Diabetes Contributes to Cholesterol Metabolism Regardless of Obesity

Simonen, Piia; Gylling, Helena; Miettinen, Tatu A.

doi:10.2337/diacare.25.9.1511

Cited by 138 publications

(91 citation statements)

References 30 publications

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“…A plausible explanation is found in recent studies of cholesterol absorption by Miettinen and colleagues. [31][32][33] They observed decreased cholesterol absorption in IR states 31,32 and overt diabetes. 33 When overweight persons underwent a weight loss diet, their cholesterol absorption increased.…”

Section: Discussionmentioning

confidence: 99%

Effects of Insulin Resistance and Obesity on Lipoproteins and Sensitivity to Egg Feeding

Knopp

Retzlaff

Fish

et al. 2003

ATVB

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Objective-This study was undertaken to determine if insulin resistance without and with obesity influences LDL response to dietary cholesterol and saturated fat. Methods and Results-We fed 0, 2, and 4 egg yolks per day to 197 healthy subjects in a 4-week, double-blind, randomized, crossover design. Subjects were dichotomized on body mass index (Ͻ27.5 and Ն27.5 kg/m 2 ) and insulin sensitivity (insulin-sensitivity index Ն4.2ϫ1.0 Ϫ4 and Ͻ4.2ϫ1.0 Ϫ4 min Ϫ1 U/mL), yielding insulin-sensitive (IS, nϭ65), insulinresistant (IR, nϭ75), and obese insulin-resistant (OIR, nϭ58) subjects. Mean fasting baseline LDL cholesterol (LDL-C) levels were higher in IR and OIR subjects (3.44Ϯ0.67 and 3.32Ϯ0.80 mol/L) than in IS subjects (2.84Ϯ0.75 mmol/L) (PϽ0.001). Progressive triglyceride elevations and HDL-C decreases were seen across the 3 groups. Ingesting 4 eggs daily yielded significant LDL-C increases of 7.8Ϯ13.7% (IS) and 3.3Ϯ13.2% (IR) (both PϽ0.05) compared with 2.4Ϯ12.6% for OIR (NS). HDL-C increases were 8.8Ϯ10.4%, 5.2Ϯ10.4%, and 3.6Ϯ9.4% in IS, IR, and OIR, respectively (all PϽ0.01). Conclusions-Insulin resistance without and with obesity is associated with elevated LDL-C as well as elevated triglyceride and low HDL-C. The elevated LDL-C cannot be explained by dietary sensitivity, because the LDL-C rise with egg feeding is less in IR persons regardless of obesity status, probably attributable to diminished cholesterol absorption. The results suggest that dietary management of insulin resistance and obesity can focus more on restricting calories and less on restricting dietary fat. (Arterioscler Thromb Vasc

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Section: Discussionmentioning

confidence: 99%

Effects of Insulin Resistance and Obesity on Lipoproteins and Sensitivity to Egg Feeding

Knopp

Retzlaff

Fish

et al. 2003

ATVB

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“…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.…”

Section: Diabetes Care 27:53-58 2004mentioning

confidence: 99%

“…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%

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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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“…Besides risk factor for cardiovascular disease, abnormalities in cholesterol metabolism have been associated with type 2 diabetes. In several cross-sectional studies, insulin resistance and obesity have been found to be associated with enhanced cholesterol synthesis and reduced cholesterol absorption [12] [13] [14] [15] [16]. Diabetic dyslipidemia is typically characterized by increased very low density lipoprotein (VLDL) and reduced high density lipoprotein (HDL), but surprisingly no change in low-density lipoprotein (LDL) cholesterol levels [17].…”

Section: Introductionmentioning

confidence: 99%

Regulation of Intestinal Cholesterol Absorption: A Disease Perspective

Iqbal¹,

Qarni²,

Hawwari³

2017

ABC

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Hypercholesterolemia promotes atherosclerosis and precise regulation of cholesterol homeostasis is essential. Besides risk factor for cardiovascular disease, abnormalities in cholesterol metabolism have been associated with type 2 diabetes. Cholesterol homeostasis in the body is maintained by de novo synthesis. Furthermore, intestinal cholesterol absorption has recently been considered as an important control point in cholesterol homeostasis. Important insights have been gained into the mechanisms of transport of cholesterol from the intestinal lumen into the enterocytes. Several transporter proteins that appear to be key players in the control of the cholesterol absorption from the intestinal lumen have been identified. Here, we review intestinal cholesterol absorption and the mechanisms underlying alterations in cholesterol absorption under physiological conditions and in diseases such as diabetes mellitus.

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Diabetes Contributes to Cholesterol Metabolism Regardless of Obesity

Cited by 138 publications

References 30 publications

Effects of Insulin Resistance and Obesity on Lipoproteins and Sensitivity to Egg Feeding

Effects of Insulin Resistance and Obesity on Lipoproteins and Sensitivity to Egg Feeding

Low Synthesis and High Absorption of Cholesterol Characterize Type 1 Diabetes

Regulation of Intestinal Cholesterol Absorption: A Disease Perspective

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