retinol-palmitate and Diabetes-Mellitus--Type-2

Exacerbated postprandial lipid responses are associated with an increased cardiovascular risk. Dietary proteins influence postprandial lipemia differently, and whey protein has a preferential lipid-lowering effect. We compared the effects of different whey protein fractions on postprandial lipid and hormone responses added to a high-fat meal in type 2 diabetic subjects.. A total of 12 type 2 diabetic subjects ingested four isocaloric test meals in randomized order. The test meals contained 100 g of butter and 45 g of carbohydrate in combination with 45 g of whey isolate (iso-meal), whey hydrolysate (hydro-meal), α-lactalbumin enhanced whey (lac-meal) or caseinoglycomacropeptide enhanced whey (CGMP-meal). Plasma concentrations of triglyceride, retinyl palmitate, free fatty acid, insulin, glucose, glucagon, glucagon-like peptide 1 and glucose-dependent insulinotropic peptide were measured before and at regular intervals until 8-h postprandially.. We found no statistical significant differences between meals on our primary variable triglyceride. The retinyl palmitate response was higher after the hydro-meal than after the iso- and lac-meal in the chylomicron-rich fraction (P=0.008) while no significant differences were found in the chylomicron-poor fraction. The hydro- and iso-meal produced a higher insulin response compared with the lac- and CGMP-meal (P<0.001). Otherwise no significant differences in the hormone responses were found in the incremental area under the curve over the 480-min period.. A supplement of four different whey protein fractions to a fat-rich meal had similar effects on postprandial triglyceride responses in type 2 diabetic subjects. Whey isolate and whey hydrolysate caused a higher insulin response.

Topics: Aged; Area Under Curve; Cardiovascular Diseases; Caseins; Chylomicrons; Diabetes Mellitus, Type 2; Dietary Fats; Dietary Proteins; Dietary Supplements; Diterpenes; Female; Glycopeptides; Humans; Hyperlipidemias; Hypolipidemic Agents; Insulin; Lactalbumin; Male; Middle Aged; Milk Proteins; Postprandial Period; Protein Hydrolysates; Retinyl Esters; Triglycerides; Vitamin A; Whey Proteins

Exaggerated and prolonged postprandial lipemia is potentially atherogenic and associated with type 2 diabetes. Limited data exist regarding the influence of dietary protein on postprandial lipemia in type 2 diabetes. We investigated, over 8-h, the acute effects of casein alone or in combination with carbohydrate on postprandial lipid and incretin responses to a fat-rich meal in type 2 diabetes.. Eleven type 2 diabetic subjects ingested four test meals in random order: an energy-free soup plus 80 g of fat (control-meal); control-meal plus 45 g carbohydrates (CHO-meal); control-meal plus 45 g of casein (PRO-meal); and PRO-meal plus 45 g carbohydrates (CHO+PRO-meal). Triglyceride and retinyl palmitate responses were measured in plasma and in a chylomicron-rich and chylomicron-poor fraction. We found no significant differences in triglyceride responses to PRO- and CHO+PRO-meal compared to the control-meal. However, the addition of casein to the CHO-meal reduced the raised triglyceride response in the chylomicron-rich fraction. Retinyl palmitate responses did not differ significantly between meals in the chylomicron-rich fraction, whereas the PRO-meal increased retinyl palmitate in the chylomicron-poor fraction. PRO- and PRO+CHO-meal increased insulin and glucagon compared to the control-meal. PRO+CHO-meal increased the glucose-dependent insulinotropic peptide response while no change in glucagon-like peptide-1 responses was detected.. The data presented suggest that casein per se did not modulate the postprandial triglyceride response in type 2 diabetes. When added to carbohydrate, casein suppressed the triglyceride response in the chylomicron-rich fraction, increased insulin and glucagon but did not affect the incretin responses.

Topics: Aged; Biomarkers; Blood Glucose; Caseins; Chylomicrons; Cross-Over Studies; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Diterpenes; Female; Glucagon; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hyperlipidemias; Hypoglycemic Agents; Incretins; Insulin; Male; Middle Aged; Postprandial Period; Retinyl Esters; Time Factors; Triglycerides; Vitamin A

