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[This corrects the article DOI: 10.1007/s13340-021-00517-2.].
RESUMEN
AIMS: Relationship between baseline eGFR and the rate of decline in eGFR was investigated in diabetic kidney disease. MATERIALS AND METHODS: Patients with type 2 diabetes with microalbuminuria (MI) (n = 124) or macroalbuminuria (MA) (n = 81) received team-based medical care to prevent the development of diabetic kidney disease. The decline in eGFR over 4 years, divided into the first year and subsequent 3 years, was estimated by linear-mixed modeling. RESULTS: The eGFR showed a rapid decline during the first year, followed by a slower decline. On multiple regression analysis, the baseline eGFR was positively correlated with HbA1c in MI and negatively correlated with carotid plaque in MI and in MA. Subsequent eGFR decline following 1-year intervention was negatively correlated with the baseline eGFR and HbA1c level at 1 year in MI, whereas it was positively correlated with baseline eGFR and negatively correlated with the amount of proteinuria at 1 year in MA. Even in maintained baseline eGFR(⧠60 ml/min/1.73 m2) at the first year, when HbA1c ⧠7.5%, eGFR reduction rate and years to ESKD were much faster and shorter, compared to the group of HbA1c < 7.5% [- 3.44 (SE 1.137) vs. - 1.695 (SE 0.431) ml/min/1.73 m2/year, and 19.4 vs. 35.7 years, respectively]. In MA, lower eGFR (< 60 ml/min/1.73 m2) and higher proteinuria (⧠2.25 g/gCre) had a much faster eGFR decline and shorter time to ESKD, compared to the group of maintained eGFR and lower proteinuria (< 2.25 g/gCre) [- 5.240 (SE 1.537) vs. - 2.67 (SE 0.997) ml/min/1.73 m2/year, and 4.41 vs. 22.8 years, respectively]. CONCLUSIONS: In MI, even in maintained eGFR, the continued increase in eGFR in response to hyperglycemia (HbA1c ⧠7.5%) led to a faster decline in renal function and in MA, lower eGFR, with an increase in proteinuria, contributed to rapid decline of renal function. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00517-2.
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To investigate the anti-atherogenic effect of metformin, we prospectively evaluated the effect of metformin treatment on common carotid intima-media thickness (CCA-IMT) in patients with type 2 diabetes. A 2-year open prospective study was performed. Thirty-six patients were treated with metformin (500-750 mg per day). CCA-IMT was measured after 1- and 2-year treatment. Changes in CCA-IMT were compared with control patients. After 2-year metformin therapy, the progression of CCA-IMT was significantly less than 56 control patients (0.02+/-0.08 mm versus 0.07+/-0.08 mm, P<0.01). Metformin therapy did not alter body weight, blood pressure, HbA1c, and serum lipids relative to the control. Thus, metformin attenuates the progression of CCA-IMT. This anti-atherogenic effect is not mediated through changes in classical cardiovascular risk factors.
Asunto(s)
Arterias Carótidas/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Metformina/uso terapéutico , Túnica Íntima/efectos de los fármacos , Túnica Media/efectos de los fármacos , Arteriosclerosis/complicaciones , Arteriosclerosis/tratamiento farmacológico , Arteriosclerosis/prevención & control , Arterias Carótidas/patología , Arterias Carótidas/fisiología , Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/tratamiento farmacológico , Enfermedad Crónica , Diabetes Mellitus Tipo 2/patología , Dietoterapia , Esquema de Medicación , Femenino , Gliclazida/uso terapéutico , Gliburida/uso terapéutico , Hemoglobina Glucada/química , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/fisiología , Humanos , Japón , Masculino , Metformina/farmacología , Persona de Mediana Edad , Estudios Prospectivos , Compuestos de Sulfonilurea/uso terapéutico , Factores de Tiempo , Túnica Íntima/patología , Túnica Íntima/fisiología , Túnica Media/patología , Túnica Media/fisiologíaRESUMEN
Insulin resistance (IR)/hyperinsulinemia and low-grade inflammation (high-sensitivity C-reactive protein [hs-CRP]) can predict cardiovascular disease. However, because IR and inflammation (IF) have not been evaluated simultaneously, it is not known whether IR and IF are independently related to cardiovascular disease. Furthermore, the combined effect of IR and IF on the prediction of cardiovascular disease is presently unknown. Thus, we measured insulin sensitivity (K index of the insulin tolerance test; KITT) and hs-CRP in 350 Japanese patients with type 2 diabetes, and followed them for 1-7 years (mean, 4.5 years). During the follow-up, 33 patients died and 53 patients developed non-fatal coronary artery disease or stroke (endpoint). Age, systolic blood pressure, current smoking, past history of cardiovascular disease, KITT, and hs-CRP independently and significantly correlated with endpoint. One-S.D. difference was associated with a significant increase of relative risk in KITT (1.45; 95% CI 1.09-1.91) and hs-CRP (1.30; 1.04-1.67). When patients were subdivided to tertile, the relative risk in the highest tertile of KITT was 1.76 (95% CI 1.01-3.11) and hs-CRP was 2.00 (1.03-3.85) compared with the patients with lowest tertile. The relative risk in the highest tertile of both KITT and hs-CRP was 5.32 (1.18-24.0) compared with the lowest tertile of both values. In conclusion, low-grade IF and IR are independently related to all-cause of death and cardiovascular disease in Japanese patients with type 2 diabetes. Coexistence of low-grade IF and IR amplify this effect.
