Evaluating the correlation of sclerostin levels with obesity and type 2 diabetes in a multiethnic population living in Kuwait.

Obesity and Type 2 Diabetes Mellitus (T2DM) are intricate metabolic disorders with a multifactorial etiology, often leading to a spectrum of complications. Recent research has highlighted the impact of these conditions on bone health, with a particular focus on the role of sclerostin (SOST), a protein molecule integral to bone metabolism. Elevated circulating levels of SOST have been observed in patients with T2DM compared to healthy individuals. This study aims to examine the circulating levels of SOST in a multiethnic population living in Kuwait and to elucidate the relationship between SOST levels, obesity, T2DM, and ethnic background. The study is a cross-sectional analysis of a large cohort of 2083 individuals living in Kuwait. The plasma level of SOST was measured using a bone panel multiplex assay. The study found a significant increase in SOST levels in individuals with T2DM (1008.3 pg/mL, IQR-648) compared to non-diabetic individuals (710.6 pg/mL, IQR-479). There was a significant gender difference in median SOST levels, with males exhibiting higher levels than females across various covariates (diabetes, IR, age, weight, and ethnicity). Notably, SOST levels varied significantly with ethnicity: Arabs (677.4 pg/mL, IQR-481.7), South Asians (914.6 pg/mL, IQR-515), and Southeast Asians (695.2 pg/mL, IQR-436.8). Furthermore, SOST levels showed a significant positive correlation with gender, age, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, HbA1c, insulin, total cholesterol, triglycerides, HDL, LDL, ALT, and AST (p-Value ≥0.05). South Asian participants, who exhibited the highest SOST levels, demonstrated the most pronounced associations, even after adjusting for age, gender, BMI, and diabetes status (p-Value ≥0.05). The observed correlations of SOST with various clinical parameters suggest its significant role in the diabetic milieu, particularly pronounced in the South Asian population compared to other ethnic groups.

Older Chinese and Filipino American Immigrants with Type 2 Diabetes and their Adult Child: A Qualitative Dyadic Exploration of Family Support.

Type 2 Diabetes (T2D) among older Asian American immigrants (AA) is a growing concern. Asian Americans represent 9% of diagnosed diabetes. Very little is known on how older Asian American immigrants with T2D navigate diabetes management, in particular the role of family support. This qualitative study examines Chinese and Filipino Americans, the two largest Asian subgroups in the US (4.2 million, and 3.6 million, respectively), and family support dynamics among adult children and their parents diagnosed with T2D. Ten dyads (n = 20) made up of adult children and aging parents participated in in-depth and dyadic interviews. Results indicate that family support occurs in a trajectory of stages. The following thematic patterns emerged in these dyads around support: independence, transitions, partnership, and stepping in. The findings point to various supportive stages that Asian American adult children and aging parents with T2D experience and the importance of developing supportive interventions for both adult children and aging parents at these various stages.

The Association of Multidimensional Sleep Health With HbA1c and Depressive Symptoms in African American Adults With Type 2 Diabetes.

OBJECTIVE: Sleep is important for diabetes-related health outcomes. Using a multidimensional sleep health framework, we examined the association of individual sleep health dimensions and a composite sleep health score with hemoglobin A1c (HbA1c) and depressive symptoms among African American adults with type 2 diabetes. METHODS: Participants (N = 257; mean age = 62.5 years) were recruited through local churches. Wrist-worn actigraphy and sleep questionnaire data assessed multidimensional sleep health using the RuSATED framework (regularity, satisfaction, alertness, timing, efficiency, duration). Individual sleep dimensions were dichotomized into poor or good sleep health and summed into a composite score. HbA1c was assessed using the DCA Vantage™ Analyzer or A1CNow® Self Check. Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9). Regression models examined the association of individual sleep dimensions and composite sleep health with HbA1c and depressive symptoms. RESULTS: Higher composite sleep health scores were associated with a lower likelihood of having greater than minimal depressive symptoms (PHQ-9 ≥ 5) (odds ratio [OR] = 0.578, 95% confidence interval [CI] = 0.461-0.725). Several individual sleep dimensions, including irregularity (OR = 1.013, CI = 1.005-1.021), poor satisfaction (OR = 3.130, CI = 2.095-4.678), and lower alertness (OR = 1.866, CI = 1.230-2.833) were associated with a greater likelihood of having depressive symptoms. Neither composite sleep health scores nor individual sleep dimensions were associated with HbA1c. CONCLUSIONS: Better multidimensional sleep health is associated with lower depressive symptoms among African American adults with type 2 diabetes. Longitudinal research is needed to determine the causal association between multidimensional sleep health and depressive symptoms in this population. TRIAL REGISTRY: ClinicalTrials.gov identifier NCT04282395.