Insulin resistance is thought to be central to the pathogenesis of diabetic dyslipidaemia. We hypothesised that improving insulin sensitivity would improve fasting and postprandial triglyceride metabolism in patients with type 2 diabetes. To this aim we studied fasting and postprandial lipaemia in type 2 diabetic patients before and after sensitisation to insulin with pioglitazone, compared with that observed in patients on an insulin-providing regime.. In a double-blind placebo-controlled protocol, 22 patients with type 2 diabetes were randomly allocated to receive either pioglitazone (45 mg/day) or glibenclamide (5 mg/day), for a 20-week period. Fasting and postprandial lipid metabolism were investigated at baseline and at the end of the treatment period. A group of non-diabetic subjects was also studied.. Compared with glibenclamide treatment, pioglitazone treatment decreased fasting triglyceride, glucose and insulin levels and the homeostasis model assessment score of insulin resistance. Decreased fasting triglyceride after pioglitazone treatment was due to reduced VLDL triglyceride, particularly VLDL-2. Lipoprotein lipase activity was unchanged by pioglitazone treatment but hepatic lipase showed a significant decrease. Pioglitazone treatment lowered total postprandial triglyceride, as well as chylomicron- and chylomicron-remnant retinyl palmitate levels to normal. Glucose disposal improved but remained abnormal.. Insulin sensitisation with pioglitazone has major effects in restoring postprandial lipaemia to normal, while also correcting fasting hypertriglyceridaemia; both factors may have consequences for atherogenic risk in diabetes.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Diet; Diterpenes; Fatty Acids, Nonesterified; Female; Health; Humans; Insulin; Lipid Metabolism; Lipoprotein Lipase; Lipoproteins; Liver; Male; Middle Aged; Pioglitazone; Retinyl Esters; Thiazolidinediones; Triglycerides; Vitamin A

Premixed insulin analogues reduce postprandial hyperglycemia in patients with Type 2 diabetes in comparison to premixed regular insulin. Insulin also plays an important role in the regulation of postprandial lipid metabolism. It is known that increased levels of postprandial insulin reduce postprandial hyperlipemia but, on the other hand, no information exists with regard to the possible effect of insulin analogues in comparison to human insulin.. 12 subjects (3 men; age 59 +/- 5 years; BMI 30.5 +/- 5.9 kg/m2, duration of diabetes 9 +/- 1 years, HbA1c 8.33 +/- 1.1 %) already on therapy with premixed insulin were treated either with biphasic human insulin (BHI30) or with biphasic insulin aspart (BIAsp30) (1.3 IU fast acting insulin/12 g KH) in the setting of a standardized test meal. Serum levels of glucose, insulin, C-peptide and triglycerides as well as retinylpalmitate in plasma and chylomicron remnants were determined before and up to 8 hours after the meal.. As was to be expected, therapy with BIAsp30 reduced the maximum increase of postprandial glucose from 7.10 +/- 2.00 mmol/l to 5.27 +/- 1.83 mmo/l (p = 0.007) compared to BHI30 insulin. In the same way, the maximum increase of triglycerides (from 2.33 +/- 1.03 to 1.65 +/- 0.69 mmol/l, p = 0.014) was reduced. The AUC 0 - 8 for triglycerides was not significantly influenced (34.20 +/- 19.86 vs. 31.46 +/- 16.21 mmol x 8 h/l) but the incremental area over baseline (AOB 0 - 8) was significantly reduced from 8.02 +/- 4.35 to 6.12 +/- 3.94 mmol x 8 h/l (p = 0.024).. Compared to conventional human premixed insulin the prandial therapy with biphasic insulin aspart results not only in an improvement of glucose tolerance but also in a significant reduction of postprandial hyperlipemia.

Topics: Biphasic Insulins; Chylomicron Remnants; Chylomicrons; Cross-Over Studies; Diabetes Mellitus, Type 2; Diterpenes; Female; Humans; Hyperlipidemias; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Postprandial Period; Retinyl Esters; Time Factors; Vitamin A

To assess postprandial lipidemia in normotriglyceridaemic type 2 diabetic patients treated with diet only, 12 non-obese patients (8 males, hemoglobin A(1c) [HbA(1c)] 6.80 +/- 0.67%) and 14 controls of similar age, body mass index (BMI), and fasting triglyceride (Tg) were given a test meal (58 g fat, 100,000 IU vitamin A). Fasting low-density lipoprotein (LDL) cholesterol (LDLc), high-density lipoprotein (HDL) cholesterol (HDLc), free fatty acids, and apolipoprotein B (apoB), and fasting and postprandial Tg, retinylpalmitate (RP), LDL size, glucose, and insulin were measured. The homeostasis assessment model (HOMA) index and lipoprotein (Lpl) and hepatic (HL) lipase activities were estimated. Patients showed lower fasting HDLc (1.12 +/- 0.26 v 1.40 +/- 0.28 mmol/L, P =.02) and a trend towards smaller LDL particles, which was significant 4 hours postprandially (25.86 +/- 0.40 v 26.16 +/- 0.30 nm, P =.04). The area under the curve of Tg (AUC-Tg) and RP, and Lpl were similar, but HL was higher in patients (156.63 +/- 23.89 v 118 +/- 43.27 U/L, P =.011). HL correlated inversely with LDL size and directly with the HOMA index. In conclusion, normotriglyceridemic type 2 diabetic patients with insulin resistance but relatively preserved insulin secretion show low fasting HDLc and increased HL, but normal postprandial lipidemia.

