Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is a health problem that is reaching epidemic proportions. Extreme obesity (body mass index [BMI] > or =40 kg/m2) is a type of obesity that usually does not respond to medical treatment, with surgery being the current treatment of choice. Extreme obesity is associated with cardiovascular disease, type 2 diabetes, dyslipidemia, and hypertension. Recently, obesity has been related with high rate of renal lesions, but renal function and renal parameters in extreme obesity scarcely are documented. The objective of this study was to evaluate the effect of weight loss after bariatric surgery (BS) on BP, renal parameters, and renal function in 61 extremely obese (EO) patients after 24 mo of follow-up. A total of 61 EO adults (37 women) were studied prospectively before and 24 mo after surgery. Control subjects were 24 healthy, normal-weight adults (15 women). Anthropometric, BP, and renal parameters were determined. Presurgery weight, BMI, GFR, 24-h proteinuria, and 24-h albuminuria were higher in the EO patients than in control subjects (P < 0.001). All parameters improved at 12 mo after BS. However, during the second year of follow-up, only 24-h albuminuria (P = 0.006) and BMI (P = 0.014) continued to improve. At 24 mo after BS, obesity-related renal alterations considerably improved. This improvement was observed mainly in the first year after surgery, when the majority of weight loss occurred. However, 24-h albuminuria still improves during the second year of follow-up. It is possible that this decrease in 24-h albuminuria is not GFR related but rather is attributable to the persistence of the decrease in BMI and to the improvement of other weight-related metabolic factors.
 ...
PMID:Effect of drastic weight loss after bariatric surgery on renal parameters in extremely obese patients: long-term follow-up. 1713 Feb 64

The objective of this study was to assess the relationship between urinary albumin excretion (UAE) and GF across the spectrum of the glucose metabolism abnormalities in a large population of patients with hypertension. The Microaluminuria en Pacientes con Glucemia Basal Alterada (MAGAL) is a multicenter, cross-sectional study that was carried out by 1723 primary care physicians. A total of 6227 patients with essential hypertension (in three groups: [1] normal fasting glucose <100 mg/dl, [2] impaired fasting glucose > or =100 to 126 mg/dl, and [3] type 2 diabetes) were analyzed in this substudy. GFR was estimated by using the Modification of Diet in Renal Disease (MDRD) abbreviated equation. A single first-morning urine albumin/creatinine ratio was measured using Bayer reagent strip Microalbustix, a semiquantitative method. Abnormal UAE was defined as an albumin/creatinine ratio > or =3.4 mg/mmol (equivalent to > or =30 mg/g). The prevalence of abnormal UAE, > or =3.4 mg/mmol, increased across the spectrum of glucose abnormalities: 39.7, 46.2, 48.6, and 65.6% for normoglycemic, low-range, and high-range impaired fasting glucose and diabetes, respectively. UAE was positively related to SBP (P = 0.003) and inversely to GFR (P < 0.001). Renal insufficiency (GFR <60 ml/min per 1.73 m2) was present in 21.8% of the patients, more frequently older patients, women, and those with diabetes. The factors that were related to renal insufficiency were UAE > or =3.4 mg/mmol (odds ratio 1.86; 95% confidence interval 1.60 to 2.17) and diabetes (odds ratio 1.62; 95% confidence interval 1.29 to 2.04). There is a close relationship between abnormal UAE and renal insufficiency in essential hypertension. This is more marked in patients with diabetes and moderate in patients with high-range impaired fasting glucose.
 ...
PMID:Urinary albumin excretion and glomerular filtration rate across the spectrum of glucose abnormalities in essential hypertension. 1713 Feb 68

