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Independent correlates of urinary albumin excretion within the normoalbuminuric range in patients with type 2 diabetes: The Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study

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Abstract

Aims

Within the normoalbuminuric range, low albuminuria (LA, 10–29 mg/24 h) is associated with higher adverse cardiovascular and renal outcomes than normal albuminuria (NA, <10 mg/24 h). This cross-sectional analysis of the cohort from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study was aimed at assessing the independent correlates of LA versus NA in patients with type 2 diabetes.

Methods

This analysis involved 11,538 normoalbuminuric patients (73.2 % of the entire RIACE cohort): 6023 (52.2 %) with NA and 5515 (47.8 %) with LA. Binary logistic regression analysis with backward conditional variable selection was applied to assess the independent correlates of LA versus NA.

Results

Compared with NA subjects, LA patients were more frequently males, older and with family history of hypertension, had longer diabetes duration, lower HDL cholesterol, and higher haemoglobin (Hb) A1c, triglycerides, and blood pressure (BP), use of anti-hyperglycaemic and anti-hypertensive drugs, and prevalence of metabolic syndrome, retinopathy, chronic kidney disease, any cardiovascular disease, myocardial infarction, and coronary and peripheral events. Men with LA were also more frequently current or former smokers and had higher body mass index, waist circumference, and non-HDL cholesterol. Independent correlates of LA were age (OR 1.018), family history of hypertension (OR 1.321), smoking status (former, OR 1.158; current, OR 1.237), HbA1c (OR 1.062), waist circumference (OR 1.050), triglycerides (OR 1.001), and diastolic BP (OR 1.014), together with use of anti-hyperglycaemic and anti-hypertensive agents.

Conclusions

Several risk factors are associated with increased albuminuria within the normoalbuminuric range. As most of these factors are potentially modifiable, treating them aggressively might reduce the excess risk associated with LA.

Trial registration

NCT00715481; www.ClinicalTrials.gov.

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Abbreviations

AER:

Albumin excretion rate

ACR:

Albumin-to-creatinine ratio

CVD:

Cardiovascular disease

eGFR:

Estimated glomerular filtration rate

DM:

Diabetes mellitus

T2DM:

Type 2 DM

RIACE:

Renal insufficiency and cardiovascular events

NA:

Normal albuminuria

LA:

Low albuminuria

T1DM:

Type 1 DM

ROADMAP:

Randomised Olmesartan and Diabetes Microalbuminuria Prevention

BP:

Blood pressure

BMI:

Body mass index

MS:

Metabolic syndrome

HbA1c :

Haemoglobin A1c

CKD:

Chronic kidney disease

DR:

Diabetic retinopathy

OHA:

Oral hypoglycaemic agents

RAS:

Renin–angiotensin system

DHP:

Dihydropyridine

PP:

Pulse pressure

OR:

Odds ratio

CI:

Confidence interval

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Acknowledgments

The authors thank the RIACE Investigators for participating in this study (see the complete list as online Appendix).

Author information

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Giuseppe Penno & Anna Solini

  2. Division of Endocrinology and Metabolic Diseases, University of Verona, Verona, Italy

    Giacomo Zoppini

  3. Diabetes Unit, University of Siena, Siena, Italy

    Cecilia Fondelli

  4. Endocrinology and Diabetes Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy

    Roberto Trevisan

  5. Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy

    Monica Vedovato

  6. Department of Clinical and Biological Sciences, University of Turin, Orbassano, Turin, Italy

    Franco Cavalot

  7. Department of Internal Medicine, University of Turin, Turin, Italy

    Gabriella Gruden

  8. Department of Medical Sciences, University of Foggia, Foggia, Italy

    Olga Lamacchia

  9. Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy

    Luigi Laviola

  10. Diabetes Unit, IRCCS “Cà Granda - Ospedale Maggiore Policlinico” Foundation, Milan, Italy

    Emanuela Orsi

  11. Department of Clinical and Molecular Medicine, “La Sapienza” University, Via di Grottarossa, 1035-1039, 00189, Rome, Italy

    Giuseppe Pugliese

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  1. Giuseppe Penno
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  2. Anna Solini
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  3. Giacomo Zoppini
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  9. Olga Lamacchia
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Renal Insufficiency Cardiovascular Events (RIACE) Study Group

Corresponding author

Correspondence to Giuseppe Pugliese.

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Funding sources

This work was supported by the Research Foundation of the Italian Society of Diabetology (Fo.Di.Ri) and the Diabetes, Endocrinology, and Metabolism (DEM) Foundation, and by unconditional grants from Eli-Lilly, Takeda, Chiesi Farmaceutici and Boehringer-Ingelheim. The sponsors had no role in design and conduct of the study; collection, management, and interpretation of the data; or preparation, review, and approval of the manuscript.

Conflict of interest

The authors declare no relevant conflict of interest to disclose.

Ethical standard

The study was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments. The protocol was approved by the locally appointed ethics committees, and participants gave informed consent.

Human and Animal Rights disclosure

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent disclosure

Informed consent was obtained from all patients for being included in the study.

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Penno, G., Solini, A., Zoppini, G. et al. Independent correlates of urinary albumin excretion within the normoalbuminuric range in patients with type 2 diabetes: The Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study. Acta Diabetol 52, 971–981 (2015). https://doi.org/10.1007/s00592-015-0789-x

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