Topics: Apolipoproteins B; Area Under Curve; Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Diabetes Mellitus, Type 2; Diterpenes; Electrophoresis, Polyacrylamide Gel; Fatty Acids, Nonesterified; Female; Humans; Insulin; Lipids; Male; Middle Aged; Postprandial Period; Retinyl Esters; Triglycerides; Vitamin A

The primary goal of the present study was to examine the effects of improved glycaemic control associated with glipizide treatment on postprandial lipaemia in non-insulin-dependent diabetic patients. The metabolism of triglyceride-rich lipoproteins of intestinal origin was assessed by measuring the retinyl palmitate content in plasma and the Svedberg flotation index (Sf) > 400 and Sf 20-400 lipoprotein fractions. Fasting plasma glucose concentrations (14.5 +/- 0.5 vs 9.0 +/- 0.5 mmol/l), glycated haemoglobin levels (13.1 +/- 0.6 vs. 9.7 +/- 0.6%), and daylong plasma glucose concentrations were all significantly lower after glipizide treatment (p < 0.001). The improvement in glycaemic control was associated with increases in insulin-mediated glucose uptake (p < 0.001) and plasma post-heparin lipoprotein and hepatic lipolytic activities (p < 0.02). Both fasting plasma triglyceride (3.09 +/- 0.51 vs 2.37 +/- 0.34 mmol/l), and postprandial triglyceride concentrations (p < 0.05-0.001) were lower following glipizide treatment, associated with a significant fall in retinyl palmitate content in all three lipoprotein fractions (p < 0.02-0.001), with the most substantial decrease seen in the Sf20-400 fraction. These data indicate that glipizide-induced improvement in glycaemic control was associated with changes in the metabolism of triglyceride-rich lipoproteins of intestinal origin that would be anticipated to reduce risk of coronary heart disease in non-insulin-dependent diabetic patients.

Topics: Blood Glucose; Cholesterol; Circadian Rhythm; Diabetes Mellitus, Type 2; Diterpenes; Eating; Fatty Acids, Nonesterified; Female; Glipizide; Glycated Hemoglobin; Humans; Lipase; Lipoprotein Lipase; Lipoproteins; Liver; Male; Middle Aged; Reference Values; Retinyl Esters; Triglycerides; Vitamin A

The effect of gemfibrozil on postprandial lipoprotein metabolism was investigated in a 12-week, randomized, double-blind, placebo-controlled trial in 20 non-insulin-dependent diabetic patients with moderate hypertriglyceridemia. The patients were given a meal containing 78 g of fat and 345,000 units of vitamin A to label chylomicrons and their remnants. Plasma obtained at various times during the fat-load test was separated into six fractions by gradient-density ultracentrifugation. Gemfibrozil reduced the postprandial triglyceride response, measured as the area under the time-dependent concentration curve, on average by 32% in whole plasma, by 38% in the Svedberg flotation unit (Sf) 1,100-3,200 chylomicron fraction, by 36% in Sf 400-1,100 chylomicrons, and by 38% in the Sf 60-400 lipoproteins. Retinyl palmitate, a measure of intestinally derived particles, was reduced in plasma by 34%, in Sf 1,100-3,200 by 46%, in Sf 400-1,100 by 44%, and in Sf 60-400 by 37%. All these reductions were significant in comparison with the placebo group. Particles with Sf < 60 were not significantly affected. In contrast to earlier observations in healthy subjects, no significant negative correlations existed between postprandial lipemia and high density lipoprotein cholesterol or the postheparin lipoprotein lipase activity. The reduction of the potentially atherogenic chylomicron remnants may decrease the risk of atherosclerosis in non-insulin-dependent diabetes mellitus, a hypothesis that awaits testing in prospective studies.