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Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 2/complicaciones , Inflamación , Resistencia a la Insulina , Factores de Edad , Presión Sanguínea/fisiología , Proteína C-Reactiva/análisis , Causas de Muerte , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Fumar/efectos adversosRESUMEN
The aim of this study was to investigate whether combination therapy of alpha-glucosidase inhibitor and a sulfonylurea (SU) drug can prolong the duration of good glycemic control compared with SU alone in patients with type 2 diabetes. The open prospective study included 124 Japanese patients with type 2 diabetes and inadequate glycemic control (hemoglobin A(1c) [HbA(1c)] gt; 7.0%). Patients were given either voglibose plus a SU compound (glibenclamide or gliclazide, n = 61) or SU drug alone (n = 63). The first 6-month run-in period (targeted to HbA(1c) /= 8.0%). Fifty patients on combination therapy and 48 patients on SU alone completed the trial. During the follow-up, 21 patients on combination therapy and 30 patients on SU alone showed deterioration of glycemic control and reached the endpoint (P =.04). The combination therapy significantly prolonged the duration of good glycemic control (HbA(1c) < 8.0%) compared with SU alone by Kaplan-Meier estimated survival analysis using a log-rank test (P =.02). Thus, combination therapy with voglibose and a SU agent prolongs the duration of good glycemic control compared with SU alone in patients with type 2 diabetes.
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Glucemia/análisis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Gliclazida/uso terapéutico , Gliburida/uso terapéutico , Inhibidores de Glicósido Hidrolasas , Inositol/análogos & derivados , Inositol/uso terapéutico , Compuestos de Sulfonilurea/uso terapéutico , Diabetes Mellitus Tipo 2/sangre , Quimioterapia Combinada , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Factores de TiempoRESUMEN
Serum concentrations of soluble adhesion molecules, eg, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin are elevated in patients with type 2 diabetes. However, little is known about the role of obesity or abnormal fat distribution in inducing upregulation of adhesion molecules. To investigate this issue, soluble ICAM-1, VCAM-1, and E-selectin levels were evaluated in 40 obese and 30 nonobese patients with type 2 diabetes. Both groups were matched for age, sex, and glycosylated hemoglobin (HbA(1c)) levels. Computed tomography (CT) was used to measure the abdominal subcutaneous and visceral fat areas. Soluble ICAM-1 and VCAM-1 levels did not differ significantly between obese and nonobese patients. However, serum concentrations of soluble E-selectin were significantly higher in obese than in nonobese patients (90 +/- 7 v 56 +/- 4 ng/mL, P <.01). Soluble E-selectin levels significantly correlated with body mass index, subcutaneous fat area, and visceral fat area (Rho = 0.48, 0.37, and 0.30, respectively). Stepwise multiple regression analysis showed that body mass index (F = 16.7), but not subcutaneous and visceral fat areas (F = 0.29 and 0.01, respectively), significantly and independently correlated with soluble E-selectin levels. Our results suggest that obesity may induce endothelial activation or increased shedding of cell surface E-selectin that leads to subsequent increase in soluble E-selectin levels. The high serum concentrations of E-selectin closely correlated with increased total fat volume, but not with regional fat distribution.