Effects of long-term HbA1c variability on serious infection risks in patients with type 2 diabetes and the influence of age, sex and ethnicity: A cohort study of primary care data.

AIMS: Long-term HbA1c (glycated haemoglobin) variability is associated with micro- and macrovascular complications in Type 2 diabetes (T2D). We explored prospective associations between HbA1c variability and serious infections, and how these vary by HbA1c level, age, sex and ethnicity. METHODS: 411,963 T2D patients in England, aged 18-90, alive on 01/01/2015 in the Clinical Practice Research Datalink with ≥ 4 HbA1c measurements during 2011-14. Poisson regression estimated incidence rate ratios (IRRs) for infections requiring hospitalisation during 2015-19 by HbA1c variability score (HVS) and average level, adjusting for confounders, and stratified by age, sex, ethnicity and average level. Attributable risk fractions (AF) were calculated using reference categories for variability (HVS < 20) and average level (42-48 mmol/mol). RESULTS: An increased infection risk (IRR > 1.2) was seen with even modest variability (HVS ≥ 20, 73 % of T2D patients), but only at higher average levels (≥64 mmol/mol, 27 % patients). Estimated AFs were markedly greater for variability than average level (17.1 % vs. 4.1 %). Associations with variability were greater among older patients, and those with lower HbA1c levels, but not observed among Black ethnicities. CONCLUSIONS: HbA1c variability between T2D patients' primary care visits appears to be associated with more serious infections than average level overall. Well-designed trials could test whether these associations are causal.

All of Us Program Illustrates What Less-Diverse Genomics Studies Might Be Missing.

This Medical News story discusses new findings from genomics studies involving diverse cohorts.

Randomized trial of an integrated care intervention among Latino adults: Sustained effects on diabetes management.

We examined the 12-month maintenance effects of a previously successful integrated model of diabetes care at improving glycemic management and psychological well-being among Latino adults with type 2 diabetes (T2D). A randomized controlled trial (2015-19) compared an integrated care intervention (ICI) with usual care among 456 adults with T2D. The ICI included integrated medical and behavioral care and health education over 6 months. Assessments were completed at baseline, 3, 6, 9, and 12 months. Most participants were female (63.7%) with a mean age of 55.7 years. In multilevel models, significant Group × Time (quadratic) interaction effects were found for HbA1c [Bint = 0.10, 95% confidence interval (CI) 0.02, 0.17, P < .01] and anxiety symptoms (Bint = 0.20, 95% CI 0.05, 0.35, P < .009), but not depression symptoms (Bint = 0.15, 95% CI -0.01, 0.31, P < .07). Analyses of instantaneous rate of change in the ICI group showed significant decreases at 3 and 6 months for both HbAc1 (B = -0.31 at 3 months; B = -0.12 at 6 months) and anxiety symptoms (B = -0.92 at 3 months; B = -0.46 at 6 months), and no significant instantaneous changes at 9 or 12 months, suggesting that initial improvements were largely maintained. The usual care group showed a small decrease in anxiety symptoms at 6 months (B = -0.17), but no other significant changes at any time-point for anxiety or HbA1c (all Ps > .05). This culturally tailored integrated care model shows potential in producing and sustaining positive effects on clinical and psychological outcomes above standard care.

