**1. Introduction**

Globally, the number of persons with diabetes mellitus is rising, with the International Diabetes Federation estimating that there were 463 million cases of the disease in 2019 and that there would be 700.2 million cases by 2045 [1]. The prevalence of type 2 diabetes mellitus (T2DM) among South Korean adults rapidly increased over the past decades from 1.5% in 1971 to 13.7% in 2016 [2]. The economic burden of diabetes mellitus in Korea was USD 18,293 million in 2019 [3]. Moreover, the per capita cost increased nearly four times, from USD 3991 to USD 11,965, when the number of complications due to diabetes mellitus increased from one to three or more [3]. Patients with T2DM are at a higher risk of cardiovascular mortality, all-cause mortality, and comorbidities, including cardiovascular disease, cerebrovascular disease, and peripheral vascular disease [4]. Therefore, preventive strategies for T2DM have been emphasized to reduce this disease burden [4].

The two main characteristics of T2DM are target tissue insulin resistance and a relative deficiency of insulin production from pancreatic β-cells [5]. Over recent years, numerous studies have demonstrated a synergistic interaction between inflammation-related insulin resistance [6]. The emerging role of chronic low-grade inflammation in insulin

**Citation:** Kwon, Y.-J.; Park, H.-M.; Lee, J.-H. Inverse Association between Oxidative Balance Score and Incident Type 2 Diabetes Mellitus. *Nutrients* **2023**, *15*, 2497. https:// doi.org/10.3390/nu15112497

Academic Editor: Giuseppe Della Pepa

Received: 27 April 2023 Revised: 21 May 2023 Accepted: 22 May 2023 Published: 27 May 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

resistance and β-cell dysfunction in T2DM has engendered increasing attention in targeting inflammation to advance the prevention and management of the disease [7].

A recent meta-analysis elucidated that a coalescence of low-risk lifestyle behaviors (such as appropriate body weight, healthy eating habits, light alcohol consumption, regular exercise, and smoking cessation) resulted in an 80% reduction in the risk of developing T2DM [8]. This finding aligns with a previous study emphasizing the balance between antioxidants and oxidative stress in chronic diseases [9]. Smoking is a powerful pro-oxidant, and the burden of oxidative stress could be exacerbated through the secondary release of oxygen radicals from inflammation status [9]. Therefore, several studies proposed a link between chronic disease and the oxidative balance score (OBS) [10–17]. The OBS evaluates the oxidative balance of the lifestyle pattern of a subject in terms of the incorporated consumption of anti- and pro-oxidants [10,12,18]. Lifestyle (cigarette smoking and alcohol drinking), healthy body weight (obesity and abdominal obesity), and healthy diet (lower intakes of saturated fatty acid [SFA], omega-6 poly-unsaturated fatty acid [PUFA], iron and high intakes of vitamin C, vitamin E, omega-3 PUFA, selenium, and beta-carotene) could be involved as OBS components [10].

To the best of our knowledge, no previous study has comprehensively examined OBS and the incidence of T2DM in the middle-aged and elderly. Therefore, we prospectively investigated the development of T2DM according to the OBSs of tertile groups from a large-population, community-based Korean cohort observed over 16 years.

#### **2. Materials and Methods**

#### *2.1. Study Population*

We used the Korean Genome and Epidemiology Study (KoGES)-Ansan and Ansung, embedded in the KoGES, a large, community-based study in Korea. The study design and procedures were detailed in a previous study [19]. KoGES-Ansan and Ansung included 10,030 adults aged from 40 to 69 years. This survey was conducted between 2001 and 2002 and followed up every two years. For the present study, we included participants with the eighth follow-up, conducted between 2017 and 2018. Initially, a total of 10,030 participants received a health examination and questionnaire. Subsequently, we excluded participants with T2DM at baseline (*n* = 1351), those with missing data to evaluate T2DM (*n* = 2), those with missing data to calculate OBSs (*n* = 601), and those who did not follow up after the baseline survey (*n* = 707). Finally, a total of 7369 participants (3485 men and 3884 women) were included in this analysis. The flow chart is shown in Figure 1. All participants in this study provided informed consent. This study protocol was approved by the Nowon Eulji Medical Center's Institutional Review Board (approval number: 2021-09-025) and followed the ethical criteria of the 1964 Declaration of Helsinki and its subsequent amendments.

**Figure 1.** Flowchart of the study population selection.

#### *2.2. Assessment of Oxidative Balance Score*

The OBS was calculated as the sum of seven pro-oxidant factors and six antioxidant factors selected based on previous studies [10–17]. The scheme of OBS is described in Table 1. Pro-oxidant factors include SFA, omega-6 PUFA, total iron intake, smoking status, drinking status, obesity status, and abdominal obesity status. Each question was scored 0, 1, or 2. The scores for SFA, omega-6 PUFA, and total iron intake were assigned 0 through 2 points according to the sex-specific tertile values of each variable corresponding to low (score 2), intermediate (score 1), and high (score 0). For smoking status, the scores for never smoker, former smoker, and current smoker were 2, 1, and 0, respectively. For drinking status, the scores for a non-drinker, mild drinker (1–19 g/day in men, 1–9 g/day in women), and moderate drinker (20–29 g/day in men, 10–19 g/day in women) were 2, 1, and 0, respectively. Zero points were given for people with obesity, one point was given for people who were overweight, and 2 points were given for people within a normal weight range. Zero points were given for people with abdominal obesity. Antioxidant factors include intakes of omega-3 PUFA, vitamin C, vitamin E, selenium, and beta-carotene and physical activity. The scores for omega-3 PUFA, vitamin C, vitamin E, selenium, and beta-carotene intake were assigned 0 through 2 points according to the sex-specific tertile values of each variable corresponding to high (score 2), intermediate (score 1), and low (score 0). Two points were given for high-intensity physical activity, one for moderate physical activity, and 0 for low physical activity. The sums of the OBSs ranged from 0 to 26 points. We classified the participants into sex-specific tertile groups according to OBSs.

**Table 1.** Oxidative balance score assignment scheme.


\* Low, intermediate, and high categories correspond to sex-specific tertile values among participants in the KoGES at the baseline survey. Abbreviations: P, pro-oxidant; A, antioxidant; PUFA, poly-unsaturated fatty acid; MET, metabolic equivalent of task; KoGES, Korean Genome and Epidemiology Study.

#### *2.3. Assessment of T2DM*

T2DM was characterized as the presence of one or more of the following criteria: (1) a fasting plasma glucose level of 126 mg/dL or higher, (2)a2h after 75 g oral glucose tolerance test plasma glucose level of 200 mg/dL or higher, (3) glycosylated hemoglobin of 6.5% or higher, (4) treatment with oral anti-diabetic medicine, or (5) treatment with insulin therapy [20].