Previous studies have shown that the selective aldosterone blocker eplerenone, in doses of up to 200 mg/d, reduces albuminuria in patients with type 2 diabetes. This study was conducted to ascertain whether lower doses of eplerenone (50 or 100 mg/d) co-administered with the angiotensin-converting enzyme (ACE) inhibitor enalapril would produce a similar antialbuminuric effect while obviating the hyperkalemia observed previously. After open-label run-in with enalapril 20 mg/d, patients with diabetes and a urinary albumin:creatinine ratio (UACR) > or = 50 mg/g were randomly assigned to receive enalapril plus one of three double-blind daily treatments for 12 wk: placebo, eplerenone 50 mg (EPL50), or eplerenone 100 mg (EPL100). After week 4, amlodipine 2.5 to 10 mg/d was allowed for BP control (systolic/diastolic BP < or = 130/80 mmHg). The primary study end points were the percentage change from baseline at week 12 in UACR and the incidence of hyperkalemia. Secondary end points included percentage changes from baseline in UACR at weeks 4 and 8 and changes from baseline in systolic and diastolic BP. Treatment with EPL50 or EPL100 but not placebo significantly reduced albuminuria from baseline. By week 12, UACR was reduced by 7.4% in the placebo group, by 41.0% in the EPL50 group, and by 48.4% in the EPL100 group (both eplerenone groups, P < 0.001 versus placebo). The incidences of sustained and severe hyperkalemia were not significantly different in any of the three treatment arms and did not differ on the basis of quartile of estimated GFR (all NS). For the secondary end points, both eplerenone treatment groups significantly reduced albuminuria from baseline as early as week 4 (P < 0.001), whereas placebo treatment (including enalapril) did not result in any significant decreases in UACR. Systolic BP decreased significantly in all treatment groups at all time points, but, generally, all treatment groups experienced similar decreases in BP. Co-administration of EPL50 or EPL100 with an ACE inhibitor as compared with an ACE inhibitor alone significantly reduces albuminuria in patients with diabetes without producing significant increases in hyperkalemia.
 ...
PMID:Selective aldosterone blockade with eplerenone reduces albuminuria in patients with type 2 diabetes. 1769 11

Recent studies questioned the existence of a specific renoprotective effects of ACE-inhibitors (ACE-i) and angiotensin receptor blockers (ARBs) besides their blood pressure lowering effect. In the ALLHAT study patients were randomly assigned to receive chlorthalidone, amlodipine and lisinopril. Results showed that, even in patients with reduced GFR, neither lisinopril nor amlodipine was superior to chlorthalidone in reducing the rate of development of ESRD or a 50% or greater decrement in GFR. Because of inclusion criteria the ALLHAT population was selected as at low risk for renal outcomes. Moreover, over 50% of the patients who were randomized to lisinopril either never received the medication or received the lower possible dose. Casas et al selected RCT comparing ACE-i and ARBs with other regimens. They concluded that ACE-i and ARBs are not more renoprotective that can be explained by lowering of blood pressure (BP) in diabetic nephropathy, while in non diabetic kidney disease a blood pressure independent renoprotective effect is uncertain. They made a very heterogeneous selection of trials that was dominated by the ALLHAT study; the analysis was not based on individual patient data. The Benedict Study showed that in hypertensive, normoalbuminuric patients with type 2 diabetes, BP reduction and ACE-i therapy both independently may prevent microalbuminuria. ACE-i therapy is particularly effective when BP is poorly controlled. We conclude that the recommendation of the Guidelines to use ACE-i and/or ARBs as first-line antihypertensive drugs for renoprotection in patients with diabetic and non diabetic kidney disease is still valid.
 ...
PMID:[Antihypertensive therapy and renoprotection: do we really need to block the renin-angiotension system?]. 1788 9

