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COVID-19 , Diabetes Mellitus Tipo 2 , Glucemia , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Hemoglobina Glucada/análisis , Control Glucémico , Humanos , Hipoglucemiantes/uso terapéutico , Estudios Retrospectivos , SARS-CoV-2 , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: The aim of this study was to determine the level of awareness of hypoglycemia, the level of fear for hypoglycemia, and the response to hypoglycemic events among insulin-treated diabetes patients from Central and Eastern Europe (CEE). The impact of hypoglycemia on the use of healthcare resources and patient productivity was also assessed. METHODS: This was a multicenter, non-interventional, two-part, patient self-reported questionnaire study that comprised both a retrospective cross-sectional evaluation and a prospective observational evaluation. Study participants were insulin-treated adult patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) from CEE. RESULTS: Most patients (85.4% T1DM and 83.6% T2DM) reported normal hypoglycemia awareness. The median hypoglycemia fear score was 5 out of 10 for T1DM and 4 out of 10 for T2DM patients. Patients increased glucose monitoring, consulted a doctor/nurse, and/or reduced the insulin dose in response to hypoglycemia. As a consequence of hypoglycemia, patients took leave from work/studies or arrived late and/or left early. Hospitalization was required for 31 (1.2%) patients with T1DM and 66 (2.1%) patients with T2DM. CONCLUSION: Hypoglycemia impacts patients' personal and social functioning, reduces productivity, and results in additional costs, both direct (related to increased use of healthcare resources) and indirect (related to absenteeism. FUNDING: Novo Nordisk.
RESUMEN
OBJECTIVE: We evaluated the addition of liraglutide to metformin in type 2 diabetes followed by intensification with basal insulin (detemir) if glycated hemoglobin (A1C) ≥7%. RESEARCH DESIGN AND METHODS: In 988 participants from North America and Europe uncontrolled on metformin ± sulfonylurea, sulfonylurea was discontinued and liraglutide 1.8 mg/day added for 12 weeks (run-in). Subsequently, those with A1C ≥7% were randomized 1:1 to 26 weeks' open-label addition of insulin detemir to metformin + liraglutide (n = 162) or continuation without insulin detemir (n = 161). Patients achieving A1C <7% continued unchanged treatment (observational arm). The primary end point was A1C change between randomized groups. RESULTS: Of 821 participants completing the run-in, 61% (n = 498) achieved A1C <7% (mean change -1.3% from 7.7% at start), whereas 39% (n = 323) did not (-0.6% from 8.3% at start). During run-in, 167 of 988 (17%) withdrew; 46% of these due to gastrointestinal adverse events. At week 26, A1C decreased further, by 0.5% (from 7.6% at randomization) with insulin detemir (n = 162) versus 0.02% increase without insulin detemir (n = 157) to 7.1 and 7.5%, respectively (estimated treatment difference -0.52 [95% CI -0.68 to -0.36]; P < 0.0001). Forty-three percent of participants with insulin detemir versus 17% without reached A1C <7%. Mean weight decreased by 3.5 kg during run-in, then by 0.16 kg with insulin detemir or 0.95 kg without insulin detemir. In the randomized phase, no major hypoglycemia occurred and minor hypoglycemia rates were 0.286 and 0.029 events per participant-year with and without insulin detemir (9.2 vs. 1.3%). CONCLUSIONS: Supplementation of metformin with liraglutide and then insulin detemir was well tolerated in the majority of patients, with good glycemic control, sustained weight loss, and very low hypoglycemia rates.