phytosterols and Diabetes-Mellitus--Type-2

Natural products in the form of functional foods have become increasingly popular due to their protective effects against life-threatening diseases, low risk of adverse effects, affordability, and accessibility. Plant components such as phytosterol, in particular, have drawn a lot of press recently due to a link between their consumption and a modest incidence of global problems, such as Type 2 Diabetes mellitus (T2DM), cancer, and cardiovascular disease. In the management of diet-related metabolic diseases, such as T2DM and cardiovascular disorders, these plant-based functional foods and nutritional supplements have unquestionably led the market in terms of cost-effectiveness, therapeutic efficacy, and safety. Diabetes mellitus is a metabolic disorder categoriszed by high blood sugar and insulin resistance, which influence major metabolic organs, such as the liver, adipose tissue, and skeletal muscle. These chronic hyperglycemia fallouts result in decreased glucose consumption by body cells, increased fat mobilisation from fat storage cells, and protein depletion in human tissues, keeping the tissues in a state of crisis. In addition, functional foods such as phytosterols improve the body's healing process from these crises by promoting a proper physiological metabolism and cellular activities. They are plant-derived steroid molecules having structure and function similar to cholesterol, which is found in vegetables, grains, nuts, olive oil, wood pulp, legumes, cereals, and leaves, and are abundant in nature, along with phytosterol derivatives. The most copious phytosterols seen in the human diet are sitosterol, stigmasterol, and campesterol, which can be found in free form, as fatty acid/cinnamic acid esters or as glycosides processed by pancreatic enzymes. Accumulating evidence reveals that phytosterols and diets enriched with them can control glucose and lipid metabolism, as well as insulin resistance. Despite this, few studies on the advantages of sterol control in diabetes care have been published. As a basis, the primary objective of this review is to convey extensive updated information on the possibility of managing diabetes and associated complications with sterol-rich foods in molecular aspects.

Topics: Diabetes Mellitus, Type 2; Diet; Humans; Insulin Resistance; Phytosterols; Sterols

Dietary guidelines for many Western countries base their edible oil and fat recommendations solely on saturated fatty acid content. This study aims to demonstrate which nutritional and bioactive components make up commonly consumed edible oils and fats; and explore the health effects and strength of evidence for key nutritional and bioactive components of edible oils. An umbrella review was conducted in several stages. Food composition databases of Australia and the United States of America, and studies were examined to profile nutrient and bioactive content of edible oils and fats. PUBMED and Cochrane databases were searched for umbrella reviews, systematic literature reviews of randomized controlled trials or cohort studies, individual randomized controlled trials, and individual cohort studies to examine the effect of the nutrient or bioactive on high-burden chronic diseases (cardiovascular disease, type 2 diabetes mellitus, obesity, cancer, mental illness, cognitive impairment). Substantial systematic literature review evidence was identified for fatty acid categories, tocopherols, biophenols, and phytosterols. Insufficient evidence was identified for squalene. The evidence supports high mono- and polyunsaturated fatty acid compositions, total biophenol content, phytosterols, and possibly high α-tocopherol content as having beneficial effects on high-burden health comes. Future dietary guidelines should use a more sophisticated approach to judge edible oils beyond saturated fatty acid content.

Topics: Diabetes Mellitus, Type 2; Dietary Fats; Fats; Fatty Acids; Humans; Nutrients; Phytosterols; Plant Oils

The efficacy and safety of phytosterols for the management of dyslipidemia are reviewed.. Phytosterols have been evaluated in over 40 clinical trials. The incorporation of 2 g of phytosterols daily into margarine, mayonnaise, orange juice, olive oil, low-fat milk, yogurt, and tablets is associated with significant reductions in low-density-lipoprotein (LDL) cholesterol from baseline over 1-12 months in adults with normal or high cholesterol, in children, and in patients with type 2 diabetes mellitus. Phytosterol dosages of 1.6-3 g daily have been shown to reduce LDL cholesterol by 4.1-15% versus placebo within the first month of therapy. One meta-analysis found mean reductions of 10-11%, but results vary. Several placebo-controlled trials found that the addition of phytosterols to statin therapy was associated with reductions of 7-20% in LDL cholesterol for up to 1.5 years. Overall, phytosterols are useful for reducing LDL cholesterol in patients who cannot reach their treatment goal by diet alone or who are taking maximum tolerated doses of statins. These products offer an alternative to statins in patients who cannot take statins or whose statin dosage is restricted because of potential drug interactions or concomitant diseases. Commonly reported adverse effects are primarily gastrointestinal in nature.. Phytosterol therapy produces an average 10-11% reduction in LDL cholesterol concentration, but it is unknown whether this effect persists beyond two years. Phytosterol products are well tolerated and have few drug interactions, but their long-term safety has not been established. Current evidence is sufficient to recommend phytosterols for lowering LDL cholesterol in adults.

Topics: Adult; Animals; Child; Cholesterol, LDL; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Dyslipidemias; Herb-Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Phytosterols

We performed a meta-analysis of five randomized, placebo-controlled trials to characterize the impact of plant sterols/stanols on plasma lipids in patients with type 2 diabetes. Upon meta-analysis, plant sterols/stanols significantly reduced total and LDL cholesterol, with a trend towards improvement in HDL. No beneficial effect on triglycerides was apparent.

Topics: Anticholesteremic Agents; Cholesterol; Cholesterol, LDL; Diabetes Mellitus, Type 2; Humans; Lipids; Phytosterols; Randomized Controlled Trials as Topic; Research Design; Sitosterols; Triglycerides

Based on what is known of the components of plant-based diets and their effects from cohort studies, there is reason to believe that vegetarian diets would have advantages in the treatment of type 2 diabetes. At present there are few data on vegetarian diets in diabetes that do not in addition have weight loss or exercise components. Nevertheless, the use of whole-grain or traditionally processed cereals and legumes has been associated with improved glycemic control in both diabetic and insulin-resistant individuals. Long-term cohort studies have indicated that whole-grain consumption reduces the risk of both type 2 diabetes and cardiovascular disease. In addition, nuts (eg, almonds), viscous fibers (eg, fibers from oats and barley), soy proteins, and plant sterols, which may be part of the vegetarian diet, reduce serum lipids. In combination, these plant food components may have a very significant impact on cardiovascular disease, one of the major complications of diabetes. Furthermore, substituting soy or other vegetable proteins for animal protein may also decrease renal hyperfiltration, proteinuria, and renal acid load and in the long term reduce the risk of developing renal disease in type 2 diabetes. The vegetarian diet, therefore, contains a portfolio of natural products and food forms of benefit for both the carbohydrate and lipid abnormalities in diabetes. It is anticipated that their combined use in vegetarian diets will produce very significant metabolic advantages for the prevention and treatment of diabetes and its complications.

