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.

This 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.

The 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.

The 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.

The 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.

OBJECTIVE

To assess the diagnostic accuracy of point-of-care screening using Medios™ Artificial Intelligence (AI) in the diagnosis of diabetic retinopathy (DR).

This is a multi-center, cross-sectional, instrument validation study among adult Filipinos with Type 2 diabetes seen at Endocrine specialty clinics from May to November 2021. Retinal images were captured by a minimally trained nurse using the Remedio Fundus on Phone (FOP). Images were interpreted separately by the Medios™ AI and three retina specialists. The primary outcome measure is the accuracy of Medios™™ AI in diagnosing DR compared to retina specialists’ findings using sensitivity and specificity, predictive values, and likelihood ratios.

A total of 182 subjects with Type 2 diabetes were included in the study. The sensitivity and specificity of the Medios™ AI in diagnosing any DR were 73.68% (95%CI, 57.99-85.03) and 83.74% (95%CI, 79.35-87.35), respectively, compared with the retinal specialists’ findings using the same images. The positive and negative predictive values were 34.57% (95%CI, 25.12-45.41) and 96.47% (95%CI, 93.62-98.07). The positive and negative likelihood ratios were 4.53 (95%CI, 4.26 4.82) and 0.31 (95%CI, 0.26-0.38). The overall diagnostic accuracy of Medios™ AI in detecting DR was 82.69% (95%CI, 78.47-86.23).

The Medios™ AI system showed acceptable diagnostic accuracy when used as a point-of-care screening tool in detecting DR among patients with Type 2 diabetes seen at Endocrine specialty clinics. This technology can be a useful screening tool for endocrinologists as it is relatively inexpensive, safe, and easily performed. It can also shorten the lead time from screening to referral and intervention.

Objective: This study aims to determine the association of serum magnesium with distal symmetric peripheral neuropathy among persons with type 2 diabetes mellitus (DM). Methodology: A cross-sectional analytical study among adult Filipinos with Type 2 DM. Logistic regression was used to determine the association of serum magnesium with DSPN diagnosed by the Michigan Neuropathy Screening Instrument. The null hypothesis was rejected at 0.05α-level of significance. Results: The average serum magnesium levels were similar between those with versus without DSPN (2.06 ± 0.32 vs 2.05 ± 0.23, p = 0.873); the same was seen for corrected magnesium. There is insufficient evidence to demonstrate a significant statistical difference between those with and without DSPN in relation to glycemic control (HbA1c and FBS). Likewise, there is no significant statistical correlation between serum magnesium levels with HbA1c, FBS, BMI, or duration of diabetes. Conclusion This present study could not demonstrate any association between DSPN and serum magnesium, even after adjusting for age, sex, and comorbidity.
Magnesium ; Diabetic Neuropathies

Objectives: This study aims to determine the effect of the COVID-19 pandemic on the incidence, severity, and outcome of children diagnosed with diabetic ketoacidosis admitted in a tertiary pediatric hospital. Materials and Methods: Two groups were identified as the basis for classification: pre-pandemic (2017 to 2019) and COVID-19 pandemic (2020 to 2022). The Mann‐Whitney U test was utilized to test for the differences in continuous variables, while Pearson’s chi‐squared test was used to test for differences in categorical variables. Results: The study involved 136 participants, 63 of whom were recorded in the pre-pandemic period and 73 during the COVID-19 pandemic period. Data revealed no conclusive relationship between sex (p=0.578), age (p=0.225), or height (p=0.876) across the two time frames. However, data showed significant difference between the weight (p=0.007) and BMI (p=0.003) of children with DKA pre-pandemic and during pandemic. This implies that marked changes in weight and BMI reflect possible changes in health behaviors, healthcare access, or other variables that may have altered during the COVID-19 pandemic. Furthermore, there was no discernible difference between pre-pandemic and COVID-19 in terms of severity, incidence, or the amount of time between the onset of symptoms and consultation. Conclusion The demographic and clinical characteristics of patients with DKA across the two study periods indicate a degree of stability in patient profiles. Despite the unique circumstances of the pandemic, patient outcomes in terms of glycemic control and mortality were like those observed pre-pandemic. The significant difference in weight and BMI emphasizes how crucial it is to monitor and respond to modifications in the nutritional status and metabolic health of DKA patients during times of crisis, like the COVID-19 pandemic. Comprehending these changes can provide focused treatments aimed at promoting the best possible health outcomes for susceptible patient groups.
Diabetic Ketoacidosis ; Diabetes Mellitus ; COVID-19