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/uso terapéutico , Insulina de Acción Prolongada/uso terapéutico , Metformina/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Femenino , Péptido 1 Similar al Glucagón/administración & dosificación , Péptido 1 Similar al Glucagón/uso terapéutico , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Insulina Detemir , Insulina de Acción Prolongada/administración & dosificación , Liraglutida , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Unlike most antihyperglycaemic drugs, glucagon-like peptide-1 (GLP-1) receptor agonists have a glucose-dependent action and promote weight loss. We compared the efficacy and safety of liraglutide, a human GLP-1 analogue, with exenatide, an exendin-based GLP-1 receptor agonist. METHODS: Adults with inadequately controlled type 2 diabetes on maximally tolerated doses of metformin, sulphonylurea, or both, were stratified by previous oral antidiabetic therapy and randomly assigned to receive additional liraglutide 1.8 mg once a day (n=233) or exenatide 10 microg twice a day (n=231) in a 26-week open-label, parallel-group, multinational (15 countries) study. The primary outcome was change in glycosylated haemoglobin (HbA(1c)). Efficacy analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00518882. FINDINGS: Mean baseline HbA(1c) for the study population was 8.2%. Liraglutide reduced mean HbA(1c) significantly more than did exenatide (-1.12% [SE 0.08] vs -0.79% [0.08]; estimated treatment difference -0.33; 95% CI -0.47 to -0.18; p<0.0001) and more patients achieved a HbA(1c) value of less than 7% (54%vs 43%, respectively; odds ratio 2.02; 95% CI 1.31 to 3.11; p=0.0015). Liraglutide reduced mean fasting plasma glucose more than did exenatide (-1.61 mmol/L [SE 0.20] vs -0.60 mmol/L [0.20]; estimated treatment difference -1.01 mmol/L; 95% CI -1.37 to -0.65; p<0.0001) but postprandial glucose control was less effective after breakfast and dinner. Both drugs promoted similar weight losses (liraglutide -3.24 kg vs exenatide -2.87 kg). Both drugs were well tolerated, but nausea was less persistent (estimated treatment rate ratio 0.448, p<0.0001) and minor hypoglycaemia less frequent with liraglutide than with exenatide (1.93 vs 2.60 events per patient per year; rate ratio 0.55; 95% CI 0.34 to 0.88; p=0.0131; 25.5%vs 33.6% had minor hypoglycaemia). Two patients taking both exenatide and a sulphonylurea had a major hypoglycaemic episode. INTERPRETATION: Liraglutide once a day provided significantly greater improvements in glycaemic control than did exenatide twice a day, and was generally better tolerated. The results suggest that liraglutide might be a treatment option for type 2 diabetes, especially when weight loss and risk of hypoglycaemia are major considerations. FUNDING: Novo Nordisk A/S.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/uso terapéutico , Péptidos/uso terapéutico , Ponzoñas/uso terapéutico , Análisis de Varianza , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Exenatida , Femenino , Péptido 1 Similar al Glucagón/efectos adversos , Péptido 1 Similar al Glucagón/agonistas , Péptido 1 Similar al Glucagón/química , Péptido 1 Similar al Glucagón/uso terapéutico , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/química , Inyecciones Subcutáneas , Modelos Lineales , Liraglutida , Modelos Logísticos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Péptidos/efectos adversos , Péptidos/química , Resultado del Tratamiento , Ponzoñas/efectos adversos , Ponzoñas/química , Pérdida de Peso/efectos de los fármacosRESUMEN
BACKGROUND: The mutation of the IRS-1 gene is one of the genetic risk factors which, it is speculated, is associated with insulin resistance or predisposition to type 2 diabetes. The aim of our study was to evaluate the association between the Gly972Arg polymorphism in the IRS-1 gene and birth weight in newborn children with adequate gestational age. MATERIAL AND METHODS: 100 newborn children with adequate gestational age (38-42 weeks), whose mother had no disorders during pregnancy, were studied. Genomic DNA was extracted from umbilical cord blood leukocytes, and Gly972Arg polymorphism in the IRS-1 gene was genotyped using the PCR-based method. RESULTS: Birth weight was significantly lower in the newborn with the IRS-1 Gly972Arg polymorphism compared with a control group (3161.75 +/- 380.86 g vs. 3427.92 +/- 468.86 g). Body length and head circumference at birth were also lower in the neonates with that polymorphism (54.38 +/- 3.13 cm vs. 52.69 +/- 2.91 cm, and 34.08 +/- 1.47 vs. 33.63 +/- 0.81, respectively). CONCLUSIONS: The results suggest that the Gly972Arg genotype is associated with lower birth weight, body length and head circumference in neonates with adequate gestational age.
