Long-term commuting times and air quality relationship to COVID-19 in São Paulo.

The Coronavirus Disease 2019 (COVID-19) epidemic is an unprecedented global health crisis and the effects may be related to environmental and socio-economic factors. In São Paulo, Brazil, the first death occurred in March 2020 and since then the numbers have grown to 175 new deaths per day in April 2021, positioning the city as the epicenter of the number of cases and deaths in Brazil. São Paulo is one of the largest cities in the world with more than 12 million inhabitants, a fleet of about 8 million vehicles and frequent pollutant concentrations above recommended values. Social inequalities are evident in the municipality, similarly to other cities in the world. This paper focuses on transportation activities related to air pollution and associated with cardiovascular and respiratory diseases especially on people who developed comorbidities during their whole life. This study relates travel trip data to air quality analysis and expanded to COVID-19 disease. This work studied the relationship of deaths in São Paulo due to COVID-19 with demographic density, with family income, with the use of public transport and with atmospheric pollution for the period between March 17th, 2020 and April 29th, 2021. The main results showed that generally passenger kilometers traveled, commuting times and air quality related diseases increase with residential distance from the city center, and thus, with decreasing residential density. PM2.5 concentrations are positively correlated with COVID-19 deaths, regions with high urban densities have higher numbers of deaths and long-distance frequent trips can contribute to spread of the disease.

Executive summary: Updates to the dietary treatment of prediabetes and type 2 diabetes mellitus. / Resumen ejecutivo: actualización en el tratamiento dietético de la prediabetes y la diabetes mellitus tipo 2.

Adequate lifestyle changes significantly reduce the cardiovascular risk factors associated with prediabetes and type 2 diabetes mellitus. Therefore, healthy eating habits, regular physical activity, abstaining from using tobacco, and good sleep hygiene are recommended for managing these conditions. There is solid evidence that diets that are plant-based; low in saturated fatty acids, cholesterol, and sodium; and high in fiber, potassium, and unsaturated fatty acids are beneficial and reduce the expression of cardiovascular risk factors in these subjects. In view of the foregoing, the Mediterranean diet, the DASH diet, a low-carbohydrate diet, and a vegan-vegetarian diet are of note. Additionally, the relationship between nutrition and these metabolic pathologies is fundamental in targeting efforts to prevent weight gain, reducing excess weight in the case of individuals with overweight or obesity, and personalizing treatment to promote patient empowerment. This document is the executive summary of an updated review that includes the main recommendations for improving dietary nutritional quality in people with prediabetes or type 2 diabetes mellitus. The full review is available on the webpages of the Spanish Society of Arteriosclerosis, the Spanish Diabetes Society, and the Spanish Society of Internal Medicine.

[Solving one of the pieces of the puzzle: COVID-19 and type 2 diabetes]. / Resolviendo una de las piezas del puzle: COVID-19 y diabetes tipo 2.

The emergence of the COVID-19 pandemic represents an enormous challenge. Given the considerable presence of type 2 diabetes mellitus in the current population, the pandemic is a health issue that requires an effort to provide better responses to our patients who are more vulnerable to the onset of infection and who are candidates for presenting more severe symptoms. This document attempts to address the relationship between COVID-19 infection and type 2 diabetes mellitus. To this end, we will briefly analyse whether the epidemiological data support this association and, subsequently, go in depth on the pathophysiological mechanisms that might connect the 2 diseases.

Obesity is a chronic disease. Positioning statement of the Diabetes, Obesity and Nutrition Workgroup of the Spanish Society of Internal Medicine (SEMI) for an approach centred on individuals with obesity. / La obesidad es una enfermedad crónica. Posicionamiento del grupo de trabajo de Diabetes, Obesidad y Nutrición de la Sociedad Española de Medicina Interna (SEMI) por un abordaje centrado en la persona con obesidad.

