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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal clearances and extraction ratios for 51Cr-EDTA and PAH were studied in six young patients with insulin-dependent diabetes. The duration of the disease was 1 to 4 years, and no patient had signs of diabetic complications. Catheterization of the right renal vein and the left brachial artery was performed. The extraction ratios for 51Cr-EDTA, PAH, and glucose were determined at two different levels of blood glucose. Clearance for 51Cr-EDTA was increased by 9.7% and for PAH by 8.5% compared to normal control subjects while the extraction ratios for 51Cr-EDTA and PAH were normal. Extraction ratio for glucose was very low. There was no correlation between the individual HbA1 values and the clearances for 51Cr-EDTA and PAH. Extraction ratios for these substances were not influenced by acute changes in blood glucose level. The normal PAH extraction ratio indicates that PAH clearance is a reliable estimate of RPF in early insulin-dependent diabetes.
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PMID:Renal extraction ratios for 51Cr-EDTA, PAH, and glucose in early insulin-dependent diabetic patients. 681 14

Hyperfiltration occurs early in diabetes mellitus and has been implicated in the development of microalbuminuria. Our aim was to re-examine the controversial relationship between glycaemic control and glomerular filtration (GFR) in normoalbuminuric, normotensive, non-obese patients with short duration Type 1 diabetes mellitus (DM). We studied 75 Type 1 DM patients, 35 male, aged 18-42 years, with a duration of diabetes of 4-8 years. GFR was determined by inulin clearance; hyperfiltration was defined as above 145 ml min(-1) 1.73 m(-2) (equivalent to 2 SD above mean for a control population). Analysis was by paired Student's t-testing and linear regression. GFR correlated significantly with HbA1c (r= 0.47, p < 0.0001) and fructosamine (r= 0.24, p = 0.035). Mean HbA1c and fructosamine in the 13 patients with hyperfiltration was significantly higher than in the rest of the group (HbA1c: 9.2% (95% C.I. 7.9-10.4%) vs 7.6 % (7.2-7.9), p= 0.002; fructosamine: 479 micromol l(-1) (450-507) vs 410 micromol l(-1) (388-432), p = 0.009. This significant difference persisted even when the two highest values of HbA1c or fructosamine were removed from analysis. Effective renal plasma flow, assessed by PAH clearance, also correlated in all patients with HbA1c (r=0.31, p=0.039). We conclude that poor glycaemic control directly correlates with hyperfiltration and renal hyperperfusion in early Type 1 DM.
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PMID:Long-term glycaemic control directly correlates with glomerular filtration rate in early Type 1 diabetes mellitus before the onset of microalbuminuria. 986 73

Thromboxane (TX) A2 plays important roles on renal injuries in streptozotocin (STZ)-induced diabetic rats, whereas its role on the renal injuries in non-insulin-dependent diabetic (NIDDM) rats remains unknown. We evaluated the effects of an intravenous infusion of TXA2 synthetase inhibitor (OKY-046, 6 mg/kg/h) on the clearances on inulin and para-aminohippurate (Cin, C(PAH)) in a spontaneously NIDDM rats, Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 8), and Long-Evans Tokushima Otsuka (LETO) rats (n = 7), served as control rats, at the age of 40-44 weeks. OLETF rats showed obesity, moderate hyperglycemia, and hyperinsulinemia. Urinary excretion of TXB2 was slightly higher and the ratio of TXB2 to 6-keto prostaglandin F1alpha (6-kPG) was significantly higher in OLETF rats (TXB2/6-kPG: 0.22 +/- 0.04 versus 0.12 +/- 0.02, P < 0.05). Both Cin and C(PAH) were significantly higher in OLETF rats than in LETO rats (Cin: 1.1 +/- 0.1 versus 0.7 +/- 0.1 mL/min/100 g BW, C(PAH): 3.1 +/- 0.2 versus 2.3 +/- 0.3 mL/min/100gBW, P < 0.01). OKY-046 did not restore Cin and C(PAH) in OLETF rats although it significantly decreased urinary excretion of TXB2, and thus ameliorated TXB2/6-kPG in OLETF rats. These data suggested that TXA2 was not involved in the renal hyperfiltration in OLETF rats at the age of 40-44 weeks, and that TXA2 might contribute to renal injuries in OLETF rats through mechanisms other than hemodynamic injury.
J Diabetes Complications
PMID:Effect of acute thromboxane A2 inhibition on the renal hemodynamics in a spontaneously non-insulin-dependent diabetic rat, Otsuka Long-Evans Tokushima Fatty rat. 1061 56