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Proteínas Adaptadoras Transductoras de Señales/genética , Peso al Nacer/genética , Recién Nacido Pequeño para la Edad Gestacional/fisiología , Resistencia a la Insulina/genética , Polimorfismo Genético , Receptor de Insulina/genética , Diabetes Mellitus Tipo 2/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Recién Nacido , Proteínas Sustrato del Receptor de Insulina , Masculino , MutaciónAsunto(s)
Hipertensión/genética , Peptidil-Dipeptidasa A/genética , Riñón Poliquístico Autosómico Dominante/genética , Polimorfismo Genético , Insuficiencia Renal/genética , Adulto , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Hipertensión/diagnóstico , Hipertensión/etiología , Masculino , Persona de Mediana Edad , Riñón Poliquístico Autosómico Dominante/complicaciones , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/etiologíaRESUMEN
BACKGROUND: In previous reports of end-stage renal disease (ESRD) patients, family history of ESRD was associated with race, younger age, higher education levels and ESRD etiology. This study aimed to analyze how often Polish caucasian dialysis patients reported relatives with ESRD, and to evaluate which risk factors are associated with family history of ESRD. METHODS: 4808 ESRD patients provided data about renal disease etiology, diabetes and hypertensive status of first- and second-degree relatives, socioeconomic status and education level. RESULTS: Reported ESRD etiologies were: chronic glomerular disease, 19.4 %; diabetic nephropathy, 11.3%; interstitial nephritris, 11.2%; hypertension, 7.8%; polycystic kidney disease (PKD), 7.1%; other or no response, 40.0%. Positive ESRD family history was reported by 745 patients (15.5%); positive history of diabetes, 932 (19.4%); hypertension, 1904 (39%). Positive ESRD family history according to kidney disease etiology was: PKD, 53.1%; glomerulonephritis, 12%; diabetic nephropathy, 11.9%; hypertension, 11.8%; interstitial nephritis, 10.8%. PKD as ESRD etiology (odds ratio (OR) 8.06, 95% confidence interval (CI) 6.35-10.23, p < 0.0001), positive family history of diabetes (OR 1.64, 95% CI 1.34-1.99, p < 0.0001) and positive history of hypertension (OR 1.64, 95% CI 1.39-1.95, p < 0.0001), were independently associated with positive ESRD history. Patients with later ESRD onset had a less frequent positive ESRD family history: for ESRD < 45 yrs, 16% (OR 1.0); 45-64 yrs, 14.4% (OR 0.83, 95% CI 0.70-0.99); > or = 65 yrs, 9.2 % (OR 0.5, 95% CI 0.35-0.72). CONCLUSIONS: Results of our study strongly support the contention that familial predisposition contributes to ESRD development.
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Predisposición Genética a la Enfermedad , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/genética , Adulto , Distribución por Edad , Anciano , Estudios de Cohortes , Intervalos de Confianza , Femenino , Humanos , Incidencia , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Linaje , Polonia/epidemiología , Probabilidad , Sistema de Registros , Diálisis Renal , Medición de Riesgo , Distribución por Sexo , Análisis de SupervivenciaRESUMEN
BACKGROUND: Cardiovascular disease is the most common cause of morbidity and mortality among long-term renal transplant recipients, and hyperlipidemia is an important risk factor for the development of cardiovascular and peripheral vascular disease. The prevalence of post-transplantation hyperlipidemia ranges from 16% to 78% of recipients. Lipid-lowering strategy with the use of statins has been shown shown to reduce the cardiovascular risks related to hyperlipidemia, but concomitant use of HMG-CoA reductase inhibitors and cyclosporine A may increase the risk of rhabdomyolysis or myoglobinuric acute graft failure due to drug-drug interactions with cyclosporine A. CASE REPORT: We describe the case of a 53-year-old woman, a renal transplant recipient, who developed rhabdomyolysis following simvastatin lipid-lowering therapy. Immunosuppressive treatment included cyclosporine A, azathioprine and prednisone. After 32 days of simvastatin treatment she was hospitalized for profound muscle pain and weakness with a rise in serum creatine kinase to 60.000 IU/l and serum creatinine to 147 Kmol/l. No further deterioration in renal graft function during hospitalization was observed. 10 days after simvastatin was stopped and the daily CyA dose was reduced the patient was asymptomatic, with serum creatine kinase 67 IU/l and serum creatinine level within normal range. CONCLUSIONS: Renal transplant recipients treated with cyclosporin A, and also receiving statins for postransplantational hyperlipidemia, as well as for the prophylaxis of chronic rejection, should be monitored carefully both for CyA blood levels and for possible muscle toxicity.
