leptin and Albuminuria

Interval walking training has demonstrated more pronounced positive effects on physical fitness and metabolism in type 2 diabetes (T2D), compared to continuous walking. One of the pathogenic mechanisms of T2D is associated with derangements in leptin/adiponectin axis, which might predispose affected individuals to vascular inflammation and albuminuria. The aim of this study was to investigate the effects of interval walking training delivered through smart mobile devices upon albuminuria and leptin/adiponectin ratio in patients with T2D.. Patients with T2D aged 35-75 were randomized into control (n = 26) and interval training (IT, n = 14) groups. Patients in IT group had to perform three 60-min interval walking sessions (3 min intervals of slow and fast walking with the intensity of 40% and 70% of the peak energy expenditure) per week delivered by smartphone application for four months. The adherence to training was monitored remotely. Outcome measures were albuminuria, leptin/adiponectin ratio, obesity indicators, and glycaemic control. Leptin and adiponectin concentration was measured in serum samples by Luminex technology.. In the IT group compared to control group, we observed a statistically significant decrease in albuminuria (p = .002) and leptin/adiponectin ratio (p = .01), as well as a decrease in HbA1c close to statistical significance (p = .09). In IT group, changes in leptin/adiponectin ratio correlated significantly with changes in hip circumference (p = .024).. Interval walking training is beneficial for vascular health in T2D via impact on albuminuria and leptin/adiponectin ratio.

Topics: Adiponectin; Adult; Aged; Albuminuria; Diabetes Mellitus, Type 2; Exercise Therapy; Female; Humans; Leptin; Male; Middle Aged; Mobile Applications; Smartphone; Walking

Adipocytokines represent a molecular link between metabolic factors and vascular function. The purpose of our study was to investigate the relationship between adiponectin, leptin and renal function parameters in patients with glomerular filtration rate (GFR) above 90 ml/min/m(2) and type 2 diabetes.. In 52 patients, plasma (P-) and urinary (U-) adiponectin and leptin were determined by radioimmunoassay and ELISA, respectively. Kidney function was assessed with GFR (plasma iohexol clearance) and albuminuria (radioimmunoassay).. The patients were aged 58+/-8 years and had a mean BMI value of 31.2+/-5.2 kg/m(2). Our measurements yielded the following values, expressed as median (25th percentile, 75th percentile): P-adiponectin 11.0 (7.1, 14.5) microg/ml, P-leptin 20.7 (9.6, 35.9)ng/ml, U-adiponectin 0.8 (0.3, 1.2) microg/mg creatinine, and U-leptin 1.0 (0.4, 1.9) microg/mg creatinine. Albuminuria correlated with P-adiponectin (R=-0.31, p=0.03), and GFR correlated with U-leptin (R=-0.32, p=0.04).. Adiponectin and leptin are associated with parameters of renal function already at the stage of apparently normal kidney function in type 2 diabetes. The exact mechanisms of the adipocyte-vasculature axis still remain to be elucidated.

Topics: Adipocytes; Adiponectin; Aged; Albuminuria; Body Mass Index; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Kidney; Leptin; Male; Middle Aged; Prospective Studies

Lack of leptin is implicated in insulin resistance and other metabolic abnormalities in generalized lipodystrophy; however, the efficacy, safety, and underlying mechanisms of leptin-replacement therapy in patients with generalized lipodystrophy remain unclear.. Seven Japanese patients with generalized lipodystrophy, two acquired and five congenital type, were treated with the physiological replacement dose of recombinant leptin during an initial 4-month hospitalization followed by outpatient follow-up for up to 36 months.. The leptin-replacement therapy with the twice-daily injection dramatically improved fasting glucose (mean +/- SE, 172 +/- 20 to 120 +/- 12 mg/dl, P < 0.05) and triglyceride levels (mean +/- SE, 700 +/- 272 to 260 +/- 98 mg/dl, P < 0.05) within 1 wk. The leptin-replacement therapy reduced insulin resistance evaluated by euglycemic clamp method and augmented insulin secretion at glucose tolerance test with different responses between acquired and congenital types. Improvement of the fatty liver was also observed. The efficacy and safety of the once-daily injection were comparable to those of the twice-daily injection. The leptin-replacement therapy ameliorated macro- and microalbuminuria and showed no deterioration of neuropathy and retinopathy of these patients. The leptin-replacement therapy is beneficial to diabetic complications and lipodystrophic ones. Two patients developed antileptin antibodies but not neutralizing antibodies. The therapy was well tolerated, and its effects were maintained for up to 36 months without any notable adverse effects such as hypoglycemia, high blood pressure, or reduction of bone mineral density.. The present study demonstrates the efficacy and safety of the long-term leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy.

Topics: Adolescent; Adult; Albuminuria; Blood Glucose; Child; Diabetes Complications; Fatty Liver; Female; Follow-Up Studies; Glucose Clamp Technique; Glucose Tolerance Test; Hormone Replacement Therapy; Humans; Hyperinsulinism; Injections, Subcutaneous; Insulin Resistance; Leptin; Lipodystrophy; Male; Time Factors; Treatment Outcome; Triglycerides

Telmisartan, a new angiotensin II type 1 receptor blocker (ARB), was recently reported to stimulate PPARgamma, and stronger effects of Telmisartan on insulin sensitivity has been expected than the class effect of ARB. In the present study, we examined the effects of Telmisartan on insulin sensitivity and adipokine levels in hypertensive and type 2 diabetic patients. Outpatients with both hypertension and type 2 diabetes mellitus (n=36; male 23, female 13), received 20-40mg Telmisartan orally once daily for 6 months. Physical examinations and blood or urine tests were performed before and 3 or 6 months after starting Telmisartan treatment. Results were statistically compared using Wilcoxon analysis. Telmisartan treatment for 3 or 6 months reduced systolic and diastolic blood pressure and urinary albumin excretion. Fasting plasma glucose, HbA1c, total and HDL-cholesterol, triglyceride, body weight, BMI and waist length were not changed. Fasting IRI and HOMA-IR were significantly decreased after Telmisartan treatment, suggesting the improved insulin sensitivity. Total and high molecular adiponectin were not changed. Interestingly, serum leptin was significantly increased by 3 months Telmisartan treatment, suggesting a possible involvement of leptin in improved insulin sensitivity. In conclusion, Telmisartan improved insulin resistance with increased serum leptin level in hypertensive and type 2 diabetic patients.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Benzoates; Blood Pressure; Body Mass Index; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diet, Diabetic; Female; Humans; Hypertension; Hypoglycemic Agents; Leptin; Lipids; Male; Middle Aged; Telmisartan