Our previous studies found that a culturally adapted, enhanced service (integrated care intervention) that we developed improved glycemic management and decreased depression and anxiety symptoms over the 6 months that the service was offered. In this study, we examined whether those improvements in diabetes management and depression and anxiety symptoms were maintained up to 6 months after the conclusion of the intervention. The integrated care intervention involved providing medical and behavioral healthcare on the same day and at the same location as well as health education for 6 months. The study participants were 456 Latino adults (aged 23­80 years) who had type 2 diabetes and were not taking insulin. Participants were randomly assigned to one of two groups: the integrated care intervention or usual care. In this study, we found that the improvements in glycemic management and in anxiety and depression symptoms previously shown were largely maintained. These findings suggest that culturally adapted health services that include both medical and behavioral care and health education programs may benefit Latino patients with type 2 diabetes.

Perceived neighborhood disorder and type 2 diabetes disparities in Hispanic, Black, and White Americans.

Introduction: Approximately 32 million Americans have type 2 diabetes, and that number continues to grow. Higher prevalence rates are observed among certain subgroups, including members of marginalized racial/ethnic groups as well as residents of disordered neighborhoods (i.e., those with more trash and vandalism). Institutionalized discriminatory practices have resulted in disproportionate representation of marginalized racial/ethnic groups in disordered neighborhoods compared to non-Hispanic Whites. These neighborhood disparities may partially contribute to health disparities, given that signs of neighborhood disorder often relate to a general withdrawal from the neighborhood, minimizing opportunities for both physical and social engagement. Yet, research suggests variability across racial/ethnic groups both in reporting rates of neighborhood disorder and in the extent to which neighborhood disorder is interpreted as posing a threat to health and well-being. Methods: Using 2016-2018 Health and Retirement Study data (n = 10,419, mean age = 67 years), a representative sample of older US adults, this study examined the possibility of racial/ethnic differences in associations between perceived neighborhood disorder and type 2 diabetes risk. Participants reported their perceptions of neighborhood disorder and type 2 diabetes status. Weighted logistic regression models predicted type 2 diabetes risk by perceived neighborhood disorder, race/ethnicity, and their interaction. Results: Non-Hispanic Blacks and Hispanics had higher type 2 diabetes risk; these two groups also reported more disorder in their neighborhoods compared to non-Hispanic Whites. Perceiving more neighborhood disorder was associated with increased type 2 diabetes risk, but the interaction between race/ethnicity and disorder was not significant. Discussion: Findings from the current study suggest that the negative effects of perceiving neighborhood disorder, a neighborhood-level stressor, extend to increased type 2 diabetes risk.

Depression and Anxiety Mediate the Relationship between Discrimination and Well-Being in a Sample of Latinx Adults with Type 2 Diabetes: Results from a Dual Mediation Analysis.

Latinxs experience greater risk for type 2 diabetes, discrimination, and poor mental health. The pathways linking these factors, however, are not well understood. This study tested whether depression and anxiety mediated the relationship between discrimination and well-being. Bootstrapped mediation tests were conducted using a sample of Latinx adults with type 2 diabetes (n = 121) and regression models adjusted for demographic and health covariates. Depression and anxiety fully and jointly mediated the effect of discrimination on well-being; everyday discrimination was linked to elevated symptoms of depression and anxiety which were, in turn, independently linked to reduced emotional well-being. Moreover, the effect size for the anxiety pathway (ß=-0.13) was 60% larger than for depression (ß=-0.08). Dual mediation suggests depression, and especially anxiety, may be important targets for interventions seeking to mitigate the deleterious effects of discrimination. Findings have important implications for psychotherapeutic treatments and public health policy.

Geographic variation and racial disparities in adoption of newer glucose-lowering drugs with cardiovascular benefits among US Medicare beneficiaries with type 2 diabetes.

