The Molecular Mechanisms of the Relationship between Insulin Resistance and Parkinson's Disease Pathogenesis.

Parkinson's disease (PD) is a degenerative condition resulting from the loss of dopaminergic neurons. This neuronal loss leads to motor and non-motor neurological symptoms. Most PD cases are idiopathic, and no cure is available. Recently, it has been proposed that insulin resistance (IR) could be a central factor in PD development. IR has been associated with PD neuropathological features like α-synuclein aggregation, dopaminergic neuronal loss, neuroinflammation, mitochondrial dysfunction, and autophagy. These features are related to impaired neurological metabolism, neuronal death, and the aggravation of PD symptoms. Moreover, pharmacological options that involve insulin signaling improvement and dopaminergic and non-dopaminergic strategies have been under development. These drugs could prevent the metabolic pathways involved in neuronal damage. All these approaches could improve PD outcomes. Also, new biomarker identification may allow for an earlier PD diagnosis in high-risk individuals. This review describes the main pathways implicated in PD development involving IR. Also, it presents several therapeutic options that are directed at insulin signaling improvement and could be used in PD treatment. The understanding of IR molecular mechanisms involved in neurodegenerative development could enhance PD therapeutic options and diagnosis.

The Impact and Effectiveness of Weight Loss on Kidney Transplant Outcomes: A Narrative Review.

Obesity is a worldwide epidemic that leads to several non-communicable illnesses, including chronic kidney disease (CKD). Diet and lifestyle modifications have shown a limited impact in the treatment of obesity. Because the group of end-stage renal disease (ESRD) patients examined in this study had limited access to kidney transplantation (KT), patients with obesity were thought to be at an increased risk of intraoperative and postoperative KT complications. Although bariatric surgery (BS) is now recognized as the gold standard treatment for morbid obesity, its role in ESRD or kidney transplant patients remains unknown. It is critical to know the correlation between weight loss and complications before and after KT, the impact of the overall graft, and patients' survival. Hence, this narrative review aims to present updated reports addressing when to perform surgery (before or after a KT), which surgical procedure to perform, and again, if strategies to avoid weight regain must be specific for these patients. It also analyzes the metabolic alterations produced by BS and studies its cost-effectiveness pre- and post-transplantation. Due to the better outcomes found in KT recipients, the authors consider it more convenient to perform BS before KT. However, more multicenter trials are required to provide a solid foundation for these recommendations in ERSD patients with obesity.

The Impact of a Very-Low-Calorie Ketogenic Diet in the Gut Microbiota Composition in Obesity.

The very-low-calorie KD (VLCKD) is characterized by a caloric intake of under 800 kcal/day divided into less than 50 g/day of carbohydrate (13%) and 1 to 1.5 g of protein/kg of body weight (44%) and 43% of fat. This low carbohydrate intake changes the energy source from glucose to ketone bodies. Moreover, clinical trials have consistently shown a beneficial effect of VLCKD in several diseases, such as heart failure, schizophrenia, multiple sclerosis, Parkinson's, and obesity, among others. The gut microbiota has been associated with the metabolic conditions of a person and is regulated by diet interactions; furthermore, it has been shown that the microbiota has a role in body weight homeostasis by regulating metabolism, appetite, and energy. Currently, there is increasing evidence of an association between gut microbiota dysbiosis and the pathophysiology of obesity. In addition, the molecular pathways, the role of metabolites, and how microbiota modulation could be beneficial remain unclear, and more research is needed. The objective of the present article is to contribute with an overview of the impact that VLCKD has on the intestinal microbiota composition of individuals with obesity through a literature review describing the latest research regarding the topic and highlighting which bacteria phyla are associated with obesity and VLCKD.

Signals for Muscular Protein Turnover and Insulin Resistance in Critically Ill Patients: A Narrative Review.

