Diet sugars and cardiovascular disease

[Guest guest]

Hi All,

I thought although CR receives only some

rather passing attention in the below, the issue

of the glycemic index of our food and the glycemia

that we may consequently suffer play a larger role

for us.

A good introduction to the topic may be:

http://lists.calorierestriction.org/cgi-bin/wa?

A2=ind0411 & L=crsociety & P=R1549 & D=0 & X=5F1CA53A791170A5E5 & Y=old542000@ya

hoo.com

http://tinyurl.com/4auja

The papers in the post above refers to reference 51

in the below pdf excerpts and are in http://tinyurl.com/4fxzj

for:

Ann Intern Med. 2004 Nov 2;141(9):738; author reply 738-9.

Overall, lower carbohydrates diets are preferred among

us for CR. I would tend to, reluctantly, agree. It goes

against my palate and thrifty disposition.

Dickinson S, Brand- J.

Glycemic index, postprandial glycemia and cardiovascular disease.

Curr Opin Lipidol. 2005 Feb;16(1):69-75.

PMID: 15650566 [PubMed - in process]

Purpose of review: Several lines of evidence indicate that

exaggerated postprandial glycemia puts individuals without diabetes

at greater risk of developing cardiovascular disease. In large,

prospective observational studies, including metaanalyses, higher 120

min post-load blood glucose and glycated hemoglobin (a measure of

average blood glucose level over time) independently predict

cardiovascular mortality and morbidity in individuals without

diabetes. These findings imply that the glycemic nature of dietary

carbohydrates may also be relevant. We aim to provide a clearer

perspective on how the glycemic impact of carbohydrates may modulate

development of cardiovascular disease.

Recent findings: In ecological studies, average dietary glycemic

index (a measure of the postprandial glycemic potential of

carbohydrates) and glycemic load (average glycemic index × amount of

carbohydrate) predicts coronary infarct and cardiovascular disease

risk factors, including HDL cholesterol, triglycerides and C-reactive

protein. In short-term intervention studies of overweight and

hyperlipidemic patients, low glycemic index diets lead to

improvements in cardiovascular disease risk factors, including

reduced LDL cholesterol and improved insulin sensitivity, as well as

greater body fat loss on energy-restricted diets. Molecular studies

indicate that physiological hyperglycemia induces overproduction of

superoxide by the mitochondrial electron-transport chain, resulting

in inflammatory responses and endothelial dysfunction.

Summary: Taken together, the findings suggest that conventional

high-carbohydrate diets with their high glycemic index may be

suboptimal, particularly in insulin-resistant individuals. Because

around one in four adults has impairments in postprandial glucose

regulation, the glycemic potential of carbohydrates warrants further

investigation in cardiovascular disease prevention.

Abbreviations BMI: body mass index; CRP: C-reactive protein; CVD:

cardiovascular disease; HbA1c: hemoglobin A1c; HOMA: homeostasis

model assessment; IGT: impaired glucose tolerance; PPG postprandial

glycem.

Introduction

Over the past decade, dietary advice to reduce the risk of

cardiovascular disease (CVD) and obesity has recommended

carbohydrates in place of saturated fatty acids, with little emphasis

on the nature of the carbohydrate. There is concern, however, that

some high-carbohydrate diets may increase the risk of CVD, type 2

diabetes and obesity, especially those that exaggerate postprandial

glycemic and insulin responses and dyslipidemia [1•,2•]. In this

context, the use of the glycemic index approach to classifying

carbohydrates has provided insights that the traditional separation

of carbohydrates into starch and sugars has not [3]. The glycemic

index compares carbohydrates gram for gram in individual foods,

providing a numerical, evidence-based index of postprandial glycemia

[4]. A lower glycemic index suggests a slower rate of digestion and

absorption of the sugars and starches in foods but may also indicate

greater hepatic and peripheral extraction of the products of

carbohydrate digestion [5]. The glycemic index has provoked

controversy, particularly in relation to diebetic diets but there is

agreement that moderate-to high carbohydrate based on low glycemic

index foods (not low carbohydrate diets) provide a benefit to

glycemic control [6••].

Several lines of evidence support the hypothesis that an excessive

rise in blood glucose levels after a meal increases the risk of

chronic disease. The first is that dominated by the

term `postprandial or post-challenge glycemia' (PPG) and its

continuous relationship to cardiovascular and total mortality in

individuals with or without diabetes. The second area is that denoted

by the keywords `glycemic index' and `glycemic load' (the product of

the glycemic index of specific foods and the carbohydrate content per

serving). A third avenue of research indicates that hyperglycemia,

even within the normal nondiabetic range, is directly involved in

pathogenic processes because it creates oxidative stress. This review

aims to bring the three areas together to provide a clearer

perspective on how the glycemic impact of carbohydrates may modulate

the development of CVD.

