Low Insulin-Like Growth Factor-1 Level in Obesity Nephropathy: A New Risk Factor?

INTRODUCTION: IGF-1 (insulin-like growth factor-1) is a hormone involved in cell growth and other important processes. In the kidney, IGF-1 has a stimulating effect, increasing the blood flow and glomerular filtration rate. Although many experimental animal studies regarding the role of IGF-1 in the kidney have been conducted, few human studies are available in the literature. Obesity is a cause of renal failure, and several glomerular lesions associated with obesity have been described. However, no studies regarding the levels of IGF-1 in morbidly obese patients with renal injury associated with obesity have been conducted. AIM: To determine the serum IGF-1 concentrations in morbidly obese patients with normal renal function but with different types of early obesity-related glomerular lesions and to evaluate the possible relationship between IGF-1 and the presence of renal lesions. METHODS: Eighty morbidly obese patients with renal biopsy, including 11 patients with no evidence of renal lesion, 17 patients with single glomerulomegaly, 21 patients with single podocyte hypertrophy, 10 patients with glomerulomegaly and podocyte hypertrophy, 5 patients with focal segmental hyalinosis, and 16 patients with increased mesangial matrix and/or mesangial proliferation, participated in this study. Biological parameters, including serum IGF-1 concentrations with the standard deviation score for age (SDS-IGF-1), were determined for all patients. RESULTS: Eighty patients (50 women and 30 men) with a mean BMI of 52.63 ± 8.71 and a mean age of 42.40 ± 9.45 years were included in this study. IGF-1, IGF-1 SDS and IGF-1BP3 levels according to the renal injury were compared (normal glomeruli: IGF-1 = 190.17 ± 72.46; glomerulomegaly: IGF-1 = 122.3 ± 50.05; podocyte hypertrophy: IGF-1 = 119.81 ± 60.34; focal segmental hyalinosis: IGF-1 170.98 ± 100.83, increased mesangial matrix and/or mesangial proliferation: IGF-1 117.73 ± 63.87). Statistically significant differences were observed between serum levels of IGF-1 and between the levels of SDS-IGF-1 by comparing the group without glomerular lesion with the group formed by patients with any type of glomerular injury. Logistic regression analysis was performed, with the dependent variable defined as the glomerular injury. In the multivariate analysis, only SDS-IGF-1 was associated with glomerular injury, and low levels of IGF-1 SDS were a risk factor for kidney injury. CONCLUSIONS: Our study demonstrates that low IGF-1 serum levels are associated with renal lesions in morbidly obese patients without overt clinical renal manifestations.

Obesity, inflammation, and kidney disease.

Obesity and extreme obesity are associated with a wide range of well known comorbidities (cardiovascular disease, dyslipidemia, hypertension, diabetes mellitus, metabolic syndrome). Recently, the association between obesity and renal involvement has been accepted since several epidemiological and pathological studies support this relationship. However, the physiopathological mechanism of this association is not completely understood. Different mechanisms have been implicated in the production of these renal lesions. Between them, metabolic alterations and inflammatory adipocytokines have been suggested. This paper is a review of the association between inflammatory adipocytokines or metabolic syndrome with renal involvement. We also briefly report our experience in a cohort of extremely obese patients.

Plasma adiponectin distribution in a Mediterranean population and its association with cardiovascular risk factors and metabolic syndrome.