Sarcopenia in critically ill patients is a highly prevalent comorbidity. It is associated with a higher mortality rate, length of mechanical ventilation, and probability of being sent to a nursing home after the Intensive Care Unit (ICU). Despite the number of calories and proteins delivered, there is a complex network of signals of hormones and cytokines that affect muscle metabolism and its protein synthesis and breakdown in critically ill and chronic patients. To date, it is known that a higher number of proteins decreases mortality, but the exact amount needs to be clarified. This complex network of signals affects protein synthesis and breakdown. Some hormones regulate metabolism, such as insulin, insulin growth factor glucocorticoids, and growth hormone, whose secretion is affected by feeding states and inflammation. In addition, cytokines are involved, such as TNF-alpha and HIF-1. These hormones and cytokines have common pathways that activate muscle breakdown effectors, such as the ubiquitin-proteasome system, calpain, and caspase-3. These effectors are responsible for protein breakdown in muscles. Many trials have been conducted with hormones with different results but not with nutritional outcomes. This review examines the effect of hormones and cytokines on muscles. Knowing all the signals and pathways that affect protein synthesis and breakdown can be considered for future therapeutics.

The Effect of Statins on Serum Vitamin D Concentrations Among Older Adults.

Background Randomized and observational studies have previously reported inconsistent results for the direct association between statin therapy and 25, hydroxyvitamin D [25(OH)D] levels. Thus, the present study aimed to examine the relationship between statin use and 25(OH)D and its metabolites concentrations in a large nationally representative sample of older adults. Methods This study was conducted using data from the National Health and Nutrition Examination Survey. Participants were asked to show the medication containers of all the products used in the previous 30 days, and the prescription of statins was defined on the three-level nested therapeutic classification scheme of Cerner Multum's Lexicon. General linear models adjusted for potential confounders were created to compare 25(OH)D concentrations between older adults taking statins and those who did not.  Results A total of 6,261 participants with a mean age of 69.5 years comprised the study sample. Of those, 40.2% were taking statins with a median length of therapy of 5 years. Adjusted mean 25(OH)D3 and 25(OH)D levels were 3.3 and 4.4 nmol/L higher among participants taking statins than those who did not, respectively. Moreover, this association was consistently seen regardless of the duration of therapy and particularly in subjects taking simvastatin, atorvastatin, or rosuvastatin. In subgroup analyses according to BMI categories and vitamin D intake, higher 25(OH)D levels were also seen among statin users. By contrast, this association was attenuated among those with a daily vitamin D between 400 and 800 and >800 IU. Conclusion Older adults on statin therapy had significantly higher serum 25(OH)D concentrations. Additional research should be conducted to define the mechanism of this association and determine if the pleiotropic effects attributed to statins may be mediated by vitamin D.

Multi-institutional experience of genetic diagnosis in Ecuador: National registry of chromosome alterations and polymorphisms.

BACKGROUND: Detection of chromosomal abnormalities is crucial in various medical areas; to diagnose birth defects, genetic disorders, and infertility, among other complex phenotypes, in individuals across a wide range of ages. Hence, the present study wants to contribute to the knowledge of type and frequency of chromosomal alterations and polymorphisms in Ecuador. METHODS: Cytogenetic registers from different Ecuadorian provinces have been merged and analyzed to construct an open-access national registry of chromosome alterations and polymorphisms. RESULTS: Of 28,806 karyotypes analyzed, 6,008 (20.9%) exhibited alterations. Down syndrome was the most frequent autosome alteration (88.28%), followed by Turner syndrome (60.50%), a gonosome aneuploidy. A recurrent high percentage of Down syndrome mosaicism (7.45%) reported here, as well as by previous Ecuadorian preliminary registries, could be associated with geographic location and admixed ancestral composition. Translocations (2.46%) and polymorphisms (7.84%) were not as numerous as autosomopathies (64.33%) and gonosomopathies (25.37%). Complementary to conventional cytogenetics tests, molecular tools have allowed identification of submicroscopic alterations regions or candidate genes which can be possibly implicated in patients' symptoms and phenotypes. CONCLUSION: The Ecuadorian National Registry of Chromosome Alterations and Polymorphisms provides a baseline to better understand chromosomal abnormalities in Ecuador and therefore their clinical management and awareness. This data will guide public policy makers to promote and financially support cytogenetic and genetic testing.

Optimal waist circumference cutoff values for predicting metabolic syndrome among older adults in Ecuador.