Impaired glucose metabolism

Impaired glucose metabolism is surprisingly common even in those

without diabetes. In Australia, almost 25% of approximately 11 000

adults surveyed in the Australian Diabetes, Obesity and Lifestyle

study had either diabetes or impaired glucose metabolism, including

impaired glucose tolerance (IGT) and impaired fasting glucose [7]. On

a worldwide basis, abnormal glucose metabolism is more common in

indigenous, South Asian, Chinese and Asian-Indian populations, with

lower prevalence in Caucasians [8•]. IGT indicates not only the

presence of insulin resistance but also loss of early first phase

insulin secretion. While many individuals accommodate higher

carbohydrate intake by increasing insulin sensitivity, others require

increased insulin secretion to maintain normal glucose homoeostasis

[9]. Because [beta]-cell defects may also be present, insulin

secretion may be compromised over the long term. A significant

proportion of individuals will therefore display postprandial

glycemia (PPG) as they age. The implications of this defect are

important because every meal, particularly high-carbohydrate meals,

represents a challenge to glucose homoeostasis. While a 75 g glucose

load may not be `physiological' in a strict sense, it is not

materially different in glycemic impact to a typical meal containing

50 or 75 g starch or sugars. On a scale where glucose = 100, the

glycemic index of most modern starchy foods is above 70, including

bread, potatoes, rice and breakfast cereals [4]. While additional fat

and protein in a meal reduce the glycemic response, the rank order of

responses to different carbohydrates in the mixed meal is still

predicted by the glycemic index of the single foods [10•]. Low-fat,

high-carbohydrate meals based on high glycemic index food sources

produce the highest day-long glycemic profiles [11••].

Post-challenge glycemia as a risk factor for cardiovascular disease

A high 2 h post-challenge blood glucose level is increasingly

recognized as an important independent risk factor for CVD in

individuals without diabetes. The heightened risk in people with

diabetes is well established, beginning well before the development

of diabetes when only moderate increases in PPG are present [12].

Moreover, poor control of hyperglycemia plays a significant role in

progression of CVD in people with diabetes. While large, prospective

clinical trials have shown a direct relationship between the degree

of glycemia and diabetic microvascular complications, the link to

macrovascular complications is less clear. In the UK Prospective

Diabetes Study, for example, higher levels of glycated hemoglobin A1c

(HbA1c) did not predict a significantly greater risk of CVD [13]. In

people with diabetes, however, HbA1c reflects average blood glucose

levels rather than postprandial `spikes' and does not distinguish

between larger and smaller fluctuations in PPG [14]. In recent years,

controlling PPG per se has become the focus of new therapeutic

approaches to reduce the burden of CVD complications in people with

diabetes.

In prospective cohort studies, high post-challenge blood glucose

is associated with all-cause and CVD mortality. The relative risk is

up to three times greater when comparing extreme quintiles or

quartiles [15,16]. Most recently, Levitan et al. [17••] conducted a

meta-analysis of 39 reports in nondiabetic populations of the risk of

CVD in relation to 120 min post-load glucose values. The group with

the highest post-challenge blood glucose had a 27% greater risk of

CVD than the group with the lowest glucose levels and the relative

risk was higher in women than men (1.56 versus 1.23). Adjustment for

traditional CVD risk factors attenuated but did not abolish the

relationship. Glycemic `spikes' have also been more strongly

associated with carotid intima-media thickness than fasting glucose

or HbA1c [18]. Hanefeld et al. [19] showed that intima-media

thickness increased 13% comparing the lowest and highest quintiles of

2 h PPG in a group of 403 European individuals without diabetes.

nsen et al. [20••] found a strong, independent relationship

between HbA1c in around 6000 individuals without diabetes and the

risk of developing hard plaques. The odds ratio was 5.8 in the

highest quintile of HbA1c and remained significant after adjustment

for possible confounders, including body mass index (BMI),

hypertension and physical activity. Increased risk was present even

at modestly elevated levels of HbA1c.