Topics: Adult; Aged; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Diet, Vegetarian; Edible Grain; Female; Humans; Male; Middle Aged; Nuts; Phytosterols; Soybean Proteins

Topics: Diabetes Mellitus, Type 2; Humans; Hypercholesterolemia; Lipoproteins; Phytosterols; Sensitivity and Specificity; Structure-Activity Relationship

Cross-sectional studies have shown that obesity is associated with lower intestinal cholesterol absorption and higher endogenous cholesterol synthesis. These metabolic characteristics have also been observed in patients with type 2 diabetes, metabolic syndrome, steatosis or cholestasis. The number of intervention studies evaluating the effect of weight loss on these metabolic characteristics is, however, limited, while the role of the different fat compartments has not been studied into detail. In a randomized trial, abdominally obese men (N = 54) followed a 6-week very low caloric (VLCD) diet, followed by a 2 week weight-maintenance period. Non-cholesterol sterols were measured at baseline and after 8 weeks, and compared to levels in lean participants (N = 25). After weight loss, total cholesterol (TC)-standardized cholestanol levels increased by 0.18 µmol/mmol (p < 0.001), while those of campesterol and lathosterol decreased by 0.25 µmol/mmol (p < 0.05) and 0.39 µmol/mmol (p < 0.001), respectively. Moreover, after weight loss, TC-standardized lathosterol and cholestanol levels were comparable to those of lean men. Increases in TC-standardized cholestanol after weight loss were significantly associated with changes in waist circumference (p < 0.01), weight (p < 0.001), BMI (p < 0.001) and visceral fat (p < 0.01), but not with subcutaneous and intrahepatic lipids. In addition, cross-sectional analysis showed that visceral fat fully mediated the association between BMI and TC-standardized cholestanol levels. Intrahepatic lipid content was a partial mediator for the association between BMI and TC-standardized lathosterol levels. In conclusion, diet-induced weight loss decreased cholesterol synthesis and increased cholesterol absorption. The increase in TC-standardized cholestanol levels was not only related to weight loss, but also to a decrease in visceral fat volume. Whether these metabolic changes ameliorate other metabolic risk factors needs further study.

Topics: Biomarkers; Cholestanol; Cholesterol; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diet, Reducing; Humans; Male; Obesity; Phytosterols; Weight Loss

Sodium/glucose cotransporter 2 (SGLT2) inhibitors decrease plasma triglyceride levels and slightly increase low-density lipoprotein (LDL-c) and high-density lipoprotein cholesterol (HDL-c). However, the mechanisms underlying such changes in the blood lipid profile remain to be determined. We investigated how empagliflozin affects plasma markers of cholesterol absorption and synthesis, and evaluated the relationship between changes in these markers and blood lipids in patients with type 2 diabetes.. In a randomized, active-controlled, open-label trial, 51 patients were randomly allocated in 2:1 ratio to receive empagliflozin 10 mg/day (n = 32) or standard therapy (n = 19) for 12 weeks. We measured plasma levels of lathosterol as a marker of cholesterol synthesis, and campesterol and sitosterol as markers of cholesterol absorption, at baseline and 12 weeks after treatment. In the empagliflozin group, serum HDL-c, but not LDL-c, significantly increased between baseline and 12 weeks (54.4 ± 16.3 vs. 58.8 ± 19.6 mg/dl; p = 0.0006), whereas in the standard therapy group, HDL-c and LDL-c remained unchanged. In the empagliflozin group, plasma campesterol also increased significantly (4.14 ± 1.88 vs. 4.90 ± 2.26 μg/ml, p = 0.0008), whereas no change in plasma campesterol or sitosterol was found in the control group. Although plasma lathosterol showed no change in the whole empagliflozin group, it decreased significantly in patients who were not taking statins. In statin non-users, plasma lathosterol decreased significantly after treatment with empagliflozin (2.71 ± 0.99 vs. 1.91 ± 0.99 μg/ml, p < 0.05). In the empagliflozin group, changes in plasma campesterol correlated positively with changes in HDL-c.. Empagliflozin increases serum campesterol, a marker of cholesterol absorption, in patients with type 2 diabetes. This increase may be associated with SGLT2 inhibitor-induced increases in HDL cholesterol.

Topics: Benzhydryl Compounds; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Glucosides; Humans; Phytosterols

Anagliptin, a dipeptidyl peptidase-4 inhibitor, is reported to reduce the level of low-density lipoprotein cholesterol (LDL-C). The underlying mechanism of this effect and effect on lipid metabolism however remains uncertain.. We therefore evaluate the effects of anagliptin on lipid metabolism-related markers compared with those of sitagliptin. The study was a secondary analysis using data obtained from the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. This trial in patients with type 2 diabetes at a high risk of cardiovascular events and on statin therapy showed that anagliptin reduced LDL-C levels to a greater extent than sitagliptin. Cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol) markers were measured at baseline and 52 weeks in the study cohort (n = 353).. There was no significant difference in the changes of campesterol or sitosterol between the two treatment groups (p = 0.85 and 0.55, respectively). Lathosterol concentration was increased significantly at 52 weeks with sitagliptin treatment (baseline, 1.2 ± 0.7 μg/mL vs. 52 weeks, 1.4 ± 1.0 μg/mL, p = 0.02), whereas it did not change in the anagliptin group (baseline, 1.3 ± 0.8 μg/mL vs. 52 weeks, 1.3 ± 0.7 μg/mL, p = 0.99). The difference in absolute change between the two groups showed a borderline significance (p = 0.06).. These findings suggest that anagliptin reduces LDL-C level by suppressing excess cholesterol synthesis, even in combination with statin therapy. Trial registration ClinicalTrials.gov number NCT02330406. https://clinicaltrials.gov/ct2/show/NCT02330406; registered January 5, 2015.