INTRODUCTION: Obesity is a chronic, complex and multifactorial metabolic disease involved in the development of chronic noncommunicable diseases such as type 2 diabetes mellitus, cardiovascular disease and cancer. The care of individuals with obesity is an essential part of the holistic approach provided by internal medicine to patients. MATERIAL AND METHODS: Between September 2019 and January 2020, we distributed an online survey to the members of the Spanish Society of Internal Medicine. We prepared a Strengths, Weaknesses, Opportunities, and Threats analysis using the responses and, using the nominal group technique, developed the recommendations. RESULTS: We obtained 599 responses. The respondents mean age was 44.4±11 years, and 52.1% were women. Some 91.8% of the internists evaluate their patients to rule out the comorbidities associated with obesity, mainly type 2 diabetes mellitus (96.2%), cardiovascular disease (88.9%) and obesity-associated hypoventilation syndrome (73%), among others. Some 79.9% provided indications on lifestyle changes. Some 64.1% and 74.9% of the respondents knew the indications for the drugs and bariatric surgery, respectively. Some 93.8% and 83% of the respondents considered obesity and excess weight a chronic disease, and 88.7% considered it a disease of specific interest to internists, who should take an active and leading role in its treatment (85.3%). CONCLUSIONS: The objective of the present document is to determine the degree of understanding and sensitivity of internists regarding the management of obesity and to develop a consensus of recommendations for the Spanish Society of Internal Medicine based on the scientific evidence and the opinion of its members.

Dietary fat may modulate adipose tissue homeostasis through the processes of autophagy and apoptosis.

PURPOSE: Obesity increases the risk of cardiovascular disease, type 2 diabetes mellitus and cancer development. Autophagy and apoptosis are critical processes for development and homeostasis in multicellular organisms and have been linked to a variety of disorders. We aimed to investigate whether the quantity and quality of dietary fat can influence these processes in the adipose tissue of obese people. METHODS: A randomized, controlled trial within the LIPGENE study assigned 39 obese people with metabolic syndrome to 1 of 4 diets: (a) a high-saturated fatty acid diet, (b) a high-monounsaturated fatty acid (HMUFA) diet, and (c, d) two low-fat, high-complex carbohydrate diets supplemented with long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) or placebo (LFHCC), for 12 weeks each. RESULTS: We found an increase in the expression of autophagy-related BECN1 and ATG7 genes after the long-term consumption of the HMUFA diet (p = 0.001 and p = 0.004, respectively) and an increase in the expression of the apoptosis-related CASP3 gene after the long-term consumption of the LFHCC and LFHCC n-3 diets (p = 0.001 and p = 0.029, respectively). CASP3 and CASP7 gene expression changes correlated with HOMA index. CONCLUSION: Our results suggest that the processes of autophagy and apoptosis in adipose tissue may be modified by diet and that the consumption of a diet rich in monounsaturated fat may contribute to adipose tissue homeostasis by increasing autophagy. They also reinforce the notion that apoptosis in adipose tissue is linked to insulin resistance. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00429195.

Hepatic insulin resistance both in prediabetic and diabetic patients determines postprandial lipoprotein metabolism: from the CORDIOPREV study.

