Plasma homocysteine is related to albumin excretion rate in patients with diabetes mellitus: a new link between diabetic nephropathy and cardiovascular disease?

Abstract

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.

Relationship between homocysteine and non-dipper pattern in patients with type 2 diabetes mellitus

“…We know that Hcy levels are higher in type 2 DM patients (30,31). In our study, we found Hcy levels even higher in the diabetic group than in the control group (respectively 12.3 ± 6.5 µmol/L and 10.8 ± 4.6 µmol/L ), but this difference had not statistical significance.…”

Homocysteine Induces Protein Kinase C Activation and Stimulates c-Fos and Lipoprotein Lipase Expression in Macrophages

“…Plasma Hcys concentrations are elevated in patients with diabetes (58,59), and a relationship between hyperhomocysteinemia and increased risk of cardiovascular morbidity and mortality has been established in patients with type 2 diabetes (6 -10). We previously demonstrated that Mo LPL, a proatherogenic protein, is increased in patients with type 2 diabetes (30) and that peripheral factors are, at least partly, responsible for this alteration (30 -32).…”

Determining the Relationship Between Homocysteinemia and Biomarkers of Inflammation, Oxidative Stress and Functional Kidney Status in Patients with Diabetic Nephropathy

“…development of nephropathy, whereas diabetes mellitus per se most likely is not the cause of increased plasma homocysteine levels (24). HHcy may occur also in microalbuminuric patients with mild forms of renal dysfunction (7,17,25).…”

“…The study had previously been approved by an institutional ethics committee and all included subjects had approved their participation. A total of 8 4 subjects were included: 64 with diabetes mellitus type 2 (42 males/22 females) and with the presence of diabetic nephropathy (persistent urinary albumin excretion (UAE) >30 mg/24 h) (16,17), divided into two groups according to their fasting plasma tHcy levels [the first group with HHcy (the normal range in our laboratory was 5-12 mmol/L), and the second with NHcy], and 20 healthy controls (12 males/8 females).…”