Target Values of Cardiovascular Risk Factors Are Not Associated with All-Cause Mortality in Patients with Type 2 Diabetes Mellitus

<div><p>Background</p><p>To investigate prospectively the relationship between target values of glycated hemoglobin, blood pressure and LDL-cholesterol, as considered in a combined fashion, and all-cause mortality in patients with type 2 diabetes mellitus.</p><p>Methods</p><p>Two cohorts of patients with type 2 diabetes mellitus, the Gargano Mortality Study (n=810) and the Foggia Mortality Study (n=929), were investigated. A weighted target risk score was built as a weight linear combination of the recommended targets reached by each patient.</p><p>Results</p><p>In the Gargano Mortality Study and in the Foggia Mortality Study (mean follow up=7.4 and 5.5 years, respectively), 161 (19.9%) and 220 (23.7%) patients died, with an age and sex adjusted annual incidence rate of 2.1 and 2.8 per 100 person-years, respectively. In both study samples the weighted target risk score tended to be linearly associated with all-cause mortality (HR for one point increment=1.30, 95% CI: 1.11-1.53, p=0.001, and HR=1.08, 95% CI: 0.95-1.24, p=0.243, respectively). When the two cohorts were pooled and analyzed together, a clear association between weighted target risk score and all-cause mortality was observed (HR for one point increment=1.17, 95% CI:1.05-1.30, p=0.004). This counterintuitive association was no longer observable in a model including age, sex, body mass index, smoking habit, estimated glomerular filtration rate, albuminuria and anti-diabetic, anti-hypertensive and anti-dyslipidemic treatment as covariates (HR for one point increment=0.99, 95% CI: 0.87-1.12, p=0.852).</p><p>Conclusions</p><p>In a real life clinical set of patients with type 2 diabetes mellitus, the combination of recommended target values of established cardiovascular risk factors is not associated with all-cause mortality.</p></div

Baseline clinical features of 1739 patients with type 2 diabetes from Gargano Mortality Study and Foggia Mortality Study.

<p>Data are reported as mean±standard deviation or frequencies (n) and percentages (%), for continuous and categorical variables, respectively.</p><p>GMS: Gargano Mortality Study; FMS: Foggia Mortality Study; BMI: body mass index; LDL: low density lipoprotein; e-GFR: estimated-glomerular filtration rate; OAD: oral antidiabetes drugs.</p><p>Baseline clinical features of 1739 patients with type 2 diabetes from Gargano Mortality Study and Foggia Mortality Study.</p

Survival adjusted curves from fully-adjusted multivariable Cox regression, according to the various groups of target attainment.

<p>Survival adjusted curves from fully-adjusted multivariable Cox regression, according to the various groups of target attainment.</p

Association between serum resistin levels and low eGFR (<60ml/min/1.73m²).

<p>SGR: San Giovanni Rotondo;</p><p>OR (95% CI) are given for SD increase of resistin levels.</p><p>Model 1: unadjusted (Boston sample adjusted by coronary artery disease status-yes/no).</p><p>Model 2: adjusted by smoking habits, BMI, waist circumference, diabetes duration, HbA1c, insulin treatment, hypertension and lipid-lowering therapy (Boston sample adjusted by coronary artery disease status-yes/no).</p><p>*Since the effect in SGR was different than that in Boston sample (p for OR values heterogeneity being = 0.014), individual data meta-analysis was carried out by using random effects</p><p>Association between serum resistin levels and low eGFR (<60ml/min/1.73m²).</p

Clinical characteristics of patients from SGR and FG studies.

<p>Continuous variables were reported as mean ± SD whereas categorical variables were reported as total frequency and percentages. SGR: San Giovanni Rotondo; FG: Foggia; BMI: Body Mass Index; HbA1c: glycated hemoglobin;, ACE/RAS: angiotensin-converting enzyme/renin-angiotensin system; eGFR: estimated glomerular filtration rate.</p><p>Clinical characteristics of patients from SGR and FG studies.</p

Association between serum adiponectin levels and low GFR (< 60ml/min/1.73m²).

<p>SGR: San Giovanni Rotondo; FG: Foggia;</p><p>OR (95% CI) are given for 1 SD increase of adiponectin levels.</p><p>Model 1: unadjusted.</p><p>Model 2: adjusted by sex, smoking habits, BMI, waist circumference, diabetes duration, HbA1c, ACR and anti-hyperglycemic, anti-hypertensive and anti-dyslipidemic treatments.</p><p>*Since the effect in SGR was not different than that in FG sample (p for OR values heterogeneity being = 0.56), individual data meta-analysis was carried out by using fixed effects.</p><p>Pooled analysis were adjusted by study sample.</p><p>Association between serum adiponectin levels and low GFR (< 60ml/min/1.73m²).</p

Clinical characteristics of patients from SGR and Boston studies.

<p>Continuous variables were reported as mean ± SD whereas categorical variables were reported as total frequency and percentages. SGR: San Giovanni Rotondo; BMI: Body Mass Index; HbA1c: glycated haemoglobin;, eGFR: estimated glomerular filtration rate.</p><p>Clinical characteristics of patients from SGR and Boston studies.</p

Association between serum resistin levels and eGFR (continuous trait).

<p>SGR: San Giovanni Rotondo.</p><p>The β linear coefficients represent the change in eGFR level for 1SD increase in resistin. SE: standard error.</p><p>Model 1 = unadjusted (Boston sample was adjusted by coronary artery disease status-yes/no).</p><p>Model 2 = adjusted by smoking habits, BMI, waist circumference, diabetes duration, HbA1c, insulin treatment, hypertension and lipid-lowering therapy (Boston sample was adjusted by coronary artery disease status-yes/no).</p><p>*Since the effect in SGR was different than that in Boston sample (p for beta values heterogeneity being = 3.3*10⁻⁶), individual data meta-analysis was carried out by using random effects.</p><p>Association between serum resistin levels and eGFR (continuous trait).</p

Association between serum adiponectin levels and eGFR, considered as a continuous trait.

<p>SGR: San Giovanni Rotondo; FG: Foggia. p value obtained from lnGFR.</p><p>The β linear coefficients represent the change in eGFR level (ml/min/1.73m²) for 1.SD increase in adiponectin. SE: standard error.</p><p>Model 1: unadjusted.</p><p>Model 2: adjusted by sex, smoking habits, BMI, waist circumference, diabetes duration, HbA1c, ACR and anti-hyperglycemic, anti-hypertensive and anti-dyslipidemic treatments.</p><p>*Since the effect in SGR tended to be different than that in FG sample (p for β values heterogeneity being = 0.15), individual data meta-analysis was carried out in a conservative fashion by using random effects.</p><p>Pooled analysis were adjusted by study sample.</p><p>Association between serum adiponectin levels and eGFR, considered as a continuous trait.</p