Introducing a new component of the metabolic syndrome: Low cholesterol absorption

Department of Medicine, the Division of Internal Medicine, University of Helsinki, Helsinki, Finland.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 08/2000; 72(1):82-8.
Source: PubMed


Weight reduction is the recommended treatment of obese type 2 diabetes, but the effects of weight reduction on cholesterol metabolism are poorly understood.
We investigated glucose, cholesterol, and lipoprotein metabolism at baseline and 2 y after weight reduction in obese patients with type 2 diabetes consuming an isoenergetic diet.
Sixteen subjects were randomly chosen to consume a very-low-energy or low-energy diet for 3 mo, after which they consumed a weight-maintenance diet for up to 2 y. Cholesterol absorption and metabolism, LDL and HDL kinetics, and variables of glucose metabolism were studied at baseline and 2 y.
Baseline serum sex hormone binding globulin (SHBG) was significantly related to cholesterol absorption efficiency, and serum glucose and insulin concentrations were associated with cholesterol synthesis. After 2 y, body weight was reduced by 6 +/- 1 kg (P < 0.01), body mass index by 6% (P < 0.05), and blood glucose by 14% (P < 0.01); the ratio of serum SHBG to insulin increased by 66% (P < 0.05). Serum and VLDL, LDL, and HDL triacylglycerol were significantly reduced by 13-24%. Despite unchanged serum concentrations of cholesterol, cholesterol absorption efficiency and the ratio of serum plant sterols to cholesterol-indicators of cholesterol absorption-increased by 28% (P < 0.01) and 20-31% (P < 0. 05 for both), respectively; the fractional removal of LDL apolipoprotein B decreased. Fecal excretion of cholesterol as neutral sterols decreased significantly by 11%. Changes in body weight were significantly negatively correlated with changes in ratios of cholesterol to serum plant sterols and cholestanol.
Baseline cholesterol absorption and synthesis were related to respective serum SHBG, glucose, and insulin values. Weight reduction increased cholesterol absorption and improved variables of glucose metabolism. These results suggest that low cholesterol absorption and high synthesis may be part of the insulin resistance syndrome.

