Erik J M van Bommel1, Danique Ruiter2, Marcel H A Muskiet2, Michaël J B van Baar2, Mark H H Kramer2, Max Nieuwdorp2, Jaap A Joles3, Petter Bjornstad4,5, Daniël H van Raalte2. 1. Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUmc, Amsterdam, the Netherlands e.vanbommel@amsterdamumc.nl. 2. Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUmc, Amsterdam, the Netherlands. 3. Department of Nephrology and Hypertension, University Medical Center, Utrecht, the Netherlands. 4. Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado School of Medicine, Aurora, CO. 5. Section of Endocrinology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO.
Abstract
OBJECTIVE: Impaired insulin sensitivity is associated with hyperfiltration (i.e., elevated glomerular filtration rate [GFR]) in adolescents with type 2 diabetes (T2D) and adults with prediabetes. Yet, these relationships are based on studies that relied on estimated GFR (eGFR), estimates of insulin sensitivity, or both. We aimed to verify the relationship between insulin sensitivity and renal hemodynamic function by gold standard methods in adults with T2D. RESEARCH DESIGN AND METHODS: Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp (M value) (glucose infusion rate in mg/kglean/min) and renal hemodynamic function by urinary inulin (GFR) and para-aminohippuric acid (effective renal plasma flow [ERPF]) clearances in participants with T2D without overt kidney disease. Filtration fraction (FF) (GFR/ERPF) was calculated. Relationships between insulin sensitivity and renal hemodynamic parameters were examined by multivariable linear regression. Renal hemodynamic parameters were examined across tertiles of M values. RESULTS: We tested 44 adults with T2D, of whom 77% were male, with mean ± SD age 63 ± 7 years, BMI 31.2 ± 4.0 kg/m2, and HbA1c 7.4 ± 0.6%. Average GFR was 110 ± 26 mL/min, with an FF of 22.1 ± 2.8% and median 24-h urinary albumin excretion of 11.3 mg (interquartile range 5.8-17.0). Average M value was 5.6 ± 2.9 mg/kglean/min. Insulin sensitivity inversely correlated with GFR (r = -0.44, P < 0.01) and FF (r = -0.40, P < 0.01), and these associations remained significant after multivariable adjustments for age, sex, renin-angiotensin system inhibitor use, and HbA1c. In addition, GFR, FF, and urinary albumin excretion were highest in the participants in the lowest M value tertile. CONCLUSIONS: For the first time, we demonstrate that impaired insulin sensitivity is associated with intrarenal hemodynamic dysfunction by gold standard techniques in adults with T2D treated with metformin monotherapy.
OBJECTIVE: Impaired insulin sensitivity is associated with hyperfiltration (i.e., elevated glomerular filtration rate [GFR]) in adolescents with type 2 diabetes (T2D) and adults with prediabetes. Yet, these relationships are based on studies that relied on estimated GFR (eGFR), estimates of insulin sensitivity, or both. We aimed to verify the relationship between insulin sensitivity and renal hemodynamic function by gold standard methods in adults with T2D. RESEARCH DESIGN AND METHODS: Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp (M value) (glucose infusion rate in mg/kglean/min) and renal hemodynamic function by urinary inulin (GFR) and para-aminohippuric acid (effective renal plasma flow [ERPF]) clearances in participants with T2D without overt kidney disease. Filtration fraction (FF) (GFR/ERPF) was calculated. Relationships between insulin sensitivity and renal hemodynamic parameters were examined by multivariable linear regression. Renal hemodynamic parameters were examined across tertiles of M values. RESULTS: We tested 44 adults with T2D, of whom 77% were male, with mean ± SD age 63 ± 7 years, BMI 31.2 ± 4.0 kg/m2, and HbA1c 7.4 ± 0.6%. Average GFR was 110 ± 26 mL/min, with an FF of 22.1 ± 2.8% and median 24-h urinary albumin excretion of 11.3 mg (interquartile range 5.8-17.0). Average M value was 5.6 ± 2.9 mg/kglean/min. Insulin sensitivity inversely correlated with GFR (r = -0.44, P < 0.01) and FF (r = -0.40, P < 0.01), and these associations remained significant after multivariable adjustments for age, sex, renin-angiotensin system inhibitor use, and HbA1c. In addition, GFR, FF, and urinary albumin excretion were highest in the participants in the lowest M value tertile. CONCLUSIONS: For the first time, we demonstrate that impaired insulin sensitivity is associated with intrarenal hemodynamic dysfunction by gold standard techniques in adults with T2D treated with metformin monotherapy.
Authors: Lennart Tonneijck; Mark M Smits; Marcel H A Muskiet; Trynke Hoekstra; Mark H H Kramer; A H Jan Danser; Piet M Ter Wee; Michaela Diamant; Jaap A Joles; Daniël H van Raalte Journal: Diabetes Care Date: 2016-09-01 Impact factor: 19.112
Authors: Toralf Melsom; Ulla Dorte Mathisen; Ole C Ingebretsen; Trond G Jenssen; Inger Njølstad; Marit D Solbu; Ingrid Toft; Bjørn O Eriksen Journal: Diabetes Care Date: 2011-05-18 Impact factor: 19.112
Authors: Katherine R Tuttle; George L Bakris; Rudolf W Bilous; Jane L Chiang; Ian H de Boer; Jordi Goldstein-Fuchs; Irl B Hirsch; Kamyar Kalantar-Zadeh; Andrew S Narva; Sankar D Navaneethan; Joshua J Neumiller; Uptal D Patel; Robert E Ratner; Adam T Whaley-Connell; Mark E Molitch Journal: Diabetes Care Date: 2014-10 Impact factor: 19.112