Glycemic index, glycemic load and cardiovascular disease risk

Studies incorporating the glycemic index and glycemic load provide

the second line of evidence that excessive PPG increases the risk of

CVD. In this context, the glycemic index allows a more physiological

basis for comparing carbohydrates than the traditional starch versus

sugar classification. This is because there is no clear distinction

between the size of the carbohydrate molecule or chain length and the

level of PPG. Indeed, many modern starchy foods produce higher levels

of glycemia than sugar-containing foods [4]. Dairy products, fruits

and chocolate confectionery in particular may contain high levels of

simple sugars, yet have low glycemic index values (<50). At the other

extreme, many low-fat, high-starch foods have exceptionally high

glycemic index values (>80), although pasta and legumes are important

exceptions. Moreover, dietary fiber is not a reliable predictor of

PPG, particularly in respect of flour-based products. Most wheatmeal

breads and high-fiber breakfast cereals have high glycemic index

values that are similar to their refined counterparts [4]. For this

reason, using the glycemic index is a more precise instrument for

teasing out the effects of PPG per se on disease risk.

Glycemic load is defined as the product of the carbohydrate

content per serving of food and its glycemic index. It was introduced

by Harvard researchers to derive a `global' estimate of postprandial

glycemia and insulin demand [3]. Recent studies have validated the

concept in a physiological sense. Servings of food with the same

glycemic load produced similar levels of postprandial glycemia, and

step-wise increases in glycemic load gave predictable increases in

glycemia and insulinemia [21]. Moreover, when four isoenergetic diets

of differing glycemic load were compared in mixed meals over 10 h,

they produced the expected rank order of responses [10•]. Diets based

on large quantities of carbohydrates from high glycemic index sources

such as bread, potatoes and breakfast cereals therefore have the

highest glycemic load and theoretically the highest levels of PPG.

Liu et al. [22] were the first to consider glycemic index,

glycemic load and CVD using data from 75 000 women in the Nurses'

Health Study. During 10 years of follow-up, dietary glycemic load was

directly associated with risk of coronary heart disease after

adjustment for known confounders, including fiber. The relative risk

comparing highest and lowest quintiles was 1.98 and was most evident

among women with a BMI above 23. In addition, infarct risk was not

predicted by the amounts of sugar or starch in the diet.

Two studies, one large and one small, found no strong association

between glycemic index and nonfatal myocardial infarction. In the

Zutphen study of elderly men [23], for example, the relative risk was

only 1.11 from lowest to highest tertile of glycemic index.

Similarly, in an Italian population of 433 men without diabetes [24],

glycemic index was not significantly related to disease risk, except

in the subgroup of men over 60 years with a BMI greater than 25. One

of the particular strengths of the Harvard research, however, is the

quality of the glycemic index database. of the

University of Toronto, who first proposed a glycemic index of foods,

coded the Harvard database and tested some of the key foods. Because

many breads and cereal products have unknown glycemic index values,

extrapolation may be a significant source of error and create bias

towards the null hypothesis.

Glycemic index, glycemic load and dyslipidemia

The glycemic index and glycemic load may influence risk of CVD via

mechanisms other than PPG. HDL cholesterol is a powerful predictor of

the development of CVD. In metabolic studies, diets with increased

carbohydrates are recognized to reduce HDL cholesterol concentration

and increase triglycerides [25]. But quality of the carbohydrate may

also be important in this regard. HDL cholesterol has been found to

correlate with the glycemic index of the diet in different countries

and population groups [26–28]. In a cross-sectional study of middle-

aged British adults, the glycemic index was the only dietary variable

significantly related to serum HDL cholesterol and a stronger

predictor than dietary fat [29]. Using data from nearly 14 000

Americans in the Third National Health and Nutrition Examination

Survey, Ford and Liu [28] found an inverse relationship between

glycemic index and glycemic load and HDL cholesterol across all

subgroups of participants categorized by sex or BMI.

Dietary glycemic load has also been directly related to fasting

triglyceride levels. In a subgroup of 185 healthy post-menopausal

women from the NHS, both glycemic index and carbohydrate contributed

independently to a strong positive association between glycemic load

and fasting triglycerides [27]. The relationship was steeper and

stronger in those with a higher BMI. For the lowest and highest

quintiles of glycemic load, the mean triglycerides were 0.92 and 2.24

mM in the women with BMI greater than 25, and 1.02 and 1.42 in women

with BMI less than or equal to 25. In this same cohort, glycemic load

was also associated with increasing levels of C-reactive protein

(CRP), a measure of chronic low-grade inflammation [30]. In obese

subjects, Harbis et al. [31•] found that high glycemic index

carbohydrates create a detrimental postprandial pattern in

triglyceride-rich lipoproteins derived from both hepatic and

intestinal sources. These data support the physiological relevance of

glycemic load, particularly in those prone to insulin resistance.