Topics: Arteriosclerosis; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diterpenes; Female; Food; Gemfibrozil; Humans; Lipids; Lipoproteins; Male; Middle Aged; Retinyl Esters; Triglycerides; Vitamin A

The effect of dietary composition on concentrations of postprandial lipoproteins was studied in eight sulfonylurea-treated patients with noninsulin dependent diabetes mellitus. Two diets were consumed by each patient for 2 weeks in random order, one contained (as percent of total calories) 15% protein, 40% fat, and 45% carbohydrate (CHO), whereas the other consisted of 15% protein, 25% fat, and 60% CHO. At the end of each dietary period, patients were given Vitamin A (60,000 U/m2) with their noon meal, and the concentration of triglyceride (TG) and retinyl esters in plasma and two lipoprotein fractions (Sf > 400 and Sf 20-400) determined over the next 12 h. The results indicated that both postprandial TG and retinyl ester concentrations were higher in plasma (Sf > 400, and Sf 20-400 lipoproteins), when patients ate the 25% fat/60% CHO diet. Thus, replacing saturated fat with CHO accentuates the magnitude of postprandial lipemia. Since TG-rich lipoproteins may be atherogenic, appropriate dietary advice for patients with type 2 diabetes may deserve reappraisal.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Diterpenes; Food; Humans; Insulin; Lipids; Lipoproteins; Male; Middle Aged; Retinyl Esters; Triglycerides; Vitamin A

Vitamin A is an essential nutrient with vital biological functions. The present study investigated the effect of different doses of vitamin A palmitate at different time intervals on thyroid hormones and glycemic markers.. Male rats were administrated vitamin A palmitate at different doses (0, 0.7, 1.5, 3, 6, and 12 mg/kg, oral) and samples were collected at different time intervals of 2, 4, and 6 weeks. The levels of vitamin A, thyroid hormones (T3, T4, and TSH), deiodinases (Dio1 and Dio3), glycemic markers (blood insulin and fasting glucose levels, HOMA IR and HOMA β), retinol-binding protein 4 (RBP4) and the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) were measured.. The findings demonstrated that long-term supplementation with high doses of vitamin A palmitate resulted in hypothyroidism (lower T3 and T4 levels and elevated TSH levels) as well as upregulation of Dio1 and Dio3 expression levels. This effect was associated with elevated glucose and insulin levels, enhanced HOMA IR, and decreased HOMA B index. In addition, prolonged vitamin A supplementation significantly increased RBP4 levels that upregulated the expression of PEPCK.. High doses of vitamin A supplementation increased the risk of hypothyroidism, modulated insulin sensitivity, and over a long period, increased the incidence of type 2 diabetes mellitus associated with oxidative stress and hepatitis.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Dietary Supplements; Glucose; Hypothyroidism; Insulin; Insulin Resistance; Insulins; Iodide Peroxidase; Male; Phosphoenolpyruvate; Rats; Rats, Wistar; Thyroid Hormones; Thyrotropin; Vitamin A

Obesity is a major risk factor for type 2 diabetes, which is caused mainly by insulin resistance. Retinol binding protein 4 (RBP4) is the only specific transport protein for retinol in the serum. RBP4 level is increased in the diabetic state and high-fat condition, indicating that retinol metabolism may be affected under these conditions. However, the precise effect of diabetes and high fat-induced obesity on retinol metabolism is unknown. In this study, we examined differences in retinol metabolite levels in rat models of diet-induced obesity and type 2 diabetes (Goto-Kakizaki [GK] rat). Four-week-old male Wistar and GK rats were given either a control diet (AIN-93G) or a high-fat diet (HFD, 40% fat kJ). After 15 weeks of feeding, the RBP4 levels increased by 2-fold in the serum of GK rats but not HFD-fed rats. The hepatic retinol concentration of HFD-fed rats was approximately 50% that of the controls (P < .01). In contrast, the renal retinol concentrations of GK rats increased by 70% (P < .01). However, expression of RARβ in the kidney, which was induced in a retinoic acid-dependent manner, was downregulated by 90% (P < .01) in GK rats. In conclusion, diabetes and obesity affected retinol metabolism differently, and the effects were different in different peripheral tissues. The impact of HFD may be limited to the storage of hepatic vitamin A as retinyl palmitate. In particular, our data indicate that renal retinoic acid production might represent an important target for the treatment of type 2 diabetes mellitus.

Topics: Adipose Tissue; Animals; Blood Glucose; Diabetes Mellitus, Type 2; Diet, High-Fat; Dietary Fats; Diterpenes; Down-Regulation; Insulin; Kidney; Liver; Male; Obesity; Rats; Rats, Wistar; Receptors, Retinoic Acid; Retinol-Binding Proteins, Plasma; Retinyl Esters; Vitamin A

