Altered Taste Function in Young Individuals With Type 1 Diabetes

Past studies on altered taste function in individuals with type 1 diabetes have yielded inconsistent results. We therefore evaluated taste recognition and possible association with personal and diseases characteristics in young individuals with type 1 diabetes and healthy controls. Taste recognition and intensity for 6-n-propylthiouracil (PROP), quinine, citric acid, sucrose, and sodium chloride were assessed using a filter paper method in 276 participants with type 1 diabetes and 147 healthy controls. Personal and clinical data were recorded for all participants during a baseline visit. Regression analysis was adjusted for sex, age, and standardized BMI. Overall, 47% of participants with type 1 diabetes vs. 63.5% of healthy controls recognized all tastes (p = 0.006). Moreover, a lower capacity for recognizing the bitter taste of PROP and the sour taste of citric acid was found in participants with type 1 diabetes compared to healthy controls (p = 0.014 and p = 0.003, respectively). While no significant effect of glycemic control on taste recognition was found, an association with lower age at onset emerged. Our findings suggest an impaired taste perception in individuals with type 1 diabetes, possibly linked to age at onset.

APOE4 Allele, Sex, and Dementia Risk in Parkinson’s Disease: Lessons From a Longitudinal Cohort

Introduction The effect of APOE4 allele on dementia risk is well established in Alzheimer’s disease and Parkinson’s disease (PD). However, it is unknown if sex modifies this relationship. We sought to determine the effect of sex on the relationship between APOE4 status and incident cognitive decline in PD. Methods Data from the prospectively collected longitudinal National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) and Neuropathology Data Set (NDS) were analyzed. The NACC develops and maintains data from approximately 29 National Institutes of Aging-funded Alzheimer's Disease Research Centers. Further details may be found at the NACC web site ( www.alz.washington.edu ). The visit at which diagnosis of PD was made was termed the baseline visit. All patients with a PD diagnosis but without dementia at the baseline visit were included in the analyses. Results Presence of APOE4 allele was associated with higher odds (OR = 7.4; P < .001) of subsequent diagnosis of dementia and with a faster time to developing dementia ( P = .04). Those with APOE4 allele were more likely to have neuropathology associated with Alzheimer’s disease than those without APOE4 allele. We did not find any difference by sex. There were no differences between Lewy body pathology or neuron loss in the substantia nigra between the 2 groups. Sex was not associated with dementia risk in PD (OR = 0.53, P = .15) or with the time to dementia onset ( P = .22). Sex did not modify the relationship between the APOE4 allele and dementia onset in PD patients ( P = .12) Conclusions APOE4 allele status in PD may be a predictor of cognitive decline in PD but does not appear to be modified by sex.

Parkinson’s Disease Motor Subtypes Change with the Progression of the Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up

Background: Motor phenotype (MP) can be associated with a different prognosis in Parkinson’s disease (PD), but it is not fixed and can change over time. Objective: Our aim was to analyze how the MP changed over time and to identify factors associated with the changes in PD patients from a multicenter Spanish PD cohort. Methods: PD patients who were recruited from January-2016 to November-2017 (baseline visit; V0) and evaluated again at a 2-year±30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this study.MP was calculated at both visits based on Jankovic classification in TD (tremor dominant), IND (indeterminate), or PIGD (postural instability and gait difficulty). Sociodemographic and clinical data were collected, including serum biomarkers. Results: Five hundred eleven patients (62.57±8.59 years old; 59.2%males) were included in the study. At V0, MP was: 47.4%(242/511) TD; 36.6%(187/511) PIGD; 16%(82/511) IND. Up to 38%(194/511) of the patients changed their phenotype from V0 to V2, being the most frequent from TD to IND (8.4%) and from TD to PIGD (6.7%). A worse cognitive status (OR = 0.966) and less autonomy for activities of daily living (OR = 0.937) at V0 and a greater increase in the globalNMS burden (OR = 1.011) from V0 to V2 were associated with changing from TD to another phenotype after 2-year follow-up. Conclusion: The MP in PD can change over time. With disease progression, the percentage of cases with non-tremoric MP increases. PD patients who changed from TD to postural instability and gait difficulty increased NMS burden significantly.