Background The incidence and clinical manifestations of cardiovascular disease (CVD) differ between blacks and whites. Biomarkers that reflect important pathophysiological pathways may provide a window to allow deeper understanding of racial differences in CVD. Methods and Results The study included 2635 white and black participants from the Dallas Heart Study who were free from existing CVD. Cross-sectional associations between race and 32 biomarkers were evaluated using multivariable linear regression adjusting for age, traditional CVD risk factors, imaging measures of body composition, renal function, insulin resistance, left ventricular mass, and socioeconomic factors. In fully adjusted models, black women had higher lipoprotein(a), leptin, d-dimer, osteoprotegerin, antinuclear antibody, homoarginine, suppression of tumorigenicity-2, and urinary microalbumin, and lower adiponectin, soluble receptor for advanced glycation end products and N-terminal pro-B-type natriuretic peptide versus white women. Black men had higher lipoprotein(a), leptin, d-dimer, high-sensitivity C-reactive protein, antinuclear antibody, symmetrical dimethylarginine, homoarginine, high-sensitivity cardiac troponin T, suppression of tumorigenicity-2, and lower adiponectin, soluble receptor for advanced glycation end products, and N-terminal pro-B-type natriuretic peptide versus white men. Adjustment for biomarkers that were associated with higher CVD risk, and that differed between blacks and whites, attenuated the risk for CVD events in black women (unadjusted hazard ratio 2.05, 95% CI 1.32, 3.17 and adjusted hazard ratio 1.15, 95% CI 0.69, 1.92) and black men (unadjusted hazard ratio 2.39, 95% CI 1.64, 3.46, and adjusted hazard ratio 1.21, 95% CI 0.76, 1.95). Conclusions Significant racial differences were seen in biomarkers reflecting lipids, adipokines, and biomarkers of endothelial function, inflammation, myocyte injury, and neurohormonal stress, which may contribute to racial differences in the development and complications of CVD.

Topics: Adiponectin; Adult; Albuminuria; Antibodies, Antinuclear; Arginine; Biomarkers; Black or African American; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Female; Fibrin Fibrinogen Degradation Products; Homoarginine; Humans; Interleukin-1 Receptor-Like 1 Protein; Leptin; Linear Models; Lipoprotein(a); Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Osteoprotegerin; Peptide Fragments; Proportional Hazards Models; Receptor for Advanced Glycation End Products; Troponin T; White People

Topics: Albuminuria; Animals; Antibodies, Neutralizing; Diabetic Nephropathies; Disease Progression; Humans; Interleukin-17; Kidney; Leptin; Male; Mice; Mice, Transgenic; Th17 Cells

Puumala hantavirus (PUUV) infected patients typically suffer from acute kidney injury (AKI). Adipokines have inflammation modulating functions in acute diseases including AKI. We examined plasma levels of three adipokines (resistin, leptin, and adiponectin) in acute PUUV infection and their associations with disease severity.. This study included 79 patients hospitalized due to acute PUUV infection. Plasma resistin, leptin, adiponectin, as well as IL-6 and CRP, were measured at the acute phase, recovery phase and one year after hospitalization.. Plasma resistin levels were significantly higher in the acute phase compared to the recovery phase and one year after (median resistin 28 pg/mL (11-107) vs. 17 pg/mL (7-36) vs. 14 pg/mL (7-31), p<0.001). Maximum resistin concentration correlated with maximum plasma creatinine levels (r = 0.63; p<0.001). The higher the amount of albuminuria in the urine dipstick test (0-1+, 2+ or 3+) at admission, the higher the median of maximum resistin (24.7 pg/mL, 25.4 pg/mL and 39.6 pg/mL, respectively, p = 0.002). High resistin was also an independent risk factor for severe AKI (creatinine ≥353.6μmol/L) (OR 1.08, 95% CI 1.02-1.14). Neither plasma leptin nor adiponectin level had any correlation with creatinine concentration or the amount of albuminuria.. Plasma resistin independently associates with the severity of AKI in acute PUUV infection. The association of resistin with the amount of albuminuria suggests that the level of plasma resistin is not only influenced by renal clearance but could have some role in the pathogenesis of AKI during PUUV infection.

Topics: Acute Disease; Acute Kidney Injury; Adiponectin; Adult; Aged; Albuminuria; Biomarkers; C-Reactive Protein; Cohort Studies; Convalescence; Female; Hemorrhagic Fever with Renal Syndrome; Hospitalization; Humans; Interleukin-6; Leptin; Male; Middle Aged; Puumala virus; Resistin; Severity of Illness Index

We previously showed the deleterious effects of increased dietary protein on renal manifestations and glucose metabolism in leptin receptor-deficient (db) mice. Here, we further examined its effects on glucose metabolism, including urinary C-peptide. We also orally administered mixtures corresponding to low- or high-protein diets to diabetic mice.. In diet experiments, under pair-feeding (equivalent energy and fat) conditions using a metabolic cage, mice were fed diets with different protein content (L diet: 12 % protein, 71 % carbohydrate, 17 % fat; H diet: 24 % protein, 59 % carbohydrate, 17 % fat) for 15 days. In oral administration experiments, the respective mixtures (L mixture: 12 % proline, 71 % maltose or starch, 17 % linoleic acid; H mixture: 24 % proline, 59 % maltose or starch, 17 % linoleic acid) were supplied to mice. Biochemical parameters related to glucose metabolism were measured.. The db-H diet mice showed significantly higher water intake, urinary volume, and glucose levels than db-L diet mice but similar levels of excreted urinary C-peptide. In contrast, control-H diet mice showed significantly higher C-peptide excretion than control-L diet mice. Both types of mice fed H diet excreted high levels of urinary albumin. When maltose mixtures were administered, db-L mixture mice showed significantly higher blood glucose after 30 min than db-H mixture mice. However, db mice administered starch-H mixture showed significantly higher blood glucose 120-300 min post-administration than db-L mixture mice, although both groups exhibited similar insulin levels.. High-protein, low-carbohydrate diets deteriorated diabetic conditions and were associated with insufficient insulin secretion in db mice. Our findings may have implications for dietary management of diabetic symptoms in human patients.

Topics: Albuminuria; Animals; Blood Glucose; Body Weight; C-Peptide; Carbohydrate Metabolism; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, Carbohydrate-Restricted; Dietary Carbohydrates; Dietary Proteins; Insulin; Insulin Secretion; Leptin; Male; Maltose; Mice; Mice, Inbred C57BL; Mice, Knockout; Starch

The relationship between obesity and the development of cardiovascular disease is well established. However, the underlying mechanisms contributing to vascular disease and increased cardiovascular risk in the obese remain largely unexplored. Since leptin exerts direct vascular effects, we investigated leptin and the relationship thereof with circulating markers of vascular damage, namely plasminogen activator inhibitor-1 antigen (PAI-1(ag)), von Willebrand factor antigen (vWF(ag)) and urinary albumin-to-creatinine ratio (ACR). The study included a bi-ethnic population of 409 African and Caucasian teachers who were stratified into lean (<0.5) and obese (⩾0.5) groups according to waist-to-height ratio. We obtained ambulatory blood pressure measurements and determined serum leptin levels, PAI-1(ag), vWF(ag) and ACR, as markers of vascular damage. The obese group had higher leptin (P<0.001) and PAI-1(ag) (P<0.001) levels and a tendency existed for higher vWF(ag) (P=0.068). ACR did not differ between the two groups (P=0.21). In single regression analyses positive associations existed between leptin and all markers of vascular damage (all P<0.001) only in the obese group. After adjusting for covariates and confounders in multiple regression analyses, only the association between leptin and PAI-1(ag) remained (R(2)=0.440; β=0.293; P=0.0021). After adjusting for gender, ethnicity and age, additional analyses indicated that leptin also associated with fibrinogen and clot lysis time in both lean and obese groups, which in turn is associated with 24- h blood pressure and pulse pressure. This result provides evidence that elevated circulating leptin may directly contribute to vascular damage, possibly through mechanism related to thrombotic vascular disease.