The occurrence of hyperuricemia is frequently associated with diabetic ketoacidosis (DKA), however, crystalluria from the precipitation of calcium oxalate, uric acid, or urate crystals, is less known. Metabolic derangements during DKA, especially acidic urinary pH and hyperuricosuria are the main risk factors for uric acid crystals and stones. Here we report a case of uric acid crystalluria following the recovery phase of DKA.
Crystalluria ; Uric Acid ; Diabetic Ketoacidosis

OBJECTIVE

To determine if dilated smartphone photography with a 3D-printed adaptor for a fundus lens can be an alternative screening tool for diabetic retinopathy.

This was a single-center, prospective, comparative study of 102 eyes of patients with diabetes mellitus. DR screening was performed using binocular indirect ophthalmoscopy (BIO) as the reference standard, alongside two imaging modalities: a traditional fundus camera and a smartphone equipped with a 3D-printed adaptor. Coded images were evaluated by three masked retina specialists. Sensitivity, specificity, predictive values, and likelihood ratios were calculated for both imaging modalities.

DR gradings of both imaging modalities were compared to BIO and showed very good agreement (κ 0.94-0.96 95% CI 0.93-0.99). Both have high levels of interobserver reliability (kappa value 0.88-0.92 95% CI 0.84-0.96) and intraobserver reliability (kappa value 0.85-1.00 95% CI 0.64-1.00). Smartphone and Visucam 500 images can detect presence of DR with a sensitivity of 93.9% (95% CI 83.1-98.7) and 91.8% (95% CI 80.4- 97.7); and a specificity of 90.6% (95% CI 79.3-96.9) and 92.5% (95% CI 81.8-97.9), respectively, as well as the presence of vision threatening DR with a sensitivity of 100% (95% CI 91.2-100) and specificity of 85.5% (95% CI 74.2-93.1). Image quality was similar between the two imaging modalities (P=1.00).

Smartphone-based imaging with an attached 3D-printed adaptor offers high sensitivity and reliability comparable to a traditional fundus camera, and can be used an alternative for DR screening.

Diabetic kidney disease is an important microvascular complication of diabetes and the leading cause of end-stage renal disease. Its pathological characteristics mainly include epithelial mesenchymal transition(EMT) in glomerulus, podocyte apoptosis and autophagy, and damage of glomerular filtration barrier. Transforming growth factor-β(TGF-β)/Smad signaling pathway is specifically regulated by a variety of mechanisms, and is a classic pathway involved in physiological activities such as apoptosis, proliferation and differentiation. At present, many studies have found that TGF-β/Smad signaling pathway plays a key role in the pathogenesis of diabetic kidney disease. Traditional Chinese medicine has significant advantages in the treatment of diabetic kidney disease for its multi-component, multi-target and multi-pathway characteristics, and some traditional Chinese medicine extracts, traditional Chinese medicines and traditional Chinese medicine compound prescription improve the renal injury of diabetic kidney disease by regulating TGF-β/Smad signaling pathway. This study clarified the mechanism of TGF-β/Smad signaling pathway in diabetic kidney disease by expounding the relationship between the key targets of the pathway and diabetic kidney disease, and summarized the research progress of traditional Chinese medicine in the treatment of diabetic kidney disease by interfering with TGF-β/Smad signaling pathway in recent years, to provide reference for drug research and clinical treatment of diabetic kidney disease in the future.
Humans ; Diabetic Nephropathies/genetics* ; Medicine, Chinese Traditional ; Kidney/pathology* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Epithelial-Mesenchymal Transition ; Smad Proteins/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Diabetes Mellitus/genetics*