Topics: Aged; Biomarkers; Cholesterol; Cholesterol, LDL; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Male; Middle Aged; Phytosterols; Pyrimidines; Sitagliptin Phosphate; Sitosterols; Time Factors; Treatment Outcome

Managing cardiovascular disease (CVD) risk factors, e.g., dyslipidemia in type-2 diabetes mellitus (T2DM) is critically important as CVD is the most common cause of death in T2DM patients. This study aimed to investigate the effect of plant sterols (PS) on lowering both elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG).. In a double-blind, randomized, placebo-controlled, parallel study, 161 individuals at increased risk of and with established T2DM, consumed low-fat spreads without or with added PS (2 g/d) for 6 weeks after a 2-week run-in period. Increased risk of developing T2DM was defined by the Australian T2DM Risk Assessment Tool (AUSDRISK). Fasting serum/plasma total cholesterol (TC), LDL-C, TG, high-density lipoprotein cholesterol (HDL-C), glucose and insulin were measured at baseline and after 6 weeks. Effects on acute and chronic postprandial blood lipids, glucose and insulin were measured over 4-h in 39 individuals with T2DM following a mixed meal challenge without and with added 2 g/d PS at week 6. The study was registered at clinicaltrials.gov (NCT02288585).. Hundred fifty-one individuals completed the study and 138 (57% men, 43% women; 44 with and 94 at risk of T2DM) were included in per protocol analysis. Baseline LDL-C and TG were 3.8 ± 1.0 and 2.5 ± 0.8 mmol/l, respectively. PS intake significantly lowered fasting LDL-C (-4.6%, 95%CI -1.2; -8.0; p = 0.009), TC (-4.2%, 95%CI -1.2; -7.1; p = 0.006) and TG (-8.3%, 95% -1.1, -15.0; p = 0.024) with no significant changes in HDL-C, glucose or insulin. Postprandial lipid (TG, TC, LDL-C, HDL-C, remnant cholesterol), glucose and insulin responses did not differ.. In individuals at risk of and with established T2DM and with elevated TG and LDL-C, 2 g/d of PS results in dual LDL-C plus TG lowering. Postprandial lipid or glycemic responses did not differ between PS and control treatment.

Topics: Adult; Australia; Blood Glucose; Cholesterol, LDL; Diabetes Mellitus, Type 2; Double-Blind Method; Dyslipidemias; Female; Humans; Insulin; Male; Middle Aged; Phytosterols; Risk Assessment; Treatment Outcome; Triglycerides

The mechanism responsible for the lipid-lowering effect of dipeptidyl peptidase-4 (DPP-4) inhibitors remains unknown in humans. We evaluated the effect of anagliptin on serum lipid profiles, including cholesterol synthesis and absorption markers, in Japanese patients with type 2 diabetes.. Thirty patients with type 2 diabetes (20 - 70 years old, low-density lipoprotein cholesterol (LDL-C) level over 120 mg/dl, and no history of treatment with antidiabetic or antihyperlipidemic drugs) were enrolled. One hundred milligrams of anagliptin were administered twice a day for a month.. After treatment of anagliptin, the LDL-C and total cholesterol (TC) levels did not decrease overall, but the TC level decreased significantly in 28 patients whose HbA1c levels decreased. Lathosterol decreased significantly, whereas no changes in campesterol, sitosterol or cholestanol were observed.. These results of our study show no significant change in LDL-C, a tendency of decrease in TC and non-high-density lipoprotein cholesterol (non-HDL-C) after treatment of anagliptin for 1 month. Anagliptin therapy decreased the cholesterol synthesis marker lathosterol without changing cholesterol absorption markers.

Topics: Adult; Aged; Biomarkers; Cholestanol; Cholesterol; Cholesterol, LDL; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Lipids; Lipoproteins, HDL; Male; Middle Aged; Phytosterols; Pilot Projects; Pyrimidines; Sitosterols; Young Adult

To date, there are very few clinical reports that have compared the effects of ezetimibe on lipid parameters between hypercholesterolemic patients with and without type 2 diabetes mellitus (T2DM). In this study, we recruited patients for hypercholesterolemic groups with T2DM (n = 42; men/women = 24/18; HbA1c = 6.7 ± 5.4%) and without T2DM (n = 21; men/women = 7/14; HbA1c = 5.3 ± 0.4%). Patients were prescribed ezetimibe at a dose of 10 mg/daily for the course of the 12-week study. At baseline and after 12 weeks of treatment, several lipid parameters, including serum low-density-lipoprotein cholesterol (LDL-C), non-high-density-lipoprotein cholesterol (non-HDL-C), high-sensitivity C-reactive protein (hs-CRP), and cholesterol synthesis/absorption-related markers, were measured. Compared with those at the baseline, the levels of LDL-C, non-HDL-C, campesterol, and sitosterol were significantly reduced after 12 weeks of ezetimibe treatment in both groups. After adjusting for confounding factors, such as age, gender, smoking, and BMI, the levels of LDL-C and non-HDL-C displayed significantly greater reductions in the patients with T2DM (-25.1 ± 13.6% in LDL-C, -20.5 ± 11.2% in non-HDL-C) than those without T2DM (-20.5 ± 7.8% in LDL-C, P < 0.05; -17.4 ± 7.6% in non-HDL-C, P < 0.05). The reduction of the level of cholestanol was significantly and positively correlated with those of LDL-C and non-HDL-C in the patients with T2DM. Taken together, these findings indicate that ezetimibe could reduce the levels of atherogenic lipoproteins to a greater extent in hypercholesterolemic patients with T2DM than in those without T2DM.

Topics: Aged; Azetidines; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cholestanol; Cholesterol; Cholesterol, LDL; Diabetes Mellitus, Type 2; Ezetimibe; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Lipids; Male; Middle Aged; Phytosterols; Sitosterols

To determine the effects of statin treatment and omega-3 polyunsaturated fatty acid supplementation on plasma plant sterol concentrations and cholesterol synthesis in patients with type 2 diabetes.. Plant sterol concentrations and lanosterol (a marker of cholesterol synthesis) were measured using a high sensitivity assay to assess the effect of double-blind daily treatment for 4 months with atorvastatin 20mg or placebo and, in a 2 × 2 factorial design, omega-3 ethyl esters 90 2g or placebo.. 658 patients were included in a per protocol analysis. The 4 treatment groups had similar mean [SD] age (63.5 years [11.7]), HbA(1c) (6.9% [1.1]) and diabetes duration (median 4 years [inter-quartile range 2, 8]). Atorvastatin treatment alone reduced low density lipoprotein (LDL) cholesterol by 1.4 mmol/l (44%, p<0.001), triglycerides by 0.3 mmol/l (20%, p<0.0001) and lanosterol by 0.36 μmol/l (72%, p<0.001). There was no significant placebo adjusted change in median [95% confidence intervals] total plant sterol concentrations (-0.77 μmol/l [inter-quartile range -2.13, 0.59]), although they were increased significantly with omega-3-acid EE90 treatment (3.23 μmol/l [1.28, 5.17]). There was a 27% smaller reduction in LDL cholesterol with atorvastatin treatment in low cholesterol synthesisers with high absorption, defined by changes at or above the median lanosterol and campesterol levels, respectively, compared with the obverse group (difference 0.42 mmol/l [0.21, 0.62]).. Treatment with atorvastatin in type 2 diabetes did not change median total plasma plant sterol concentrations, but LDL cholesterol was reduced most efficaciously in high cholesterol synthesisers with low intestinal cholesterol absorption.. Current controlled trials number ISRCTN: 76737502 (http://isrctn.org).

