Outpatient measurement of arterial stiffness in patients with type 2 diabetes and obesity.

BACKGROUND: Pulse wave velocity (PWV) is a marker of arterial stiffness. The aim of the present study was to compare PWV in patients with type 2 diabetes mellitus (T2DM) or obesity and healthy subjects in an outpatient setting. METHODS: A cross-sectional study was conducted in patients with obesity without T2DM (n = 37), T2DM without obesity (n = 40), T2DM plus obesity (n = 43), and healthy controls (n = 114). Outpatient measurements of the finger-toe PWV (ftPWV) were made. RESULTS: Mean (± SD) ftPWV was higher in men than in women (10.57 ± 5.02 vs 9.14 ± 3.68 m/s, respectively P = 0.006) and was positively correlated with age (r2 = 0.31, P < 0.0001), body mass index (r2 = 0.03, P = 0.01), systolic blood pressure (SBP; r2 = 0.06, P < 0.0001), and right (r2 = 0.03, P = 0.01) and left (r2 = 0.03, P = 0.01) ankle-brachial index (ABI). Age, SBP and ABI remained significantly correlated with ftPWV in the stepwise regression analysis. Mean ftPWV in controls and in patients with obesity, T2DM, and T2DM plus obesity was 8.32 ± 2.68, 9.50 ± 3.38, 11.29 ± 4.34, and 12.36 ± 6.67 m/s, respectively (P < 0.0001). These differences remained significant after adjustments for sex, age, SBP, and ABI (P = 0.008). Although ftPWV was higher in patients with than without macrovascular complications (13.11 ± 6.25 vs 10.40 ± 4.54 m/s, respectively; P = 0.006) in univariate analysis, this was not so in the multivariate-adjusted model. CONCLUSIONS: Outpatient-measured ftPWV was correlated with age, SBP, and ABI. It was higher in patients with T2DM and obesity compared with healthy controls. The highest ftPWV was observed in patients with both T2DM and obesity.

Lower-extremity amputation as a marker for renal and cardiovascular events and mortality in patients with long standing type 1 diabetes.

BACKGROUND: We evaluated the risks of renal and cardiovascular complications, and mortality associated with lower extremity amputation (LEA) in patients with type 1 diabetes. METHODS: We studied two cohorts of people with long standing type 1 diabetes: GENEDIAB (n = 456) and GENESIS (n = 611). Subsets of the cohorts (n = 260, n = 544) were followed for 9 and 5 years, respectively. Outcomes were the incidence of end stage renal disease (ESRD), myocardial infarction, stroke and mortality during follow-up. Analyses were performed in pooled cohorts. RESULTS: The prevalence of LEA at baseline was 9.3 % (n = 99). A positive history of LEA was associated with the baseline prevalence of established (OR 4.50, 95 % CI 2.33-8.91, p < 0.0001) and advanced diabetic nephropathy (OR 5.50, 95 % CI 2.89-10.78, p < 0.0001), ESRD (OR 2.86, 95 % CI 1.43-5.50, p = 0.004), myocardial infarction (OR 3.25, 95 % CI 1.68-6.15, p = 0.0006) and stroke (OR 3.88, 95 % CI 1.67-8.72, p = 0.002, adjusted for sex, age, and cohort membership). A positive history of LEA at baseline was associated with the incidence during follow-up of ESRD (HR 2.69, 95 % CI 1.17-6.20, p = 0.02), and myocardial infarction (HR 3.53, 95 % CI 1.79-6.97, p = 0.0001). History of LEA was also associated with increased risk for all-cause (HR 3.55, 95 % CI 2.05-6.16, p < 0.0001), cardiovascular (HR 3.30, 95 % CI 1.36-8.02, p = 0.008), infectious disease (HR 5.18, 95 % CI 1.13-23.84, p = 0.03) and other-cause mortality (HR 2.81, 95 % CI 1.09-7.26, p = 0.03). History of LEA at baseline was associated with a 40 % reduction in the duration of survival in the subset of patients who died during follow-up. Population attributable risk of the history of LEA at baseline for total mortality during follow-up was 0.31. CONCLUSIONS: Patients with LEA have a higher risk of ESRD, myocardial infarction and cardiovascular and non-cardiovascular mortality. Our results highlight the importance of LEA as a key-predictor for major vascular events and premature death in type 1 diabetic patients.

Plasma Copeptin and Decline in Renal Function in a Cohort from the Community: The Prospective D.E.S.I.R. Study.

