Unexpected Dual Task Benefits on Cycling in Parkinson Disease and Healthy Adults: A Neuro-Behavioral Model

BackgroundWhen performing two tasks at once, a dual task, performance on one or both tasks typically suffers. People with Parkinson’s disease (PD) usually experience larger dual task decrements on motor tasks than healthy older adults (HOA). Our objective was to investigate the decrements in cycling caused by performing cognitive tasks with a range of difficulty in people with PD and HOAs.MethodsTwenty-eight participants with Parkinson’s disease and 20 healthy older adults completed a baseline cycling task with no secondary tasks and then completed dual task cycling while performing 12 tasks from six cognitive domains representing a wide range of difficulty.ResultsCycling was faster during dual task conditions than at baseline, and was significantly faster for six tasks (all p<.02) across both groups. Cycling speed improved the most during the easiest cognitive tasks, and cognitive performance was largely unaffected. Cycling improvement was predicted by task difficulty (p<.001). People with Parkinson’s disease cycled slower (p<.03) and showed reduced dual task benefits (p<.01) than healthy older adults.ConclusionsUnexpectedly, participants’ motor performance improved during cognitive dual tasks, which cannot be explained in current models of dual task performance. To account for these findings, we propose a model integrating dual task and acute exercise approaches which posits that cognitive arousal during dual tasks increases resources to facilitate motor and cognitive performance, which is subsequently modulated by motor and cognitive task difficulty. This model can explain both the improvement observed on dual tasks in the current study and more typical dual task findings in other studies.     

Revised Case Finding Protocol for Dysglycemia in Chile: A Call for Action in Other Populations

ObjectiveGuidelines recommend case finding for dysglycemia (prediabetes and type 2 diabetes [T2D]) in adults or youth older than 10 years with overweight/obesity, but increased adiposity has not been associated with dysglycemia in some Hispanic populations. This study aims to determine the prevalence of dysglycemia in this population using simplified criteria independent of body mass index and age to request an oral glucose tolerance test (OGTT).MethodsCross-sectional retrospective analysis of medical records from a clinical center in Chile (2000-2007). OGTT was obtained from any patient with 1 cardiometabolic risk factor (CMRF) independent of age and body mass index.ResultsIn total, 4969 adults (mean age ± SD) 45.7 ± 15.9 years and 509 youths 16.6 ± 3.0 years were included. The prevalence (%, 95% CI) of prediabetes doubled that of T2D in youths (14.1%, 1.4-17.4 vs 6.3%, 4.5-8.7) and tripled it in adults (36.0%, 34.7-37.4 vs 10.7%, 9.8-11.5). In underweight and normal-weight adults, 22% (12.0-36.7) and 29.2% (26.4-32.1) had prediabetes, whereas 4.9% (1.3-16.1) and 8.8% (7.2-10.7) had T2D, respectively. In normal weight youths, 10.5% (6.7-15.9) and 2.9% (1.2-6.6) had prediabetes and T2D, respectively. In adults, but not in youths, most dysglycemia categories were related to overweight/obesity.ConclusionThis study supports a public health policy to identify more people at risk for cardiovascular disease by implementing a revised case finding protocol for dysglycemia using OGTT in even normal weight patients over 6 years of age when there is at least 1 CMRF. Reanalysis of case finding protocols for cardiometabolic risk in other populations is warranted.     

Cycling on a Bike Desk Positively Influences Cognitive Performance

PurposeCycling desks as a means to reduce sedentary time in the office has gained interest as excessive sitting has been associated with several health risks. However, the question rises if people will still be as efficient in performing their desk-based office work when combining this with stationary cycling. Therefore, the effect of cycling at 30% Wmax on typing, cognitive performance and brain activity was investigated.MethodsAfter two familiarisation sessions, 23 participants performed a test battery [typing test, Rey auditory verbal learning test (RAVLT), Stroop test and Rosvold continuous performance test (RCPT)] with electroencephalography recording while cycling and sitting on a conventional chair.ResultsTyping performance, performance on the RAVLT and accuracy on the Stroop test and the RCPT did not differ between conditions. Reaction times on the Stroop test and the RCPT were shorter while cycling relative to sitting (p < 0.05). N200, P300, N450 and conflict SP latency and amplitude on the Stroop test and N200 and P300 on the RCPT did not differ between conditions.ConclusionsThis study showed that typing performance and short-term memory are not deteriorated when people cycle at 30% Wmax. Furthermore, cycling had a positive effect on response speed across tasks requiring variable amounts of attention and inhibition.     

