Low-versus high-carbohydrate diet: Insulin resistance

[Guest guest]

Hi All,

This subject appears to come up again and again, but it

may be of our long term interest to continue to re-

evaluate the plus and minuses of higher carbohydrate

versus lower carbohydrate diets.

This review focuses on how the different diets and

their constituents may influence insulin resistance.

What should be the nature of whatever carbohydrates

or other macronutrients that we eat? The issues of good

versus bad fats, what level of protein in our diet is best

and what the nature of our carbohydrates in our diets to

utilize for our macronutrients are a very important issues

in my and many opinions and much more so for CRers.

Our diets as CRers may increase the importance of our

macronutrient compositions in foods that we eat in that

protein may be relatively more important than carbohydrates,

I begrudgingly am required to say.

Vegetables, and some fruits, maybe should constitute

the major foods that we eat.

Insulin resistance may be of reduced importance for

CRers. That said, what our optimum blood levels of

glucose/insulin should be continue to appear on our

dietary selection agenda.

Schwenke DC.

Insulin resistance, low-fat diets, and low-carbohydrate diets:

time to test new menus.

Curr Opin Lipidol. 2005 Feb;16(1):55-60.

PMID: 15650564 [PubMed - in process]

Purpose of review: Insulin resistance increases the risk of

cardiovascular disease and diabetes, and the risk of cardiovascular

disease increases further once diabetes has developed. As insulin

resistance is a precursor to diabetes, it is critically important to

identify cost-effective means, such as dietary changes, by which to

reduce insulin resistance. The purpose of this review is to evaluate

recent findings concerning dietary composition and insulin

resistance, with particular focus on low-fat diets compared with the

currently popular low-carbohydrate diets.

Recent findings: Recent findings indicate little support for the

value of low-carbohydrate diets as therapies for insulin resistance.

In contrast, the limited data available suggest that the higher fat

content of typical low-carbohydrate diets may exacerbate insulin

resistance in the long term. Preliminary data indicate that proteins

from different sources may have differing effects on insulin

resistance. Preliminary data also suggest the potential value of

whole grains, fruits and vegetables in therapeutic diets to reduce

insulin resistance.

Summary: Current evidence supports the inclusion of whole grains,

fruits and vegetables, and lean sources of animal proteins including

low-fat dairy products in dietary therapies for insulin resistance.

Those who wish to follow a low-carbohydrate diet should be encouraged

to follow a new menu low in fat, and with most of the protein derived

from plant sources.

Abbreviations HOMA: Homeostasis Model Assessment; QUICKI:

Quantitative Insulin Sensitivity Check Index.

Introduction

Insulin resistance increases the risk of cardiovascular disease,

type 2 diabetes, stroke, hypertension, polycystic ovary disease, and

certain forms of cancer [1•,2]. The risk of cardiovascular disease is

further increased once diabetes has developed [3]. This is of

significance because cardiovascular diseases are the single most

important cause of mortality in the USA [4]. Most individuals with

type 2 diabetes present with insulin resistance [5]. Obesity

increases risk of insulin resistance [6•], and recently prevalence of

obesity has increased continuously in both sexes and all age groups

[7–9]. Thus, unless the alarming trend for increasing obesity can be

reversed, the numbers of persons with insulin resistance and type 2

diabetes are likely to increase dramatically in coming decades. Thus,

it is critically important to find cost-effective strategies for

reducing insulin resistance, such as dietary prescriptions.

So-called `low-carbohydrate diets', including the Atkins diet, the

South Beach diet, and the Zone diet (for review see [10•]), are

currently very popular. Due to the profound health implications of

insulin resistance, it is important to understand the influence of

these diets on insulin resistance. The purpose of this review is to

provide an update on the contribution of dietary composition to

insulin resistance, with a particular focus on dietary protein and

dietary fat.

Insulin resistance and dietary fat saturation

As reviewed recently [10•], previous studies have demonstrated

that isocaloric diets enriched in monounsaturated fatty acids improve

glycemic control in individuals with type 2 diabetes, while insulin

sensitivity in those without diabetes is increased by diets with

isocaloric substitution of monounsaturated fatty acids for saturated

fatty acids. More limited data suggest that saturated and trans fatty

acids increase insulin resistance while data for n-3 and n-6

polyunsaturated fatty acids are both limited and inconsistent [10•].

Two recent studies considered how dietary fat saturation influences

insulin sensitivity [11•,12•]. One study reported that, under

metabolic ward conditions, young normoglycemic men and women who were

fed a very high fat diet (70% of energy) containing predominately

polyunsaturated fat for 5 days had increased insulin sensitivity as

assessed by the Quantitative Insulin Sensitivity Check Index (QUICKI)

while a diet of similar composition but containing predominately

saturated fat did not alter the QUICKI [11•]. Another study in

normoglycemic men showed that 6 weeks of supplementation with fish

oil providing 2.5 g of n-3 polyunsaturated fatty acids

(eicosapantaenoic acid + docosahexaenoic acid) did not alter insulin

resistance as estimated by the Homeostasis Model Assessment (HOMA)

[12•]. However, previous studies have differentiated fatty acids

based on saturation only, without considering potential differences

in the effects of fatty acids of equivalent saturation but differing

chain lengths [11•,12•,13–17]. Many of these studies provided no

[11•,14–17] or limited [12•] information on individual fatty acids

present in test diets. Thus, it is not known whether the effect of

fatty acid saturation on insulin sensitivity differs according to

fatty acid chain length, as is the case for lipids and lipoproteins

[18]. Thus, much remains to be learned concerning the influence of

individual fatty acids on insulin resistance.

