Association Between Phthalates Exposure and Renal Function Impairment in TYpe 2 Diabetes

NCT03622957 | Unknown

• 1 other identifier: PURITY - Protocol 2
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The global incidence of diabetic nephropathy (DN) is increasing, with no appreciable reduction in the percent of patients progressing toward end stage renal disease (ESRD) and dialysis (Tuttle et al, 2014, Winocour et al, 2018). Therefore, identification of modifiable risk factors and early biomarkers of progressive decline in kidney function is an urgent clinical need. Phthalates are environmental and dietary contaminants with a various array of use that are identified in many consumer and industrial products; among them, di-(2-ethylhexyl) phthalate (DEHP) and its metabolites (mono 2-ethylhexyl phthalate (MEHP), 5OH-MEHP (MEHHP) and 5oxo-MEHP (MEOHP)) are widely used (Kato et al 2004, Braun et al, 2013). They partially distribute to the human tissues and their urinary and serum levels are directly related; therefore, urinary concentration of phthalates is commonly used as proxy of their exposure in humans (Kato et al 2004). While the association between phthalates exposure and development of T2D is currently being explored (Dong et al 2017, Dales et al, 2018), little is known about their role in DN. Recent observations show that DEHP and its metabolites are associated with a higher prevalence of low-grade albuminuria and in children exposed to higher phthalates concentrations (Trasande et al, 2014, Wu et al, 2018), however such association has yet to be verified in adults. The environmental ubiquity of the phthalates enhances the importance of investigating the potential relation between their exposure and different degrees of renal function. (Kato et al 2004, Kataria et al, 2015). Given this premise, the investigators will explore this potential association in a population of subjects with T2D consecutively referring to the outpatient diabetes clinic in Santa Chiara Hospital, Pisa, enrolled on a volunteer basis. During their routine visit at Santa Chiara Hospital outpatient diabetes clinic participants will provide the results of blood tests prescribed as per standard clinical practice along with a first morning, overnight fasting, urine sample collected in a phthalates-free container. The investigators will record the participants' clinical history, physical examination and anthropometric measurements, will measure their renal function, evaluated by eGFR (calculated with the CDK-EPI formula), albumin excretion, fasting glucose, HbA1c%, and the exposure to phthalates, assessed by total concentrations of MEHP, MEOHP, MEHHP and adjusted for urinary creatinine. In this way, the investigators aim to point out the relationship of urinary phthalates with higher degrees of albuminuria and/or lower eGFR after adjustment for all potential confounders, including therapies.

Conditions

Diabetes Mellitus, Type 2; Albuminuria; Cardiovascular Risk Factor

Outcome Measures

Primary Outcomes (3)

• Phthalates exposure [ug/g]

  Concentrations of metabolites of DEHP \[ug/ml\] in a first morning spot urine sample (obtained during clinical visit) measured by ultra-HPLC coupled with electrospray ionization/quadrupole time-of-flight MS and then normalized for urinary creatinine \[g/ml\].

  Single routine clinical visit

• Albuminuria [mg/g]

  Grade of albuminuria measured by albuminuria/creatininuria ratio \[mg/g\] in a first morning spot urine sample (obtained during clinical visit).

  Single routine clinical visit

• Glomerular Filtration Rate [ml/min/1.73m2]

  GFR measured by eGFR (calculated with CDK-EPI formula). Creatinine \[mg/dL\] is measured in a serum sample (obtained during clinical visit). Physiological parameters (age, sex, race) are obtained during clinical visit.

  Single routine clinical visit

Secondary Outcomes (1)

• CV Events (Yes/No)

  Single routine clinical visit

Study Arms (1)

Type 2 diabetes subjects

Type 2 diabetes subjects consecutively referring to Santa Chiara, Pisa diabetes outpatients clinic

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Type 2 diabetes individuals referring to our outpatient clinics

You may qualify if:

• Age 18-85 years, T2D diagnosis, T2D duration \>6 months,

You may not qualify if:

• occurring acute clinical conditions, eGFR \<15 ml/min/1.73m2, BMI \> 40 Kg/m2.

