phytosterols and Diabetes-Mellitus--Type-1

We investigated the effect of plant stanol esters (STAEST) on serum total and LDL cholesterol concentrations and endothelial function in subjects with type 1 diabetes (T1D). In addition, the changes in the relative serum markers of cholesterol metabolism were recorded. In a parallel, randomized, double-blind study the intervention group (n = 11) consumed STAEST spread (2g/day stanols) and the control group (n=8) the same spread containing no added stanols for 12 weeks. At baseline, brachial artery diameter was negatively correlated with serum HDL cholesterol concentration (r = -0.476, P < 0.05), but not with total or LDL cholesterol concentrations or serum non-cholesterol sterol ratios to cholesterol. Flow-mediated dilatation was positively associated with serum absorption marker ratios to cholesterol, significantly so with the sitosterol ratio (r = 0.467, P < 0.05). During the intervention, serum total and LDL cholesterol concentrations were reduced by 4.9 and 6.9% from baseline in the STAEST group, and by 10.8 and 16.1% from controls, respectively (P < 0.05 for all). No significant changes in HDL cholesterol and serum triglyceride concentrations were found. The STAEST consumption reduced serum campesterol and sitosterol ratios by 17-21% (P<0.05) from baseline, but the relative serum synthesis markers were not changed. Brachial artery diameter and flow-mediated dilatation did not change during the investigation. In conclusion, STAEST significantly reduced serum total and LDL cholesterol concentrations and serum plant sterol ratios without affecting HDL and triglyceride concentrations in subjects with T1D. STAEST had no effect on endothelial function.

Topics: Adult; Blood Pressure; Cholesterol, LDL; Diabetes Mellitus, Type 1; Double-Blind Method; Endothelium; Female; Humans; Male; Middle Aged; Phytosterols; Sitosterols; Treatment Outcome; Triglycerides

The aim of this study was to determine the impact of dietary plant sterols and stanols on sterol incorporation and sterol-regulatory gene expression in insulin-treated diabetic rats and nondiabetic control rats. Diabetic BioBreeding (BB) and control BB rats were fed a control diet or a diet supplemented with plant sterols or plant stanols (5 g/kg diet) for 4 weeks. Expression of sterol-regulatory genes in the liver and intestine was assessed by real-time quantitative polymerase chain reaction. Diabetic rats demonstrated increased tissue accumulation of cholesterol and plant sterols and stanols compared to control rats. This increase in cholesterol and plant sterols and stanols was associated with a marked decrease in hepatic and intestinal Abcg5 (ATP-binding cassette transporter G5) and Abcg8 (ATP-binding cassette transporter G8) expressions in diabetic rats, as well as decreased mRNA levels of several other genes involved in sterol regulation. Plant sterol or plant stanol supplementation induced the accumulation of plant sterols and stanols in tissues in both rat strains, but induced a greater accumulation of plant sterols and stanols in diabetic rats than in control rats. Surprisingly, only dietary plant sterols decreased cholesterol levels in diabetic rats, whereas dietary plant stanols caused an increase in cholesterol levels in both diabetic and control rats. Therefore, lower expression levels of Abcg5/Abcg8 in diabetic rats may account for the increased accumulation of plant sterols and cholesterol in these rats.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Cholesterol, Dietary; Diabetes Mellitus, Type 1; Dietary Fats; Gene Expression; Intestine, Small; Lipoproteins; Liver; Membrane Transport Proteins; Phytosterols; Polymerase Chain Reaction; Rats; Rats, Inbred BB; RNA, Messenger

It has been suggested that plant sterol absorption is increased in type 1 diabetes mellitus (T1DM) and that this may relate to the increased cardiovascular risk seen in T1DM. The cardiovascular benefit of lowering low-density lipoprotein-cholesterol with statin medication has also been shown to be influenced by plant sterol absorption.. The relationship between sterol concentrations, coronary artery disease (CAD), and the use of statin medications in T1DM was compared between participants with CAD (Minnesota codes 1.1, 1.2, 1.3, 4.1-4.3, 5.1-5.3, and 7.1; n = 82), from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, and those without (n = 213). Serum sterol concentrations reflecting cholesterol absorption (β-sitosterol and campesterol) and synthesis (desmosterol and lathosterol) were assayed and analyzed by gas chromatography and were expressed as a ratio of total cholesterol (×10(3)).. No differences were observed in markers of cholesterol absorption between individuals with and without CAD. In patients with CAD, significantly lower levels were observed for both sterol markers reflecting cholesterol synthesis compared with individuals without CAD [desmosterol: 0.34 vs 0.42, respectively (P = 0.003); lathosterol 0.47 vs 0.54, respectively (P = 0.019)]. Further stratification by statin medication use revealed significantly lower levels of synthesis-reflecting sterols in individuals taking statin medication, particularly those with CAD.. Although previous reports suggest that higher levels of cholesterol absorption in T1DM potentially increase cardiovascular risk in this population, the present data suggest no differences in cholesterol absorption between T1DM individuals with and without CAD.