Topics: Adult; Albuminuria; Blood Pressure; Body Composition; Body Height; Creatinine; Ethnicity; Female; Hemodynamics; Humans; Leptin; Life Style; Male; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; South Africa; von Willebrand Factor; Waist Circumference

The role of hyperleptinemia in cardiovascular diseases is well known; however, in the renal tissue, the exact site of leptin's action has not been established. This study was conducted to assess the effect of leptin treatment for 7 and 28 days on renal function and morphology and the participation of angiotensin II (Ang II), through its AT1 receptor. Rats were divided into four groups: sham, losartan (10 mg/kg/day, s.c.), leptin (0.5 mg/kg/day for the 7 days group and 0.25 mg/kg/day for the 28 days group) and leptin plus losartan. Plasma leptin, Ang II and endothelin 1 (ET-1) levels were measured using an enzymatic immuno assay. The systolic blood pressure (SBP) was evaluated using the tail-cuff method. The renal plasma flow (RPF) and the glomerular filtration rate (GFR) were determined by p-aminohippuric acid and inulin clearance, respectively. Urinary Na+ and K+ levels were also analyzed. Renal morphological analyses, desmin and ED-1 immunostaining were performed. Proteinuria was analyzed by silver staining. mRNA expression of renin-angiotensin system (RAS) components, TNF-α and collagen type III was analyzed by quantitative PCR. Our results showed that leptin treatment increased Ang II plasma levels and progressively increased the SBP, achieving a pre-hypertension state. Rats treated with leptin 7 days showed a normal RPF and GFR, but increased filtration fraction (FF) and natriuresis. However, rats treated with leptin for 28 showed a decrease in the RPF, an increase in the FF and no changes in the GFR or tubular function. Leptin treatment-induced renal injury was demonstrated by: glomerular hypertrophy, increased desmin staining, macrophage infiltration in the renal tissue, TNF-α and collagen type III mRNA expression and proteinuria. In conclusion, our study demonstrated the progressive renal morphological changes in experimental hyperleptinemia and the interaction between leptin and the RAS on these effects.

Topics: Albuminuria; Angiotensin II; Animals; Blood Pressure; Feeding Behavior; Hemodynamics; Immunohistochemistry; Kidney; Kidney Tubules; Leptin; Male; Peptides; Polymerase Chain Reaction; Rats, Wistar; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; RNA, Messenger; Systole; Time Factors; Weight Gain

The link between diabetic retinopathy (DR) and adipokines is controversial. Some studies suggest that visceral fat and adipokines could be additional risk factors for DR. The aim of this study was to determine the relationship between abdominal fat or adipokine secretion and DR in patients with type 2 diabetes mellitus (DM).. A total of 179 patients with type 2 DM were included. Each patient underwent measurement of plasma adiponectin and leptin and an evaluation of body fat distribution (visceral and subcutaneous) with MRI. The severity of DR was evaluated according to the classification of the American Academy of Ophthalmology. Patients were classified in 3 groups: absence of DR, mild and moderate DR, and advanced DR (severe, proliferative and laser-treated DR).. There were no significant differences between the 3 groups for adiponectin, leptin and visceral or subcutaneous fat accumulation. Patients with DR had a mean duration of diabetes, serum creatinine concentration and percentage of macroalbuminuria significantly higher than patients without DR (p < 0.001, p = 0.003 and p < 0.001, respectively). Serum adiponectin increased with the diabetic nephropathy stage (p = 0.007).. Our study suggests that body fat distribution and adipokine secretion are not associated with DR in patients with type 2 DM.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Albuminuria; Body Fat Distribution; Creatinine; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Leptin; Magnetic Resonance Imaging; Male; Middle Aged

Resistant hypertension (RHTN) includes patients with controlled blood pressure (BP) (CRHTN) and uncontrolled BP (UCRHTN). In fact, RHTN patients are more likely to have target organ damage (TOD), and resistin, leptin and adiponectin may affect BP control in these subjects. We assessed the relationship between adipokines levels and arterial stiffness, left ventricular hypertrophy (LVH) and microalbuminuria (MA). This cross-sectional study included CRHTN (n=51) and UCRHTN (n=38) patients for evaluating body mass index, ambulatory blood pressure monitoring, plasma adiponectin, leptin and resistin concentrations, pulse wave velocity (PWV), MA and echocardiography. Leptin and resistin levels were higher in UCRHTN, whereas adiponectin levels were lower in this same subgroup. Similarly, arterial stiffness, LVH and MA were higher in UCRHTN subgroup. Adiponectin levels negatively correlated with PWV (r=-0.42, P<0.01), and MA (r=-0.48, P<0.01) only in UCRHTN. Leptin was positively correlated with PWV (r=0.37, P=0.02) in UCRHTN subgroup, whereas resistin was not correlated with TOD in both subgroups. Adiponectin is associated with arterial stiffness and renal injury in UCRHTN patients, whereas leptin is associated with arterial stiffness in the same subgroup. Taken together, our results showed that those adipokines may contribute to vascular and renal damage in UCRHTN patients.

Topics: Adipokines; Adiponectin; Aged; Albuminuria; Antihypertensive Agents; Biomarkers; Blood Chemical Analysis; Blood Pressure Monitoring, Ambulatory; Body Mass Index; Brazil; Cross-Sectional Studies; Disease Progression; Drug Resistance; Echocardiography, Doppler; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Leptin; Linear Models; Male; Middle Aged; Multivariate Analysis; Prognosis; Pulse Wave Analysis; Resistin; Statistics, Nonparametric; Vascular Resistance; Vascular Stiffness

The relationship between plasma levels of adiponectin and cardiovascular events is inconclusive. We evaluated the clinical characteristics of people with high plasma adiponectin and high plasma leptin levels.. Thousand seven hundred participants recruited from visitors to the Anti-Aging Doc were divided into four groups by combining the bipartiles of plasma adiponectin and leptin levels in men and women separately: AL, high adiponectin and high leptin; Al, high adiponectin and low leptin; al, low adiponectin and low leptin; aL, low adiponectin and high leptin. Body composition, including visceral fat area and thigh muscle cross-sectional area (CSA), brachial-ankle pulse wave velocity (baPWV), periventricular hyperintensity, and urinary albumin excretion, were determined.. Twenty percent of the studied population fell within the AL group. This group had a significantly higher visceral fat area than the Al group. Thigh muscle CSA was lowest in the AL group among groups. baPWV, brain white matter lesions, and albuminuria findings in the AL group were significantly higher than those of the Al group. Multiple and logistic regression analyses with confounding parameters further confirmed that plasma adiponectin was not an independent determinant for brain and renal small vessel-related disease.. These findings suggest that the plasma level of adiponectin alone is not enough for the risk stratification of cardiovascular disease. Leptin resistance associated with skeletal muscle loss in addition to obesity may need to be addressed to identify high risk people with high plasma adiponectin levels.

