RESUMEN
AIM: Cluster of differentiation 81 (CD81) is a cell surface protein involved in cell development, activation, growth, and motility. Recent studies have suggested that CD81 is a marker of dedifferentiated ß-cells under conditions of metabolic stress, such as progressive diabetes. However, the clinical significance of changes in soluble serum CD81 (sCD81) in diabetic individuals remains unknown. The aim of this study was to investigate whether serum sCD81 concentrations differ between subjects with diabetes and normal glucose tolerance (NGT), and whether sCD81 changes during a 75 g oral glucose tolerance test (OGTT). MATERIALS AND METHODS: We recruited 101 subjects who had completed an OGTT. According to the test results, the participants were divided into diabetes mellitus (DM) and NGT groups. Participants with prediabetes were excluded from the analysis. During the OGTT, sCD81 levels were measured at 0 and 120 min. We compared changes in sCD81 between the groups. RESULTS: In the DM group, soluble sCD81 levels were significantly higher at baseline and 120 min in the OGTT compared with the normal group (0.59 (0.22-1.05) ng/mL vs. 0.25 (0.81-0.67) ng/mL, 0.55 (0.17-0.96) ng/mL vs. 0.21 (0.92-0.78) ng/mL, p = 0.006 and 0.029, respectively). The soluble sCD81 levels in the NGT group remained unchanged (p = 0.658), while those in the DM group were significantly decreased during the OGTT (p = 0.003). CONCLUSION: Soluble sCD81 levels were elevated in individuals with type 2 diabetes, such that changes in sCD81 were only observed during the OGTT in the DM group. Soluble sCD81 may have potential as a new diagnostic marker for type 2 diabetes.
RESUMEN
Background: Eicosapentaenoic acid (EPA) is an omega-3 fatty acid that protects against cardiovascular diseases in patients with hypertriglyceridemia and may have pleotropic effects beyond lowering triglycerides. Many degenerative diseases, such as atherosclerosis and diabetes, are related to cellular senescence as a pathophysiological mechanism. We aimed to examine whether EPA could protect vascular endothelial cells under stress conditions against stress-induced accelerated senescence (SIAS). Methods: Cultured human umbilical vein endothelial cells (HUVECs) were exposed to H2O2 as oxidative stress and a high glucose concentration with palmitate as a glucolipotoxic condition. Changes in cell viability, apoptosis, lactate dehydrogenase release, and cell cycle analysis were measured by cell counting kit-8 assay, annexin V/ propidium iodide staining, and enzyme-linked immunosorbent assay, respectively. EPA was applied in stress conditions. The degree of senescence was measured by senescence-associated beta-galactosidase staining and p16 staining using immunofluorescence. Apoptosis and cellular senescence-related proteins were measured by Western blotting. Results: Cultured HUVECs under oxidative and glucolipotoxic stresses revealed accelerated senescence and increased apoptosis. These changes were markedly reversed by EPA administration, and the expressions of apoptosis and cellular senescence-related proteins were reversed by EPA treatment. Conclusion: EPA effectively protects HUVECs against SIAS, which may be one of its pleotrophic effects.
Asunto(s)
Ácido Eicosapentaenoico , Peróxido de Hidrógeno , Humanos , Ácido Eicosapentaenoico/farmacología , Peróxido de Hidrógeno/farmacología , Células Endoteliales de la Vena Umbilical Humana , Estrés Oxidativo , Senescencia Celular , Apoptosis , Células CultivadasRESUMEN
BACKGROUND: Diabetic peripheral polyneuropathy is the most common chronic complication of type 2 diabetes. Neuropathic pain is challenging to manage, and various drugs are required to control it, decreasing treatment adherence. Pregabalin, a ligand that binds to alpha-2-delta subunits of the presynaptic calcium channel, has been approved by the Food and Drug Administration for the treatment of diabetic neuropathic pain. In this study, we will compare the efficacy, safety, treatment satisfaction, and compliance between pregabalin sustained-release (SR) tablets and pregabalin immediate-release (IR) capsules in type 2 diabetic patients with peripheral neuropathic pain. METHODS: This study is a randomized, active-controlled, parallel, open-label, multicenter, phase 4 clinical trial (trial registration NCT05624853). Type 2 diabetic patients with glycosylated hemoglobin below 10% and peripheral neuropathic pain who have been taking pregabalin 150 mg/d or more for more than 4 weeks will be randomly assigned to pregabalin SR tablet (150 mg once a day, n = 65) or pregabalin IR capsule (75 mg twice a day, n = 65) therapy for 8 weeks. The primary outcome will be the efficacy of SR pregabalin after 8 weeks of treatment, which will be assessed by visual analog scale measurements. The secondary outcomes will include changes in several parameters, such as quality of life, treatment satisfaction, quality of sleep, and drug compliance. DISCUSSION: In thus study, we aim to demonstrate that pregabalin SR tablets are associated with better compliance and satisfaction compared with pregabalin IR capsules, despite similar efficacy.