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Ciclosporina/uso terapéutico , Hipolipemiantes/efectos adversos , Inmunosupresores/uso terapéutico , Rabdomiólisis/inducido químicamente , Simvastatina/efectos adversos , Adulto , Interacciones Farmacológicas , Femenino , Humanos , Hiperlipidemias/tratamiento farmacológico , Trasplante de RiñónRESUMEN
BACKGROUND/AIMS: There is evidence that hereditary predisposition contributes to the development of diabetic nephropathy and hypertension. Polymorphisms in the genes for bradykinin receptors (B(1)R and B(2)R) were found to be associated with decreased risk of the development of end-stage renal disease. This study examines whether B(1)R G(-699)C and B(2)R C(181)T polymorphisms are associated with microalbuminuria or overt nephropathy, or blood pressure variation in type 2 diabetic subjects. METHODS: B(1)R and B(2)R polymorphisms were determined in 153 type 2 diabetic patients with microalbuminuria, 132 with overt nephropathy (macroalbuminuria or chronic renal failure), and 161 patients with normoalbuminuria despite diabetes duration longer than 10 years. RESULTS: Distributions of the examined polymorphisms did not differ between patients with microalbuminuria or overt nephropathy, compared to normoalbuminuric control subjects. Patients carrying the B(2)R T allele had lower DBP, compared with non-carriers: 83.6 +/- 12.0 vs. 87.4 +/- 12.1 mm Hg, p < 0.05. Among patients not receiving ACEI, both SBP and DBP was significantly lower in B(2)R T allele carriers, compared to non-carriers (137.2 +/- 20.3 vs. 146.5 +/- 21.7 mm Hg, and 80.3 +/- 11.9 vs. 85.8 +/- 11.6 mm Hg, p < 0.05). CONCLUSIONS: Examined polymorphisms are not associated with the increased risk of incipient or overt nephropathy in type 2 diabetic patients. B(2)R C(181)T polymorphism may contribute to blood pressure variation in these subjects.
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Presión Sanguínea/genética , Diabetes Mellitus Tipo 2/genética , Nefropatías Diabéticas/genética , Polimorfismo Genético , Receptores de Bradiquinina/genética , Albuminuria/genética , Albuminuria/orina , Alelos , Estudios de Casos y Controles , Creatinina/orina , Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/orina , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: Type 2 diabetic patients are at increased risk for cardiovascular morbidity and mortality. Increased left ventricular mass also predicts a higher incidence of cardiovascular events. Angiotensin II is a potent mediator of myocardial growth, and angiotensin II can be produced in the heart by angiotensin I-converting enzyme (ACE) and heart chymase (CMA). The aim of this study was to establish the role of ACE gene insertion/deletion (I/D) and CMA gene CMA/B polymorphisms in determining left ventricular mass in type 2 diabetic patients. MATERIAL/METHODS: Echocardiographic measurements, ACE gene I/D and CMA/B genotypes were determined in 154 type 2 diabetic patients. RESULTS: Mean LVMI was higher among DD homozygotes compared to heterozygotes and II homozygotes (128.9 g/m2 vs. 120.5 g/m2 and 120.4 g/m2, respectively), but the difference was not statistically significant (ANOVA P=0.12). A similar effect was observed for the CMA/B polymorphism, where mean LVMI were 126.6 g/m2, 122.1 g/m2 and 118.2 g/m2, for carriers of AA, AG and GG genotype, respectively (not statistically significant, P=0.33). ACE I/D and CMA/B polymorphism were also analyzed jointly, and carriers of both DD and AA genotypes were found to have significantly higher LVMI values (P=0.05) than non-carriers (133.0 g/m2 and 121.2 g/m2, for 21 DD and AA carriers vs. 133 non-carriers). In multivariate analysis, the presence of DD and AA genotypes was independently associated with LVMI (P=0.04). CONCLUSIONS: Our results may suggest the additive effect of ACE and CMA gene polymorphisms on the increase in left ventricular mass in NIDDM patients.