AIMS: To determine optimal waist circumference cutoff values for predicting metabolic syndrome (MetS) among adults aged 60 years and older in Ecuador. MATERIAL AND METHODS: The National Survey of Health, Wellbeing, and Aging survey was used to describe the prevalence of MetS according to standard definitions. Receiver operating characteristics (ROC) curve analyses and the Younden index J (YI) were performed to examine optimal waist circumference cutoff values for predicting MetS. Moreover, the prevalence of MetS according to country-specific waist circumference cutoff values was compared with those using standard definitions. RESULTS: Among 2306 participants with a mean age of 70.6 years, the optimal waist circumference cutoff value for predicting MetS was 90.7 cm in women with a sensitivity of 66.1%, specificity of 65.6% and YI of 0.31. In men, a waist circumference of 91.2 cm with a sensitivity of 73.2%, specificity of 62.8%, and YI of 0.36 was the optimal cutoff point for predicting MetS. In general, applying country-specific cutoff values decreased the prevalence of MetS among older Ecuadorian women. In men, except with the ATP III definition, similar MetS prevalence rates were seen whether the country-specific or standard waist circumference cutoff values were applied. CONCLUSIONS: The optimal waist circumference cutoff values for predicting metabolic syndrome among older Ecuadorians adults were 90.7 cm for women and 91.2 cm for men. Moreover, current standard definitions of abdominal obesity may overestimate the prevalence of MetS, particularly in Latin American women.

Mutational analysis of CFTR in the Ecuadorian population using next-generation sequencing.

The frequency distributions of cystic fibrosis variants are heterogeneous in Ecuador because of the genetic admixture of its population. The aim of this study was to identify disease-causing variants among Ecuadorian cystic fibrosis (CF) patients by next-generation sequencing (NGS) of the entire cystic fibrosis transmembrane conductance regulator (CFTR) gene. The results showed an approximation of the frequencies of pathogenic variants in the population under study and an optimal mutation panel for routine first-line CF molecular diagnosis. One hundred and forty-one patients with suspected CF from the 3 largest Ecuadorian cities (Guayaquil, Quito, and Cuenca) were studied. One hundred and seventy mutated alleles were detected in eighty-five individuals. Twenty-eight disease-causing variants were identified, with p.Phe508del and p.His609Arg being the most frequent (both 24.7%) followed by p.Gly85Glu (11.1%), p.Leu15Pro (9.4%), p.Asn1303Lys (4.1%), and p.Gly542* (2.3%). Together, these variants constituted 76.44% of the detected disease-causing variants. The following six novel potentially disease-associated variants were detected: 3 deletions (CFTR_dele10, CFTR_dele12, and c.2672delA), 1 nonsense variant (p.Cys491*), 1 missense variant (p.Trp496Arg), and 1 complex allele (p.[Gly253Arg;Gly451Val]). The remaining mutations occurred in isolation and were present in the databases.

Salud cardiovascular en habitantes de Atahualpa: características y correlatos / Cardiovascular health status in Atahualpa residents: characteristics and correlates

RESUMEN Las enfermedades vasculares son consideradas como las nuevas epidemias de salud en América Latina debido al aumento en la expectativa de vida y a cambios en el estilo de vida de sus habitantes. El conocimiento del estado de salud cardiovascular (SCV) de estas poblaciones es mandatorio para implementar estrategias costo-efectivas dirigidas a reducir la prevalencia de estas enfermedades en la región. En el Proyecto Atahualpa se ha valorado el estado de SCV de los participantes, utilizando los marcadores de salud propuestos por la Asociación Americana del Corazón. El estudio basal incluyó 616 sujetos libres de enfermedad cerebrovascular y cardiopatía isquémica, con edad ≥40 años. De estos, el 2.1% tuvieron un estado de salud ideal, el 28.1% intermedio y el 69.8% pobre. Los peores marcadores incluyeron presión arterial, glucosa en ayunas e índice de masa corporal. La posibilidad de tener un estado de SCV pobre estuvo aumentada en sujetos ≥60 años y en aquellos con escolaridad primaria. Luego, comparamos el estado de SCV de nuestra población con la de hispanos enrolados en el NOMAS, y encontramos que los residentes de Atahualpa tuvieron mejores marcadores de salud, con excepción de los niveles de glucosa en ayunas. La posibilidad de tener 5-7 marcadores en rango ideal fue más elevada en los residentes de Atahualpa, independientemente de la edad. También realizamos un estudio para valorar la SCV dependiendo del aislamiento social y encontramos que el vivir solo se asoció con un peor estado de SCV. Otros estudios mostraron relación entre ciertas patologías del sueño y un peor estado de SCV. Finalmente, hemos empezado el programa "conoce tus números", el cual sumado a charlas comunitarias, se encuentra dirigido a mejorar la SCV de los residentes de Atahualpa y reducir la incidencia de eventos vasculares en la región.

