Healthy lifestyle behaviors, mediating biomarkers, and risk of microvascular complications among individuals with type 2 diabetes: A cohort study

Healthy lifestyle behaviors, mediating biomarkers, and risk of microvascular complications among individuals with type 2 diabetes: A cohort study

Abstract

Methods and findings

This retrospective cohort study included 15,104 patients with T2D free of macro- and microvascular complications at baseline (2006 to 2010) from the UK Biobank. Healthy lifestyle behaviors included noncurrent smoking, recommended waist circumference, regular physical activity, healthy diet, and moderate alcohol drinking. Outcomes were ascertained using electronic health records. Over a median of 8.1 years of follow-up, 1,296 cases of the composite microvascular complications occurred, including 558 diabetic retinopathy, 625 diabetic kidney disease, and 315 diabetic neuropathy, with some patients having 2 or 3 microvascular complications simultaneously. After multivariable adjustment for sociodemographic characteristics, history of hypertension, glycemic control, and medication histories, the hazard ratios (95{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} confidence intervals (CIs)) for the participants adhering 4 to 5 low-risk lifestyle behaviors versus 0 to 1 were 0.65 (0.46, 0.91) for diabetic retinopathy, 0.43 (0.30, 0.61) for diabetic kidney disease, 0.46 (0.29, 0.74) for diabetic neuropathy, and 0.54 (0.43, 0.68) for the composite outcome (all Ps-trend ≤0.01). Further, the population-attributable fraction (95{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} CIs) of diabetic microvascular complications for poor adherence to the overall healthy lifestyle (<4 low-risk factors) ranged from 25.3{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} (10.0{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}, 39.4{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}) to 39.0{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} (17.7{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}, 56.8{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}). In addition, albumin, HDL-C, triglycerides, apolipoprotein A, C-reactive protein, and HbA1c collectively explained 23.20{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} (12.70{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}, 38.50{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}) of the associations between overall lifestyle behaviors and total diabetic microvascular complications. The key limitation of the current analysis was the potential underreporting of microvascular complications because the cases were identified via electronic health records.

Author summary

Introduction

Diabetes is a global public health crisis affecting greater than 0.5 billion adults worldwide [1]. Diabetic microvascular complications including diabetic retinopathy, diabetic neuropathy, and diabetic kidney disease have placed a significant health and economic burden borne by individuals, families, and health systems [2,3]. For example, diabetic retinopathy, the leading cause of vision loss, is present in nearly 30{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} of patients with diabetes [4]. Furthermore, both diabetic kidney disease and diabetic neuropathy may develop in approximately 50{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} of patients with diabetes [5,6]. Therefore, it is paramount to identify cost-effective strategies to prevent and delay the development of microvascular complications in patients with diabetes.

Beyond the glucose control by medications, the American Diabetes Association guideline has highlighted that both caregivers and patients should focus on how to optimize lifestyle behaviors to improve diabetes care [7]. Although lifestyle behaviors that are generally recommended, e.g., normal weight, no smoking, moderate alcohol drinking, healthy diet, and physically active, have been associated with lower risks of microvascular complications [814], to our best knowledge, the magnitudes of the joint association of multiple lifestyle factors with the development of microvascular complications in diabetes have not yet been quantified, which may have substantial public health implications on translating epidemiological findings to meaningful public health actions. In addition, several studies have linked lifestyle behaviors with a range of intermediate variables including lipid profile [15,16], liver function biomarkers [15,1719], renal function biomarkers [20,21], blood pressure indices [22], glucose metabolism measures [23], and systemic inflammatory factors [15,16]; however, whether and the extent to which these metabolic biomarkers could mediate the association between lifestyle behaviors and diabetic microvascular complications remains unclear.

To shed light on the potential favorable association of overall lifestyle behaviors on microvascular complications in patients with diabetes, we examined the joint association of multiple lifestyle behaviors, including waist circumference (WC), smoking status, habitual diet, physical activity, and alcohol intake with risks of total microvascular complications, diabetic retinopathy, diabetic neuropathy, and diabetic kidney disease among patients with type 2 diabetes (T2D) who participated in the UK Biobank study. In addition, we also comprehensively evaluated the effect of a series of blood biomarkers on mediating the relationship between lifestyle behaviors and diabetic microvascular complications.

Methods

Study population

The UK Biobank is a large community-based prospective cohort study for common diseases of middle and older adults including over 500,000 participants aged 37 to 73 years from 22 sites across England, Scotland, and Wales between March 2006 and October 2010. Extensive data were obtained through touchscreen questionnaires, physical measurements, and biological samples at recruitment. Specific methods of data collection have been described previously [24,25].

Our sample of 15,104 was generated by including patients with T2D identified by using the algorithms method developed by the UK Biobank study [26] and excluding participants with prevalent macro- or microvascular complication cases, had incomplete information on lifestyle behaviors, or withdrawal from the study. The flowchart of patients included in the current study is present in S1 Fig.

The study was approved by the North West Multi-Centre Research Ethics Committee, the National Information Governance Board for Health and Social Care in England and Wales, and the Community Health Index Advisory Group in Scotland. All participants provided written informed consent. In the current analysis, we employed the UK Biobank study to test a priori hypothesis; we did not publish an analysis plan before conducting analyses between January 2022 and March 2022. The associations between lifestyle factors and the risk of microvascular complications in participants without excluding those with macrovascular complications and stratified analysis by preexisting cardiovascular disease (CVD) status were performed in response to peer review in July 2022. This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline (S1 Checklist).

Measurements of lifestyle behaviors

Five lifestyle behaviors, namely, WC, smoking status, physical activity, habitual diet, and alcohol intake, were evaluated in the current analysis. We used WC instead of body mass index (BMI) to avoid the potential obesity paradox [27,28] as evidence found an obesity paradox when obesity was measured by BMI but not when measured by WC in patients with diabetes [29]. WC was measured using the Wessex nonstretchable sprung tape measurement, and low-risk WC was defined as <80 cm for women and <94 cm for men [30,31]. Data on smoking status were self-reported, and noncurrent smoking was defined as low-risk behavior. The frequency of all types of alcohol intake was reported using 6 predefined categories, between never to daily or almost daily. For participants who reported to drink alcohol, data on the average monthly or weekly alcohol intake from 6 types of alcohol beverages were collected. We calculated the average units of alcohol intake using the abovementioned information and defined low-risk drinking as moderate drinking (1 to 14 g/day for women or 1 to 28 g/day for men). Data on the type and duration of physical activity were derived from the questionnaire. Leisure-time physical activity score based on the 5 activities undertaken in the last 4 weeks was computed by multiplying the metabolic equivalent of task [MET] score of each activity by the minutes performed [32,33]. Light DIY (do-it-yourself), walking for pleasure, other exercises (e.g., swimming, cycling, keep fit, bowling), heavy DIY, and strenuous sports were given 1.5, 3.5, 4.0, 5.5, and 8.0 METs, respectively [34]. The midpoints of the frequency and duration of physical activities were used to calculate the time spent on each activity. We then classified the top third of the physical activity score as the low-risk group. In addition, we generated a dietary score to reflect the overall diet quality including 10 components, namely, fruits, vegetables, whole grains, fish, dairy, vegetable oils, refined grains, processed meat, unprocessed meat, and sugar-sweetened beverages. Low-risk diet was defined as meeting 5 or more ideal diet components [35]. Participants with each low-risk behavior were assigned 1 point; otherwise, 0 points. The overall healthy lifestyle score was the sum of individual score of the 5 lifestyle behaviors, ranging from 0 to 5, with higher score indicating healthier lifestyle.

Assessment of the circulating biomarkers

Blood samples were collected from consenting participants at recruitment, separated by components and stored at UK Biobank (−80°C and LN2) until analysis. Blood biomarkers were externally validated with stringent quality control in the UK Biobank; full details on assay performance have been given elsewhere [36]. We selected the potential biological biomarkers mediating the association between lifestyle factors and microvascular complications based on knowledge of potential pathways, including glycemic control determined by glycated hemoglobin (HbA1c), lipid profile (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], triglycerides, apolipoprotein A, apolipoprotein B, and lipoprotein A), liver function (alanine aminotransferase [ALT], alkaline phosphatase [ALP], aspartate aminotransferase [AST], gamma glutamyltransferase [GGT], total bilirubin, total protein, and albumin), renal function (cystatin C, creatinine, urate, and urea), inflammation (C-reactive protein [CRP], and white blood cell count), and blood pressure indices (systolic blood pressure [SBP] and diastolic blood pressure [DBP]).