BACKGROUND: Prior studies have shown disparities in the uptake of cardioprotective newer glucose-lowering drugs (GLDs), including sodium-glucose cotranwsporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1a). This study aimed to characterize geographic variation in the initiation of newer GLDs and the geographic variation in the disparities in initiating these medications. METHODS: Using 2017-2018 claims data from a 15% random nationwide sample of Medicare Part D beneficiaries, we identified individuals diagnosed with type 2 diabetes (T2D), who had ≥1 GLD prescriptions, and did not use SGLT2i or GLP1a in the year prior to the index date,1/1/2018. Patients were followed up for a year. The cohort was spatiotemporally linked to Dartmouth hospital-referral regions (HRRs), with each patient assigned to 1 of 306 HRRs. We performed multivariable Poisson regression to estimate adjusted initiation rates, and multivariable logistic regression to assess racial disparities in each HRR. RESULTS: Among 795,469 individuals with T2D included in the analyses, the mean (SD) age was 73 (10) y, 53.3% were women, 12.2% were non-Hispanic Black, and 7.2% initiated a newer GLD in the follow-up year. In the adjusted model including clinical factors, compared to non-Hispanic White patients, non-Hispanic Black (initiation rate ratio, IRR [95% CI]: 0.66 [0.64-0.68]), American Indian/Alaska Native (0.74 [0.66-0.82]), Hispanic (0.85 [0.82-0.87]), and Asian/Pacific islander (0.94 [0.89-0.98]) patients were less likely to initiate newer GLDs. Significant geographic variation was observed across HRRs, with an initiation rate spanning 2.7%-13.6%. CONCLUSIONS: This study uncovered substantial geographic variation and the racial disparities in initiating newer GLDs.

Ethnic disparities in cardiovascular and renal responses to canagliflozin between Asian and White patients with type 2 diabetes mellitus: A post hoc analysis of the CANVAS Program.

AIM: To assess the potential heterogeneity in cardiovascular (CV), renal and safety outcomes of canagliflozin between Whites and Asians, as well as these outcomes in each subgroup. MATERIALS AND METHODS: The CANVAS Program enrolled 10 142 patients with type 2 diabetes, comprising 78.34% Whites and 12.66% Asians. CV, renal and safety outcomes were comprehensively analysed using Cox regression models, while intermediate markers were assessed using time-varying mixed-effects models. Racial heterogeneity was evaluated by adding a treatment-race interacion term. RESULTS: Canagliflozin showed no significant racial disparities in the majority of the CV, renal and safety outcomes. The heterogeneity (p = .04) was observed on all-cause mortality, with reduced risk in Whites (hazard ratio 0.84; 95% confidence interval 0.71-0.99) and a statistically non-significant increased risk in Asians (hazard ratio 1.64; 95% confidence interval 0.94-2.90). There was a significant racial difference in acute kidney injury (p = .04) and a marginally significant racial heterogeneity for the composite of hospitalization for heart failure and CV death (p = .06) and serious renal-related adverse events (p = .07). CONCLUSION: Canagliflozin reduced CV and renal risks similarly in Whites and Asians; however, there was a significant racial discrepancy in all-cause mortality. This distinction may be attributed to the fact that Asian patients exhibited diminished CV protection effects and more renal adverse events with canagliflozin, potentially resulting from the smaller reductions in weight and uric acid. These findings highlight the importance of investigating the impact of race on treatment response to sodium-glucose cotransporter-2 inhibitors and provide more precise treatment strategies.

Cultural Influences on Making Nutritional Adjustments in Type 2 Diabetes in Pakistan: The Perspectives of People Living With Diabetes and Their Family Members.

In Pakistan, type 2 diabetes is widespread, and although dietary recommendations from healthcare professionals are critical to its treatment, cultural norms can have a great influence on the dietary habits of people living with diabetes (PLwD). Understanding the social aspects of the lives of PLwD is crucial when examining the effectiveness of nutritional recommendations and adjustments. This study investigated (1) how PLwD and their family members adjust their nutrition to the recommendations of healthcare professionals to manage type 2 diabetes mellitus (T2DM) and (2) what do PLwD and their family members perceive as enablers and barriers to the necessary nutritional adjustments for managing T2DM. Prime consideration was given to experiences of living in Pakistan as the cultural context. Semi-structured interviews were conducted with 30 PLwD and 17 family members; the data were analysed thematically. Three themes emerged: (i) 'Influence of family system, gender, and age on meals prepared at home': family hierarchy and opinions based on gender and age can enable or hinder nutritional adjustment in meals prepared at home; (ii) 'Temptations of "unhealthy" foods, festivals, cultural interactions, and social etiquette': family/social interactions at home, gatherings, or festivities can affect PLwD's ability to resist temptations to eat foods prohibited by healthcare professionals; and (iii) 'Folk knowledge, folk remedy, and the balance between culture and Western medicine': PLwD and their family members in Pakistan hold strong beliefs concerning foods' medicinal properties. Power dynamics within families need to be considered when making nutritional recommendations. Medical guidelines should acknowledge personal agency and cultural beliefs.