Asunto(s)
Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Neuralgia , Humanos , Pregabalina/uso terapéutico , Preparaciones de Acción Retardada , Analgésicos/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Calidad de Vida , Cápsulas/uso terapéutico , Resultado del Tratamiento , Neuralgia/tratamiento farmacológico , Neuralgia/etiología , Neuropatías Diabéticas/tratamiento farmacológico , Comprimidos , Método Doble CiegoRESUMEN
OBJECTIVE: In patients with type 2 diabetes who were inadequately controlled with metformin and sulphonylurea, we compared the glucose-lowering efficacy, cardiometabolic parameters and safety of two drugs, ipragliflozin, a sodium-glucose cotransporter-2 inhibitor, and sitagliptin, a dipeptidyl peptidase-4 inhibitor. MATERIALS AND METHODS: Patients with 7.5%-9.0% glycated haemoglobin treated with metformin and sulphonylurea were randomly assigned to ipragliflozin (50 mg, n = 70) or sitagliptin (100 mg, n = 70) therapy for 24 weeks. Measures of glycaemic control, fatty liver indices, other metabolic parameters and subclinical atherosclerosis were compared by a paired t-test before and after 24 weeks of treatment. RESULTS: Mean glycated haemoglobin levels decreased from 8.5% to 7.5% in the ipragliflozin group and from 8.5% to 7.8% in the sitagliptin group, resulting in a 0.34% between-group difference (95% confidence interval, 0.10%-0.43%, p = .088). Fasting and postprandial 2-h glucose levels also showed a similar trend, with a greater reduction with ipragliflozin therapy. An increase of over 70% in ketone levels and a decrease in whole body and abdominal fat masses were observed with ipragliflozin treatment. Fatty liver indices also improved with ipragliflozin treatment. Despite no difference in carotid intima-media thickness and ankle-brachial index, ipragliflozin therapy improved flow-mediated vasodilation, reflecting endothelial function, while sitagliptin did not. The safety profile did not differ between the two groups. CONCLUSIONS: Ipragliflozin add-on therapy can be a viable option for better glycaemic control with multiple vascular and metabolic benefits in patients with type 2 diabetes who are inadequately controlled with metformin and sulphonylurea.
Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Hígado Graso , Metformina , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Fosfato de Sitagliptina/efectos adversos , Metformina/efectos adversos , Hemoglobina Glucada , Grosor Intima-Media Carotídeo , Glucemia/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Resultado del Tratamiento , Hipoglucemiantes/efectos adversos , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Compuestos de Sulfonilurea/uso terapéutico , Quimioterapia Combinada , Hígado Graso/tratamiento farmacológicoRESUMEN
Soluble epidermal growth factor receptor (sEGFR) levels are elevated in patients with type 2 diabetes mellitus (T2DM) and positively correlate with blood glucose and cholesterol levels. However, how cholesterol-lowering treatment in patients with T2DM affects the sEGFR level is unknown. Therefore, we investigated the change of serum sEGFR after cholesterol-lowering treatment in type 2 diabetic patients with hypercholesterolemia. This study is a non-randomized, prospective observational study. A total of 115 patients were treated in either the rosuvastatin monotherapy group (R group, 5 mg/day, n = 59) or the rosuvastatin/ezetimibe combination therapy group (RE group, 5 mg/10 mg/day, n = 56) for 12 weeks. We measured serum levels of lipids and sEGFR using an ELISA kit before and after 12 weeks of treatment in each group. The low-density lipoprotein cholesterol (LDL-C) level was significantly reduced (from 130.27 ± 27.09 to 76.24 ± 26.82 mg/dL; P < .001) after 12 weeks of treatment and more so in the RE group than in the R group (from 131.68 ± 28.72 to 87.13 ± 27.04 mg/dL, P < .001 in the R group; from 128.78 ± 25.58 to 64.75 ± 21.52 mg/dL, P < .001 in the RE group; R vs RE group, P < .001). The sEGFR level was significantly decreased after 12 weeks of treatment (from 50.34 ± 13.31 to 45.75 ± 11.54 ng/mL; P = .007). The RE group only showed a significant reduction in the sEGFR level after treatment (from 50.94 ± 12.10 to 44.80 ± 11.36 ng/mL; P = .007). Moreover, the sEGFR level was significantly reduced only when the LDL-C level was significantly reduced (from 50.46 ± 10.66 to 46.24 ± 11.86 ng/mL; P = .043). The serum sEGFR level was significantly reduced by cholesterol-lowering treatment with rosuvastatin alone or rosuvastatin/ezetimibe. We suggested that sEGFR may play a significant role in insulin resistance (IR) and inflammation, which are central pathophysiological mechanisms. We confirmed the possibility of using sEGFR as a biomarker to predict a good response to lipid-lowering treatment in type 2 diabetes patients with hypercholesterolemia.
Asunto(s)
Anticolesterolemiantes , Diabetes Mellitus Tipo 2 , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hipercolesterolemia , Colesterol , LDL-Colesterol , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Quimioterapia Combinada , Receptores ErbB/uso terapéutico , Ezetimiba/uso terapéutico , Humanos , Hipercolesterolemia/tratamiento farmacológico , Rosuvastatina Cálcica/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: The protein encoded by mitogen-inducible gene 6 (MIG6) plays an essential role in the regulation of cholesterol homeostasis and bile acid synthesis in mice. However, the physiological functions of MIG6 remain poorly understood in humans. Therefore, we aimed to evaluate the relationship between the serum MIG6 concentration and low-density lipoprotein (LDL)-cholesterol in patients undergoing cholesterol-lowering treatment. METHODS: We performed a non-randomized, prospective controlled trial. In total, 63 patients with type 2 diabetes and hypercholesterolemia were treated using either rosuvastatin monotherapy or rosuvastatin/ezetimibe combination therapy for 12 weeks. We then compared their serum lipid and MIG6 concentrations before and after treatment. RESULTS: The serum LDL-cholesterol concentration of the participants significantly decreased and the concentration of MIG6 significantly increased during treatment. In addition, higher pre-treatment serum concentrations of MIG6 were associated with larger reductions in LDL-cholesterol, regardless of the therapeutic agent used. CONCLUSIONS: Serum MIG6 concentration significantly increases alongside the reduction in LDL-cholesterol achieved using cholesterol-lowering therapies in patients with diabetes and hypercholesterolemia. This is the first study to provide evidence that MIG6 may be involved in human cholesterol metabolism.CRIS registration number: KCT0003477. https://cris.nih.go.kr.