This study investigates the association between serum cystatin C, serum creatinine concentrations, N-acetyl-beta-D-glucosaminidase (NAG enzymuria), urine alpha1-microglobulin (alpha1-MG) and beta2-microglobulin (beta2-MG) levels in subjects with type 2 diabetes (n=40, 20M/20F, age range 25-65 years; duration of diabetes 8-10 years) and age- and gender-matched healthy controls (n= 20). Exclusion criteria were absence of gross proteinuria, hypertension, dyslipidaemia or cardiovascular disease. Fasting blood samples and mid-stream specimen of urine (MSSU) were collected and serum creatinine, cystatin C, urine creatinine, NAG enzymuria, alpha1-MG and beta2-MG were measured. Diabetic subjects were separated into two groups based on albumin:creatinine concentration ratio. Group A: <3.5 (mg/mmol creatinine), group B: 3.5-35 (mg/mmol creatinine). While serum creatinine concentrations remained within the laboratory reference range for all groups, serum cystatin C concentration (mg/L) was significantly increased in group B (1.79 +/- 0.42 [mean +/- SD] compared to both control [0.81 +/- 0.10] and group A values [0.95 +/- 0.10]; both P<0.001). NAG enzymuria (units/mmol creatinine) was increased in both diabetic groups compared to control values (group B: 122 +/- 7, group A: 70 +/- 5, controls 27 +/- 2, all P<0.001). alpha1-microglobulin (microg/mmol creatinine) concentrations, similar in both the control group and group A diabetics at 1.10 +/- 0.10 and 1.11 +/- 0.21, respectively, were significantly elevated in group B at 2.10 +/- 0.41 (both P<0.01). Similarly, elevated beta2-MG (microg/mmol creatinine) levels were also observed in group B compared to both group A and control values (3.20 +/- 0.21 vs. 1.80 +/- 0.51 and 0.91 +/- 0.11, respectively; both P<0.001). In addition, group B levels were significantly higher than group A (P<0.001). These observations suggest that serum cystatin C is a more appropriate and effective biomarker for the overall estimation of GFR than serum creatinine values. In addition, increased serum cystatin C values were also associated with early renal tubular insult in subjects with type 2 diabetes, as characterised by increased NAG enzymuria, alpha1- and beta2-microglobulin excretion.
 ...
PMID:Serum cystatin C, enzymuria, tubular proteinuria and early renal insult in type 2 diabetes. 1791 Feb 81

In the past, hyperfiltration and increased glomerular capillary pressure have been identified as important determinants of the development of DN (diabetic nephropathy). Recently, some basic research and clinical reviews on DN have omitted identifying hyperfiltration as an important risk factor. At the same time, different rodent models of DN have been described without and with documented hyperfiltration. In the present review, the importance of hyperfiltration is reassessed, reviewing key clinical and research studies, including the first single nephron studies in a mouse model of DN. From clinical studies of Type 1 and Type 2 diabetes mellitus, it is clear that many patients do not have early hyperfiltration and, even when present, its contribution to subsequent DN remains uncertain. Key mechanisms underlying hyperfiltration in rodent models are reviewed. Findings on intrarenal NO metabolism and the control of single-nephron GFR (glomerular filtration rate) in rodent models of DN are also presented. Characterization of valid experimental models of DN should include a careful delineation of the absence or presence of early hyperfiltration, with special efforts made to establish the specific role hyperfiltration may play in the emergence of DN.
 ...
PMID:Can rodent models of diabetic kidney disease clarify the significance of early hyperfiltration?: recognizing clinical and experimental uncertainties. 1806 76

Heavy proteinuria is a major determinant of progression to ESRD for patients with chronic nephropathies and reducing proteinuria should be a key target for renoprotective therapy. In the Remission Clinic, we applied a multimodal intervention to target urinary proteins in 56 consecutive patients who had >3 g proteinuria/d despite angiotensin-converting enzyme inhibitor therapy. We compared the rate of GFR decline and incidence of ESRD in this cohort with 56 matched historical reference subjects who had received conventional therapy titrated to a target BP. During a median follow-up of 4 yr, the monthly rate of GFR decline was significantly lower in the Remission Clinic cohort (median -0.17 versus -0.56 ml/min per 1.73 m2; P < 0.0001), and ESRD events were significantly reduced (3.6 versus 30.4% reached ESRD). Follow-up BP, cholesterol, and proteinuria were lower in Remission Clinic patients than in reference subjects, such that disease remission or regression was achieved in up to 50% of patients who would have been otherwise expected to progress rapidly to ESRD on conventional therapy. Proteinuria reduction independently predicted a slower rate of GFR decline and ESRD incidence, but response to treatment differed depending on the underlying disease. Regarding safety, no patient was with drawn because of hyperkalemia. In summary, multidrug treatment titrated to urinary protein level can be safely and effectively applied to normalize proteinuria and to slow the loss of renal function significantly,especially among patients without type 2 diabetes and with otherwise rapidly progressing chronic nephropathies.
 ...
PMID:Role of remission clinics in the longitudinal treatment of CKD. 1883 82

