Relationship between plasma leptin levels and the tumor necrosis factor-alpha system in obese subjects.

OBJECTIVE: To evaluate the relationship between plasma leptin and the tumor necrosis factor-alpha (TNFalpha), TNF receptor p60 (TNF-R1) and TNF receptor p80 (TNF-R2) concentrations in obese subjects. DESIGN: Case-control study. SETTING: Outpatient's Service for Prevention and Treatment of Obesity at the University Hospital. MEASUREMENTS: Body mass index (BMI), waist circumference, hip circumference, waist-to-hip ratio (WHR), fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance (HOMA IR), plasma leptin, TNFalpha, TNF-R1 and TNF-R2 concentrations were evaluated in obese subjects (n = 42) and in age- and gender-matched, lean healthy controls (n = 16). RESULTS: In obese subjects, fasting plasma glucose and insulin, HOMA IR, plasma leptin, TNFalpha, TNF-R1 and TNF-R2 concentrations were significantly higher than in controls. Furthermore, females showed higher leptin, TNF-R1 and TNF-R2 plasma concentrations compared to males, in both control and obese subjects. In control subjects, plasma leptin concentrations showed a direct correlation with BMI (r=0.74, P<0.001), hip circumference (r=0.94, P<0.001), TNF-R1 (r=0.79, P<0.001) and TNF-R2 (r=0.64, P<0.01), and a negative correlation with WHR (r=-0.58, P<0.05). In obese subjects, we found a direct correlation between plasma leptin concentrations and BMI (r=0.67, P<0.001), hip circumference (r=0.66, P<0.001), fasting glucose (r=0.37, P<0.05), fasting insulin (r=0.31, P<0.05), HOMA IR (r=0.38, P<0.05), TNF-R1 (r=0.71, P<0.001) and TNR-R2 (r=0.66, P<0.001), while a negative correlation was found between circulating leptin and WHR (r=-0.44, P<0.01). In multivariate analysis, plasma leptin concentrations were significantly associated with BMI (P=0.015) and gender (P=0.047) in the control group, while in obese subjects, plasma leptin showed a significant association with BMI (P=0.019) and TNF-R1 (P=0.012). CONCLUSIONS: Our results are consistent with the hypothesis that the TNFalpha system could be involved in the regulation of plasma leptin concentrations in obese subjects.

Changes in plasma, erythrocyte, and platelet magnesium levels in normotensive and hypertensive obese subjects during oral glucose tolerance test.

We evaluated the 75-g oral glucose tolerance test (OGTT)-induced modifications in glucose, insulin, and norepinephrine plasma concentrations, and in plasma, erythrocyte, and platelet magnesium levels in two groups of obese subjects (normotensive obese, NT-Ob, N = 19; hypertensive obese, HT-Ob, N = 15), and in a group of healthy control subjects (N = 12). During OGTT we detected a reduction in plasma magnesium concentrations and an increase in erythrocyte and platelet magnesium levels in the controls, whereas in both normotensive and hypertensive obese subjects, there was a reduction in plasma, erythrocyte, and platelet magnesium levels. Furthermore, no statistically significant difference was detected among the groups studied as regards delta-plasma magnesium. On the other hand, delta-erythrocyte magnesium and delta-platelet magnesium were negative in the NT-Ob (delta-erythrocyte magnesium: -0.24+/-0.08 mmol/L; delta-platelet magnesium: -0.49+/-0.09 micromol/10(8) cells) and HT-Ob (delta-erythrocyte magnesium: -0.20+/-0.10 mmol/L; delta-platelet magnesium: -0.50+/-0.11 micromol/10(8) cells) groups, and positive in control subjects (delta-erythrocyte magnesium: 0.40+/-0.08 micromol/L; delta-platelet magnesium: 0.47+/-0.09 mmol/ 10(8) cells). Finally, a direct correlation was found between delta-norepinephrine and delta-erythrocyte magnesium (r = 0.80, P < .01) in the control group, and a negative correlation was detected between delta-norepinephrine and delta-platelet magnesium (r = -0.58, P < .05) in the HT-Ob group. Our results seem to indicate that the insulin resistance status, the hyperglycemia, and the disregulation of the adrenergic system in obese subjects could be involved in the pathogenesis of the magnesium homeostasis impairment observed in the obese subjects.

Antihypertensive drug therapy and hypoglycemia in elderly diabetic patients treated with insulin and/or sulfonylureas. Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA).