Topics: Anticholesteremic Agents; Atorvastatin; Cholesterol; Cholesterol, LDL; Diabetes Mellitus, Type 2; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Eicosapentaenoic Acid; Heptanoic Acids; Humans; Lanosterol; Phytosterols; Pyrroles; Triglycerides

The purpose of this study was to determine whether supplements of plant sterols and/or glucomannan improve lipid profile and cholesterol biosynthesis in mildly hypercholesterolemic type II diabetic and non-diabetic subjects and to compare the response of these two subject groups to the treatments.. A randomized, crossover study consisting of four phases of 21 days, with each phase separated by a 28-day washout.. The Mary Emily Clinical Nutrition Research Unit of McGill University.. Eighteen non-diabetic individuals and 16 type II diabetic individuals aged 38-74 years.. Subjects were supplemented with plant sterols (1.8 g/day), glucomannan (10 g/day), a combination of glucomannan and plant sterols, and a placebo, provided in the form of bars.. Overall plasma cholesterol concentrations were lowered (P<0.05) after combination treatment (4.72+/-0.20 mmol/l) compared to control (5.47+/-0.18 mmol/l). Plasma low-density lipoprotein (LDL) cholesterol concentrations were decreased (P<0.05) after glucomannan (3.16+/-0.14 mmol/l) and combination treatments (2.95+/-0.16 mmol/l) compared to control (3.60+/-0.16 mmol/l). The results of lipid profiles did not differ between subject groups. Overall plasma lathosterol concentrations, an index of cholesterol biosynthesis, were lowered (P<0.05) after the combination treatment compared to the plant sterol treatment.. The results suggest that glucomannan and a combination of glucomannan and plant sterols substantially improves plasma LDL cholesterol concentrations.. Forbes Medi-Tech Inc., Vancouver, British Columbia, Canada.

Topics: Adult; Aged; Cathartics; Cholesterol; Cholesterol, LDL; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Synergism; Drug Therapy, Combination; Female; Humans; Hypercholesterolemia; Lipid Metabolism; Male; Mannans; Middle Aged; Phytosterols

Because of hyperglycemia and hyperinsulinemia, diabetic persons have higher cholesterol synthesis and lower cholesterol absorption rates than do nondiabetic persons. Differences in plant sterol efficacy between diabetic and nondiabetic persons have not been examined.. The objective was to compare the degree of response of plasma lipid concentrations and glycemic control to plant sterol consumption in a controlled diet between hypercholesterolemic type 2 diabetic and nondiabetic subjects.. Fifteen nondiabetic subjects and 14 diabetic subjects participated in a double-blinded, randomized, crossover, placebo-controlled feeding trial. The diet included 1.8 g/d of either plant sterols or cornstarch placebo over 21 d, separated by a 28-d washout period.. Plant sterol consumption significantly reduced (P < 0.05) LDL-cholesterol concentrations from baseline in both nondiabetic and diabetic subjects by 15.1% and 26.8%, respectively. The diabetic subjects had significantly (P < 0.05) lower absolute concentrations of total cholesterol after treatment than did the nondiabetic subjects; however, there was no significant difference in the percentage change from the beginning to the end of the trial. There was also a significant decrease (P < 0.05) in absolute non-HDL-cholesterol concentrations after treatment in both groups.. The results showed that plant sterols are efficacious in lowering LDL cholesterol and non-HDL cholesterol in both diabetic and nondiabetic persons. Plant sterol consumption may exist as a dietary management strategy for hypercholesterolemia in persons with type 2 diabetes.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Erythrocytes; Fatty Acids; Female; Glycated Hemoglobin; Humans; Hypercholesterolemia; Insulin; Male; Middle Aged; Phytosterols; Phytotherapy; Treatment Outcome

Phytosterol-enriched margarines are known to significantly lower total and LDL cholesterol, but little is known about the effect of such margarines in subjects with type 2 diabetes.. Investigation of the effect of a phytosterol-enriched spread in subjects with type 2 diabetes mellitus on serum lipids, Hb(A1c), and blood glucose under free-living conditions.. Randomized, placebo-controlled, double-blind clinical trial in two parallel groups over 12 weeks; 85 type 2 diabetic patients with serum LDL cholesterol levels >/= 3.60 mmol/l and without hypolipidemic medication were included in the study. Participants consumed 2 x 10 g of spread with or without 8 % phytosterol-esters daily. Fasting blood samples were analyzed at 0, 4, 8, and 12 weeks.. After 4 weeks, total and LDL cholesterol were significantly reduced in the phytosterol group by 5.2 % and 6.8 %, respectively, compared to baseline (p < 0.05). After 8 and 12 weeks, these reductions became smaller and were not significant any more compared to baseline or between the groups, but a repeated measurement analysis demonstrated a significant difference for both variables between the two groups (each p < 0.05). HDL cholesterol was significantly increased in the phytosterol group compared to the placebo group after 8 and 12 weeks, but there was no overall difference in the repeated measurement analysis between the two groups. In the phytosterol group, there was a small reduction in Hb(A1c) compared to the control group which was only significant after 4 weeks.. This clinical study shows that a phytosterol-enriched spread is effective in lowering total and LDL cholesterol in subjects with type 2 diabetes but also illustrates the difficult maintenance under free-living conditions over time. Although this effect is modest, it may contribute to decreasing the elevated risk of cardiovascular disease in type 2 diabetes.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Food, Fortified; Fructosamine; Glycated Hemoglobin; Humans; Lipids; Male; Margarine; Middle Aged; Phytosterols; Residence Characteristics