Enhanced and prolonged postprandial triglyceride responses involve increased cardiovascular disease risk in type 2 diabetes. Dietary fat and carbohydrates profoundly influence postprandial hypertriglyceridemia, whereas little information exists on the effect of proteins.. The objective was to compare the effects of the proteins casein, whey, cod, and gluten on postprandial lipid and incretin responses to a high-fat meal in persons with type 2 diabetes.. A crossover study was conducted in 12 patients with type 2 diabetes. Blood samples were collected over 8 h after ingestion of a test meal containing 100 g butter and 45 g carbohydrate in combination with 45 g casein (Cas-meal), whey (Whe-meal), cod (Cod-meal), or gluten (Glu-meal). We measured plasma concentrations of triglycerides, retinyl palmitate (RP), free fatty acids, insulin, glucose, glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic peptide.. The incremental area under the curve for triglyceride was significantly lower after the Whe-meal than after the other meals. The RP response was lower after the Whe-meal than after the Cas-meal and Cod-meal in the chylomicron-rich fraction and higher after the Whe-meal than after Cod- and Glu-meals in the chylomicron-poor fraction. Free fatty acids were most pronouncedly suppressed after the Whe-meal. The glucose response was lower after the Whe-meal than after the other meals, whereas no significant differences were found in insulin, glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic peptide responses.. The data suggest that as a supplement to a fat-rich meal in patients with type 2 diabetes, whey protein seems to outperform other proteins in terms of postprandial lipemia improvement, possibly because of the formation of fewer chylomicrons or increased clearance of chylomicrons. The trial was registered at ClinicalTrials.gov as NCT00817973.

Topics: Aged; Animals; Blood Glucose; Caseins; Cross-Over Studies; Diabetes Mellitus, Type 2; Dietary Fats; Dietary Proteins; Diterpenes; Fatty Acids, Nonesterified; Female; Fishes; Glucagon; Glutens; Glycated Hemoglobin; Humans; Insulin; Lipids; Male; Meat; Middle Aged; Milk Proteins; Postprandial Period; Retinyl Esters; Triglycerides; Vitamin A; Whey Proteins

The oral fat load tests used to study postprandial lipemia are complex and costly and time consuming. A simplified fat load test could be more convenient and more appropriate in routine clinical practice because of the number of lipid determinations required.. We evaluated the capacity of a postprandial test model that reduced the number of blood samples taken in thirty three normal weight controls and 17 normotriglyceridemic obese patients (study 1), 10 normolipidemic type 2 diabetic patients and 7 healthy controls (study 2), and 10 hyperlipidemic type 2 diabetic patients studied before and after hypolipidemic therapy (study 3). Blood samples were taken before and up to 8 hours after giving the oral fat load containing retinol. Triglyceride (TG) and retinyl palmitate (RP) concentrations in the plasma, chylomicrons (CM) and non-chylomicron (nCM) fractions were measured. Postprandial lipid responses using conventional area under the curves (AUCc using 5 to 7 lipid determinations) were compared to a 3-point test that uses only three sample points to predict the area under the curve (AUCp: triglycerides at T0, triglycerides at average peak-time (T4), and triglycerides at T8).. The AUCc and AUCp for triglycerides and retinyl palmitate were highly correlated in each of the groups and whatever the lipid subfraction (r=0.664 - 0.995, p<0.0001). When incremental AUC (iAUC) were used, the coefficients of correlation for triglycerides remained highly significant between iAUCc and iAUCp (r=0.718 - 0.979, p<0.01 - 0.0001). The same trend of differences was found between cases and controls when AUCp was used instead of AUCc. The means of differences between AUCc and AUCp for triglyceride values were small (0.34 - 0.74 mmol/L.h), and the confidence intervals were acceptable considering the range of the AUCs values (5.60 to 79.8 mmol/L.h for plasma triglycerides).. We found that data obtained with a simplified model of AUC using only 3 points to analyse postprandial lipemia are well correlated with those obtained by conventional AUC, and that the AUCp allows to the same conclusions as AUCc when healthy subjects were compared to patients with altered postprandial metabolism. Thus AUCp may be a good evaluation of the AUCc, and the simplified 3-point protocol may well be used and suitable for studies on large groups of subjects who are eligible for an oral fat load test.

Topics: Area Under Curve; Body Mass Index; Body Weight; Chylomicrons; Diabetes Mellitus, Type 2; Dietary Fats; Diterpenes; Female; Humans; Hypertriglyceridemia; Hypoglycemic Agents; Male; Models, Biological; Obesity; Postprandial Period; Reference Values; Retinyl Esters; Time Factors; Triglycerides; Vitamin A