Association between secondhand smoke exposure and new-onset hypertension in self-reported never smokers verified by cotinine

Background/Aims: There is no study assessing the effect of changes of secondhand smoke (SHS) exposure and new-onset hypertension. We investigated the effect of a change of SHS exposure status on new-onset hypertension in self-reported and cotinine-verified never smokers.Methods: Out of individuals enrolled in the Kangbuk Samsung Health Study between 2011 and 2016, 87,486 self-reported and cotinine-verified never smokers without hypertension at baseline visit were included with a median follow-up of 36 months. Individuals were divided into four groups on the basis of their SHS exposure status at baseline and at follow-up: no, new, former, and sustained SHS exposure groups.Results: The incidence rates per 10,000 person-year of new-onset hypertension in no, new, former, and sustained SHS exposure groups were 84.7, 113.3, 102.0, and 123.7, respectively (p < 0.001). A multivariable Cox-hazard analyses showed that new and sustained SHS exposure groups increased their hazard ratio (HR) for new-onset hypertension compared to no SHS exposure group (HR, 1.31; 95% confidence interval [CI], 1.08 to 1.60 for new SHS exposure group; and HR, 1.24; 95% CI, 1.06 to 1.45 for sustained SHS exposure group). However, being part of the former SHS exposure group did not increase the risk of new-onset hypertension (HR, 0.91; 95% CI, 0.81 to 1.03).Conclusions: This study showed that either new, or sustained SHS exposure, but not former SHS exposure, increased the risk for new-onset hypertension in self-reported never smokers verified as nonsmokers by urinary cotinine. These findings show the possibility that changing exposure to SHS even for a relatively short period can modify the risk of new-onset hypertension in self-reported and cotinine-verified never smokers.

Additive roles of tobacco and cannabis co-use in relation to delay discounting in a sample of heavy drinkers

Rationale Alcohol use disorder (AUD) is associated with steeper delay discounting rates; however, it is unknown whether substance co-use, particularly cannabis use, has an additive effect on discounting rates among heavy drinkers. Furthermore, it is unclear whether substance co-use and delay discounting are independently associated with AUD severity. Objectives The purpose of this study was to determine whether alcohol, tobacco, and cannabis co-use impacts delay discounting rates. We also sought to determine whether substance co-use and delay discounting were associated with AUD symptom counts. Methods The study sample was culled from several human laboratory studies and consisted of 483 heavy drinking individuals who completed a baseline visit (prior to experimental procedures). Participants were divided into groups based on self-reported alcohol, tobacco, and cannabis use during the past 30 days: alcohol only (n = 184), alcohol + cigarettes (n = 89), alcohol + cannabis (n = 82), and tri-use (n = 128). We examined discounting rates across the 4 groups and used multiple linear regression to test whether co-use and delay discounting were associated with AUD symptoms. Results After adjusting for covariates, individuals in the alcohol + cannabis group and the tri-use group had steeper discounting rates relative to the alcohol-only group. In addition, tri-use and delay discounting rates were independently correlated with a greater number of AUD symptoms. Conclusions Delay discounting rates were significantly greater among subgroups reporting cannabis use providing partial support for an additive effect, while also highlighting the importance of co-use substance type. Both tri-use and delay discounting were associated with greater AUD severity, which may provide relevant intervention targets.

The Dynamic Effect of Non-CYP3A4-Metabolized and CYP3A4-Metabolized Statins on Clopidogrel Resistance in Patients With Cerebral Infarction

Objective: To explore the treatment effect of statins used together with clopidogrel on cerebral infarction (CI).Methods: One hundred and thirty non-clopidogrel resistant patients were divided into a dynamic clopidogrel resistant (DCR) group and a continuous Non clopidogrel resistance (NCR) group. Patients were randomly assigned to AC group (atorvastatin 40 mg/d + clopidogrel, 51 patients) and RC group (rosuvastatin 20 mg/d + clopidogrel, 47 patients). The patient’s platelet aggregation rate (PAR) was measured on visit 0 (baseline), visit 1 (1 week after clopidogrel alone treatment), and visits 2 to 4 (one, three, and 6 months after clopidogrel plus statins treatment). The platelet reactivity index (PRI) was assessed on visits 0, 2, and 4, and clopidogrel thiol metabolite (H4) levels was measured on visits 2 and 4. DNA sequencing was used to determine CYP3A4, CYP2C9, and CYP2C19 genotypes in all patients.Results: PAR, PRI, and H4 levels, DCR ratio, and the genotype frequencies of CYP2C9*3εC, CYP2C19*2εA, and CYP2C19*3εA of both groups were similar (p &gt; 0.05). CYP2C19εA *2 and *3 were independent risk factors for DCR (p &lt; 0.05).Conclusion: Clopidogrel combined with atorvastatin does not affect platelet inhibition and does not increase the incidence of DCR. The incidence of DCR in the Chinese population is high and is related to CYP2C19εA.