Topics: Adiponectin; Aged; Albuminuria; Ankle Brachial Index; Blood Flow Velocity; Body Composition; Female; Humans; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Risk Factors; Sarcopenia; Vascular Stiffness

The intercellular adhesion molecule-1 (ICAM-1) and leptin are important inflammatory biomarkers. We investigated whether plasma-soluble ICAM-1 levels were related to the diabetic nephropathy and systemic inflammation. One hundred forty-seven type 2 diabetic patients and 46 healthy control subjects were studied. Plasma sICAM-1 concentrations were significantly higher in the diabetic groups than controls and increased significantly as diabetic nephropathy advanced. Plasma sICAM-1 levels were positively correlated with body mass index, fasting and postprandial blood glucose, urinary albumin excretion, and negatively correlated with creatinine clearance. Multiple regression analysis showed that plasma leptin levels were associated with a significant increase in plasma sICAM-1 levels. In cultured HUVECs, leptin increased ICAM-1 production in a dose-dependent manner, and this stimulating effect of leptin on ICAM-1 expression was reversed by MEK inhibitor, PD98059. Overall, these findings suggest that activation of leptin synthesis in a diabetic environment promotes ICAM-1 activation via mitogen-activated protein kinase pathway in type 2 diabetic patients.

Topics: Albuminuria; Blood Glucose; Body Mass Index; Cells, Cultured; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Enzyme Activation; Fasting; Female; Flavonoids; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leptin; Male; MAP Kinase Signaling System; Middle Aged; Mitogen-Activated Protein Kinases; Protein Kinase Inhibitors

The plasma leptin/adiponectin (L/A) ratio has been proposed as a preferential marker of atherosclerosis susceptibility compared to leptin and adiponectin alone. We determined the extent to which the L/A ratio predicts incident cardiovascular disease (CVD) taking account of clinical risk factors, microalbuminuria, the total cholesterol/HDL cholesterol (TC/HDL-C ratio), triglycerides, high sensitive C-reactive protein (hs-CRP) and insulin sensitivity (homeostasis model assessment (HOMA(ir))).. A community-based prospective nested case-control study was carried out in 103 non-diabetic men who developed a first cardiovascular event (cases) and 106 male control subjects (no clinically manifest CVD and no lipid lowering drug use at baseline; median follow-up of 3.0 and 10.5 years, respectively). Plasma leptin, adiponectin, the leptin/adipnectin (L/A) ratio, as well as hs-CRP, HOMA(ir) and the TC/HDL-C ratio were determined at baseline.. Plasma leptin levels and the L/A ratio were higher in cases vs. controls (p=0.002 for both), but the difference in adiponectin was not significant (p=0.10). Age-adjusted incident CVD was associated with plasma leptin, adiponectin and the L/A ratio (p=0.045 to p=0.001). The relationships of incident CVD with plasma leptin (p=0.19) and adiponectin (p=0.073) lost statistical significance after additional adjustment for smoking, waist circumference, hypertension, microalbuminuria, the TC/HDL-C ratio, hs-CRP and HOMA(ir). In this fully adjusted analysis, the L/A ratio remained predictive of incident CVD (hazard ratio: 1.40 (95% CI 1.05-1.87), p=0.024).. This study suggests that the L/A ratio may be a preferential marker of a first cardiovascular event in men compared to plasma leptin and adiponectin levels alone.

Topics: Adiponectin; Adult; Aged; Albuminuria; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Cholesterol; Follow-Up Studies; Humans; Incidence; Insulin Resistance; Leptin; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; Triglycerides

To clarify the association of serum leptin levels with progression of diabetic kidney disease in patients with type 2 diabetes (T2D).. This was an observational cohort study of 668 patients with T2D. Patients were classified into three groups by sex-specific tertile of leptin levels. Outcome measurements were the rate of change in estimated glomerular filtration rate (eGFR) and progression to a more advanced stage of albuminuria.. Patients with low or high leptin levels had a steeper eGFR decline (-2.07 and -2.14 mL/min/1.73 m(2)/year) than those with midrange leptin levels (-0.82 mL/min/1.73 m(2)/year; P < 0.01), whereas patients with low leptin levels had an elevated risk of progression of albuminuria as compared with those with high leptin levels (hazard ratio 3.125 [95% CI 1.302-7.499]).. Both low and high serum leptin levels were risk factors for kidney function decline. Meanwhile, lower serum leptin levels were associated with progression of albuminuria.

Topics: Aged; Albuminuria; Asian People; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Female; Glomerular Filtration Rate; Humans; Leptin; Male; Middle Aged; Risk Factors

Postmenopausal women (PMW) are at greater risk for salt-sensitive hypertension and insulin resistance than premenopausal women. Peroxisome-proliferator-activated receptor-gamma (PPARgamma) agonists reduce blood pressure (BP) and insulin resistance in humans. As in PMW, ovariectomy (OVX) increases salt sensitivity of BP and body weight in Dahl salt-sensitive (DS) rats. This study addressed whether rosiglitazone (ROSI), a PPARgamma agonist, attenuates salt-sensitive hypertension in intact (INT) and OVX DS rats, and if so, whether insulin resistance, nitric oxide (NO), oxidative stress, and/or renal inflammation were contributing mediators. Telemetric BP was similar in OVX and INT on low salt diet (0.3% NaCl), but was higher in OVX than INT on high salt (8% NaCl). ROSI reduced BP in OVX and INT on both low and high salt diet, but only attenuated salt sensitivity of BP in OVX. Nitrate/nitrite excretion (NO(x); index of NO) was similar in INT and OVX on low salt diet, and ROSI increased NO(x) in both groups. High salt diet increased NO(x) in all groups but ROSI only increased NO(x) in OVX rats. OVX females exhibited insulin resistance, increases in body weight, plasma leptin, cholesterol, numbers of renal cortical macrophages, and renal MCP-1 and osteopontin mRNA expression compared to INT. ROSI reduced cholesterol and macrophage infiltration in OVX, but not INT. In summary, PPARgamma activation reduces BP in INT and OVX females, but attenuates the salt sensitivity of BP in OVX only, likely due to increases in NO and in part to reductions in renal resident macrophages and inflammation.

