Insulin Secretion, Sensitivity, and Kidney Function in Young Individuals With Type 2 Diabetes

Petter Bjornstad; Ye Ji Choi; Carson Platnick; Susan Gross; Phoom Narongkiatikhun; Isabella Melena; Lauryn Remmers; Madison Baca; Grant Schutte; Tyler Dobbs; Tim Vigers; Laura Pyle; Lynette Driscoll; Kalie Tommerdahl; Jessica Kendrick; Helen C. Looker; Allison Dart; David Cherney; Daniel H. van Raalte; Anand Srivastava; Luping Li; Pottumarthi Prasad; Bjornstad Lab

doi:10.2337/dc23-1818

Insulin Secretion, Sensitivity, and Kidney Function in Young Individuals With Type 2 Diabetes

Petter Bjornstad, Ye Ji Choi, Carson Platnick, Susan Gross, Phoom Narongkiatikhun, Isabella Melena, Lauryn Remmers, Madison Baca, Grant Schutte, Tyler Dobbs, Tim Vigers, Laura Pyle, Lynette Driscoll, Kalie Tommerdahl, Jessica Kendrick, Helen C. Looker, Allison Dart, David Cherney, Daniel H. van Raalte, Anand SrivastavaLuping Li, Pottumarthi Prasad, Bjornstad Lab

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

OBJECTIVE b-Cell dysfunction and insulin resistance magnify the risk of kidney injury in type 2 diabetes. The relationship between these factors and intraglomerular hemody-namics and kidney oxygen availability in youth with type 2 diabetes remains in-completely explored. RESEARCH DESIGN AND METHODS Fifty youth with type 2 diabetes (mean age ± SD 16 ± 2 years; diabetes duration 2.3 ± 1.8 years; 60% female; median HbA_1c 6.4% [25th, 75th percentiles 5.9, 7.6%]; BMI 36.4 ± 7.4 kg/m²; urine albumin-to-creatinine ratio [UACR] 10.3 [5.9, 58.0] mg/g) 21 control participants with obesity (OCs; age 16 ± 2 years; 29% female; BMI 37.6 ± 7.4 kg/m²), and 20 control participants in the normal weight category (NWCs; age 17 ± 3 years; 70% female; BMI 22.5 ± 3.6 kg/m²) underwent iohexol and p-aminohippurate clearance to assess glomerular filtration rate (GFR) and renal plasma flow, kidney MRI for oxygenation, hyperglycemic clamp for insulin secretion (acute C-peptide response to glucose [ACPRg]) and disposition index (DI; ×10³ mg/kg lean/min), and DXA for body composition. RESULTS Youth with type 2 diabetes exhibited lower DI (0.6 [0.0, 1.6] vs. 3.8 [2.4, 4.5] × 10³ mg/kg lean/min; P < 0.0001) and ACPRg (0.6 [0.3, 1.4] vs. 5.3 [4.3, 6.9] nmol/L; P < 0.001) and higher UACR (10.3 [5.9, 58.0] vs. 5.3 [3.4, 14.3] mg/g; P = 0.003) and intraglomerular pressure (77.8 ± 11.5 vs. 64.8 ± 5.0 mmHg; P < 0.001) compared with OCs. Youth with type 2 diabetes and OCs had higher GFR and kidney oxygen availability (relative hyperoxia) than NWCs. DI was associated inversely with intra-glomerular pressure and kidney hyperoxia. CONCLUSIONS Youth with type 2 diabetes demonstrated severe b-cell dysfunction that was associated with intraglomerular hypertension and kidney hyperoxia. Similar but attenuated findings were found in OCs.

Original language	English
Pages (from-to)	409-417
Number of pages	9
Journal	Diabetes Care
Volume	47
Issue number	3
DOIs	https://doi.org/10.2337/dc23-1818
Publication status	Published - 1 Mar 2024

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Bjornstad, P., Choi, Y. J., Platnick, C., Gross, S., Narongkiatikhun, P., Melena, I., Remmers, L., Baca, M., Schutte, G., Dobbs, T., Vigers, T., Pyle, L., Driscoll, L., Tommerdahl, K., Kendrick, J., Looker, H. C., Dart, A., Cherney, D., van Raalte, D. H., ... Bjornstad Lab (2024). Insulin Secretion, Sensitivity, and Kidney Function in Young Individuals With Type 2 Diabetes. Diabetes Care, 47(3), 409-417. https://doi.org/10.2337/dc23-1818

@article{bea629a1853743b5a6feefbec175e39a,

title = "Insulin Secretion, Sensitivity, and Kidney Function in Young Individuals With Type 2 Diabetes",

abstract = "OBJECTIVE b-Cell dysfunction and insulin resistance magnify the risk of kidney injury in type 2 diabetes. The relationship between these factors and intraglomerular hemody-namics and kidney oxygen availability in youth with type 2 diabetes remains in-completely explored. RESEARCH DESIGN AND METHODS Fifty youth with type 2 diabetes (mean age ± SD 16 ± 2 years; diabetes duration 2.3 ± 1.8 years; 60% female; median HbA1c 6.4% [25th, 75th percentiles 5.9, 7.6%]; BMI 36.4 ± 7.4 kg/m2; urine albumin-to-creatinine ratio [UACR] 10.3 [5.9, 58.0] mg/g) 21 control participants with obesity (OCs; age 16 ± 2 years; 29% female; BMI 37.6 ± 7.4 kg/m2), and 20 control participants in the normal weight category (NWCs; age 17 ± 3 years; 70% female; BMI 22.5 ± 3.6 kg/m2) underwent iohexol and p-aminohippurate clearance to assess glomerular filtration rate (GFR) and renal plasma flow, kidney MRI for oxygenation, hyperglycemic clamp for insulin secretion (acute C-peptide response to glucose [ACPRg]) and disposition index (DI; ×103 mg/kg lean/min), and DXA for body composition. RESULTS Youth with type 2 diabetes exhibited lower DI (0.6 [0.0, 1.6] vs. 3.8 [2.4, 4.5] × 103 mg/kg lean/min; P < 0.0001) and ACPRg (0.6 [0.3, 1.4] vs. 5.3 [4.3, 6.9] nmol/L; P < 0.001) and higher UACR (10.3 [5.9, 58.0] vs. 5.3 [3.4, 14.3] mg/g; P = 0.003) and intraglomerular pressure (77.8 ± 11.5 vs. 64.8 ± 5.0 mmHg; P < 0.001) compared with OCs. Youth with type 2 diabetes and OCs had higher GFR and kidney oxygen availability (relative hyperoxia) than NWCs. DI was associated inversely with intra-glomerular pressure and kidney hyperoxia. CONCLUSIONS Youth with type 2 diabetes demonstrated severe b-cell dysfunction that was associated with intraglomerular hypertension and kidney hyperoxia. Similar but attenuated findings were found in OCs.",

author = "Petter Bjornstad and Choi, {Ye Ji} and Carson Platnick and Susan Gross and Phoom Narongkiatikhun and Isabella Melena and Lauryn Remmers and Madison Baca and Grant Schutte and Tyler Dobbs and Tim Vigers and Laura Pyle and Lynette Driscoll and Kalie Tommerdahl and Jessica Kendrick and Looker, {Helen C.} and Allison Dart and David Cherney and {van Raalte}, {Daniel H.} and Anand Srivastava and Luping Li and Pottumarthi Prasad and {Bjornstad Lab} and Pierre Saulnier and Nelson, {Robert G.} and Johnson, {Richard J.} and Nadeau, {Kristen J.}",

note = "Publisher Copyright: {\textcopyright} 2024 by the American Diabetes Association.",

year = "2024",

month = mar,

day = "1",

doi = "10.2337/dc23-1818",

language = "English",

volume = "47",

pages = "409--417",

journal = "Diabetes Care",

issn = "0149-5992",

publisher = "American Diabetes Association Inc.",

number = "3",

}

Bjornstad, P, Choi, YJ, Platnick, C, Gross, S, Narongkiatikhun, P, Melena, I, Remmers, L, Baca, M, Schutte, G, Dobbs, T, Vigers, T, Pyle, L, Driscoll, L, Tommerdahl, K, Kendrick, J, Looker, HC, Dart, A, Cherney, D, van Raalte, DH, Srivastava, A, Li, L, Prasad, P & Bjornstad Lab 2024, 'Insulin Secretion, Sensitivity, and Kidney Function in Young Individuals With Type 2 Diabetes', Diabetes Care, vol. 47, no. 3, pp. 409-417. https://doi.org/10.2337/dc23-1818

TY - JOUR

T1 - Insulin Secretion, Sensitivity, and Kidney Function in Young Individuals With Type 2 Diabetes

AU - Bjornstad, Petter

AU - Choi, Ye Ji

AU - Platnick, Carson

AU - Gross, Susan

AU - Narongkiatikhun, Phoom

AU - Melena, Isabella

AU - Remmers, Lauryn

AU - Baca, Madison

AU - Schutte, Grant

AU - Dobbs, Tyler

AU - Vigers, Tim

AU - Pyle, Laura

AU - Driscoll, Lynette

AU - Tommerdahl, Kalie

AU - Kendrick, Jessica

AU - Looker, Helen C.

AU - Dart, Allison

AU - Cherney, David

AU - van Raalte, Daniel H.

AU - Srivastava, Anand

AU - Li, Luping

AU - Prasad, Pottumarthi

AU - Bjornstad Lab

AU - Saulnier, Pierre

AU - Nelson, Robert G.

AU - Johnson, Richard J.

AU - Nadeau, Kristen J.