Sponsors & Collaborators

• University of Pisa: lead
• Istituto di Fisiologia Clinica CNR: collaborator

Study Sites (1)

University of Pisa

Pisa, 56125, Italy

Location

Related Publications (10)

• Tuttle KR, Bakris GL, Bilous RW, Chiang JL, de Boer IH, Goldstein-Fuchs J, Hirsch IB, Kalantar-Zadeh K, Narva AS, Navaneethan SD, Neumiller JJ, Patel UD, Ratner RE, Whaley-Connell AT, Molitch ME. Diabetic kidney disease: a report from an ADA Consensus Conference. Diabetes Care. 2014 Oct;37(10):2864-83. doi: 10.2337/dc14-1296.

  PMID: 25249672 BACKGROUND

• Winocour PH. Diabetes and chronic kidney disease: an increasingly common multi-morbid disease in need of a paradigm shift in care. Diabet Med. 2018 Mar;35(3):300-305. doi: 10.1111/dme.13564. Epub 2018 Jan 8.

  PMID: 29247554 BACKGROUND

• Kato K, Silva MJ, Reidy JA, Hurtz D 3rd, Malek NA, Needham LL, Nakazawa H, Barr DB, Calafat AM. Mono(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-oxohexyl) phthalate as biomarkers for human exposure assessment to di-(2-ethylhexyl) phthalate. Environ Health Perspect. 2004 Mar;112(3):327-30. doi: 10.1289/ehp.6663.

  PMID: 14998748 BACKGROUND

• Braun JM, Sathyanarayana S, Hauser R. Phthalate exposure and children's health. Curr Opin Pediatr. 2013 Apr;25(2):247-54. doi: 10.1097/MOP.0b013e32835e1eb6.

  PMID: 23429708 BACKGROUND

• Dong R, Zhao S, Zhang H, Chen J, Zhang M, Wang M, Wu M, Li S, Chen B. Sex Differences in the Association of Urinary Concentrations of Phthalates Metabolites with Self-Reported Diabetes and Cardiovascular Diseases in Shanghai Adults. Int J Environ Res Public Health. 2017 Jun 5;14(6):598. doi: 10.3390/ijerph14060598.

  PMID: 28587233 BACKGROUND

• Dales RE, Kauri LM, Cakmak S. The associations between phthalate exposure and insulin resistance, beta-cell function and blood glucose control in a population-based sample. Sci Total Environ. 2018 Jan 15;612:1287-1292. doi: 10.1016/j.scitotenv.2017.09.009. Epub 2017 Sep 8.

  PMID: 28898934 BACKGROUND

• Trasande L, Sathyanarayana S, Trachtman H. Dietary phthalates and low-grade albuminuria in US children and adolescents. Clin J Am Soc Nephrol. 2014 Jan;9(1):100-9. doi: 10.2215/CJN.04570413. Epub 2013 Oct 31.

  PMID: 24178978 BACKGROUND

• Wu CF, Hsiung CA, Tsai HJ, Tsai YC, Hsieh HM, Chen BH, Wu MT. Interaction of melamine and di-(2-ethylhexyl) phthalate exposure on markers of early renal damage in children: The 2011 Taiwan food scandal. Environ Pollut. 2018 Apr;235:453-461. doi: 10.1016/j.envpol.2017.12.107. Epub 2018 Jan 6.

  PMID: 29310089 BACKGROUND

• Kataria A, Trasande L, Trachtman H. The effects of environmental chemicals on renal function. Nat Rev Nephrol. 2015 Oct;11(10):610-25. doi: 10.1038/nrneph.2015.94. Epub 2015 Jun 23.

  PMID: 26100504 BACKGROUND

• Mengozzi A, Carli F, Biancalana E, Della Latta V, Seghieri M, Gastaldelli A, Solini A. Phthalates Exposure as Determinant of Albuminuria in Subjects With Type 2 Diabetes: A Cross-Sectional Study. J Clin Endocrinol Metab. 2019 May 1;104(5):1491-1499. doi: 10.1210/jc.2018-01797.

  PMID: 30462244 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

First morning spot urine sample

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Albuminuria

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Proteinuria; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Anna Solini, Associate Professor, MD, PhD

CONTACT

+39 050993482; anna.solini@med.unipi

Alessandro Mengozzi, MD

CONTACT

+ 39050993640; alessandro.mengozzi@medmcs.unipi.it

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, MD, PhD

Study Record Dates

• First Submitted: August 6, 2018
• First Posted: August 9, 2018
• Study Start: August 10, 2018
• Primary Completion: September 3, 2018
• Study Completion: September 3, 2018
• Last Updated: August 10, 2018

Record last verified: 2018-08

Locations

IT (1)