Insulin resistance, dietary protein, fat and carbohydrate

A number of recent studies have investigated how diets with

protein, fat, or both increased at the expense of carbohydrate

influenced insulin resistance [19••–21••,22•,23•,24••,25••] (Table

1). These studies included individuals with a variety of clinical

characteristics, used a variety of designs and degrees of dietary

control, and differing methods to assess insulin resistance. Four of

these studies considered interventions modeling the currently popular

low-carbohydrate diets [21••,22•,23•,24••]. In all, the dietary

invention was not well controlled and insulin resistance was assessed

by less than ideal methods. The dietary composition achieved for the

studies that reported such information [22•,23•,24••] indicated less

carbohydrate restriction than prescribed. Importantly, both of the

studies that reported on 12-month follow-up of very low carbohydrate

diets observed one or more deaths in the low-carbohydrate diet group

compared with no deaths in the low-fat diet group [23•,24••]. Thus,

the data do not support the long-term safety of low-carbohydrate

diets.

Among the seven studies that substituted protein, fat, or both at

the expense of carbohydrate, only one found the lower carbohydrate

diet slightly reduced insulin resistance [23•]. However, that study

is limited not only by poor dietary compliance, but also by

substantial dropout (40%) of participants before the end of the 6-

month intervention. Importantly, the 12-month follow-up of that

population could not demonstrate any difference in insulin

sensitivity between the carbohydrate restricted and the conventional

low-fat diet groups [24••].

One group evaluated a diet in which protein was increased to 30%

at the expense of carbohydrate [19••]. In the first 16-week phase,

diet was well controlled by providing key foods accounting for 60% of

the energy consumed by participants [19••]. As the diets were well

balanced in terms of percentage of energy from fat and fat

saturation, the interpretation of the comparison of these diets was

facilitated. In the following unsupervised phase described in a later

paper [20••], the composition of the diets consumed by the two groups

converged. Insulin sensitivity did not differ between the two diets

either at the end of the controlled diet phase or the end of the

unsupervised phase [19••,20••].

One particularly well designed study compared a low-fat (20%),

high-carbohydrate diet with a diet in which fat was doubled to 40% by

selective increase in monounsaturated fat [25••]. All meals were

prepared in a metabolic kitchen, and insulin sensitivity was assessed

by the hyperinsulinemic, euglycemic clamp. Unlike the other studies

discussed above, these diets were not hypoenergetic, but rather were

fed ad libitum. This study could not detect any difference in insulin

sensitivity between dietary groups. Thus, there is no convincing

evidence to date that variation in distribution of energy among

protein, fat, and carbohydrate has any significant influence on

insulin sensitivity.

One study that has provided information on the interactive

contribution of insulin resistance and dietary fat to weight change

over 14 years [26••] is of potential importance in improving insulin

sensitivity in the long term. Interestingly, this study found weight

gain during 14 years among those with insulin resistance at baseline

(as estimated by QUICKI) to be greatest for those who consumed a

higher percentage of energy from fat. While this observation remains

to be replicated, it does raise concerns regarding the value of high-

fat diets for treating insulin resistance, as weight gain would be

expected to further increase insulin resistance in these individuals.

Insulin resistance and source of dietary protein

Little is known on how different types of dietary proteins could

influence insulin resistance. Studies that have investigated the

effects of low-carbohydrate diets on insulin sensitivity employed

test diets that were either documented [19••,20••,22•] or likely

[23•,24••] to have been high in animal proteins. No dietary

intervention in human individuals has evaluated the importance of

dietary protein source on insulin resistance. However, several

studies in animals may be informative [27•,28•]. One study indicated

that, compared with cooked red meat, whey protein reduced a measure

of insulin resistance, and that the reduction in insulin resistance

was greater for 32% compared with 8% whey protein [27•]. Another

study reported that dietary cod protein prevented experimentally

induced insulin resistance while soy protein or casein, another

protein from milk, were not effective [28•].