ABSTRACT Stroke and cardiovascular diseases will be the next epidemics in Latin America due to changes in lifestyle and increased life expectancy. Knowledge of cardiovascular health (CVH) status of the population is mandatory to implement cost-effective strategies directed to reduce the burden of vascular diseases in the region. In the Atahualpa Project, we assessed the CVH status of participants using the metrics proposed by the American Heart Association. The basal study included 616 subjects free of stroke and ischemic heart disease aged ≥40 years. Of these, 2.1% had ideal, 28.1% had intermediate and 69.8% had poor CVH status. Poorest metrics were blood pressure, fasting glucose, and BMI. The odds for having a poor CVH status were increased in persons aged ≥ 60 years and in those with only primary school education. Then, we compared our results with the Hispanic population of the Northern Manhattan Stroke Study (NOMAS), and found that Atahualpa residents had significantly better metrics than those enrolled in the NOMAS, with the exception of fasting glucose levels. Likewise, the odds for having 5 to 7 ideal metrics were also better in Atahualpa residents, irrespective of age. We also conducted a case-control study to assess the CVH status of Atahualpa residents according to their living arrangements, and found that social isolation was associated with a worse CVH status in this population. A couple of studies showed correlation between some sleep related disorders and poor CVH status. We have also started an ongoing program called "known your numbers", which, together with community talks, is directed to improve the CVH status and to reduce the burden of vascular diseases in the region.

Prevalence of abdominal obesity and its association with cardio metabolic risk factors among older adults in Ecuador.

AIMS: To describe the prevalence of abdominal obesity and its association with cardio metabolic risk factors among older adults in Ecuador. MATERIALS AND METHODS: The present study used data from the National Survey of Health, Wellbeing, and Aging survey to examine the prevalence of abdominal obesity according to certain demographic, behavioral, and health characteristics of the participants. Logistic regression models adjusted for potential confounders were used to evaluate the association of abdominal obesity with cardio metabolic risk factors. RESULTS: Of 2053 participants aged 60 years and older, the prevalence of abdominal obesity was 65.9% (95% CI; 62.2%, 69.4%) in women and 16.3% (95% CI; 13.8%, 19.2%) in men. Notably, a higher prevalence of abdominal obesity was seen among residents in the urban areas of the country, those who reported their race as black or mulatto, individuals with sedentary lifestyle and obesity, and older adults with greater number of comorbidities. Moreover, after adjustment for potential confounders, women with abdominal obesity were 2.0, 2.8, and 1.6 times more likely to have diabetes, the metabolic syndrome, and hypertriglyceridemia as compared with those without, respectively. Likewise, men with abdominal obesity had 51% and 22% higher rates of hypertension and diabetes than their non-obese counterparts, respectively. CONCLUSIONS: the prevalence of abdominal obesity is high among older adults in Ecuador. Moreover, abdominal obesity is significantly associated with cardio metabolic risk factors. Therefore, further research is needed to evaluate sociodemographic and nutritional determinants of this emerging public health burden among older Ecuadorians.

Cardiovascular health status and metabolic syndrome in Ecuadorian natives/Mestizos aged 40 years or more with and without stroke and ischemic heart disease--an atahualpa project case-control nested study.

