The dose–response effect of insulin sensitivity on albuminuria in children according to diabetes type

Mottl, Amy K.; Divers, Jasmin; Dabelea, Dana; Maahs, David M.; Dolan, Lawrence M.; Pettitt, David J.; Marcovina, Santica M.; Imperatore, Giuseppina; Pihoker, Catherine; Mauer, Michael; Mayer‐Davis, Elizabeth J.

doi:10.1007/s00467-015-3276-2

Cited by 11 publications

(11 citation statements)

References 47 publications

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“…Recently, Zeng et al[94], showed that the ORAI (calcium release-activated calcium channels) are also accountable for the internalization of albumin in proximal tubular epithelial cells via clathrin-mediated endocytosis and expression of these channels is insulin-dependent. In concordance with previous studies, Mottl et al[95] showed that the urinary ACR was positively associated with insulin-resistant young Type 2 diabetic subjects. Moreover, insulin treatment under high-glucose conditions increased megalin expression and albumin internalization in OK cells[96].…”

Section: Renal Ir In Proteinuriasupporting

confidence: 91%

Insulin receptors in the kidneys in health and disease

Singh

Sharma

Kumari

et al. 2019

WJN

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Insulin is an important hormone that affects various metabolic processes, including kidney function. Impairment in insulin’s action leads to insulin resistance in the target tissue. Besides defects in post-receptor insulin signaling, impairment at the receptor level could significantly affect insulin sensitivity of the target tissue. The kidney is a known target of insulin; however, whether the kidney develops “insulin resistance” is debatable. Regulation of the insulin receptor (IR) expression and its function is very well studied in major metabolic tissues like liver, skeletal muscles, and adipose tissue. The physiological relevance of IRs in the kidney has recently begun to be clarified. The credit goes to studies that showed a wide distribution of IR throughout the nephron segments and their reduced expression in the insulin resistance state. Moreover, altered renal and systemic metabolism observed in mice with targeted deletion of the IR from various epithelial cells of the kidney has strengthened this proposition. In this review, we recapitulate the crucial findings from literature that have expanded our knowledge regarding the significance of the renal IR in normal- and insulin-resistance states.

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Section: Renal Ir In Proteinuriasupporting

confidence: 91%

Insulin receptors in the kidneys in health and disease

Singh

Sharma

Kumari

et al. 2019

WJN

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“…In a recently published study, SEARCH examined insulin resistance in relation to urinary albumin to creatinine ratio (UACR) in both type 1 and type 2 diabetes. This study indicated that there was an inverse association between insulin resistance and UACR in type 2 diabetes only and that below an insulin sensitivity index of 4.7, the relationship was stronger, suggesting a possible threshold effect [32]. …”

Section: Complications and Comorbiditiesmentioning

confidence: 99%

Type 2 Diabetes in Youth: New Lessons from the SEARCH Study

Jensen

Dabelea

2018

Curr Diab Rep

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This body of evidence illustrates that type 2 diabetes continues to increase in incidence, although this increase may be partially attributable to increased surveillance. Disease management is influenced by the transition from adolescent to adult care and psychosocial factors may also contribute. This evidence also describes a high prevalence of disease-associated complications and comorbidities. Risk factors for cardiovascular disease are also highly prevalent. The SEARCH for Diabetes in Youth study continues to inform our understanding of the descriptive epidemiology and natural history of type 2 diabetes in youth. As the cohort matures, new opportunities emerge for building on our understanding of how youth-onset type 2 diabetes impacts future health.

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“…Urine albumin and creatinine were measured as previously described. 21 Blood was processed, and fresh plasma, serum and urine samples were shipped on cold packs by overnight courier to the study central laboratory where analysis of GAD-65 antibodies, insulinoma-associated-2 antibodies, Zinc-T8 autoantibodies, cholesterol, triglycerides and HbA1c was performed as previously described. 22,23 The Bouvet equation was used to calculate estimated glomerular filtration rate (eGFR) at the follow-up visit.…”

Section: Subjects Materials and Methodsmentioning

confidence: 99%

“…The insulin sensitivity score was utilized only in analyses of the type 2 diabetes group due to previous work underscoring its strong association in type 2 but not type 1 diabetes. 21,29…”

Section: Subjects Materials and Methodsmentioning

confidence: 99%

The early natural history of albuminuria in young adults with youth-onset type 1 and type 2 diabetes

Kahkoska

Isom

Divers

et al. 2018

Journal of Diabetes and its Complications

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AIMS: To determine among adolescents and young adults with youth-onset type 1 diabetes and type 2 diabetes the rates and risk factors for albuminuria regression and progression. The research hypothesis was that youth with type 2 diabetes would be more likely to show progression of albuminuria. METHODS: Data from SEARCH, a longitudinal observational study of youth-onset type 1 diabetes (N=1316) and type 2 diabetes (N=143) were analyzed. Urine albumin:creatinine ratio (UACR) was measured from random urine specimens at baseline and follow-up visits (mean 7 years later). Albuminuria regression was defined as halving of baseline UACR when baseline UACR was ≥30μg/mg; progression was defined as doubling of baseline UACR when follow-up UACR was ≥30μg/mg, respectively. Multivariable regression assessed risk factors associated with low-risk albuminuria category (combined persistently-low albuminuria and regression) versus moderate-risk albuminuria category (combined persistently-high albuminuria and progression). RESULTS: Albuminuria progression was more common in type 2 diabetes versus type 1 diabetes (15.4% versus 6.0%, p<0.001). Moderate-risk albuminuria was associated with increasing HbA1c (adjusted OR (aOR)=1.3, 95% CI 1.1–1.6) and lack of private health insurance (aOR=2.7, 95%CI 1.1–6.5) in type 1 diabetes; and African American race (OR=4.6, 95% CI 1.2–14.2), lower estimated insulin sensitivity score (aOR=2.1, 95% CI 1.4–3.3), baseline UACR (aOR=3.2, 95% CI 1.7–5.8), and follow-up estimated glomerular filtration rate (eGFR) (10-unit increase aOR=1.3, 95% CI 1.0, 1.5) in type 2 diabetes. CONCLUSIONS: In the first decade of diabetes duration, kidney complications in type 2 diabetes are significantly more aggressive than in type 1 diabetes and may be associated with less modifiable risk factors including race, insulin sensitivity, and eGFR. Interventions are needed even at very early stages of disease to reduce the long-term consequences of diabetic kidney disease in youth-onset diabetes.

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The dose–response effect of insulin sensitivity on albuminuria in children according to diabetes type

Cited by 11 publications

References 47 publications

Insulin receptors in the kidneys in health and disease

Insulin receptors in the kidneys in health and disease

Type 2 Diabetes in Youth: New Lessons from the SEARCH Study

The early natural history of albuminuria in young adults with youth-onset type 1 and type 2 diabetes

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