RESUMEN
BACKGROUND AND AIMS: Basal insulin analogues have a reduced risk of hypoglycaemia compared with NPH insulin, but hypoglycaemia still remains a major impediment to achieving recommended fasting plasma glucose (FPG) targets in patients with diabetes. Insulin degludec (IDeg) is a new basal insulin that forms soluble multihexamers after subcutaneous injection resulting in an ultra-long duration of action and stable glucose-lowering effect. The aim of this analysis was to compare the effect of IDeg on FPG and nocturnal confirmed hypoglycaemia as compared to insulin glargine (IGlar). METHODS AND RESULTS: Data were included from seven phase 3a, randomised, open-label, treat-to-target clinical trials in which once-daily IDeg was compared with once-daily IGlar. Two trials included a total of 957 patients with type 1 diabetes (T1D) and five trials included a total of 3360 patients with type 2 diabetes (T2D); all trials were 26 or 52 weeks in duration. Confirmed hypoglycaemia was defined as plasma glucose <3.1 mmol/L or severe episodes requiring assistance, and nocturnal hypoglycaemia occurred between 00:01 and 05:59. In all trials, the mean end-of-trial FPG was lower for IDeg than IGlar, reaching statistical significance in three trials. Similarly, IDeg was associated with a lower rate of nocturnal confirmed hypoglycaemia vs. IGlar, which was statistically significant in three trials, regardless of type of diabetes or background therapy. CONCLUSION: This analysis shows that the lower rate of nocturnal confirmed hypoglycaemia seen with IDeg relative to IGlar is accompanied by a reduced mean FPG, in particular in patients with T2D.
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Glucemia/análisis , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemia/inducido químicamente , Insulina Glargina/uso terapéutico , Insulina de Acción Prolongada/uso terapéutico , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Ayuno , Humanos , Insulina Glargina/efectos adversos , Insulina de Acción Prolongada/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
AIMS: The efficacy and safety of insulin degludec (IDeg) was compared with insulin detemir (IDet), both administered once daily (OD) as basal treatment in participants with type 1 diabetes mellitus (T1DM). The primary outcome was non-inferiority of IDeg to IDet in glycated haemoglobin (HbA1c) reduction after 26 weeks. METHODS: This multinational, 26-week, controlled, open-label, parallel-group trial randomized adults with T1DM to IDeg or IDet as OD basal insulin treatment combined with mealtime bolus insulin aspart (IAsp). Participants with T1DM treated with any basal-bolus insulin regimen for ≥ 12 months prior to the trial, a mean HbA1c ≤ 10.0% (85.8 mmol/mol) and body mass index (BMI) ≤ 35.0 kg/m(2) at screening participated in the trial (IDeg: N = 302; IDet: N = 153). RESULTS: After 26 weeks, HbA1c decreased 0.73% (8.0 mmol/mol) (IDeg) and 0.65% (7.1 mmol/mol) (IDet) [estimated treatment difference (ETD) IDeg-IDet: -0.09% (-0.23; 0.05)95% CI (-10.0 mmol/mol [-2.6; 0.6]95% CI ); confirming non-inferiority]. Mean fasting plasma glucose improved in both groups, and was lower with IDeg than IDet [ETD IDeg-IDet: -1.66 mmol/l (-2.37; -0.95)95% CI , p < 0.0001]. The rate of confirmed hypoglycaemia was similar with IDeg and IDet [45.83 vs. 45.69 episodes per patient-year of exposure (PYE); estimated rate ratio (RR) IDeg/IDet: 0.98 (0.80; 1.20)95% CI , p = 0.86]. The rate of nocturnal confirmed hypoglycaemia was lower with IDeg than IDet [4.14 vs. 5.93 episodes per PYE; RR IDeg/IDet: 0.66 (0.49; 0.88)95% CI , p = 0.0049]. Adverse event profiles were similar between groups. CONCLUSION: IDeg administered OD in basal-bolus therapy effectively improved long-term glycaemic control in participants with T1DM with a lower risk of nocturnal confirmed hypoglycaemia than IDet.