We performed this case control study to evaluate the risk of hypoglycemia associated with the use of antihypertensive drugs in older hospitalized diabetic patients treated with sulfonylureas and/or insulin. All diabetic patients admitted during 4 months in 1988, month in 1991, 4 months in 1993 and 4 months in 1995 (n = 3477, mean age 71.4 +/- 0.2 years, 1542 males and 1935 females) were enrolled in the study. During the four annual surveys 86 patients (mean age 71.1 +/- 1.4 years, 33 males and 53 females) presented hypoglycemia during hospital stay. The patients who presented hypoglycemia were less frequently users of sulfonylureas and more frequently users of a combination of insulin and sulfonylureas. Use of antihypertensive drugs was similar in the two groups studied, and among potentially interacting drugs considered in the analysis, sulfonamides were more frequently used in patients who experienced hypoglycemia. Moreover, patients with hypoglycemia used a higher number of drugs, had a longer length of stay and had a greater prevalence of hypoglycemia as admission problem. Finally, although not significant, liver and renal diseases were more frequent among patients with hypoglycemia. In the multivariate analysis, contemporary use of insulin and sulfonylureas, liver disease and length of stay were significantly associated with hypoglycemia, while none of the antihypertensive drugs showed a significant association with the occurrence of hypoglycemia during hospital stay. Our results indicate that antihypertensive drugs do not increase the risk of hypoglycemia in elderly diabetic patients.

[Obesity and hypertension: the role of magnesium]. / Obesità ed ipertensione: ruolo del magnesio.

We focus on the recent "ionic hypothesis", in which an alteration of ionic metabolism represents a peculiar event in the pathogenesis of obesity and hypertension. We report the results from our original studies in which we evaluated intraplatelet magnesium levels. In a study on normotensive and hypertensive patients with non insulin-dependent diabetes mellitus and healthy control subjects, we showed a common reduction of plasma, erythrocyte and platelet magnesium levels in both normotensive and hypertensive diabetics with respect to control. Anyway, hypertensive diabetics showed a greater reduction of intraplatelet magnesium concentrations when compared to normotensive diabetics. Using the same technique, we found reduced erythrocyte and platelet magnesium concentrations in patients with essential hypertension with respect to the control group. In a successive study, we found, in the group of normotensive obese, that erythrocyte and platelet magnesium levels were significantly lower than those of the control group, while in hypertensive obese patients a reduction of plasma magnesium levels has been also detected. In conclusion, in these studies has been confirmed the existence of a reduction of the intracellular magnesium concentrations, which is common in hypertensive and obese patients.

[Leptin: adipocyte hormone]. / Leptina: ormone adipocitario.

The authors reviewed the most recent literature on leptin, a protein produced by adipocytes which exerts its action on hypothalamus, modifying eating behavior and inhibiting the lust for food consumption. This one appeared to be the main, if not the only, physiologic action of leptin. Later leptin has been acknowledged a major role in the homeostasis. The regulation of the synthesis, and the mechanisms by which the protein modulates both food intake and energetic balance have been evaluated, and the hypotheses on the regulatory function exerted by leptin on the homeostasis, by acting on neuroendocrine system, on sexual maturity and fertility, on the sympathetic nervous system, on hemopoiesis and hydroelectrolytic balance have been discussed, some of which being already supported by experimental evidences.

Increased transforming growth factor-beta1 plasma concentration is associated with high plasma 3,3',5'-tri-iodothyronine in elderly patients with nonthyroidal illnesses.

OBJECTIVE: To study transforming growth factor-beta1 (TGF-beta1) plasma concentrations in elderly patients with nonthyroidal illnesses (NTI). DESIGN: Case-control study. METHODS: We measured plasma concentrations of tri-iodothyronine (T3), reverse T3 (rT3), thyroxine (T4), free T3 (fT3) and free T4 (fT4) estimates, TSH, and TGF-beta1 in 48 elderly NTI patients consecutively admitted in our Division of Internal Medicine and Metabolic Diseases, and in 11 healthy age- and sex-matched controls. RESULTS: The data on thyroid hormones enabled us to identify three groups: Group A, subjects (8 patients) with T3 and fT3 levels comparable to those in controls: Group B, subjects (30 patients) with T3 and fT3 levels lower than controls but rT3 levels comparable to those of controls; Group C, subjects (10 patients) with T3 and fT3 levels lower than those of controls and higher rT3 levels. The patients of Group C showed higher plasma levels of TGF-beta1 compared with controls. Moreover, we found a positive correlation between TGF-beta1 and rT3 (rs = 0.38, P < 0.01) in the whole group of NTI patients. CONCLUSIONS: Our data seem to confirm the hypothesis that TGF-beta1 could play a role in the pathogenesis of some modifications of thyroid function observed in patients with nonthyroidal illnesses.

Plasma interleukin-2 levels and thyroid function in elderly patients with nonthyroidal illness.