Statistical analysis

Comparisons of baseline characteristics across the categories of the overall healthy lifestyle score were made using ANOVA or chi-squared test. We also compared the differences between patients included in the current analysis and those who were excluded due to missing values. Person-years were calculated from the date of recruitment to the date of death, first endpoint, lost to follow-up, or the end of follow-up, whichever came first. The lost to follow-up variable in the UK Biobank has been created by amalgamating data from 5 possible sources: (1) Death reported to UK Biobank by a relative; (2) NHS records indicate they are lost to follow-up; (3) NHS records indicate they have left the UK; (4) UK Biobank sources report they have left the UK; (5) Participant has withdrawn consent for future linkage. The end of follow-up dates were 1 April 2017, 17 September 2016, and 1 November 2016, for centers in England, Wales, and Scotland, respectively. Cox proportional hazards regression models were used to calculated hazard ratios (HRs) and 95{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} confidence intervals (CIs) for the associations of individual lifestyle behaviors and overall healthy lifestyle score with risks of total and individual microvascular complications in patients with T2D. We imputed the missing values of covariates (≤7{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}) using multiple imputations by chained equations with 5 imputations (SAS PROC MI with a fully conditional specification method and PROC MIANALYZE). Linear regression model and logistic regression model with all the covariates in the fully adjusted model were used to impute continuous variables and categorical variables, respectively. The percentage of missing values are present in S1 Table.

Three models were built. In Model 1, we adjusted for age (continuous, years), sex (male, female), Townsend Deprivation Index (continuous), and race/ethnicity (White, others). In Model 2, we further adjusted for education attainment (college or university degree, A/AS levels or equivalent or O levels/GCSEs, NVQ or HND or HNC or equivalent or other professional qualifications, none of the above), sleep duration (<6, 6 to 8, or ≥9 hours/day), family history of CVD (yes, no), family history of hypertension (yes, no), and prevalence of hypertension (yes, no). Finally, in Model 3, diabetes duration (continuous, years), HbA1c (continuous, mmol/mol), use of diabetes medication (none, only oral medicine, insulin, and others), use of antihypertensive medication (yes, no), use of lipid-lowing medication (yes, no), and use of aspirin (yes, no) were additionally adjusted. Further, restricted cubic spline analysis was applied to test dose–response relationships between the healthy lifestyle score and risks of outcomes. We also calculated the population-attributable fractions (PAFs) using the {e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}par SAS Macro (https://www.hsph.harvard.edu/donna-spiegelman/software/par/) to estimate the proportion of microvascular complications that could theoretically be avoided if all participants adhered to 4 or more low-risk lifestyle behaviors.

Mediation effects of biomarkers on the associations of overall lifestyle score with risks of total and individual microvascular complications were evaluated using mediation package in R. Indirect, direct, and total effects for each mediator were computed via combining the mediator and outcome models with the adjustment of all the covariates in Model 3. Nonparametric bootstrap resampling was used to compute the CIs of the proportions of mediations. We selected the available biomarkers from the UK Biobank for the mediation analyses based on knowledge of potential causal pathways to predisposing to microvascular complications or mortality [19,3740]. The selected biomarkers were considered as potential mediators following two-step analysis. First, we assessed the associations of all biomarkers with the overall lifestyle score using the multivariable-adjusted linear regression models. Second, we evaluated the associations of biomarkers that were significantly associated with the overall lifestyle score, with risks of all the outcomes using the multivariable-adjusted Cox regression model. We then chose the biomarkers significantly associated with each outcome for the mediation analysis accordingly.

In addition, stratified analyses were conducted by age (≤60, >60 years), sex (female, male), education (less than college, college, or above), diabetes duration (≤3, >3 years), use of diabetes medication (yes, no), and HbA1c (≤53, >53 mmol/mol). Interactions between the overall healthy lifestyle score and stratified factors on the risk of outcomes were examined using the likelihood ratio test by adding product terms in the multivariable-adjusted Cox models. Further, we examined the associations of different combinations of low-risk lifestyle behaviors with outcomes.

Several sensitivity analyses were conducted to test the robustness of our results. First, to minimize the potential reverse causation, we performed the analysis among patients with T2D after excluding the cases that occurred within 2 years of follow-up. Second, we generated the overall lifestyle score using low-risk drinking defined as moderate alcohol drinking and never drinking and repeated the main analysis using the new lifestyle score. Third, we constructed the healthy lifestyle score using BMI or waist-to-hip ratio instead of WC. Fourth, we generated a weighted healthy lifestyle score and examined the associations of the weighted healthy lifestyle score with risks of outcomes. Fifth, we investigated the association between the overall lifestyle score and risk of diabetic kidney disease, and mediation analysis for diabetic kidney disease with additional adjustment for kidney function biomarkers. Sixth, we performed the analysis via including the patients with CVD (n = 3,397) at baseline and stratified the associations by preexisting CVD status. Finally, given the potential competing risk of death highlighted during the peer review process, we assessed the associations of healthy lifestyle score with risks of microvascular complications using both the cause-specific hazard model and Fine and Gray subdistribution methods.

We used SAS V.9.4 and R software version 4.0.2 (R Foundation for Statistical Computing) for all statistical analyses. A two-tailed P < 0.05 was considered to be statistically significant.

Results

Baseline characteristics

Among 15,104 participants with T2D (60.3{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} male; mean age, 59.3 years), there were 3,406 (22.6{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}), 6,080 (40.3{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}), 4,062 (26.9{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}), 1,556 (10.3{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}) having 0 or 1, 2, 3, and 4 or 5 low-risk lifestyle behaviors, respectively. The baseline characteristics are shown in Table 1. Participants with more low-risk lifestyle behaviors were more likely to be men, White, less deprived, highly educated, sleep recommended hours, have a lower level of HbA1c, and have a lower prevalence of hypertension. They were less likely to use aspirins and medications for diabetes, dyslipidemia, and hypertension. In addition, compared the participants who were excluded due to missing values, those included in the current analysis were more likely to be men, White, less deprived, highly educated, noncurrent smokers, physically active, moderate alcohol drinkers, and eat healthier (S2 Table).

Lifestyle behaviors and outcomes

During 117,445 person-years of follow-up (median 8.1 years; interquartile range 7.3 to 8.8 years; maximum 11.9 years), there occurred 1,639 (10.9{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}) deaths and 1,296 (8.6{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}) composite microvascular complications cases, including 558 (3.7{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}) diabetic retinopathy, 625 (4.1{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}) diabetic kidney disease, and 315 (2.1{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}) diabetic neuropathy. Among all the cases, one case of diabetic kidney disease was uniquely identified from death records. S3 Table shows the associations between individual lifestyle behaviors and all the outcomes. Being physically active, with lower WC, and moderate alcohol intake were associated with a lower risk of microvascular complications, while noncurrent smoking and healthy diet were not. The overall healthy lifestyle score was associated with lower risks of all the outcomes in a dose–response manner (all Ps for linear trend ≤0.01; Table 2 and Figs 1 and S2). Compared with participants with 0 to 1 low-risk lifestyle behavior, participants with 4 to 5 low-risk lifestyle behaviors had HRs (95{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} CIs) of 0.65 (0.46, 0.91) for diabetic retinopathy, 0.43 (0.30, 0.61) for diabetic kidney disease, 0.46 (0.29, 0.74) for diabetic neuropathy, and 0.54 (0.43, 0.68) for the composite microvascular complications, respectively. For each number increment in low-risk lifestyle behavior, there was a 13{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} lower risk of diabetic retinopathy (HR, 0.87; 95{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} CI: 0.80, 0.95), 22{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} lower risk of diabetic kidney disease (HR, 0.78; 95{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} CI: 0.72, 0.85), 27{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} lower risk of diabetic neuropathy (HR, 0.73; 95{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} CI: 0.65, 0.83), and a 18{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} lower risk of the composite microvascular complications (HR, 0.82; 95{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} CI: 0.77, 0.87).

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Fig 1. Dose–response relationship of the healthy lifestyle score with risk of microvascular complications among individuals with T2D.

X-axis showed the numbers of low-risk lifestyle behaviors, and y-axis showed the HRs of the composite microvascular complications (A), diabetic retinopathy (B), diabetic kidney disease (C), and diabetic neuropathy (D). Black curves were HRs, and grey zones were 95{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} CIs. Multivariable-adjusted models were adjusted for age (continuous, years), sex (male, female), ethnicity (White, others), education attainment (college or university degree, A/AS levels or equivalent or O levels/GCSEs or equivalent or other professional qualifications, or none of the above), Townsend Deprivation Index (continuous), sleep duration (<6, 6–8, or ≥9 hours/day), family history of CVD (yes, no), family history of hypertension (yes, no), prevalence of hypertension (yes, no), diabetes duration (continuous, years), HbA1c (continuous, mmol/mol), use of diabetes medication (none, only oral medication pills, or insulin or others), use of antihypertensive medication (yes, no), use of lipid-lowing medication (yes, no), and use of aspirin (yes, no). All P-nonlinearity were ≥0.09 and all P for overall association were <0.001 (except for diabetic retinopathy: P for overall association = 0.008). CI, confidence interval; CVD, cardiovascular disease; HR, hazard ratio; T2D, type 2 diabetes.


https://doi.org/10.1371/journal.pmed.1004135.g001

In addition, the estimated PAFs of nonadherence to 4 or more low-risk lifestyle factors were 39.0{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} (17.7{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}, 56.8{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}) for diabetic kidney disease and 25.3{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} (10.0{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}, 39.4{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}) for the composite microvascular complications (Table 2).