Peer Support to Enhance Type 2 Diabetes Prevention Among African American and Latino Adults.

Social support occurs within complex social networks that are diffusely embedded within the social determinants of health. Social networks operate through five primary interconnected pathways: (1) provision of social support; (2) social influence; (3) social engagement; (4) social capital; and (5) social cohesion. Research has demonstrated that increased social support can have a beneficial impact on Type 2 Diabetes (T2DM) prevention and outcomes through culturally tailored Diabetes Prevention Programs in minority communities. Further research is needed to fully measure the impact of social network peer support on T2DM outcomes to better operationalize and scale up community specific interventions.

Pharmaceutical management of type 2 diabetes among Indigenous Australians living in urban or rural locations: a comparative study using a national general practice database.

INTRODUCTION: Type 2 diabetes is more prevalent among Aboriginal and Torres Strait Islander Peoples, especially those living in rural than urban areas. However, little is known about how diabetes is managed in different settings. OBJECTIVE: To investigate differences in the prevalence of diabetes and the prescription of antidiabetic medications for Aboriginal and/or Torres Strait Islander Peoples living in urban or rural Australia. DESIGN: Cross-sectional study using de-identified electronic medical records of 29,429 Aboriginal and/or Torres Strait Islander adults (60.4% females; mean age 45.2 ± 17.3 years) regularly attending 528 'mainstream' Australian general practices (MedicineInsight) in 2018. FINDINGS: The prevalence of diabetes was 16.0%, and it was more frequent among those living in rural areas (22.0; 95% CI 19.3-24.4) than inner regional (17.6%; 95% CI 16.0-19.2) or major cities (15.8%; 95% CI 14.7-17.0; p < 0.001). The highest prevalence of diabetes was for males living in rural settings (25.0%). Of those with diabetes, 71.6% (95% CI 69.0-74.0) were prescribed antidiabetics, with a similar frequency in urban and rural areas (p = 0.291). After adjustment for sociodemographics, the only difference in diabetes management was a higher prescription of sulfonylureas in rural areas than in major cities (OR 1.39; 1.07-1.80). DISCUSSION: The prevalence of diabetes was similar to other national data, although we found it was more frequent amongst Aboriginal and/or Torres Strait Islander males, especially those from rural areas. CONCLUSION: Despite current recommendations, one-in-four Indigenous Australians with diabetes were not prescribed antidiabetics. The clinical significance of more frequent prescriptions of sulfonylureas in rural locations remains unclear.

Associations between human cytomegalovirus infection and type 2 diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVE: Multiple studies have reported a potential contribution of human cytomegalovirus (HCMV) to the pathogenesis of type 1 diabetes and post-transplantation diabetes. However, the association between HCMV and type 2 diabetes mellitus (T2DM) remains unclear. In this paper, we employ the meta-analysis approach to investigate the potential correlation between HCMV infection and T2DM. METHOD: The data of our study were collected from PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure and WAN FANG databases from inception to November 2022. Using the Review Manager V.5.4 software, the meta-analysis was performed. RESULTS: A total of 18 139 patients from 22 studies were included in our analysis. In the Asian subgroup, the patients with T2DM group had a significantly higher frequency of HCMV infection and older age compared with the healthy group. In the European, the frequency of HCMV infection in the T2DM was lower than the healthy group, although this difference was not statistically significant. After adjusting for demographic factors, the adjusted OR of T2DM for risk of by HCMV status was not found to be significant (adjusted OR=1.19, 95% CI=0.88 to 1.62, p>0.05). Additionally, T2DM with vasculopathy had a significantly higher rate of HCMV infection compared with those without vasculopathy (OR=1.87, 95% CI=1.24 to 2.83, p<0.05). Among T2DM with HCMV infection, there were significant increases in fasting blood glucose levels and the proportion of CD8+ T lymphocytes. Conversely, fasting blood insulin levels, the proportion of CD4+ T lymphocyte and the CD4+/CD8+ ratio were significantly decreased compared with the healthy group. CONCLUSION: At present, the available evidence does not provide a clear understanding of whether there is a significant association between T2DM and HCMV infection. Additionally, T2DM with HCMV infection exhibited significantly worse blood glucose regulation and immune markers, as well as a higher frequency of vasculopathy. PROSPERO REGISTRATION NUMBER: CRD42022342066.