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Anticolesterolemiantes , LDL-Colesterol , Diabetes Mellitus Tipo 2 , Ezetimiba , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hipercolesterolemia , Rosuvastatina Cálcica , Proteínas Supresoras de Tumor , Proteínas Adaptadoras Transductoras de Señales/sangre , Anticolesterolemiantes/uso terapéutico , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Quimioterapia Combinada , Ezetimiba/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/sangre , Hipercolesterolemia/tratamiento farmacológico , Estudios Prospectivos , Rosuvastatina Cálcica/uso terapéutico , Proteínas Supresoras de Tumor/sangreRESUMEN
BACKGROUND: Early diagnosis and treatment of type 2 diabetes can delay the onset of microvascular and macrovascular complications. Therefore, the identification of a novel biomarker for diagnosing diabetes is necessary. In the present study, the role of serum soluble leucine-rich repeats and immunoglobulin like domains 2 (sLRIG2) was investigated as a diagnostic biomarker of type 2 diabetes. METHODS: A total of 240 subjects with newly diagnosed type 2 diabetes (n=80), prediabetes (n=80), or normal glucose tolerance (NGT; n=80) were included in this study. The fasting serum sLRIG2 level was measured using a quantitative sandwich enzyme immunoassay technique with an enzyme-linked immunosorbent assay (ELISA). Serum sLRIG2 levels were compared among the three groups, and the associations of serum sLRIG2 levels with clinical variables were investigated. RESULTS: Serum sLRIG2 levels were significantly higher in subjects with type 2 diabetes (16.7±8.0 ng/mL) than in subjects without diabetes (NGT group: 12.3±5.3 ng/mL, P<0.001; prediabetes group: 13.2±5.8 ng/mL, P=0.002). Glycosylated hemoglobin (HbA1c: r=0.378, P<0.001) and blood glucose (fasting: r=0.421, P<0.001; 2-hour postprandial: r=0.433, P<0.001) correlated more strongly with sLRIG2 than any other clinical variables. CONCLUSIONS: The serum sLRIG2 levels correlated with glucose parameters; thus, sLRIG2 might be a novel diagnostic biomarker for type 2 diabetes.
RESUMEN
Dipeptidyl peptidase (DPP)-4 inhibitors are oral anti-diabetic medications that block the activity of the ubiquitous enzyme DPP-4. Inhibition of this enzyme increases the level of circulating active glucagon-like peptide (GLP)-1 secreted from L-cells in the small intestine. GLP-1 increases the glucose level, dependent on insulin secretion from pancreatic ß-cells; it also decreases the abnormally increased level of glucagon, eventually decreasing the blood glucose level in patients with type 2 diabetes. DPP-4 is involved in many physiological processes other than the degradation of GLP-1. Therefore, the inhibition of DPP-4 may have numerous effects beyond glucose control. In this article, we review the pleiotropic effects of DPP-4 inhibitors beyond glucose control, including their strong beneficial effects on the stress induced accelerated senescence of vascular cells, and the possible clinical implications of these effects.
RESUMEN
Brown adipose tissue (BAT) is an anti-obese and anti-diabetic tissue that stimulates energy expenditure in the form of adaptive thermogenesis through uncoupling protein 1 (UCP1). Mitogen-inducible gene-6 (Mig-6) is a negative regulator of epidermal growth factor receptor (EGFR) that interacts with many cellular partners and has multiple cellular functions. We have recently reported that Mig-6 is associated with diabetes and metabolic syndrome. However, its function in BAT is unknown. We generated a brown adipocyte-specific Mig-6 knock-in mouse (BKI) to examine the role of Mig-6 in BAT. Mig-6 BKI mice had improved glucose tolerance on a normal chow diet. Mig-6 BKI mice also revealed activated thermogenesis and the size of the BAT lipid droplets was reduced. Additionally, Mig-6 regulated cAMP-PKA signaling-induced UCP1 expression in brown adipocytes. Taken together, these results demonstrate that Mig-6 affects glucose tolerance and thermogenesis in BAT.