Mediation analysis

All the biomarkers were significantly associated with the overall lifestyle score except for total protein, lipoprotein A, and SBP (S4 Table). The associations between the selected biomarkers and all outcomes are shown in S5 Table. Six significant mediators were detected on the associations of lifestyle score with risk of the composite microvascular complications and diabetic kidney disease, namely, albumin, HDL-C, triglycerides, apolipoprotein A, CRP, and HbA1c. The relationship between the lifestyle behaviors and risk of diabetic neuropathy was mediated by cystatin C, GGT, total bilirubin, albumin, HDL-C, triglycerides, apolipoprotein A, CRP, and HbA1c with the proportion of mediation effect ranging from 3.22{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} to 11.35{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}. Collectively, the mediators explained 23.20{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}, 24.40{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}, and 31.90{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} of the associations of overall lifestyle behaviors with composite microvascular complications, diabetic kidney disease, and diabetic neuropathy, respectively. In addition, our data showed that among all the potential biomarkers, only HbA1c was a significant mediator that explained 15.26{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} of the relationship between the overall lifestyle score and risk of diabetic retinopathy (Table 3).

Secondary analysis and sensitivity analysis

Consistent results were observed when analyses were stratified by age, sex, education, diabetes duration, use of hypoglycemic medication, and HbA1c level. No significant interaction was observed between the healthy lifestyle score and the stratified factors on the outcomes considering multiple comparisons (S3 Fig). Further, the results of different combinations of low-risk lifestyle factors showed that the increased numbers of low-risk lifestyle factors were associated with graded lower risks of diabetic retinopathy, diabetic kidney disease, diabetic neuropathy, and the composite microvascular complications (S6 Table).

In the sensitivity analyses, the results were generally robust when excluding patients with events that occurred within the first 2 years of follow-up, defining low-risk alcohol intake as moderate drinking and nondrinking, generating the lifestyle score using BMI or waist-to-hip ratio instead of WC, or generating the overall lifestyle score as a weighted score (S7S10 Tables). The association between overall lifestyle behaviors and risk of diabetic kidney disease was slightly attenuated when estimated glomerular filtration rate (eGFR) was additionally adjusted, and the results of mediation analysis for diabetic kidney disease were largely unchanged with the additional adjustment of eGFR (S11 and S12 Tables). Further, we observed similar results when patients with preexisting CVD were included and in patients with preexisting CVD, although diabetic retinopathy did not reach statistical significance in patients with preexisting CVD probably due to the insufficient power (S13 and S14 Tables). Finally, consistent results were demonstrated when we used 2 competing risk models accounting for the death (S15 Table).

Discussion

In this retrospective cohort study of patients with T2D, adherence to a greater number of healthy lifestyle behaviors, including recommended WC, noncurrent smoking, physically active, healthy diet, and moderate alcohol drinking, was inversely associated with lower risks of diabetic retinopathy, diabetic kidney disease, diabetic neuropathy, and the composite microvascular complications. For each number increment in low-risk lifestyle behavior, there was an 18{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} lower risk of developing diabetic microvascular complications. Moreover, the results of PAFs suggested that 25.3{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} of the diabetic microvascular complications could have been avoided if the patients with T2D had 4 or more healthy lifestyle behaviors. In addition, the mediators collectively explained 23.20{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} of the associations between the overall healthy lifestyle score and diabetic microvascular complications. Specifically, CRP, albumin, HbA1c, and lipids profile (HDL-C, triglycerides, and apolipoprotein A) could explain 4.44{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} to 10.69{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} of the association between overall lifestyle behaviors and the total diabetic microvascular complications.

Our study contributes to the literature regarding the influence of combined healthy lifestyle behaviors on the risk of diabetic microvascular complications. To date, many studies have been performed to evaluate the relationship between individual lifestyle behaviors and risk of diabetic microvascular complications; however, the joint association of multiple lifestyle behaviors with microvascular complications remains unknown. For example, the Irish Longitudinal Study showed that a history of smoking was associated with a higher risk of developing microvascular complications [8]. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) studies demonstrated that adherence to a healthy dietary pattern (the Alternate Healthy Eating Index) [9], being physically active, and moderate alcohol consumption [12] were associated with a lower risk of incident chronic kidney disease among patients with T2D. Furthermore, general obesity and abdominal obesity were associated with higher risks of diabetic kidney disease [41], diabetic retinopathy [13], and diabetic neuropathy [42].

However, the results of lifestyle interventions on microvascular complications among patients with diabetes or impaired glucose tolerance in clinical trials were inconsistent. The Steno-2 randomized trial including 160 patients with T2D and persistent microalbuminuria showed pharmacological therapies in combination with lifestyle behavior modifications, including adopting a healthy diet, engaging regular physical activity, and participating in smoking cessation courses, significantly reduced the risk of diabetic nephropathy, retinopathy, and neuropathy [43]. Further, the China Da Qing Diabetes Prevention Study including 577 participants with impaired glucose tolerance reported that healthy diet and exercise interventions in combination resulted in a 47{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} reduction in the diabetic retinopathy incidence, but no beneficial effects were observed for diabetic nephropathy or neuropathy [44]. In addition, the Look AHEAD trial consisting of 5,145 overweight or obese patients with T2D, which focused on weight management through increased energy deficit and physical activity, resulted in a significant decrease in chronic kidney disease [45], but not diabetic neuropathy measured by physical examinations [46]. Notably, microvascular complications were not predefined primary outcomes in these trials and small numbers of cases might partially explained the heterogeneities in these findings (e.g., 296 cases of very-high-risk chronic kidney disease in the Look AHEAD trial). Further trials with proper designs are needed to corroborate our findings in the future.

Our mediation analyses contribute to better understanding the lower risk of microvascular complications associated with lifestyle behaviors. Our data showed that the associations of overall lifestyle behaviors with diabetic kidney disease, diabetic neuropathy, and total microvascular complications may be explained by the improvement in glycemic control, liver function, lipid profile, and systemic inflammation, with lifestyle behaviors related lower risk of diabetic neuropathy might be additionally explained by kidney function amelioration. However, our data showed that the association between lifestyle and diabetic retinopathy was mainly through the glycemic control rather than other pathways. Our results corroborate prior findings from the observational studies. For example, intensive lifestyle intervention including physical activity and healthy diet recommendations could benefit glycemic control [47]. Adherence to a combined healthy lifestyle score including healthy diet, physically active, nonsmoking, healthy sleep, and social support were associated with lower concentrations of inflammatory markers [48]. Chronic Renal Insufficiency Cohort (CRIC) Study showed that combined healthy lifestyle characterized as physically active, nonsmoking, and BMI ≥25 kg/m2 were associated with lower risks of atherosclerotic events and kidney function decline among patients with chronic kidney disease [20]. Furthermore, lifestyle modifications including promoting healthy diet, physical activity, and weight loss could significantly improve liver function, renal function, lipid profile, endothelial dysfunction, and reduce systemic inflammation in interventional studies [4954].

The current study is among the first to investigate the relationship between the overall lifestyle behaviors and diabetic microvascular complications. The strengths of this study included the large sample size, long period of follow-up, and extensive collection of data on clinical biomarkers, which allowed us to comprehensively evaluate the potential mechanisms underlying the observed associations. Despite the strengths, this study should be interpreted in the light of its potential limitations. First, as the microvascular complications were identified via hospital inpatient records and death registries, there might be underreporting of the cases, for example, primary care data were not completely available currently. Second, the self-reported and one-time assessment of lifestyle behaviors data are susceptible to measurement errors. In addition, information on lifestyle behaviors was collected at recruitment and the behaviors may change over time; hence, the observed associations might be attenuated due to nondifferential misclassification bias. Third, mediation analysis assumes causality between lifestyles behaviors and biological biomarkers, although both the lifestyle behaviors and biological mediators were assessed at the same time in the UK Biobank. Future studies with repeatedly measured data are required to replicate our findings. Fourth, our study is limited in terms of ethnic diversity (>85{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} Whites); our results may not be directly generalized to other ethnic groups. Fifth, our study was based on a retrospective sampling from the UK Biobank study; hence, the causality should be interpreted with caution. Sixth, the UK Biobank is not representative of the general population of the UK, particularly relating to socioeconomic deprivation, lifestyles, and noncommunicable disease, with evidence of the healthy volunteer selection bias. Finally, residual or unknown confounding could not be excluded due to the observational study design, although we have in our effort to adjust for the potential confounding factors.

Supporting information

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OSU research sheds light on why not all obese patients develop type 2 diabetes

OSU research sheds light on why not all obese patients develop type 2 diabetes

PORTLAND, Ore. (KTVZ) – Researchers at Oregon State University have invented a new analytical technique that sheds gentle on an enduring secret concerning variety 2 diabetes: Why some obese clients develop the disorder and some others don’t.