Genetic and environmental determinants play critical roles in insulin resistance and beta-cell function. A model of the complex feedback system for maintenance of glucose tolerance has been developed that reflects the constraint of glycemia within narrow physiologic limits. The "glucose homeostasis" model is described by insulin sensitivity (S(I)), glucose disposition (S(G)), acute insulin response to glucose (AIR(G)), and disposition index (DI). Relatively little is known about the genetic basis of glucose homeostasis phenotypes or their relationship to risk of diabetes and atherosclerotic cardiovascular disease. A genome scan for glucose homeostasis phenotypes in nondiabetic subjects has been carried out in African-American (n = 21) and Hispanic (n = 45) extended families as part of the IRAS Family Study. In African-American families, there was significant evidence for linkage of DI between D11S2371 and D11S2002 (logarithm of odds [LOD] = 3.21) at 81 cM, and in the combined sample of African-American and Hispanic families, there was evidence at GATA117D01 (140 cM) on chromosome 11 (LOD = 2.21). Evidence of linkage was also observed for S(I) in Hispanic (LOD = 2.28, between D15S822 and GTTTT001) and AIR(G) in African-American families (LOD = 2.73, between D4S1625 and D4S1629; and LOD = 2.56 at PAH (phenylalanine hydroxylase) on chromosome 12). These results provide impetus for future positional cloning of quantitative trait loci (QTLs). Identifying genes in these regions should provide insight into the nature of the metabolic syndrome and diabetes, and facilitate the development of more effective therapies for prevention and treatment of diabetes and other diseases associated with disordered glucose metabolism.
Diabetes 2004 Jul
PMID:Identification of quantitative trait loci for glucose homeostasis: the Insulin Resistance Atherosclerosis Study (IRAS) Family Study. 1522 Feb 12

Functional lateralities are of interest due to their relationship with cerebral lateralisation and language development. However, genes influencing sidedness remain elusive. We measured direction and consistency of hand, foot, and eye preference in 584 Mexican-Americans from families participating in the San Antonio Family Diabetes/Gallbladder Study. Using maximum-likelihood-based variance components methods, we estimated weak (.11 <or= h2<or=.17) but significant heritability for foot preference, eye preference, several hand preferences (writing, drawing, throwing, using scissors, using spoon, striking match), and a composite hand preference trait. Self-reported handedness was significantly heritable (h2=.57), whereas hand preference for opening a box or using a toothbrush or knife was not. Many trait pairs had significant genetic correlations, and all had significant environmental correlations. Using genome-wide multipoint linkage screens using 382 highly informative autosomal STR markers, we identified suggestive linkage signals for drawing (LOD 2.10) and writing (LOD 2.00) hand preference on chromosome 12q21-23, in the region flanked by markers D12S1300 and PAH. A suggestive signal (LOD 2.46) for eye preference occurred on chromosome 22pter, near marker D22S420. No obvious candidate genes occur in these regions. Our results indicate that genes are an important component of side preferences, and suggest chromosomal regions for further investigation.
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PMID:Heritability and linkage analysis of hand, foot, and eye preference in Mexican Americans. 1696 40