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Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada/efectos de los fármacos , Hipoglucemiantes/administración & dosificación , Insulina Aspart/administración & dosificación , Insulina de Acción Prolongada/administración & dosificación , Adulto , Análisis de Varianza , Diabetes Mellitus Tipo 1/sangre , Esquema de Medicación , Femenino , Humanos , Masculino , Comidas , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIMS: Assessment of the long-term safety and efficacy of liquid inhaled insulin via AERx insulin Diabetes Management System (iDMS) in a basal/bolus treatment regimen of adults with Type 1 diabetes. METHODS: Patients were randomized 2 : 1 to prandial inhaled (n = 205) or subcutaneous (s.c.) (n = 99) insulin, plus one/two daily injections of neutral protamine Hagedorn (NPH) insulin for 12 months. The primary endpoints were pulmonary function tests (PFT) and baseline changes in chest X-rays at 12 months. Safety and efficacy assessments were measured at regular intervals. RESULTS: PFTs after 12 months were comparable between the groups, except for reduced per cent of predicted carbon monoxide lung diffusing capacity with inhaled insulin (difference: -2.03%, P = 0.04) occurring after the first 3 months and then stabilizing. There were no apparent treatment differences in chest X-rays. Overall risk of hypoglycaemia [risk ratio (RR) 1.02, P = 0.83] and adverse events were comparable between groups. Risk of nocturnal hypoglycaemia was higher in the inhaled group (RR 1.58, P = 0.001). Cough [10% (inhaled); 3% (s.c.)] tended to be mild in nature. Inhaled insulin was non-inferior to s.c. insulin for change in glycated haemoglobin (HbA(1c)) after 12 months [difference 0.18% (CI 95%-0.04; 0.39)]. At trial end, mean laboratory measured fasting plasma glucose was lower in the inhaled group (inhaled 9.2 mmol/l; s.c. 11.7 mmol/l; difference: -2.53 mmol/l, P < 0.001). CONCLUSIONS: The safety and efficacy results in this trial were similar to those reported with other inhaled insulins; however, inhaled insulin using AERx iDMS requires further optimization to reduce nocturnal hypoglycaemia before it has comparable safety and efficacy to s.c. insulin aspart.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Administración por Inhalación , Adulto , Esquema de Medicación , Femenino , Humanos , Inyecciones Subcutáneas/métodos , Masculino , Persona de Mediana Edad , Medición de RiesgoRESUMEN
AIMS: To study whether microalbuminuria, endothelial dysfunction and low-grade inflammation are associated with the presence and progression of diabetic retinopathy. METHODS: Patients with Type 2 diabetes (n = 328) attending a diabetes clinic were followed for 10 years and examined annually during the last 7 years. Retinopathy was assessed after pupillary dilatation by direct ophthalmoscopy (baseline) and two-field 60 degrees fundus photography (follow-up). Urinary albumin excretion, and markers of endothelial function (von Willebrand factor, tissue-type plasminogen activator, soluble E-selectin (sE-selectin), and soluble vascular cell adhesion molecule 1) and inflammatory activity (C-reactive protein and fibrinogen) were determined. RESULTS: The prevalence of retinopathy was 33.8%. The median diabetes duration at baseline was 7 years (interquartile range 2-12 years). The highest tertiles of baseline urinary albumin excretion and glycated haemoglobin (HbA(1c)) were associated with prevalent retinopathy: odds ratio (OR) 95% confidence interval (CI) 2.80 (1.44-5.46) and 2.19 (1.11-4.32), respectively. Progression of retinopathy occurred in 188 patients. The second and third tertiles of baseline sE-selectin were associated with progression of retinopathy [1.44 (1.04-2.01) and 1.61 (1.19-2.18)] but not independently of HbA(1c). None of the other markers was significantly associated with the presence or progression of retinopathy. High baseline HbA(1c) was significantly associated with progression of retinopathy: 1.65 (1.21-2.25). CONCLUSIONS: In this population of patients with Type 2 diabetes who attended a diabetes clinic, there was some evidence for a role of endothelial dysfunction in the progression of retinopathy. We could not demonstrate a role for low-grade inflammation. Our study emphasizes the importance of glycaemic control in the development and progression of retinopathy.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Retinopatía Diabética/diagnóstico , Endotelio Vascular/metabolismo , Vasculitis Retiniana/complicaciones , Vasos Retinianos/metabolismo , Proteína C-Reactiva/análisis , Estudios de Cohortes , Diabetes Mellitus Tipo 2/metabolismo , Retinopatía Diabética/metabolismo , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Vasculitis Retiniana/metabolismoRESUMEN