Style 2 diabetes is a severe metabolic illness that influences around 1 in 10 People in america. Previously regarded as adult-onset diabetic issues, it is a serious condition affecting the way the human body metabolizes glucose, a sugar which is a critical resource of electricity. This type of diabetes is routinely associated with being overweight.

For some sufferers, that usually means their body does not adequately answer to insulin – it resists the effects of insulin, the hormone developed by the pancreas that opens the door for sugar to enter cells. In the later on disorder phases, when the pancreas is fatigued, patients never create adequate insulin to maintain usual glucose amounts.

In both scenario, sugar builds up in the bloodstream and, if still left untreated, the influence impairs lots of important organs, at times to disabling or lifetime-threatening levels. A important possibility aspect for type 2 diabetes is staying overweight, typically a consequence of having too considerably extra fat and sugar in mixture with reduced bodily action.

Andrey Morgun and Natalia Shulzhenko of OSU and Giorgio Trinchieri of the National Cancer Institute made a novel analytical strategy, multi-organ network assessment, to discover the mechanisms driving early-phase systemic insulin resistance.

The experts sought to find out which organs, biological pathways and genes are playing roles.

Findings, which demonstrate that a individual kind of intestine microbe sales opportunities to white adipose tissue containing macrophage cells – significant cells that are component of the immune technique – affiliated with insulin resistance, had been posted in the Journal of Experimental Medication.

In the human system, white adipose tissue is the most important form of unwanted fat.

“Our experiments and evaluation forecast that a higher-unwanted fat/substantial-sugar diet principally acts in white adipose tissue by driving microbiota-relevant destruction to the power synthesis system, major to systemic insulin resistance,” mentioned Morgun, affiliate professor of pharmaceutical sciences in the OSU Higher education of Pharmacy. “Treatments that modify a patient’s microbiota in strategies that focus on insulin resistance in adipose tissue macrophage cells could be a new therapeutic system for kind 2 diabetes.”

The human intestine microbiome options extra than 10 trillion microbial cells from about 1,000 various bacterial species.

Morgun and Shulzhenko, an associate professor in OSU’s Carlson Faculty of Veterinary Medication, in before investigation formulated a computational approach, transkingdom community evaluation, that predicts precise types of germs controlling the expression of mammalian genes related to distinct clinical conditions this kind of as diabetes.

“Type 2 diabetic issues is a global pandemic, and the variety of diagnoses is expected to preserve escalating above the up coming 10 several years,” Shulzhenko reported. “The so-identified as ‘western diet’ – superior in saturated fats and refined sugars – is 1 of the major factors. But intestine micro organism have an crucial job to enjoy in mediating the outcomes of diet program.”

In the new research, the experts relied on both equally transkingdom network assessment and multi-organ network examination. They also performed experiments in mice, looking at the intestine, liver, muscle and white adipose tissue, and examined the molecular signature – which genes were being being expressed – of white adipose tissue macrophages in obese human clients.

“Diabetes induced by the western diet plan is characterised by microbiota-dependent mitochondrial hurt,” Morgun claimed. “Adipose tissue has a predominant purpose in systemic insulin resistance, and we characterised the gene expression plan and the essential learn regulator of adipose tissue macrophage that are affiliated with insulin resistance. We identified that the Oscillibacter microbe, enriched by a western diet regime, leads to an increase of the insulin-resistant adipose tissue macrophage.”

The researchers insert, on the other hand, that Oscillibacter is likely not the only microbial regulator for expression of the key gene they discovered – Mmp12 – and that the Mmp12 pathway, even though clearly instrumental, is in all probability not the only vital pathway, based on which gut microbes are existing.

“We formerly confirmed that Romboutsia ilealis worsens glucose tolerance by inhibiting insulin concentrations, which may possibly be applicable to a lot more sophisticated levels of variety 2 diabetes,” Shulzhenko said.

Zhipeng Li, Manoj Gurung, Jacob W. Pederson, Renee Greer, Stephany Vasquez-Perez and Hyekyoung You of the Carlson School of Veterinary Medicine and Richard Rodrigues, Jyothi Padiadpu, Nolan Newman, and Kaito Hioki from College or university of Pharmacy also participated in this analysis, as did researchers from the National Cancer Institute, Nationwide Institute of Allergy and Infectious Ailments and Monash College in Australia.

The National Institutes of Wellbeing and the Oregon Clinical Research Basis supported this research.

Global Game-Based Learning Market Size, Share & Industry Trends Analysis Report By Component, By End User, By Deployment Type, By Game Type, By Regional Outlook and Forecast, 2021

Global Game-Based Learning Market Size, Share & Industry Trends Analysis Report By Component, By End User, By Deployment Type, By Game Type, By Regional Outlook and Forecast, 2021
ReportLinker

ReportLinker

The Global Game-Based Learning Market size is expected to reach $32. 6 billion by 2027, rising at a market growth of 19. 6{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} CAGR during the forecast period. Game-based learning is built on the idea of teaching through repetition, failure, and goal achievement.

New York, April 04, 2022 (GLOBE NEWSWIRE) — Reportlinker.com announces the release of the report “Global Game-Based Learning Market Size, Share & Industry Trends Analysis Report By Component, By End User, By Deployment Type, By Game Type, By Regional Outlook and Forecast, 2021 – 2027” – https://www.reportlinker.com/p06249495/?utm_source=GNW
This is the foundation of video gaming. The player starts out slowly and gradually increases their abilities until they can easily navigate the most difficult levels. Well-designed games have enough challenge to keep the player interested while remaining simple enough to win.

This same technique is applied to teaching a curriculum in game-based learning. Students collaborate toward a common objective, making decisions and dealing with the repercussions of their decisions. They learn and practice the proper method to do things on a regular basis. As a result, rather than passive learning, active learning occurs.

Game traits and principles are interwoven within learning activities in game-based learning. Learning activities encourage student engagement and motivation to learn in this setting. Points systems, badges, leaderboards, discussion boards, quizzes, and classroom response systems are all part of game-based learning. Points may be rewarded academically, such as an extra week to complete an assignment after achieving a specific threshold. Students can earn badges for achieving a certain level of achievement, and classroom response systems like Kahoot or Top Hat reward engagement with points.

By incorporating video game design and components into learning environments, game-based learning tries to encourage students and arouse their interest. This strategy simplifies complex concepts while also providing an engaging and fun learning experience. In addition, it provides students’ ownership of their learning, encourages them to move to a lateral thinking approach, allows them to study diverse disciplines, and makes the learning process more viable. As a result, game-based learning has become one of the most popular educational segments in the world.

COVID-19 Impact

The closure of educational facilities owing to the COVID-19 epidemic leads imperatively to the utilization of technological advancements and the Internet for ensuring the continuity of learning. In this direction, Game-based Learning can be beneficial to teaching and learning as most students prefer to use their mobile devices, such as smartphones or tablets. Moreover, incorporating gaming into the educational process can boost students’ motivation for learning and improve their learning outcomes.

Game-based learning has numerous potentialities for facilitating the transformation of learning and education in ways that are appropriate to address the challenges posed by the COVID-19, while also providing benefits that are relevant and long-lasting well after the pandemic has passed. Digital game-based learning and gamification, for example, are enabled by modern ICT technologies and allow for the creation of communal learning experiences that are not confined by the physical limits of a classroom.

Market Growth Factors:

The rise in the number of smartphone and internet users

According to figures from the International Telecommunication Union 2020, 62.6 percent of Asia’s total population has internet connectivity and witnessed a growth of 2,268 percent since 2000. Due to growing disposable income, the presence of some of the world’s leading players, and other conducive factors, Europe and North America are making substantial growth in innovative learning methods. The demand for game-based learning in these regions is due to the ever-growing internet penetration rates. In the same year, Africa had relatively low internet penetration than other regions. In the upcoming years, the growing number of smartphone users is likely to play a significant role in creating demand for innovative learning methods like game-based learning. According to UN, Eurostat, and other similar agencies’ figures, there were approximately 5.27 billion smartphone or mobile users in the globe in 2020, accounting for approximately 67.1 percent of the population.

Demand for augmented reality, virtual reality, and artificial intelligence (AI) in education is on the rise

AR-enabled games are being developed by companies; players can use AR technologies to sketch pictures and show off their creations. The use of augmented reality and virtual reality in on-the-job training is rapidly expanding. Kentucky Fried Chicken (KFC) began its culinary training with virtual reality. The virtual reality environment can be used to train personnel without the risk of making mistakes.

Panning Slides, Vertical Parallax, Horizontal Parallax, Layered Display, and 360 interactions are examples of displays created by companies. This creates a 3D effect by displaying multiple elements of sub-topics on the same screen. To develop really engaging learning experiences, companies use a combination of 3D animation, 2D animation, augmented reality, virtual reality, original audio, and well-honed instructional design concepts to produce turnkey immersive learning solutions.

