While still in its infancy, ChatGPT (Generative Pretrained Transformer), introduced in November 2022, is bound to hugely impact many industries, including healthcare, medical education, biomedical ...research, and scientific writing. Implications of ChatGPT, that new chatbot introduced by OpenAI on academic writing, is largely unknown. In response to the Journal of Medical Science (Cureus) Turing Test - call for case reports written with the assistance of ChatGPT, we present two cases one of homocystinuria-associated osteoporosis, and the other is on late-onset Pompe disease (LOPD), a rare metabolic disorder. We tested ChatGPT to write about the pathogenesis of these conditions. We documented the positive, negative, and rather troubling aspects of our newly introduced chatbot's performance.
Triglycerides have long been recognized as a cardiovascular disease risk factor. However, their precise role in atherosclerosis and potential utility as a therapeutic target remains debated topics. ...This review aims to shed light on these aspects by exploring the complex relationship between triglycerides and atherosclerosis from pathophysiological and pharmacological perspectives.
Triglycerides, primarily carried by chylomicrons and very low-density lipoproteins, play an essential role in energy storage and utilization. Dysregulation of triglyceride homeostasis and triglyceride- rich lipoproteins metabolism often leads to hypertriglyceridemia and subsequently increases atherosclerosis risk. Triglyceride-rich lipoproteins remnants interact with arterial wall endothelial cells, get retained in the subendothelial space, and elicit inflammatory responses, thereby accelerating atherogenesis.
Despite the clear association between high triglyceride levels and increased cardiovascular disease risk, intervention trials targeting triglyceride reduction have produced mixed results. We discuss a range of triglyceride-lowering agents, from fibrates to omega-3 fatty acids, with a focus on their mechanism of action, efficacy, and major clinical trial outcomes. Notably, the role of newer agents, such as angiopoietin-like protein 3 and apolipoprotein C3 inhibitors, is also explored. We highlight the challenges and controversies, including the ongoing debate on the causal role of triglyceride in atherosclerosis and the discordant outcomes of recent clinical trials. The potential confounding effects of associated risk factors, such as elevated apolipoprotein B, insulin resistance, and metabolic syndrome, are considered.
In conclusion, this review underscores the importance of a nuanced approach to understanding the role of triglycerides in atherosclerosis and their potential as a therapeutic target. Further research is needed to unravel the complex interplay between triglycerides, triglyceride-rich lipoproteins, and associated factors in atherosclerosis pathogenesis and refine triglyceride-targeted therapeutic strategies.
Cardiovascular diseases and osteoporosis, seemingly unrelated disorders that occur with advanced age, share major pathogenetic mechanisms contributing to accelerated atherosclerosis and bone loss. ...Hyperhomocysteinemia (hHcy) is among these mechanisms that can cause both vascular and bone disease. In its more severe form, hHcy can present early in life as homocystinuria, an inborn error of metabolic pathways of the sulfur-containing amino acid methionine. In its milder forms, hHcy may go undiagnosed and untreated into adulthood. As such, hHcy may serve as a potential therapeutic target for cardiovascular disease, osteoporosis, thrombophilia, and neurodegeneration, collectively representing accelerated aging. Multiple trials to lower cardiovascular risk and improve bone density with homocysteine-lowering agents, yet none has proven to be clinically meaningful. To understand this unmet clinical need, this review will provide mechanistic insight into the pathogenesis of vascular and bone disease in hHcy, using homocystinuria as a model for accelerated atherosclerosis and bone density loss, a model for accelerated aging.
Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Although commonly seen as a milder elevation of homocysteine levels in adult patients, on rare occasions, the internist ...may face extremely elevated homocysteine levels (>100 µmol/L). In such rare cases, the search for a monogenic disease is warranted. In this report, we present a patient with classical homocystinuria, where the diagnosis was delayed due to various factors. The patient experienced a constellation of symptoms over an extended period, including visual problems, recurrent thrombosis, and neurodevelopmental delay. Delayed diagnosis of genetic diseases is problematic, as patients may grow from pediatric care to adult internal medicine, where knowledge and exposure to such a rare genetic disorder are limited. A diagnosis was finally confirmed with amino acid profiling, revealing extremely elevated homocysteine levels, which were reduced with sequential treatment modalities, including folate, vitamin B12, vitamin B6, methionine restriction, and betaine. We also present derangements in other amino acids, namely, methionine, taurine, serine, and urea cycle products. With treatment, a progressive increase in body weight is noticed. Furthermore, we present a novel finding of increased levels of ß-aminoisobutyric acid with homocysteine-lowering treatment. ß-aminisobutyric acid is a myokine that potentiates some of the metabolic benefits of exercising muscle such as improved insulin resistance and browning of white adipose tissue.
Background The prevalence of chronic kidney disease (CKD) is increasing in the United States, caused in part by older age and increasing prevalences of hypertension and type 2 diabetes. CKD is silent ...and undetected until advanced stages. The study of populations with earlier stages of kidney disease may improve outcomes of CKD. Methods The Kidney Early Evaluation Program (KEEP), a National Kidney Foundation program, is a targeted community-based health-screening program enrolling individuals 18 years and older with diabetes, hypertension, or family history of kidney disease, diabetes, or hypertension. Participants who had received transplants or were on regular dialysis treatment were excluded from this analysis. The National Health and Nutrition Examination Survey (NHANES) 1999-2004 was a nationally representative cross-sectional survey; participants were interviewed in their homes and/or received standardized medical examinations in mobile examination centers. Results Of the 61,675 KEEP participants, 16,689 (27.1%) were found to have CKD. In the NHANES sample of 14,632 participants, 2,734 (15.3%) had CKD. Older age, smoking, obesity, diabetes, hypertension, and cardiovascular disease were associated significantly with CKD in both KEEP and NHANES ( P < 0.05 for all). Of note, the likelihood for CKD in African Americans differed between KEEP (odds ratio, 0.81; P < 0.001) and NHANES (odds ratio, 1.10; P = 0.2). Conclusion A greater prevalence of CKD was detected in the KEEP screening than in the NHANES data. KEEP has the limitations common to population-screening studies and conclusions for population-attributable risk may be limited. The targeted nature of the KEEP screening program and the large sample size with clinical characteristics comparable to NHANES validates KEEP as a valuable cohort to explore health associations for the CKD and at-risk-for-CKD populations in the United States.
Metformin: an update Kirpichnikov, Dmitri; McFarlane, Samy I; Sowers, James R
Annals of internal medicine,
07/2002, Letnik:
137, Številka:
1
Journal Article
Recenzirano
Metformin is an insulin-sensitizing agent with potent antihyperglycemic properties. Its efficacy in reducing hyperglycemia in type 2 diabetes mellitus is similar to that of sulfonylureas, ...thiazolidinediones, and insulin. Metformin-based combination therapy is often superior to therapy with a single hypoglycemic agent. The antihyperglycemic properties of metformin are mainly attributed to suppressed hepatic glucose production, especially hepatic gluconeogenesis, and increased peripheral tissue insulin sensitivity. Although the precise mechanism of hypoglycemic action of metformin remains unclear, it probably interrupts mitochondrial oxidative processes in the liver and corrects abnormalities of intracellular calcium metabolism in insulin-sensitive tissues (liver, skeletal muscle, and adipocytes) and cardiovascular tissue.