Asunto(s)
Tejido Adiposo Pardo/metabolismo , Glucosa/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Animales , Homeostasis , Ratones , TermogénesisRESUMEN
BACKGROUND: Dipeptidyl peptidase 4 (DPP-4) inhibitors have been used to treat type 2 diabetes mellitus (T2DM) via inhibition of the enzymatic activity of DPP-4 in degrading active circulating glucagon-like peptide-1. In addition to their glucose-lowering effect, DPP-4 inhibitors have pleiotropic effects. Cellular senescence regarded as important pathophysiological mechanism underlying many degenerative diseases, including atherosclerosis. This study was performed to examine whether the DPP-4 inhibitor, anagliptin, can directly protect against stress-induced accelerated senescence (SIAS) of vascular endothelial cells, regardless of changes in ambient glucose level. METHODS: Cultured human umbilical vein endothelial cells (HUVECs) were exposed to various concentrations of H2O2, and a fixed high concentration of glucose (25 mM) with varying concentrations of palmitate. Changes in cell viability, senescence-associated beta-galactosidase (SA-ß-Gal), p16 protein, markers of endoplasmic reticulum (ER) stress, NOX4, NLRP inflammasome, lactate dehydrogenase (LDH) release and interleukin (IL) 1ß levels were measured by Cell Counting Kit-8 assay, immunofluorescent staining, Western blotting, and enzyme-linked immunosorbent assay, respectively before and after application of anagliptin. RESULTS: The application of oxidative and glucolipotoxic stresses markedly increased the degree of SIAS of HUVECs, represented by increased SA-ß-Gal immunopositivity and p16 protein expression. Aggravation of ER stress and inflammatory response were also observed through increased levels of ATF4, CHOP, peIF2α, NOX4, NLRP inflammasome, LDH, and IL1ß. These changes were markedly reversed by the administration of anagliptin. CONCLUSIONS: The DPP-4 inhibitor anagliptin effectively protects HUVECs against SIAS, suggesting its potential use in the development of new treatment strategies for aging.
RESUMEN
Obesity is a prevalent and complex disease. The prevalence of obesity in Korea increased from 29.7% in 2010 to 35.7% in 2018, with the prevalence of abdominal obesity being 23.8% in 2018. Obesity contributes to medical costs and socioeconomic burden due to associated comorbidities. The treatment and management of obesity is changing based on new clinical evidence. The 2020 Korean Society for the Study of Obesity Guideline for the Management of Obesity in Korea summarizes evidence-based recommendations and treatment guidelines.
RESUMEN
PURPOSE: Androgens are steroid hormones that are very important in the sexual development and the maintenance of male reproductive system, and also have diverse actions in non-reproductive tissues, including potent antioxidant capacity. Type 2 diabetes mellitus is caused by tissue insulin resistance and insufficient insulin secretion from the pancreatic ß-cells. The progressive decline of pancreatic ß-cells in diabetes is closely related with the severity of disease. We wanted to know whether dihydrotestosterone (DHT) can protect insulin secreting pancreatic ß-cells from apoptosis and accelerated senescence induced by oxidative stress. MATERIALS AND METHODS: Cultured INS-1 cells were used. Various concentrations of H2O2 were applied to exert oxidative stresses. The degrees of apoptosis, accelerated senescence, and the changes of the expressions of related signaling molecules after the application of DHT were analyzed by CCK-8, p16 expression, SA-ß-Gal staining, reverse transcription polymerase chain reactions and Western blots. RESULTS: The application of H2O2 significantly increased (p<0.05) the degree of senescence and apoptosis of cultured INS-1 ß-cells. DHT not only showed anti-oxidant protective capacity, but also significantly reduced (p<0.05) the degree of accelerated senescence. CONCLUSIONS: DHT effectively protects pancreatic islet INS-1 ß-cells from H2O2 induced oxidative stress.
RESUMEN
This report presents the status of diabetic neuropathy (DN) in Korea as determined using a National Health Insurance ServiceNational Sample Cohort (NHIS-NSC). Annual prevalences of DN were estimated by age and gender using descriptive statistics. Pharmacological treatments for DN were also analyzed. The annual prevalence of DN increased from 24.9% in 2006 to 26.6% in 2007, and thereafter, gradually subsided to 20.8% in 2015. In most cases, pharmacological treatments involved a single drug, which accounted for 91.6% of total prescriptions in 2015. The most commonly used drugs (in decreasing order) were thioctic acid, an anti-convulsive agent, or a tricyclic antidepressant. In conclusion, the prevalence of DN decreased over the 10-year study period. Thioctic acid monotherapy was usually prescribed for DN. To reduce the socio-economic burden of DN, more attention should be paid to the diagnosis of this condition and to the appropriate management of patients.