Market Restraining factors:

Lack of IT infrastructure at schools and colleges and low internet accessibility

It is challenging to set up IT infrastructure in schools and businesses. They’ll need to set up servers like a cloud server, a dedicated server, and a shared server, among other things. Each server has its own set of benefits and drawbacks. The expense of running a cloud server is high. Moreover, it is still not feasible for many educations as well as other institutions to incorporate game-based learning solutions in their curriculum due to the high initial investment. Corporations must also establish a software that incorporates a learning management system (LMS). Hundreds of LMS are available on the market; some are commercial, while others, like MOODLE, are open-source. It is challenging to compare the features of each LMS to their training demands and budget, and then choose the best LMS.

Component Outlook

Based on Component, the market is segmented into Solution and Services. The Services segment garnered a significant revenue share of the Game-based Learning market in 2020. This is because these services assist end users with the development of game-based learning solutions as well as the installation, deployment, and continuing support of such solutions. Certain service providers assist end-users in developing tailored solutions for their businesses. In the game-based learning market, implementation services allow businesses to customize, install, configure, and deploy a game-based learning solution to meet their specific business needs. These services allow businesses to tailor a game-based learning solution to their specific training workflow and user hierarchy, hence enhancing the delivery and efficacy of the training.

End User Outlook

Based on End User, the market is segmented into Education, Consumer, Healthcare, Retail & eCommerce, Government & Defense, Manufacturing, IT & Telecom, and Others. In 2020, the Education segment acquired the biggest revenue share of the Game-based learning market. In this industry, game-based learning is utilized in flashcard-type games like a duel, simulation games (Plantville), quiz games (Kahoot), interactives (Funbrain), reality testing games (chemistry VR), puzzles (crossword), and strategy games (Europa universals). Students are motivated and interested in game-based learning because it is unique. The rapid feedback that learners and educators receive as a result of the gaming technique is a significant feature that both learners and educators benefit from.

Deployment Type Outlook

Based on Deployment Type, the market is segmented into Cloud and On-Premise. In 2020, the Cloud segment held the largest revenue share of the game-based learning market. This is because a rising number of educational institutions are inclined towards the games-based learning models on cloud platforms. This is due to the cloud platform’s advantages, which include minimal implementation costs, improved performance, tailored services, and flexibility. Cloud-based deployment of game-based learning solutions is further encouraged by simpler and more effective data processing methodologies, huge storage, and easy switching between projects.

Game Type Outlook

Based on Game Type, the market is segmented into Training, knowledge & skill-based Games, Assessment & Evaluation Games, AI-based Games, AR VR Games, Language Learning Games and Others. In 2020, the AI-based games segment obtained a promising revenue share of the game-based learning market. Adaptive learning – that is, learning information that automatically and constantly adapts to the learner’s competence and knowledge based on their input – is one effective method artificial intelligence will supplement game-based learning. This implies synthesizing data on a player’s actions, abilities, and learning styles in a game-based learning setting, then using that data to give content tailored to that individual’s needs.

Regional Outlook

Based on Regions, the market is segmented into North America, Europe, Asia Pacific, and Latin America, Middle East & Africa. In 2020, North America emerged as the leading region in the overall Game-based learning market. In addition, the region would showcase a similar kind of trend even during the forecasting period. In terms of end-user adoption of game-based learning solutions, North America has been a very open and competitive market. It is the most advanced region in terms of implementing a game-based learning system. Within traditional-based learning solutions, it has been particularly receptive to integrating the latest technological breakthroughs, such as integration technologies with AI, cloud, and mobile technologies. The strict government standards and regulations created for numerous industries are a primary economic factor for this region.

The market research report covers the analysis of key stake holders of the market. Key companies profiled in the report include Kahoot! AS, Spin Master Corp., Breakaway Games, Raptivity (Harbinger Group), StratBeans Consulting Pvt. Ltd., Schell Games, BYJU’S (Tangible Play, Inc.), Frontier Developments plc, Bublar Group AB (Vobling AB), and Recurrence, Inc.

Strategies Deployed in Game-Based Learning Market

Jan-2022: Schell Games introduced Lost Recipes – an upcoming educational game that allows a person to explore authentic cooking across time and cultures in VR. In Lost Recipes, a person can take on the role of a Ghost Chef in training, preparing meals for spirits from the Greek, Chinese, and Maya civilizations who want to pass down their favorite dish’s ancient recipes.

Nov-2021: Kahoot! formed a partnership with Minecraft, a sandbox video game developed by the Swedish video game developer Mojang Studios. Following the partnership, the companies rolled out free learning content as part of their Hour of Code: TimeCraft program. This partnership would provide an interactive learning experience within the world of Minecraft and on Kahoot!, making the world of coding even more exciting and accessible.

Nov-2021: Kahoot! unveiled Kahoot!+ Study, a new offering developed for higher education students. Kahoot!+ Study enables students to develop unique study experiences and expedite their learning for final exam season and throughout the school year. Higher education students can get rid of tedious study sessions and experience entertaining and active learning with the Kahoot!+ Study membership plans.

Sep-2021: Kahoot! came into a partnership with Star Wars, an American epic space opera multimedia franchise. This partnership features Yoda, Luke Skywalker, Princess Leia, C-3PO, BB-8, and Chewbacca are among the characters and droids from the Star Wars franchise to offer collections of ready-to-play kahoots on Kahoot! Academy. Through this partnership, Kahoot! Academy provides an innovative way to engage in learning for its millions of users across the world.

Sep-2021: Kahoot! took over Clever, a privately-held, California-based company that is one of the most broadly-used digital learning platforms in U.S. K-12 education. Moreover, the two companies would together offer enhanced digital learning solutions and offerings for educators, students, parents, schools, and districts globally, assisting learners to discover their complete learning potential.

Jul-2021: Kahoot! introduced a new integration with GIPHY. This integration would provide a free feature that enables all Kahoot! users to include GIPHY content – including GIFs and animated stickers – to their Kahoot! learning games.

May-2021: Osmo formed a partnership with In Motion, the largest airport-based electronics retailer in North America, and its sister venues iStore and Soundbalance, which provide advanced and diverse premium electronics for tech-savvy businesses and leisure travelers. Traveling with technology is a necessity for today’s parents, even for their children, who are looking for the greatest items and entertainment to use while on the road. Moreover, because tablet technology makes it easier to use while flying, kids may effortlessly play Osmo’s fun learning activities for kids.

Oct-2020: Osmo introduced Math Wizard educational games series, which allows kids to learn math at their own pace and assists parents increase pandemic schooling. For children aged six to eight, Osmo has developed a new curriculum-inspired Math Wizard series. The series teaches mathematics using games that are engaging, hands-on, narrative-driven, and adventure-based, in which children learn math by touching and manipulating things and playing with everyday math applications.

Oct-2020: Spin Master took over Rubik’s Brand, owner of the world-famous Rubik’s Cube. Following the acquisition, Spin Master intends to build on the Rubik’s brand’s legacy, with plans for more innovation across the Rubik’s offerings and wider distribution across the Company’s global reach.

Jul-2018: Schell Games rolled out HoloLAB Champions, a new game through which it brought VR into the chemistry labs. The new game is designed to be used in conjunction with a classroom curriculum and is aimed at high school students aged 14 to 18. The game, which is available for download through the Steam online platform, teaches chemical skills and allows players to learn through virtual experiments in a game show format.

May-2018: Recurrence extended its partnership with Penn State University, one of the best universities in the world. Following the partnership, the Recurrence offers The Signature Case Study, a business simulation in which students play high-level executive roles like CEO or CFO as they lead an airline through a series of obstacles based on real-world data.

Scope of the Study

Market Segments covered in the Report:

By Component

• Solution

• Services

By End User

• Education

• Consumer

• Healthcare

• Retail & eCommerce

• Government & Defense

• Manufacturing

• IT & Telecom

• Others

By Deployment Type

• Cloud

• On-premise

By Game Type

• Training, knowledge & skill-based Games

• Assessment & Evaluation Games

• AI-based Games

• AR VR Games

• Language Learning Games

• Others

By Geography

• North America

o US

o Canada

o Mexico

o Rest of North America

• Europe

o Germany

o UK

o France

o Russia

o Spain

o Italy

o Rest of Europe

• Asia Pacific

o China

o Japan

o India

o South Korea

o Singapore

o Malaysia

o Rest of Asia Pacific

• LAMEA

o Brazil

o Argentina

o UAE

o Saudi Arabia

o South Africa

o Nigeria

o Rest of LAMEA

Companies Profiled

• Kahoot! AS

• Spin Master Corp.

• Breakaway Games

• Raptivity (Harbinger Group)

• StratBeans Consulting Pvt. Ltd.

• Schell Games

• BYJU’S (Tangible Play, Inc.)

• Frontier Developments plc

• Bublar Group AB (Vobling AB)

• Recurrence, Inc.