BACKGROUND: Knowledge of regional-specific cardiovascular risk factors is mandatory to reduce the growing burden of stroke and ischemic heart disease in Latin American populations. We conducted a population-based case-control study to assess which risk factors are associated with the occurrence of vascular events in natives/mestizos living in rural coastal Ecuador. METHODS: We assessed the cardiovascular health (CVH) status and the presence of the metabolic syndrome in all Atahualpa residents aged 40 years or more with stroke and ischemic heart disease and in randomly selected healthy persons to evaluate differences in the prevalence of such risk factors between patients and controls. RESULTS: A total of 120 persons (24 with stroke or ischemic heart disease and 96 matched controls) were included. A poor CVH status (according to the American Heart Association) was found in 87.5% case-patients and 81.3% controls (P = .464). The metabolic syndrome was present in the same proportion (58.3%) of case-patients and controls. Likewise, both sets of risk factors (poor CVH status and the metabolic syndrome) were equally prevalent among both groups (58.3% versus 49%, P = .501). CONCLUSIONS: This case-control study suggests that none of the measured risk factors is associated with the occurrence of vascular events. It is possible that some yet unmeasured risk factors or an unknown genetic predisposition may account for a sizable proportion of stroke and ischemic heart disease occurring in the native/mestizo population of rural coastal Ecuador.

Prevalence of the metabolic syndrome and its correlation with the cardiovascular health status in stroke- and ischemic heart disease-free Ecuadorian natives/mestizos aged ≥40 years living in Atahualpa: a population-based study.

AIMS: Epidemiologic studies assessing cardiovascular risk factors affecting a given population may prove cost-effective to reduce the burden of cardiovascular diseases in the developing world. We evaluated the prevalence of the metabolic syndrome in Atahualpa, a village representative of rural coastal Ecuador. METHODS: Prevalence of the metabolic syndrome and its correlation with the cardiovascular (CVH) status was assessed in a door-to-door survey performed in stroke- and ischemic heart disease-free Ecuadorian native/mestizos aged ≥40 years. RESULTS: The metabolic syndrome was diagnosed in 288 (55.7%) out of 517 persons. Worst individual components were: increased waist circumference (75%), increased fasting glucose (68.1%) and high blood pressure (56.5%). Prevalence of individual components of this condition varied according to age, gender, education, and alcohol intake. However, no differences were found in the odds for having the metabolic syndrome when persons were stratified according to these parameters. A poor CVH status was found in 80.2% persons with and in 55.9% without the metabolic syndrome (p<0.0001). CONCLUSIONS: Prevalence of the metabolic syndrome in Atahualpa is high. Most persons with the metabolic syndrome also have a poor CVH status. However, sizable subsets only have either the metabolic syndrome or a poor CVH status. Stratification of cardiovascular risk according to whether the person has both, one, or none of these two sets of risk factors would be of value to evaluate if the metabolic syndrome, a poor CVH status or the combination of both, better predict the occurrence of vascular outcomes in the long-term follow-up.

Living alone and cardiovascular health status in residents of a rural village of coastal Ecuador (The Atahualpa Project).

OBJECTIVES: Knowledge of region-specific factors affecting the cardiovascular health (CVH) is mandatory to reduce the growing burden of stroke and ischemic heart disease in rural areas of Latin American. We conducted a population-based case-control study to assess the CVH status of Atahualpa residents-a rural village representative of Coastal Ecuador-according to their living arrangements. METHODS: All Atahualpa residents aged ≥40 years and free of stroke or ischemic heart disease that lived alone were identified during a door-to-door census, and their CVH status was compared to that of a sample of residents that lived with relatives. Four controls individually matched for age, gender, education, job and alcohol intake, and randomly selected from different households, were selected for each case-person. RESULTS: A total of 185 persons (37 who lived alone and 148 matched controls) were included. A poor CVH status was found in 89.2 % case-patients and 72.3 % controls (p = 0.03). We found significantly worse levels of physical activity (p < 0.0001) and non-significant trends for worse healthy diet and glucose levels among case-persons than controls. CONCLUSIONS: This study suggests that social isolation is associated with a worse CVH in rural coastal Ecuador. An ongoing community-based intervention may prove effective to improve CVH status in these social isolated persons.