BACKGROUND/AIMS: Previous evidences have shown the presence of a prolonged and exaggerated postprandial response in type 2 diabetes mellitus (T2DM) and its relation with an increase of cardiovascular risk. However, the response in prediabetes population has not been established. The objective was to analyze the degree of postprandial lipemia response in the CORDIOPREV clinical trial (NCT00924937) according to the diabetic status. METHODS: 1002 patients were submitted to an oral fat load test meal (OFTT) with 0.7 g fat/kg body weight [12 % saturated fatty acids (SFA), 10 % polyunsaturated fatty acids (PUFA), 43 % monounsaturated fatty acids (MUFA), 10 % protein and 25 % carbohydrates]. Serial blood test analyzing lipid fractions were drawn at 0, 1, 2, 3 and 4 h during postprandial state. Postprandial triglycerides (TG) concentration at any point >2.5 mmol/L (220 mg/dL) has been established as undesirable response. We explored the dynamic response in 57 non-diabetic, 364 prediabetic and 581 type 2 diabetic patients. Additionally, the postprandial response was evaluated according to basal insulin resistance subgroups in patients non-diabetic and diabetic without pharmacological treatment (N = 642). RESULTS: Prevalence of undesirable postprandial TG was 35 % in non-diabetic, 48 % in prediabetic and 59 % in diabetic subgroup, respectively (p < 0.001). Interestingly, prediabetic patients displayed higher plasma TG and large triacylglycerol-rich lipoproteins (TRLs-TG) postprandial response compared with those non-diabetic patients (p < 0.001 and p = 0.003 respectively). Moreover, the area under the curve (AUC) of TG and AUC of TRLs-TG was greater in the prediabetic group compared with non-diabetic patients (p < 0.001 and p < 0.005 respectively). Patients with liver insulin resistance (liver-IR) showed higher postprandial response of TG compared with those patients with muscle-IR or without any insulin-resistance respectively (p < 0.001). CONCLUSIONS: Our findings demonstrate that prediabetic patients show a lower phenotypic flexibility after external aggression, such as OFTT compared with nondiabetic patients. The postprandial response increases progressively according to non-diabetic, prediabetic and type 2 diabetic state and it is higher in patients with liver insulin-resistance. To identify this subgroup of patients is important to treat more intensively in order to avoid future cardiometabolic complications.

A gene variation (rs12691) in the CCAT/enhancer binding protein α modulates glucose metabolism in metabolic syndrome.

BACKGROUND AND AIMS: CCAAT/enhancer-binding protein alpha (CEBPA) is a transcription factor involved in adipogenesis and energy homeostasis. Caloric restriction reduces CEBPA protein expression in patients with metabolic syndrome (MetS). A previous report linked rs12691 SNP in CEBPA to altered concentration of fasting triglycerides. Our objective was to assess the effects of rs12691 in glucose metabolism in Metabolic Syndrome (MetS) patients. METHODS AND RESULTS: Glucose metabolism was assessed by static (glucose, insulin, adiponectin, leptin and resistin plasma concentrations) and dynamic (disposition index, insulin sensitivity index, HOMA-IR and acute insulin response to glucose) indices, performed at baseline and after 12 weeks of 4 dietary interventions (high saturated fatty acid (SFA), high monounsaturated fatty acid (MUFA), low-fat and low-fat-high-n3 polyunsaturated fatty acid (PUFA)) in 486 subjects with MetS. Carriers of the minor A allele of rs12691 had altered disposition index (p = 0.0003), lower acute insulin response (p = 0.005) and a lower insulin sensitivity index (p = 0.025) indicating a lower insulin sensitivity and a lower insulin secretion, at baseline and at the end of the diets. Furthermore, A allele carriers displayed lower HDL concentration. CONCLUSION: The presence of the A allele of rs12691 influences glucose metabolism of MetS patients.

[Survival analysis]. / Análisis de supervivencia.

Survival analysis is a statistical method that assesses the time between an initial event (inclusion of the subject in the study) and a final event, which occurs when the subject presents a previously defined characteristic. Its objective is to estimate, taking into account the time variable, the probability of a certain event occurring. It has the particularity of accepting incomplete participation times and assuming that all the factors involved in the study are homogeneous. There are several methods to calculate the probability of survival, the most used are the Kaplan-Meier and the actuarial.

Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patients.

The low-grade inflammation observed in obesity has been associated with a high-fat diet, though this relation is not fully understood. Bacterial endotoxin, produced by gut microbiota, may be the linking factor. However, this has not been confirmed in obese patients. To study the relationship between a high-fat diet and bacterial endotoxin, we analyzed postprandial endotoxemia in morbidly obese patients after a fat overload. The endotoxin levels were determined in serum and the chylomicron fraction at baseline and 3 h after a fat overload in 40 morbidly obese patients and their levels related with the degree of insulin resistance and postprandial hypertriglyceridemia. The morbidly obese patients with the highest postprandial hypertriglyceridemia showed a significant increase in lipopolysaccharide (LPS) levels in serum and the chylomicron fraction after the fat overload. Postprandial chylomicron LPS levels correlated positively with the difference between postprandial triglycerides and baseline triglycerides. There were no significant correlations between C-reactive protein (CRP) and LPS levels. The main variables contributing to serum LPS levels after fat overload were baseline and postprandial triglyceride levels but not glucose or insulin resistance. Additionally, superoxide dismutase activity decreased significantly after the fat overload. Postprandial LPS increase after a fat overload is related to postprandial hypertriglyceridemia but not to degree of insulin resistance in morbidly obese patients.