Unique Offerings

• Exhaustive coverage

• Highest number of market tables and figures

• Subscription based model available

• Guaranteed best price

• Assured post sales research support with 10{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} customization free
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Type 2 Diabetes Mellitus in Latinx Populations in the United States: A Culturally Relevant Literature Review

Type 2 Diabetes Mellitus in Latinx Populations in the United States: A Culturally Relevant Literature Review

Type 2 diabetes mellitus (T2DM) affects 10.5{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} of Americans (34.2 million), with a disproportionate number being of Latinx or Hispanic descent [1]. The term “Latinx” is the “non-binary form of Latino or Latina,” meaning any individual with ancestry in Latin America [2]. Hispanic refers to someone from a Spanish-speaking country, which includes both Latin American countries and Spain [2]. When viewing age-adjusted prevalence among ethnic minorities, Latinx populations are ranked the second highest (12.5{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}) of all ethnicities [1]. Within the Latinx population in the United States, the prevalence among different ethnicities is as follows: Mexicans (14.4{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}), Puerto Ricans (12.4{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}), Central/South Americans (8.3{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}), and Cubans (6.5{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}) [1]. The disproportionate prevalence of diabetes in these Latinx communities within the United States is also demonstrated in their country of origin. For example, the prevalence of diabetes in Mexico is 13.5{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}, in Puerto Rico it is 13.7{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf}, and in Cuba it is 9.6{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} [3]. Latinx Americans are known to have higher rates of uncontrolled T2DM, as indicated by higher hemoglobin A1c levels [4]. Poorly controlled T2DM is associated with worse outcomes, including subsequent cardiovascular disease, retinopathy, and chronic kidney disease (CKD) [4]. Deaths from T2DM in Latinx populations are also 1.25 times higher than non-Latinx populations [5]. Disparities experienced by Latinx Americans are apparent in the trends and statistics of disease prevalence among this community, for example, though T2DM is the major cause of CKD in Latinx individuals, those with CKD maintain poor management of T2DM, lack medication adherence, may be unaware of the association of CKD with T2DM, and have the potential to progress to ominous disease faster than non-Latinx communities [6,7]. The COVID-19 pandemic has further emphasized health disparities experienced by Latinx Americans, as these populations are experiencing higher rates of COVID-19 infection, potentially due to their increased likelihood of having a comorbid condition, such as T2DM [8]. These disparities underline the importance of understanding the cultural considerations of T2DM in Latinx communities, including risk factors and access to care. This commentary with a modified scoping review aims to build off the existing “Caribbean Diaspora Healthy Nutrition Outreach Project (CDHNOP): A Qualitative and Quantitative Approach to Caribbean Health” [9] by further exploring the current data available on the Latinx community related to T2DM and its associated comorbidities. This manuscript is meant to provide a general overview of the literature available on these topics and discuss the need for a more inclusive, personalized, and comprehensive approach to improving the health of Latinx communities.

Methods

Protocol

This study is a scholarly literature review with elements of a scoping review. We intended to primarily conduct a commentary but decided to incorporate aspects of Arksey and O’Malley’s scoping review framework for data collection [10]. Specifically, we loosely included some of their designated stages, including identifying a research question, identifying relevant studies, study selection, and summarizing the collected data. This study design was selected partially due to the sparsity of available data in the field of underserved and underrepresented communities.

Identifying the Research Question

The first step in this commentary included determining the research questions that would be addressed in our scoping review. Our research question was: “What is known from the existing literature about Type 2 Diabetes in Latinx populations?” We intentionally chose a more ambiguous research question because we wanted to maintain a wide approach to generate a larger breadth of coverage, as suggested by Arksey and O’Malley.

Identifying the Relevant Studies

Our search strategy included searching specific keywords on PubMed and Google Scholar for each area of interest in our study. Search strings always included “type 2 diabetes” AND “hispanic” OR “latinx.” Depending on the topic of interest, additional search terms would be added to the above string. Examples of these search strings include: type 2 diabetes AND hispanic OR latinx AND genetics, type 2 diabetes AND hispanic OR latinx AND obesity, type 2 diabetes AND hispanic OR latinx AND physical activity, type 2 diabetes AND hispanic OR latinx AND barriers to healthcare, and so on. These searches were conducted for each area of interest in our study, including genetics, obesity, cardiovascular disease, retinopathy, CKD, diet, physical activity, barriers to healthcare, cultural beliefs, management, and acculturation.

Study Selection

Due to the ambiguity of our research questions and basic search strings, a large number of irrelevant studies were generated on our initial search. Three reviewers performed data extraction and appraisal independently while adhering to loosely set inclusion and exclusion criteria to maintain some consistency in decision-making. The inclusion criteria included articles with a focus on Latinx populations, Hispanics, type 2 diabetes, cultural beliefs, diet, management, or comorbid conditions and sequelae of type 2 diabetes, including obesity, cardiovascular disease, hyperlipidemia, retinopathy, and CKD. Exclusion criteria included articles published before 2001. The decision to exclude articles was discussed among reviewers, and these articles were discarded after unanimous agreement. Some reasons for the exclusion of articles that may have otherwise met inclusion criteria include poor study design, lack of peer review, small sample size, study on the wrong population or focus on only one specific Latinx subgroup, or lack of significant findings.

Summarizing the Collected Data

Data collected from our literature review were directly used in the creation of our commentary piece. This commentary, which incorporated elements of the scoping review framework in the identification and selection of relevant articles, aimed to present a narrative account of the existing literature answering our primary research questions. The collected data were summarized in a paragraph format, organized by the area of focus (e.g., genetics, barriers to healthcare, etc.), and used to discuss the significance of culturally relevant care. Of note, scoping reviews do not aim to synthesize evidence or aggregate findings, as that is more the role of a systematic review.

Genetics of Latinx individuals contributing to T2DM

T2DM is a multifactorial disease with both modifiable and non-modifiable risk factors contributing to its development [11]. Though an emphasis is traditionally placed on environmental and modifiable risk factors, genetics also significantly contributes to the development of the disease as evidenced by greater rates of the disease in Latinx populations [11]. Genome-wide association studies (GWAS) have uncovered more than 100 genetic loci associated with the development of T2DM [12]; however, the accuracy of the resultant polygenic risk scores in the Latinx population is compromised by the fact that only 2{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} of the studied population is of Hispanic ancestry [11,12]. Few GWAS have been performed on Latinx populations in the United States, likely due to challenges in genetic mapping which may be attributable to the variability of their genome from the three main ancestries (American, European, and West African) [12]. Disruptions of SLC16A11 in Mexicans and Latin Americans have been associated with the development of T2DM due to altered fatty acid and lipid metabolism [12]. More recently, a GWAS of T2DM in the Latinx population in the United States identified two previously known association signals at the KCNQ1 locus [12]. Additionally, a novel single-nucleotide polymorphism (SNP) (SNP rs 1049549), likely an African ancestry-specific allele, was found to be consistent with T2DM across the Latinx population of the United States [13]. In accordance with a similar genetic risk score to European and Chinese populations, the Latinx population of the United States experiences a 7{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} increased risk of T2DM per associated allele [13].

Pathophysiological factors of T2DM in Latinx population

In addition to genetics, characteristics of the Latinx population that contribute to the development of T2DM include increased insulin resistance, compromised beta cell function and accelerated senescence, and an altered microbiome [10]. It has been suggested that the increased insulin resistance seen in the Latinx population is the result of higher obesity rates or genetic predisposition; it is likely due to a combinatorial effect [10]. One consequence of increased insulin resistance is a compensatory increased insulin secretion by pancreatic beta cells, which contributes to beta cell dysfunction and advanced senescence at a younger biological age than other ethnic groups [10]. As beta cell function ceases, the diagnosis of T2DM is made. Finally, the effect of an altered microbiome on the development of T2DM is not unique to the Latinx population; however, the reflection of the acculturated Latinx diet and antibiotic usage may be a unique explanation for the susceptibility of this population to the development of T2DM [10].

Comorbidities of T2DM in Latinx individuals

Several comorbidities associated with T2DM are seen at higher rates in Latinx populations, including obesity, cardiovascular equivalents, CKD, and retinopathy [14].

Obesity

Obesity, the presence of excess adipose tissue, is a well-known comorbid condition of T2DM and is one of the most important modifiable risk factors [14]. Due to the intertwining pathophysiology of obesity and T2DM, the term “diabesity” has been used to describe the coexistence of these diseases [15]. On a mechanistic basis, excess adipose causes adipocytes to hypertrophy and induces a configurational membrane change that interferes with the function of glucose transporters, resulting in increased insulin, or insulin resistance [16]. In turn, the impaired insulin resistance results in an increased amount of free fatty acids and the accumulation of excess adipose which, due to lipotoxicity of increased free fatty acids, contributes to heightened insulin resistance [17]. The most accepted screening tool for obesity, BMI, has been thoroughly evaluated in Hispanic populations. The Hispanic Community Health Study/Study of Latinos found a direct correlation between BMI and the prevalence of diabetes among Hispanic/Latinx populations [18]. Hispanic populations, both in the United States and their home countries, have higher rates of obesity than many other ethnic groups [19]. In 2017-2018, obesity in American Hispanics above 20 years was 44.8{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} prevalent, which is more than the non-Hispanic white and Asian populations and only less than the non-Hispanic black population [20]. In the younger population, Hispanics demonstrate the highest prevalence of youth obesity in the country, affecting 25.6{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} of this population [21]. Multiple explanations exist for the increased prevalence of obesity in Hispanics, the most influential of which may be sociocultural factors. In addition to diet and lack of exercise, the ideal body image in Hispanic populations has been described as “full-figured” due to the perceived connection with “wealth, affluence, and tranquility” [22].