Topics: Benzhydryl Compounds; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucosides; Humans; Phytosterols

Topics: Benzhydryl Compounds; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucosides; Humans; Motivation; Phytosterols; Sodium-Glucose Transporter 2 Inhibitors

Changes in cholesterol absorption and cholesterol synthesis may promote dyslipidemia and cardiovascular disease in individuals with type 2 diabetes mellitus (T2DM).. To assess cholesterol synthesis and absorption in lean individuals, obese individuals, and individuals with T2DM.. We measured lathosterol and lanosterol (markers of cholesterol synthesis) as well as campesterol and β-sitosterol (markers of cholesterol absorption) in the serum of 15 to 26 years old individuals with T2DM (n = 95), as well as their lean (n = 98) and obese (n = 92) controls.. Individuals with T2DM showed a 51% increase in lathosterol and a 65% increase in lanosterol compared to lean controls. Similarly, obese individuals showed a 31% increase in lathosterol compared to lean controls. Lathosterol and lanosterol were positively correlated with body mass index, fasting insulin and glucose, serum triglycerides, and C-reactive protein, and negatively correlated with HDL-cholesterol. In contrast, campesterol and β-sitosterol were not altered in individuals with T2DM. Moreover, campesterol and β-sitosterol were negatively correlated with body mass index, fasting insulin, and C-reactive protein and were positively correlated with HDL-cholesterol.. Adolescents and young adults with T2DM show evidence of increased cholesterol synthesis compared to non-diabetic lean controls. These findings suggest that T2DM may promote cardiovascular disease by increasing cholesterol synthesis, and provide additional rationale for the use of cholesterol synthesis inhibitors in this group.

Topics: Adolescent; Adult; Biomarkers; Body Mass Index; Case-Control Studies; Cholesterol; Diabetes Mellitus, Type 2; Humans; Obesity; Phytosterols; Sitosterols; Young Adult

Hyperlipidemia,as one of the severe risk factors of cardiovascular disease,could easily trigger atherosclerosis,coronary heart disease,peripheral vascular disease,pancreatitis,etc.,and could also increase the incidence of type 2 diabetes and fatty liver disease. Improving dyslipidemia could slow down the progression of atherosclerosis and reduce the risk of coronary heart disease. This is of great importance for prevention and treatment of cardiovascular disease. Phytosterols are natural active ingredients in plants. Many researches have shown that phytosterols have significant lipid-lowering activity,which could effectively lower blood cholesterol and triglyceride levels. Foods containing phytosterols have been widely used as therapeutic diets for improving dyslipidemia. In the early years,it was believed that the lipid-lowering effect of phytosterols was achieved by competitively inhibiting the absorption of dietary cholesterol in the intestine since phytosterols had similar chemical structures with cholesterol. In further researches in recent years,more progress has been made in the lipid-lowering mechanisms of phytosterols. In this paper,PubMed and Web of Science were used to review the cholesterol-lowering and triglyceride-lowering mechanisms of phytosterols according to the available data published,so as to use phytosterols more rationally in clinical application to improve hyperlipidemia and other induced diseases.

Topics: Cholesterol; Diabetes Mellitus, Type 2; Humans; Hyperlipidemias; Hypolipidemic Agents; Phytosterols; Triglycerides

Nymphaea stellata (Willd.) has been used in traditional medicine for centuries to treat several illnesses, including diabetes. However, scientific evidence supporting its mechanism of action is lacking. Here, we showed that an N. stellata flower chloroform extract (NSFCExt) has significant plasma glucose lowering ability. Furthermore, an active compound was identified and purified by column chromatography, and the structure of this compound, nymphayol, was determined by X-ray crystallographic analysis. Nymphayol was tested for its effects on insulin secretion by RIN-5F cells cultured in low or high glucose medium; we found that nymphayol treatment improved glucose-stimulated insulin secretion in vitro. Additionally, insulin sensitization and glucose uptake were increased in L6 myotubes. Nymphayol was administered to type 2 diabetic male Wistar rats at several doses (5, 10 or 20 mg/kg/day) for 45 days. After nymphayol administration, the plasma glucose concentration was significantly (p⩽0.05) lower (60.33%) than in control diabetic rats, and the plasma insulin level increased in a dose-dependent manner. In addition, the cellular insulin response was analyzed in type 2 diabetic rats; oral administration of nymphayol increased IRS1 phosphorylation and GLUT4 protein expression in liver and muscle. Nymphayol significantly (p⩽0.05) restored the levels of HbA1c, hepatic glycogen and hepatic glucose-metabolizing enzyme (hexokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, glycogen synthase and glycogen phosphorylase) activity in diabetic rats. The administration of glibenclamide, a reference drug (600 μg/kg), also produced a significant (p⩽0.05) reduction in blood glucose in STZ-nicotinamide induced diabetic rats. The results suggest that nymphayol may be a useful therapy for diabetes because it stimulates insulin secretion and promotes glucose absorption.

Topics: Animals; Biological Transport; Blood Glucose; Body Weight; Cell Line; Cell Proliferation; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Drinking; Gene Expression Regulation; Glucose; Glucose Transporter Type 4; Glycated Hemoglobin; Glycogen; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Liver; Male; Muscle Fibers, Skeletal; Phytosterols; Rats; Rats, Wistar; Reactive Oxygen Species

Topics: Adipose Tissue; Atherosclerosis; Blood Pressure; Capsaicin; Cardiovascular Diseases; Databases, Factual; Diabetes Mellitus, Type 2; Dietary Fats; Dietary Proteins; Endotoxemia; Feeding Behavior; Flavonoids; Fructose; Glycation End Products, Advanced; Humans; Hypertension; Hyperuricemia; Lipid Metabolism; Neuroimaging; Obesity; Phytosterols; Stroke; Thermogenesis

We investigated how liver fat content (LFC) influences cholesterol metabolism by quantifying liver fat using proton magnetic resonance spectroscopy and by measuring the serum concentrations of lathosterol, a marker of cholesterol synthesis, and sitosterol and campesterol, two markers of cholesterol absorption. We also evaluated whether this relationship could be modified by statin therapy. The study was conducted in 263 patients with type 2 diabetes, 137 of whom (52.0%) received statin therapy.. One hundred and sixty-five patients (62.7%) had steatosis (LFC>5.5%). We performed specific analyses in patients without statin therapy and in patients treated with statin therapy. In both groups, the lathosterol to cholesterol ratio correlated positively with LFC, and in multivariate analysis, the lathosterol to cholesterol ratio was associated with LFC independently of age, gender and BMI. Sitosterol and campesterol concentrations were not associated with LFC.. Our study suggests that in patients with type 2 diabetes, LFC is associated with an increase in cholesterol synthesis that is independent of obesity or diabetes mellitus. Statin therapy does not modify this relationship.