To determine whether interleukin-2 (IL-2) plasma concentrations are modified in patients with nonthyroidal illness (NTI) and thyroid function alterations, we measured plasma concentrations of T(3), T(4), free T(3) (FT(3)), free T(4) (FT(4)), TSH, and IL-2 in 34 elderly NTI patients and in 25 age- and sex-matched healthy controls. IL-2 was detectable in 11 of the 34 patients. Patients with detectable IL-2 plasma levels had significantly lower plasma T(3) and FT(3) concentrations when compared to those with undetectable IL-2. Moreover, IL-2 plasma levels were positively correlated to reverse T(3) (rT(3)), (r(S)=0.67, P<0.05), and negatively to FT(3) concentrations (r(S) =-0.64, P<0.05). These observations suggest that some of the alterations in thyroid hormone levels seen in NTI are associated with elevated plasma concentrations of IL-2.

Reduced plasma concentrations of transforming growth factor beta1 (TGF-beta1) in obese women.

OBJECTIVE: To evaluate Transforming Growth Factor beta1, (TGF-beta1) plasma concentrations and the possible relationship between this growth factor and various hormones in obese women. DESIGN: Case-control study. SETTING: Outpatient's Service for the Prevention and Treatment of Obesity at the University Hospital. SUBJECTS: Twenty-five women with mild to moderate obesity, and 15 non-obese healthy women were used as controls. MEASUREMENTS: Evaluation of TGF-beta1, insulin, prolactin, sex-hormone binding globulin, androstenedione, free triiodothyronine, free tetraiodothyronine, thyroid-stimulating hormone, dehydroepiandrosterone-sulfate, testosterone, insulin-like growth factor 1, cortisol and adrenocorticotropic hormone plasma concentrations in obese women. Blood samples were taken from fasting subjects for the determination of the above parameters. RESULTS: In obese women plasma TGF-beta1 concentrations were lower than in controls. The obese subjects also had lower GH, IGF-1 and SHBG plasma concentrations and increased insulinaemia. A positive correlation was found between TGF-beta1 and both IGF-1 (r = 0.52; P < 0.01) and DHEA-S (r = 0.43; P < 0.05), while a negative correlation was found between TGF-beta1 and SHBG (r = -0.49; P < 0.05). CONCLUSIONS: The reduction in TGF-beta1, an antilipogenic factor, may play a role in the pathogenesis of obesity and could be involved in the development of some obesity-related endocrine alterations.

Reduced intraplatelet magnesium concentrations in elderly patients with non-insulin dependent diabetes mellitus (NIDDM).

Intraplatelet magnesium concentrations were evaluated in 50 non-insulin dependent diabetes mellitus (NIDDM) patients divided into two groups of 25 each (<60 or >65 years) and in a control group of 30 healthy subjects, divided into two age-matched subgroups of 15 each. In all patients magnesium concentrations were assayed in plasma, erythrocytes and platelets by means of direct current plasma spectrometry. Plasma, erythrocyte and platelet magnesium levels in healthy elderly subjects were found to be comparable to those in the group of younger healthy subjects, whereas plasma, erythrocyte and platelet magnesium levels in diabetics were lower than in controls. The reduction in intraplatelet magnesium concentrations found in elderly diabetics was greater than in the younger diabetics. In diabetics, moreover, an inverse correlation was found between platelet magnesium and age, but not between plasma or erythrocyte magnesium and age. Our findings show that aging can influence the alterations in the metabolism and compartmentalization of magnesium determined by type 2 diabetes mellitus. This condition may underlie platelet function alterations which, in turn, can exacerbate vascular complications from diabetes.

Altered platelet magnesium and plasma and urinary soluble form of intercellular adhesion molecule I (sICAM-1) concentrations in insulin dependent diabetes mellitus (IDDM) patients with microalbuminuria.

Magnesium concentrations in plasma, erythrocyte and platelet, and plasma and urine levels of the soluble form of Intercellular Adhesion Molecule-1 (sICAM-1) were evaluated in subjects with insulin dependent diabetes mellitus (IDDM) with or without microalbuminuria, and in a control group of healthy subjects. Using a recently introduced technique, we found that magnesium concentrations in platelets in diabetic subjects with microalbuminuria were lower than in diabetics with normal albuminuria (1.859 +/- 0.47 vs 2.065 +/- 0.62 mumol/10(8) cells; P < 0.05). Moreover, IDDM subjects had higher plasma sICAM-1 levels than control subjects; no difference, however, was found between sICAM-1 concentrations in the two groups of diabetics. An inverse correlation was found between intraplatelet magnesium and plasma sICAM-1 levels (r = - 0.64; P < 0.05) in the diabetics with microalbuminuria. It is concluded that the reduced intraplatelet magnesium content may contribute to the progression of the vascular complications in IDDM subjects with microalbuminuria.