AIMS: To compare glycaemic control and risk of hypoglycaemia of twice-daily insulin detemir with once-daily insulin glargine in subjects with Type 1 diabetes. METHODS: In this 26-week, multicentre, open-label, parallel-group trial, 320 subjects with Type 1 diabetes received either insulin detemir twice daily or insulin glargine once daily. each in combination with premeal insulin aspart. RESULTS: After 26 weeks, HbA(1c) had decreased from 8.8 to 8.2% in the insulin detemir group and from 8.7 to 8.2% in the insulin glargine group. Home-measured fasting plasma glucose (PG) was lower with insulin glargine than with insulin detemir (7.0 vs. 7.7 mmol/l, P < 0.001). The overall shape of the home-measured nine-point PG profiles was comparable between treatments (P = 0.125). Overall, there was no significant difference in within-subject variation in PG (P = 0.437). Within-subject variation in predinner PG was lower with insulin detemir than with insulin glargine (P < 0.05). The overall risk of hypoglycaemia was similar with no differences in confirmed hypoglycaemia. However, the risk of severe and nocturnal hypoglycaemia was 72% and 32%, respectively, lower with insulin detemir than with insulin glargine (P < 0.05). Body weight gain was not significantly different comparing insulin detemir and insulin glargine (0.52 kg vs. 0.96 kg, P = 0.193). CONCLUSIONS: Treatment with twice-daily insulin detemir or once-daily insulin glargine, each in combination with insulin aspart, resulted in similar glycaemic control. The overall risk of hypoglycaemia was comparable, whereas the risks of both severe and nocturnal hypoglycaemia were significantly lower with insulin detemir.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Adolescente , Adulto , Anciano , Austria , Glucemia/análisis , Diabetes Mellitus Tipo 1/sangre , Quimioterapia Combinada , Femenino , Alemania , Hemoglobina Glucada/análisis , Humanos , Insulina/análogos & derivados , Insulina/uso terapéutico , Insulina Aspart , Insulina Detemir , Insulina Glargina , Insulina de Acción Prolongada , Masculino , Persona de Mediana Edad , Factores de Riesgo , Sudáfrica , Resultado del TratamientoRESUMEN
AIMS: This study compared the effect of insulin detemir on glycaemic control (HbA(1c), fasting plasma glucose and variability thereof) with that of Neutral Protamine Hagedorn human isophane (NPH) insulin, both combined with insulin aspart, in children with Type 1 diabetes mellitus, and compared the safety of these treatments. METHODS: In this 26-week, open-label, randomized (2 : 1), parallel-group study, 347 (140 prepubertal and 207 pubertal) children with Type 1 diabetes, aged 6-17 years, received insulin detemir (n = 232) or NPH insulin (n = 115) once or twice daily, according to the prestudy regimen, plus premeal insulin aspart. RESULTS: The mean HbA(1c) decreased by approximately 0.8% with both treatments. After 26 weeks, the mean difference in HbA(1c) was 0.1% (95% confidence interval -0.1, 0.3) (insulin detemir 8.0%, NPH insulin 7.9%). Within-subject variation in self-measured fasting plasma glucose was significantly lower with insulin detemir than with NPH insulin (SD 3.3 vs. 4.3, P < 0.001), as was mean fasting plasma glucose (8.4 vs. 9.6 mmol/l, P = 0.022). The risk of nocturnal hypoglycaemia (22.00-07.00 h) was 26% lower with insulin detemir (P = 0.041) and the risk of 24-h hypoglycaemia was similar with the two treatments (P = 0.351). The mean body mass index (BMI) Z-score was lower with insulin detemir (P < 0.001). CONCLUSIONS: Basal-bolus treatment with insulin detemir or NPH insulin and premeal insulin aspart in children and adolescents with Type 1 diabetes mellitus improved HbA(1c) to a similar degree. The lower and more predictable fasting plasma glucose, lower risk of nocturnal hypoglycaemia and lower BMI observed with insulin detemir are clinically significant advantages compared with NPH insulin.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina Isófana/uso terapéutico , Insulina/análogos & derivados , Adolescente , Niño , Relación Dosis-Respuesta a Droga , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Prueba de Tolerancia a la Glucosa/métodos , Humanos , Hipoglucemia/prevención & control , Insulina/uso terapéutico , Insulina Detemir , Insulina de Acción Prolongada , Masculino , Factores de RiesgoRESUMEN
AIMS/HYPOTHESIS: Raised N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with a poor cardiac outcome in non-diabetic populations. Elevated NT-proBNP predicts excess morbidity and mortality in diabetic patients with an elevated urinary albumin excretion rate. This study investigated the prognostic value of NT-proBNP in a cohort of type 2 diabetic patients. SUBJECTS, MATERIALS AND METHODS: In a prospective observational follow-up study, 315 type 2 diabetic patients with normoalbuminuria (n=188), microalbuminuria (n=80) and macroalbuminuria (n=47) at baseline were followed for a median (range) of 15.5 (0.2-17.0) years. Plasma NT-proBNP concentrations were determined by immunoassay at baseline. Endpoints were overall and cardiovascular mortality. RESULTS: Of the patients, 162 died (51%), 119 of them (74%) due to cardiovascular causes. All-cause mortality was increased in patients with NT-proBNP in the second and third tertiles (hazard ratios [95% CI] compared with the first tertile, 1.70 [1.08-2.67] and 5.19 [3.43-7.88], p<0.001). These associations persisted after adjustment for urinary albumin excretion rate, glomerular filtration rate and conventional cardiovascular risk factors (covariate adjusted hazard ratios 1.46 [0.91-2.33] and 2.54 [1.56-4.14], p<0.001). This increased mortality was attributable to more cardiovascular deaths in the second and third NT-proBNP tertile (unadjusted hazard ratios 1.63 [0.96-2.77] and 4.88 [3.01-7.91], p<0.001; covariate adjusted 1.37 [0.79-2.37] and 2.26 [1.27-4.02], p=0.01). When patients with normo-, micro- and macroalbuminuria were analysed separately, NT-proBNP levels above the median (62 ng/l) were consistently associated with increased overall and cardiovascular mortality in all three groups (p<0.001). CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes, elevated circulating NT-proBNP is a strong predictor of the excess overall and cardiovascular mortality, this predictor status being independent of urinary albumin excretion rate and conventional cardiovascular risk factors.
