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 (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. 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 (<25 years) or adult-onset (≥25 years). Associations between clinical and morphometric parameters and age of 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<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 nm vs. 490±114nm, p=0.002) and mesangial fractional volume (0.31±0.10 vs. 0.27±0.08, p=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. Conclusion: Younger age of T2D onset strongly associates with more severe kidney structural lesions. Studies are underway to elucidate the pathways underlying these associations.

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

Diabetes Care ◽

10.2337/dc21-1688 ◽

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 <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 < 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.

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The Association Between Age of Onset of Type 2 Diabetes with Long-term Risk of End Stage Kidney Disease: A National Registry Study

10.2337/figshare.12273110.v1 ◽

2020 ◽

Author(s):

Jedidiah I Morton ◽

Danny Liew ◽

Stephen P McDonald ◽

Jonathan E Shaw ◽

Dianna J Magliano

Keyword(s):

Type 2 Diabetes ◽

Kidney Disease ◽

Cumulative Incidence ◽

Age Of Onset ◽

End Stage Kidney Disease ◽

Onset Of Diabetes ◽

End Stage ◽

Effect Of Age

Objective: The long-term risk of end-stage kidney disease (ESKD) in type 2 diabetes is poorly described, as is the effect that younger age of diabetes onset has on this risk. Therefore, we aimed to estimate the effect of age of onset on the cumulative incidence of ESKD from onset of type 2 diabetes. Research Design and Methods: This study included 1,113,201 people with type 2 diabetes registered on the Australian National Diabetes Services Scheme (NDSS) followed from 2002 until 2013. The NDSS was linked to the Australia and New Zealand Dialysis and Transplant Registry and the Australian National Death Index. Results: Between 2002 and 2013, there were 7,592 incident cases of ESKD during 7,839,075 person-years of follow up. In the first 10-15 years following onset of diabetes, the incidence of ESKD was highest in those with an older age of onset of diabetes, whereas over longer durations of diabetes the incidence of ESKD became higher in those with younger-onset diabetes. After 40 years of diabetes, the cumulative incidence of ESKD was 11.8% and 9.3% in those diagnosed with diabetes aged 10-29 and 30-39 years, respectively. When death from ESKD without renal replacement therapy was included, incidence of ESKD remained higher in older onset diabetes for the initial 20 years, with no clear effect of age thereafter. Conclusions: The long-term risk of ESKD in type 2 diabetes is high, which disproportionately affects those with younger-onset of diabetes as they are more likely to survive to longer diabetes durations.

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Erlotinib appears to produce prolonged remission of insulin-requiring type 2 diabetes associated with metabolic syndrome and chronic kidney disease

The British Journal of Diabetes ◽

10.1177/1474651412442694 ◽

2012 ◽

Vol 12 (2) ◽

pp. 87-90 ◽

Cited By ~ 6

Author(s):

Marvin B. Brooks

Keyword(s):

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Kinase Inhibitor ◽

Growth Factor Receptor ◽

Oral Medication ◽

Oral Glucose ◽

Epidermal Growth

Patients with metabolic syndrome are at higher risk for type 2 diabetes and for chronic kidney disease. Metformin is the oral medication of choice for the treatment of type 2 diabetes in the absence of chronic kidney disease. There is a need for another oral glucose lowering agent for use in metabolic syndrome with type 2 diabetes and chronic kidney disease. We submit the first report of erlotinib, a once-daily oral medication for the treatment of non-small-cell lung cancer associated with specific genetic mutations, appearing to eliminate the need for insulin in insulin-requiring type 2 diabetes associated with metabolic syndrome and chronic kidney disease. The mechanism by which erlotinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor may improve glycaemic control is unknown. Potential possibilities are explored.

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

Kidney International ◽

10.1111/j.1523-1755.2005.00523.x ◽

2005 ◽

Vol 68 (3) ◽

pp. 1267-1274 ◽

Cited By ~ 19

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

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The Association Between Age of Onset of Type 2 Diabetes and the Long-term Risk of End-Stage Kidney Disease: A National Registry Study

Diabetes Care ◽

10.2337/dc20-0352 ◽

2020 ◽

Vol 43 (8) ◽

pp. 1788-1795 ◽

Cited By ~ 2

Author(s):

Jedidiah I. Morton ◽

Danny Liew ◽

Stephen P. McDonald ◽

Jonathan E. Shaw ◽

Dianna J. Magliano

Keyword(s):

Type 2 Diabetes ◽

Kidney Disease ◽

Age Of Onset ◽

National Registry ◽

Registry Study ◽

End Stage Kidney Disease ◽

End Stage

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282-OR: The Association of Age of Onset of Type 2 Diabetes with Long-Term Risk of End Stage Kidney Disease: A National Registry Study

Diabetes ◽

10.2337/db20-282-or ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 282-OR

Author(s):

JEDIDIAH I. MORTON ◽

DANNY LIEW ◽

STEPHEN MCDONALD ◽

JONATHAN E. SHAW ◽

DIANNA J. MAGLIANO

Keyword(s):

Type 2 Diabetes ◽

Kidney Disease ◽

Age Of Onset ◽

National Registry ◽

Registry Study ◽

End Stage Kidney Disease ◽

End Stage

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The Association Between Age of Onset of Type 2 Diabetes with Long-term Risk of End Stage Kidney Disease: A National Registry Study

10.2337/figshare.12273110 ◽

2020 ◽

Author(s):

Jedidiah I Morton ◽

Danny Liew ◽

Stephen P McDonald ◽

Jonathan E Shaw ◽

Dianna J Magliano

Keyword(s):

Type 2 Diabetes ◽

Kidney Disease ◽

Cumulative Incidence ◽

Age Of Onset ◽

End Stage Kidney Disease ◽

Onset Of Diabetes ◽

End Stage ◽

Effect Of Age

Objective: The long-term risk of end-stage kidney disease (ESKD) in type 2 diabetes is poorly described, as is the effect that younger age of diabetes onset has on this risk. Therefore, we aimed to estimate the effect of age of onset on the cumulative incidence of ESKD from onset of type 2 diabetes. Research Design and Methods: This study included 1,113,201 people with type 2 diabetes registered on the Australian National Diabetes Services Scheme (NDSS) followed from 2002 until 2013. The NDSS was linked to the Australia and New Zealand Dialysis and Transplant Registry and the Australian National Death Index. Results: Between 2002 and 2013, there were 7,592 incident cases of ESKD during 7,839,075 person-years of follow up. In the first 10-15 years following onset of diabetes, the incidence of ESKD was highest in those with an older age of onset of diabetes, whereas over longer durations of diabetes the incidence of ESKD became higher in those with younger-onset diabetes. After 40 years of diabetes, the cumulative incidence of ESKD was 11.8% and 9.3% in those diagnosed with diabetes aged 10-29 and 30-39 years, respectively. When death from ESKD without renal replacement therapy was included, incidence of ESKD remained higher in older onset diabetes for the initial 20 years, with no clear effect of age thereafter. Conclusions: The long-term risk of ESKD in type 2 diabetes is high, which disproportionately affects those with younger-onset of diabetes as they are more likely to survive to longer diabetes durations.

Download Full-text