There is good evidence supporting more extensive use of metformin in type 2 diabetes, in reducing morbidity and mortality. The evidence for a real problem from metformin-induced lactic acidosis is weak, and the risks of alternative agents are often overlooked. We have examined the available data regarding metformin that might cause concern in patients with kidney disease, and find it to be extremely limited. There is no good data on which to offer guidance, but it seems likely that metformin can be used in patients with GFR 60-90 ml/min but at reduced dose at lower levels of GFR, and can probably be safely used at GFRs from 30-60 ml/min but with the same caution as with any renally excreted drug. The risks (often overlooked) and benefits of alternative hypoglycaemic agents should be considered carefully. The overall evidence that metformin causes major harm is poor.
 ...
PMID:Metformin: effective and safe in renal disease? 1836 3

It is unknown whether chronic kidney disease (CKD) is associated with nonalcoholic fatty liver disease among patients with type 2 diabetes. We followed 1760 outpatients with type 2 diabetes and normal or near-normal kidney function and without overt proteinuria for 6.5 yr for the occurrence of CKD (defined as overt proteinuria and/or estimated GFR <60 ml/min per 1.73 m(2)). During follow-up, 547 participants developed incident CKD. Nonalcoholic fatty liver disease, diagnosed by liver ultrasound and exclusion of other common causes of chronic liver disease, was associated with a moderately increased risk for CKD (hazard ratio 1.69; 95% confidence interval 1.3 to 2.6; P < 0.001). Adjustments for gender, age, body mass index, waist circumference, BP, smoking, diabetes duration, glycosylated hemoglobin, lipids, baseline estimated GFR, microalbuminuria, and medications (hypoglycemic, lipid-lowering, antihypertensive, or antiplatelet drugs) did not appreciably attenuate this association (hazard ratio 1.49; 95% confidence interval 1.1 to 2.2; P < 0.01). In conclusion, our findings suggest that nonalcoholic fatty liver disease is associated with an increased incidence of CKD in individuals with type 2 diabetes, independent of numerous baseline confounding factors.
 ...
PMID:Increased risk of CKD among type 2 diabetics with nonalcoholic fatty liver disease. 1838 24

Aim of the investigation was to study safety of therapy with metformin and its effect on clinical, hemodynamic, functional and neurohumoral status in patients with chronic heart failure and type 2 diabetes mellitus DM). Eighty one patients with light and moderate NYHA functional class (FC) II-III CHF, left ventricular ejection fraction < 45%, and DM were examined. As a result of randomization 2 groups were formed: with active (n=41) and usual (n=40) treatment. In active group with achievement of target levels of glycemia 24 (59%) patients were on oral hypoglicemic drags, 17 (41) patients received. All patients were on basal therapy of CHF. Initially efficacy and safety of metformin was investigated in a cohort of active treatment (jn metformin n=29, control n=12), including patients who were prescribed metformin not for the whole period. In addition in active group analysis was carried out among patients, who continually were treated with metformin for 12 months (n=30) in comparison with patients never treated with metformin (n=8). Total duration of the period of treatment and supervision was 12 months. Control examination was conducted before randomization, after 6 months of treatment, at the end of the study and included assessment of clunico-functional status of patients, renal function (GFR), neurohumoral profile (MNUP, NA, AII). The state of carbohydrate metabolism was assessed with the help of determination of HBA1C level and test with nutritional load given as of common breakfast -- 2-3 in the course of which fasting and postprandial level (in 2 hours after breakfast) of glucose (GLC), and fasting insulin and C-peptide. Overall safety of metformin was confirmed -- throughout whole period of follow up with different variants of comparative analysis no cases of lactic acidosis were revealed. Practical lack of positive influence of metformin on glycemia at its initially not high level was accompanied with improvement of FC CHF, parameters of central hemodynamics, augmentation of functional capacities of patients, improvement of quality of life, lowering of number of decompensations of CHF and diminishment of degree of activation of SAS. It can be suggested that this dynamics is conditioned by the presence of cardioprotective properties in metformin what allows to recommend its application in patients with CHF and type 2 DM.
 ...
PMID:[Efficacy and safety of the use of metformin in patients with chronic heart failure and type 2 diabetes mellitus. results of the study "rational effective mulicomponent therapy in the battle against diabetes mellitus in patients with chronic heart failure"]. 1842 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>