The high risk of cardiovascular disease in patients with diabetes mellitus, particularly in those with nephropathy, is not completely explained by classical risk factors. A high plasma homocysteine concentration is an independent risk factor for cardiovascular disease but information on its association with diabetes is limited. Fasting homocysteine concentrations were measured in the plasma of 165 diabetic patients (75 with insulin-dependent [IDDM]; 90 with non-insulin-dependent diabetes [NIDDM]) and 56 non-diabetic control subjects. Other measurements included the prevalence of diabetic complications, glycaemic control, lipid and lipoprotein levels, vitamin status and renal function tests. Patients with NIDDM had higher homocysteine levels than control subjects, whereas IDDM patients did not (9.2 +/- 4.5 vs 7.7 +/- 2 micromol/l, p < 0.01; and 7.0 +/- 3 vs 7.4 +/- 2 micromol/l, NS). Univariate correlations and multiple regression analysis showed albumin excretion rate to be the parameter with the strongest independent association with homocysteine. Patients with both types of diabetes and nephropathy had higher plasma homocysteine concentrations than those without nephropathy. Increases of homocysteine in plasma were related to increases in the severity of the nephropathy. Fasting hyperhomocysteinaemia was considered as the mean of the plasma homocysteine for all control subjects (7.5 +/- 2.1 micromol/l) + 2 SD (cut-off = 11.7 micromol/l). Nephropathy was present in 80 % of diabetic patients with fasting hyperhomocysteinaemia. In conclusion, increases in fasting homocysteine in diabetic patients are associated with increased albumin excretion rate, especially in those with NIDDM, thus providing a potential new link between microalbuminuria, diabetic nephropathy and cardiovascular disease.

BackgroundThe objective of the study was to describe the baseline health-related quality of life (HRQOL) in a cohort of children and adolescents with type 1 diabetes mellitus (T1DM), and analyze its associated clinical and sociodemographic factors, assessing HRQOL through internet.MethodsThis was a descriptive study of 136 patients with T1DM from 5 hospitals in Catalonia, Spain (72 girls, mean age 13.4 years (range 8–19). Inclusion criteria were more than 6 months from diagnosis, more than 8 years old and without cognitive problems. Sociodemographic (age, sex, family level of education, type of family and origin) and clinical variables (type of insulin therapy, duration of disease, adherence to treatment, body mass index and HbA1c) were collected. HRQOL was assessed using the EuroQol-5D (EQ-5D-Y) and KIDSCREEN, collected via web. Mental health status was assessed using the Strengths and Difficulties Questionnaire. Multiple linear regression models were adjusted.ResultsPhysical-well-being mean scores were lower (worse) than the European average (<50) and especially in girls, older children (>11 years old), those from single-parent families, and those with low adherence. Older children and patients with poor metabolic control (HbA1c >7,5% [58 mmol/mol]) showed worse scores in the KIDSCREEN-10 index. Similar results were observed with the EQ-5D-Y. Multivariate models showed that age, single-parent families, adherence and mental health were the most influential factors.ConclusionsDiabetic patients report similar HRQOL than the population of the same age with slightly worse physical well-being. The study shows some factors to be taken into account to improve HRQOL, and also the feasibility of using web to collect information in clinical practice.

Atherosclerosis is the major cause of death in the diabetic population. Hyperglycaemia per se is an independent risk factor for the development of cardiovascular disease, in spite of the coexistence of other known risk factors, such as hyperlipidaemia and hypertension [1,2]. Elevated concentrations of low density lipoproteins (LDL) are also a major risk factor in the general population [3,4]. However, LDL levels are usually normal in both insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes (NIDDM) [2,5].It has been postulated that the increased cardiovascular risk for diabetic patients could be related, among other factors, to LDL qualitative modifications such as oxidation and glycation. These modifications impair LDL cellular catabolism, leading to loss of affinity for LDL receptors in fibroblasts, increased accumulation of cholesteryl esters in macrophages, and immunological responses [6,7]. In Diabetologia (1996) Summary We evaluated the effect of improving glycaemic control with intensive insulin therapy on LDL susceptibility to oxidation, electronegative LDL proportion, and LDL subfraction phenotype in a group of 25 patients with short-duration insulin-dependent diabetes mellitus (IDDM); 25 matched healthy control subjects were also studied. LDL susceptibility to oxidation was measured by continuous monitoring of conjugated diene formation. Electronegative LDL was isolated by anion exchange chromatography, and quantified as percentage of total LDL. Six LDL subfractions were isolated by density gradient ultracentrifugation and phenotype A or B classified as the quotient (LDL1-LDL3)/(LDL4-LDL6). Compared to the control group, IDDM subjects with poor glycaemic control showed higher electronegative LDL (19.03 ± 10.09 vs 9.59 ± 2.98 %, p < 0.001), similar LDL subfraction phenotype and lower susceptibility to oxidation (lag phase 45.6 ± 8.8 vs 41.2 ± 4.7 min, p < 0.05). After three months of intensive insulin therapy, HbA 1 c decreased from 10.88 ± 2.43 to 5.69 ± 1.54 % (p < 0.001), and electronegative LDL to 13.84 ± 5.15 % (p < 0.05). No changes in LDL susceptibility to oxidation or LDL subfraction phenotype were observed. Electronegative LDL appeared significantly correlated to HbA 1 c and fructosamine (p < 0.01 and p < 0.001) only in poorly controlled IDDM patients. These findings suggest that high electronegative LDL in IDDM subjects is related to the degree of glycaemic control, and could therefore be due to LDL glycation rather than to LDL oxidation or changes in LDL subfraction phenotype.

Low HDL-C is the most frequent dyslipidemic disorder in patients with poorly controlled insulin-treated type 1 diabetes, and a high proportion show LDL-C levels requiring intervention. Less favorable lipid profiles could explain the absence of sex protection in diabetic women. The improvement caused by glycemic optimization puts forward intensive therapy as the initial treatment of choice for dyslipidemia in poorly controlled type 1 diabetes.