Topics: Albuminuria; Animals; Biomarkers; Blood Glucose; Blood Pressure; Body Weight; Chemokine CCL2; Cholesterol; Estradiol; Feeding Behavior; Female; Gene Expression Regulation; Immunohistochemistry; Inflammation; Insulin; Kidney; Leptin; Nitrates; Nitrites; Osteopontin; Ovariectomy; Rats; Rats, Inbred Dahl; RNA, Messenger; Rosiglitazone; Thiazolidinediones

GH deficiency (GHD) is often associated with cardiovascular risk factors, including abdominal fat accumulation, hypercholesterolemia, and increased C-reactive protein. Despite the presence of these risk factors, adults with congenital lifetime isolated GHD (IGHD) due to an inactivating mutation in the GHRH receptor gene do not have premature atherosclerosis.. The aim was to study the serum levels of adiponectin and leptin (antiatherogenic and atherogenic adipokine, respectively), and the urinary albumin excretion (UAE) in these IGHD individuals.. We conducted a cross-sectional study of 20 IGHD individuals (seven males; age, 50.8 +/- 14.6 yr) and 22 control subjects (eight males; age, 49.9 +/- 11.5 yr).. Anthropometric factors, body composition, blood pressure, serum adiponectin, leptin, and UAE were measured.. Adiponectin was higher [12.8 (7.1) vs. 9.7 (5) ng/ml; P = 0.041] in IGHD subjects, whereas no difference was observed in leptin [7.3 (6.3) vs. 9.3 (18.7 ng/ml] and UAE [8.6 (13.8) vs. 8.5 (11.1) microg/min].. Subjects with lifetime untreated IGHD have an adipokine profile with high adiponectin and normal leptin levels that may delay vascular damage and lesions of the renal endothelium.

Topics: Adiponectin; Adult; Aged; Albuminuria; Cross-Sectional Studies; Female; Human Growth Hormone; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Receptors, Neuropeptide; Receptors, Pituitary Hormone-Regulating Hormone; Regression Analysis

Chronic kidney disease (CKD) is a significant public health problem that leads to end-stage renal disease (ESRD) with as many as 2 million people predicted to need therapy worldwide by 2010. Obesity is a risk factor for CKD and leptin, the obesity hormone, correlates with body fat mass and markers of renal function. A number of clinical and experimental studies have suggested a link between serum leptin and kidney disease. We hypothesised that variants in the leptin gene (LEP) may be associated with markers of CKD in indigenous black Africans.. Black South Africans of Xhosa (distinct cultural Bantu-speaking population) descent were recruited for the study and four common polymorphisms of the LEP (rs7799039, rs791620, rs2167270 and STS-U43653 [ENSSNP5824596]) were analysed for genotype and haplotype association with urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), Serum creatinine (Scr) and serum leptin level. In one of the four single nucleotide polymorphisms (SNPs) we examined, an association with the renal phenotypes was observed. Hypertensive subjects with the T allele (CT genotype) of the ENSSNP5824596 SNP had a significantly higher eGFR (p = 0.0141), and significantly lower Scr (p = 0.0137). This was confirmed by haplotype analysis. Also, the haplotype GAAC had a modest effect on urine albumin-to-creatinine ratio in normotensive subjects (p = 0.0482).. These results suggest that genetic variations of the LEP may be associated with phenotypes that are markers of CKD in black Africans.

Topics: Adult; Albuminuria; Alleles; Base Sequence; Black People; Chronic Disease; Creatinine; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genotype; Glomerular Filtration Rate; Haplotypes; Humans; Hypertension; Kidney Diseases; Leptin; Linkage Disequilibrium; Male; Middle Aged; Polymorphism, Single Nucleotide; South Africa

Microalbuminuria portends an increased risk for renal and cardiovascular diseases in diabetes. In this pilot study, we determined the effect of weight loss induced by different types of bariatric surgery on albuminuria in severely obese type 2 diabetic (T2DM) subjects.. Fifteen consecutive T2DM patients (9M/6F, 51+/-14 years, body mass index (BMI) 49+/-9 kg/m2, HbA1c 7.2+/-1.1 percent) undergoing either Roux-en-Y gastric bypass (RYGB; N=9) or other types of bariatric surgery (N=6) underwent determination of urine albumin/creatinine ratio (UACR) and adipokine and insulin sensitivity during a mixed meal tolerance test performed 2 weeks prior to and 6 months following surgery.. Following RYGB, there was a significant decrease in BMI ((-4.74)+/-(-5.05) kg/m2), fasting glucose, cholesterol, and leptin levels. Insulin sensitivity (Matsuda index [12.05+/-3.81, p=0.003]) and high molecular weight (HMW) adiponectin increased significantly along with a significant reduction in UACR (median, 36 mg/g [7-94] vs. 27 mg/g [5.5-42.5], p=0.01). The reduction in UACR following RYGB was inversely correlated with the Matsuda index (r=-0.74), p=0.02) and HMW adiponectin (r=(-0.67), p=0.04). In contrast, despite reduction in BMI ((-4.11)+/-(-4.10) kg/m2) following other types of bariatric surgery (n=6), there was no significant improvement in insulin sensitivity (0.88+/-2.40, p=0.63), UACR, or HMW adiponectin levels.. RYGB in severely obese DM subjects is associated with a reduction in albuminuria that correlates to the improvement in insulin sensitivity and HMW adiponectin. The data point to a need for larger studies to confirm these findings and evaluate the micro-macrovascular benefits including renal parenchymal benefits of different types of bariatric surgery in T2DM.

Topics: Adiponectin; Albuminuria; Bariatric Surgery; Blood Glucose; Body Mass Index; Cholesterol; Creatinine; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Molecular Weight; Obesity, Morbid; Pilot Projects; Risk Factors; Weight Loss

To investigate the possibility of depending on adiponectin and leptin as early predictors of microvascular complications in type 1 diabetic subjects.. We studied 63 type 1 diabetic subjects from the National Institute of Diabetes (30 normoalbuminuric and 33 microalbuminuric). Clinical, demographic characteristics and kidney function tests were monitored. Plasma levels of adiponectin, leptin, interlukein-6 (IL-6), and the high sensitive C-reactive protein (CRP) were measured in these subjects.. Microalbuminuric subjects showed a significant elevation in adiponectin levels and a significant decrease in leptin levels as compared to normoalbuminuric subjects. Adiponectin showed a significant positive correlation with microalbuminuria concentrations while leptin showed a significant negative correlation with both fasting blood glucose and glycated hemoglobin A(1c).. The results of this study introduced the possibility of depending on adiponectin and leptin as early, reliable, and sensitive predictors for the microvascular complications monitored by microalbuminuria concentration and glycemic control indices.

