Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using I131 VLDL selectively labelled in the B-apoprotein and I125 LDL injected simultaneously into the patient we have derived some quantitative measures of VLDL and LDL metabolism in man. The effects of insulin resistance, associated with idiopathic hypertriglyceridaemia, adult onset diabetes and diabetic lipodystrophy on the metabolic behaviour of these molecules were also assessed. In the normal subjects 72-83% of the total daily plasma VLDL B-apoprotein flux was metabolised via a pathway which involved its ultimate conversion to plasma LDL, while 21-28% was degraded without such conversion. The amount of B-apoprotein metabolised by either of these routes was proportionate to the flux rate and the two pathways accounted for the total VLDL B-apoprotein removed from the plasma. In patients with idiopathic hypertriglyceridaemia and in the adult onset diabetics the total plasma VLDL B-apoprotein flux was higher than normal, indicating increased production of this apoprotein. On the other hand, the flux rate of plasma VLDL B-apoprotein in the patients with diabetic lipodystrophy was normal, suggesting that the increase in the circulating mass of these molecules was due to impaired clearance. In all the patients, however, the fractions of the total flux either converted to LDL or degraded were lower than normal, suggesting that insulin resistance limited the removal of this apoprotein by these pathways. The results also indicate that a fraction of the total VLDL removed from the plasma has been retained in an extravascular compartment, possibly representing VLDL molecules trapped in the vascular structures. In the control and the insulin resistant subjects the quantity of LDL apoprotein catabolised per day agreed closely with the amount derived from VLDL B-apoprotein conversion, suggesting that VLDL-B-apoprotein serves as the main source of LDL apoprotein. In patients with idiopathic hypertriglyceridaemia and in adult onset diabetics the absolute turnover rate of plasma LDL apoprotein was higher than normal, while in the lipodystrophic patients it was reduced. It is suggested that the increase in LDL turnover seen in the former groups could be an additive factor in the deposition of lipid rich material in arterial walls.
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PMID:The metabolic fate of plasma lipoproteins in normal subjects and in patients with insulin resistance and endogenous hypertriglyceridaemia. 18 13

In people with diabetes, the concentration of an individual lipoprotein or apolipoprotein can be highly variable and is totally different in the two major forms of the disease. Alterations in the concentrations of major lipids and lipoproteins are well characterized in both IDDM and NIDDM. In general, the lipoprotein pattern is antiatherogenic in individuals with IDDM who are treated and have optimal glycemic control. In contrast, NIDDM is associated with atherogenic changes of serum lipids and lipoproteins regardless of the mode of treatment. In people with both types of diabetes, the distribution of apoE phenotype seems to be similar to that in nondiabetic populations. IDDM patients with microalbuminuria show atherogenic changes of lipoproteins and have elevated levels of Lp(a), which is a risk factor of coronary artery disease. Whether glycemic control influences the concentration of Lp(a) is still an open question. An important issue is that the concentration of a lipoprotein can be normal without excluding compositional abnormalities that are potentially atherogenic. Such alterations are present in people with both IDDM and NIDDM. Consequently, it has been questioned whether the target values to start treatment should be lower in diabetic than in nondiabetic populations.
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PMID:Quantitative and qualitative lipoprotein abnormalities in diabetes mellitus. 152 30

Levels of cardiovascular risk factors were determined in 75 patients with Type 2 diabetes mellitus. The patients were divided into three groups according to their urinary protein excretion (UPE): (a) normal proteinuria (less than or equal to 70 mg d-1); (b) microproteinuria (70-500 mg d-1); and (c) macroproteinuria (greater than 500 mg d-1). A significant stepwise increase in mean systolic blood pressure, LDL-cholesterol and fibrinogen levels was observed from the first to the third investigated group of patients. Mean apoprotein B levels were significantly increased in the group with macroproteinuria compared to the other two groups. Significant linear correlations were found between UPE and LDL-cholesterol, total cholesterol, apoprotein B, creatinine, systolic blood pressure and diabetes duration. In summary, it is concluded that the levels of some cardiovascular risk factors increase with the stage of proteinuria in Type 2 diabetes mellitus.
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PMID:Levels of cardiovascular risk factors in type 2 diabetes mellitus are dependent on the stage of proteinuria. 154 31