Obesity and the relation between joint exposure to ambient air pollutants and incident type 2 diabetes: A cohort study in UK Biobank

BackgroundAir pollution has been related to incidence of type 2 diabetes (T2D). We assessed the joint association of various air pollutants with the risk of T2D and examined potential modification by obesity status and genetic susceptibility on the relationship.Methods and findingsA total of 449,006 participants from UK Biobank free of T2D at baseline were included. Of all the study population, 90.9% were white and 45.7% were male. The participants had a mean age of 56.6 (SD 8.1) years old and a mean body mass index (BMI) of 27.4 (SD 4.8) kg/m². Ambient air pollutants, including particulate matter (PM) with diameters ≤2.5 μm (PM_2.5), between 2.5 μm and 10 μm (PM_2.5–10), nitrogen dioxide (NO₂), and nitric oxide (NO) were measured. An air pollution score was created to assess the joint exposure to the 4 air pollutants. During a median of 11 years follow-up, we documented 18,239 incident T2D cases. The air pollution score was significantly associated with a higher risk of T2D. Compared to the lowest quintile of air pollution score, the hazard ratio (HR) (95% confidence interval [CI]) for T2D was 1.05 (0.99 to 1.10, p = 0.11), 1.06 (1.00 to 1.11, p = 0.051), 1.09 (1.03 to 1.15, p = 0.002), and 1.12 (1.06 to 1.19, p < 0.001) for the second to fifth quintile, respectively, after adjustment for sociodemographic characteristics, lifestyle factors, genetic factors, and other covariates. In addition, we found a significant interaction between the air pollution score and obesity status on the risk of T2D (p-interaction < 0.001). The observed association was more pronounced among overweight and obese participants than in the normal-weight people. Genetic risk score (GRS) for T2D or obesity did not modify the relationship between air pollution and risk of T2D. Key study limitations include unavailable data on other potential T2D-related air pollutants and single-time measurement on air pollutants.ConclusionsWe found that various air pollutants PM_2.5, PM_2.5–10, NO_2, and NO, individually or jointly, were associated with an increased risk of T2D in the population. The stratified analyses indicate that such associations were more strongly associated with T2D risk among those with higher adiposity.

Xiang Li and co-workers study the potential influence of obesity on associations between air pollutants and incidence of type 2 diabetes.     

Serum 25-hydroxyvitamin D levels are associated with carotid atherosclerosis in normotensive and euglycemic Chinese postmenopausal women: the Shanghai Changfeng study

Background

Obesity is associated with the onset of type 2 diabetes mellitus (T2D), but reports conflict regarding the association between obesity and macrovascular complications. In this study, we investigated associations between cardiovascular risk factors and body mass index (BMI) and glycemic control in non–insulin-treated patients with T2D.

Methods

Authors gathered cross-sectional data from five observational studies performed in Spain. Generalized logit models were used to analyze the relationship between cardiovascular risk factors (independent variables) and 5 BMI strata (<25 kg/m², 25 to <30 kg/m², 30 to <35 kg/m², 35 to <40 kg/m², ≥40 kg/m²) and 5 glycated hemoglobin (HbA1c) strata (≤6.5%, >6.5–7%, >7–8%, >8–9%, >9%) (dependent outcomes).

Results

In total, data from 6442 patients were analyzed. Patients generally had mean values of investigated cardiovascular risk factors outside recommended thresholds. Younger patients had higher BMI, triglyceride levels and HbA1c than their older counterparts. Diastolic blood pressure, systolic blood pressure and triglyceride levels were directly correlated with BMI strata, whereas an inverse correlation was observed between BMI strata and high-density lipoprotein cholesterol (HDL-C) levels, patient age, and duration of T2D. Increased duration of T2D and total cholesterol levels, and decreased HDL-C levels were associated with a higher HbA1c category. BMI and HbA1c levels were not associated with each other.

