Predictors and Determinants of Albuminuria in People with Prediabetes and Diabetes Based on Smoking Status: A Cross-Sectional Study Using the UK Biobank Data

Abstract

Background: Smoking is attributed to both micro- and macrovascular complications at any stage of metabolic deregulation including prediabetes, particularly those who develop the disease at a young age. Current global diabetes prevention programmes appear to be glucocentric, and do not fully acknowledge the ramifications of cardiorenal risk factors in smokers. A more holistic approach is needed to prevent vascular complications in people with prediabetes and diabetes. Considering albuminuria as a surrogate marker for both micro- and macrovascular complications, we investigated the relationship between smoking status and albuminuria in people with prediabetes and diabetes, and explored how this relationship is affected by age, antihypertensive, and cholesterol-lowering medications.

Methods: A logistic regression model was fitted on UK Biobank dataset with 502,490 participants. A subgroup analysis investigated the effect of age, smoking status, antihypertensive and cholesterol-lowering medications on this relationship in people with prediabetes and diabetes.

Findings: Compared with non-smokers, the odds of albuminuria in smokers with prediabetes and diabetes were 1.43 (95% CI 1.16 - 1.77), and 1.29 (95% CI 1.02 – 1.64), respectively. People younger than 50 with prediabetes, and diabetes were at increased risk of albuminuria, compared with those over 50 years old, with OR 1.62 and 1.34, respectively. The odds of albuminuria remained statistically significantly high, in prediabetes and diabetes groups, despite being on anti-hypertensive, and cholesterol-lowering medications. The odds of albuminuria were not attenuated in ex-smokers either with prediabetes or diabetes.

Interpretation: Smokers with prediabetes are at a higher risk of albuminuria than those with diabetes. The risk in ex-smokers did not decline to a statistically significant level, presumably due to insufficient lag period since quitting. Current strategies for cholesterol and hypertension management may not be sufficient to reduce the risk of albuminuria in people both with prediabetes and diabetes. Smoking cessation and continued abstinence in people with prediabetes and diabetes should be promoted in order to prevent future vascular complications. Screening for albuminuria should be incorporated in the NHS health check.

Funding Information: No external funding was received for this study.

Declaration of Interests: DK declares no duality of interest. This publication is undertaken using UK Biobank data under application no – 61894 and is a part of MD thesis. JPS receives funding from the Wellcome Trust/Royal Society via a Sir Henry Dale Fellowship (ref: 211182/Z/18/Z) and an NIHR Oxford Biomedical Research Centre (BRC) Senior Fellowship. For open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. JRA is supported by a NIHR Clinician Scientist Award (CS 2018-18-ST2-007) SdeL reports that through his university, he has had grants not directly relating to this work, from AstraZeneca, GSK, Sanofi, Seqirus, and Takeda for vaccine research and membership of advisory boards for AstraZeneca, Sanofi and Seqirus. KK is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and the NIHR Leicester Biomedical Research Centre (BRC). Prof Khunti has acted as a consultant and speaker for Amgen, AstraZeneca, Bayer, Novartis, Novo Nordisk, Roche, Sanofi-Aventis, Lilly, Servier and Merck Sharp & Dohme. He has received grants in support of investigator and investigator-initiated trials from AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Pfizer, Boehringer Ingelheim and Merck Sharp & Dohme. KK has received funds for research, honoraria for speaking at meetings and has served on advisory boards for AstraZeneca, Lilly, Sanofi-cool=Aventis, Merck Sharp & Dohme and Novo Nordisk. MJD reports personal fees from Novo Nordisk, Sanofi-Aventis, Lilly, Merch Sharp & Dohme, Boehringer Ingelheim, Astra Zeneca, Janssen, Servier, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceuticals International Inc. She has also received grants from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, Janssen outside the submitted work 24 KK and MJD are members of the National Institute for Health and Clinical Excellence public health guidance on preventing type 2 diabetes and both are advisers to the UK epartment of Health for the NHS health checks programme. All other authors have nothing to confirm.

Ethics Approval Statement: This is a retrospective cross-sectional study using the UK Biobank (UKB) data. UK Biobank received ethics approval from the Northwest Multi-centre Research Ethics Committee (MREC). It has also received approval from the National Information Governance Board for Health & Social Care (NIGB). For this study, ethics approval was also granted by the Research Ethics Committee, Sheffield School of Health and Related Research, University of Sheffield Application No 038586, 09/03/2021).

Keywords: - Albuminuria, Prediabetes, Type 2 diabetes, and Smoking