P-selectin gene genotypes or haplotypes and cardiovascular complications in type 2 diabetes mellitus.

BACKGROUND AND AIM: Increased levels of sP-selectin, a member of the selectin family involved in the transient attachment of leukocytes to endothelial cells, are found in a number of conditions including diabetes and ischemic heart disease. A number of polymorphisms in the gene encoding P-selectin have been identified. The purpose of the present study was to explore the role of three non-synonymous P-selectin gene polymorphisms, Tyr715Pro, Asn562Asp and Ser290Asn, in determining the risk of macrovascular complications in type 2 diabetic patients. METHODS AND RESULTS: Following a cross-sectional case-control design from 837 Italian type 2 diabetics, 301 cases with at least one episode of angina pectoris (AP), acute myocardial infarction (AMI), stroke, transient ischemic attacks (TIA) or peripheral arterial disease (PAD) were compared with 536 controls free of ischemic vascular complications in the period preceding the examination. Case subjects had longer duration of diabetes at the time of examination and were older as compared with controls. Hypertension and male sex were over-represented among cases. Allele frequency and genotype distribution of the three polymorphic variants did not show any significant preferential association in groups of cases or controls. Odds ratios also indicated no effect on risk of cardiovascular disease even after adjustment for potentially confounding variables. There was a strong allelic association between Tyr715Pro and Asn562Asp (D' = -0.99, P < 0.0001). Ser290Asn was in linkage disequilibrium with Tyr715Pro (D' = 0.43, P = 0.15) and in almost complete equilibrium with Asn562Asp (D' = 0.05, P = 0.5). Haplotype phase inferred from genotypic data revealed the presence of 6 haplotypes. Global test of significance showed no difference in three marker haplotype distribution between cases and controls (P = 0.88, df = 5). CONCLUSIONS: The present study excludes a major contribution of Tyr715Pro, Asn562Asp and Ser290Asn P-selectin polymorphisms to a susceptibility to ischemic vascular complications in type 2 diabetes.

Homocysteine levels are associated with the severity of peripheral arterial disease in Type 2 diabetic patients.

BACKGROUND: Homocysteine levels are positively associated with the risk of cardiovascular disease. They might be determined by both MTHFR677C-->T polymorphisms and folate or B-vitamin status. OBJECTIVES: To investigate the possible association between plasma homocysteine levels and its genetic or environmental determinants and either the presence or the severity of peripheral arterial disease (PAD), in Type 2 diabetic patients. METHODS: From a cohort of 944 patients with Type 2 diabetes, 135 patients with PAD were selected, and frequency-matched for age and sex with 219 Type 2 diabetic control patients without macrovascular complications. According to the increasing severity of the disease, patients were divided into PAD1 (only diffuse calcifications of the arteries without any stenosis or occlusion), PAD2 (one or two stenosis or occlusions) and PAD3 (three or more). RESULTS: Homocysteine levels were similar in control and case patients (10.3 micromol L-1 vs. 10.7 micromol L-1, P = 0.53); however, a significant increase was found in PAD3 patients: odds ratio = 2.77 (95% confidence interval 1.14, 6.72) for patients with homocysteine levels above the median vs. those under the median in multivariate analysis. Although all significantly associated with homocysteine levels, neither MTHFR genotype nor folic acid or vitamin B12 levels were associated with severity of PAD. A significant interaction (P < 0.05) was found between folic acid and MTHFR polymorphism in determining the levels of homocysteine. CONCLUSIONS: In Type 2 diabetes, homocysteine was associated with the angiographic severity of PAD, but neither the genotypes nor vitamin levels contributed to this association.

A high-score Mediterranean dietary pattern is associated with a reduced risk of peripheral arterial disease in Italian patients with Type 2 diabetes.