Conclusions

As insulin-naïve patients with T2D became more obese, cardiovascular risk factors became more pronounced. Higher BMI was associated with younger age and shorter duration of T2D, consistent with the notion that obesity at an early age may be key to the current T2D epidemic. Glycemic control was independent of BMI but associated with abnormal lipid levels. Further efforts should be done to improve modifiable cardiovascular risk factors.

     

Dietary Diversity,Diet Cost,and Incidence of Type 2 Diabetes in the United Kingdom: A Prospective Cohort Study

BackgroundDiet is a key modifiable risk factor for multiple chronic conditions, including type 2 diabetes (T2D). Consuming a range of foods from the five major food groups is advocated as critical to healthy eating, but the association of diversity across major food groups with T2D is not clear and the relationship of within-food-group diversity is unknown. In addition, there is a growing price gap between more and less healthy foods, which may limit the uptake of varied diets. The current study had two aims: first, to examine the association of reported diversity of intake of food groups as well as their subtypes with risk of developing T2D, and second, to estimate the monetary cost associated with dietary diversity.ConclusionsA diet characterized by regular consumption of all five food groups and by greater variety of dairy, fruit, and vegetable subtypes, appears important for a reduced risk of diabetes. However, such a diet is more expensive. Public health efforts to prevent diabetes should include food price policies to promote healthier, more varied diets.     

Genetic variability in sodium-glucose cotransporter 2 influences glycemic control and risk for diabetic retinopathy in type 2 diabetes patients

BackgroundGluconeogenesis and renal glucose excretion in kidneys both play an important role in glucose homeostasis. Sodium-glucose cotransporter (SGLT2), coded by the SLC5A2 gene is responsible for reabsorption up to 99% of the filtered glucose in proximal tubules. SLC5A2 genetic polymorphisms were suggested to influence glucose homeostasis. We investigated if common SLC5A2 rs9934336 polymorphism influences glycemic control and risk for macro or microvascular complications in Slovenian type 2 diabetes (T2D) patients.MethodsAll 181 clinically well characterized T2D patients were genotyped for SLC5A2 rs9934336 G>A polymorphism. Associations with glycemic control and T2D complications were assessed with nonparametric tests and logistic regression.ResultsSLC5A2 rs9934336 was significantly associated with increased fasting blood glucose levels (P<0.001) and HbA1c levels under the dominant genetic model (P=0.030). After adjustment for T2D duration, significantly higher risk for diabetic retinopathy was present in carriers of at least one polymorphic SLC5A2 rs9934336 A allele compared to non-carriers (OR=7.62; 95%CI=1.65-35.28; P=0.009).ConclusionsOur pilot study suggests an important role of SLC5A2 polymorphisms in the physiologic process of glucose reabsorption in kidneys in T2D patients. This is also the first report on the association between SLC5A2 polymorphism and diabetic retinopathy.     

How should we monitor the cardiovascular benefit of sodium–glucose cotransporter 2 inhibition?

Background

High N-terminal pro-brain-type natriuretic peptide levels have been associated with a lower risk of type 2 diabetes mellitus (T2D). However, less is known about other cardiac stress biomarkers in this context. Here we evaluated the association of mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-arginine vasopressin (copeptin), C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM) with incident T2D and changes in glucose metabolism.

Methods

We performed a prospective cohort study using data from the population-based KORA F4/FF4 study. 1773 participants (52.3% women) with MR-proANP measurements and 960 (52.7% women) with copeptin, CT-proET-1 and MR-proADM measurements were included. We examined associations of circulating plasma levels of MR-proANP, copeptin, CT-proET-1 and MR-proADM with incident T2D, the combined endpoint of incident prediabetes/T2D and with fasting and 2 h-glucose, fasting insulin, HOMA-IR, HOMA-B and HbA1c at follow-up. Logistic and linear regression models adjusted for age, sex, waist circumference, height, hypertension, total/HDL cholesterol ratio, triglycerides, smoking, physical activity and parental history of diabetes were used to compute effect estimates.

Results

During a median follow-up time of 6.4 years (25th and 75th percentiles: 6.0 and 6.6, respectively), 119 out of the 1773 participants and 72 out of the 960 participants developed T2D. MR-proANP was inversely associated with incident T2D (odds ratio [95% confidence interval]: 0.75 [0.58; 0.96] per 1-SD increase of log MR-proANP). Copeptin was positively associated with incident prediabetes/T2D (1.29 [1.02; 1.63] per 1-SD increase of log copeptin). Elevated levels of CT-proET-1 were associated with increased HOMA-B at follow-up, while elevated MR-proADM levels were associated with increased fasting insulin, HOMA-IR and HOMA-B at follow-up. These associations were independent of previously described diabetes risk factors.

