Increased Serum Levels of Lipoprotein(a) in Diabetes Mellitus and Their Reduction With Glycemic Control

Bruckert, Éric; Davidoff, P; Grimaldi, A.; Truffert, J; Giral, Philippe; Doumith, R.; Thervet, F; Gennes, J. L. De

doi:10.1001/jama.1990.03440010033016

Cited by 80 publications

(23 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar observations were made in diabetes mellitus for ascorbate (37) and Lp(a) (38). Despite different causes, the progression of these diseases is dependent on the integrity and stability of the tissue, particularly the extracellular matrix (39).…”

Section: Lp(a) and Ascorbate In Cancer And Diabetes Mellitussupporting

confidence: 74%

Hypothesis: lipoprotein(a) is a surrogate for ascorbate.

Rath

Pauling

1990

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The concept that lipoprotein (a) [Lp(a)] is a surrogate for ascorbate is suggested by the fact that this lipoprotein is found generally in the blood of primates and the guinea pig, which have lost the ability to synthesize ascorbate, but only rarely in the blood of other animals. Properties of Lp(a) that are shared with ascorbate, in accordance with this hypothesis, are the acceleration of wopnd healing and other cell-repair mechanisms, the strengthening of the extracellular matrix (e.g., in blood vessels), and the prevention of lipid peroxidation. High plasma Lp(a) is associated with coronary heart disease and other forms ofatherosclerosis in humans, and the incidence of cardiovascular disease is decreased by elevated ascorbate. Similar observations have been made in cancer and diabetes. We have formulated the hypothesis that Lp(a) is a surrogate for ascorbate in humans and other species and have marshaled the evidence bearing on this hypothesis.Lipoproteins consist of particles, each of which is a globule of lipid molecules surrounded by an apoprotein shell. Lipoprotein(a) [Lp(a)] was discovered by Blumberg et al. (1) and by Berg (2). It shares with low density lipoprotein (LDL) its lipid and apoprotein composition-mainly apoprotein B-100 (apo B), consisting of a polypeptide chain of 4536 amino acid residues. The unique feature of Lp(a) is an additional glycoprotein, designated apoprotein(a) [apo(a)], which is linked to apo B by disulfide groups. The cDNA sequence of apo(a) (3) shows a striking homology to plasminogen, with multiple repeats of kringle 4, one kringle 5, and a protease domain. The isoforms of apo(a) vary in the range of 300 to 800 kDa and differ mainly in their genetically determined number of kringle 4 structures (3); apo(a) has no plasmin-like protease activity (4), but a serine protease activity has been demonstrated recently (5). Like plasminogen, Lp(a) has been shown to bind to lysine-Sepharose, immobilized fibrin and fibrinogen (6), and the plasminogen receptor on endothelial cells (7)(8)(9). This binding is inhibited by E-aminocaproic acid, certain other amines, and plasminogen.

show abstract

Section: Lp(a) and Ascorbate In Cancer And Diabetes Mellitussupporting

confidence: 74%

Hypothesis: lipoprotein(a) is a surrogate for ascorbate.

Rath

Pauling

1990

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Bruckert et al (25) first described the effect of improved metabolic control for 21 days in 10 IDDM subjects. They described a significant reduction in Lp(a) concentrations from 46 to 29 mg/dl (P < 0.001), and they found a statistically significant correlation between the degree of improvement in GHb and the amount of decrease in Lp(a) (r = 0.70).…”

Section: Early Studies On Lp(a) and Diabetesmentioning

confidence: 99%

Lipoprotein(a) and Diabetes: An update

Haffner

1993

Diabetes Care

View full text Add to dashboard Cite

On the basis of the available data (much of which is contradictory), I suggest that the following might summarize the role of Lp(a) in diabetes currently. 1. Lp(a) in IDDM: Concentrations are probably elevated. Concentrations are probably related to metabolic control. Concentrations are increased with microalbuminuria. 2. Lp(a) in NIDDM: Concentrations are not elevated. Concentrations do not change with metabolic control. Too few data exist to make an assessment of relation of Lp(a) to microalbuminuria in NIDDM. 3. Lp(a) and CHD in diabetes: Little current evidence shows that Lp(a) is a risk factor for CHD in diabetes. More studies--especially prospective studies with larger numbers of subjects--need to be done.

show abstract

“…Non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) have recently been reported to be associated with elevated levels of Lp(a), sometimes proportionately to the severity of hyperglycemia (9)(10)(11)(12)(13)(14)(15)(16). However, additional studies have demonstrated that this association appears to be nonexistent in patients with NIDDM (17)(18)(19)(20) and possibly patients with IDDM (20)(21)(22), but may be related to the presence of proteinuria or microalbuminuria (23)(24)(25)(26)(27)(28).…”

mentioning

confidence: 99%

“…In several studies, the level of Lp(a) decreased in diabetic subjects who received intensive insulin therapy associated with improved glycemia (10,11). In three small studies, there was no change in the serum level of Lp(a) after improved glycemic control (19,30,31).…”

mentioning

confidence: 99%

The Relationship Between Serum Lipoprotein(a) and Insulinemia in Healthy Nondiabetic Adult Men

Hagemenas

Connor

1994

Diabetes Care

View full text Add to dashboard Cite

The results of these studies have shown that serum concentrations of insulin and testosterone, BMI, and strenuous exercise appear to account for the majority of predicted nongenetic variability in serum levels of Lp(a). These observations suggest the possibility in this group of healthy men that serum concentrations of Lp(a) may be modulated by a complex interplay between insulin action, obesity, androgen levels, and strenuous exercise.

show abstract

Increased Serum Levels of Lipoprotein(a) in Diabetes Mellitus and Their Reduction With Glycemic Control

Cited by 80 publications

References 4 publications

Hypothesis: lipoprotein(a) is a surrogate for ascorbate.

Hypothesis: lipoprotein(a) is a surrogate for ascorbate.

Lipoprotein(a) and Diabetes: An update

The Relationship Between Serum Lipoprotein(a) and Insulinemia in Healthy Nondiabetic Adult Men

Contact Info

Product

Resources

About