Topics: Adiponectin; Adolescent; Albuminuria; Biomarkers; Blood Glucose; C-Reactive Protein; Child; Child, Preschool; Diabetes Mellitus, Type 1; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Fasting; Female; Glycated Hemoglobin; Humans; Interleukin-6; Kidney Function Tests; Leptin; Male; Predictive Value of Tests; Regression Analysis; Vascular Diseases

The purpose of this study was to determine the long-term impact of obesity and related metabolic abnormalities in the absence and presence of hypertension on renal injury and salt-sensitivity of blood pressure. Markers of renal injury and blood pressure salt sensitivity were assessed in 52- to 55-wk-old normotensive melanocortin-4 receptor-deficient (MC4R-/-) mice and lean C57BL/6J wild-type (WT) mice and in 22-wk-old MC4R-/- and WT mice made hypertensive by N(G)-nitro-L-arginine methyl ester (L-NAME) in the drinking water for 8 wk. Old MC4R-/- mice were 60% heavier, hyperinsulinemic, and hyperleptinemic but had similar mean arterial pressure (MAP) as WT mice (115 +/- 2 and 117 +/- 2 mmHg) on normal salt diet (0.4% NaCl). A high-salt diet (4.0% NaCl) for 12 days did not raise MAP in obese or lean mice [DeltaMAP: MC4R (-/-) 4 +/- 2 mmHg; WT, 2 +/- 1 mmHg]. Obese MC4R-/- mice had 23% greater glomerular tuft area and moderately increased GFR compared with WT mice. Bowman's space, total glomerular area, mesangial matrix, urinary albumin excretion (UAE), renal TGF-beta and collagen expression were not significantly different between old MC4R-/- and WT mice. Renal lipid content was greater but renal macrophage count was markedly lower in MC4R-/- than WT mice. Mild increases in MAP during L-NAME treatment (approximately 16 mmHg) caused small, but greater, elevations in UAE, renal TGF-beta content, and macrophage infiltration in MC4R-/- compared with WT mice without significant changes in glomerular structure. Thus despite long-term obesity and multiple metabolic abnormalities, MC4R-/- mice have no evidence of renal injury or salt-sensitivity of blood pressure. These observations suggest that elevations in blood pressure may be necessary for obesity and related metabolic abnormalities to cause major renal injury or that MC4R-/- mice are protected from renal injury by mechanisms that are still unclear.

Topics: Age Factors; Albuminuria; Animals; Biomarkers; Blood Pressure; Body Weight; Disease Models, Animal; Glomerular Filtration Rate; Heart Rate; Hyperinsulinism; Hypertension; Kidney; Kidney Diseases; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Receptor, Melanocortin, Type 4; Sodium Chloride, Dietary

Obesity and hypertension have been identified as cardiovascular risk factors that contribute to the progression of end-stage renal disease. To examine the mechanisms by which a high-fat diet and hypertension contribute to endothelial dysfunction and renal injury, 8-week-old male spontaneously hypertensive rats and Wistar rats were fed a high-fat (36% fat) or a normal-fat (7% fat) diet for 10 weeks. The high-fat diet increased body weight in Wistar and hypertensive rats by 25 and 31 g, respectively. Systolic blood pressure was higher in the hypertensive rats compared with Wistar rats; however, blood pressure was unaltered by the high-fat diet. Afferent arteriole response to acetylcholine was impaired in the high-fat groups after just 3 weeks. Renal macrophage infiltration was increased in the hypertensive high-fat group compared with others, and monocyte chemoattractant protein-1 excretion was increased in both of the high-fat-fed groups. Renal PCR arrays displayed significant increases in 2 inflammatory genes in hypertensive rats fed a normal diet, 1 gene was increased in high-fat-fed Wistar rats, whereas 12 genes were increased in high-fat-fed hypertensive rats. Urinary albumin excretion was increased in the hypertensive rats compared with the Wistar rats, which was further exacerbated by the high-fat diet. Glomerular nephrin expression was reduced and desmin was increased by the high-fat diet in the hypertensive rats. Our results indicate that endothelial dysfunction precedes renal injury in normotensive and spontaneously hypertensive rats fed a high-fat diet, and hypertension with obesity induces a powerful inflammatory response and disruption of the renal filtration barrier.

Topics: Albuminuria; Animals; Arterioles; Biomarkers; Blood Glucose; Blood Pressure; Body Weight; Chemokine CCL2; Cholesterol; Cytokines; Dietary Fats; Dose-Response Relationship, Drug; Endothelium, Vascular; Gene Expression Profiling; Inflammation; Inflammation Mediators; Insulin Resistance; Kidney; Kidney Cortex; Leptin; Macrophages; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, CCR1; RNA, Messenger

Microalbuminuria increases cardiovascular risk and is considered a metabolic disorder. Low glomerular filtration rate is also associated with increased cardiovascular risk, but the relation of low glomerular filtration rate to metabolic disorders is not well understood.. Designed as a cross-sectional, epidemiologic study, the Insulin Resistance Atherosclerosis Study was conducted in four centers: San Antonio (Texas), San Luis Valley (Colorado), and Oakland and Los Angeles (California). The Modification of Diet in Renal Disease equation was used to classify individuals without diabetes and with normoalbuminuria (n = 856; age 40 to 69 yr) by the presence or absence of low glomerular filtration rate (<60 ml/min per 1.73 m(2)). A direct marker of insulin resistance, the insulin sensitivity index, was measured by the frequently sampled intravenous glucose tolerance test.. Low glomerular filtration rate was related to hypertension and the metabolic syndrome. Low glomerular filtration rate was associated with fasting insulin concentration and insulin sensitivity index. Low glomerular filtration rate was also associated with insulin concentration after adjustment for potential determinants of glomerular filtration rate but was not associated with insulin sensitivity index.. Low glomerular filtration rate is associated with increased insulin concentration in individuals without diabetes and with normoalbuminuria. Longitudinal analyses are needed to determine whether insulin concentration (insulin resistance) precedes the deterioration of renal function.

Topics: Adult; Aged; Albuminuria; C-Reactive Protein; Cross-Sectional Studies; Diabetes Mellitus; Fasting; Glomerular Filtration Rate; Humans; Hypertension; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Southwestern United States

The aims of this study were to measure serum levels of brain-derived neurotrophic factor (BDNF) in patients with type 2 diabetes mellitus (T2DM) and to investigate the association of these BDNF levels with biomarkers of glucose metabolism and insulin resistance.. We studied 112 patients with T2DM and 80 age- and gender-matched control subjects.. Serum BDNF levels were significantly lower in patients with T2DM compared to control subjects (15.5+/-5.2 ng/mL vs. 20.0+/-7.3 ng/mL, P<0.01). In patients with T2DM, BDNF levels were significantly higher in females than in males (P<0.01). In the female patients, BDNF was positively related to immunoreactive insulin (IRI) (rho=0.458, P<0.05) and HOMA-R (rho=0.444, P<0.05). Stepwise multiple regression analysis showed a significant relationship between BDNF and IRI (F=5.294, P<0.05) in female patients with diabetes.. These findings suggest that BDNF may contribute to glucose metabolism.