Conclusions

High plasma concentrations of MR-proANP contributed to a lower risk of incident T2D, whereas high plasma concentrations of copeptin were associated with an increased risk of incident prediabetes/T2D. Furthermore, high plasma concentrations of CT-proET-1 and MR-proADM were associated with increased insulin resistance. Our study provides evidence that biomarkers implicated in cardiac stress are associated with incident T2D and changes in glucose metabolism.

     

Weight Cycling and the Risk of Developing Type 2 Diabetes among Adult Women in the United States

Objective: To assess the role of weight cycling independent of BMI and weight change in predicting the risk of developing type 2 diabetes. Research Methods and Procedures: A six‐year follow‐up of 46, 634 young and middle‐aged women in the Nurses’ Health Study II was conducted. Women who had intentionally lost ≥20 lbs at least three times between 1989 and 1993 were classified as severe weight cyclers. Women who had intentionally lost ≥10 lbs at least three times were classified as mild weight cyclers. The outcome was physician‐diagnosed type 2 diabetes. Results: Between 1989 and 1993, ～20% of the women were mild weight cyclers, and 1.6% were severe weight cyclers. BMI in 1993 was positively associated with weight‐cycling status (p < 0.001). During 6 years of follow‐up (1993 to 1999), 418 incident cases of type 2 diabetes were documented. BMI in 1993 had a strong association with the risk of developing diabetes. Compared with women with a BMI between 17 and 22 kg/m², those with a BMI between 25 and 29.9 kg/m² were approximately seven times more likely to develop diabetes, and those with a BMI ≥35 kg/m² were 63 times more likely to be diagnosed with type 2 diabetes. After adjustment for BMI, neither mild (relative risk = 1.11, 95% confidence interval, 0.89 to 1.37) nor severe (relative risk = 1.39, 95% confidence interval, 0.90 to 2.13) weight cycling predicted risk of diabetes. Discussion: Weight cycling was strongly associated with BMI, but it was not independently predictive of developing type 2 diabetes.     

体型肥胖2型糖尿病患者血清胆红素、胆汁酸、25(OH)D3水平及与胰岛素抵抗的关系研究

摘要 目的：探讨体型肥胖2型糖尿病（T2DM）患者血清胆红素、胆汁酸（BA）、25羟维生素D3[25(OH)D₃]水平及其与胰岛素抵抗（IR）的关系。方法：选取2018年1月-2019年12月我院就诊的240例T2DM患者,根据体重指数（BMI）将患者分为T2DM-N组84例,T2DM-OW组92例,T2DM-OB组64例。分别测定总胆红素（TBIL）、间接胆红素（IBIL）、直接胆红素（DBIL）、胆汁酸（BA）、25(OH)D₃等指标。以胰岛素抵抗指数（HOMA-IR）为因变量,行多元线性回归,分析IR的危险因素。结果：T2DM-OB组BMI、BA、甘油三酯（TG）、空腹血糖（FPG）、餐后2小时血糖（2hPG）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）、C反应蛋白（CRP）高于T2DM-N组,DBIL、25(OH)D₃低于T2DM-N组,差异均有统计学意义（P<0.05）。Pearson相关性分析显示,HOMA-IR与BMI、BA呈正相关（P<0.05),与DBIL、25(OH)D₃呈负相关（P<0.05);多元线性回归分析显示BMI升高,25(OH)D₃、DBIL下降为IR的危险因素（P<0.05）。结论：肥胖的T2DM患者存在IR及血脂紊乱,心血管疾病患病风险增加,BA水平升高,DBIL、25(OH)D₃水平下降,机体慢性低度炎症水平升高,除了BMI,25(OH)D₃、DBIL水平下降亦有可能是体型肥胖T2DM患者IR的重要危险因素。     

