Diabetes, Hypertension, and Kidney Disease in the Pima Indians

1996 ◽  
pp. 75-84
Author(s):  
William C. Knowler ◽  
Robert G. Nelson ◽  
David J. Pettitt
Keyword(s):  
Kidney Disease ◽  
Pima Indians

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

2022 ◽  
Author(s):  
Helen C. Looker ◽  
Laura Pyle ◽  
Tim Vigers ◽  
Cameron Severn ◽  
Pierre Saulnier ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Age Of Onset ◽  
Tissue Injury ◽  
Kidney Tissue ◽  
Glomerular Sclerosis ◽  
Oral Glucose ◽  
Adult Onset ◽  
Pima Indians

<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<sup>th</sup>-75<sup>th</sup> 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>

scholarly journals Molecular Programs of Glomerular Hyperfiltration in Early Diabetic Kidney Disease

2021 ◽  
Author(s):  
Vidar T. N. Stefansson ◽  
Viji Nair ◽  
Toralf Melsom ◽  
Helen C. Looker ◽  
Laura H. Mariani ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Mesangial Cells ◽  
Early Stage ◽  
Pima Indians ◽  
Cellular Mechanisms ◽  
Early Diabetes ◽  
Diabetic Kidney ◽  
Transcriptional Signature ◽  
Urine Albumin

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.

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

Diabetes Care ◽  
2022 ◽  
Author(s):  
Helen C. Looker ◽  
Laura Pyle ◽  
Tim Vigers ◽  
Cameron Severn ◽  
Pierre J. Saulnier ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Tissue Injury ◽  
Age At Onset ◽  
Kidney Tissue ◽  
Oral Glucose ◽  
Onset Age ◽  
Adult Onset ◽  
Pima Indians

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.

scholarly journals Predominant effect of kidney disease on mortality in Pima Indians with or without type 2 diabetes

2005 ◽  
Vol 68 (3) ◽  
pp. 1267-1274 ◽  
Author(s):  
Meda E. Pavkov ◽  
Peter H. Bennett ◽  
Maurice L. Sievers ◽  
Jonathan Krakoff ◽  
Desmond E. Williams ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Pima Indians ◽  
Predominant Effect

Diabetic Kidney Disease in Pima Indians

Diabetes Care ◽  
1993 ◽  
Vol 16 (1) ◽  
pp. 335-341 ◽  
Author(s):  
R. G. Nelson ◽  
W. C. Knowler ◽  
D. J. Pettitt ◽  
M. F. Saad ◽  
P. H. Bennett
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Pima Indians ◽  
Diabetic Kidney

DIABETES, HYPERTENSION, AND KIDNEY DISEASE IN THE PIMA INDIANS.

2010 ◽  
pp. 857-870
Author(s):  
William C Knowler ◽  
Robert G Nelson ◽  
David J Pettitt
Keyword(s):  
Kidney Disease ◽  
Pima Indians

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

2022 ◽  
Author(s):  
Helen C. Looker ◽  
Laura Pyle ◽  
Tim Vigers ◽  
Cameron Severn ◽  
Pierre Saulnier ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Age Of Onset ◽  
Tissue Injury ◽  
Kidney Tissue ◽  
Glomerular Sclerosis ◽  
Oral Glucose ◽  
Adult Onset ◽  
Pima Indians

<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<sup>th</sup>-75<sup>th</sup> 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>

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