Relationship between serum erythropoietin levels and rT3, T4 concentrations in elderly patients with non-thyroidal illnesses.

Thyroid function, plasma erythropoietin and tumor necrosis factor (TNF-alpha) concentrations were measured in 28 elderly patients with chronic non-thyroidal illnesses (NTI) and in 8 healthy subjects as a control group. In the NTI group, the existence of an impairment of thyroid function has been demonstrated in about 85% of the subjects, with a lower T(3) concentration; a low T(3) syndrome with low T(3) levels and high reverse-T(3) (rT(3)) plasma concentrations could be found in 25% of the subjects. A direct correlation between erythropoietin and rT(3) and an inverse correlation between erythropoietin and T(4) were found on NTI patients with endocrine abnormalities.

Magnesium levels in plasma, erythrocyte, and platelet in hypertensive and normotensive patients with type II diabetes mellitus.

The authors, by means of a recently introduced method, evaluated the intraplatelet concentrations of magnesium in 45 normotensive patients with type II diabetes mellitus, in 45 hypertensive diabetics and in 15 healthy controls. They also evaluated plasma and erythrocyte concentrations of the cation through direct current plasma spectrometer. Both normotensive and hypertensive diabetics showed a reduction in plasma, erythrocyte, and platelet concentrations of magnesium compared to controls. On the contrary, no significant difference was found between hypertensive and normotensive diabetics with regard to plasma and erythrocyte magnesium, whereas intraplatelet assay of the ion pointed out significantly lower concentrations of magnesium in hypertensive compared to normotensive patients (56.4 +/- 9.0 vs 60.7 +/- 10.2 micrograms/10(8) cells--p < 0.05). The authors believe that intraplatelet assay of magnesium may be the most reliable method for the evaluation of the cation in hypertensive diabetics, probably because platelets share common features with smooth muscle cells, including the alpha-2-adrenoceptor cyclase system and a coupling mechanism concerning the calcium-dependent contraction.

Effects of oral magnesium supplementation on plasma lipid concentrations in patients with non-insulin-dependent diabetes mellitus.

We evaluated the effects of oral magnesium supplementation on plasma lipid concentrations in patients with non-insulin-dependent diabetes mellitus. Twenty-six persons with non-insulin-dependent diabetes mellitus received 4.5 g magnesium pidolate/d for one month, and 17 persons received placebo. Before and at the end of the treatment period cholesterol concentration, triglycerides, LDL cholesterol, HDL cholesterol, and plasma and erythrocyte magnesium were evaluated. Chronic magnesium supplementation produced a significant reduction of plasma cholesterol and LDL cholesterol, and an increase of HDL cholesterol. These results suggest that oral supplementation of magnesium may be useful in the treatment of hyperlipidaemia in patients with non-insulin-dependent diabetes mellitus.

[The role of magnesium in glucose homeostasis: therapeutic implications]. / Ruolo del magnesio nella omeostasi glucidica: implicazioni terapeutiche.

The authors examined the literature on the close relationship of magnesium to carbohydrate metabolism. It was found that a diabetic condition is apt to bring about marked changes in body magnesium content and its compartmental distribution, and that the administration of dietary magnesium supplements can have a favorable influence on metabolic control, thus reducing insulin requirement and counteracting the progression of late diabetic complications.

The influence of hypercholesterolemia on some aspects of immune pattern in the elderly.

In order to investigate if age related dislipidemia was associated with immunological changes in vivo, humoral, soluble and cellular immune parameters were evaluated both in elderly with and without hypercholesterolemia and in young adults. Significantly increased IgG and IgA values were found in hypercholesterolemic aged compared to the other groups. Increased plasma neopterin levels (a pteridine generally used as a marker of macrophage activity) were reported in healthy aged subjects, whereas a lesser degree of the activation of the macrophage system was found in the hypercholesterolemic aged subjects. Compared with the young controls, an increase of interleukin 2 receptor expressing cells and of the IL-2 soluble receptors was noticeable in healthy aged subjects, whereas in hypercholesterolemic aged subjects only a minor increase of the IL-2 membrane receptor was noticed. We suggest that hypercholesterolemia may play a role in immune function in aging.

[Erythropoietin: current aspects and prospects]. / Eritropoietina: attualità e prospettive.

Authors have reviewed recent literature on erythropoietin. They report new information regarding synthesis, modulation, changes during several diseases and the possibility for a clinical use of erythropoietin for the correction of many anaemias. Finally the Authors report some personal observations about the physiopathology of erythropoietin. They have studied the circadian rhythm, action of aging and the prostaglandin system, and plasma levels of E. in patients with anaemia of active rheumatoid arthritis.