p38 mitogen-activated protein kinase (p38) has been implicated in mediating vascular smooth muscle and mesangial cell contraction in response to several vasoactive factors, including angiotensin II. Early stages of diabetic nephropathy are associated with renal hemodynamic changes that are, at least in part, attributable to the dysbalance of vasoactive factors that control afferent and efferent arteriolar tone resulting in increased glomerular capillary pressure. Vascular and renal p38 have been found to be activated in diabetes. Therefore, p38 may be involved in the control of systemic and renal hemodynamics in diabetes. To address this issue, mean arterial blood pressure (MAP), glomerular filtration rate (GFR, inulin clearance), renal plasma flow (RPF, PAH clearance), metabolic parameters, and plasma renin concentrations (PRC) were determined in streptozotocin-diabetic rats (DM), and in age-matched non-diabetic controls (C), administered with the p38 inhibitor SB 239063 (SB, 50 mg/bwt, p.o.) or with vehicle. Furthermore, renal vascular responses to p38 inhibition (SB 202190, 25 microM) before and after stimulation with the endothelium-dependent vasodilator acetylcholine (ACh) were studied in vitro in tertiary branches of the renal artery from separate groups of DM and C rats, using a fixed support and a force transducer in a myograph system. SB treatment was associated with marked reductions in MAP and GFR in both C and DM rats, whereas RPF remained unchanged, as compared with vehicle-treated animals. Observed differences in MAP and renal hemodynamics were not associated with changes in urinary sodium excretion or PRC. Incubation of KCl-contracted renal arteries from both C and DM rats with the p38 inhibitor resulted in progressive and significant vasorelaxation. Also, vessels from control and diabetic rats treated with the p38 inhibitor exhibited enhancement of ACh-induced vasorelaxation. These data indicate the role of p38 in the control of systemic and renal hemodynamics both in normal and in diabetic rats. The observed effects of p38 inhibition could be mediated at least in part by enhancement of endothelium-dependent vasodilation.
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PMID:Effects of p38 mitogen-activated protein kinase inhibition on blood pressure, renal hemodynamics, and renal vascular reactivity in normal and diabetic rats. 1802 96

The association of 9 urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) with serum C-reactive protein (CRP) was investigated using the National Health and Nutrition Examination Survey (NHANES) 2003-2004. The unweighted number of participants included was 999, which represented 139,362,776 persons in the non-institutionalized US population. In adjusted logistic regressions, two OH-PAHs, 2-hydroxyphenanthrene and 9-hydroxyfluorene, were associated with elevated CRP (>3mg/l). Logistic regressions were adjusted for age, gender, race, exercise, body mass index, smoking status, diabetes, and hypertension. 2-Hydroxyphenanthrene >148ng/g creatinine had an odds ratio of 3.17 (95% CI 1.73-5.81) compared to 2-hydroxyphenanthrene < or =48ng/g creatinine, and 9-hydroxyfluorene >749ng/g creatinine had an odds ratio of 2.28 (95% CI 1.08-4.83) compared to 9-hydroxyfluorene < or =160ng/g creatinine. Intermediate levels of 2-hydroxyphenanthrene (49-148ng/g creatinine), and 9-hydroxyfluorene (161-749ng/g creatinine) were also significantly associated with elevated CRP compared to the respective reference categories. In a combined analysis, OH-PAHs were classified as low, medium, and high. Low OH-PAH was 2-hydroxyphenanthrene < or =48ng/g creatinine and 9-hydroxyfluorene < or =160ng/g creatinine. High OH-PAH was 2-hydroxyphenanthrene >148ng/g creatinine or 9-hydroxyfluorene >749ng/g creatinine. Participants not assigned to the low or high categories were classified as having medium OH-PAH concentrations. Compared to the low OH-PAH group, high OH-PAH had an odds ratio of 3.60 (95% CI 2.01-6.46) in an adjusted logistic regression. Given that inflammation (characterized here by CRP) is an important factor in the development of atherosclerosis and cardiovascular disease, these results suggest a role for OH-PAHs in the progression of atherosclerosis.
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PMID:Association of urinary polycyclic aromatic hydrocarbons and serum C-reactive protein. 1983 15