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Diabetes Mellitus Tipo 2/genética , Ventrículos Cardíacos/patología , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Serina Endopeptidasas/genética , Anciano , Quimasas , Diabetes Mellitus Tipo 2/patología , Ecocardiografía , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/enzimología , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los ÓrganosRESUMEN
BACKGROUND: It has been recently suggested that the presence of the methylenetetrahydrofolate reductase gene 677TT genotype is associated with younger age at initiation of dialysis, thus raising a hypothesis that younger renal patients carrying the TT genotype are at higher risk to develop end-stage renal disease. The aim of this study was to test the association between the C677T polymorphism and the presence of end-stage renal disease using a family-based study design. MATERIAL AND METHOD: C677T polymorphism was genotyped in a group of 247 family trios (offspring affected with end-stage renal disease, dialysed or conservatively treated, and both parents). Transmission/disequilibrium test (TDT) was used to evaluate allele transmission from heterozygous parents to affected offspring. RESULTS: The TDT analysis revealed no significant deviation in the transmission of the MTHFR C677T alleles to CRF patients (51 vs. 49% for the C allele and T allele transmission, respectively). We observed a significant relationship between MTHFR genotypes and total plasma homocysteine (tHcy), as well as folate concentration. Also, plasma tHcy and folate were negatively correlated. CONCLUSION: Our results did not show any association between the MTHFR reductase C677T polymorphism and the increased risk of the development of end-stage renal disease. Whether this polymorphism contributes to the faster rate of decline of renal function in renal patients, must be evaluated further.
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Ácido Fólico/sangre , Homocisteína/sangre , Fallo Renal Crónico/sangre , Fallo Renal Crónico/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Factores de Edad , Progresión de la Enfermedad , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Genotipo , Humanos , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Diálisis Renal , Factores de RiesgoRESUMEN
BACKGROUND: The presence of a complex phenotype of type 2 diabetes results from impaired insulin secretion and action, whereas the mechanism of action of sulfonylurea derivatives, most commonly used in the treatment of type 2 diabetes, is based on their ability to directly inhibit the ATP-sensitive potassium channel (KATP), which leads to b-cell depolarization, subsequent influx of calcium and then insulin exocytosis. It has recently been demonstrated in healthy subjects that molecular variants of the gene encoding for the KATP subunit - sulfonylurea receptor gene (SUR1) are associated with a decreased response of insulin secretion to intravenous injection of tolbutamide, a sulfonylurea derivative. In this study we tested whether a molecular variant of the SUR1 gene, 16-3t, has a different distribution in type 2 diabetic patients with early failure of sulfonylurea therapy, compared to patients treatable with sulfonylurea despite long diabetes duration. MATERIAL/METHODS: The SUR1 polymorphism was genotyped in 68 type 2 diabetic patients who required insulin treatment and had known diabetes duration L 5 years, compared to 99 patients receiving oral agents (sulfonylurea alone or in combination with metformin or acarbose) with known diabetes duration of at least 15 years. RESULTS: We observed no significant differences in SUR1 16-3t genotype distributions or allele frequencies between the two examined groups. CONCLUSIONS: Our study provides evidence against a major impact of the SUR1 c16-3t polymorphism on the long-term effectiveness of therapy with sulfonylurea derivatives in type 2 diabetic patients.
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Transportadoras de Casetes de Unión a ATP , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Insulina/uso terapéutico , Polimorfismo Genético , Canales de Potasio de Rectificación Interna , Canales de Potasio/genética , Receptores de Droga/genética , Compuestos de Sulfonilurea/uso terapéutico , Frecuencia de los Genes , Genotipo , Humanos , Polonia , Canales de Potasio/metabolismo , Receptores de Droga/metabolismo , Receptores de Sulfonilureas , Resultado del TratamientoRESUMEN
Genetic factors have been reported to play an important role in the predisposition to development of pregnancy-induced hypertension (PIH). On the other hand, there is strong evidence that genetic factors play important role in the predisposition to essential hypertension. Recently, the plausible "candidate gene" for the development of hypertension is SA gene. The aim of our study was to assess the association of the SA gene with the susceptibility to PIH. For that purpose, the SA gene A1A2 polymorphism was studied in 124 women (median age 28 yrs) suffering from PIH in comparison with 148 healthy pregnant women (median age 28 yrs). Genotyping was performed using methods based on polymerase chain reaction. In this study we found statistically significant more frequent of genotype A1A1 occurrence in the patients with PIH when compared to healthy pregnant controls. The frequency of A1 allele was also significant higher in PIH in comparison with controls (chi 2 test.) Based upon the results of our study we can suspect that the SA gene Pst1 polymorphism is associated with the predisposition to PIH in caucasian women.