BACKGROUND/AIMS: In recent days, chronic kidney disease (CKD) is becoming an increasing public health problem. Identification of factors contributing to its progression is crucial for designing preventive interventions. Previous studies suggested that chronically high vasopressin is deleterious to the renal function. We evaluated plasma copeptin, a surrogate of vasopressin, as a predictor for renal function decline in a community cohort. METHODS: Plasma copeptin was measured at baseline in 1,234 participants from the D.E.S.I.R. study, a prospective cohort from the French general population. All participants were followed for 9 years. Progression towards CKD during follow-up was defined as an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2 on at least one follow-up visit. We have also considered the criterion 'Certain Drop in eGFR' proposed by the Kidney Disease Improving Global Outcomes (KDIGO) group. RESULTS: Progression towards CKD was observed in 86 (7.0%) participants. Factors like age, female gender, plasma copeptin and use of angiotensin converting enzyme inhibitor or angiotensin 2 receptor blocker at baseline were positively associated, and eGFR inversely associated with CKD progression during follow-up. The hazard ratio per unit of log10-transformed plasma copeptin was 1.65 (95% CI 1.06-2.54) and p=0.02. Copeptin was similarly associated with CKD and this was observed when we considered the KDIGO criterion: OR 3.03 (95% CI 1.21-7.57), p=0.02. CONCLUSION: The plasma copeptin level was independently and positively associated with progression towards CKD in a community-based cohort. Our results add to the available evidence for a deleterious effect of high vasopressin on renal health not only in selected groups of patients with CKD but also in the general population.

Impact of morbid obesity on the kidney function of patients with type 2 diabetes.

AIMS: Type 2 diabetes and obesity impair kidney function. We examined their respective contributions to urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in patients with type 2 diabetes and morbid obesity. METHODS: Cross-sectional, monocentric study of kidney function in patients with type 2 diabetes classified into four body mass index (BMI) stages: non-obese (<25 kg/m(2), n=157); overweight (25 to <30, n=311); obesity (30 to <40, n=310); and morbid obesity (≥40, n=77), with 84 similarly staged controls without diabetes. UAE classes were defined as normal (<30 µg/mg creatinine), microalbuminuria (30-299), or macroalbuminuria (≥300) from 3 consecutive urine samples. GFR was measured by (51)Cr EDTA plasma disappearance (adjusted and unadjusted to 1.73 m(2) body surface area, as obesity increases body surface). RESULTS: Participants with type 2 diabetes had same age, diabetes duration, and HbA1c across BMI stages. UAE was higher in participants with type 2 diabetes (p<0.0001), and increased with obesity stages (p<0.0001). After adjustment for age, sex, systolic blood pressure and type 2 diabetes status, morbid obesity was associated with a risk of microalbuminuria (OR 1.99, 95%CI 1.35-2.98, p=0.0007) and macroalbuminuria (OR 2.33, 95%CI 1.25-4.22, p=0.006). The body surface adjusted GFR was lower in patients with type 2 diabetes than in controls (p<0.0001), and declined with obesity stages, contrary to controls. An interaction of diabetes and obesity was seen with unadjusted GFR values (p=0.002). CONCLUSIONS: Morbid obesity interacts with type 2 diabetes to aggravate UAE and GFR. Treatment strategies should focus on both conditions to protect kidney function in these patients.

Plasma copeptin and renal outcomes in patients with type 2 diabetes and albuminuria.

OBJECTIVE: Plasma copeptin, a surrogate for vasopressin, was associated with albuminuria in population-based studies. These associations are consistent with the effect of vasopressin on albuminuria observed in humans and rodents. The objective of this study was to determine whether plasma copeptin is an independent marker of risk of renal events in people with type 2 diabetes and albuminuria. RESEARCH DESIGN AND METHODS: We studied 3,101 participants of the DIABHYCAR trial (6-year follow-up) with type 2 diabetes and albuminuria. A renal event was defined as doubling of serum creatinine or development of end-stage renal disease. RESULTS: During follow-up, 86 renal events occurred in 76 subjects (2.45%). Incidences by tertiles of baseline plasma copeptin were 1.06% (T1), 1.45% (T2), and 4.84% (T3). They were 2.43% (T1), 5.11% (T2), and 11.81% (T3) for the subset of subjects with macroalbuminuria at baseline (n = 729). Hazard ratio for plasma copeptin tertiles as a risk for renal events was 4.79 (95% CI, 2.48-9.24; P < 0.0001; for T3 vs. T1). In a stepwise regression analysis, urinary albumin excretion and plasma copeptin remained positively associated and HDL cholesterol and estimated glomerular filtration rate were inversely associated with the incidence of renal events. These independent predictors explained ∼18% of the variance of the outcome. The yearly variations of estimated glomerular filtration rate by copeptin tertiles were -1.43 ± 0.51 (T1), -2.29 ± 0.49 (T2), and -3.52 ± 0.44 mL/min/1.73 m2 per year (T3) (P = 0.005) in subjects with macroalbuminuria. CONCLUSIONS: Plasma copeptin may help to identify subjects with diabetic chronic kidney disease who are at high risk for renal function decline.