Topics: Adiponectin; Aged; Albuminuria; Blood Glucose; Blood Pressure; Brain-Derived Neurotrophic Factor; Creatinine; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Patient Selection; Reference Values

To evaluate the effect of weight loss after bariatric surgery (BS) on peripheral adipocytokines, renal parameters and other cardiovascular risk factors (CVRFs).. A total of 70 (41 women) extremely obese adults were prospectively studied before and 12 months after surgery.. 24 (15 women) normal-weight adults. Anthropometric, biochemical and renal parameters were recorded.. Presurgery, adiponectin (ADPN) was lower, whereas leptin, insulin resistance, C-reactive protein, creatinine clearance and albuminuria were higher in patients than controls (P<0.001). All parameters improved postsurgery. Changes in ADPN correlated negatively with leptin, insulin resistance, albumin, C-reactive protein, and creatinine clearance. Multiple regression analysis: using changes in ADPN as the dependent variable, only changes in insulin resistance (P=0.005) and albumin (P=0.019) were significant independent determinants for changes in ADPN. No statistical differences were found in relation to the degree of obesity.. Patients changed to obesity type I after surgery. This implies a substantial improvement of CVRFs including ADPN, creatinine clearance and albuminuria. Changes in plasma ADPN correlated negatively with insulin resistance and with albuminemia but not with renal parameters. The lack of differences between different degrees of obesity suggests that the relationship between weight and CVRFs no longer exists when obesity becomes very extreme.

Topics: Adiponectin; Adult; Albuminuria; Bariatric Surgery; C-Reactive Protein; Cardiovascular Diseases; Creatinine; Female; Humans; Insulin Resistance; Kidney; Leptin; Male; Metabolic Clearance Rate; Middle Aged; Obesity; Prospective Studies; Serum Albumin; Weight Loss

Because of increasing evidence that white blood cells (WBCs) play a role in the development and progression of diabetes complications, this study aimed to investigate the relation of circulating total and differential leukocyte counts to nephropathy in patients with type 2 diabetes. Plasma leptin levels were also measured to investigate their role in peripheral leukocytosis.. For this study, 1,480 subjects with type 2 diabetes who were enrolled in a disease management program were stratified according to urinary microalbumin and serum creatinine measurements. The total and differential leukocyte profiles of peripheral blood were measured and plasma leptin was examined by enzyme-linked immunosorbent assay. Demographic and potential metabolic confounding factors were analyzed with linear and logistic regression to calculate the effects of leukocyte count on diabetic nephropathy.. The peripheral total WBC, monocyte, and neutrophil counts increased in parallel with the advancement of diabetic nephropathy. In contrast, the lymphocyte count decreased. When WBC counts were analyzed per quartile and as continuous variables after adjusting for age, sex, and other known risk factors with multiple regression analysis, peripheral total WBC, monocyte, neutrophil, and lymphocyte counts were independently and significantly associated with diabetic nephropathy. Plasma leptin levels increased in patients with nephropathy and correlated significantly with total WBC count (r = 0.194, P = 0.014).. Because leukocytes are activated and secrete cytokines in the diabetic state and leptin stimulates leukocyte proliferation and differentiation, our results suggest that circulating leukocytes contribute to the development and progression of nephropathy, partially through the effects of leptin, in patients with type 2 diabetes.

Topics: Albuminuria; Biomarkers; Creatinine; Diabetic Nephropathies; Female; Humans; Leptin; Leukocyte Count; Leukocytosis; Lymphocyte Count; Male; Middle Aged; Regression Analysis; Risk Factors

The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with end-stage renal disease (ESRD). Adiponectin is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk for CVD.. In a cohort of 204 (62% males) ESRD patients aged 52 +/- 1 years the following parameters were studied: presence of CVD, body composition, plasma adiponectin (N= 107), cholesterol, triglycerides, HDL-cholesterol, serum leptin, high-sensitivity C-reactive protein (hs-CRP), urinary albumin excretion (UAE), and single-nucleotide polymorphisms (SNPs) in the apM1 gene at positions -11391, -11377, 45, and 276. Thirty-six age- (52 +/- 2 years) and gender-matched (64% males) healthy subjects served as control subjects.. Markedly (P < 0.0001) elevated median plasma adiponectin levels were observed in ESRD patients (22.2 microg/mL), especially type 1 diabetic patients (36.8 microg/mL), compared to control subjects (12.2 microg/mL). Log plasma adiponectin correlated to visceral fat mass (R=-0.29; P < 0.01) and Log hs-CRP (R=-0.26; P < 0.01). In a stepwise (forward followed by backward) multiple regression model only type-1 diabetes (P < 0.001) and visceral fat mass (P < 0.05) were independently associated with plasma adiponectin levels. The adiponectin gene -11377 C/C genotype was associated with a lower prevalence of CVD (25 vs. 42%) compared to the G/C genotype.. The present cross-sectional study demonstrates that, whereas genetic variations seem to have a minor impact on circulating adiponectin levels, lower visceral fat mass and type 1 diabetes mellitus are associated with elevated plasma adiponectin levels in ESRD patients. Furthermore, low levels of adiponectin are associated with inflammation in ESRD.

Topics: Adiponectin; Albuminuria; Biomarkers; Body Composition; C-Reactive Protein; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Female; Fibrinogen; Genetic Variation; Glomerular Filtration Rate; Humans; Intercellular Signaling Peptides and Proteins; Kidney Failure, Chronic; Leptin; Lipids; Male; Middle Aged; Phenotype; Proteins

Leptin plays an important role in the regulation of body weight and energy balance. Women have higher circulating leptin level than men. In this study, we examined serum leptin concentrations in Type 2 diabetic men and women with or without nephropathy. Fasting plasma glucose (FPG), lipid profile, and serum leptin concentrations were measured in 34 Type 2 diabetic patients with nephropathy (DMN), 12 normoalbuminuric Type 2 diabetic subjects (DM) and 34 non-diabetic control subjects, all matched for age and body mass index (BMI).. Patients with diabetic nephropathy had lower high-density lipoprotein cholesterol and higher triglyceride, FPG, urinary albumin/creatinine ratio (ACR) and serum creatinine than the other two groups. There was a significant trend in serum leptin concentrations (P<0.001, analysis of variance ANOVA) across the three groups with the main difference being detected between DMN and control subjects (DMN: 17.5 +/- 16.8 ng/ml, DM: 14.6 +/- 10.5 ng/ml and control: 9.1 +/- 7.1 ng/ml). Women had higher serum leptin concentration than men in the control group (12.5 +/- 7.3 ng/ml versus 4.2 +/- 2.0 ng/ml, P=0.001) and in the DM group (18.9 +/- 11 ng/ml versus 8.6 +/- 5.9 ng/ml, P=0.07) whereas this gender difference was not observed in the DMN group (18.6 +/- 17.0 ng/ml versus 16.8 +/- 17.0 ng/ml, P=0.754). On multivariate analysis, ACR (=0.411, P<0.001) and BMI (=0.240, P=0.002) were independently associated with serum leptin concentrations (R2=0.194, F=22.1, P<0.001) in the whole group. In the DMN group, ACR (=0.370, P=0.016) was the only independent determinant of serum leptin concentrations (R2=0.159, F=11.4, P=0.016). Serum leptin concentrations were higher in Type 2 diabetic patients with nephropathy than normoalbuminuric diabetic patients and controls. Diabetic men with nephropathy had proportionally higher serum leptin such that the gender difference in leptin observed in non-nephropathic individuals was abolished.

