Increased Urinary Albumin Excretion, Insulin Resistance, and Related Cardiovascular Risk Factors in Patients With Type 2 Diabetes

Cosmo, Salvatore De; Minenna, A; Ludovico, Oznelle; Mastroianno, Sandra; Giorgio, A. Di; Pirro, Leonardo; Trischitta, Vincenzo

doi:10.2337/diacare.28.4.910

Cited by 93 publications

(67 citation statements)

References 33 publications

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“…Cigarette smoking, which is five times more prevalent among Persian men compared to women, 26 leads to reduced relaxant responses of the cutaneous microcirculation 27 as well as to blunted basal and stimulated nitric oxide bioactivity. 28 Consistent with the findings in the present study, De Cosmo et al 29 showed that, in patients with type 2 diabetes, increased urinary albumin excretion is associated with cardiovascular risk factors, which is significantly higher in men than in women. In a study on healthy individuals, Verhave et al 30 showed that cardiovascular risk factors and urinary albumin excretion rate are significantly correlated only in men.…”

Section: Discussionsupporting

confidence: 81%

Gender Difference in Albuminuria and Ischemic Heart Disease in Type 2 Diabetes

Nakhjavani

Morteza²,

Jenab³

et al. 2011

Clinical Medicine & Research

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Objective: The value of urinary albumin excretion in the prediction of myocardial ischemia in men and women with type 2 diabetes is not well understood. We questioned whether gender influences the albuminuria-ischemic heart disease relationship in patients with type 2 diabetes. Methods:We designed a matched case-control study of 926 patients with albuminuria (cases) and 926 age and body mass index matched patients without albuminuria (controls). Ischemic heart disease was defined as the presence of (1) history of angina pectoris or angina equivalent symptoms and critical care unit admission, (2) myocardial infarction and/or electrocardiographic evidence of Q-wave myocardial infarction, (3) coronary revascularization and/or stenting, (4) positive myocardial singlephoton emission computed tomography scan, (5) ischemic ST-segment or T-wave changes, and (6) positive stress testing. Results:Patients with albuminuria had a lower glomerular filtration rate and a longer diabetes duration than patients without albuminuria. In the group of cases, there were a greater number of men with ischemic heart disease (120 of 370; 32.4%) compared to women (97 of 559; 17.4%) (P<0.001). The odds ratio of having ischemic heart disease according to the presence or absence of albuminuria was 1.25 [95% CI: 1.01-1.56] (P<0.05) in all studied populations, 0.79 [95% CI: 0.51-1.21] (P=0.14) in women, and 2.84 [95% CI: 1.68-4.79] (P<0.001) in men. We showed that diabetes duration, high-density lipoprotein, low-density lipoprotein, and hemoglobin A 1c influence albuminuria in women, while diabetes duration, fasting blood sugar, and diastolic blood pressure influence albuminuria in men. Conclusions:Men with albuminuria are at increased risk of ischemic heart disease compared to women. This may be related to the role of high-density lipoprotein on the albuminuria-gender relationship.

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Section: Discussionsupporting

confidence: 81%

Gender Difference in Albuminuria and Ischemic Heart Disease in Type 2 Diabetes

Nakhjavani

Morteza²,

Jenab³

et al. 2011

Clinical Medicine & Research

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“…This is in line with experimental data suggesting that insulin resistance and hyperglycemia contribute to malfunction and loss of podocytes, which are considered initial steps in the development of diabetic nephropathy and albuminuria (10)(11)(12)(13). Clinical studies addressing this issue were mainly performed in diabetic patients and have largely, but not consistently, confirmed an association between insulin resistance and microalbuminuria in this setting (10)(11)(12)(13)(14)(15)(16)(17)(18). Data in nondiabetic populations are sparse and show conflicting results (19)(20)(21)(22).…”

