Plasma Non-Cholesterol Sterols in Patients with Non-Insulin Dependent Diabetes Mellitus

Wh, Sutherland; Scott, Russell S.; Cj, Lintott; Mc, Robertson; Sa, Stapely; C, Cox

doi:10.1055/s-2007-1003287

Cited by 39 publications

(17 citation statements)

References 13 publications

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“…Dietary plant sterols can be absorbed [16] and inhibit cholesterol absorption. However, low plant sterol proportions in NIDDM subjects were suggested to reflect a lowered cholesterol absorption efficiency, although unchanged lathosterol proportion did not indicate compensatorily increased cholesterol synthesis [38]. In fact, the latter and high bile acid synthesis have been observed in some NIDDM subgroups [37,39,40], these findings being in agreement with the present results.…”

Section: Discussionsupporting

confidence: 91%

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment

Gylling

Miettinen

1994

Diabetologia

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Summary Cholesterol absorption and metabolism and LDL and HDL kinetics were investigated in 11 hypercholesterolaemic non-insulin-dependent diabetic men off and on a hypolipidaemic treatment with sitostanol ester, (3 g sitostanol daily) dissolved in rapeseed oil margarine, by a double-blind crossover study design. Serum total, VLDL and LDL cholesterol and apoprotein B fell significantly by 6 + 2,12 + 6, 9 + 3 and 6 + 2 %, mean + SEM, and HDL cholesterol was increased by 11 + 4 % (p < 0.05) by sitostanol ester. LDL cholesterol and apoprotein B were significantly decreased in the dense (1.037-1.055 g/ml), but not light, LDL subfraction due to a significantly diminished transport rate for LDL apoprotein B, while the fractional catabolic rate was unchanged. HDL kinetics, measured with autologous apoprotein A I, was unaffected by sitostanol ester. Cholesterol absorption efficiency was markedly reduced from 25 + 2 to 9 + 2 % (p < 0.001) during sitostanol ester followed by proportionately decreased serum plant sterol proportions. Cholesterol precursor sterol proportions in serum, fecal neutral sterol excretion, and cholesterol synthesis, cholesterol transport, and biliary secretion were all significantly increased by sitostanol ester. We conclude that the sitostanol ester-induced decrease in cholesterol absorption compensatorily stimulated cholesterol synthesis, had no effect on fractional catabolic rate, but decreased transport rate for LDL apoprotein B so that serum total, VLDL and LDL cholesterol levels were decreased. Dietary rapeseed oil margarine rich in sitostanol ester was well tolerated, appears to be safe from the nutritional point of view and effective for lowering VLDL and LDL cholesterol and increasing HDL cholesterol in hypercholesterolaemic non-insulin-dependent diabetic subjects. [Diabetologia (1994) 37: 773-780]

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Section: Discussionsupporting

confidence: 91%

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment

Gylling

Miettinen

1994

Diabetologia

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“…Research suggests that predisposition to the development of type 2 diabetes may be due to genetic differences, although the specific genes involved have not yet been identified. Type 2 diabetes has been associated with high synthesis and low absorption of cholesterol, indicating a link between glucose and cholesterol metabolism (47)(48)(49)(50). Indeed, our study opens the possibility that genetic variations relating to cellular cholesterol management may play a role in this genetic predisposition for type 2 diabetes.…”

Section: Discussionmentioning

confidence: 62%

Direct Effect of Cholesterol on Insulin Secretion

et al. 2007

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OBJECTIVE-Type 2 diabetes is often accompanied by abnormal blood lipid and lipoprotein levels, but most studies on the link between hyperlipidemia and diabetes have focused on free fatty acids (FFAs). In this study, we examined the relationship between cholesterol and insulin secretion from pancreatic ␤-cells that is independent of the effects of FFAs. RESEARCH DESIGN AND METHODS-Several methodswere used to modulate cholesterol levels in intact islets and cultured ␤-cells, including a recently developed mouse model that exhibits elevated cholesterol but normal FFA levels. Acute and metabolic alteration of cholesterol was done using pharmacological reagents.RESULTS-We found a direct link between elevated serum cholesterol and reduced insulin secretion, with normal secretion restored by cholesterol depletion. We further demonstrate that excess cholesterol inhibits secretion by downregulation of metabolism through increased neuronal nitric oxide synthase dimerization.CONCLUSIONS-This direct effect of cholesterol on ␤-cell metabolism opens a novel set of mechanisms that may contribute to ␤-cell dysfunction and the onset of diabetes in obese patients.