Asunto(s)
Diabetes Mellitus , Neuropatías Diabéticas , Estudios de Cohortes , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/epidemiología , Humanos , Programas Nacionales de Salud , Prevalencia , República de Corea/epidemiologíaRESUMEN
Obesity is a serious and growing worldwide health challenge associated with type 2 diabetes mellitus, cardiovascular disease, osteoarthritis, some cancers, sleep apnea, asthma, and nonalcoholic fatty liver. The Korean Society for the Study of Obesity recommends that pharmacotherapy should be considered when intensive lifestyle modifications fail to achieve a weight reduction in obese patients with a body mass index ≥25 kg/m2. Long-term medications for obesity have traditionally fallen into two major categories: centrally acting anorexiant medications and peripherally acting medications, such as orlistat. In this paper, we provide an overview of the anti-obesity medications currently available for the long-term and individualized treatment of obesity.
RESUMEN
AIMS: In 2011, we demonstrated that an individualized health management system employing advanced medical information technology, designated ubiquitous (u)-healthcare, was helpful in achieving glycemic control without hypoglycemia in patients with diabetes. Following this, we generated a new multidisciplinary u-healthcare system by upgrading our clinical decision support system (CDSS) rule engine and integrating a physical activity-monitoring device and dietary feedback into a comprehensive package. METHODS: In a randomized, controlled clinical trial, patients with type 2 diabetes aged over 60 years were assigned randomly to a self-monitored blood glucose (SMBG) group (N = 50) or u-healthcare group (N = 50) for 6 months. The primary endpoint was the proportion of patients achieving glycated hemoglobin (HbA1c) <7 % without hypoglycemia. Changes in body composition and lipid profiles were also investigated. The u-healthcare group was educated to use a specially designed glucometer and an activity monitor that automatically transferred test results to a hospital-based server. An automated CDSS rule engine generated and sent patient-specific messages about glucose, diet, and physical activity to their mobile phones and a Web site. RESULTS: After 6 months of follow-up, the HbA1c level was significantly decreased in the u-healthcare group [8.0 ± 0.7 % (64.2 ± 8.8 mmol/mol) to 7.3 ± 0.9 % (56.7 ± 9.9 mmol/mol)] compared with the SMBG group [8.1 ± 0.8 % (64.9 ± 9.1 mmol/mol) to 7.9 ± 1.2 % (63.2 ± 12.3 mmol/mol)] (P < 0.01). The proportion of patients with HbA1c < 7 % without hypoglycemia was greater in the u-healthcare group (26 %) than in the SMBG group (12 %; P < 0.05). Body fat mass decreased and lipid profiles improved in the u-healthcare group but not in the SMBG group. CONCLUSION: This u-healthcare service provided effective management for older patients with type 2 diabetes (ClinicalTrial.Gov: NCT01137058).
Asunto(s)
Diabetes Mellitus Tipo 2/terapia , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Composición Corporal , Sistemas de Computación , Dieta , Método Doble Ciego , Ejercicio Físico , Retroalimentación , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Ambulatorio , Medicina de Precisión , Telemedicina/métodosRESUMEN
BACKGROUND AND AIM: Effective medicines have not been introduced for insulin resistance-related fatty liver. The efficacy and safety of treatment between a combination of metformin and carnitine-orotate complex and metformin alone in a 12-week, double-blind, randomized, placebo-controlled study on drug-naïve patients with impaired glucose metabolism and fatty liver were compared. METHODS: Fifty-two patients with fasting glucose 100-240 mg/dL or glycosylated hemoglobin (HbA1c) ≥ 6.0% and alanine aminotransferase (ALT) 40-250 IU/L were randomized to receive metformin (250 mg t.i.d.), or metformin (250 mg t.i.d.) and carnitine-orotate complex (300 mg t.i.d.) for 12 weeks (n = 26 per group). The primary end-point was a change from baseline ALT level. Secondary end-points were changes in fasting glucose, HbA1c, aspartate aminotransferase levels, mitochondrial DNA (mtDNA) copy number in the peripheral blood, and urinary output of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress. RESULTS: The combined treatment reduced ALT level significantly more than metformin alone (-51.5 ± 33.2 IU/Lâ vs -16.7 ± 31.3 IU/L, P = 0.001). The HbA1c levels also decreased significantly in both groups but there was no significant difference between them (-0.9% ± 1.0% vs -0.7% ± 0.9%). Treatment with the complex decreased the urinary 8-hydroxy-2'-deoxyguanosine level and increased mtDNA copy number significantly compared with metformin alone (both P < 0.05). No severe adverse events were observed. CONCLUSION: A 12-week treatment with metformin and carnitine-orotate complex significantly improved liver function enzyme levels. This was associated with changes in oxidative stress and mtDNA copy number compared with metformin alone in patients with impaired glucose metabolism and fatty liver (clinical trial number: KCT0000193).