Body mass interacts with fat quality to determine the postprandial lipoprotein response in healthy young adults.

BACKGROUND AND AIMS: Postprandial lipemia predicts the evolution of cardiovascular disease. Obesity is associated with an increase in the magnitude of postprandial lipemia. Our objective was to evaluate the influence of body mass index (BMI) on the effects of acute ingestion of different types of fat on the postprandial lipemic response. METHODS AND RESULTS: Twenty-one healthy men followed a 4-week baseline diet and then consumed three fat-loaded meals that included 1g fat/kg body wt (65%fat) according to a randomized crossover design. The compositions of the three meals were olive oil meal (22% saturated fatty acids (SFA), 38% monounsaturated fatty acids (MUFA), 4% polyunsaturated fatty acids (PUFA)); butter meal (35% SFA, 22% MUFA, 4% PUFA); walnuts meal (20% SFA, 24% MUFA, 16% PUFA, and 4% α-linolenic acid). Higher-weight (HW) subjects (BMI greater than the median 26.18 kg/m(2), n = 11) presented higher incremental area under the curve (iAUC) for triglycerides (TG), both in large- and small-TG rich lipoproteins (TRL) than lower-weight (LW) subjects (BMI<26.18 kg/m(2), n = 10) (p<0.05), and a similar trend for plasma TG (p = 0.084). Moreover, HW subjects presented higher concentrations for small TRL-cholesterol and small TRL-TG in different timepoints of the postprandial lipemia after the intake of enriched walnuts or butter meals compared with the olive oil-enriched meal (p < 0.05) No significant differences were observed between the three types of meals in the postprandial response of LW subjects. CONCLUSION: HW subjects present a greater postprandial response than LW subjects, and they benefit from the consumption of monounsaturated fatty acids from olive oil, to lower their levels of TRL particles during the postprandial state.

SEA 2022 Standards for Global Control of Cardiovascular Risk. / Estándares SEA 2022 para el control global del riesgo cardiovascular.

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to better knowledge of vascular disease, its prevention and treatment. It is well known that cardiovascular diseases are the leading cause of death in our country and entail a high degree of disability and health care costs. Arteriosclerosis is a multifactorial disease and therefore its prevention requires a global approach that takes into account the different risk factors with which it is associated. Therefore, this document summarizes the current level of knowledge and includes recommendations and procedures to be followed in patients with established cardiovascular disease or at high vascular risk. Specifically, this document reviews the main symptoms and signs to be evaluated during the clinical visit, the laboratory and imaging procedures to be routinely requested or requested for those in special situations. It also includes vascular risk estimation, the diagnostic criteria of the different entities that are cardiovascular risk factors, and makes general and specific recommendations for the treatment of the different cardiovascular risk factors and their final objectives. Finally, the document includes aspects that are not usually referenced in the literature, such as the organization of a vascular risk consultation.

Consumption of diets with different type of fat influences triacylglycerols-rich lipoproteins particle number and size during the postprandial state.