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Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/mortalidad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Albuminuria/epidemiología , Creatinina/sangre , Angiopatías Diabéticas/epidemiología , Nefropatías Diabéticas/epidemiología , Retinopatía Diabética/epidemiología , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/epidemiología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Análisis de Supervivencia , Factores de TiempoRESUMEN
AIMS: Hypoglycaemia remains a major barrier preventing optimal glycaemic control in Type 1 diabetes due to the limitations of conventional insulin preparations. We investigated whether basal-bolus therapy with insulin detemir (detemir), a new soluble basal insulin analogue, was more effective in reducing the risk of hypoglycaemia compared with NPH insulin (NPH). METHODS: In this multinational, open-label, cross-over trial, 130 individuals with Type 1 diabetes received detemir and NPH twice daily in a randomized order in combination with premeal insulin aspart (IAsp) during two 16-week treatment periods. Risk of hypoglycaemia was based on self-measured plasma glucose (SMPG) and self-reported episodes during the last 10 weeks of each period. RESULTS: Risk of nocturnal and overall hypoglycaemia was, respectively, 50% and 18% lower with detemir than with NPH (P < 0.001). A total of 19 severe hypoglycaemic episodes occurred during treatment with detemir compared with 33 with NPH (NS). HbA(1c) decreased by 0.3% point with both treatments and was comparable at 7.6% (+/- sem 0.06%, 95% confidence interval -0.106, 0.108) after 16 weeks with similar doses of basal insulin. Within-person variation in mean plasma glucose was lower with detemir than with NPH (sd 3.00 vs. 3.33, P < 0.001), as was prebreakfast SMPG (P < 0.0001). CONCLUSIONS: Detemir was associated with a significantly lower risk of hypoglycaemia compared with NPH at similar HbA1c when used in combination with mealtime IAsp. The more consistent plasma glucose levels observed with detemir may allow people to aim for tighter glycaemic control without an increased risk of hypoglycaemia.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Insulina Isófana/uso terapéutico , Insulina/análogos & derivados , Adulto , Estudios Cruzados , Diabetes Mellitus Tipo 1/complicaciones , Quimioterapia Combinada , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/complicaciones , Insulina/uso terapéutico , Insulina Aspart , Insulina Detemir , Insulina de Acción Prolongada , Masculino , Resultado del TratamientoRESUMEN
AIMS/HYPOTHESIS: First-phase insulin release and coordinated insulin pulsatility are disturbed in Type 2 diabetes. The present study was undertaken to explore a possible influence of the oral prandial glucose regulator, repaglinide, on first-phase insulin secretion and high-frequency insulin pulsatility in Type 2 diabetes. METHODS: We examined 10 patients with Type 2 diabetes in a double-blind placebo-controlled, cross-over design. The participants were treated for 6 weeks with either repaglinide [2-9 mg/day (average 5.9 mg)] or placebo in random order. At the end of each treatment period, first-phase insulin secretion was measured. Entrainment of insulin secretion was assessed utilizing 1-min glucose bolus exposure (6 mg/kg body weight every 10 min) for 60 min during (A) baseline conditions, i.e. 12 h after the last repaglinide/placebo administration, and (B) 30 min after an oral dose of 0.5 mg repaglinide/placebo with subsequent application of time-series analyses. RESULTS: Postprandial (2-h) blood glucose was significantly reduced by repaglinide after 5 weeks of treatment (P < 0.001). The fall in HbA(1c) did not reach statistical significance (P = 0.07). AUC(ins,0-12 min) during the first-phase insulin secretion test was enhanced (P < 0.05). In addition, glucose entrained insulin secretory burst mass and amplitude increased markedly (burst mass: repaglinide, 44.4 +/- 6.0 pmol/l/pulse vs. placebo, 31.4 +/- 3.3 pmol/l/pulse, P < 0.05; burst amplitude: repaglinide, 17.7 +/- 2.4 pmol/l/min vs. placebo, 12.6 +/- 1.3 pmol/l/min, P < 0.05) while basal insulin (non-pulsatile) secretion was unaltered. After acute repaglinide exposure (0.5 mg) basal insulin secretion increased significantly (P < 0.05). Neither acute nor chronic repaglinide administration influenced frequency or regularity of insulin pulses during entrainment. CONCLUSION/INTERPRETATION: Repaglinide augments first-phase insulin secretion as well as high-frequency insulin secretory burst mass and amplitude during glucose entrainment in patients with Type 2 diabetes, while regularity of the insulin release process was unaltered.