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“…In the latter patients, cholesterol absorption efficiency has frequently been found to be low (3,13,19), ratios of cholestanol and plant sterols to cholesterol are also low in serum (3,4,19), whereas synthesis of cholesterol measured with either the ratios of the precursor sterols to cholesterol or sterol balance technique are high (3,5,6,12,15), and biliary secretion and fecal output of cholesterol is elevated (3,5,6). The findings are also found in obese subjects (20,21) but are detectable also in type 2 diabetic subjects without obesity (22) or in non diabetic subjects with a highnormal glucose level (23).…”

Section: Ratios Of Noncholesterol Sterols and Squalene To Cholesterolmentioning

confidence: 99%

“…Cholesterol absorption efficiency and serum plant sterols, reflecting cholesterol absorption (2), are low in type 2 diabetes (3,4), and synthesis of cholesterol and its biliary and fecal elimination are increased (3,5,6). Type 1 diabetes has less advanced dyslipidemia (7), yet obliterating arterial disease, both microvascular and macrovascular, develops frequently, and myocardial infarction is also an important cause of death in these patients.…”

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confidence: 99%

Low Synthesis and High Absorption of Cholesterol Characterize Type 1 Diabetes

et al. 2004

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OBJECTIVE -Streptozotocin-induced type 1 diabetes in experimental animals inhibits cholesterol synthesis and increases cholesterol absorption. In contrast to human type 2 diabetes, virtually no information is available on cholesterol synthesis and absorption in type 1 diabetes.RESEARCH DESIGN AND METHODS -We studied the variables of cholesterol metabolism in 27 patients with type 1 diabetes and in 10 patients with type 2 diabetes matched for body weight, using cholesterol precursor sterol ratios to cholesterol as surrogate markers of synthesis, and those of cholestanol and plant sterols of cholesterol absorption. Glucose control was good in all subjects.RESULTS -Total and HDL cholesterol and LDL triglycerides were higher in type 2 than in type 1 diabetes. Serum sterols, measured also in VLDL, intermediate-density lipoprotein (IDL), LDL, and HDL, were transported up to Ͼ90% by LDL and HDL in type 1 diabetes. The ratios of all absorption sterols in serum and in each lipoprotein were higher, and those of the synthesis markers, especially cholestenol and lathosterol, were lower in type 1 than in type 2 diabetes.CONCLUSIONS -In contrast to type 2 diabetes, the findings in type 1 diabetes could be related to low expression of ABC G/5 G/8 genes, resulting in high absorption of cholesterol and sterols in general and low synthesis of cholesterol. Diabetes Care 27:53-58, 2004D yslipidemia characterizes patients with type 2 diabetes, showing normal or modestly increased cholesterol, small dense LDL, reduced HDL cholesterol, and modestly increased serum triglycerides with altered metabolism of triglyceride-rich lipoproteins (1). Cholesterol absorption efficiency and serum plant sterols, reflecting cholesterol absorption (2), are low in type 2 diabetes (3,4), and synthesis of cholesterol and its biliary and fecal elimination are increased (3,5,6). Type 1 diabetes has less advanced dyslipidemia (7), yet obliterating arterial disease, both microvascular and macrovascular, develops frequently, and myocardial infarction is also an important cause of death in these patients. The relatively normal lipid pattern is apparently a reason that scientific interest has been less frequently focused to metabolism of serum lipids in patients with type 1 than type 2 diabetes. For instance, there is virtually no information on cholesterol absorption or synthesis in patients with type 1 diabetes. However, serum plant sterols were increased in a group of poorly controlled patients with type 1 diabetes but no more at intensified insulin treatment (8). That lack of insulin might actually improve cholesterol absorption and downregulate hepatic cholesterol synthesis is indicated by streptozotocin-induced diabetes in experimental animals (9). To this end, our intention was to study cholesterol metabolism in type 1 diabetes, and in the present study we investigated surrogate markers of cholesterol absorption and synthesis by measuring serum noncholesterol sterols in patients with type 1 diabetes and compared the results with those in type 2 diabetes....

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Plasma Non-Cholesterol Sterols in Patients with Non-Insulin Dependent Diabetes Mellitus

Cited by 39 publications

References 13 publications

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment

Direct Effect of Cholesterol on Insulin Secretion

Low Synthesis and High Absorption of Cholesterol Characterize Type 1 Diabetes

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