Dataset Information

Insulin Sensitivity and Renal Hemodynamic Function in Metformin-Treated Adults With Type 2 Diabetes and Preserved Renal Function.

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/kg_lean/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 HbA_1c 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/kg_lean/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 HbA_1c. 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.

SUBMITTER: van Bommel EJM

PROVIDER: S-EPMC7118247 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Insulin Sensitivity and Renal Hemodynamic Function in Metformin-Treated Adults With Type 2 Diabetes and Preserved Renal Function.

van Bommel Erik J M EJM Ruiter Danique D Muskiet Marcel H A MHA van Baar Michaël J B MJB Kramer Mark H H MHH Nieuwdorp Max M Joles Jaap A JA Bjornstad Petter P van Raalte Daniël H DH

Diabetes care 20191029 1

<h4>Objective</h4>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.<h4>Research design and methods< ...[more]

PMID: 31662305

Similar Datasets

Project description:BackgroundCardiovascular disease is the leading cause of mortality in type 1 diabetes mellitus (T1DM) and relates strongly to insulin resistance (IR). Lean and obese adolescents with T1DM have marked IR. Metformin improves surrogate markers of IR in T1DM, but its effect on directly measured IR and vascular health in youth with T1DM is unclear. We hypothesized that adolescents with T1DM have impaired vascular function and that metformin improves this IR and vascular dysfunction.MethodsAdolescents with T1DM and control participants underwent magnetic resonance imaging of the ascending (AA) and descending aorta to assess pulse wave velocity, relative area change, and maximal (WSSMAX) and time-averaged (WSSTA) wall shear stress. Participants with T1DM also underwent assessment of carotid intima-media thickness by ultrasound, brachial distensibility by DynaPulse, fat and lean mass by dual-energy x-ray absorptiometry, fasting laboratories after overnight glycemic control, and insulin sensitivity by hyperinsulinemic-euglycemic clamp (glucose infusion rate/insulin). Adolescents with T1DM were randomized 1:1 to 3 months of 2000 mg metformin or placebo daily, after which baseline measures were repeated.ResultsForty-eight adolescents with T1DM who were 12 to 21 years of age (40% body mass index [BMI] ≥90th percentile; 56% female) and 24 nondiabetic control participants of similar age, BMI, and sex distribution were enrolled. Adolescents with T1DM demonstrated impaired aortic health compared with control participants, including elevated AA and descending aorta pulse wave velocity, reduced AA and descending aorta relative area change, and elevated AA and descending aorta WSSMAX and WSSTA. Adolescents with T1DM in the metformin versus placebo group had improved glucose infusion rate/insulin (12.2±3.2 [mg·kg-1·min-1]/μIU/μL versus -2.4±3.6 [mg·kg-1·min-1]/μIU/μL, P=0.005; 18.6±4.8 [mg·lean kg-1·min-1]/μIU/μL versus -3.4±5.6 [mg·lean kg-1·min-1]/μIU/μL, P=0.005) and reduced weight (-0.5±0.5 kg versus 1.6±0.5 kg; P=0.004), BMI (-0.2±0.15 kg/m2 versus 0.4±0.15 kg/m2; P=0.005), and fat mass (-0.7±0.3 kg versus 0.6±0.4 kg; P=0.01). Glucose infusion rate/insulin also improved in normal-weight participants (11.8±4.4 [mg·kg-1·min-1]/μIU/μL versus -4.5±4.4 [mg·kg-1·min-1]/μIU/μL, P=0.02; 17.6±6.7 [mg·lean kg-1·min-1]/μIU/μL versus -7.0±6.7 [mg·lean kg-1·min-1]/μIU/μL, P=0.02). The metformin group had reduced AA WSSMAX (-0.3±0.4 dyne/cm2 versus 1.5±0.5 dyne/cm2; P=0.03), AA pulse wave velocity (-1.1±1.20 m/s versus 4.1±1.6 m/s; P=0.04), and far-wall diastolic carotid intima-media thickness (-0.04±0.01 mm versus -0.00±0.01 mm; P=0.049) versus placebo.ConclusionsAdolescents with T1DM demonstrate IR and impaired vascular health compared with control participants. Metformin improves IR, regardless of baseline BMI, and BMI, weight, fat mass, insulin dose, and aortic and carotid health in adolescents with T1DM. Metformin may hold promise as a cardioprotective intervention in T1DM.Clinical trial registrationURL: https://www.clinicaltrials.gov . Unique identifier: NCT01808690.

Project description:BackgroundType 2 diabetes causes cardio-renal complications and is treated with different combination therapies. The renal hemodynamics profile of such combination therapies has not been evaluated in detail.MethodsPatients (N = 97) with type 2 diabetes were randomized to receive either empagliflozin and linagliptin (E+L group) or metformin and insulin glargine (M+I group) for 3 months. Renal hemodynamics were assessed with para-aminohippuric acid and inulin for renal plasma flow (RPF) and glomerular filtration rate (GFR). Intraglomerular hemodynamics were calculated according the Gomez´ model.ResultsTreatment with E+L reduced GFR (p = 0.003), but RPF remained unchanged (p = 0.536). In contrast, M+I not only reduced GFR (p = 0.001), but also resulted in a significant reduction of RPF (p < 0.001). Renal vascular resistance (RVR) decreased with E+L treatment (p = 0.001) but increased with M+I treatment (p = 0.001). The changes in RPF and RVR were different between the two groups (both padjust < 0.001). Analysis of intraglomerular hemodynamics revealed that E+L did not change resistance of afferent arteriole (RA) (p = 0.116), but diminished resistance of efferent arterioles (RE) (p = 0.001). In M+I group RA was increased (p = 0.006) and RE remained unchanged (p = 0.538). The effects on RA (padjust < 0.05) and on RE (padjust < 0.05) differed between the groups.ConclusionsIn patients with type 2 diabetes and preserved renal function treatment with M+I resulted in reduction of renal perfusion and increase in vascular resistance, in contrast to treatment with E+I that preserved renal perfusion and reduced vascular resistance. Moreover, different underlying effects on the resistance vessels have been estimated according to the Gomez model, with M+I increasing RA and E+L predominantly decreasing RE, which is in contrast to the proposed sodium-glucose cotransporter 2 inhibitor effects.Trial registrationThe study was registered at www.clinicaltrials.gov (NCT02752113) on April 26, 2016.

Dataset Information

Insulin Sensitivity and Renal Hemodynamic Function in Metformin-Treated Adults With Type 2 Diabetes and Preserved Renal Function.

Objective

Research design and methods

Results

Conclusions

Publications

Insulin Sensitivity and Renal Hemodynamic Function in Metformin-Treated Adults With Type 2 Diabetes and Preserved Renal Function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets