Association of insulin resistance with arterial stiffness in nondiabetic peritoneal dialysis patients

Background  

Insulin resistance is a risk factor for cardiovascular morbidity and mortality in the general and end-stage renal disease populations. In this study, we investigated the association between insulin resistance and arterial stiffness in nondiabetic peritoneal dialysis (PD) patients.     

Correlation of microalbuminuria and outcome in patients with extensive burns

Background. Microalbuminuria, often referred to as the urinaryalbumin–creatinine ratio (ACR), is thought to be a reflectionof increased capillary permeability associated with the systemicinflammatory response syndrome, and has been found to be predictiveof outcome in several studies. Therefore, we explored the usefulnessof ACR as a predictor of mortality, and whether there was acorrelation between ACR and     

Insulin resistance precedes microalbuminuria in patients with insulin-dependent diabetes mellitus

Background. Insulin resistance has been associated with hypertension and with renal complications in patients with type 1 diabetes mellitus. Causal relationships have not been fully explained. Methods. We investigated whether insulin resistance precedes microalbuminuria by measuring insulin resistance with a euglycaemic clamp in combination with indirect calorimetry in 16 uncomplicated type 1 diabetic patients and in six healthy control subjects. The patients had over 10 year duration of diabetes, and were expected to experience either a complication-free or complicated disease course within the next few years. They have thereafter been followed for the development of microalbuminuria for 3 years. Results. In a euglycaemic insulin clamp glucose disposal was lower in diabetic patients compared with control subjects (7.5±2.9 and 12.6±2.0 mg/kg LBM/min; P<0.002), mainly due to impaired glucose storage (4.3±2.3 vs 8.6±1.6 mg/kg LBM/min; P<0.001). Three years later seven IDDM patients had albumin excretion rate over 30 mg/24 h; glucose disposal (5.5±2.1 vs 9.0±2.2 mg/kg LBM/min; P<0.01) had been lower in patients who developed microalbuminuria compared with those who remained normoalbuminuric. Conclusions. Insulin resistance predicts the increment in urinary albumin excretion. Insulin resistance depends mainly on impaired glucose storage in uncomplicated IDDM.     

Perirenal fat associated with microalbuminuria in obese rats

Purpose

To determine whether perirenal fat is associated with increased urinary albumin excretion and whether perirenal fat affects renal vascular endothelial function in obese rats.

Methods

Wistar rats were randomly divided into normal and obesity group, which were fed with normal and high-fat diet, respectively. Blood and urine samples were collected. Endothelial function of the aorta was determined by measuring endothelium-dependent vasodilatation. Renal tissues were collected for CD34 immunohistochemistry and free fatty acids (FFA) measurement. Levels of glomerular nitric oxide (NO) and reactive oxygen species (ROS) were measured.

Results

After 24 weeks, plasma FFA, high-sensitivity C-reactive protein, and malondialdehyde levels were elevated and were significantly higher in renal venous blood than in jugular venous blood in obese rats. Urinary albumin/creatinine ratio, glomerular CD34 expression, glomerular ROS level, and renal cortex FFA levels were higher in obese rats. Endothelial dysfunction was more severe in the infra-renal aorta than in the thoracic aorta in obese rats. Plasma adiponectin and glomerular NO levels were lower in obese rats.

Conclusion

Perirenal fat is associated with increased urinary albumin excretion in obese rats. The mechanism may be renal vascular endothelial dysfunction caused by increased oxidative stress and activation of inflammatory molecular pathways due to elevated FFA and low adiponectin levels.     

Characteristics and risk factors of intrarenal arterial lesions in patients with IgA nephropathy.

BACKGROUND: Although the clinical importance of immunoglobulin-A nephropathy (IgAN) is widely recognized, the characteristics of intrarenal arterial lesions in this disease and the main factors associated with them have not been studied extensively, and a large-scale analysis of intrarenal arterial lesions in IgAN has not been performed. METHODS: To clarify these issues, we investigated the prevalence, underlying factors and significance of intrarenal arterial lesions in 1005 patients with IgAN. We distinguished different degrees of severity of small artery and arteriolar lesions (mild, moderate and severe), using a semi-quantitative scoring system. We compared the arterial lesions of IgAN patients with those of 627 non-IgAN patients, who had mesangial proliferating glomerulonephritis without IgA deposits, and of 221 patients with membranous nephropathy (MN). RESULTS: The IgAN patients with arterial lesions were significantly younger than the non-IgAN and MN patients (mean ages 34.6 vs 40.4 and 47.7 years, respectively). The prevalence of intrarenal small artery and arteriolar lesions was 54.6% in IgAN patients, compared with 26.6 and 47.1% in non-IgAN and MN patients, respectively; the percentages of moderate/severe arterial lesions were 37.0 vs 21.6 and 23.1%, respectively; and the percentages of hyaline changes were 43.7 vs 16.8 and 21.2%, respectively. The differences in the prevalence of lesions between IgAN patients and the two other groups were statistically significant for all three parameters. Our search for possible relationships between arterial-arteriolar lesions and various indirect outcome markers disclosed significant associations with hypertension, higher serum creatinine and uric acid, high urinary protein excretion, glomerulosclerosis, tubular atrophy and interstitial fibrosis. Furthermore, these parameters were changed more markedly in IgAN patients with moderate/severe arterial lesions and hyaline changes than in IgAN patients who had mild arterial lesions and wall thickening alone. CONCLUSIONS: The prevalence of small intrarenal arterial-arteriolar lesions was higher in IgAN patients than in non-IgAN and MN patients; moreover, the lesions in IgAN patients were associated with younger age, were more severe and exhibited a higher degree of hyaline changes. Finally, the severity of small arterial- arteriolar lesions was linked to several markers of adverse outcome.     

Increased renal arterial resistance predicts the course of renal function in type 2 diabetes with microalbuminuria

Type 2 diabetic patients often die because of end-stage renal failure, but no definitive reliable factor predicting long-term renal outcome has been identified. We tested whether a renal arterial resistance index (R/I) > or =80, using Doppler ultrasound technique, was predictive of worsening renal function. The primary end points of the study were 1) the course of glomerular filtration rate (GFR) and 2) the albumin excretion rate in 157 microalbuminuric, hypertensive, type 2 diabetic patients after a 7.8-year follow-up period (range 7.1-9.2). Kaplan-Meier curves for the primary end point (decrease of GFR > or = -3.0 ml/min per 1.73 m(2) per year) was two to three times more frequently observed in patients with R/I > or =80. Four- to fivefold fewer patients showed a regression to normoalbuminuria during the follow-up period from baseline microalbuminuria in the cohort with R/I > or =80. Overt proteinuria did develop in 24% of patients with R/I > or =80 and in 5% of patients with R/I <80 (P < 0.01). In conclusion, intrarenal arterial resistance appears to play a nontrivial role in deteriorating renal function in type 2 diabetic patients. R/I is a noninvasive diagnostic procedure, which strongly predicts the outcome of renal function in type 2 diabetic patients, even when GFR patterns are still normal.     

Percutaneous nephrolithotomy in a patient with intrarenal arterial aneurysm

We report the case of a male patient with a left renal pelvic stone 2.5 cm in maximum diameter and a large upper pole intrarenal arterial aneurysm on the same side. The stone was treated with percutaneous nephrolithotomy (PCNL). This procedure was feasible even in this difficult clinical setting. Puncture of a calyx located at a safe distance from the aneurysm and meticulous surgical technique were essential in realizing the best possible outcome. To our knowledge, this is the first case of PCNL performed on a patient with a renal stone and an intrarenal arterial aneurysm.     

Intraoperative arterial oxygenation in obese patients.

Although obese patients have been shown to represent a particularly high risk group with respect to hypoxemia both pre and postoperatively, no data exist to delineate the intraoperative arterial oxygenation pattern of these patients. Furthermore, no one has studied the effects of a change in operative position or a subdiaphragmatic laparotomy pack on arterial oxygenation (PaO2). Sixty-four adults undergoing jejunoileal bypass for morbid exogenous obesity, with a mean weight of 142.0 +/- 31.4 kg and a mean age of 33.3 +/- 10.4 years, were studied. Twenty-five patients (Group I) were maintained in the supine position throughout the operative procedure, while the remaining 39 patients (Group II) were changed to a 15 degrees head down position 15 minutes after a control blood sample was taken. Four additional markedly obese patients were studied to determine the effect of an abdominal pack of PaO2 values. The following findings were demonstrated: 1) 40% oxygen did not uniformly produce adequate arterial oxygenation for intra-abdominal surgery in otherwise healthy obese patients; 2) placement of a subdiaphragmatic abdominal laparotomy pack without a change in operative position resulted in a consistent fall in PaO2 in each patient to less than 65 mm Hg even though 40% oxygen was being administered; and 3) a change from supine to a 15 degrees head down operative position resulted in a significant (P less than 0.001) reduction in mean PaO2 (73.0 +/- 26.3 mm Hg). Seventy-seven per cent of these patients demonstrated PaO2 values of less than 80 mm Hg on 40% oxygen. Because of these findings, serious consideration should be given to the routine use of the Trendelenberg position intraoperatively in obese patients. However, if one elects this posture, prudence would dictate careful monitoring and maintenance of arterial oxygenation. Certainly, in obese patients, the intraoperative combination of the head down position and a subdiaphragmatic laparotomy pack should be avoided. In addition, since our data were collected in obese but otherwise healthy, young patients free of cardiorespiratory disease, special attention should be directed at the continuous measurement of arterial oxygenation in the older obese patient with either intrinsic dysfunction of vital organs (heart, lung, liver, kidney) or surgical disorders (peritonitis, sepsis).     

Lipoprotein insulin resistance score in nondiabetic patients with obesity after bariatric surgery

BackgroundLipoprotein insulin resistance (LPIR) score is a composite biomarker representative of atherogenic dyslipidemia characteristic of early insulin resistance. It is elevated in obesity and may provide information not captured in glycosylated hemoglobin and homeostatic model assessment for insulin resistance. While bariatric surgery reduces diabetes incidence and resolves metabolic syndrome, the effect of bariatric surgery on LPIR is untested.ObjectivesWe sought to assess the effects of Roux-en-Y gastric bypass and sleeve gastrectomy on LPIR in nondiabetic women with obesity.SettingNonsmoking, nondiabetic, premenopausal Hispanic women, age ≥18 years, undergoing Roux-en-Y gastric bypass or sleeve gastrectomy at Bellevue Hospital were recruited for a prospective observational study.MethodsAnthropometric measures and blood sampling were performed preoperatively and at 6 and 12 months postoperatively. LPIR was measured by nuclear magnetic resonance spectroscopy.ResultsAmong 53 women (Roux-en-Y gastric bypass, n = 22; sleeve gastrectomy, n = 31), mean age was 32 ± 7 years and body mass index 44.1 ± 6.4 kg/m². LPIR was reduced by 35 ± 4% and 46 ± 4% at 6 and 12 months after surgery, respectively, with no difference by procedure. Twenty-seven of 53 patients met International Diabetes Federation criteria for metabolic syndrome preoperatively and had concomitant higher homeostatic model assessment for insulin resistance, glycosylated hemoglobin, nonhigh-density lipoprotein-cholesterol and LPIR. Twenty-five of 27 patients experienced resolution of metabolic syndrome postoperatively. Concordantly, the preoperative differences in homeostatic model assessment for insulin resistance, glycosylated hemoglobin, and nonhigh-density lipoprotein-cholesterol between those with and without metabolic syndrome resolved at 6 and 12 months. In contrast, patients with metabolic syndrome preoperatively exhibited greater LPIR scores at 6 and 12 months postoperatively.ConclusionThis is the first study to demonstrate improvement in insulin resistance, as measured by LPIR, after bariatric surgery with no difference by procedure. This measure, but not traditional markers, was persistently higher in patients with a preoperative metabolic syndrome diagnosis, despite resolution of the condition.     