Predictors of deterioration in cardiorespiratory fitness among healthy adults: the importance of sex and obesity

Introduction Cardiorespiratory fitness (CRF) is associated with cardiovascular co-morbidities and is a strong predictor of adverse cardiovascular outcomes. However, data on the natural history of cardiorespiratory fitness among healthy subjects is limited. Purpose This study investigated what are the predictors of deterioration in CRF over time. Methods We investigated 36,239 men and women who were annually screened in a tertiary medical center and completed an exercise stress test in all visits, with a total of 175,596 annual visits. Subjects who failed to complete maximal exercise stress test according to the Bruce protocol at their first baseline visit were excluded. In addition, subjects with less than five visits to the center or those who developed ischemic heart disease during follow-up were excluded. Fitness was categorized into age- and sex-specific quintiles (Q) according to Bruce protocol treadmill time. Change in CRF between the first baseline visit and the fifth visit was used to calculate fitness deterioration. The primary study endpoint was defined as the lower sex-specific quintile of change in metabolic equivalents (METS) between visits 1 and 5. Logistic regression models were applied. Results Final study population included 10,841 subjects. The mean age of the study population was 49±10 years, the mean BMI was 26±4, and 8107 (75%) were men. Median METS at baseline were 10.8 (IQR 9–12.6) and 11.1 (IQR 9.4–13) at the first and fifth visit, respectively (p&lt;0.001 for METS between visits). Overall, 2189 (20%) subjects met the study endpoint. CFR deterioration was higher among women as compared to men (p=0.023). Out of obesity, hypertension, fasting blood glucose, LDL, and HDL cholesterol, after adjustments for age, sex, and baseline CFR, only obesity was independently associated with fitness deterioration in the multivariate model (OR=1.4 95% CI 1.2–1.5, p&lt;0.001). The association of obesity with fitness deterioration was modified by sex such that the risk of CRF deterioration was more pronounced in women (OR=1.6 95% CI 1.3–2, p&lt;0.001) than in men (OR=1.3 95% CI 1.1–1.4, p&lt;0.001). Conclusion Obesity is an independent predictor of future CRF deterioration. The effect of obesity on future CRF deterioration is more pronounced among women as compared to men. FUNDunding Acknowledgement Type of funding sources: None.

Clinical features of familial hypercholesterolaemia in children and adults – the PMMHRI Registry

Background Familial hypercholesterolaemia (FH) affects approximately 150,000 people in Poland. However, there are many patients still unaware of this diagnosis. On the other hand, it might lead to early cardiovascular mortality and morbidity due to the lifetime exposure to high levels of LDL-C. Therefore, increased awareness of FH is very important. Purpose We aimed to evaluate the clinical features of FH in children and adults based on the preliminary data from the Polish Mother's Memorial Hospital Research Institute (PMMHRI) Registry. Methods The registry of children and adults with FH conducted in PMMHRI (2nd largest, supra-regional hospital in Poland) was established to investigate the clinical characteristics, management and clinical outcomes data of FH patients. All consecutive patients with diagnosed (genetically and/or phenotypically) FH were included in the study. Results Of 103 patients with FH, there were 16 children aged 9±3 and 87 adults aged 41±16; 59% were female. The diagnosis of FH in adults was late – at the mean age of 41 years. Among children with FH, as compared with adults, the levels of highest TC and LDL-C ever were similar. However, children presented higher mean levels of total cholesterol, LDL-C and HDL-C measured at baseline visit (Table). Interestingly there was no difference in BMI between children and adults (Table). Among adults, chronic coronary syndrome was diagnosed in 11.5% patients, from which 5.7% patients had a history of myocardial infarction and 7% patients required revascularization. The prevalence of chronic coronary disease, peripheral artery disease as well as stroke in family history was definitely higher (in 44 patients – 50%, 17 patients – 20% and 22 patients – 25%, respectively). Most of adult patients at baseline visit were prescribed statins (rosuvastatin or atorvastatin). 14 patients (13.6%) declared statin intolerance, most of them complained of muscle pain, 4.6% patients reported hepatic disturbances. The frequency of statin use in children was lower – 56% children were prescribed statin, 19% declared statin intolerance with muscle pain as the side-effect of treatment. Ezetimibe, as a part of combination therapy, was taken by 29% adult patients. PCSK9 inhibitors were prescribed (within drug program) for 11.5% adult patients. Fibrates were prescribed for 13.7% adult patients, the same was for n-3 fatty acids. Conclusions Despite definitely younger age of FH diagnosis children present higher mean levels of LDL cholesterol than adults. Therefore, the lifetime exposure to LDL cholesterol starts at a very young age. As a result, there is a need to the earlier initiation of therapy and strict monitoring of the atherosclerosis progression. On the other hand, late diagnosis of FH in adults is an unmet need, that might be associated with poorer prognosis. FUNDunding Acknowledgement Type of funding sources: None.