BACKGROUND AND AIMS: Previous evidence suggests that dietary fat could influence the composition and size of triacylglycerols-rich lipoproteins (TRL). In a controlled intervention study on healthy subjects, we evaluated the influence of 3 dietary interventions, with different types of fat on postprandial TRL particle size and number. METHODS AND RESULTS: Volunteers followed three different diets for four weeks each, according to a randomized crossover design. Western diet: 15% protein, 47% carbohydrates (CHO), 38% fat (22% saturated fatty acid (SFA)); Mediterranean diet: 15% protein, 47% CHO, 38% fat (24% monounsaturated fatty acid (MUFA)); high CHO enriched with ALNA diet: 15% protein, 55% CHO, <30% fat (8% polyunsaturated fatty acid (PUFA)). After a 12-h fast, volunteers consumed a breakfast with 1g fat and 7 mg cholesterol per kg body weight and a fat composition similar to that consumed in each of the diets: Butter meal: 35% SFA; Olive oil meal: 36% MUFA; Walnut meal: 16% PUFA, 4% α-linolenic acid. Tryglicerides (TG) in TRL (large and small TRL) were determined by ultracentrifugation and size and number of lipoprotein particles were measured with Nuclear Magnetic Resonance Spectroscopy at different time points. The olive oil meal reduced the number of total TRL postprandial particles compared with the other meals (P=0.002). Moreover, the olive oil meal also increased the TRL particle size compared with the walnut meal (P=0.001). CONCLUSION: Our data showed that short-term intake of the Mediterranean diet and the acute intake of an olive oil meal lead to the formation of a reduced number and higher-size TRL particle compared with other fat sources. These novel findings have implications for understanding the postprandial lipoprotein mechanisms, and could favour the lower cardiovascular risk in Mediterranean countries.

Polymorphism at the TRIB1 gene modulates plasma lipid levels: insight from the Spanish familial hypercholesterolemia cohort study.

BACKGROUND AND AIMS: rs17321515 SNP has been associated with variation in LDL-C, high density lipoprotein cholesterol and triglycerides concentrations. This effect has never been studied in patients with severe hypercholesterolemia. Therefore, our aims were to assess the association of the rs17321515 (TRIB1) SNP with plasma lipids concentrations and anthropometric variables and to explore the interaction between this SNP and some classic risk factors in patients with familial hypercholesterolemia (FH). METHODS AND RESULTS: rs17321515 SNP was genotyped in 531 subjects with genetic diagnosis of FH. Homozygous A/A had significantly higher waist circumference compared with G/G subjects (P = 0.006) and carriers of the minor allele G (P = 0.039). Interestingly, smokers homozygous for the A allele displayed higher plasma triglycerides concentrations (P = 0.029), higher VLDL-C levels (P = 0.023) and higher TC/HDL-C ratio (P = 0.035) than carriers of the minor allele G. In addition, homozygous A/A with the presence of arcus cornealis displayed lower plasma ApoA-I levels (P = 0.024) and higher TC/HDL-C ratio (P = 0.046) than carriers of the minor allele G. CONCLUSIONS: Smoking status and presence of arcus cornealis modulate the effect of rs17321515 (TRIB1) polymorphism on plasma lipids levels in patients with FH. These results could explain the differences in the susceptibility to coronary heart disease in these patients.

Executive summary: Updates to the dietary treatment of prediabetes and type 2 diabetes mellitus. / Resumen ejecutivo: actualización en el tratamiento dietético de la prediabetes y la diabetes mellitus tipo 2.

Adequate lifestyle changes significantly reduce the cardiovascular risk factors associated with prediabetes and type 2 diabetes mellitus. Therefore, healthy eating habits, regular physical activity, abstaining from using tobacco, and good sleep hygiene are recommended for managing these conditions. There is solid evidence that diets that are plant-based; low in saturated fatty acids, cholesterol, and sodium; and high in fiber, potassium, and unsaturated fatty acids are beneficial and reduce the expression of cardiovascular risk factors in these subjects. In view of the foregoing, the Mediterranean diet, the DASH diet, a low-carbohydrate diet, and a vegan-vegetarian diet are of note. Additionally, the relationship between nutrition and these metabolic pathologies is fundamental in targeting efforts to prevent weight gain, reducing excess weight in the case of individuals with overweight or obesity, and personalizing treatment to promote patient empowerment. This document is the executive summary of an updated review that includes the main recommendations for improving dietary nutritional quality in people with prediabetes or type 2 diabetes mellitus. The full review is available on the webpages of the Spanish Society of Arteriosclerosis, the Spanish Diabetes Society, and the Spanish Society of Internal Medicine.