Topics: Aged; Biomarkers; Cholesterol; Diabetes Mellitus, Type 2; Dyslipidemias; Fatty Liver; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Linear Models; Liver; Magnetic Resonance Spectroscopy; Male; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Phytosterols; Risk Factors; Sitosterols; Treatment Outcome

In India, Azadirachta indica is typically known as 'neem tree' and its leaves has long been used in the ayurvedic medical tradition as a treatment for diabetes mellitus. In-depth chromatographic investigation on chloroform extract resulted in identification of one new tetranortriterpenoid. Structural elucidation was established on the basis of spectral data as 24,25,26,27-tetranor-apotirucalla-(apoeupha)-1α-senecioyloxy-3α,7α-dihydroxy-14,20,22-trien-21,23-epoxy named by us as meliacinolin (1). The present study investigated the effect hypoglycaemic, hypolipidemic, oxidative stress, insulin resistance, α-glucosidase and α-amylase of 1 from A. indica. Diabetic rats were treated with 1 for 28 d and a set of biochemical parameters were studied including: glucose level, total cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. We also looked into liver function by determining glucose-6-phosphatase, glucokinase and hexokinase activities, and the effect on insulin level. While in vitro inhibition of α-glucosidase and α-amylase enzyme activities were used as indices of effect on glucose absorption. As a result we found that blood glucose level, serum biochemical parameters, hepatic enzymes, thiobarbituric acid reactive substances, and insulin level were restored in streptozotocin (STZ)-diabetic mice to normal levels with 1. Meliacinolin inhibited α-glucosidase and α-amylase activities. We conclude that meliacinolin can efficiently inhibit insulin resistance, improvement of renal function, lipid abnormalities, and oxidative stress, indicating that its therapeutic properties may be due to the interaction of meliacinolin with multiple targets involved in diabetes pathogenesis. α-Glucosidase and α-amylase inhibitors offer an effective strategy to lower the levels of post prandial hyperglycemia prevents the digestion of carbohydrates.

Topics: alpha-Amylases; Animals; Azadirachta; Biomarkers; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dyslipidemias; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Insulin; Insulin Resistance; Kidney; Liver; Male; Mice; Niacinamide; Oxidative Stress; Phytosterols; Phytotherapy; Plant Extracts; Streptozocin; Thiobarbituric Acid Reactive Substances

Cholesterol synthesis is upregulated and absorption downregulated in insulin resistance and in type 2 diabetes. We investigated whether alterations in cholesterol metabolism are observed across the glucose tolerance status, from normoglycemia through impaired glucose tolerance to type 2 diabetes, in 781 randomly selected men 45 to 70 years of age from a population-based Metabolic Syndrome in Men Study. Cholesterol metabolism was assayed using surrogate serum markers, squalene, and noncholesterol sterols. The study population was classified into subgroups according to glucose tolerance as follows: normoglycemia, impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes. LDL cholesterol did not differ between the groups. Cholesterol synthesis markers were lowest and absorption markers highest in normoglycemia. Sitosterol was lower in subjects with impaired fasting glucose compared with normoglycemic subjects (113 +/- 7 vs. 136 +/- 3 10(2) mumol/mmol of cholesterol, P < 0.05). LDL cholesterol was not associated with lathosterol/sitosterol ratio, a marker of cholesterol metabolism. Peripheral insulin sensitivity evaluated by the Matsuda index was associated with the lathosterol/sitosterol ratio in the entire population (r = -0.457, P < 0.001) and with that of lathosterol/cholestanol independently of obesity. In conclusion, cholesterol metabolism was altered already from subjects with impaired fasting glucose. Upregulated cholesterol synthesis was associated with peripheral insulin resistance independent of obesity.

Topics: Absorption; Aged; Biomarkers; Cholestanol; Cholesterol; Diabetes Mellitus, Type 2; Glucose; Humans; Insulin; Linear Models; Male; Metabolic Syndrome; Middle Aged; Obesity; Phytosterols; Squalene

We investigated the associations between indices of cholesterol metabolism and features of the metabolic syndrome (MS) in the presence and absence of type-2 diabetes (T2DM).. Men with the MS (N=140) and 10 age- and sex-matched controls were recruited. Plasma lathosterol and campesterol were measured by gas chromatography-mass spectrometry, and their ratios to total cholesterol were used to estimate cholesterol metabolism.. Compared with healthy controls, MS subjects had significantly higher lathosterol:cholesterol and lower campesterol:cholesterol ratios (p<0.05). In the MS subjects without T2DM (N=82), campesterol:cholesterol ratio was positively associated with age and negatively associated with plasma triglyceride and insulin concentrations, while in MS subjects with T2DM (N=58), the ratio was positively associated with age and adiponectin concentration, and negatively associated with BMI and insulin. Age and fasting insulin were independent predictors of campesterol:cholesterol ratio in MS subjects with T2DM. There was a significant negative association between plasma lathosterol:cholesterol with campesterol:cholesterol ratio (r=-0.436, p=0.014) in MS subjects without T2DM but not in MS subjects with T2DM.. Cholesterol absorption efficiency was lower and cholesterol synthesis higher in MS subjects with or without T2DM compared with healthy individuals. Moreover, the reciprocal relationship between cholesterol synthesis and cholesterol absorption is lost in the presence of diabetes.

Topics: Adiponectin; Apolipoprotein A-I; Apolipoproteins; Biomarkers; Blood Glucose; Blood Pressure; Cholesterol; Diabetes Mellitus, Type 2; Female; Gas Chromatography-Mass Spectrometry; Homeostasis; Humans; Male; Metabolic Syndrome; Middle Aged; Obesity; Phytosterols; Reference Values; Triglycerides

Most studies have focused on the cholesterol-lowering activity of phytosterols; however, other biological actions have also been attributed to these plant compounds. In this study, we investigated whether phytosterols could delay (progression phase) and/or reverse (regression phase) insulin resistance or type 2 diabetes mellitus in an experimental mouse model of diet-induced obesity, insulin resistance, and diabetes. Body mass, plasma lipid levels, insulin resistance, and hyperglycemia were determined. Phytosterol intake did not improve these metabolic parameters. Therefore, we were unable to substantiate any protective effect of phytosterol intake on diabetes development or regression in the mouse model used.