This study investigated the effect of multi-glycosides of Tripterygium wilfordii(GTW) on renal injury in diabetic kidney disease(DKD) rats through Nod-like receptor protein 3(NLRP3)/cysteine-aspartic acid protease-1(caspase-1)/gsdermin D(GSDMD) pyroptosis pathway and the mechanism. To be specific, a total of 40 male SD rats were randomized into the normal group(n=8) and modeling group(n=34). In the modeling group, a high-sugar and high-fat diet and one-time intraperitoneal injection of streptozotocin(STZ) were used to induce DKD in rats. After successful modeling, they were randomly classified into model group, valsartan(Diovan) group, and GTW group. Normal group and model group were given normal saline, and the valsartan group and GTW group received(ig) valsartan and GTW, respectively, for 6 weeks. Blood urea nitrogen(BUN), serum creatinine(Scr), alanine ami-notransferase(ALT), albumin(ALB), and 24 hours urinary total protein(24 h-UTP) were determined by biochemical tests. The pathological changes of renal tissue were observed based on hematoxylin and eosin(HE) staining. Serum levels of interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected by enzyme-linked immunosorbent assay(ELISA). Western blot was used to detect the expression of pyroptosis pathway-related proteins in renal tissue, and RT-PCR to determine the expression of pyroptosis pathway-related genes in renal tissue. Compared with the normal group, the model group showed high levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1β and IL-18(P<0.01), low level of ALB(P<0.01), severe pathological damage to kidney, and high protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01). Compared with the model group, valsartan group and GTW group had low levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1β and IL-18(P<0.01), high level of ALB(P<0.01), alleviation of the pathological damage to the kidney, and low protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01 or P<0.05). GTW may inhibit pyroptosis by decreasing the expression of NLRP3/caspase-1/GSDMD in renal tissue, thereby relieving the inflammatory response of DKD rats and the pathological injury of kidney.
Rats ; Male ; Animals ; Diabetic Nephropathies/genetics* ; Interleukin-18/metabolism* ; Glycosides/pharmacology* ; Tripterygium ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Rats, Sprague-Dawley ; Caspase 1/metabolism* ; Pyroptosis ; Uridine Triphosphate/pharmacology* ; Kidney ; Valsartan/pharmacology* ; RNA, Messenger/metabolism* ; Diabetes Mellitus

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.
Rats ; Animals ; Diabetic Nephropathies/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Abelmoschus/chemistry* ; Podocytes ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition ; Flavones/pharmacology* ; Insulin Resistance ; Reactive Oxygen Species ; Diabetes Mellitus

Renal tubular injury in patients with diabetic kidney disease(DKD) may be accompanied by glomerular and microvascular diseases. It plays a critical role in the progression of renal damage in DKD, and is now known as diabetic tubulopathy(DT). To explore the multi-targeted therapeutic effects and pharmacological mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese medicine for treating kidney disease, in attenuating DT, the authors randomly divided all rats into four groups: a normal control group(normal group), a DT model group(model group), a DT model+TFA-treated group(TFA group) and a DT model+rosiglitazone(ROS)-treated group(ROS group). The DT rat model was established based on the DKD rat model by means of integrated measures. After successful modeling, the rats in the four groups were continuously given double-distilled water, TFA suspension, and ROS suspension, respectively by gavage every day. After 6 weeks of treatment, all rats were sacrificed, and the samples of their urine, blood, and kidneys were collected. The effects of TFA and ROS on various indicators related to urine and blood biochemistry, renal tubular injury, renal tubular epithelial cell apoptosis and endoplasmic reticulum stress(ERS), as well as the activation of the protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP) signaling pathway in the kidney of the DT model rats were investigated. The results indicated that hypertrophy of renal tubular epithelial cells, renal tubular hyperplasia and occlusion, as well as interstitial extracellular matrix and collagen deposition occurred in the DT model rats. Moreover, significant changes were found in the expression degree and the protein expression level of renal tubular injury markers. In addition, there was an abnormal increase in tubular urine proteins. After TFA or ROS treatment, urine protein, the characteristics of renal tubular injury, renal tubular epithelial cell apoptosis and ERS, as well as the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney of the DT model rats were improved to varying degrees. Therein, TFA was superior to ROS in affecting the pathological changes in renal tubule/interstitium. In short, with the DT model rats, this study demonstrated that TFA could attenuate DT by multiple targets through inhibiting renal tubular ERS-induced cell apoptosis in vivo, and its effect and mechanism were related to suppressing the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney. These findings provided preliminary pharmacological evidence for the application of TFA in the clinical treatment of DT.
Rats ; Animals ; Abelmoschus ; Reactive Oxygen Species/metabolism* ; Flavones/pharmacology* ; Endoplasmic Reticulum Stress ; Diabetic Nephropathies/drug therapy* ; Apoptosis ; Diabetes Mellitus