supporting

confidence: 50%

Insulin Sensitivity and Albuminuria: The RISC Study

Pilz

Rutters²,

Nijpels³

et al. 2014

Diabetes Care

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OBJECTIVEAccumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN AND METHODSWe investigated 1,415 healthy, nondiabetic participants (mean age 43.9 6 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity was assessed by hyperinsulinemiceuglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTSMicroalbuminuria (UACR ‡30 mg/g) was present in fewer than 2% at either study visit. After multivariate adjustments, there was no cross-sectional association between UACR and any measure of insulin sensitivity. Neither OGIS nor HOMA-IR was significantly associated with follow-up UACR, but in a multivariate regression analysis, baseline M/I emerged as an independent predictor of UACR at follow-up (b-coefficient 20.14; P = 0.001). CONCLUSIONSIn healthy middle-aged adults, reduced insulin sensitivity, assessed by hyperinsulinemic-euglycemic clamp, is continuously associated with a greater risk of increasing albuminuria. This finding suggests that reduced insulin sensitivity either is simply related to or might causally contribute to the initial pathogenesis of albuminuria.Higher levels of albuminuria are associated with an increased risk of mortality and cardiovascular events in patients with diabetes mellitus or arterial hypertension and the general population (1-3). Insights into the pathophysiology of albuminuria are of high clinical relevance since therapeutic interventions to reduce albuminuria are often accompanied by improvements in cardiovascular outcomes (3). Microalbuminuria is also regarded as a marker of a certain form of endothelial dysfunction, but there exists still no clear picture on the direction of the cause and effect relationship (4-6). Alternatively, microalbuminuria and vascular diseases/endothelial dysfunction may also be caused by a common pathophysiologic process (7).

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“…Furthermore insulin resistance, a powerful predictor of cardiovascular events, is seen even when whole-kidney GFR still is normal (53). This finding is of note because insulin resistance also is a feature of microalbuminuria (54) and a predictor of microalbuminuria in patients with type 2 diabetes (55). Damaged endothelial cells presumably are more sensitive to the injurious effects of further insults, e.g., elevated BP, analogous to the increased susceptibility of glomeruli to higher BP in diabetes (56).…”

Section: Potential Pathogenetic Mechanismsmentioning

confidence: 65%

Cross-Talk between the Kidney and the Cardiovascular System

Amann¹,

Wanner²,

Ritz³

2006

Journal of the American Society of Nephrology

137

114

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In recent years, increasing evidence has been provided that even minor renal dysfunction is a powerful cardiovascular risk factor that induces typical cardiovascular alterations and thus predisposes to coronary heart disease as well as to noncoronary cardiovascular problems. This first had been noted in patients with diabetes but now has been confirmed amply in patients without diabetes as well. Numerous heterogeneous abnormalities have been described in patients with early renal dysfunction (e.g., microalbuminuria, reduced estimated GFR). One final common pathway seems to be endothelial cell dysfunction. The link between albuminuria and generalized endothelial cell dysfunction (as indicated by diminished flow-mediated vasodilation, markers of endothelial cell dysfunction, sloughed off endothelial cells, and high transcapillary albumin escape rate) is unclear. In patients with early renal dysfunction, a long list of classical and nonclassical cardiovascular risk factors have been identified: Elevated asymmetric dimethyl-L-arginine concentrations, markers of microinflammation, oxidative stress, features of metabolic syndrome, abnormal adipokine concentrations, dyslipidemia, inappropriate activation of the renin-angiotensin system, and sympathetic overactivity. The mechanisms that link dysfunction of the kidney and the cardiovascular system are being sought. The most interesting unifying concept, however, is deranged fetal programming linking nephron underdosing to the increased cardiovascular risk.

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Increased Urinary Albumin Excretion, Insulin Resistance, and Related Cardiovascular Risk Factors in Patients With Type 2 Diabetes

Cited by 93 publications

References 33 publications

Gender Difference in Albuminuria and Ischemic Heart Disease in Type 2 Diabetes

Gender Difference in Albuminuria and Ischemic Heart Disease in Type 2 Diabetes

Insulin Sensitivity and Albuminuria: The RISC Study

Cross-Talk between the Kidney and the Cardiovascular System

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