Topics: Animals; Cholesterol; Diabetes Mellitus, Type 2; Dietary Fats; Disease Susceptibility; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Obesity; Phytosterols

Serum non-cholesterol sterol ratios to cholesterol reflect cholesterol metabolism in non-diabetes populations. In type 2 diabetes (T2D) cholesterol metabolism is perturbed, and the role of squalene and non-cholesterol sterols has not been related to absolute cholesterol metabolism in detail.. We analyzed absolute cholesterol synthesis, absorption % of dietary cholesterol, and serum squalene and non-cholesterol sterol ratios (measured with gas-liquid chromatography) in 64 T2D subjects (age 41-74 years, BMI 21-40 kg/m(2)).. Serum precursors of cholesterol were related to cholesterol synthesis (e.g. serum squalene to cholesterol ratio vs absolute synthesis r=0.493, p<0.001), and serum cholestanol and plant sterol ratios were related to absorption % (e.g. cholestanol vs absorption %, r=0.455, p<0.001). Furthermore, the proportions of serum synthesis/absorption markers were correlated with variables of absolute cholesterol metabolism (e.g. squalene/sitosterol vs absolute synthesis/absorption %, r=0.569, p<0.001). Serum synthesis and absorption markers (lathosterol vs cholestanol, r=-0.545, r<0.001) and absolute synthesis and absorption (r=-0.540, p<0.001) were interrelated suggesting intact regulation of cholesterol metabolism in the whole study population. Absolute synthesis/absorption ratio indicated that a change of dietary cholesterol absorption by 1% changed the mean cholesterol synthesis by 27 mg/d to the opposite direction.. In T2D including varying body weight and altered cholesterol metabolism, serum non-cholesterol sterols and squalene reveal reliable information of cholesterol synthesis and absorption without complicated clinical and laboratory methods.

Topics: Adult; Aged; Biomarkers; Cholesterol; Chromatography, Gas; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Phytosterols; Squalene

Topics: Adult; Aged; Aged, 80 and over; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Erythrocytes; Fatty Acids; Female; Glycated Hemoglobin; Humans; Hypercholesterolemia; Insulin; Male; Middle Aged; Phytosterols; Phytotherapy; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Cross-Cultural Comparison; Diabetes Mellitus, Type 2; Diet, Mediterranean; Dietary Fats; Feeding Behavior; Germany; Health Surveys; Humans; Mediterranean Region; Nutritive Value; Phytosterols

Plant sterols occur naturally in plants and vegetable oils. Sitosterol and campesterol are markers of cholesterol absorption. The ratio of cholesterol endogenous synthesis to its absorption may be assessed by sitosterol, campesterol and other non-cholesterol sterols (lathosterol and squalen) serum concentration measurements. In 38 Type 2 diabetics (59.9 years, BMI 29.8 kg/m2, HbA1c 7.6%, C-peptid 0.82 nmol/l) and in 40 non-diabetics (37.2 years, BMI 25.4 kg/m2, HbA1c 5.2%, C-peptid 0.85 nmol/l) plant sterols serum concentration were measured: lathosterol (diabetics 10.64, non-diabetics 6.04 mumol/l, p = 0.09), squalen (diabetics 3.42, non-diabetics 1.78 mumol/l, p < 0.01), sitosterol (diabetics 3.91, non-diabetics 3.80 mumol/l, p = 0.60) and campesterol (diabetics 7.91, non-diabetics 8.85 mmol/l, p = 0.09). In non-diabetics squalen positive correlates with C-peptid, lathosterol with triacylglycerols and campesterol with HbA1c. In diabetics correlates diabetes compensation with plant sterols value negative. It seems that plant sterols and probably also cholesterol absorption can be influenced negative by higher value HbA1c.

Topics: Adult; Cholesterol; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Middle Aged; Phytosterols

Serum contains noncholesterol sterols, which are reliable markers of cholesterol metabolism, but their presence and importance in different lipoproteins have been insufficiently studied.. Serum and lipoprotein cholesterol precursors squalene, cholestanol, desmosterol and lathosterol (markers of cholesterol synthesis) and cholestanol and plant sterols (markers of cholesterol absorption), and absorption efficacy and absolute synthesis of cholesterol were studied at baseline and during 6-month atorvastatin (80 mg day(-1)) treatment by the sterol balance technique in men with type 2 diabetes.. At baseline, approximately 14% of serum squalene was transported by VLDL, 12% by IDL, 40% by LDL and 30% by HDL. The respective values for the noncholesterol sterols were approximately 8, 4, 61 and 26%. The squalene to cholesterol ratios were highest in VLDL and IDL, those of cholestanol, desmosterol and absorption marker sterols were gradually higher, and that of lathosterol lower from VLDL to HDL. Atorvastatin reduced LDL cholesterol by approximately 50%, decreased the absolute cholesterol synthesis and turnover by approximately 40%, but increased significantly the fractional and mass absorption of cholesterol. In accordance with the fecal data, the ratios of the precursor sterols to cholesterol were reduced (-50%), but those of squalene (+48%) and the absorption sterols increased (e.g. 2.6-fold for sitosterol) similarly in each lipoprotein, but progressively from VLDL to HDL.. Effective lowering of LDL cholesterol by large dose of statin is associated with decreased synthesis and turnover of cholesterol and increased fractional and mass absorption of cholesterol. These changes are detectable by noncholesterol sterols in serum and in different lipoprotein fractions.