PY - 2024/3/1

Y1 - 2024/3/1

N2 - OBJECTIVE b-Cell dysfunction and insulin resistance magnify the risk of kidney injury in type 2 diabetes. The relationship between these factors and intraglomerular hemody-namics and kidney oxygen availability in youth with type 2 diabetes remains in-completely explored. RESEARCH DESIGN AND METHODS Fifty youth with type 2 diabetes (mean age ± SD 16 ± 2 years; diabetes duration 2.3 ± 1.8 years; 60% female; median HbA1c 6.4% [25th, 75th percentiles 5.9, 7.6%]; BMI 36.4 ± 7.4 kg/m2; urine albumin-to-creatinine ratio [UACR] 10.3 [5.9, 58.0] mg/g) 21 control participants with obesity (OCs; age 16 ± 2 years; 29% female; BMI 37.6 ± 7.4 kg/m2), and 20 control participants in the normal weight category (NWCs; age 17 ± 3 years; 70% female; BMI 22.5 ± 3.6 kg/m2) underwent iohexol and p-aminohippurate clearance to assess glomerular filtration rate (GFR) and renal plasma flow, kidney MRI for oxygenation, hyperglycemic clamp for insulin secretion (acute C-peptide response to glucose [ACPRg]) and disposition index (DI; ×103 mg/kg lean/min), and DXA for body composition. RESULTS Youth with type 2 diabetes exhibited lower DI (0.6 [0.0, 1.6] vs. 3.8 [2.4, 4.5] × 103 mg/kg lean/min; P < 0.0001) and ACPRg (0.6 [0.3, 1.4] vs. 5.3 [4.3, 6.9] nmol/L; P < 0.001) and higher UACR (10.3 [5.9, 58.0] vs. 5.3 [3.4, 14.3] mg/g; P = 0.003) and intraglomerular pressure (77.8 ± 11.5 vs. 64.8 ± 5.0 mmHg; P < 0.001) compared with OCs. Youth with type 2 diabetes and OCs had higher GFR and kidney oxygen availability (relative hyperoxia) than NWCs. DI was associated inversely with intra-glomerular pressure and kidney hyperoxia. CONCLUSIONS Youth with type 2 diabetes demonstrated severe b-cell dysfunction that was associated with intraglomerular hypertension and kidney hyperoxia. Similar but attenuated findings were found in OCs.

AB - OBJECTIVE b-Cell dysfunction and insulin resistance magnify the risk of kidney injury in type 2 diabetes. The relationship between these factors and intraglomerular hemody-namics and kidney oxygen availability in youth with type 2 diabetes remains in-completely explored. RESEARCH DESIGN AND METHODS Fifty youth with type 2 diabetes (mean age ± SD 16 ± 2 years; diabetes duration 2.3 ± 1.8 years; 60% female; median HbA1c 6.4% [25th, 75th percentiles 5.9, 7.6%]; BMI 36.4 ± 7.4 kg/m2; urine albumin-to-creatinine ratio [UACR] 10.3 [5.9, 58.0] mg/g) 21 control participants with obesity (OCs; age 16 ± 2 years; 29% female; BMI 37.6 ± 7.4 kg/m2), and 20 control participants in the normal weight category (NWCs; age 17 ± 3 years; 70% female; BMI 22.5 ± 3.6 kg/m2) underwent iohexol and p-aminohippurate clearance to assess glomerular filtration rate (GFR) and renal plasma flow, kidney MRI for oxygenation, hyperglycemic clamp for insulin secretion (acute C-peptide response to glucose [ACPRg]) and disposition index (DI; ×103 mg/kg lean/min), and DXA for body composition. RESULTS Youth with type 2 diabetes exhibited lower DI (0.6 [0.0, 1.6] vs. 3.8 [2.4, 4.5] × 103 mg/kg lean/min; P < 0.0001) and ACPRg (0.6 [0.3, 1.4] vs. 5.3 [4.3, 6.9] nmol/L; P < 0.001) and higher UACR (10.3 [5.9, 58.0] vs. 5.3 [3.4, 14.3] mg/g; P = 0.003) and intraglomerular pressure (77.8 ± 11.5 vs. 64.8 ± 5.0 mmHg; P < 0.001) compared with OCs. Youth with type 2 diabetes and OCs had higher GFR and kidney oxygen availability (relative hyperoxia) than NWCs. DI was associated inversely with intra-glomerular pressure and kidney hyperoxia. CONCLUSIONS Youth with type 2 diabetes demonstrated severe b-cell dysfunction that was associated with intraglomerular hypertension and kidney hyperoxia. Similar but attenuated findings were found in OCs.

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U2 - 10.2337/dc23-1818

DO - 10.2337/dc23-1818

M3 - Article

C2 - 38153805

SN - 0149-5992

VL - 47

SP - 409

EP - 417

JO - Diabetes Care

JF - Diabetes Care

IS - 3

ER -

Insulin Secretion, Sensitivity, and Kidney Function in Young Individuals With Type 2 Diabetes

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