Diets with a high glycemic index or glycemic load appear to

influence the development of the metabolic syndrome. In the

Framingham Offspring Study [32•], the relative risk of having the

syndrome using the ATP1 criteria was 1.41 comparing highest and

lowest quintiles of glycemic index, independently of dietary fiber

intake. Total carbohydrate and glycemic load, however, were not

associated with prevalence of the metabolic syndrome.

Hyperinsulinemia itself, the compensatory response to PPG in the

presence of insulin resistance, may contribute directly to the

pathogenesis of CVD. In the Framingham offspring study, homeostasis

model assessment (HOMA)-insulin resistance was associated with

increasing glycemic index [32•] and similarly, in a group of healthy

children, fasting insulin was predicted by the glycemic index of the

overall diet [33•].

Intervention studies using low glycemic index diets

Several short-term clinical trials in healthy and normoglycemic,

high-risk individuals provide direct evidence that diets with a low

glycemic index improve hyperlipidemia and insulin sensitivity. In

hyperlipidemic patients without diabetes, 's group [34]

demonstrated that 4 weeks on a low glycemic index diet could reduce

total cholesterol and LDL cholesterol by around 10% and triglycerides

by around 20% in comparison with a macronutrient and fiber-matched

high glycemic index diet. HDL levels, however, remained unchanged.

Frost's group extended these findings in women with advanced CVD

awaiting bypass surgery. Glucose tolerance and insulin sensitivity

improved after 4 weeks on a low glycemic index diet (versus the high

glycemic index diet) as judged by the insulin area under the curve in

response to a glucose challenge [35]. In overweight, middle-aged men,

Brynes et al. [11••] showed that postprandial HOMA-insulin resistance

increased significantly more on a high glycemic index diet (+31%)

than a macronutrient-matched low glycemic index diet (-43%).

Similarly, Patel et al. [36•] demonstrated improved glucose tolerance

and postprandial glycemia and insulin in men scheduled for bypass

surgery. In this study, length of hospital stay after surgery was

shortened significantly in the group randomized to the low glycemic

index diet versus the high glycemic index diet (7.1 versus 9.5 days).

Low glycemic index diets have also resulted in improved lipid

metabolism in healthy, overweight individuals consuming high-

carbohydrate foods ad libitum. After a 10-week energy-restricted

intervention, Sloth et al. [37••] demonstrated no differences in

weight loss between the high and low glycemic index groups, but

significant decreases in LDL cholesterol on the low glycemic index

diet. Low glycemic index diets also have improved glucose and lipid

metabolism in patients with diabetes. A recent meta-analysis found a

significant reduction in total and LDL cholesterol in individuals

with type 2 diabetes but no effect on triglycerides and HDL

cholesterol [38••].

Intervention studies using drugs that specifically target PPG

provide direct evidence that elevated blood glucose levels affect CVD

endpoints in individuals without diabetes. In the STOP-NIDDM study,

for example, patients with IGT who had been randomized to acarbose

(an [alpha]-glucosidase inhibitor that slows carbohydrate absorption)

had half the risk of a cardiovascular event or hypertension over the

3-year period compared with those given the placebo [39••].

Furthermore, annual progression of intima-media thickness was

significantly reduced in the acarbose-treated group by around 50%

[40•]. This is an important study in the present context because the

mechanism of action can only be ascribed to the slowing of

carbohydrate absorption and consequent reduction in PPG – a property

analogous to that of low glycemic index foods. Thus, while it is

possible that low glycemic index foods improve risk by virtue of

their wholegrain nature, fiber or micronutrient content, the slowing

of carbohydrate absorption per se is probably their most important

attribute.

Glycemic index and weight control

There is increasing evidence that the glycemic index has

implications for weight control and therefore for CVD. In particular,

wide fluctuations in blood glucose and insulin levels have been

linked to appetite stimulation in human and animal studies [41]. In

one-day studies, meals containing low glycemic index carbohydrate

have been found to enhance satiety and reduce total energy intake at

the following meal [42,43]. High glycemic index meals have also been

associated with reduced fat oxidation at rest and during exercise

[44,45] and lower metabolic rate during and after weight loss [46]. A

limited number of controlled trials demonstrate faster or more

sustained weight loss on low glycemic index diets [47–49].

