Structural Lesions on Kidney Biopsy in Youth-Onset and Adult-Onset Type 2 Diabetes

<b>Objective: </b>Type 2 diabetes (T2D) is a leading cause of end stage kidney disease (ESKD) worldwide. Recent studies suggest a more aggressive clinical course of diabetic kidney disease (DKD) in youth-onset than adult-onset T2D. We compared kidney structural lesions in youth- and adult-onset T2D to determine if youth-onset was associated with greater early tissue injury.<b></b> <p><b> </b></p> <p><b>Methods: </b>Quantitative microscopy was performed on kidney tissue obtained from research kidney biopsies in 161 Pima Indians (117 women, 44 men) with T2D. Onset of T2D was established by serial oral glucose tolerance testing and participants were stratified as youth-onset (<25 years) or adult-onset (≥25 years). Associations between clinical and morphometric parameters and age of onset were tested using linear models.<b></b></p> <p><b> </b></p> <p><b>Results: </b>At biopsy, the 52 participants with youth-onset T2D were younger than the 109 with adult-onset T2D (39.1±9.9 <i>vs.</i> 51.4±10.2 years, <i>p</i><0.0001), but their diabetes duration was similar (19.3±8.1 <i>vs.</i> 17.0±7.8 years, <i>p</i>=0.09). Median urine albumin-to-creatinine ratio was higher in the youth-onset group (58 [25^th-75^th percentile, 17-470] <i>vs.</i> 27 [13-73] mg/g, <i>p</i>=0.02). Youth-onset participants had greater glomerular basement membrane (GBM) width (552±128 nm <i>vs.</i> 490±114nm, <i>p</i>=0.002) and mesangial fractional volume (0.31±0.10 <i>vs</i>. 0.27±0.08, <i>p</i>=0.001) than adult-onset participants. Percentage glomerular sclerosis, glomerular volume, mesangial fractional volume, and GBM width were also inversely associated with age of diabetes onset as a continuous variable.<b></b></p> <p><b> </b></p> <p><b>Conclusion: </b>Younger age of T2D onset strongly associates with more severe kidney structural lesions. Studies are underway to elucidate the pathways underlying these associations.</p>

Structural Lesions on Kidney Biopsy in Youth-Onset and Adult-Onset Type 2 Diabetes

<b>Objective: </b>Type 2 diabetes (T2D) is a leading cause of end stage kidney disease (ESKD) worldwide. Recent studies suggest a more aggressive clinical course of diabetic kidney disease (DKD) in youth-onset than adult-onset T2D. We compared kidney structural lesions in youth- and adult-onset T2D to determine if youth-onset was associated with greater early tissue injury.<b></b> <p><b> </b></p> <p><b>Methods: </b>Quantitative microscopy was performed on kidney tissue obtained from research kidney biopsies in 161 Pima Indians (117 women, 44 men) with T2D. Onset of T2D was established by serial oral glucose tolerance testing and participants were stratified as youth-onset (<25 years) or adult-onset (≥25 years). Associations between clinical and morphometric parameters and age of onset were tested using linear models.<b></b></p> <p><b> </b></p> <p><b>Results: </b>At biopsy, the 52 participants with youth-onset T2D were younger than the 109 with adult-onset T2D (39.1±9.9 <i>vs.</i> 51.4±10.2 years, <i>p</i><0.0001), but their diabetes duration was similar (19.3±8.1 <i>vs.</i> 17.0±7.8 years, <i>p</i>=0.09). Median urine albumin-to-creatinine ratio was higher in the youth-onset group (58 [25^th-75^th percentile, 17-470] <i>vs.</i> 27 [13-73] mg/g, <i>p</i>=0.02). Youth-onset participants had greater glomerular basement membrane (GBM) width (552±128 nm <i>vs.</i> 490±114nm, <i>p</i>=0.002) and mesangial fractional volume (0.31±0.10 <i>vs</i>. 0.27±0.08, <i>p</i>=0.001) than adult-onset participants. Percentage glomerular sclerosis, glomerular volume, mesangial fractional volume, and GBM width were also inversely associated with age of diabetes onset as a continuous variable.<b></b></p> <p><b> </b></p> <p><b>Conclusion: </b>Younger age of T2D onset strongly associates with more severe kidney structural lesions. Studies are underway to elucidate the pathways underlying these associations.</p>