Glucose-lowering drug use in migrants and native Danes with type 2 diabetes: Disparities in combination therapy and drug types.

AIM: To examine disparities in glucose-lowering drug (GLD) usage between migrants and native Danes with type 2 diabetes (T2D). MATERIALS AND METHODS: In a nationwide, register-based cross-sectional study of 253 364 individuals with prevalent T2D on December 31, 2018, we examined user prevalence during 2019 of (i) GLD combination therapies and (ii) individual GLD types. Migrants were grouped by origin (Middle East, Europe, Turkey, Former Yugoslavia, Pakistan, Sri Lanka, Somalia, Vietnam), and relative risk (RR) versus native Danes was computed using robust Poisson regression to adjust for clinical and socioeconomic characteristics. RESULTS: In 2019, 34.7% of native Danes received combination therapy, and prevalence was lower in most migrant groups (RR from 0.78, 95% confidence interval CI 0.71-0.85 [Somalia group] to 1.00, 95% CI 0.97-1.04 [former Yugoslavia group]). Among native Danes, the most widely used oral GLD was metformin (used by 62.1%), followed by dipeptidyl peptidase-4 inhibitors (13.3%), sodium-glucose cotransporter-2 inhibitors (11.9%) and sulphonylureas (5.2%), and user prevalence was higher in most migrant groups (RR for use of any oral GLD: 0.99, 95% CI 0.97-1.01 [Europe group] to 1.09, 95% CI 1.06-1.11 [Sri Lanka group]). Furthermore, 18.7% of native Danes used insulins and 13.3% used glucagon-like peptide-1 receptor agonists (GLP-1RAs), but use was less prevalent in migrants (RR for insulins: 0.66, 95% CI 0.62-0.71 [Sri Lanka group] to 0.94, 95% CI 0.89-0.99 [Europe group]; RR for GLP-1RAs: 0.29, 95% CI 0.22-0.39 [Somalia group] to 0.95, 95% CI 0.89-1.01 [Europe group]). CONCLUSIONS: Disparities in GLD types and combination therapy were evident between migrants and native Danes. Migrants were more likely to use oral GLDs and less likely to use injection-based GLDs, particularly GLP-1RAs, which may contribute to complication risk and mortality among this group.

Association of Mitochondrial HVS-I Region Variants with Type 2 Diabetes in Pakistani Diabetic Subjects.

OBJECTIVE: To analyse mitochondrial hypervariable segment I (HVS-I) variations in Pakistani type 2 diabetic subjects. STUDY DESIGN: Case-control study. Place and Duration of the Study: National Institute of Diabetes and Endocrinology, Dow University of Health Sciences, Karachi, Pakistan, between January 2019 to January 2021. METHODOLOGY: DNA from whole blood was isolated, and mitochondrial HVS-I region (16024-16370) of 92 individuals, including 47 controls and 45 diabetics, was amplified, sequenced, and analysed. RESULTS: Ninety-two variable sites in the sequenced region were identified and individuals were classified into 56 different haplotypes according to phylotree 17.0 classifications, where major haplotype M5 was nearly 2-fold higher in diabetes. Fischer's exact test revealed variant 16189T>C significantly associated with diabetes (Odds ratio = 12.9, 95% CI = 0.6917 - 2400248) as compared to controls. The authors further analysed 1000 Genomes Project data of Pakistani Control subjects (i.e. PJL, n=96) and found that besides 16189T>C (Odds ratio = 5.875, 95% CI = 1.093 - 31.57, p <0.0339), 16264C>T (Odds ratio = 16, 95% CI = 0.8026 - 314.7, p <0.0310) also showed significant association with diabetic subjects. Comparing diabetic subject data with global control population data of the 1000 Genomes Project, significant associations of eight variants in the studied region were found. CONCLUSION: Based on the results of this case-control study, it can be concluded that specific variations in the mitochondrial hypervariable segment I (HVS-I) region are significantly associated with type 2 diabetes in the Pakistani population. The major haplotype M5 was found to be higher in diabetic subjects and variants 16189T>C and 16264C>T were significantly associated with diabetes. These findings suggest that mitochondrial DNA variations may play a role in the development of type 2 diabetes in the Pakistani population. KEY WORDS: Diabetes Mellitus, HVS-1 region, Diabetic subjects, Mitochondrial genomics, Pakistani population.