Several studies in humans are consistent with the notion that the

source of dietary protein influences insulin resistance and that red

meat may not be the preferred protein in diets designed to reduce

insulin resistance. One study reported that insulin sensitivity, as

assessed by a standard insulin suppression test, was greater in lacto-

ovo vegetarians compared with persons of a similar age, gender

distribution, and body mass index who usually consumed meat (usually

animal muscle `meat eaters') daily [29]. Further, this study showed

that reducing serum ferritin in meat eaters by phlebotomy improved

insulin sensitivity, suggesting that muscle meat consumption impairs

insulin sensitivity by increasing body iron stores. As insulin

resistance increases risk of type 2 diabetes [1•], this study may

suggest an increased risk of type 2 diabetes in persons who consume

higher levels of red meat. Consistent with that idea, a recent

publication by the Health Professionals' Follow up Study cohort

[30••] reported dietary total heme iron and heme iron from red meat

(but not heme iron from other sources) to be associated with

increased risk of developing type 2 diabetes during 12 years of

follow up.

Insulin resistance and dietary pattern

In a study of overweight individuals, one group was given advice

only, another group received an intense behavioral intervention to

control hypertension (established) and a third group received the

intervention (established) together with the DASH diet: a diet low in

total (<25%) and saturated (<7%) fat with moderately increased

protein including increased amounts of low-fat dairy products and

increased amounts of whole grains, fruits and vegetables, nuts,

seeds, and legumes [31•,32]. After 6 months of intervention, insulin

sensitivity, as assessed during frequently sampled intravenous

glucose tolerance tests, was somewhat but not significantly increased

for the established group and significantly increased for the

established + DASH group.

More work will be needed to determine which aspect(s) of the DASH

diet may contribute to increased insulin sensitivity. It is possible,

however, that observational studies may provide an insight. The whole

grains, low-fat dairy products, fruits and vegetables, nuts, seeds,

and legumes are important contributors to an increased magnesium

content in the DASH diet [32]. Interestingly, within the Insulin

Resistance Atherosclerosis Study cohort, insulin sensitivity, as

assessed by minimal model analysis of frequently sampled intravenous

glucose tolerance tests, was positively associated with intake of

whole grains even after adjustment for multiple demographic and

clinical variables [33••]. The relationship between insulin

sensitivity and whole grains was no longer significant after further

adjustment for dietary fiber and dietary magnesium, suggesting that

these nutrients may account in part for the relationship between

whole grains and insulin sensitivity [33••]. Similarly, a positive

association between whole grain intake and insulin sensitivity was

recently demonstrated in adolescents [34••], and in the Framingham

Offspring Cohort [35•].

Another report in a subset of apparently healthy participants in

the Women's Health Study observed fasting insulin, a measure that is

increased in insulin-resistant persons, to be inversely associated

with dietary magnesium even after multivariate adjustment [36••].

Consistent with the notion that reduced dietary magnesium may

contribute to insulin resistance and promotes the development of type

2 diabetes, in the Women's Health Study population [36••], as well as

in the Nurses' Health Study and the Health Professionals' Follow-up

Study [37••], dietary magnesium was inversely associated with risk of

type 2 diabetes even after adjustment for relevant demographic and

clinical variables [36••,37••]. Another observational study showed

that dietary fiber, another component of whole grains and a component

of fruits and vegetables, was inversely associated with insulin

resistance [38•]. Work in animal models also suggests that brightly

colored fruits and vegetables containing pigments known as

anthocyanins have the potential to increase insulin sensitivity [39•].

Conclusion

Studies to date have suggested that monounsaturated fats as a

class increase insulin sensitivity compared with saturated fats as a

class. Despite the promising data for monounsaturated fats, evidence

for their adverse effects on atherosclerosis in nonhuman primates

[40] suggests the importance of moderation in their consumption.

Further studies with carefully controlled diets will be needed to

clarify the role of n-3 and n-6 polyunsaturated fatty acids and to

determine whether the effect of fatty acid saturation on insulin

resistance is independent of fatty acid chain length.

Similarly, much remains to be learned about the role of dietary

protein source in determining insulin resistance. Of particular

interest will be whether dairy products and fish reduce insulin

resistance compared with meats, and whether red meats increase

insulin resistance more than meats that are less rich sources of heme

iron. Another important area of future research is the potential of

plant sources of protein – perhaps soy protein or other legumes as

alternative sources of protein – that may reduce insulin resistance

compared with red meats. Whole grains are promising candidates to

reduce insulin resistance, and it is possible that fruits and

vegetables, particularly brightly pigmented varieties, may also be

important. Most of the available information on the effects of

dietary intervention on insulin resistance involved hypoenergetic

diets. As weight loss by a variety of means reduces insulin

resistance [41••,42], it may be necessary to test dietary

interventions to reduce insulin resistance in the context of both

weight loss and weight maintenance.

The effects that individual fatty acids and types of proteins have

on insulin resistance still remain to be elucidated. The existing

evidence does not support a dietary pattern that restricts

carbohydrates and focuses on animal sources of protein without

considering the saturated fatty acids present in many animal

proteins. Until research can establish the specific types of dietary

protein that most effectively reduce insulin resistance, those who

wish to follow a high-protein diet would be wise to modify the

typical high-protein content by reducing high-fat animal products and

replacing them with low-fat animal products, including dairy, and

plant proteins. Similarly, the available information supports the

inclusion of whole grains (in place of refined products) and

increased amounts of fruits and vegetables in diets to reduce insulin

resistance.