Adiponectin may play an important role in the regulation of body weight, insulin resistance, and cardiovascular disease. The aim of this study was to evaluate the distribution of adiponectin in a Mediterranean adult population and its relationship with cardiovascular risk factors and metabolic syndrome. A cross-sectional study was performed in a representative sample of 1023 subjects from a Spanish Mediterranean population. Individuals with the metabolic syndrome were identified using the diagnostic criteria of the Adult Treatment Panel III. Anthropometric parameters were measured, and biochemical analyses were performed in fasting conditions. Plasma insulin levels were measured and homeostasis model assessment of insulin resistance was calculated. Plasma adiponectin levels were measured by a commercial radioimmunoassay. Median levels of adiponectin were significantly higher in women than in men after adjusting for differences in body mass index. However, no differences in adiponectin plasma levels were observed in relation to age. Significantly lower levels of adiponectin were also observed in women with obesity, abdominal obesity, hyperglycemia or diabetes, low high-density lipoprotein cholesterol, hypertriglyceridemia, or metabolic syndrome. In men, only those with obesity, abdominal obesity, low high-density lipoprotein cholesterol, hypertriglyceridemia, or metabolic syndrome showed significantly lower plasma levels of adiponectin. In a stepwise multivariate analysis, sex, waist circumference, serum C-reactive protein serum levels, and homeostasis model assessment of insulin resistance explained 23.4% of its variability. In conclusion, adiponectin plasma levels are more closely related to the components of the metabolic syndrome in women than in men in a Mediterranean population.

[Weight loss in a patient with morbid obesity under treatment with oleoyl-estrone]. / Pérdida de peso en un paciente con obesidad mórbida en tratamiento con oleoil-estrona.

BACKGROUND AND OBJECTIVE: Oleoyl-estrone administration in rats results in loss of body fat and sparing protein via decreasing food intake and maintaining energy expenditure. Oleoyl-estrone also decreases insulin resistance and hyperlipidemia and has no direct estrogenic effects. Our objective was to determine whether oral oleoyl-estrone was effective in the treatment of morbid obesity in a voluntary patient. PATIENT AND METHOD: Oleoyl-estrone (150-300 mol/d) was given to a morbid obese man (BMI: 51.9) over 10 consecutive 21-day trial periods of oral drug intake followed by at least two months of recovery. This treatment was given without additional dietary restrictions. Plasma metabolites, hormones and enzymes were measured before treatment, during active administration and at recovery periods. RESULTS: Oleoyl-estrone decreased the body weight (38.5 kg in 27 months, final BMI: 40.5). No rebound trends were observed. No significant changes in blood parameters, plasma metabolites, hormones or enzymes were observed as a consequence of the treatment. CONCLUSIONS: Oleoyl-estrone decreased body weight in this subject without affecting metabolites or hormones, similarly to its effects in animal models. This means that oleoyl-estrone could have a marked potential as an anti-obesity drug.

Pérdida de peso en un paciente con obesidad mórbida en tratamiento con oleoil-estrona / Weight loss in a patient with morbid obesity under treatment with oleoyl-estrone

FUNDAMENTO Y OBJETIVO: La administración de oleoil-estrona a las ratas induce la pérdida de grasa, sin afectar la proteína, mediante la disminución de la ingesta y el mantenimiento del gasto energético. La oleoil-estrona además reduce la resistencia a la insulina y la hiperlipemia, y carece de efectos estrogénicos. El objetivo fue determinar si la oleoil-estrona oral es efectiva en el tratamiento de la obesidad mórbida en un paciente obeso voluntario.PACIENTE Y MÉTODO: Se administró oleoil-estrona (150-300 µµmol/día) a un varón obeso mórbido (índice de masa corporal de 51,9 kg/m2) en 10 períodos consecutivos de 21 días, seguidos en cada caso de al menos dos meses de descanso. El tratamiento se siguió sin restricciones dietéticas adicionales. Se midieron las concentraciones de algunos metabolitos plasmáticos y hormonas antes y durante el tratamiento y los períodos de descanso.RESULTADOS: El tratamiento con oleoil-estrona hizo disminuir el peso corporal (38,5 kg en 27 meses, hasta un índice de masa corporal de 40,5 kg/m2). No se observaron tendencias al rebote en el peso durante los períodos de descanso. Tampoco se observaron cambios negativos significativos en los parámetros sanguíneos, hormonas, metabolitos y enzimas plasmáticas como consecuencia del tratamiento.CONCLUSIONES: La oleoil-estrona disminuyó el peso corporal en el sujeto sin afectar las cifras de metabolitos y hormonas, de modo similar a lo observado en modelos animales. Estos resultados están de acuerdo con un claro potencial de la oleoil-estrona como fármaco antiobesidad (AU)