Hepatic lipase has a putative role in the catabolism of HDL particles and, while its activity is dependent upon insulin in the rat, no such insulin responsiveness has been demonstrated in man. We studied 21 patients with type 2 diabetes to examine whether hepatic lipase activity was influenced by hyperinsulinaemia during a 2-4 h isoglycaemic clamp study. Acute changes in lipids, lipoproteins and apolipoproteins were also documented in pre- and post-clamp serum. Hepatic lipase activity during hyperinsulinaemia was compared with activity measured after an equivalent period without insulin. For comparison, nine non-diabetic subjects (matched for age and body mass index) underwent similar clamp studies. In the control experiment without insulin, hepatic lipase activity did not change significantly (mean 9.7 (range 2.3-22.3) in the morning and 9.9 (3.0-22.5) mmol h-1 l-1 in the afternoon, NS). In contrast, after the hyperinsulinaemic clamp, hepatic lipase activity fell significantly in diabetic subjects from 12.8 (4.4-30.6) to 10.4 (3.3-31.3) mmol h-1 l-1, P less than 0.0002 along with serum triglycerides and total and LDL cholesterol. The change in hepatic lipase activity was positively related to the fasting apoprotein B concentration (Spearman r = 0.54, P = 0.016). In the normal subjects, a similar decline in hepatic lipase activity was observed during hyperinsulinaemia (from 15.1 (9.8-32.7) to 12.6 (6.3-28.3) mmol h-1 l-1, P less than 0.01) along with decreases in total, HDL and LDL cholesterol, triglycerides and apoproteins A1 and B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The response of hepatic lipase and serum lipoproteins to acute hyperinsulinaemia in type 2 diabetes. 159 86

Changes of glucose and lipid metabolism in NIDDM hypertensive patients during treatment with a new dihydropyridine derivative, nilvadipine, were examined by a randomized, crossover study comparing the results with those elicited by captopril in 18 patients for 12 weeks each. Nilvadipine (8 mg per day) and captopril retard (75 mg per day) caused a sufficient decrease in blood pressure without changing the pulse rate. Nilvadipine and captopril did not significantly change fasting plasma glucose, hemoglobin A1c, serum cholesterol, triglycerides, high-density lipoprotein cholesterol or apoprotein A-I, A-II and B levels in either of the 12-week treatments. In 75-g oral glucose tolerance tests carried out three times in each patient (before treatment and after 12 weeks of treatment with each drug), changes in plasma glucose and serum insulin levels were not significantly different among the three tests. These results demonstrate that nilvadipine as well as captopril are antihypertensive drugs without adverse effects on glucose and lipid metabolism in hypertensive patients with NIDDM.
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PMID:Comparison of the effects of nilvadipine and captopril on glucose and lipid metabolism in NIDDM patients with hypertension. 160 Aug 52

Many lipoprotein abnormalities are seen in the untreated, hyperglycemic diabetic patient. The non-insulin-dependent diabetic (NIDDM) patient with mild fasting hyperglycemia commonly has mild hypertriglyceridemia due to overproduction of TG-rich lipoproteins in the liver, associated with decreased high-density lipoprotein (HDL) cholesterol levels. The more hyperglycemic untreated NIDDM and insulin-dependent diabetic (IDDM) patient have mild to moderate hypertriglyceridemia due to decreased adipose tissue and muscle lipoprotein lipase, (LPL) activity. These patients also have decreased HDL cholesterol levels associated with defective LPL catabolism of TG-rich lipoproteins. Treatment of diabetes with oral sulfonylureas or insulin corrects most of the hypertriglyceridemia and some of the decrease in HDL cholesterol. The abnormality in adipose tissue LPL activity corrects slowly over several months of therapy. The treated IDDM patient often has normal lipoprotein levels. The treated NIDDM patient may continue to have mild hypertriglyceridemia, increased intermediate-density lipoprotein levels, small dense low-density lipoproteins (LDL) with increased apoprotein B, and decreased HDL cholesterol levels. The central, abdominal distribution of adipose tissue in IDDM is associated with insulin resistance, hypertension, and the above lipoprotein abnormalities. Improvement in glucose control, in the absence of weight gain, leads to lower triglyceride and higher HDL cholesterol levels. In addition, the diabetic patient is prone to develop other defects that, in themselves, lead to hyperlipidemia, such as proteinuria, hypothyroidism, and hypertension, treated with thiazide diuretics and beta-adrenergic-blocking agents. When a diabetic patient independently inherits a common familial form of hypertriglyceridemia, he might develop the severe hypertriglyceridemia of the chylomicronemia syndrome.
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PMID:Pathophysiology of hyperlipidemia in diabetes mellitus. 171 Jul 39