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Carbamatos/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina/metabolismo , Piperidinas/administración & dosificación , Administración Oral , Adulto , Anciano , Glucemia/análisis , Estudios Cruzados , Diabetes Mellitus Tipo 2/metabolismo , Método Doble Ciego , Femenino , Homeostasis/fisiología , Humanos , Insulina/sangre , Secreción de Insulina , Masculino , Persona de Mediana Edad , Tasa de SecreciónRESUMEN
This trial compared the efficacy and safety of basal-bolus therapy using either the soluble basal insulin analogue insulin detemir (IDet) in combination with meal-time rapid-acting analogue insulin aspart (IAsp), or NPH insulin (NPH) in combination with meal-time regular human insulin (HSI). This was a 22-week, multinational, open-labelled, symmetrically randomised, parallel group trial including 395 people with type 2 diabetes (IDet + IAsp: 195, NPH + HSI: 200). At 22 weeks, HbA1c was comparable between treatments (IDet + IAsp: 7.46%, NPH + HSI: 7.52%, P = 0.515) with decreases from baseline of 0.65% and 0.58%, respectively. Treatment with IDet + IAsp was associated with a significantly lower within-person variation in self-measured fasting plasma glucose (FPG) (SD:1.20 versus 1.54 mmol/L, p < 0.001), as well as a lower body weight gain (0.51 versus 1.13 kg, p = 0.038) than with NPH + HSI. The risk of nocturnal hypoglycaemia was 38% lower with IDet + IAsp than with NPH + HSI, but statistical significance was not attained (P = 0.14). The overall safety profile was similar between the two treatments. Basal-bolus treatment with IDet + IAsp is an effective and well tolerated insulin regimen in people with type 2 diabetes, resulting in glycaemic control comparable to that of NPH + HSI, but with the advantages of less weight gain and a lower day-to-day within-person variation in FPG.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/análogos & derivados , Insulina/uso terapéutico , Adulto , Anciano , Glucemia/análisis , Peso Corporal/efectos de los fármacos , Ritmo Circadiano , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/patología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Ayuno/sangre , Femenino , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Insulina/administración & dosificación , Insulina/efectos adversos , Insulina/agonistas , Insulina Aspart , Insulina Detemir , Insulina de Acción Prolongada , MasculinoRESUMEN
AIMS/HYPOTHESIS: The aim of the trial was to compare the efficacy and tolerability of two types of basal-bolus therapy, using either the soluble long-acting basal insulin analogue, insulin detemir, in combination with the rapid-acting analogue, insulin aspart, or NPH insulin in combination with mealtime regular human insulin. METHODS: In this 18-week, 1:1 randomised, open-labelled, parallel trial, 595 patients with Type 1 diabetes mellitus received insulin detemir or NPH insulin in the morning and at bedtime in combination with mealtime insulin aspart or regular human insulin respectively. RESULTS: Glycaemic control with insulin detemir/insulin aspart was improved in comparison with NPH insulin/regular human insulin (HbA1c: 7.88% vs 8.11%; mean difference: -0.22% point [95% CI: -0.34 to -0.10]; p<0.001). Self-measured 8-point plasma glucose profiles differed between the groups (p<0.001), with lower postprandial plasma glucose levels in the insulin detemir/insulin aspart group. Within-person day-to-day variation in plasma glucose was lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (SD: 2.88 vs 3.12 mmol/l; p<0.001). Risk of overall and nocturnal hypoglycaemia (23.00-06.00 hours) was, respectively, 21% (p=0.036) and 55% (p<0.001) lower in the insulin detemir/insulin aspart group than in the NPH insulin/regular human insulin group. Body weight (adjusted for baseline and change in HbA1c) was 1 kg lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (p<0.001). CONCLUSIONS/INTERPRETATION: Basal-bolus therapy using insulin detemir/insulin aspart offers a better balance of control and tolerability than with NPH insulin/regular human insulin. The low variability and more physiological action profiles generated with these insulin analogues resulted in improved glycaemic control with lower risk of hypoglycaemia and no concomitant body weight increase.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina Isófana/uso terapéutico , Insulina/análogos & derivados , Insulina/uso terapéutico , Adulto , Glucemia/metabolismo , Peso Corporal/fisiología , Determinación de Punto Final , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Insulina/administración & dosificación , Insulina/efectos adversos , Insulina Aspart , Insulina Detemir , Insulina Isófana/administración & dosificación , Insulina Isófana/efectos adversos , Insulina de Acción Prolongada , MasculinoRESUMEN
Prone sleep position is obviously the main risk factor for sudden infant death. Other risk factors, such as vagal overactivity particularly in the familial form, are still discussed. We here report 15 families characterized by the coexistence of vagal overactivity and sudden infant death. At least, 1 child for each family had documented [Holter or occulo-cardiac reflex (OCR)] vagal overactivity. In 5 families 2 children were affected; in 2 families 3 children were affected and in 1 family 4 children were affected. Sudden death occurred in the elderly of the family in 8 cases, in the twin in 3 cases, in the 2nd in 3 cases and in the 5th child in 1 case. Within the 15 families, at least 1 parent had experienced vagally-induced fainting or syncope in 10 cases. Familial pattern of vagal overactivity is underlined. Possible links between vagal overactivity, risk factor for suddden death and sudden death are discussed. We suggest an Holter-ECG and OCR follow-up for sudden infant death siblings with history of familial vagal overactivity (3 examinations during the 1st year of life, at 1, 3 and 9 months).