We recently completed a study in 129 young overweight volunteers

comparing four diets of varying glycemic load (i.e. they varied in

both glycemic index and carbohydrate content but not fat) over a 12-

week period. Most foods were supplied but the amount eaten was at the

discretion of the individual. The findings indicate that body fat

loss was enhanced on both the low glycemic index (55% energy as

carbohydrate, 15% protein) and the lower-carbohydrate (45%

carbohydrate, 25% protein) diet compared with the conventional low-

fat diet. Improvements in lipid metabolism, however, were

significantly greater in the low glycemic index group than in any

other groups. These findings are broadly consistent with recent

studies of very low carbohydrate diets. Reducing the glycemic load of

the diet by severe restriction in carbohydrate intake results in

faster rates of weight loss in the first 6 months and improved lipid

profiles at 12 months, even after adjustment for differences in

weight loss [50•, 51••]. However, because very low carbohydrate diets

are unavoidably high in total and saturated fat, there may be long-

term cardiovascular implications. In contrast, there are no such

concerns in respect of high-carbohydrate, low glycemic index diets.

Because manipulation of a diet's glycemic index can produce

changes in potentially confounding dietary factors, such as fiber

content, palatability and energy density, its relevance to health

remains controversial. In this context, long-term studies in animals

provide additional evidence that low glycemic index is important in

relation to weight gain, body fat and diabetes risk. Animals fed

identical diets differing only in the type of starch (high or low

glycemic index) gain body fat faster on the high glycemic index diet

[52••]. Even when fed to similar body weight, the high glycemic index-

fed rats had more body fat (+71%), less lean body mass and higher

plasma triglyceride concentrations. In addition, high glycemic index

feeding was associated with significant disruption of [beta]-cell

architecture after only 18 weeks.

Mechanisms of hyperglycemia-induced endothelial damage

Several molecular mechanisms have been implicated in glucose-

mediated vascular damage. All appear to reflect a single

hyperglycemia-induced process of overproduction of superoxide by the

mitochondrial electron-transport chain. The vascular endothelium is a

prime target because endothelial cells, unlike many other cells in

the body, are unable to regulate glucose transport across the cell

membrane [53]. Normal levels of glycemia encountered during an oral

glucose tolerance test or standard meal have been shown to acutely

decrease plasma antioxidant capacity, reflecting a significant level

of oxidative stress [54•]. Damage to the endothelium caused by high

blood glucose levels may play an important role in the development of

atherosclerosis. Upregulation of inflammatory transcription factors

such as nuclear factor-[kappa]B is an early marker of endothelial

dysfunction [55,56•]. Moderately elevated CRP, a sensitive surrogate

marker for low-level inflammation, has been linked to insulin

resistance, obesity and hyperglycemia [57•], and more recently to the

glycemic index and glycemic load of the diet. In 244 healthy, middle-

aged women, a high dietary glycemic load independently predicted

elevated plasma concentrations of CRP with a two-fold increase

comparing the lowest and the highest quintiles [30]. In lean young

volunteer studies, we found the strongest independent predictor of

fasting CRP concentration was the 120 min blood glucose levels

following a carbohydrate challenge (S. Dickinson, J. Brand-,

unpublished data).

Conclusion

Taken together, observational, interventional and experimental

studies suggest that nondiabetic levels of postprandial glycemia may

play a greater role in CVD than is generally acknowledged. Rapidly

absorbed carbohydrates and diets with a high glycemic load lead to

the highest levels of postprandial blood glucose. Recommendations to

reduce saturated fat and increase carbohydrate intake have

inadvertently encouraged greater consumption of high glycemic index

foods and thereby increased day-long glycemia. The evidence that this

may be harmful is stronger in individuals with higher BMI, insulin

resistance or impaired glucose tolerance. However, even so-called

normal levels of post-meal glycemia may not be as benign as we take

for granted.

It may therefore be timely to give greater consideration to the

glycemic potential (glycemic index) of dietary carbohydrate in

dietary recommendations. Current emphasis on increasing wholegrains

and restriction of sugar, although helpful from a micronutrient point

of view, is unlikely to improve glycemia. Furthermore, it may

alienate and discourage some consumers from adopting more effective

dietary strategies to reduce the risk of chronic disease. Encouraging

greater consumption of low glycemic index foods, however, will

require local and brand-specific knowledge of the glycemic index of

breads, breakfast cereals, rices and other cereal products.