Prevalence and Predictors Ofvitamin D Deficiency in Healthy Adults

ObjectiveVitamin D deficiency is highly prevalent in high-risk patient populations, but the prevalence among otherwise healthy adults is less well-defined. The goal of this study was to determine the prevalence and predictors of low 25-hydroxyvitamin D [25(OH)D] levels in healthy younger adults.MethodsThis was a cross-sectional study of 634 healthy volunteers aged 18-50 years performed between January, 2006 and May, 2008. We measured serum 25(OH) D and parathyroid hormone and recorded demographic variables including age, sex, race, and use of multivitamin supplements.ResultsThirty-nine percent of subjects had 25(OH)D ≤ 20 ng/mL and 64% had 25(OH)D ≤ 30 ng/mL. Predictors of lower 25(OH)D levels included male sex, black or Asian race, and lack of multivitamin use (P < 0.001 for each pre dictor). Seasonal variation in 25(OH)D levels was present in the overall cohort but was not observed in multivita min users. Lower 25(OH)D levels were associated with increased risk of elevated parathyroid hormone. Regression models predicted 25(OH)D levels ≤ 20 or ≤ 30 ng/mL with areas under the receiver operating characteristic curves of 0.76 and 0.80, respectively.ConclusionLow 25(OH)D levels are prevalent in healthy adults and may confer risk of skeletal disease. Black and Asian adults are at increased risk of deficiency and multivitamin use appears partially protective. Our models predicting low 25(OH)D levels may guide decision-making regarding whom to screen for vitamin D defi ciency. (Endocr Pract. 2012;18:914-923)     

Vaccine effectiveness against SARS-CoV-2 infection,hospitalization, and death when combining a first dose ChAdOx1 vaccine with a subsequent mRNA vaccine in Denmark: A nationwide population-based cohort study

BackgroundThe recommendations in several countries to stop using the ChAdOx1 vaccine has led to vaccine programs combining different Coronavirus Disease 2019 (COVID-19) vaccine types, which necessitates knowledge on vaccine effectiveness (VE) of heterologous vaccine schedules. The aim of this Danish nationwide population-based cohort study was therefore to estimate the VE against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and COVID-19–related hospitalization and death following the first dose of the ChAdOx1 vaccine and the combination of the ChAdOx1/mRNA vaccines.Methods and findingsAll individuals alive in or immigrating to Denmark from 9 February 2021 to 23 June 2021 were identified in the Danish Civil Registration System. Information on exposure, outcomes, and covariates was obtained from Danish national registries. Poisson and Cox regression models were used to calculate crude and adjusted VE, respectively, along with 95% confidence intervals (CIs) against SARS-CoV-2 infection and COVID-19–related hospitalization or death comparing vaccinated versus unvaccinated individuals. The VE estimates were adjusted for calendar time as underlying time and for sex, age, comorbidity, country of origin, and hospital admission. The analyses included 5,542,079 individuals (97.6% of the total Danish population). A total of 144,360 individuals were vaccinated with the ChAdOx1 vaccine as the first dose, and of these, 136,551 individuals received an mRNA vaccine as the second dose. A total of 1,691,464 person-years and 83,034 SARS-CoV-2 infections were included. The individuals vaccinated with the first dose of the ChAdOx1 vaccine dose had a median age of 45 years. The study population was characterized by an equal distribution of males and females; 6.7% and 9.2% originated from high-income and other countries, respectively. The VE against SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine was 88% (95% CI: 83; 92) 14 days after the second dose and onwards. There were no COVID-19–related hospitalizations or deaths among the individuals vaccinated with the combined vaccine schedule during the study period. Study limitations including unmeasured confounders such as risk behavior and increasing overall vaccine coverage in the general population creating herd immunity are important to take into consideration when interpreting the results.ConclusionsIn this study, we observed a large reduction in the risk of SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine, compared with unvaccinated individuals.

Mie Agermose Gram and co-workers study the effectiveness of heterologous SARS-CoV-2 vaccine combinations in the Danish population.     

