Homocysteine levels during fasting and after methionine loading in adolescents with diabetic retinopathy and nephropathy.

OBJECTIVE: To assess plasma homocysteine levels in adolescents and young adults with type 1 (insulin-dependent) diabetes with and without microvascular complications. STUDY DESIGN: Homocysteine levels were measured during fasting and after methionine loading in plasma of 61 patients with onset of diabetes before the age of 12 years and duration of disease longer than 7 years. They had an albumin excretion rate (AER) between 20 and 200 microg/min in 2 of 3 overnight urine collections in a period of 6 months and/or retinopathy. Patients with persistent microalbuminuria were divided into 2 groups: subjects with AER of 20 to 70 microg/min and patients with AER of 70 to 200 microg/min. Adolescents (n = 54) without signs of diabetic retinopathy or nephropathy and matched control subjects (n = 63) were also studied. RESULTS: Homocysteine concentrations before and after methionine load were higher in adolescents with diabetic complications than in healthy subjects (fasting values: 12. 4 +/- 7.9 micromol/L vs 7.8 +/- 4.2 micromol/L; P <.01; after methionine load: 28.1 +/- 13.2 micromol/L vs 16.6 +/- 7.3 micromol/L; P <.005). Values of 11.9 micromol/L or higher were considered to constitute fasting hyperhomocysteinemia. The increase of homocysteine concentrations was particularly evident in young diabetic patients with AER >70 microg/min (fasting values: 14.7 +/- 5.6 micromol/L; after methionine load: 34.2 +/- 12.6 micromol/L) and in patients with proliferative retinopathy (fasting values: 15.1 +/- 5.0 micromol/L; after methionine load: 36.8 +/- 12.5 micromol/L). CONCLUSIONS: Increased plasma homocysteine concentrations may contribute to increased morbidity and death from cardiovascular disease in adolescents and young adults with diabetic retinopathy and nephropathy.

Advanced glycation end products in children and adolescents with diabetes: relation to glycemic control and early microvascular complications.

OBJECTIVE: The measurement of serum advanced glycation end products (S-AGEs) in children, adolescents, and young adults with diabetes to determine whether increased S-AGE levels may be associated with long-term glycemic control and early microvascular complications. STUDY DESIGN: The study was performed in (1) 178 children and adolescents with type 1 diabetes mellitus (age range, 2 to 21 years, onset before the age of 12 years; duration longer than 2 years) without clinical and laboratory signs of microvascular complications, (2) 39 adolescents and young adults (age range, 16.1 to 28.8 years) with background or preproliferative retinopathy or persistent microalbuminuria, and (3) 98 healthy age- and sex-matched control subjects. RESULTS: S-AGEs were significantly increased in preschool and prepubertal children with diabetes and were particularly elevated in pubertal subjects with diabetes compared with control subjects. S-AGEs were markedly increased in adolescents with early microvascular complications compared with both control subjects and diabetic patients without retinopathy or nephropathy. No correlation was found between S-AGEs and albumin excretion rate or blood pressure values. Glycated hemoglobulin values and S-AGEs were significantly correlated (r = 0.32; P <.01). In children with poorly controlled diabetes (HbA1 c >10%), long-term (2 years) improvement of glycemic control resulted in a significant reduction of S-AGE levels in preschool and prepubertal children, as well as in pubertal individuals. CONCLUSIONS: S-AGE concentrations may be elevated even in preschool and prepubertal children with diabetes; this means that the risk of microvascular complications may be present at an early age. Improvement in glycemic control may be associated with a significant decrease in S-AGEs.