuncture group (P<0.01). Compared with the control group, the expression of ULK1, Beclin-1, and LC3-Ⅱ proteins was lower, and the expression of mTORC1 and p62 proteins was higher in the model group (P<0.01). Compared with the model group, the expression of ULK1, Beclin-1, and LC3-Ⅱ proteins was higher, and the expression of mTORC1 and p62 proteins was lower in the acupuncture group (P<0.01). Compared with the control group, the LncRNA SOX2OT expression was lower in the model group (P<0.01). Compared with the model group, LncRNA SOX2OT expression was higher in the acupuncture group (P<0.01).
CONCLUSION
The "spleen and stomach-regulating" acupuncture method could improve renal function in DKD rats, reduce blood glucose and urinary protein excretion, alleviate podocyte injury, and enhance podocyte autophagy. The mechanism may be related to modulation of the renal LncRNA SOX2OT/mTORC1/ULK1 pathway.
Animals
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Podocytes/cytology*
;
Diabetic Nephropathies/physiopathology*
;
Rats, Sprague-Dawley
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Male
;
Rats
;
Mechanistic Target of Rapamycin Complex 1/genetics*
;
Autophagy
;
Acupuncture Therapy
;
Autophagy-Related Protein-1 Homolog/genetics*
;
RNA, Long Noncoding/metabolism*
;
Humans
;
Signal Transduction
9.Epidemiological status, development trends, and risk factors of disability-adjusted life years due to diabetic kidney disease: A systematic analysis of Global Burden of Disease Study 2021.
Jiaqi LI ; Keyu GUO ; Junlin QIU ; Song XUE ; Linhua PI ; Xia LI ; Gan HUANG ; Zhiguo XIE ; Zhiguang ZHOU
Chinese Medical Journal 2025;138(5):568-578
BACKGROUND:
Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions.
METHODS:
Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs).
RESULTS:
The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks.
CONCLUSIONS
DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.
Humans
;
Global Burden of Disease
;
Risk Factors
;
Male
;
Female
;
Disability-Adjusted Life Years
;
Diabetic Nephropathies/epidemiology*
;
Middle Aged
;
Diabetes Mellitus, Type 2/epidemiology*
;
Adult
;
Diabetes Mellitus, Type 1/complications*
;
Aged
;
Adolescent
;
Young Adult
;
Quality-Adjusted Life Years
10.S100A9 as a promising therapeutic target for diabetic foot ulcers.
Renhui WAN ; Shuo FANG ; Xingxing ZHANG ; Weiyi ZHOU ; Xiaoyan BI ; Le YUAN ; Qian LV ; Yan SONG ; Wei TANG ; Yongquan SHI ; Tuo LI
Chinese Medical Journal 2025;138(8):973-981
BACKGROUND:
Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot.
METHODS:
Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness.
RESULTS:
In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm).
CONCLUSIONS
S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use*
;
Diabetic Foot/metabolism*
;
Humans
;
Datasets as Topic
;
Computational Biology
;
Mice, Inbred C57BL
;
Animals
;
Mice
;
Protein Interaction Maps
;
Immunohistochemistry


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