Cardiovascular Equivalents

The excess adiposity seen in overweight and obese individuals is often concurrent with cardiovascular risk equivalents including hypertension and dyslipidemia and has therefore been suggested to play a prominent role in the development of both metabolic and cardiovascular diseases [23]. Molecular dysfunction secondary to obesity and diabetes induces vascular inflammation, resulting in vasoconstriction, thrombosis, and atherogenesis [24]. As such, Latinx populations are predisposed to the development of hypertension and hyperlipidemia due to their higher BMI and rates of obesity. In addition, Hispanic populations are more likely than any other race-ethnic group in the United States to have undiagnosed, undertreated, and uncontrolled hypertension [25]. Latinx individuals also have high rates of hyperlipidemia, a common comorbidity of T2DM [26,27]. Furthermore, physical activity is inversely associated with the development of both hypertension and hypercholesterolemia [28]. Latinx communities have been documented to have lower rates of physical activity than other ethnic groups in the United States [29].

Notably, the impact of cardiovascular disease on the Hispanic population has been an object of debate. The prevalence of other cardiovascular equivalents including abdominal aortic aneurysms, peripheral arterial disease, and carotid stenosis is lower in the American Hispanic population than in the white population [30]. It has been suggested that the prevalence and mortality rate of cardiovascular disease in the Hispanic population is less than that in non-Hispanic whites; however, the leading cause of death in those with T2DM was cardiovascular disease [31]. The Hispanic Paradox, which is described as a lower mortality rate despite the presence of multiple cardiovascular risk factors and comorbidities, is a perplexing phenomenon that may be explained by psychosocial factors and discrepancies in death certificate reporting; however, the exact reason for this phenomenon has yet to be elucidated [30].

Retinopathy

In addition to Latinx populations having higher rates of T2DM comorbidities, the incidence of T2DM complications, including diabetic nephropathy and retinopathy, is also increased. Though several mechanisms explain the development of retinopathy in the setting of T2DM, microvascular damage secondary to hyperglycemia or hypertension is a shared outcome [32]. The Los Angeles Latino Eye Study noted that the incidence of diabetic retinopathy among Latinx individuals was increased when compared with other races and ethnicities [33]. American Hispanics suffer from an increased rate of undetected eye diseases coupled with one of the highest prevalence rates of visual impairment in America [34]. Additionally, in those with self-reported T2DM, nearly 30{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} showed clinical signs of diabetic retinopathy [34]. It has been suggested that Latino populations are more reluctant to utilize eye care resources due to factors including the cost and lack of knowledge of preventative ocular health measures [34]. The high incidence of visual impairment, blindness, and worsening visual acuity and the relationship of progression of disease with age highlight the importance of targeted screening programs for older Latino populations [33].

CKD

CKD is defined as an altered state of kidney structure or function for more than three months and is most commonly attributable to diabetes and hypertension [35]. The pathophysiology of CKD secondary to T2DM is a complex interplay of various histopathological, hemodynamic, and metabolic, and inflammatory pathways that lead to chronic structural changes in the kidney that compromise integrity and function [36]. The Multi-Ethnic Study of Atherosclerosis found that compared to the white population, Hispanic populations had a higher incidence of CKD defined as a glomerular filtration rate less than 60 mL/min/1.73 m2 [37]. Without intervention, the progression of CKD to end-stage renal disease (ESRD) is nearly inevitable.

A study from Northern California showed that the incidence of ESRD is 1.5-fold higher in Hispanic populations when compared to non-Hispanic whites [38]. The progression of CKD has also been shown to be 81{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} greater among Hispanic populations compared to non-Hispanic whites when adjusted for sociodemographic and clinical characteristics, particularly in individuals with T2DM [37]. Specifically, American Dominicans and Puerto Ricans were shown to have a significantly faster decline in GFR compared to the white population [37]. Notably, even with using treatment strategies, Hispanics were less likely to achieve recommended management goals, indicating a likely progression of the disease, which is illustrated by the higher number of Hispanics receiving dialysis treatment than the white population [37].

Latinx diet as a factor in the development of T2DM

One of the most prominent risk factors for developing diabetes is a carbohydrate-rich diet, which is notable in many Latinx communities. Hispanic cuisine includes staples, such as tortillas, beans, and rice, especially among Puerto Rican, Dominican, and Mexican populations [39]. These foods cause spikes in blood sugar levels and can lead to obesity [39], which predisposes patients to develop T2DM [14]. Additionally, acculturation to the United States plays a role in the dietary patterns adopted by Latinx individuals. For example, it was found that less acculturated Latinx individuals were more likely to adhere to diets higher in fiber and lower in saturated fats [40], whereas more acculturated Latinx populations consume lower amounts of starchy roots, vegetables, and more fruits [41]. Food insecurity among newly immigrated Latinx populations could also potentially be attributed to their poor dietary habits. When analyzing the participants of the 2003-2010 National Health and Nutrition Examination Survey (NHANES), food insecurity was associated with a lower healthy eating index (HEI) among all ethnicities [42]. These communities were found to have an increased intake of added sugars and empty calories [42]. Although acculturated Latinx groups consume more fruits and low-starch vegetables, they are more likely to introduce processed foods and sweets into their diets [41]. When confronted with the potential of dietary restrictions for health purposes, Latinx patients with T2DM have expressed feeling restricted and uneasy [43]. Providing these populations with culturally tailored education on the importance of a healthier lifestyle and shaping these dietary recommendations to fit their cultural norms could potentially ameliorate the rates of T2DM. The Caribbean Diaspora Healthy Nutrition Outreach Project demonstrated that providing populations with culturally tailored nutrition education was effective at changing their food and beverage selection, specifically in Cuban and Dominican communities [9].

Physical inactivity among Latinx American populations

Among the ethnic subgroups in the United States, Latinx populations display the highest rates of physical inactivity. In a 2010 National Health Interview Survey, 45{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} of Latinx individuals stated that they never engaged in physical activity in their leisure time [44]. These higher rates of physical inactivity, even when adjusted for education levels, socioeconomic status (SES), employment, marital status, family income, and poverty, remain significant when compared to non-Hispanic whites [45]. As discussed previously, the level of physical activity in these populations can be inversely associated with an increased risk of developing some of the components and sequelae of metabolic syndrome, including hypertension, hypercholesterolemia, obesity, and cardiovascular disease [28]. Several factors have been cited as barriers to leisure-time physical activity in these subgroups. Health literacy, specifically knowledge about the benefits of exercise, and access to resources to engage in physical activity were noted as key factors in their ability to become physically active [45]. Other barriers include cultural perceptions of physical activity and pre-existing gender differences present in these societies [46]. For example, one study demonstrated that the two major reasons Latinas were less likely to be involved in physical activity included: (1) their belief that it would detract from their role as caregivers [47] and (2) their self-consciousness about their appearance. Interventions focused on providing education on the benefits of exercise as well as physical activity techniques that can be done without access to a standard gym could be useful in combating the physical inactivity reported in these populations [48].

Cultural-specific interventions, aimed at using their pre-existing belief system to motivate them to become more physically active, should also be considered. For example, Latinx culture places a strong emphasis on interpersonal relationships and family. Qualitative studies of these communities demonstrated social support as a significant motivator in whether or not Latinx individuals decided to pursue the physical activity in their leisure time [49-51]. Additionally, the Caribbean Diaspora Healthy Nutrition Outreach Project demonstrated a preference for walking, playing soccer, cricket, baseball, or going dancing as a form of exercise among Caribbean individuals [9]. They found that activities such as swimming and American football were unrelatable and unpopular forms of exercise for these communities [9]. With this knowledge, providers can work to make more culturally relevant exercise recommendations to their patients to improve various metabolic disorders prevalent among Latinx populations.

Barriers to healthcare experienced by Latinx American individuals

Latinx populations in the United States suffer from lower access to healthcare than the general population due to many contributing social factors, such as health literacy, language proficiency, immigration status, SES, and level of acculturation [52]. Health literacy, broadly defined as an individual’s ability to understand and navigate the healthcare system, has been shown to greatly contribute to health disparities [53]. Compared to other ethnicities, Latinx individuals in the United States have the lowest levels of formal education, including the highest rates of those who had not finished high school and the lowest rates of those who had achieved a bachelor’s degree or higher [54]. This may be because immigrants from those regions, in particular Mexico and Central America, have the lowest level of educational attainment than other countries of origin [55]. With regard to health literacy, Latinx immigrants in the United States have lower levels of health literacy than other ethnicities [56]. Similarly, recent immigrants are more likely to be unfamiliar with the healthcare system, therefore serving as a barrier and delay to care [27]. In addition, having limited English proficiency not only restricts the care options available for Spanish-speaking patients, but further puts them at risk of misunderstanding their disease process and management plan [52]. This is of particular importance for diseases such as T2DM that require extensive active involvement from the patient, including lifestyle modifications, monitoring blood glucose, and proper medical management.