Hyperglycaemia, a raised fibrinogen, an increased serum triglyceride and a reduced HDL-cholesterol are common metabolic features of non-insulin dependent diabetes mellitus (NIDDM). Hypertension is frequently associated with NIDDM, however the influence of antihypertensive therapy on these combined factors in the diabetic is at present unclear. In a double-blind placebo-controlled crossover study in 20 stable NIDDM subjects with hypertension, the metabolic effects of 6 weeks' treatment with the alpha-blocker, doxazosin, was compared with treatment with the beta-blocker, atenolol. Similar and significant reductions in BP were produced by both drugs. Significant increases in weight, HbA1, apoprotein B, serum triglyceride and cholesterol/HDL ratio were observed with atenolol therapy. Doxazosin therapy was associated with opposite patterns of changes in fasting glucose, lipids and lipoproteins but only for serum triglyceride was difference between treatments significant. Fibrinogen was not altered by either treatment. Conclusions from this study indicate; 1) adrenergic mechanisms may be an important influence on glucose homeostasis and lipid metabolism in NIDDM and 2) the beta-blocker, atenolol, has a small adverse effect on weight, glycaemic control and the atherogenic lipid profile, whereas the alpha-blocker, doxazosin, has no such effect and may, in part, correct the disturbances of lipoprotein metabolism characteristic of NIDDM.
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PMID:Alpha-blocker therapy; a possible advance in the treatment of diabetic hypertension--results of a cross-over study of doxazosin and atenolol monotherapy in hypertensive non-insulin dependent diabetic subjects. 198 Sep 30

To investigate whether persistent microalbuminuria is related to altered levels of both lipids and apolipoproteins in Type 2 diabetes mellitus serum total-cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, apolipoprotein A-I, and apolipoprotein B were measured by standard methods in a group of Type 2 diabetic patients affected by persistent microalbuminuria (albumin excretion rate (AER) 20-200 micrograms min-1) as compared with a group of sex- and age-matched non-microalbuminuric patients (AER less than 20 micrograms min-1). The groups were stratified according to a short (less than or equal to 5 years) or a longer (greater than 5 years) duration of diagnosed diabetes. Microalbuminuria was not associated with significant changes of serum total-cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, and apolipoproteins in the group of patients with a duration of disease greater than 5 years, while microalbuminuric patients less than or equal to 5 years from diagnosis (n = 11) had serum total-cholesterol, triglycerides, LDL-cholesterol, and apoprotein B higher than non-microalbuminuric control patients (n = 26) (cholesterol 6.2 +/- 0.9 vs 5.1 +/- 1.0 mmol l-1 (p = 0.003); triglycerides 2.1 +/- 0.7 vs 1.7 +/- 1.3 mmol l-1 (p = 0.03); LDL-cholesterol 4.1 +/- 0.8 vs 3.0 +/- 0.7 mmol l-1 (p less than 0.001); apo-B 1.3 +/- 0.3 vs 1.1 +/- 0.3 g l-1 (p = 0.02). In these patients with shorter duration of diabetes many of the serum lipid measures correlated positively with AER.
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PMID:Serum lipids and lipoproteins in type 2 diabetic patients with persistent microalbuminuria. 214 34

