High density lipoprotein (HDL) metabolism in noninsulin-dependent diabetes mellitus: measurement of HDL turnover using tritiated HDL.

High density lipoprotein (HDL) kinetics were studied by injecting [3H]apoprotein A-I (apoA-I)/HDL into 12 subjects with normal glucose tolerance and 12 patients with noninsulin-dependent diabetes mellitus (NIDDM). The results indicate that the mean fractional catabolic rate (FCR) of apoA-I/HDL was significantly faster [0.63 +/- 0.07 (+/- SEM) vs. 0.39 +/- 0.02 1/day; P less than 0.001] and the apoA-I/HDL synthetic rate greater (29.4 +/- 2.9 vs. 22.9 +/- 1.3 mg/kg X day; P less than 0.02) in patients with NIDDM than in normal subjects. Furthermore, there were statistically significant inverse relationships between apoA-I/HDL FCR and plasma levels of both HDL cholesterol (r = -0.71; P less than 0.001) and apoA-I (r = -0.63; P less than 0.001). In addition, the increase in apoA-I/HDL FCR was directly related to fasting plasma glucose (r = 0.78; P less than 0.001) and insulin (r = 0.76; P less than 0.001) concentrations. These data support the view that the decrease in plasma HDL cholesterol and apoA-I levels commonly found in patients with noninsulin-dependent diabetes is due to an increase in the catabolic rate of apoA-I/HDL secondary to the defects in carbohydrate metabolism present in these patients.

[1]  G. Reaven,et al.  Role of insulin in endogenous hypertriglyceridemia. , 1967, The Journal of clinical investigation.

[2]  H. Eder,et al.  Characterization of the apolipoproteins of rat plasma lipoproteins. , 1977, Biochemistry.

[3]  C. Blum,et al.  High density lipoprotein metabolism in man. , 1977, The Journal of clinical investigation.

[4]  G. Reaven,et al.  Lipid metabolism in non-insulin-dependent diabetes mellitus: effect of glipizide therapy. , 1982, Archives of internal medicine.

[5]  E. Nikkilä.  High Density Lipoproteins in Diabetes , 1981, Diabetes.

[6]  G. Reaven.  Insulin resistance in noninsulin-dependent diabetes mellitus. Does it exist and can it be measured? , 1983, The American journal of medicine.

[7]  P. Fu,et al.  Enzymatic determination of total serum cholesterol. , 1974, Clinical chemistry.

[8]  G. Cooper,et al.  Some considerations of methodology and standardization of apolipoprotein B immunoassays. , 1983, Clinical chemistry.

[9]  P. Nestel,et al.  Turnover of apoproteins A-I and A-II of high density lipoprotein and the relationship to other lipoproteins in normal and hyperlipidemic individuals. , 1980, Metabolism: clinical and experimental.

[10]  R. Goldberg.  Lipid Disorders in Diabetes , 1981, Diabetes Care.

[11]  P. Gartside,et al.  Apolipoprotein AI and AII metabolism in patients with primary high-density lipoprotein deficiency associated with familial hypertriglyceridemia. , 1985, Metabolism: clinical and experimental.

[12]  M. Caslake,et al.  Metabolism of apolipoprotein A-I in healthy young adults. , 1978, Metabolism: clinical and experimental.

[13]  R. Havel,et al.  The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. , 1955, The Journal of clinical investigation.

[14]  G. Reaven,et al.  Relationship between insulin resistance, insulin secretion, very low density lipoprotein kinetics, and plasma triglyceride levels in normotriglyceridemic man. , 1981, Metabolism: clinical and experimental.

[15]  A. J. Valente,et al.  High-density lipoprotein cholesterol and apolipoprotein A-I levels at diagnosis in patients with non-insulin dependent diabetes , 1981, Diabetologia.

[16]  G. Reaven,et al.  Insulin secretion and action in noninsulin-dependent diabetes mellitus. Is insulin resistance secondary to hypoinsulinemia? , 1983, The American journal of medicine.

[17]  P. J. Randle,et al.  Immunoassay of insulin with insulin antibody preciptate. , 1963, Lancet.

[18]  G. Reaven,et al.  Mechanism of hypertriglyceridaemia in diabetic patients with fasting hyperglycaemia , 1980, Diabetologia.

[19]  G. Reaven,et al.  Reduced plasma high density lipoprotein-cholesterol concentrations need not increase when hyperglycemia is controlled with insulin in noninsulin-dependent diabetes mellitus. , 1986, The Journal of clinical endocrinology and metabolism.

[20]  R. Levy,et al.  The metabolism of low density lipoprotein in familial type II hyperlipoproteinemia. , 1972, The Journal of clinical investigation.

[21]  J. Sternberg,et al.  A New and Rapid Method for the Determination of Glucose by Measurement of Rate of Oxygen Consumption , 1968 .

[22]  S B Hulley,et al.  HDL Cholesterol and Other Lipids in Coronary Heart Disease: The Cooperative Lipoprotein Phenotyping Study , 1977, Circulation.

[23]  A. Pezzarossa,et al.  Evidence for an independent relationship between plasma insulin and concentration of high density lipoprotein cholesterol and triglyceride. , 1985, Atherosclerosis.

[24]  D. Thelle,et al.  THE TROMSØHEART-STUDY HIGH-DENSITY LIPOPROTEIN AND CORONARY HEART-DISEASE: A PROSPECTIVE CASE-CONTROL STUDY , 1977, The Lancet.

[25]  J. Witztum,et al.  Nonenzymatic Glucosylation of High-Density Lipoprotein Accelerates Its Catabolism in Guinea pigs , 1982, Diabetes.

[26]  R. Levy,et al.  Studies of the proteins in human plasma very low density lipoproteins. , 1969, The Journal of biological chemistry.

[27]  D. Galton,et al.  High-density and low-density lipoproteins and prevalence of vascular disease in diabetes mellitus. , 1978, British medical journal.