MHR、UACR、25（OH）D3与2型糖尿病患者下肢动脉病变的关系研究

摘要 目的：探讨单核细胞/高密度脂蛋白胆固醇（HDL-C）比值（MHR）、尿白蛋白/尿肌酐比值（UACR）、25-羟维生素D3[25（OH）D3]与2型糖尿病（T2DM）患者下肢动脉病变（LEAD）的关系。方法：选择2017年1月至2021年6月延边大学附属医院西区医院收治的195例T2DM患者,根据LEAD检查结果将患者分为LEAD组（104例）和非LEAD组（91例）。检测单核细胞、HDL-C、尿白蛋白、尿肌酐、25（OH）D3水平,计算MHR、UACR。比较两组MHR、UACR、25（OH）D3差异,单因素及多因素Logistic回归分析影响T2DM患者发生LEAD的危险因素,受试者工作特征（ROC）曲线分析MHR、UACR、25（OH）D3预测T2DM患者发生LEAD的价值。结果：LEAD组年龄、体质量指数大于非LEAD组,吸烟史、高血压比例高于非LEAD组,T2DM病程长于非LEAD组,总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、空腹血糖（FPG）高于非LEAD组,高密度脂蛋白胆固醇（HDL-C）低于非LEAD组（均P＜0.05）。LEAD组MHR、UACR高于非LEAD组,25（OH）D3水平低于非LEAD组（P＜0.05）。多因素Logistic回归分析显示,年龄过大、T2DM病程过长、高MHR、高UACR是T2DM患者发生LEAD的危险因素（P＜0.05）,高25（OH）D3是其保护因素（P＜0.05）。MHR、UACR、25（OH）D3预测T2DM患者发生LEAD的曲线下面积分别为0.728、0.755、0.759,联合三项指标后预测T2DM患者发生LEAD的曲线下面积为0.888,高于单独指标预测。结论：MHR、UACR增高和25（OH）D3水平降低与T2DM患者发生LEAD有关,联合三项指标在预测T2DM患者并发LEAD方面具有较高的价值。     

Serum zinc and risk of type 2 diabetes incidence in men: The Kuopio Ischaemic Heart Disease Risk Factor Study

ObjectivesZinc may play a role in the development of type 2 diabetes (T2D), because it is involved in antioxidant and anti-inflammatory activities. However, the role of zinc in the etiology of T2D has been poorly investigated. This study was conducted to study the association of serum zinc on T2D risk in middle-aged and older Finnish men.MethodsThis was a 20-year prospective follow-up study on 2220 Finnish men from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) who were 42 to 60 years old at baseline in 1984–1989. The main outcome was incident T2D. Serum zinc, body mass index (BMI), fasting blood glucose (FBG), serum insulin, C-reactive protein (CRP) and, in a subset of 751 participants, insulin-like growth factor-binding protein-1 (IGFBP-1), were measured. Also, the homeostatic model assessment (HOMA) was used to quantify insulin resistance (HOMA-IR), beta-cell function (HOMA-β) and insulin sensitivity (HOMA-IS).ResultsAt baseline, serum zinc was associated with higher BMI, serum insulin, HOMA-IR, HOMA-β and IGFBP-1 and lower HOMA-IS. During the average follow-up of 19.3 years, 416 men developed T2D. Men in the highest quartile of serum zinc had 60% higher risk (95% CI 20–113%; P-trend < 0.001) for incident T2D compared with the men in the lowest quartile, after multivariate adjustments. This association was attenuated after adjustment for BMI (HR = 1.39, 95% CI 1.04–1.85; P-trend = 0.013) or HOMA-IS (HR = 1.38, 95% CI 1.04–1.83; P-trend = 0.015), whereas adjustment for the other factors had only modest impact on the association.ConclusionHigher serum zinc was associated with higher risk of T2D; effects of zinc on BMI and insulin sensitivity may partly explain the association. Further prospective studies are warranted to confirm our results and explore potential mechanisms.     

FTO Gene Polymorphism Is Associated with Type 2 Diabetes through Its Effect on Increasing the Maximum BMI in Japanese Men

AimSeveral studies have demonstrated that polymorphisms within the fat-mass and obesity-associated gene (FTO) are associated with type 2 diabetes (T2D). However, whether the effects of the FTO locus on T2D susceptibility are independent of fat-mass increases remains controversial. To investigate this issue, we examined the association of FTO variants with T2D and various aspects of BMI history during adult life in a Japanese population.MethodsWe genotyped SNPs within FTO (rs1121980 and rs1558902) in 760 Japanese patients with T2D who had reached a lifetime maximum BMI (BMI_max) before or at the time of diagnosis and 693 control individuals with information regarding their BMI_max.ResultsThe BMI_max showed the strongest association with T2D risk among the BMIs evaluated in this study. In the sex-combined analysis, FTO SNPs were not associated with any of the BMI variables or with T2D, but in sex-stratified analyses, both SNPs were significantly associated with the BMI_max and rs1558902 was associated with T2D in men. The association of the SNPs with T2D remained significant after adjustments for the current BMI and age, whereas the T2D association of the SNP was no longer significant after adjustments for BMI_max and age.ConclusionsThese results suggest that the effects of FTO polymorphisms on T2D susceptibility in Japanese men are mediated through their effect on increasing the BMI_max before or at the time of diagnosis.     