Common and Distinct Genetic Architecture of Age at Diagnosis of Diabetes in South Indian and European Populations.

OBJECTIVE: South Asians are diagnosed with type 2 diabetes (T2D) more than a decade earlier in life than seen in European populations. We hypothesized that studying the genomics of age of diagnosis in these populations may give insight into the earlier age diagnosis of T2D among individuals of South Asian descent. RESEARCH DESIGN AND METHODS: We conducted a meta-analysis of genome-wide association studies (GWAS) of age at diagnosis of T2D in 34,001 individuals from four independent cohorts of European and South Asian Indians. RESULTS: We identified two signals near the TCF7L2 and CDKAL1 genes associated with age at the onset of T2D. The strongest genome-wide significant variants at chromosome 10q25.3 in TCF7L2 (rs7903146; P = 2.4 × 10-12, ß = -0.436; SE 0.02) and chromosome 6p22.3 in CDKAL1 (rs9368219; P = 2.29 × 10-8; ß = -0.053; SE 0.01) were directionally consistent across ethnic groups and present at similar frequencies; however, both loci harbored additional independent signals that were only present in the South Indian cohorts. A genome-wide signal was also obtained at chromosome 10q26.12 in WDR11 (rs3011366; P = 3.255 × 10-8; ß = 1.44; SE 0.25), specifically in the South Indian cohorts. Heritability estimates for the age at diagnosis were much stronger in South Indians than Europeans, and a polygenic risk score constructed based on South Indian GWAS explained ∼2% trait variance. CONCLUSIONS: Our findings provide a better understanding of ethnic differences in the age at diagnosis and indicate the potential importance of ethnic differences in the genetic architecture underpinning T2D.

Epidemiology of Diabetes and Atherosclerotic Cardiovascular Disease Among Asian American Adults: Implications, Management, and Future Directions: A Scientific Statement From the American Heart Association.

Asian American individuals make up the fastest growing racial and ethnic group in the United States. Despite the substantial variability that exists in type 2 diabetes and atherosclerotic cardiovascular disease risk among the different subgroups of Asian Americans, the current literature, when available, often fails to examine these subgroups individually. The purpose of this scientific statement is to summarize the latest disaggregated data, when possible, on Asian American demographics, prevalence, biological mechanisms, genetics, health behaviors, acculturation and lifestyle interventions, pharmacological therapy, complementary alternative interventions, and their impact on type 2 diabetes and atherosclerotic cardiovascular disease. On the basis of available evidence to date, we noted that the prevalences of type 2 diabetes and stroke mortality are higher in all Asian American subgroups compared with non-Hispanic White adults. Data also showed that atherosclerotic cardiovascular disease risk is highest among South Asian and Filipino adults but lowest among Chinese, Japanese, and Korean adults. This scientific statement discusses the biological pathway of type 2 diabetes and the possible role of genetics in type 2 diabetes and atherosclerotic cardiovascular disease among Asian American adults. Challenges to provide evidence-based recommendations included the limited data on Asian American adults in risk prediction models, national surveillance surveys, and clinical trials, leading to significant research disparities in this population. The large disparity within this population is a call for action to the public health and clinical health care community, for whom opportunities for the inclusion of the Asian American subgroups should be a priority. Future studies of atherosclerotic cardiovascular disease risk in Asian American adults need to be adequately powered, to incorporate multiple Asian ancestries, and to include multigenerational cohorts. With advances in epidemiology and data analysis and the availability of larger, representative cohorts, furthering refining the Pooled Cohort Equations, in addition to enhancers, would allow better risk estimation in segments of the population. Last, this scientific statement provides individual- and community-level intervention suggestions for health care professionals who interact with the Asian American population.