The mechanisms by which high-carbohydrate, low-saturated-fat diets lower LDL cholesterol (LDLC) concentrations are unknown. In this study, kinetics of VLDL, intermediate density lipoprotein (IDL), and LDL apoprotein B and VLDL triglyceride were determined in seven nondiabetic (ND) and seven non-insulin-dependent diabetic (NIDDM) Pima Indian subjects on high-fat and high-carbohydrate (HICHO) diets. Metabolic changes were similar in ND and NIDDM. On the HICHO diet, LDLC decreased (131 +/- 8 vs. 110 +/- 7 mg/dl, P less than 0.0001) in all subjects. Mean fasting and 24-h triglyceride (TG) concentrations were unchanged, as were mean production rates and fractional clearance rates (FCR) of VLDL apoB and VLDL TG. The mean VLDL apoB pool size (303 +/- 20 vs. 371 +/- 38 mg, P = 0.01) increased owing to a decrease in the mean transport rate (10.7 +/- 1.1 vs. 8.4 +/- 0.9 mg/kg fat-free mass (ffm) per day, P less than 0.0001) and the mean rate constant (2.3 +/- 0.2 vs. 1.5 +/- 0.2, P less than 0.001) for the VLDL apoB to IDL apoB conversion pathway. The mean transport rate of VLDL apoB to LDL apoB via IDL (10.2 +/- 0.9 vs. 8.0 +/- 0.8 mg/kg ffm per day, P less than 0.001) decreased. Mean LDL apoB concentrations decreased (70 +/- 5 vs. 61 +/- 5 mg/dl, P less than 0.001) on the HICHO diet. Means for total LDL apoB transport rate, LDL apoB FCR, and LDLC/apoB ratios were unchanged. In summary, the HICHO diet decreased the activity of mechanisms that convert VLDL to LDL, which contributed to the decrease in LDLC in all subjects. There was also evidence in some subjects for increased activity of LDL apoB clearance mechanisms, and a decrease in the LDLC to apoB ratio.
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PMID:Effect of a high-carbohydrate, low-saturated-fat diet on apolipoprotein B and triglyceride metabolism in Pima Indians. 220 Aug 8

Atherosclerosis is the main cause of death in diabetes mellitus. This may at least in part be due to lipoprotein abnormalities which have been described in these patients. Apolipoprotein-E is a component of most lipoprotein fractions and plays an important role in the catabolism of VLDL. The different apolipoprotein-E phenotypes determined genetically are associated with certain hyperlipoproteinemias in a various degree in nondiabetic patients. In most cases apolipoprotein-E phenotype E2/2 is characteristic for familial dysbetalipoproteinemia. Phenotype E3/2 was found to be more frequent in hypertriglyceridemia while phenotype E4/3 was associated with hypercholesterolemia as well as with type V hyperlipoproteinemia. We studied apolipoprotein-E phenotypes and serum lipids in 141 type II diabetic patients (36 normolipidemic 41 type IIa hyperlipidemic, 32 type IIb hyperlipidemic, 24 type II hyperlipidemic, 8 type V hyperlipidemic). the phenotype E3/3 was more common in normolipidemic diabetic (77.8%) than in hyperlipoproteinemic diabetic patients (42.9%) or in the control group (57.5%). On the other hand phenotype E3/2 was more frequent in hypertriglyceridemic (50%) than in normolipidemic (5.6%) or hypercholesterolemic (hyperlipoproteinemia IIa: 4.9%, IIb: 9.4%) diabetic patients. The phenotype E4/3 was more frequent in all hyperlipoproteinemic diabetic patients, especially in those having hypercholesterolemia (34.2%) or mixed hyperlipidemia (50%). In conclusion we found a strong association between apo-E2 and hypertriglyceridemia in diabetic patients. This association was stronger than the one found in the general population. The association between apo-E4 and hypercholesterolemia in diabetic patients was similar to the one described in non-diabetic patients. We therefore conclude that type II diabetes mellitus is a possible cofactor in the apolipoprotein-E2 associated hyperlipoproteinemia.
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PMID:Apolipoprotein E phenotype frequency in type II diabetic patients with different forms of hyperlipoproteinemia. 227 5


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