Topics: Adult; Albuminuria; Analysis of Variance; Body Mass Index; Case-Control Studies; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Leptin; Male; Middle Aged; Osmolar Concentration; Sex Characteristics

To evaluate the changes of serum leptin levels after weight reduction in diabetic subjects with and without microalbuminuria, we studied 10 obese healthy subjects, 12 obese diabetics with persistent microalbuminuria and 10 obese diabetic subjects without microalbuminuria. Obese diabetic patients with microalbuminuria showed serum leptin levels significantly higher than normoalbuminuric diabetics, while no difference was found between obese diabetics without microalbuminuria and healthy controls. All obese subjects followed a 12-month intensive weight reduction program during which the mean change in body mass index was similar between obese diabetic and obese healthy subjects (obese diabetics without microalbuminuria: 35.2+/-4.3 vs 29.9+/-4.1, p<0.05; obese diabetics with microalbuminuria: 35.7+/-3.9 vs 30.3+/-4.0, p<0.05; obese healthy subjects: 35.5+/-4.0 vs 30.1+/-3.9, p<0.05). The mean changes in serum leptin levels tended to be similar in two groups of subjects studied (obese diabetics without microalbuminuria: 37.6+/-4.1 vs 19.7+/-4.9, p<0.001; obese healthy subjects: 37.1+/-4.3 vs 20.1+/-5.1, p<0.001); obese microalbuminuric subjects showed higher leptin levels (42.4+/-4.0 vs 30.3+/-4.2, p<0.001) than normoalbuminuric diabetic and obese healthy subjects. In conclusion, during weight loss, independently from the quality of metabolic control, serum leptin concentrations declined in both groups of obese diabetics. The changes of leptin in diabetics seem to be similar to those observed in healthy obese subjects.

Topics: Adolescent; Albuminuria; Body Mass Index; Body Weight; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Humans; Leptin; Obesity; Weight Loss

Preperitoneal fat is an indicator of visceral fat deposition, which is closely related to atherosclerosis and coronary heart disease in obese patients. We assessed the relationship of preperitoneal fat deposition and various clinical characteristics in 90 patients with non-insulin-dependent diabetes mellitus (NIDDM). Preperitoneal and subcutaneous fat deposition were measured by ultrasonography. In both the male and female diabetics, preperitoneal fat levels were significantly higher than in age-matched healthy subjects. We also determined blood pressures, fasting plasma glucose, glycosylated hemoglobin A1c, serum lipids, fasting immunoreactive insulin (FIRI), daily urinary C-peptide (CPR), serum leptin, urinary albumin excretion and body mass index (BMI). Of these parameters, BMI, FIRI, leptin and daily urinary CPR were positively correlated with preperitoneal fat deposition. Patients with diet therapy alone showed significantly higher preperitoneal fat levels than those receiving insulin therapy. In female, patients with increased preperitoneal fat showed higher prevalence of hypertension than those with decreased fat. Macroalbuminuric patients had a lower preperitoneal fat than microalbuminuric and normoalbuminuric patients. Patients with proliferative retinopathy exhibited lower preperitoneal fat than did those without retinopathy. Preperitoneal fat levels were positively correlated with motor or sensory nerve conduction velocity.. The present findings suggest that in NIDDM patients, increased preperitoneal fat deposition is closely associated with obesity, hypertension and hyperinsulinemia, and negatively modulates diabetic microangiopathy including nephropathy, retinopathy and neuropathy.

Topics: Adipose Tissue; Albuminuria; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Fasting; Female; Humans; Hypoglycemic Agents; Insulin; Leptin; Male; Middle Aged; Neural Conduction; Peritoneum; Proteins; Reference Values; Sensation; Skin; Time Factors; Ultrasonography

Leptin levels are elevated in end-stage renal disease, suggesting an impairment of renal leptin degradation. The present study aimed to determine whether leptin levels are also elevated in patients with earlier stages of renal disease, ie, microalbuminuric and macroalbuminuric nephropathy. A total of 60 subjects were assigned to two study groups. Group A contained 10 type 2 diabetics with macroalbuminuria, 10 type 2 diabetics with normoalbuminuria, and 10 healthy control subjects. Group B contained 10 type 2 diabetics with microalbuminuria, 10 type 2 diabetics with normoalbuminuria, and 10 healthy controls. The subgroups of both study groups were matched for sex and body fatness. In group A, macroalbuminuric diabetic patients had higher serum leptin levels than the normoalbuminuric diabetics (11.90 +/- 2.98 v 4.13 +/- 0.92 ng/mL, P < .002) and control subjects (4.78 +/- 1.37 ng/mL, P < .006). In group B, microalbuminuric diabetics had higher serum leptin levels than the normoalbuminuric diabetics (21.16 +/- 5.80 v8.74 +/- 1.89 ng/mL, P < .04) and control subjects (10.06 + 3.00 ng/mL, P < .06). In both groups A and B, creatinine clearance was inversely correlated with the serum leptin level after adjusting for body fat. In conclusion, serum leptin levels are elevated in type 2 diabetic patients with microalbuminuria and macroalbuminuria, suggesting that renal leptin degradation is already impaired in the early stages of renal disease.

Topics: Adipose Tissue; Aged; Albuminuria; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Reference Values; Triglycerides

Topics: Albuminuria; Arizona; Confidence Intervals; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Fasting; Glomerular Filtration Rate; Humans; Indians, North American; Leptin; Proteins

To investigate the relationship between leptin levels and IDDM with and without microalbuminuria, fasting serum levels of leptin, insulin, insulin-like growth factor-1 (IGF-1), sex hormone-binding globulin (SHBG), testosterone (SHBG) ratio, blood pressure and body mass index (BMI) were measured in 18 normo- and 11 microalbuminuric females with >5 years of IDDM, and 24 healthy controls in late puberty. Leptin levels were higher in micro- than normoalbuminuric IDDM patients, and lower in healthy controls than in both IDDM groups (p < 0.05, respectively). In multiple regression analysis, presence of IDDM and BMI independently contributed to increased leptin values (R2 = 0.34, p < 0.001). Including IDDM females only, solely low IGF-1 and high testosterone/SHBG were associated with leptin (R2 = 0.39, p = 0.009). Albumin excretion rate (AER) was correlated to leptin (r = 0.48, p = 0.01). With AER as the dependent variable only serum leptin and diastolic blood pressure added to the regression (R2 = 0.59, p < 0.001). In conclusion, serum leptin, independently of BMI, is: (1) increased in IDDM females of late puberty; (2) associated with low IGF-1 and hyperandrogenemia, and (3) related to increased albumin excretion rate in IDDM females.

Topics: 3-Hydroxybutyric Acid; Adolescent; Adult; Albuminuria; Blood Pressure; Body Mass Index; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Fluoroimmunoassay; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Hyperandrogenism; Insulin; Insulin-Like Growth Factor I; Leptin; Proteins; Puberty; Radioimmunoassay; Regression Analysis; Sex Hormone-Binding Globulin; Testosterone