Structural Lesions on Kidney Biopsy in Youth-Onset and Adult-Onset Type 2 Diabetes

OBJECTIVE Type 2 diabetes (T2D) is a leading cause of end-stage kidney disease worldwide. Recent studies suggest a more aggressive clinical course of diabetic kidney disease in youth-onset compared with adult-onset T2D. We compared kidney structural lesions in youth- and adult-onset T2D to determine if youth onset was associated with greater early tissue injury. RESEARCH DESIGN AND METHODS Quantitative microscopy was performed on kidney tissue obtained from research kidney biopsies in 161 Pima Indians (117 women, 44 men) with T2D. Onset of T2D was established by serial oral glucose tolerance testing, and participants were stratified as youth onset (age &lt;25 years) or adult onset (age ≥25 years). Associations between clinical and morphometric parameters and age at onset were tested using linear models. RESULTS At biopsy, the 52 participants with youth-onset T2D were younger than the 109 with adult-onset T2D (39.1 ± 9.9 vs. 51.4 ± 10.2 years; P &lt; 0.0001), but their diabetes duration was similar (19.3 ± 8.1 vs. 17.0 ± 7.8 years; P = 0.09). Median urine albumin-to-creatinine ratio was higher in the youth-onset group (58 [25th–75th percentile 17–470] vs. 27 [13–73] mg/g; P = 0.02). Youth-onset participants had greater glomerular basement membrane (GBM) width (552 ± 128 vs. 490 ± 114 nm; P = 0.002) and mesangial fractional volume (0.31 ± 0.10 vs. 0.27 ± 0.08; P = 0.001) than adult-onset participants. Glomerular sclerosis percentage, glomerular volume, mesangial fractional volume, and GBM width were also inversely associated with age at diabetes onset as a continuous variable. CONCLUSIONS Younger age at T2D onset strongly associates with more severe kidney structural lesions. Studies are underway to elucidate the pathways underlying these associations.

Molecular Programs of Glomerular Hyperfiltration in Early Diabetic Kidney Disease

Hyperfiltration (HF) is a state of high glomerular filtration rate (GFR) observed in early diabetes that damages glomeruli, resulting in an iterative process of increasing filtration load on fewer and fewer remaining functional glomeruli. To delineate underlying cellular mechanisms of damage induced by HF, transcriptional profiles of kidney biopsies from Pima Indians with type 2 diabetes with or without early-stage diabetic kidney disease (DKD) were grouped into two HF categories based on annual iothalamate GFR measurements. Twenty-six participants with a peak GFR measurement within two years of biopsy were categorized as the HF group, and 26 in whom biopsy preceded peak GFR by >2 years were considered pre-HF. The HF group had higher hemoglobin A1c, higher urine albumin-to-creatinine ratio, increased glomerular basement membrane width and lower podocyte density compared to the pre-HF group. A glomerular 1240-gene transcriptional signature identified in the HF group was enriched for endothelial stress response signaling genes, including from endothelin-1, tec-kinase and TGF-β1 pathways, with the majority of the transcripts mapped to endothelial and inflammatory cell clusters in kidney single cell transcriptional data. This analysis reveals molecular pathomechanisms contributing to development of HF and early DKD and involving putative ligand-receptor pairs and downstream intracellular targets linked to cellular crosstalk between endothelial and mesangial cells.

Prediction of the Development of Gestational Diabetes Mellitus in Pregnant Women Using Machine Learning Methods

The paper is devoted to the application of machine learning methods to the prediction of the development of gestational diabetes mellitus in early pregnancy. Based on two publicly available databases, study assesses influence of such features as body mass index, thickness of triceps skin folds, ultrasound measurements of maternal visceral fat, first measured fasting glucose, and others a predictors of gestational diabetes mellitus. The supervised machine learning methods based on decision trees, support vector machines, logistic regression, k-nearest neighbors classifier, ensemble learning, Naive Bayes classifier, and neural networks were implemented to determine the best classification models for computerized gestational diabetes mellitus disease prediction. The accuracy of the different classifiers was determined and compared. Support vector machine classifier demonstrated the highest accuracy (83.0% of total correctly prognosed cases, 87.9% for healthy class, and 78.1% for gestational diabetes mellitus) in predicting the development of gestational diabetes based on features from Pima Indians Diabetes Database. Extreme gradient boosting classifier performed the best, comparing to other supervised machine learning methods, for Visceral Adipose Tissue Measurements during Pregnancy Database. It showed 87.9% of total correctly prognosed cases, 82.2% for healthy class, and 93.6% for gestational diabetes mellitus).