Lower extremity arterial revascularization in obese patients

BACKGROUND: Obesity and associated comorbidities are associated with a high rate of complications and technical difficulties after a number of surgical procedures. We studied the role of obesity in outcomes in lower extremity arterial revascularization. METHODS: We reviewed all lower extremity arterial revascularizations performed at our institution in 2000. Body mass index (BMI) greater than or equal to 30 kg/m(2) defined obesity. Perioperative outcomes, long-term survival, and graft patency were evaluated in obese and nonobese patients by using linear regression, the Fisher exact test, and Kaplan-Meier analysis. RESULTS: The study population consisted of 74 (26%) obese and 207 (74%) nonobese patients. Patient demographics of the obese and nonobese populations were similar. The mean BMI for obese patients was 35 +/- 5 kg/m(2) and in nonobese patients was 25 +/- 3 kg/m(2). The mean age of each group was 67 +/- 10 years (BMI > or =30 kg/m(2)) and 70 +/- 13 years (BMI <30 kg/m(2)). There were 45 (61%) obese men and 29 (39%) obese women. There were 128 (62%) nonobese men and 79 (38%) nonobese women. Diabetes was present in 76% of the obese and 70% of the nonobese patients. Perioperative myocardial infarction, 30-day mortality, and rate of reoperation within 30 days were not significantly different. Obese patients had higher increased postoperative wound infection rates (16% vs 7%; P = .04). Survival analysis showed 81% +/- 5% and 85% +/- 3% 1-year survival and 66% +/- 6% and 62% +/- 3% 3-year survival in obese and nonobese patients (P = .58), respectively. Kaplan-Meier estimates showed no effect of obesity on long-term graft patency, with 1-year graft patency rates of 82% +/- 6% and 81% +/- 4% in obese and nonobese patients, respectively (P = .79). CONCLUSIONS: Obese patients have similar limb salvage rates, perioperative cardiac morbidity, long-term survival rates, and long-term graft patency but have increased perioperative wound infections.     

Association of the insulin resistance syndrome and microalbuminuria among nondiabetic native Americans. The Inter-Tribal Heart Project

This study investigated the association between microalbuminuria and the insulin resistance syndrome (IRS) among nondiabetic Native Americans. In a cross-sectional survey, age-stratified random samples were drawn from the Indian Health Service clinic lists for one Menominee and two Chippewa reservations. Information was collected from physical examinations, personal interviews, and blood and urine samples. The urinary albumin:creatinine ratio (ACR) was measured using a random spot urine sample. The IRS was defined by the number of composite traits: hypertension, impaired fasting glucose (IFG), high fasting insulin, low HDL cholesterol, and hypertriglyceridemia. Among the 934 eligible nondiabetic participants, 15.2% exhibited microalbuminuria. The prevalence of one, two, and three or more traits was 27.0, 16.6, and 7.4%, respectively. After controlling for age, sex, smoking, body mass index, education, and family histories of diabetes and kidney disease, the odds ratio (OR) for microalbuminuria was 1.8 (95% confidence interval [CI], 1.1 to 2.8) for one IRS trait, 1.8 (95% CI, 1.0 to 3.2) for two traits, and 2.3 (95% CI, 1.1 to 4.9) for three or more traits (versus no traits). The pattern of association appeared weaker among women compared with men. Of the individual IRS traits, only hypertension and IFG were associated with microalbuminuria. Among these nondiabetic Native Americans, the IRS was associated with a twofold increased prevalence of microalbuminuria. Health promotion efforts should focus on lowering the prevalence of hypertension, as well as glucose intolerance and obesity, in this population at high risk for renal and cardiovascular disease.     

Postoperative arterial blood gas measurement in obese patients: effect of position on gas exchange.

The effect of position change on blood gas exchange was studied in 22 markedly obese, otherwise healthy, women both preoperatively and postoperatively. There was a statistically significant decrease in arterial oxygen tension and a simultaneous reduction both in the arterial carbon dioxide tension and the base excess with the assumption of the supine versus the semirecumbent position on postoperative days one and two. However, no positional difference was demonstrable in any variable by the third postoperative day. This study indicates that in obese patients during the first 48 hours after abdominal surgery, assumption and maintenance of the semirecumbent posture is a valuable therapeutic adjunct to improve arterial oxygenation.     