Topics: Adult; Cholesterol; Cholesterol, LDL; Coronary Artery Disease; Desmosterol; Diabetes Mellitus, Type 1; Female; Humans; Male; Middle Aged; Phytosterols; Sitosterols

Serum cholestanol and plant sterol ratios to cholesterol, surrogate markers of cholesterol absorption, are assumed to be high in type 1 diabetes (T1D), and the ratios of cholesterol precursor sterols (markers of synthesis) are assumed to be low reflecting downregulated cholesterol synthesis. To this end, we measured serum sterols with gas-liquid-chromatography in 56 men with T1D and in 18 controls to evaluate cholesterol metabolism. Subjects were categorised into tertiles by the cholestanol to cholesterol ratio of controls indicating low to high absorption of cholesterol.. The ratios of the synthesis markers were negatively related to the absorption markers in controls, but less consistently in T1D. The absorption markers were positively related to each other, but interrelation of the synthesis markers was less consistent in T1D. In the low absorbers the absorption markers were higher in T1D than in controls (e.g. sitosterol ratio 173 +/- 9 in T1D vs 135 +/- 11 10(2) x mmol/mol of cholesterol in controls, p < 0.05). In the high absorbers, the absorption markers were similar in T1D and controls, but the synthesis markers were higher in T1D than in controls (e.g. lathosterol ratio 154 +/- 10 in T1D vs 120 +/- 5 10(2) x mmol/mol of cholesterol in controls, p < 0.05).. Absorption and synthesis of cholesterol are less closely related to each other in T1D than in controls, but the markers of cholesterol absorption are interrelated also in T1D. Absorption of cholesterol is higher in T1D than in controls within the range of low absorption, but similar in those with relatively high cholesterol absorption.

Topics: Adult; Biomarkers; Body Mass Index; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 1; Humans; Intestinal Absorption; Male; Phytosterols; Reference Values

The levels of the surrogate markers of cholesterol absorption (cholestanol and plant sterols) and synthesis (cholesterol precursors) in serum have suggested that in adult type 1 diabetes, cholesterol absorption is high and synthesis is low compared with type 2 diabetic or control subjects. Accordingly, these findings were further studied in children with type 1 diabetes.. Forty-eight children with diabetes were compared with 79 age- and sex-matched control subjects. The serum ratios of cholesterol absorption and synthesis markers were measured with gas-liquid chromatography. The study population was divided into triads (combining the two lowest triads) by serum cholestanol ratios of the control subjects indicating low to high cholesterol absorption efficiency.. The ratios of the absorption and synthesis markers were similar in case and control subjects, and they were negatively related to each other in control subjects, being less consistent in diabetic patients. Thus, high cholesterol absorption was associated with low synthesis. Plant sterol ratios increased significantly with increasing cholestanol triads in both groups, but the values in the lowest triads were higher in case versus control subjects.. Homeostasis between cholesterol absorption and synthesis is maintained in control children and somewhat less consistently in those with diabetes. The higher plant sterol ratios in diabetic versus control subjects in the lowest cholestanol triads suggest that cholesterol absorption is higher in children with diabetes versus control subjects but only within the range of low cholesterol absorption.

Topics: Absorption; Adolescent; Blood Pressure; Body Mass Index; Child; Cholestanol; Cholesterol; Diabetes Mellitus, Type 1; Female; Homeostasis; Humans; Male; Phytosterols; Squalene

We examined the effect of glycemic control on the plasma plant sterol levels (a measure of cholesterol absorption efficacy) and the plasma post-heparin diamine oxidase (DAO) activity (a measure of intestinal mucosal mass) in type 1 diabetes. The plasma plant sterol levels (mmol/mol of cholesterol) and the DAO activities after 30 U/kg of intravenous heparin were determined in age- and sex-matched three groups (12 type 1 diabetic patients undergoing conventional insulin therapy, ten patients undergoing intensive insulin therapy, and ten normal subjects). All patients continued their indicated insulin regimen for 14 days with a weight-maintaining energy restricted diet. The conventional group showed a significant higher (p < 0.001) level of the fasting plasma glucose (FPG) or the glycated albumin (GA), a higher (P < 0.01) DAO activity (2-fold of the peak level), which was observed 10-30 min after the heparin injection, and a higher (P < 0.01) plasma plant sterol levels (1.5-fold) compared with those in the other two groups, respectively. The DAO activity 30 min after the heparin injection significantly correlated with either the glycated albumin (GA) concentration or the plant sterol levels in all subjects. Furthermore, the acute glycemic control by the changes of insulin regimen from conventional to intensive showed a significant reduction of the DAO activity and plant sterols in the same patients. These results suggest that glycemic control in part relates to the intestinal adaptation to cholesterol absorption efficacy in type 1 diabetes.

Topics: Adolescent; Adult; Amine Oxidase (Copper-Containing); Biomarkers; Blood Glucose; Cholesterol; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 1; Female; Glucose Tolerance Test; Glycated Serum Albumin; Glycation End Products, Advanced; Glycosylation; Heparin; Humans; Hypoglycemic Agents; Immunoenzyme Techniques; Insulin; Intestinal Absorption; Intestine, Small; Male; Phytosterols; Serum Albumin