Teknik Resampling untuk Mengatasi Ketidakseimbangan Kelas pada Klasifikasi Penyakit Diabetes Menggunakan C4.5, Random Forest, dan SVM

Penderita diabetes di seluruh dunia terus mengalami peningkatan dengan angka kematian sebesar 4,6 juta pada tahun 2011 dan diperkirakan akan terus meningkat secara global menjadi 552 juta pada tahun 2030. Pencegahan Penyakit diabetes mungkin dapat dilakukan secara efektif dengan cara mendeteksinya sejak dini. Data mining dan machine learning terus dikembangkan agar menjadi alat yang handal dalam membangun model komputasi untuk mengidentifikasi penyakit diabetes pada tahap awal. Namun, masalah yang sering dihadapi dalam menganalisis penyakit diabetes ialah masalah ketidakseimbangan class. Kelas yang tidak seimbang membuat model pembelajaran akan sulit melakukan prediksi karena model pembelajaran didominasi oleh instance kelas mayoritas sehingga mengabaikan prediksi kelas minoritas. Pada penelitian ini kami mencoba menganalisa dan mencoba mengatasi masalah ketidakseimbangan kelas dengan menggunakan pendekatan level data yaitu teknik resampling data. Eksperimen ini menggunakan R language dengan library ROSE (version 0.0-4). Dataset Pima Indians dipilih pada penelitian ini karena merupakan salah satu dataset yang mengalami ketidakseimbangan kelas. Model pengklasifikasian pada penelitian ini menggunakan algoritma decision tree C4.5, RF (Random Forest), dan SVM (Support Vector Machines). Dari hasil eksperimen yang dilakukan model klasifikasi SVM dengan teknik resampling yang menggabungkan over dan under-sampling menjadi model yang memiliki performa terbaik dengan nilai AUC (Area Under Curve) sebesar 0.80

Incidence of diabetes in South Asian young adults compared to Pima Indians

IntroductionSouth Asians (SA) and Pima Indians have high prevalence of diabetes but differ markedly in body size. We hypothesize that young SA will have higher diabetes incidence than Pima Indians at comparable body mass index (BMI) levels.Research design and methodsWe used prospective cohort data to estimate age-specific, sex, and BMI-specific diabetes incidence in SA aged 20–44 years living in India and Pakistan from the Center for Cardiometabolic Risk Reduction in South Asia Study (n=6676), and compared with Pima Indians, from Pima Indian Study (n=1852).ResultsAt baseline, SA were considerably less obese than Pima Indians (BMI (kg/m2): 24.4 vs 33.8; waist circumference (cm): 82.5 vs 107.0). Age-standardized diabetes incidence (cases/1000 person-years, 95% CI) was lower in SA than in Pima Indians (men: 14.2, 12.2–16.2 vs 37.3, 31.8–42.8; women: 14.8, 13.0–16.5 vs 46.1, 41.2–51.1). Risk of incident diabetes among 20–24-year-old Pima men and women was six times (relative risk (RR), 95% CI: 6.04, 3.30 to 12.0) and seven times (RR, 95% CI: 7.64, 3.73 to 18.2) higher as compared with SA men and women, respectively. In those with BMI <25 kg/m2, however, the risk of diabetes was over five times in SA men than in Pima Indian men. Among those with BMI ≥30 kg/m2, diabetes incidence in SA men was nearly as high as in Pima men. SA and Pima Indians had similar magnitude of association between age, sex, BMI, and insulin secretion with diabetes. The effect of family history was larger in SA, whereas that of insulin resistance was larger in Pima IndiansConclusionsIn the background of relatively low insulin resistance, higher diabetes incidence in SA is driven by poor insulin secretion in SA men. The findings call for research to improve insulin secretion in early natural history of diabetes.