Executive summary: Updates to the dietary treatment of prediabetes and type 2 diabetes mellitus.

Adequate lifestyle changes significantly reduce the cardiovascular risk factors associated with prediabetes and type 2 diabetes mellitus. Therefore, healthy eating habits, regular physical activity, abstaining from using tobacco, and good sleep hygiene are recommended for managing these conditions. There is solid evidence that diets that are plant-based; low in saturated fatty acids, cholesterol, and sodium; and high in fiber, potassium, and unsaturated fatty acids are beneficial and reduce the expression of cardiovascular risk factors in these subjects. In view of the foregoing, the Mediterranean diet, the DASH diet, a low-carbohydrate diet, and a vegan-vegetarian diet are of note. Additionally, the relationship between nutrition and these metabolic pathologies is fundamental in targeting efforts to prevent weight gain, reducing excess weight in the case of individuals with overweight or obesity; and personalizing treatment to promote patient empowerment. This document is the executive summary of an updated review that includes the main recommendations for improving dietary nutritional quality in people with prediabetes or type 2 diabetes mellitus. The full review is available on the webpages of the Spanish Society of Arteriosclerosis (SEA, for its initials in Spanish), the Spanish Diabetes Society (SED, for its initials in Spanish), and the Spanish Society of Internal Medicine (SEMI, for its initials in Spanish).

Obesity is a chronic disease. Positioning statement of the Diabetes, Obesity and Nutrition Workgroup of the Spanish Society of Internal Medicine (SEMI) for an approach centred on individuals with obesity.

BACKGROUND: Obesity is a chronic, complex and multifactorial metabolic disease involved in the development of chronic noncommunicable diseases such as type 2 diabetes mellitus, cardiovascular disease and cancer. The care of individuals with obesity is an essential part of the holistic approach provided by internal medicine to patients. MATERIAL AND METHODS: Between September 2019 and January 2020, we distributed an online survey to the members of the Spanish Society of Internal Medicine. We prepared a Strengths, Weaknesses, Opportunities, and Threats analysis using the responses and, using the nominal group technique, developed the recommendations. RESULTS: We obtained 599 responses. The respondents mean age was 44.4 ±â€¯11 years, and 52.1% were women. Some 91.8% of the internists evaluate their patients to rule out the comorbidities associated with obesity, mainly type 2 diabetes mellitus (96.2%), cardiovascular disease (88.9%) and obesity-associated hypoventilation syndrome (73%), among others. Some 79.9% provided indications on lifestyle changes. Some 64.1% and 74.9% of the respondents knew the indications for the drugs and bariatric surgery, respectively. Some 93.8% and 83% of the respondents considered obesity and excess weight a chronic disease, and 88.7% considered it a disease of specific interest to internists, who should take an active and leading role in its treatment (85.3%). CONCLUSIONS: The objective of the present document is to determine the degree of understanding and sensitivity of internists regarding the management of obesity and to develop a consensus of recommendations for the Spanish Society of Internal Medicine based on the scientific evidence and the opinion of its members.

Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers).

[Solving one of the pieces of the puzzle: COVID-19 and type 2 diabetes]. / Resolviendo una de las piezas del puzle: COVID-19 y diabetes tipo 2.

The emergence of the COVID-19 pandemic represents an enormous challenge. Given the considerable presence of type 2 diabetes mellitus in the current population, the pandemic is a health issue that requires an effort to provide better responses to our patients who are more vulnerable to the onset of infection and who are candidates for presenting more severe symptoms. This document attempts to address the relationship between COVID-19 infection and type 2 diabetes mellitus. To this end, we will briefly analyse whether the epidemiological data support this association and, subsequently, go in depth on the pathophysiological mechanisms that might connect the 2 diseases.