The lack of diversity in healthcare teams can also perpetuate inadequate access to healthcare services, as Latinx Americans are more likely to pursue treatment by Latinx physicians irrespective of their location and socioeconomic factors [52]. Their decision to choose physicians based on their cultural background and Spanish proficiency seems rooted in an inherent trust of Latinx providers, as these individuals believe that Latinx physicians can provide them with a higher quality of care solely based on their ethnicity [52,57].

SES, particularly health insurance status, is another barrier to care with Latinx individuals being more likely to be uninsured than non-Hispanic whites [52]. Specifically, nearly 20{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} of Latinx Americans are uninsured [58], with reports showing that uninsured Latinx Americans are less likely to seek medical care and treatment [59]. Undocumented immigrants have the added difficulty of not being eligible for certain federal benefits, including regular Medicaid [60,61]. Lack of insurance makes medical care less affordable due to greater out-of-pocket costs, putting additional financial strain on Latinx individuals from lower SES. This is significant when considering the high out-of-pocket costs of medications used to treat T2DM, including insulin, leading to nonadherence [62]. Additional SES barriers include limited transportation to healthcare appointments, lack of childcare during healthcare visits, and inability to take time away from work [52]. This is due to the lack of paid time off associated with many low-wage jobs [63], which Latinx individuals of lower SES tend to occupy [64].

Cultural components of management and treatment of T2DM

Perceptions of the self-management of diabetes among Latinx individuals contribute to the management of the disease. For example, a study that included predominantly Puerto Ricans in Massachusetts found that patients expressed difficulty controlling their diabetes, citing the time-intensive nature of monitoring the disease [65]. Furthermore, instead of turning to medical or social work services, these participants shared that they often turned to family or friends and then to their community or church, when they needed help with their health [65]. Similarly, a smaller study that focused on Mexican-Americans in the United States found that participants highlighted the familist aspect of diabetes care and management, with family members frequently monitoring their disease process [66]. Participants in this study also cited factors such as perceptions of the stigma of diabetes and lack of understanding of the disease process to be barriers to effective management [66].

While many Latinx individuals believe that biomedical factors, such as genetics, diet, and lack of exercise, predispose them to diabetes, many also believe that cultural beliefs and religious factors contribute to diabetes prevention and management in Latinx individuals, particularly those from lower SES [67,68]. Some Latinx populations believe that strong emotions can contribute to the development of diabetes. Specifically, susto, fear that is felt after a traumatic event, and coraje, emotions associated with social struggles, are viewed as causal factors [68]. Other Latinx individuals believe that developing diabetes is part of their fate, particularly rooted in religion, which is known as fatalismo [68]. Latinx adults have varying views on the development of diabetes, particularly when looking at the country of origin. For example, Latinx individuals from Mexico are more likely to attribute diabetes development to cultural beliefs, like those mentioned, while those from Puerto Rico are more likely to attribute diabetes development to religious belief, such as it being God’s will [67]. Thus, these differing viewpoints on the origin of diabetes make effective management more difficult, as some believe that nothing they could have done would have prevented the development of the disease, and others believe it can be effectively managed by controlling one’s emotions and through prayer [67].

Cultural beliefs can often lead to the use of commercial and herbal products for the treatment of various medical conditions, including T2DM. Common herbal remedies for the treatment of T2DM among Latinx individuals include prickly pear cactus, aloe vera, celery, and chayote [69]. The efficacy of these herbal remedies has been shown, but with uncertain implications for clinical practice; for example, while prickly pear cactus has been shown to reduce serum glucose and insulin levels, likely due to its high fiber contents and hypoglycemic properties [70], aloe vera has shown to slightly improve glycemic control, but with great heterogeneity across studies [71], substances like celery have mostly shown promise for hyperglycemia control in rat models [72]. One study found that while nearly 70{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} of Latinx patients used herbal remedies, a majority reported that they did not disclose their use of herbal remedies to providers [69]. In another study, it was found that 84{e4f787673fbda589a16c4acddca5ba6fa1cbf0bc0eb53f36e5f8309f6ee846cf} of Mexican-Americans were aware of the use of herbs to treat medical conditions but more than one-third of these participants were not familiar with the specific herbs themselves or potential adverse effects associated with their use [57]. Additionally, Latinx individuals from Mexico, Puerto Rico, and the Dominican Republic were receptive to using standard and alternative treatment methods simultaneously, especially if the referring physician was fluent in Spanish [57]. These Latinx individuals reported that physicians who spoke Spanish were more credible sources [57]. However, a large observational study found that even after adjusting for the Spanish-language fluency of their physicians, Latinx individuals with limited English proficiency were less likely to be adherent to medication regimens, including both oral medications and insulin [73].

While insulin is often a mainstay of diabetes treatment for effective blood glucose control, many Latinx individuals have negative feelings toward the use of insulin. Latinx adults have been shown to believe that the use of insulin signals advanced diabetes and is associated with the onset of complications, including blindness and toe amputations [67]. Furthermore, Latinx individuals have expressed confusion about the timing of the onset of complications in relation to insulin use, as well as the safety of the drug due to feelings of dizziness, fatigue, palpitations, shakiness, and increased appetite after starting insulin [67]. Other options to treat T2DM also exist, including GLP-1 agonists like dulaglutide, which have shown to be efficacious in lowering HbA1c and weight in Latinx individuals with diabetes [74]. These findings highlight the importance of patient education about the development of type 2 diabetes and the options for treatment within Latinx communities.

Culturally tailored diabetes education intervention programs have shown to be successful for Latinx individuals. Many of these interventions focus on educating patients about self-management behaviors, including diet, physical activity, and self-monitoring of blood glucose levels, and monitoring their progress at adhering to these behaviors over time. One randomized control trial with mostly Puerto Ricans provided patients with either standard care or an intensive behavioral intervention, known as Latinos en Control, which provided a culturally tailored model over one year to address diabetes knowledge, attitudes toward diabetes care, and self-management behavior, while taking into consideration the health literacy of participants [75]. Session attendance was associated with greater reductions in HbA1c and improvement in dietary quality, including reductions in total calories and fat percentage [75]. A more recent randomized controlled trial with a larger sample size of Latinx patients in the United States provided less intensive intervention over six months in the form of integrated medical and behavioral visits with culturally tailored diabetes self-management education sessions. The results were similar in that participants taking part in the intervention had a greater reduction in HbA1c, total cholesterol, and diastolic blood pressure [76]. A smaller 3-month educational intervention program for type 2 diabetes tailored toward Mexican-Americans in Southern California showed an improvement in glycemic control and lipid profiles of participants with improved food choices and food monitoring [77].

Physicians can also become more culturally competent to provide more culturally tailored care. Specifically, one study investigated predictors of culturally competent care toward Mexican-American individuals. They found that physicians were more likely to have culturally relevant knowledge if they participated in diverse medical education settings and had experience in community clinics. Furthermore, providers who were of Latinx ethnicity and those who had bilingual skills were also more likely to be culturally aware [78]. This highlights the need for integrating teachings on the social determinants of health into undergraduate and graduate medical education.

Acculturation and its effects on the health of Latinx populations

Acculturation is defined as the cultural changes that take place when an individual adapts to the prevailing culture of a given society [79]. The effect to which Hispanic individuals acculturate to American society is multidimensional and dependent on a variety of factors, including the country of origin, age of entry into the United States, perceived ethnicity, ethnicity of an individual’s social circle, preference of language for media and entertainment, SES, educational level, sociocultural context, religious beliefs, family values, and health care practices [80]. Hispanic individuals that immigrate to cities that are densely populated with other Hispanic communities, such as Miami and New York City, are less likely to fully acculturate to American society if they choose to socialize only within these communities [81]. In Hispanic populations, it has been found that their healthcare practices and outcomes are associated with their level of acculturation [82]. It was found that higher rates of acculturation to American society was associated with increased levels of adherence to healthcare treatments and an increased propensity to use preventative healthcare [82]. Higher levels of acculturation are not always positive, as these individuals are also more likely to have high-fat diets and exhibit poorer eating habits [83]. The evolution of the cultural beliefs of these populations to that of the dominant culture in their community is highly variable but can provide explanations for some of their attitudes toward the healthcare system [84]. Understanding the role acculturation plays, while also considering the cultural beliefs and attitudes present in Latinx individuals, allows healthcare providers to cater their care to be more culturally competent and personalized.