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Muerte Súbita del Lactante/etiología , Enfermedades del Nervio Vago/complicaciones , Electrocardiografía Ambulatoria , Salud de la Familia , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Linaje , Factores de Riesgo , Enfermedades del Nervio Vago/fisiopatologíaRESUMEN
Patients with non-insulin-dependent diabetes (NIDDM) are at independent risk of cardiovascular death. The reason is only partially understood. The aim of our study was therefore to evaluate the impact of corrected QT interval length (QTc) and QT dispersion (QT-disp) on mortality in a cohort of 324 Caucasian NIDDM patients. A resting 12-lead ECG was recorded at baseline. Maximum (QT-max) and minimum QT (QT-min) intervals were measured, and QT-max was corrected for heart rate (QTc-max). QT-disp was defined as the difference between QT-max and QT-min. QTc-max was 454 (376-671) ms(1/2) (median (range)) and QT-disp 61 (0-240) ms. Prolonged QTc interval (PQTc), defined as QTc-max > 440 ms(1/2), was present in 67% of the patients and prolonged QT-disp (PQT-disp), defined as QT-disp > 50 ms, was present in 51%. During the 9-year follow-up period, 100 patients died (52 from cardiovascular diseases). Thirty-seven percent of the patients with PQTc died compared with 17% with normal QTc interval (p<0.001). The Cox proportional hazard model, including putative risk factors at baseline, revealed the following independent predictors of all cause mortality; QTc-max (p<0.05), age (p<0.0001), albuminuria (p<0.01), retinopathy (p<0.01), HbA1c (p<0.05), insulin treatment (p<0.01), total cholesterol (p<0.01), serum creatinine (p<0.05) and presence of cardiac heart disease based on Minnesota coded ECG (p<0.001). Whereas QT-disp was not a predictor, QTc-max interval was an independent predictor of cardiovascular mortality. Our study showed a high prevalence of QTc and QT-disp abnormalities and indicated that QTc-max but not QT-disp is an independent predictor of all cause and cardiovascular mortality in NIDDM patients.
Asunto(s)
Arritmias Cardíacas/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Albuminuria/complicaciones , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To evaluate and compare the clinical course and prognosis in type 2 diabetic patients with persistent albuminuria, with biopsy-proven diabetic glomerulosclerosis (DG), or with nondiabetic glomerulopathies (NDG). RESEARCH DESIGN AND METHODS: A kidney biopsy was performed in 34 consecutive type 2 diabetic patients with persistent albuminuria (> or = 300 mg/24 h). Glomerular filtration rate (GFR) (51Cr-EDTA) was determined at least once a year, and albuminuria, arterial blood pressure, and HbA1c were determined every 3-6 months. RESULTS: The biopsy revealed DG in 26 patients (25 men/1 woman) (DG group), age 52 +/- 2 (mean +/- SEM) years, and NDG in 8 patients (7 men/1 woman) (NDG group), age 54 +/- 3 years. The patients were followed for a median of 7.7 years (range 1.0-14.2). In the DG group, GFR decreased from 82 (24-146) to 38 (2-116) ml.min-1.1.73 m-2 (P < 0.001), with a median rate of decline in GFR of 5.6 (0.3-21.6) ml.min-1.year-1, and in the NDG group, GFR decreased from 107 (89-135) to 90 (17-119) ml.min-1.1.73 m-2 (P < 0.05), with a median rate of decline in GFR of 1.3 (0.3-7.6) ml.min-1.year-1 (P < 0.05 between groups). In the DG group, albuminuria increased from 1.4 (0.3-7.2) to 2.6 (0.1-21.6) g/24 h (P < 0.05) and in the NDG group, decreased from 2.2 (0.8-8.7) to 0.8 (0.2-2.5) g/24 h (P = 0.05). Mean arterial blood pressure (MABP) decreased from 118 +/- 3 to 104 +/- 3 mmHg (P < 0.05) in the DG group, whereas it remained unchanged in the NDG group (106 +/- 3 vs. 105 +/- 3 mmHg). In the DG group, the rate of decline in GFR correlated with systolic blood pressure (r = 0.62, P < 0.001), MABP (r = 0.52, P < 0.01), albuminuria (r = 0.55, P < 0.005), and GFR at entry (r = -0.45, P < 0.05). CONCLUSIONS: Our study demonstrated a more rapid decline in GFR and a progressive rise in albuminuria in type 2 diabetic patients with DG compared with type 2 diabetic patients with NDG.