References and recommended reading

Papers of particular interest, published within the annual period

of review, have been highlighted as:

• of special interest

•• of outstanding interest

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intestinal lipoprotein accumulation in obese, insulin-resistant

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34 D, Wolever T, Kalmusky J, et al. Low-glycemic index diet

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35 Frost G, Leeds A, Trew G, et al. Insulin sensitivity in women at

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36• Patel V, Aldridge R, Leeds A, et al. Retrospective analysis of

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excellent study that investigated the long-term effects of a low-fat,

high-carbohydrate diet with either low or high glycemic index

carbohydrate treatments. Interestingly, while there was no difference

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38•• Opperman A, Venter C, Oosthuizen W, et al. Meta-analysis of the

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risk of cardiovascular disease and hypertension in patients with

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494. An important intervention study producing direct evidence for

the first time that reducing postprandial hyperglycemia, by slowing

carbohydrate absorption in the gut (and thus mimicking the effect of

low glycemic index carbohydrate), substantially reduces the risk for

cardiovascular events among patients with IGT even after adjusting

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subjects with impaired glucose tolerance. Stroke 2004; 35:1073–1078.

This study also involved participants from the STOP-NIDDM trial. The

authors went a step further from the above work and found that

acarbose treatment was associated with a 50% annual reduction in the

progression of intima-media thickening, a surrogate marker for

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41 Campfield L, F. Blood glucose dynamics and control of meal

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42 Ludwig D. Dietary glycemic index and obesity. J Nutr 2000;

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43 Warren J, Henry C, Simonite V. Low glycemic index breakfasts and

reduced food intake in preadolescent children. Pediatrics 2003;

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44 Febbraio M, Keenan J, Angus D, et al. Preexercise carbohydrate

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45 Kirwan J, Cyr- D, W, et al. Effects of moderate

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46 Agus M, Swain J, Larson C, et al. Dietary composition and

physiologic adaptations to energy restriction. Am J Clin Nutr 2000;

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47 Bouche C, Rizkalla S, Luo J, et al. Five-week, low-glycemic index

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moderately overweight nondiabetic men. Diabetes Care 2002; 25:822–

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48 Ebbeling C, Leidig M, Sinclair K, et al. A reduced-glycemic load

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49 Spieth L, Harnish J, Lenders C, et al. A low-glycemic index diet

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50• Stern L, Iqbal N, Seshadri P, et al. The effects of low-

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2004; 140:778–785. Bibliographic Links This randomized trial compared

weight loss in severely obese patients consuming a conventional

weight loss diet versus a low-carbohydrate diet over a 1-year period.

Although drop out rates were high and the results may not be

applicable to moderately overweight individuals, the low-carbohydrate

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51•• Yancy W, Olsen M, Guyton J, et al. A low-carbohydrate, ketogenic

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well controlled intervention study shows that a low-carbohydrate diet

seems to be more effective for treating obesity and hyperlipidemia

compared with a conventional low-fat approach over a 24-week period.

LDL cholesterol, however, was slightly higher on the low-carbohydrate

diet. = http://tinyurl.com/4fxzj

52•• Pawlak DB, Kushner JA, Ludwig DS. Effects of dietary glycaemic

index on adiposity, glucose homoeostasis, and plasma lipids in

animals. The Lancet 2004; 364:778–785. A very well designed and

controlled animal study demonstrating the beneficial effects of a low

versus high glycemic index diet on body composition and risk factors

for diabetes and cardiovascular disease. The strengths lie in their

controlling of potential confounding factors that arise through

manipulation of dietary glycemic index. Macronutrient, micronutrient

and fiber content were identical in the two diets while food amounts

were adjusted to maintain the same mean body weight in the groups.

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53 Brownlee M. Biochemistry and molecular cell biology of diabetic

complications. Nature 2001; 414:813–820. [Context Link]

54• Ceriello A, Hanefeld M, Leiter L, et al. Postprandial glucose

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2095. An excellent review which argues that total glycemic exposure

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55 Schmidt A, Stern D. Hyperinsulinemia and vascular dysfunction: the

role of nuclear factor-kappaB, yet again. Circ Res 2000; 87:722–724.

Ovid Full Text Bibliographic Links [Context Link]

56• Kumar A, Takada Y, Boriek A, Aggarwal B. Nuclear factor-kappaB:

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excellent review of the transcription factor nuclear factor-[kappa]B.

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57• Verma S, Chao-HungWang, Weisel RD, et al. Hyperglycemia

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Bibliographic Links In this study, endothelial cells incubated with

CRP produced proatherogenic effects which were significantly

amplified under hyperglycemic conditions.