BACKGROUND: The 'Mediterranean diet' is considered to exert protective effects on cardiovascular disease, although a wide range of dietary patterns exists among subjects living even in the same Mediterranean country. OBJECTIVE: To investigate the association between specific dietary patterns and peripheral arterial disease (PAD) in Italian Type 2 diabetes patients. DESIGN: From a cohort of 944 patients with Type 2 diabetes, 144 patients with PAD were selected, and matched for age and sex with 288 Type 2 diabetic control patients without macrovascular complications. A dietary score was elaborated from a semiquantitative food frequency questionnaire. The higher the final score, the healthier the eating habit. RESULTS: In multivariate analysis, a higher score was independently associated with a significant reduction in PAD risk [odds ratio (OR) = 0.44; 95% confidence interval (CI) 0.24, 0.83]. Diabetes duration (OR > 15 years = 2.49; 95% CI 1.45, 4.25), hypertension (OR = 2.12; 95% CI 1.31, 3.45) and butter consumption (OR = 2.6; 95% CI 1.15, 3.68) were also significantly associated with PAD. The dietary score significantly improved the predictive value of models based on duration of diabetes and hypertension. (LSR = 2.19, DF = 7, P < 0.001). The effect of a high dietary score on the risk of PAD was independent of diabetes duration and hypertension. CONCLUSION: In Italian Type 2 diabetics, a higher dietary score has a protective role against PAD. The use of butter increases the risk of PAD even in patients regularly consuming olive oil. Dietary advice may be helpful for the prevention of PAD in diabetics even in populations traditionally accustomed to a Mediterranean dietary habit.

Relationship between patient practice-oriented knowledge and metabolic control in intensively treated Type 1 diabetic patients: results of the validation of the Knowledge and Practices Diabetes Questionnaire.

AIMS: To validate a newly developed questionnaire for the measurement of patients' knowledge and practices, with particular attention to its ability in predicting HbA1c levels. RESEARCH DESIGN AND METHODS: The Knowledge and Practices Diabetes Questionnaire (KPDQ) is a questionnaire composed of two scales, investigating patient knowledge and practices. Twenty-two questions, 12 dealing with patients' knowledge and 10 relative to patients' practices, were initially identified. Factor analysis and reliability analysis were used to validate the questionnaire. The ability of the two scales in predicting metabolic control was then evaluated. The questionnaire was administered to a population of Type 1 diabetic subjects intensively treated and regularly attending the diabetes outpatient clinic of Pescara General Hospital. The mean of all HbA1c measurements performed after patients were taken in charge by the clinic was used as an indicator of metabolic control. RESULTS: Out of 133 Type 1 patients identified, 77 (58 %) filled in the questionnaire. Respondents had a mean age (+/- SD) of 37 +/- 13 years and a mean diabetes duration of 13 +/- 9 years. The application of factor and reliability analyses led to the definition of two final scales composed of 10 (Knowledge Score, KS) and 5 items (Practice Score, PS), respectively. Item-scale correlation was > or = 0.40 for all the items investigated. Cronbach's alpha coefficient exceeded the value of 0.70 for both scales. The mean number of HbA1c determinations during a median period of observation of 4 years was of 11 +/- 5. The mean HbA1c value for the whole population was of 7.0% +/- 1.4, while the proportion of patients with values < or = 7.0% was of 57%. After adjusting for clinical and patient-related characteristics, the KS was the only independent predictor of metabolic control. Patients in the lowest quartile of the KS showed a more than 20-fold increased risk of having mean HbA1c values > or = 7.0% as opposed to those in the highest quartile (odds ratio, OR=23.3;p=0.009). No association emerged between metabolic control and PS. CONCLUSIONS: The KPDQ presents excellent psychometric properties. The KS also shows a very impressive association with the mean HbA1c values over a period of 4 years. These findings are particularly remarkable in that many studies have failed in documenting such a relationship. The KS can thus be considered as a quick and efficient screening tool to be used in an ambulatory setting to monitor the level of practice-oriented knowledge of patients with Type 1 diabetes as well as to identify those subjects who need individualized educational interventions.