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    • "Specifically, obesity is associated with reduced intestinal cholesterol absorption [17]; hence the cholesterol lowering effects from the plant sterols in nuts will be blunted when cholesterol absorption rates are low. Insulin resistant states, the hallmark of overweight and obese persons with T2D, increase cholesterol synthesis and also reduce intestinal absorption [18]. Therefore, enhanced cholesterol flux in hepatocytes down-regulates LDL-C receptors and makes them refractory to changes in dietary fatty acids, and a decreased cholesterol flux through enterocytes reduces the cholesterol-raising response to dietary cholesterol and enhances the aforementioned cholesterol-lowering effect of plant stanols. "
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    ABSTRACT: According to the American Diabetes Association (ADA), the nutritional goals for patients with type 2 diabetes (T2D) are to achieve an optimal nutrient intake to maintain normal blood glucose levels and a lipid profile. Peanuts are nutrient dense foods that contain high levels of monounsaturated fat (MUFA) and are a natural source of arginine, fiber, phytosterols, resveritrol, niacin, folate, vitamin E and magnesium, which have the potential for improving blood lipids and glycemic control. This study sought to evaluate the effect of a peanut enriched ADA meal plan on the nutrient profile of the total diet and cardiometabolic parameters in adults with T2D. This was a randomized, prospective 24-week parallel-group clinical trial with 60 adults with T2D [age range 34-84 years; body mass index (BMI) range 17.2-48.7 kg/m2]. Subjects consumed an ADA meal plan containing ~20% of energy from peanuts (peanut group) or a peanut-free ADA meal plan (control group). Weight, BMI, waist circumference (WC) and nutrient intake from 24-hour recalls were measured every 4 weeks and fasting blood glucose (FBG), HbA1c and blood lipids were measured every 12 weeks. A mixed-model repeated-measures analysis of covariance was performed to assess the significance of changes in the cardiometabolic parameters. A higher polyunsaturated fat (PUFA) to saturated fat diet ratio and higher intake of MUFA, PUFA, alpha-tocopherol, niacin and magnesium was observed in the peanut group as compared to the control group (P < 0.01-P = 0.04). Both groups experienced mild reductions in weight, BMI, and WC during the study (P = 0.01-P = 0.03), however there were no differences between the two groups in these measurements or in FBG, HbA1c or blood lipids. For each kilogram of weight loss in the entire cohort there were associations for reductions in WC of 0.48 cm (P < 0.01), FBG of 0.11 mmol/l (P = 0.01) and HbA1c of 0.07% (P < 0.01). Daily consumption of a peanut enriched (46 g/d) ADA meal plan over 24-weeks improves the nutrient profile of the total diet and is compatible with weight management and improvement in specific blood lipids.Trial registration: NCT00937222.
    Nutrition Journal 01/2014; 13(1):10. DOI:10.1186/1475-2891-13-10 · 2.60 Impact Factor
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    • "The reason for this discrepancy is not yet clear. Moreover, cholesterol synthesis, such as that reflected by lathosterol levels, has been shown to be increased in MetS and obesity [14] [15] [16] [17] [18] [19]. In the non- MetS group, the responders showed higher basal levels of lathosterol/ TC than non-responders. "
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    ABSTRACT: Background Ezetimibe may be more effective in patients with high cholesterol absorption than in patients with low cholesterol absorption. This prospective study was performed to evaluate the effect of ezetimibe on hypercholesterolemia in patients with metabolic syndrome (MetS). Methods and results 81 patients with hypercholesterolemia in the presence or absence of MetS (MetS or non-MetS group) initially received ezetimibe (10 mg/day). In both groups, the levels of total cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and the ratio of LDL-C to HDL-C (L/H) significantly decreased with treatment. A ratio of lathosterol to TC (lathosterol/TC) in the MetS group was significantly higher than that in the non-MetS group before treatment. Lathosterol/TC significantly increased after treatment in both groups, and campesterol/TC and sitosterol/TC significantly decreased. The non-MetS group, but not the MetS group, showed a significant increase in cholesterol/TC after treatment. Finally, we divided all of the patients into two groups (responders and non-responders) according to the percent changes in LDL-C after treatment. Male gender (p = 0.037), the presence of MetS (p = 0.026) and lower levels of L/H (p = 0.006) were independent factors that predicted a response to ezetimibe. Conclusions The lipid-lowering effect of ezetimibe in MetS was comparable to that in non-MetS. Treatment with ezetimibe may be effective in males with MetS and relatively lower levels of L/H.
    IJC Metabolic and Endocrine 12/2013; 1:7–12. DOI:10.1016/j.ijcme.2013.10.001
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    • "It was recently demonstrated that lifestyle intervention with weight reduction reduced both hypopnoea and especially apnoea indices and also other obesity related risk factors for cardiovascular diseases in a vast majority of patients with mild OSA, highlighting the importance of an early lifestyle intervention [20]. Similarly, weight reduction decreases cholesterol synthesis and increases cholesterol absorption in type 2 diabetics [21] [22]. It would be interesting to know whether in subjects with OSA weight reduction alters also cholesterol metabolism, and whether the reduction in apnoea and hypopnoea indices are related to cholesterol metabolism beyond obesity. "
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    ABSTRACT: To evaluate whether parameters of obstructive sleep apnoea (OSA) associate with cholesterol metabolism before and after weight reduction, 42 middle-aged overweight subjects with mild OSA were randomised to intensive lifestyle intervention (N = 23) or to control group (N = 18) with routine lifestyle counselling only. Cholesterol metabolism was evaluated with serum noncholesterol sterol ratios to cholesterol, surrogate markers of cholesterol absorption (cholestanol and plant sterols) and synthesis (cholestenol, desmosterol, and lathosterol) at baseline and after 1-year intervention. At baseline, arterial oxygen saturation (SaO2 ) was associated with serum campesterol (P < 0.05) and inversely with desmosterol ratios (P < 0.001) independently of gender, BMI, and homeostasis model assessment index of insulin resistance (HOMA-IR). Apnoea-hypopnoea index (AHI) was not associated with cholesterol metabolism. Weight reduction significantly increased SaO2 and serum cholestanol and decreased AHI and serum cholestenol ratios. In the groups combined, the changes in AHI were inversely associated with changes of cholestanol and positively with cholestenol ratios independent of gender and the changes of BMI and HOMA-IR (P < 0.05). In conclusion, mild OSA seemed to be associated with cholesterol metabolism independent of BMI and HOMA-IR. Weight reduction increased the markers of cholesterol absorption and decreased those of cholesterol synthesis in the overweight subjects with mild OSA.
    Cholesterol 05/2013; 2013(14):769457. DOI:10.1155/2013/769457
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