Retarded post-prandial (pp) lipid clearance is potentially a major component of the increased cardiovascular risk incurred by hypertriglyceridaemic non-insulin-dependent diabetic mellitus (NIDDM) patients. The effect of bezafibrate (Bz, 400 mg per day for 5 weeks on chylomicron (CM) and remnant clearance after loads of 100 g of fat and vitamin A was therefore explored in 10 male patients (glycaemia 11.9 +/- 3.3 TG 4.5 +/- 2.4 mmol L(-1)). In all subjects CM-TG and retinyl palmitate (RP) were reduced by 50%, but 8-h non-CM (remnant) RP decreased only in initially mildly hypertriglyceridaemic subjects (-35%, P < 0.05), while in three patients with very elevated initial TG (epsilon3/3, epsilon3/2 and epsilon2/2 genotypes) 8-h remnant RP increased by 100%. The decrease in pp CM-TG correlated with that of fasting Sf 20-400 (r = 0.686, P = 0.026), suggesting that improved lipolysis was a major determinant of hypolipidaemic effect. Apo CIII synthesis is known to be depressed by Bz: concentrations were lower under Bz (P < 0.05). A positive correlation (r = 0.880, P < 0.001) with fasting TG before treatment and its disappearance after treatment suggested an involvement of high concentrations with hypertriglyceridaemia. Post-prandial non-esterified fatty acids were decreased by 35 in correlation with a significant (-19%, P < 0.05) improvement in fasting glycaemia (r = 0.801, P < 0.005). These results suggest that Bz acts both on lipolysis and on removal of CM remnants, but that removal can become saturated when lipolysis is massively improved.

Topics: Aged; Apolipoprotein C-III; Apolipoproteins C; Bezafibrate; Blood Glucose; Chylomicrons; Diabetes Mellitus, Type 2; Dietary Fats; Diterpenes; Fatty Acids, Nonesterified; Humans; Lipoproteins; Male; Middle Aged; Postprandial Period; Retinyl Esters; Triglycerides; Vitamin A

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with postprandial lipoprotein clearance defects that are correlated with the fasting hypertriglyceridemia widely observed in NIDDM patients. The aim of this study was to determine if such postprandial disturbances are found in NIDDM patients strictly normotriglyceridemic in the fasting state, and if the apolipoprotein E (apo E) polymorphism influences postprandial metabolism of intestinally derived lipoproteins. The vitamin A-fat loading test was used in 18 normotriglyceridemic NIDDM patients and seven normotriglyceridemic obese controls, and postprandial triglyceride (TG) and retinyl palmitate (RP) concentrations were evaluated in total plasma, and in the chylomicron (Sf > 1,000) and nonchylomicron (Sf < 1,000) fractions isolated by ultracentrifugation. NIDDM patients exhibited an amplified response of both TG and RP as compared with obese controls in the three fractions. Incremental TG response to the oral fat load was strongly correlated with fasting TG level (r = .80, P < .0001) in the whole study population. Postprandial lipoprotein profiles were distinguished in NIDDM patients according to apo E phenotype: despite normal fasting TG levels in E3/3 (n = 6), E2/3 (n = 6), and E3/4 (n = 6), postprandial RP response was twofold to threefold higher in E2/3 and E3/4 patients than in the common E3/3 phenotype. Contrasting lower postprandial TG increment and lower fasting and postprandial high-density lipoprotein (HDL) and HDL3 cholesterol levels were observed in E3/4 versus E3/3 patients, possibly reflecting modifications in lipid content of the postprandial lipoproteins driven by a differential lipid transfer activity depending on apo E isoform. These data indicate an enhanced postprandial lipemia in normotriglyceridemic NIDDM patients, and demonstrate the influence of apo E polymorphism on their lipoprotein clearance. Postprandial alterations of lipoprotein remnants may thus accelerate atherogenesis even in normotriglyceridemic NIDDM patients.

Topics: Adult; Apolipoproteins E; Cholesterol, HDL; Chylomicrons; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Fats; Diterpenes; Eating; Female; Humans; Lipoproteins; Lipoproteins, HDL; Male; Middle Aged; Obesity; Phenotype; Polymorphism, Genetic; Retinyl Esters; Triglycerides; Vitamin A

The authors evaluated serum retinol, retinol-binding protein (RBP), and beta-carotene levels to elucidate the retinoid metabolism in non-insulin-dependent diabetes mellitus (NIDDM). The mean retinol levels by gender (1.83 mumol/L for females and 2.24 mumol/L for males) in diabetics were higher than those (1.31 mumol/L for females and 1.82 mumol/L for males) in control subjects (P < 0.0001, P < 0.01, respectively). The mean retinol/RBP ratios (0.95 for females and 0.97 for males) of diabetics were higher than those of the control subjects (0.60 for females and 0.64 for males) and of male patients having impaired glucose tolerance (0.55) (P < 0.0001). Lipid-lowering medication significantly decreased retinol, with decreasing apolipoprotein C-II but without a commensurate decrease in RBP. The retinol levels had a positive correlation with apolipoprotein C-II in all or normolipidemic patients with diabetes and control subjects. The high retinol/RBP ratio implies that an excessive or free retinol possibly exists in NIDDM. An alternative metabolism of retinol is inferred to underlie NIDDM without direct influences of cholesterol or triglyceride themselves.