Integrating polygenic risk scores in the prediction of type 2 diabetes risk and subtypes in British Pakistanis and Bangladeshis: A population-based cohort study

BackgroundType 2 diabetes (T2D) is highly prevalent in British South Asians, yet they are underrepresented in research. Genes & Health (G&H) is a large, population study of British Pakistanis and Bangladeshis (BPB) comprising genomic and routine health data. We assessed the extent to which genetic risk for T2D is shared between BPB and European populations (EUR). We then investigated whether the integration of a polygenic risk score (PRS) for T2D with an existing risk tool (QDiabetes) could improve prediction of incident disease and the characterisation of disease subtypes.Methods and findingsIn this observational cohort study, we assessed whether common genetic loci associated with T2D in EUR individuals were replicated in 22,490 BPB individuals in G&H. We replicated fewer loci in G&H (n = 76/338, 22%) than would be expected given power if all EUR-ascertained loci were transferable (n = 101, 30%; p = 0.001). Of the 27 transferable loci that were powered to interrogate this, only 9 showed evidence of shared causal variants. We constructed a T2D PRS and combined it with a clinical risk instrument (QDiabetes) in a novel, integrated risk tool (IRT) to assess risk of incident diabetes. To assess model performance, we compared categorical net reclassification index (NRI) versus QDiabetes alone. In 13,648 patients free from T2D followed up for 10 years, NRI was 3.2% for IRT versus QDiabetes (95% confidence interval (CI): 2.0% to 4.4%). IRT performed best in reclassification of individuals aged less than 40 years deemed low risk by QDiabetes alone (NRI 5.6%, 95% CI 3.6% to 7.6%), who tended to be free from comorbidities and slim. After adjustment for QDiabetes score, PRS was independently associated with progression to T2D after gestational diabetes (hazard ratio (HR) per SD of PRS 1.23, 95% CI 1.05 to 1.42, p = 0.028). Using cluster analysis of clinical features at diabetes diagnosis, we replicated previously reported disease subgroups, including Mild Age-Related, Mild Obesity-related, and Insulin-Resistant Diabetes, and showed that PRS distribution differs between subgroups (p = 0.002). Integrating PRS in this cluster analysis revealed a Probable Severe Insulin Deficient Diabetes (pSIDD) subgroup, despite the absence of clinical measures of insulin secretion or resistance. We also observed differences in rates of progression to micro- and macrovascular complications between subgroups after adjustment for confounders. Study limitations include the absence of an external replication cohort and the potential biases arising from missing or incorrect routine health data.ConclusionsOur analysis of the transferability of T2D loci between EUR and BPB indicates the need for larger, multiancestry studies to better characterise the genetic contribution to disease and its varied aetiology. We show that a T2D PRS optimised for this high-risk BPB population has potential clinical application in BPB, improving the identification of T2D risk (especially in the young) on top of an established clinical risk algorithm and aiding identification of subgroups at diagnosis, which may help future efforts to stratify care and treatment of the disease.

Sam Hodgson and colleagues investigate whether the common genetic differences associated with type 2 diabetes in people of European ancestry can be transferred to people of British Pakistani and Bangladeshi ancestry, integrating a novel polygenic risk score with an established clinical risk score.     