Cholesterol determination in body is important in diagnosis of diseases like coronary heart disease, arteriosclerosis, diabetes, and obstructive jaundice. This research aims at developing fluorimetric cholesterol biosensors based on self-assembled mesoporous alginate-silica (Algilica) microspheres. For preparing the biosensor, Pt-(II)-octaethylporphine (PtOEP; oxygen sensitive metalloporphyrin) dye has been loaded in the Algilica microspheres using the solvent-mediated precipitation method. Cholesterol oxidase (ChOx) was then covalently conjugated to PtOEP/Algilica microspheres using EDC and NHS reagents. PtOEP dye and enzyme encapsulation, activity and stability were then analyzed. Layer-by-layer self-assembly was finally performed using PAH and PSS polyelectrolytes to minimize leaching of the biosensor components. The prepared biosensor exhibited linearity over a range of 0.77-2.5 mM O(2) (K(SV) : 0.097/mM of O(2) ) obtained using from Stern-Volmer plots. The biosensor response to standard cholesterol displayed a linear analytical range from 1.25 to 10 mM of cholesterol with regression coefficient of 0.996 (1.25-3.75 mM), 0.976 (1.25-6 mM), and 0.959 (1.25-10 mM) and response time of 10 min. Thus, the prepared cholesterol biosensor shows great potential in the diagnosis of hypercholesterolemia.
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PMID:Cholesterol biosensors based on oxygen sensing alginate-silica microspheres. 2144 85

Diabetic nephropathy is a progressive and generalized vasculopathic condition associated with abnormal angiogenesis. We aim to determine whether changes in renal microvascular (MV) density correlate with and play a role in the progressive deterioration of renal function in diabetes. We hypothesize that MV changes represent the early steps of renal injury that worsen as diabetes progresses, initiating a vicious circle that leads to irreversible renal injury. Male nondiabetic (ND) or streptozotocin-induced diabetic (D) Sprague-Dawley rats were followed for 4 or 12 wk. Renal blood flow and glomerular filtration rate (GFR) were measured by PAH and (125)I-[iothalamate], respectively. Renal MV density was quantified ex vivo using three-dimensional micro computed tomography and JG-12 immunoreactivity. Vascular endothelial growth factor (VEGF) levels (ELISA) and expression of VEGF receptors and factors involved in MV remodeling were quantified in renal tissue by Western blotting. Finally, renal morphology was investigated by histology. Four weeks of diabetes was associated with increased GFR, accompanied by a 34% reduction in renal MV density and augmented renal VEGF levels. However, at 12 wk, while GFR remained similarly elevated, reduction of MV density was more pronounced (75%) and associated with increased MV remodeling, renal fibrosis, but unchanged renal VEGF compared with ND at 12 wk. The damage, loss, and subsequent remodeling of the renal MV architecture in the diabetic kidney may represent the initiating events of progressive renal injury. This study suggests a novel concept of MV disease as an early instigator of diabetic kidney disease that may precede and likely promote the decline in renal function.
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PMID:Microvascular disease precedes the decline in renal function in the streptozotocin-induced diabetic rat. 2203 55

Intrarenal tissue hypoxia is an acknowledged common pathway to end-stage renal disease in clinically common conditions associated with development of chronic kidney disease, such as diabetes and hypertension. In diabetic kidneys, increased oxygen metabolism mediated by mitochondrial uncoupling results in decreased kidney oxygen tension (PO2) and contributes to the development of diabetic nephropathy. The present study investigated whether increased intrarenal oxygen metabolism per se can cause intrarenal tissue hypoxia and kidney damage, independently of confounding factors such as hyperglycemia and oxidative stress. Male Sprague-Dawley rats were untreated or treated with either triiodothyronine (T3, 10 g/kg bw/day, subcutaneously for 10 days) or the mitochondria uncoupler dinitrophenol (DNP, 30 mg/kg bw/day, oral gavage for 14 days), after which in vivo kidney function was evaluated in terms of glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, Transonic, PAH clearance), cortical PO2 (Clark-type electrodes), kidney oxygen consumption (QO2), and proteinuria. Administration of both T3 and DNP increased kidney QO2 and decreased PO2 which resulted in proteinuria. However, GFR and RBF were unaltered by either treatment. The present study demonstrates that increased kidney metabolism per se can cause intrarenal tissue hypoxia which results in proteinuria. Increased kidney QO2 and concomitantly reduced PO2 may therefore be a mechanism for the development of chronic kidney disease and progression to end-stage renal disease.
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PMID:Increased kidney metabolism as a pathway to kidney tissue hypoxia and damage: effects of triiodothyronine and dinitrophenol in normoglycemic rats. 2385 70


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