Topics: Anticholesteremic Agents; Antioxidants; Apolipoprotein C-II; Apolipoprotein C-III; Apolipoproteins C; beta Carotene; Blood Glucose; Carotenoids; Cholesterol; Diabetes Mellitus, Type 2; Diterpenes; Female; Humans; Hypercholesterolemia; Lovastatin; Male; Middle Aged; Retinol-Binding Proteins; Retinyl Esters; Sex Characteristics; Simvastatin; Triglycerides; Vitamin A

Conventional factors do not fully account for the increased cardiovascular risk in NIDDM but, because of the underlying disorders in lipid metabolism, the postprandial state can be expected to induce temporary changes of a potentially atherogenic nature. The response to a 1000-kcal meal (70% lipid; 100,000 IU vitamin A) over 8 h was compared in 10 normoponderal, normotriglyceridemic NIDDM male patients and 12 controls. In patients lipolysis was normal, but remnant clearance was delayed (P < 0.02) and apo E concentrations were lower. LDL-C decreased postprandially, more in patients (P < 0.05), while LDL-PL accumulated in controls but not in patients. As a result UC:PL decreased in controls (P < 0.05) not in patients. The distribution of LDL subclasses shifted towards large particles in controls (LDL-I, 42%; LDL-II, 50%; LDL-III, 7.6% at 6 h) and smaller ones in patients (LDL-I, 29%; LDL-II, 56%; LDL-III, 16% at 6 h). In controls only, the percentage of LDL-III correlated negatively with apo E (r = -0.97, P < 0.001) suggesting that apo E promotes removal of light particles before they reach LDL-III and may be a limiting factor in patients. We conclude that the postprandial state is potentially more atherogenic in normoponderal, normotriglyceridemic patients than in controls: remnant clearance is delayed, the UC:PL ratio of LDL fails to decrease postprandially as it does in controls, limiting the acceptor capacity of LDL for UC, and the distribution of LDL subclasses is shifted towards a more atherogenic profile.

Topics: Analysis of Variance; Apolipoproteins B; Apolipoproteins E; Blood Glucose; Case-Control Studies; Cholesterol; Diabetes Mellitus, Type 2; Dietary Fats; Diterpenes; Humans; Lipoproteins, LDL; Male; Phospholipids; Radioimmunoassay; Retinyl Esters; Triglycerides; Vitamin A

To investigate whether abnormalities in alimentary lipemia explain the increased risk of coronary artery disease (CAD) in subjects with non-insulin-dependent diabetes mellitus (NIDDM), we performed an oral vitamin A fat-load test in four groups of men (each n = 15): 1) NIDDM and angiographically verified CAD (DM+CAD+): 2) CAD but no diabetes (DM-CAD+); 3) NIDDM but no CAD, excluded by an exercise thallium scan (DM+CAD-); and 4) healthy control subjects (DM-CAD-). The groups were matched for age and body mass index. Plasma obtained after an overnight fast and 2, 3, 4, 6, 9, 12, and 24 h after a fatty meal (78 g fat, 345,000 IU retinyl palmitate [RP]) was separated by density gradient ultracentrifugation into six fractions of triglyceride (TG)-rich lipoproteins: Svedberg flotation units (Sf) > 3200, Sf 1100-3200, Sf 400-1100, Sf 60-400, Sf 20-60, and Sf 12-20. TG, RP, and cholesterol concentrations were measured in plasma and in each lipoprotein fraction. Postprandial plasma TG responses were significantly larger in both NIDDM groups than in the healthy control group. The most marked differences were observed in the Sf 60-400 lipoproteins, whether measured as TG or RP responses. However, there were no differences between the DM+CAD+ and DM+CAD- groups. The between-group differences in alimentary lipemia were only partially explained by fasting TG levels. In contrast to the healthy subjects, no significant negative correlation was observed in the NIDDM patients between alimentary lipemia and lipoprotein lipase activity, implying an abnormality of the lipolysis of TG-rich particles in NIDDM. Levels of atherogenic postprandial remnant lipoproteins are increased in NIDDM. However, in this study the magnitude of alimentary lipemia did not distinguish NIDDM patients with CAD from those without CAD symptoms and normal exercise thallium scans.