The insulin sensitivity index in nondiabetic man. Correlation between clamp-derived and IVGTT-derived values

Although the minimal-model-based insulin sensitivity index (S1) can be estimated from the results of a simple 180-min intravenous glucose tolerance test (IVGTT), its relationship to widely accepted but technically more difficult clamp-based techniques has not been resolved in humans. Therefore we measured S1 by standard IVGTT, modified IVGTT, and clamp methods in 10 nondiabetic men with %IBW of 109 +/- 12 (mean +/- SD). In the euglycemic clamp studies, insulin was infused to bring insulin levels (IRI) from basal, 8 +/- 4 microU/ml, to plateaus of 21 +/- 5 and 35 +/- 6 microU/ml. S1[clamp], measured as the increase in glucose (G) clearance per increase in IRI [delta INF/(delta IRI X G)], averaged 0.29 +/- 0.09 ml/kg X min per microU/ml. In the IVGTT studies, 300 mg/kg G was given as an i.v. bolus, and G and IRI were measured for 180 min; in the modified (mod) IVGTT, tolbutamide (300-500 mg) was given i.v. 20 min after the G to observe the effect of an IRI peak on G removal after G level was free of initial "mixing" effects. The S1 estimated by computer did not differ significantly between standard [(6.9 +/- 3.4) X 10(-4) min-1 per microU/ml] and modified [(6.7 +/- 3.5) X 10(-4) min-1 per microU/ml] tests, indicating no bias due to the differing insulin patterns and levels. There was a strong positive correlation between S1 (mod IVGTT) and S1(clamp): r = 0.84; N = 10; P less than 0.002. The correlation between S1(standard IVGTT) and S1(clamp) was 0.54, suggesting the modified test is less "noisy." Nonetheless, in eight euglycemic women with a wider range of adiposity, S1(standard IVGTT) has been significantly correlated with %IBW (r = -0.72) and basal IRI (r = -0.84). The correlation between S1 measures by clamp and IVGTT methods provides one step toward validation of the minimal model for studies of insulin action in man.     

Prevalence, severity and predictors of HOMA-estimated insulin resistance in diabetic and nondiabetic patients with end-stage renal disease

BACKGROUND: Prevalence of insulin resistance (IR) is increased in type 2 diabetes and in end-stage renal disease (ESRD). IR is associated with advanced atherosclerosis and is an independent predictor for cardiovascular disease in diabetes and ESRD patients. We investigated prevalence, severity, predictors and relation to vascular diseases by the homeostasis model assessment (HOMA-IR) in diabetic and nondiabetic ESRD patients. METHODS: ESRD patients with type 2 diabetes (n = 27) and nondiabetic ESRD patients (n = 35) were included in the study. IR was assessed with the HOMA-IR using fasting glucose and insulin levels. Additionally, serum levels of C-peptide, HbA1c, triglycerides, cholesterol and C-reactive protein and blood pressure were assessed. RESULTS: Median HOMA-IR was significantly higher in the diabetic ESRD patients than in the nondiabetic ESRD patients (6.3 [range 0.7-61.7] vs. 2.4 [range 0.3-5.7]; p < 0.001). Systolic blood pressure and triglycerides were significantly higher in patients with higher HOMA-IR, whereas HDL cholesterol was significantly lower in those patients. Only nondiabetic patients with increased HOMA-IR had significantly higher C-peptide levels than those with lower HOMA-IR (14.9 + 5.7 vs. 9.0 + 4.3, p = 0.004). Vascular disease prevalence was significantly higher in diabetic patients with higher HOMA-IR than in those with lower HOMA-IR. CONCLUSIONS: Prevalence and severity of HOMA-IR was greater in diabetic ESRD patients than in those without diabetes. In diabetic patients low HDL cholesterol was the only predictor for higher HOMA-IR, whereas in nondiabetic patients a high C-peptide level was the only predictor for higher HOMA-IR. The prevalence of vascular diseases is associated with higher HOMA-IR in ESRD patients.