Asunto(s)
Albuminuria/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/fisiopatología , Tasa de Filtración Glomerular , Biopsia , Presión Sanguínea , Colesterol/sangre , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/patología , Nefropatías Diabéticas/mortalidad , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: A high plasma total homocysteine (tHcy) concentration is a risk factor for cardiovascular disease in the nondiabetic population and in nondiabetic patients with end-stage renal disease. METHODS: We prospectively evaluated the impact of tHcy concentrations on mortality in 211 white non-insulin-dependent diabetic (NIDDM) patients of less than 70 years of age at entry (61 with microalbuminuria and 44 with macroalbuminuria). They were followed for a median of 6.4 (range 0.2 to 7.1) years. RESULTS: At the end of the follow-up period, 49 of 211 (23%) patients had died, 30 (61%) from cardiovascular disease. Univariate Cox survival analysis revealed that baseline tHcy level (1 micromol/liter) was associated with an increased all-cause mortality risk of 1.11 [95% confidence interval (CI) 1.08 to 1.15, P < 0.0001], and a cardiovascular mortality risk of 1.09 (CI 1.03 to 1.16, P < 0.01). The six-year cumulative all-cause mortality hazard was 44%, 14%, and 15% in the high (tHcy >/= 8.2 micromol/liter), the middle (tHcy 6. 2-8.1 micromol/liter), and the low (tHcy
Asunto(s)
Albuminuria/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/mortalidad , Homocisteína/sangre , Adulto , Anciano , Albuminuria/complicaciones , Enfermedades Cardiovasculares/complicaciones , Dinamarca/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
Endothelial dysfunction is a prevalent phenomenon in non-insulin dependent diabetic (NIDDM) patients with hypertension and albuminuria, and may contribute to the development and progression of cardiovascular disease, which is the main cause of the high morbidity and mortality observed in these patients. Therefore the aim of our study was to evaluate whether inhibition of angiotensin-converting enzyme (with lisinopril 10-20 mg day-1) could ameliorate endothelial dysfunction more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg day-1), usually in combination with a diuretic. We performed a 12-month prospective, randomized, double-blind, parallel study in 43 hypertensive NIDDM patients with diabetic nephropathy (21 treated with lisinopril and 22 with atenolol). The following variables were measured: 24-h ambulatory blood pressure (ABP); transcapillary escape rate of albumin (TERalb; i.e. initial disappearance of intravenously injected 125I-labelled human serum albumin); serum concentrations of von Willebrand factor (vWF), using ELISA, and urinary albumin excretion rate (UAE). Data are presented for 32 patients (16 lisinopril and 16 atenolol; age 60 years, SD 8; 25 males) out of 35 who completed the study and had valid measurements of TERalb. At baseline the two groups were comparable; TERalb (8.5 (SEM 0.6) vs. 7.2 (0.4)%); vWF (2.09 (range 0.82-4.34) vs. 1.97 (0.95-3.86) IU ml-1; UAE 916 (x/divided by antilog SEM 1.3) vs. 1444 (1.2), and mean ABP 110 (SEM 3) vs. 113 (2) mmHg, in the lisinopril and atenolol group, respectively. During follow up, the mean ABP was equally reduced in the lisinopril and atenolol group, by 12 (SEM 2) vs. 10 (2) mmHg, respectively, TERalb decreased in the lisinopril group by 0.6 (SEM 0.7)%, whereas it increased in the atenolol group 1.5 (0.5)%; the mean difference was 2.2% (95% CI, 0.5 to 3.9; p = 0.015). UAE was reduced by 45% (95% CI, 25 to 60) in the lisinopril group vs. 10% (-15 to 30) in the atenolol group (p = 0.014). Serum vWF was not changed during follow up in either group. Our study suggests that lisinopril has both reno- and vasculoprotective properties in hypertensive NIDDM patients with diabetic nephropathy.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/complicaciones , Endotelio Vascular/fisiopatología , Hipertensión/tratamiento farmacológico , Lisinopril/uso terapéutico , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antihipertensivos/farmacología , Atenolol/farmacología , Atenolol/uso terapéutico , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/fisiopatología , Método Doble Ciego , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Lisinopril/farmacología , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Estudios Prospectivos , Renina/sangreRESUMEN
The aim of our study was to evaluate whether inhibition of ACE (lisinopril 10-20 mg/day) can reduce the rate of decline in kidney function more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg/day), usually in combination with a diuretic. We performed a prospective, randomized, parallel study for 42 months, double blind for the first 12 months and single blind thereafter. Forty-three (21 lisinopril and 22 atenolol) hypertensive NIDDM patients with diabetic nephropathy were enrolled. Data from 36 patients (17 lisinopril and 19 atenolol, 60 +/- 7 years of age, 27 men) who completed at least 12 months of the study period are presented. At baseline, the two groups were comparable: glomerular filtration rate (51Cr-EDTA plasma clearance) was 75 +/- 6 and 74 +/- 8 ml x min(-1) x 1.73 m(-2), mean 24-h ambulatory blood pressure (A&D TM2420) was 110 +/- 3 and 114 +/- 2 mmHg, and 24-h urinary albumin excretion rate was 961 (range 331-5,727) and 1,578 (476-5,806) mg/24 h in the lisinopril and atenolol groups, respectively. The mean follow-up time was similar, 37 and 35 months in the lisinopril and atenolol groups, respectively. Mean ambulatory blood pressure was equally reduced in the two groups, 12 +/- 