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Tejido Adiposo/fisiopatología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus/sangre , Selectina E/sangre , Obesidad , Abdomen/fisiopatología , Tejido Adiposo/diagnóstico por imagen , Glucemia , Composición Corporal , Índice de Masa Corporal , Estudios de Casos y Controles , Colesterol/sangre , HDL-Colesterol/sangre , Complicaciones de la Diabetes , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Hemoglobina Glucada/análisis , Humanos , Molécula 1 de Adhesión Intercelular/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Análisis de Regresión , Solubilidad , Tomografía Computarizada por Rayos X , Molécula 1 de Adhesión Celular Vascular/sangreRESUMEN
Different autoimmune mechanisms may be involved in childhood- and adult-onset type 1 diabetes. Our aim was to explore the differences in IA-2 autoantibody epitope recognition between childhood- and adult-onset type 1 diabetes. Therefore, in vitro synthesized radiolabeled IA-2ic (amino acid 601-979), IA-2JM (amino acid 557-629), and IA-2PTP (amino acid 630-979) were used to analyze the IA-2 autoantibody epitope specificities in 93 patients with new-onset type 1 diabetes. Among 93 patients with type 1 diabetes the prevalences of autoantibodies to GAD, IA-2ic, and insulin were 69.9%, 58.1%, and 45.2%, respectively. The prevalence of IA-2ic autoantibodies in patients with childhood-onset type 1 diabetes (aged Asunto(s)
Autoanticuerpos/inmunología
, Diabetes Mellitus Tipo 1/inmunología
, Diabetes Mellitus Tipo 2/inmunología
, Epítopos/inmunología
, Adolescente
, Adulto
, Edad de Inicio
, Especificidad de Anticuerpos
, Niño
, Diabetes Mellitus Tipo 1/fisiopatología
, Diabetes Mellitus Tipo 2/fisiopatología
, Femenino
, Glutamato Descarboxilasa/inmunología
, Humanos
, Insulina/inmunología
, Isoenzimas/inmunología
, Masculino
, Persona de Mediana Edad
RESUMEN
To investigate the relationships between serum concentrations of soluble adhesion molecules and hyperglycemia, insulin resistance, or other conventional risk factors in type 2 diabetes, we measured soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), insulin sensitivity, and conventional risk factors in 150 Japanese type 2 diabetic patients without apparent diabetic macroangiopathy. High serum concentrations of sVCAM-1 and sE-selectin were observed in patients with type 2 diabetes. Serum concentrations of soluble adhesion molecules were not significantly influenced by sex, hypertension, dyslipidemia, or microangiopathy. Spearman correlation showed that sVCAM-1 concentrations correlated significantly with fasting plasma glucose (FPG), fasting C-peptide, and insulin sensitivity [K index of the insulin tolerance test (K(ITT))] (rho=0.19,0.23, and -0.23, respectively). Soluble E-selectin concentrations correlated significantly with body mass index (BMI), FPG, fasting C-peptide, insulin sensitivity, and triglyceride (rho=0.33,0.42,0.26,-0.48, and 0.29, respectively). Multiple regression analysis showed that FPG, fasting C-peptide, and total cholesterol were independent factors that correlated with sVCAM-1 levels. BMI, FPG, and insulin sensitivity were independent factors that correlated with sE-selectin levels. Serum concentrations of sE-selectin significantly increased associated with clustering of conventional risk factors those obesity, hypertension, dyslipidemia, and current smoking (P<0.01). Thus, sVCAM-1 and sE-selectin levels are related to both hyperglycemia and insulin resistance. Soluble E-selectin levels may be related to obesity, hyperglycemia, and insulin resistance and may reflect the presence of a multiple risk factor clustering syndrome.
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Moléculas de Adhesión Celular/sangre , Diabetes Mellitus Tipo 2/sangre , Hiperglucemia/sangre , Resistencia a la Insulina , Glucemia/análisis , Índice de Masa Corporal , Péptido C/sangre , Colesterol/sangre , Selectina E/sangre , Ayuno , Femenino , Humanos , Molécula 1 de Adhesión Intercelular/sangre , Masculino , Persona de Mediana Edad , Factores de Riesgo , Solubilidad , Triglicéridos/sangre , Molécula 1 de Adhesión Celular Vascular/sangreRESUMEN
If a strong association between intima-media thickness of the common carotid artery (CCA-IMT) and ischemic stroke can be determined in diabetic subjects, it may be a useful predictor to help identify patients at high risk of ischemic stroke. To investigate the relative contribution of CCA-IMT to ischemic stroke in patients with type 2 diabetes, we measured CCA-IMT and other conventional risk factors in 438 Japanese patients with type 2 diabetes, including 45 with ischemic stroke and 393 controls. Stroke patients were characteristically and significantly older with higher body mass index, longer duration of diabetes, likely to be smokers, higher blood pressure, and higher total cholesterol compared with the controls. CCA-IMT in stroke patients (1.23 +/- 0.04 mm) was significantly greater than in control patients (0.95 +/- 0.01 mm, P <.01). CCA-IMT in stroke patients was still significantly greater than controls after adjustment for age, sex, body mass index, and smoking status (P <.05). A 0.1-mm increase in CCA-IMT was associated with 1.80-fold increase in the odds ratio of stroke in diabetic patients (95%confidence interval [CI], 1.49 to 2.17; P <.01). Four independent factors were found to correlate significantly with CCA-IMT: age, systolic blood pressure, HbA(1c), and high-density lipoprotein (HDL) cholesterol. Thus, thickening of the intima-media of common carotid arteries is associated with ischemic stroke in type 2 diabetic patients. To prevent ischemic stroke, strict control of diabetes, hypertension, and dyslipidemia and monitoring of CCA-IMT may be important.