Topics: Aged; Anticholesteremic Agents; Atorvastatin; Cholesterol; Cholesterol, LDL; Diabetes Mellitus, Type 2; Feces; Heptanoic Acids; Humans; Hypercholesterolemia; Intestinal Absorption; Lipids; Lipoproteins; Liver; Male; Middle Aged; Phytosterols; Pyrroles; Squalene

Weight reduction in obese type 2 diabetes increases the absorption efficiency of cholesterol and serum plant sterol levels from baseline. However, there is no information on the effects of acute restriction of calories and lack of dietary cholesterol and plant sterols on serum cholesterol precursor and plant sterols and on cholesterol metabolism. Thus, 10 obese (BMI>30 kg/m(2)) type 2 diabetes subjects consumed very low energy diet virtually free of cholesterol, cholestanol and plant sterols for 3 months.. Serum sterols were measured with gas-liquid chromatography.. Body weight was reduced by 15.5+/-1.7 kg (p<0.001), serum cholesterol by 21+/-3%, triglycerides 45+/-5%, glucose 23+/-3%, insulin 59+/-5% and HbAIc by 8+/-2%, whereas serum sex hormone binding globulin increased by 108+/-25% (p<0.05-0.001 for all). Serum desmosterol and lathosterol to cholesterol ratios (indicators of cholesterol synthesis) were significantly decreased by 20% suggesting that cholesterol synthesis was suppressed. Serum squalene ratio was unchanged. Despite lack of dietary plant sterols and cholestanol, serum campesterol and sitosterol ratios (indicators of cholesterol absorption efficiency) only tended to decrease, whereas serum cholestanol ratio, also an absorption indicator, was increased by 33+/-3% (p<0.001), and its ratios to campesterol and sitosterol were increased by 60% and 31%, suggesting that sterol absorption efficiency might have been increased and their turnover reduced.. In obese type 2 diabetes, restriction of calories and dietary sterols improved markedly control of diabetes, decreased serum cholesterol precursor sterols suggesting that cholesterol synthesis was decreased, but only tended to decrease serum values of plant sterols probably due to their release from the adipose tissues associated with their impaired turnover.

Topics: Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Humans; Male; Middle Aged; Obesity; Phytosterols; Squalene; Sterols; Weight Loss

Cholesterol metabolism was studied in 64 subjects with type 2 diabetes who had body weight ranging from normal to obese, to find out whether weight interferes with cholesterol metabolism in diabetes.. Cholesterol absorption was measured with peroral isotopes and by assaying serum plant sterol and cholestanol to cholesterol ratios, cholesterol synthesis with sterol balance, and measuring serum cholesterol precursor ratios.. The study population was divided into normal-weight (body mass index, 24.1 +/- 0.4 kg/m2; mean +/- SEM; n = 20) and obese (31.0 +/- 0.5 kg/m2; n = 44) groups. Despite similar serum cholesterol and blood glucose values, fecal neutral sterol excretion, cholesterol and bile acid synthesis, cholesterol turnover (1649 +/- 78 vs. 1077 +/- 52 mg/d; p < 0.001), and serum cholesterol precursors were higher, and cholesterol absorption % (32 +/- 1 vs. 40 +/- 2%; p < 0.05), serum cholestanol, and plant sterols were lower in the obese vs. the non-obese groups. Serum sex hormone-binding globulin was positively associated with variables of cholesterol absorption, whereas blood glucose, serum insulin, and body mass index were associated with variables of cholesterol synthesis. In multiple stepwise regression analysis, cholesterol absorption percentage (R2 = 24%) and body mass index (R2 = 15%) were the only variables explaining the variability of cholesterol synthesis.. Body weight, through its entire range, regulates cholesterol metabolism in type 2 diabetes such that with increasing insulin resistance, cholesterol absorption is lowered and cholesterol synthesis increased.

Topics: Absorption; Bile Acids and Salts; Blood Glucose; Body Mass Index; Body Weight; Cholestanol; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Feces; Female; Humans; Insulin; Lipids; Lipoproteins; Male; Middle Aged; Obesity; Phytosterols; Regression Analysis; Sex Hormone-Binding Globulin; Sterols

Cholesterol and lipoprotein metabolism was studied in mildly hypercholesterolemic nonobese men with NIDDM to find out which metabolic parameters regulate serum cholesterol level in these NIDDM subjects.. Nonobese NIDDM subjects (n = 13) and control subjects (n = 18) with serum cholesterol > or = 6.0 and triglycerides < or = 2.5 mmol/l were studied on a similar monoene-enriched diet. Cholesterol absorption was studied with peroral double isotopes and by measuring serum plant sterols with gas-liquid chromatography; cholesterol synthesis was studied by measuring sterol balance and by measuring serum cholesterol precursor sterols; and LDL kinetics was measured with 131I-labeled autologous apoprotein (apo) B.. Cholesterol absorption was significantly lower in NIDDM subjects than in the control subjects, as detected by low serum plant sterol levels and absorption percentage (23 vs. 29%, P < 0.05). Cholesterol synthesis was significantly higher in NIDDM subjects than in the control subjects, as detected by precursor sterols or balance data (18 vs. 12 mg.kg-1.day-1, P < 0.01), cholesterol turnover (19 vs. 13 mg.kg-1.day-1, P < 0.01), and LDL apo B removal (0.343 vs. 0.267 pools/day, P < 0.01). Serum total and LDL cholesterol levels were inversely correlated with cholesterol synthesis, which was positively related to the catabolism of LDL apo B and negatively related to cholesterol absorption efficiency.. In this small selected group of mildly hypercholesterolemic nonobese NIDDM subjects, the regulation of serum cholesterol levels was achieved by the homeostasis between cholesterol absorption, synthesis, and LDL fractional catabolism. Cholesterol turnover and removal of LDL apo B were high in NIDDM subjects, compared with the control subjects, whereas cholesterol absorption efficiency was abnormally low Because of the relatively small number of selected subjects, the present results are not directly applicable to the overall NIDDM population.

Topics: Absorption; Apolipoproteins B; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Cholesterol, LDL; Diabetes Mellitus, Type 2; Dietary Fats; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Phytosterols; Reference Values

Plasma plant sterol concentrations (an index of cholesterol absorption efficiency) and plasma lathosterol concentration (an index of cholesterol synthesis rate) were measured in 52 patients with non-insulin dependent diabetes mellitus (NIDDM) and 36 non-diabetic controls. Plasma plant sterol concentrations were significantly (P less than 0.01) lower in diabetic patients (campesterol: men -36%, women -48%; betasitosterol: men -35%, women -42%). Fasting serum insulin levels were inversely correlated with plasma plant sterol concentrations in diabetic patients (campesterol: r = -0.347, P = 0.012; betasitosterol: r = -0.345, P = 0.012) and in non-diabetic men (campesterol: r = -0.578, P = 0.039; betasitosterol: r = -0.702, P = 0.008). Serum insulin levels were also correlated significantly with plasma lathosterol concentration in diabetic patients (r = 0.295, P = 0.034). The results of this study suggest that absorption of plant sterols and possibly cholesterol from the diet may be reduced in hyperinsulinemic diabetics.

Topics: Adult; Aged; Cholesterol; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Male; Middle Aged; Phytosterols; Sitosterols