Topics: Aged; Apolipoproteins E; Blood Glucose; Cholesterol; Coronary Disease; Diabetes Mellitus, Type 2; Dietary Fats; Diterpenes; Humans; Hypertriglyceridemia; Insulin; Lipase; Lipoprotein Lipase; Lipoproteins; Lipoproteins, HDL; Lipoproteins, IDL; Lipoproteins, VLDL; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Retinyl Esters; Triglycerides; Vitamin A

Vitamin A was administered to eight patients with noninsulin-dependent diabetes mellitus in conjunction with the two different test meals containing (as percentage of total calories) either 15% protein, 60% carbohydrate (CHO), and 25% fat or 15% protein, 40% CHO, and 45% fat. The vitamin A and test meals were given at noon (4 h after a standard breakfast), and blood was obtained hourly from noon to midnight for measurement of plasma glucose, insulin, triglyceride (TG), and cholesterol concentrations; concentrations of TG and cholesterol in Sverdberg floatation (Sf) unit above 400 and Sf 20-400 lipoproteins; retinyl ester concentration in plasma; and both Sf more than 400 and Sf 20-400 lipoproteins. The postprandial TG response in plasma, Sf more than 400 lipoproteins, and Sf 20-400 lipoproteins from noon to midnight was only slightly higher than values seen after consumption of the 60% CHO diet, which contained much less fat (25% vs. 45%) and the retinyl ester concentration was actually higher in both lipoprotein fractions after the diet containing the smallest amount of fat (60% CHO). Furthermore, the cholesterol concentration in the plasma and two lipoprotein fractions was identical after the two diets, despite the great difference in fat content. These data indicate that the acute ingestion of high CHO (60%), low fat (25%) diets by patients with noninsulin-dependent diabetes mellitus led to little or no decrease in postprandial plasma or lipoprotein TG or cholesterol concentrations and an actual increase in concentration of potentially atherogenic small chylomicron and/or chylomicron remnants.

Topics: Aged; Analysis of Variance; Cholesterol; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dietary Fats; Diterpenes; Eating; Humans; Intestinal Mucosa; Lipoproteins; Male; Middle Aged; Retinyl Esters; Time Factors; Triglycerides; Vitamin A

Postprandial lipoprotein metabolism may be important in atherogenesis and has not been studied in detail in noninsulin-dependent diabetes mellitus (NIDDM). We used the vitamin A fat-loading test to label triglyceride-rich lipoprotein particles of intestinal origin after ingestion of a high fat mixed meal containing 60 g fat/m2 and 60,000 U vitamin A/m2 in 12 untreated NIDDM subjects with normotriglyceridemia (NTG; triglycerides, less than 1.7 mmol/L), 7 untreated NIDDM subjects with moderate hypertriglyceridemia (HTG; triglycerides, 1.7-4.7 mmol/L), and 8 age- and weight-matched normotriglyceridemic nondiabetic controls. The postprandial triglyceride increment was greater in NIDDM with HTG (P = 0.0001) and correlated strongly in all groups with the fasting triglyceride concentration (r = 0.83; P = 0.0001). Retinyl palmitate measured in whole plasma, an Sf greater than 1000 chylomicron fraction, and an Sf less than 1000 nonchylomicron fraction was also significantly greater in NIDDM with HTG, but did not differ significantly between NIDDM with NTG and controls. In NIDDM with HTG, chylomicrons appeared to be cleared at a slower rate, as evidenced by the significantly later intersection of the chylomicron and nonchylomicron retinyl palmitate response curves (13.7 h in HTG NIDDM vs. 8.5 h in NTG NIDDM vs. 7.3 h in controls; P less than 0.01). Although fasting FFA levels were similar in all three groups, the HTG diabetic subjects had a late postprandial surge in FFAs that lasted for up to 14 h. The postprandial FFA elevation in all groups correlated with the fasting triglyceride concentration (r = 0.57; P less than 0.002) and postprandial triglyceride increment (r = 0.80; P = 0.0001). The fasting core triglyceride content of the HDL particles in NIDDM with HTG was significantly elevated compared to those in NIDDM with NTG and controls (21.0% vs. 14.0% vs. 14.1% respectively; P less than 0.05), and this increased proportionately in all groups after the meal at the expense of cholesteryl ester, the increase correlating with total plasma postprandial triglyceride increment (r = 0.51; P less than 0.01). We conclude that moderate fasting hypertriglyceridemia in NIDDM is predictive of a constellation of postprandial changes in lipids and lipoproteins that may potentiate the already unfavorable atherogenic fasting lipid profile in these subjects.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diterpenes; Eating; Fasting; Fatty Acids, Nonesterified; Forecasting; Heparin; Humans; Hypertriglyceridemia; Insulin; Lipase; Lipids; Lipoproteins; Pancreatic Hormones; Retinyl Esters; Vitamin A