Background Elderly individuals with chronic kidney disease (CKD) have high rates of comorbid conditions, including cardiovascular disease and its risk factors, and CKD-related complications. In ...individuals aged ≥ 65 years, we sought to describe the prevalence of CKD determined from laboratory test results in the Kidney Early Evaluation Program (KEEP; n = 27,017) and National Health and Nutrition Examination Survey (NHANES) 1999-2006 (n = 5,538) and the prevalence of diagnosed CKD determined from billing codes in the Medicare 5% sample (n = 1,236,946). In all 3 data sources, we also explored comorbid conditions and CKD-related complications. Methods CKD was identified as decreased estimated glomerular filtration rate (<60 mL/min/1.73 m2 ) or increased albumin-creatinine ratio in KEEP and NHANES; CKD was identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes in Medicare. Investigated comorbid conditions included diabetes, hypertension, high cholesterol level, coronary artery disease, congestive heart failure, cerebrovascular disease, peripheral vascular disease, and cancer, and CKD-related complications included anemia, hypocalcemia, hyperphosphatemia, and hyperparathyroidism. Results The prevalence of CKD was ∼44% in both KEEP and NHANES participants, and the prevalence of diagnosed CKD was 7% in Medicare beneficiaries. In all 3 data sets, the prevalence of CKD or diagnosed CKD was higher in participants aged ≥ 80 years and those with comorbid conditions. For KEEP and NHANES participants, the prevalence of most comorbid conditions and CKD complications increased with decreasing estimated glomerular filtration rate. For participants with CKD stages 3-5, a total of 29.2% (95% CI, 27.8-30.6) in KEEP and 19.9% (95% CI, 17.0-23.1) in NHANES had anemia, 0.7% (95% CI, 0.4-0.9) and 0.6% (95% CI, 0.3-1.3) had hypocalcemia, 5.4% (95% CI, 4.7-6.1) and 6.4% (95% CI, 5.1-8.0) had hyperphosphatemia, and 52.0% (95% CI, 50.4-53.6) and 30.0% (95% CI, 25.9-34.3) had hyperparathyroidism, respectively. Conclusions CKD is common in the elderly population and is associated with high frequencies of concomitant comorbid conditions and biochemical abnormalities. Because CKD is not commonly diagnosed, greater emphasis on physician education may be beneficial.
To examine mediating effects of sleep quality and duration on the association between T2D and QoL among Medicare beneficiaries 65+.
Data from the Medicare Health Outcome Survey (2015–2020) were used. ...The outcome was QoL (physical and mental health component-summary scores PCS and MCS) measured by the Veterans-Rand-12. The main predictor was diagnosed T2D. Mediators were sleep duration and sleep quality. The effect modifier was race/ethnicity. Structural Equation Modeling was used to estimate moderated-mediating effects of sleep quality and duration across race/ethnicity.
Of the 746,400 Medicare beneficiaries, 26.7% had T2D, and mean age was 76 years (SD ± 6.9). Mean PCS score was 40 (SD ± 12.2), and mean MCS score was 54.0 (SD ± 10.2). Associations of T2D with PCS and MCS were negative and significant. For all racial/ethnic groups, those with T2D reported lower PCS. For White, Black, Asian, and Hispanic beneficiaries only, those with T2D reported lower MCS. The negative impact of T2D on PCS and MCS was mediated through sleep quality, especially very bad sleep quality.
Improving sleep may lead to improvement in QoL in elderly adults with T2D.
•T2D is associated with lower physical and mental QoL in all racial/ethnic groups.•Bad sleep mediates the T2D-Physical QoL link regardless of race/ethnicity.•Sleep may enhance QoL in elderly adults with T2D depending on their race/ethnicity.
Diabetes and the Eye familiarizes the reader with the relationship between diabetes mellitus and the visual system. It presents a discussion about the diabetes epidemic and the many ways the disease ...can cause vision loss, with several types of vision disorders covered in separate chapters. Information about new frontiers in the treatment of ophthalmic disorders is also presented to reflect the advances being made in the clinic. Key features: - presents detailed coverage of vision loss in diabetes in 12 organized and easy to read chapters - includes a discussion on the diabetes epidemic - covers a wide range of vision disorders, of different parts of the eye - includes information on current practices in eye care and management for diabetic patients - includes information about relevant diagnostic tools This book serves as a useful handbook for medical students, residents in ophthalmology, community and academic ophthalmologists, as well as members of the internal medicine and family practice communities.
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