Long-Term Glycemic Variability Is Associated With Arterial Stiffness in Chinese Adults

ObjectiveThe aim of the study was to investigate the association between the visit-to-visit variability (VVV) of fasting plasma glucose (FPG) and arterial stiffness in Chinese adults.MethodsWe performed a cohort study involving 2002 Chinese adults with no history of myocardial infarction or stroke. All the participants attended three visits (the baseline visit in 2008, the 2nd visit in 2009 and the 3rd visit in 2013). We used four measures to define the VVV of FPG across the three visits: the standard deviation (SD), the coefficient of variation (CV), the average successive variability (ASV) and the variability independent of the mean (VIM). We used brachial-ankle pulse wave velocity (ba-PWV) to measure arterial stiffness at the 2nd and the 3rd visits.ResultsCompared with the lowest tertile of all the four measurements of VVV of FPG, significantly increased levels of ba-PWV change, ratio of ba-PWV change and the occurrence of the elevated ba-PWV were found in the highest tertile. The odds ratio (OR) and 95% confidence interval (CI) comparing participants in the highest tertile vs. the lowest tertile of FPG-SD was 1.37 (1.01-1.86) for risks of having elevated ba-PWV, even after adjustment for covariates including the mean FPG. Similar results were found for FPG-CV and FPG-VIM.ConclusionGreater long-term variability of FPG was associated with an increased risk of arterial stiffness, suggesting that the VVV of FPG could be used for an early detection of subclinical atherosclerosis.

Incidence and related risk factors of radiographic knee osteoarthritis: a population-based longitudinal study in China

Objective To explore the incidence and risk factors for radiographic knee osteoarthritis (ROA) in a suburban area of China. Methods Shunyi Osteoarthritis Study was a population-based, longitudinal study of knee osteoarthritis in Shunyi, a suburban area of Beijing, China. A total of 1295 residents aged over 50 years were recruited with fully informed by randomized cluster sampling and were followed up 3 years later. At the time of baseline and follow-up visits, participants completed a home interview questionnaire and received a clinical examination including height, weight, range of motion (ROM), chair stand test, 50-foot walk test, and weight-bearing posterior-anterior semi-flexed view of radiographs at tibiofemoral joints. The incident ROA for a knee was defined if its KL grade was no more than grade 1 at baseline visit and no less than grade 2 at the follow-up visit. A patient without ROA in both knees at the baseline visit and with ROA in at least one knee at the follow-up visit was viewed as an incident case of ROA in patient level. Generalized linear model and generalized estimating equation were performed to examine the association between socio-demographic factors, physical function as well as baseline knee joint condition, and incident ROA in patient and knee level. Results A total of 1295 residents were recruited at baseline in 2014, and 962 (74.3%) residents were followed in 2017. The annual cumulative incidence of ROA was 3.6% at knee level and 5.7% at patient level. Older age (per year, adjusted odds ratio (OR) = 1.079; 95% confidence interval (CI), 1.042-1.117), overweight (adjusted OR = 2.086; 95% CI, 1.286-3.385), female (adjusted OR = 1.756; 95% CI, 1.074-2.877), less ROM (per degree, adjusted OR = 0.952; 95% CI, 0.923-0.983) and Kellgren and Lawrence (KL) grade 1 at baseline (adjusted OR = 8.527; 95% CI, 5.489-13.246) were risk factors for incident ROA. Conclusion The incidence of knee ROA in Chinese suburban area was high. Advanced age, female, overweight, less range of motion, and KL grade 1 at baseline were associated with an increased risk of incident ROA.