Asunto(s)
Carnitina/administración & dosificación , Hígado Graso/tratamiento farmacológico , Trastornos del Metabolismo de la Glucosa/tratamiento farmacológico , Metformina/administración & dosificación , Ácido Orótico/administración & dosificación , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Glucemia/análisis , Variaciones en el Número de Copia de ADN , ADN Mitocondrial/sangre , ADN Mitocondrial/genética , Método Doble Ciego , Combinación de Medicamentos , Determinación de Punto Final , Ayuno/sangre , Hígado Graso/diagnóstico , Hígado Graso/etiología , Femenino , Trastornos del Metabolismo de la Glucosa/diagnóstico , Trastornos del Metabolismo de la Glucosa/etiología , Hemoglobina Glucada/análisis , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Efecto PlaceboRESUMEN
Age-related body composition changes such as sarcopenia and obesity affect functional decline in the elderly. We investigated the relationship between body composition parameters and functional limitation in older Korean adults. We enrolled 242 men and 231 women aged ≥ 65 yr from the Korean elderly cohort. We used appendicular skeletal muscle mass (ASM) divided by height(2) (ASM/Ht(2)) and ASM divided by weight (ASM/Wt). The isokinetic strength of knee extensor muscles were measured using an isokinetic device. Functional limitations were assessed using the Short Physical Performance Battery (SPPB) score less than nine. Men within the bottom tertile of ASM/Ht(2) confer an increased risk for functional limitation compared with those within the top tertile (OR, 6.24; 95% CI, 1.78-22.0). However, in women, subjects within the lowest ASM/Wt tertile had a higher risk compared with those within the highest tertile instead of ASM/Ht(2) (OR, 7.60; 95% CI, 2.25-25.7). Leg muscle strength remained the strong measure even after controlling for muscle mass only in women. Only large waist circumference was positively associated with functional limitation only in women. We might consider a different muscle index to assess functional limitation according to the gender.
Asunto(s)
Composición Corporal , Rodilla/fisiología , Fuerza Muscular/fisiología , Obesidad/epidemiología , Sarcopenia/epidemiología , Anciano , Envejecimiento , Índice de Masa Corporal , Femenino , Humanos , Masculino , Músculo Esquelético/fisiología , Obesidad/metabolismo , República de Corea/epidemiología , Sarcopenia/metabolismo , Factores Sexuales , Circunferencia de la CinturaRESUMEN
We describe an unusual case of systemic lupus erythematosus with pulmonary manifestations presenting as hypoglycemia due to anti-insulin receptor antibodies. A 38-year-old female suffered an episode of unconsciousness and was admitted to hospital where her blood glucose was found to be 18 mg/dL. During the hypoglycemic episode, her serum insulin level was inappropriately high (2,207.1 pmol/L; normal range, 18 to 173) and C-peptide level was elevated (1.7 nmol/L; normal range, 0.37 to 1.47). Further blood tests revealed the presence of antinuclear antibodies, anti-double-stranded DNA antibodies, and anti-Ro/SSA, anti-La/SSB, anti-ribonucleoprotein, and anti-insulin receptor antibodies. A computed tomography scan of the abdomen, aimed at tumor localization, such as an insulinoma, instead revealed ground-glass opacities in both lower lungs, and no abnormal finding in the abdomen. For a definitive diagnosis of the lung lesion, video-associated thoracoscopic surgery was performed and histopathological findings showed a pattern of fibrotic non-specific interstitial pneumonia.