2 and 10 +/- 2 mmHg in the lisinopril and atenolol groups, respectively. Glomerular filtration rate declined in a biphasic manner with a faster initial (0 to 6 months) change of 1.25 +/- 0.49 and 0.81 +/- 0.29 ml x min(-1) x month(-1) followed by a slower sustained decline (6 to 42 months) of 0.59 +/- 0.10 and 0.54 +/- 0.13 ml x min(-1) x month(-1) in the lisinopril and atenolol groups, respectively. No significant differences were observed in either initial or sustained decline in glomerular filtration rate between the two groups. Urinary albumin excretion was reduced (% reduction of baseline) more in the lisinopril than in the atenolol group, at 55 (95% CI 29-72) and 15% (-13 to 34), respectively (P = 0.01). In conclusion, the relentless decline in kidney function characteristically found in hypertensive NIDDM patients with diabetic nephropathy can be reduced equally effectively by two antihypertensive treatments, the beta-blocker atenolol and the ACE inhibitor lisinopril.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/fisiopatología , Hipertensión Renal/tratamiento farmacológico , Riñón/efectos de los fármacos , Anciano , Albuminuria/tratamiento farmacológico , Albuminuria/fisiopatología , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Animales , Antihipertensivos/efectos adversos , Atenolol/efectos adversos , Atenolol/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/complicaciones , Método Doble Ciego , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Hipertensión Renal/fisiopatología , Riñón/fisiología , Lisinopril/efectos adversos , Lisinopril/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Conejos , Método Simple Ciego , Factores de TiempoRESUMEN
The aim of our cross-sectional case-control study was to evaluate putative mechanisms of the increased cardiac morbidity and mortality in NIDDM patients with or without diabetic nephropathy. Fifty-one NIDDM patients with diabetic nephropathy (38 males, age 61 +/- 8 years, group 1), 53 NIDDM patients with normoalbuminuria (42 males, 61 +/- 7 years, group 2), and 22 non-diabetic control subjects (15 males, 58 +/- 8 years, group 3) were investigated. Previous antihypertensive treatment was withdrawn 2 weeks before the study. Left ventricular mass index (LVMI) and systolic function were determined by echocardiography. LVMI was elevated, mean +/- SE, in group 1: 157 +/- 6 g m(-2), and in group 2: 139 +/- 7 g m(-2), as compared with group 3: 95 +/- 5 g m(-2) (p < 0.001, for both), and in group 1 as compared with group 2 (p = 0.05). The prevalence of left ventricular hypertrophy (LVH) (LVMI > 131 g m(-2) in men and > 100 gm(-2) in women) was much higher in group 1: 75% (95% CI, 60-86), and group 2: 51% (95% CI, 37-65), as compared with group 3: 9% (95% CI, 1-29) (p < 0.001, for both), and in group 1 as compared with group 2 (p < 0.01). Shortening fraction of the left ventricle, % +/- SE, was relatively reduced in group 1: 32.5 +/- 1.1%, and group 2: 33.4 +/- 1.1%, as compared with group 3: 41.2 +/- 1.2% (p < 0.01, for both). In a subgroup of 26 normoalbuminuric normotensive NIDDM patients, LVMI was higher than in 14 normotensive non-diabetic control subjects: 137 +/- 10 g m(-2) vs 96 +/- 7 g m(-2), respectively (p < 0.005). The prevalence of LVH was 42% (95% CI, 23-63) and 14% (95% CI, 2-43) (p = 0.07) in these two groups, respectively. In conclusion, normotensive and hypertensive NIDDM patients with and without diabetic nephropathy frequently suffer from LVH and relatively reduced systolic function which may constitute independent risk factors for fatal and non-fatal cardiac events.
Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/patología , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/patología , Hipertrofia Ventricular Izquierda/complicaciones , Hipertrofia Ventricular Izquierda/patología , Factores de Edad , Anciano , Albuminuria/metabolismo , Antihipertensivos/uso terapéutico , Presión Sanguínea , Índice de Masa Corporal , Estudios de Casos y Controles , Estudios Transversales , Ecocardiografía , Femenino , Hemoglobina Glucada/metabolismo , Frecuencia Cardíaca , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Hemoglobinas , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio , Isquemia Miocárdica , Volumen Plasmático , Renina/sangre , Factores Sexuales , Sodio/orina , Factores de TiempoRESUMEN
Extensively described since Gallvardin's reports, the electrical features of salves of ventricular tachycardia in an apparently healthy heart are now well known. The usual benign nature of this arrhythmia is acknowledged, seldom contradicted by isolated clinical cases. Although chronicity is the rule in young adults, there have been a few publications concerning the natural history of these tachycardias in the paediatric age group. The authors report three cases of episodic sustained ventricular tachycardia in older children, presenting at an average of 7 years of age (range 5 to 9 years) and followed up for an average of 7 years (range: 5.5 to 9 years). These three children were treated for an average of 4.5 years (range: 3 to 5.5 years). All treatment was finally withdrawn when stable permanent sinus rhythm without ventricular extrasystoles was restored and confirmed over an average period of 2 years (range 10 months to 3.5 years), an average of 4 (range 3 to 7) successive normal Holter recordings at several months' interval. The outcome in children to spontaneous regression after several years would seem to make radiofrequency ablation more dangerous than useful given the benign nature of the arrhythmia and its good response to pharmacological intervention.