Racial and Ethnic Cardiometabolic Risk Disparities in the Type 1 Diabetes Exchange Clinic Registry Cohort

ObjectiveTo determine whether individuals from a historically underrepresented racial group have a higher cardiometabolic risk than historically represented individuals with type 1 diabetes (T1D) considering socioeconomic deprivation.MethodsWe used the multivariable logistic and linear regression models to examine socioeconomic deprivation (upper 10th percentile) by race/ethnicity interaction for each cardiometabolic risk factor and cardiometabolic risk burden score, respectively, across 6320 zip code tabulation areas. We also determined the age-adjusted prevalence of low, moderate, and high cardiometabolic risks defined as 0, 1 to 2, and 3 or more risk factors for hypertension, obesity, dyslipidemia, and off-target glycemia for non-Hispanic White (n = 15 746), non-Hispanic Black (n = 1019), Hispanic (n = 1115), and other (n = 887), respectively.ResultsThe sample comprised 18 767 adolescents and adults with T1D. Those identifying as non-Hispanic Black were more likely to have a high cardiometabolic risk profile, including a 4.5-fold increase in the odds of off-target glycemia, a twofold increase in the odds of systolic hypertension, and 0.29 (unadjusted) and 0.46 (adjusted) increases in a higher cardiometabolic risk burden compared with non-Hispanic White individuals (P < .01). Those identifying as Hispanic had a 3.4-fold increase in the odds of off-target glycemia but were less likely to be overweight/obese or have systolic hypertension compared with non-Hispanic White. However, the lower likelihood of overweight/obesity and hypertension did not persist after considering covariates.ConclusionThere is a need to investigate additional determinants of racially/ethnically underrepresented cardiometabolic health, including structural racism and implicit bias in cardiometabolic care for individuals with T1D.     

Occupational exposure to solar ultraviolet B radiation and risk of prostate cancer in Danish men

ObjectivesFormer epidemiological studies have indicated that solar ultraviolet B radiation (UV) may reduce the risk of prostate cancer, however, the evidence is inconclusive. To contribute with evidence, the present study aimed to evaluate the association between occupational UV exposure and prostate cancer in Danish men.MethodsA total of 12,268 men diagnosed with primary prostate cancer before age 70 were identified via the Danish Cancer Registry. The Danish Civil Registration System was used to randomly select five male controls matched on year of birth, alive and free of prostate cancer at the time of diagnosis of the index case. Full individual-level employment history was retrieved from the Danish Supplementary Pension Fund Register and linked to a job exposure matrix to assess occupational UV exposure. Conditional logistic regression was used to estimate odds ratios (ORs) with corresponding 95 % confidence intervals.ResultsWe observed an inverse association between ever exposure to occupational UV and prostate cancer (OR=0.93, 95 % CI: 0.89–0.97). Longer duration of exposure (≥20 years: OR=0.90, 95 % CI: 0.84–0.96) and highest cumulative exposure (OR=0.90, 95 % CI: 0.84–0.96) were both inversely associated with disease risk.ConclusionsThe present study indicates a modest protective effect from occupational UV exposure on the risk of prostate cancer. This finding needs further attention in future large-scale studies.     

Risk for Coexistent Autoimmune Diseases in Familial and Sporadic Type 1 Diabetes is Related to Age at Diabetes Onset

ObjectiveType 1 diabetes (T1D) is frequently associated with other autoimmune diseases (AIDs). Although most of T1D patients are sporadic cases (S-T1D), 10% to 15% have a familial form (F-T1D) involving 2 or more first-degree relatives. This study evaluated the effect of T1D family aggregation and age onset on AIDs occurrence.MethodsIn this observational, cross-sectional, case-control, single center study, we enrolled 115 F-T1D and 115 S-T1D patients matched for gender, age, T1D age onset, and duration. With respect to T1D age onset (before or after 18 years), both groups were further subdivided into young- or adult-onset F-T1D and young- or adult-onset S-T1D. The presence of organ-specific antibodies and/or overt AIDs was evaluated.ResultsThe F-T1D group had a higher percentage of AIDs (29.8% vs 18.4%, P = .04) and a significant earlier onset of AIDs at Cox regression analysis (P = .04) than the S-T1D group. Based on multivariate analysis, the adult-onset F-T1D subgroup had the highest prevalence of both additional organ-specific antibodies (60.5%) and overt AIDs (34.9%), whereas the adult S-T1D subgroup was the least frequently involved (29.1% and 12.7%, respectively). In F-T1D patients, offsprings develop T1D and AIDs earlier than their parents do.ConclusionsIn T1D patients, familial aggregation and adult-onset of T1D increase the risk for coexistent AIDs. These clinical predictors could guide clinicians to address T1D patients for the screening of T1D-related AIDs.