Glycemic Index and Chronic Disease Risk (Mostly in Women)

"Would you like some high-glycemic index bread?"

"Would you like some high-glycemic index bread?"

I recently blogged about glycemic index (GI), glycemic load (GL), and glycemic diets in preparation for today’s post.

The concept of glycemic index was introduced by Jenkins et al in 1981 at the University of Toronto.

Studies investigating the association between disease risk and GI/GL have been inconsistent.  By “inconsistent,” I mean some studies have made an association in one direction or the other, and other studies have not.  Diseases possibly associated with high-glycemic diets have included diabetes, cardiovascular disease, cancer, gallbladder disease, and eye disease.

“Diet” in this post refers to a habitual way of eating, not a weight loss program.

Researchers with the University of Sydney (Sydney, Australia) identified the best-designed published research reports investigating the relationship between certain chronic diseases and glycemic index and load.  The studied diseases were type 2 diabetes, coronary heart disease, stroke, breast cancer, colorectal cancer, pancreatic cancer, endometrial cancer, ovarian cancer, gallbladder disease, and eye disease.


Literature databases were searched for articles published between 1981 and March, 2007.  The researchers found 37 studies that enrolled 1,950,198 participants ranging in age from 24 to 76, with BMI’s averaging 23.5 to 29.  These were human prospective cohort studies with a final outcome being occurrence of a chronic disease (not its risk factors).  Twenty-five of the studies were conducted in the U.S., five in Canada, five Europe, and two in Australia.  Ninety percent of participants were women [for reasons not discussed].  Food frequency questionnaires were used in nearly all the studies.  Individual studies generated between 4 to 20 years of follow-up, and 40,129 new cases of target diseases were identified.

Associations between GI, GL, and risk of developing a chronic disease were measured as rate ratios comparing the highest with the lowest quantiles.  For example, GI and GL were measured in the study population.  The population was then divided into four groups (quartiles), reflecting lowest GI/GL to medium to highest GI/GL diets.  The lowest GI/GL quartile was compared with the highest quartile to see if disease occurrence was different between the groups.  Some studies broke the populations into tertiles, quintiles, deciles, etc.


Comparing the highest with the lowest quantiles, studies with a high GI or GL independently

  • increased the risk of type 2 diabetes by 27 (GL) or 40% (GI)
  • increased the risk of coronary heart disease by 25% (GI)
  • increased the risk of gallbladder disease by 26% (GI) or 41% (GL) [gallstones and biliary colic, I assume, but the authors don’t specify]
  • increased the risk of breast cancer by 8% (GI)
  • increased risk of all studied diseases (11) combined by 14% (GI) or 9% (GL)

Overall, high GI was more strongly associated with chronic disease than was high GL
So low-GI diets may offer greater protection against disease than low-GL diets.

Comments from the Researchers

They speculate that low-GI diets may be more protective than low-GL because the latter can include low-carb foods such as cheese and meat, and low-GI, high-carb foods.  Both eating styles will reduce glucose levels after meals while having very different effects in other areas such as pancreas beta cell function, free fatty acid levels, triglyceride levels, and effects on satiety.

High GI and high GL diets, independently of known confounders, modestly increase the risk of chronic lifestyle-related diseases, with more pronounced effects for type 2 diabetes, coronary heart disease, and gallbladder disease.

Direct quotes:

. . . 90% of participants were female; therefore, the findings may not be generalizable to men.

There are plausible mechanism linking the development of certain chronic diseases with high-GI diets.  Specifically, 2 major pathways have been proposed to explain the association with type 2 diabetes risk.  First the same amount of carbohydrate from high-GI food produces higher blood glucose concentrations and a greater demand for insulin.  The chronically increased insulin demand may eventually result in pancreatic beta cell failure, and, as a consequence, impaired glucose tolerance.  Second, there is evidence that high-GI diets may directly increase insulin resistance through their effect on glycemia, free fatty acids, and counter-regulatory hormone secretion.  High glucose and insulin concentrations are associated with increased risk profiles for cardiovascular disease, including decreased concentrations of HDL cholesterol, increased glycosylated protein, oxidative status, hemostatic variables, and poor endothelial function

Low-GI and/or low-GL diets are independently associated with a reduced risk of certain chronic diseases.  In diabetes and heart disease, the protection is comparable with that seen for whole grain and high fiber intakes.  The findings support the hypothesis that higher postprandial glycemia is a universal mechanism for disease progression.

My Comments

Studies like this tend to accentuate the differences in eating styles since they compare the highest with the lowest post-prandial (after meal) glucose levels.  Most people are closer to the middle of the pack, so a person there has potentially less to gain by moving to a low-GI diet.  But still some to gain, on average, particularly in regards to avoiding type 2 diabetes and coronary heart disease.

[To be fair, many population-based studies use this same quantile technique.  It increases the odds of finding a statistically significant difference.]

Only two of the 37 studies examined coronary heart disease, the cause of heart attacks.  One study was the massive Nurses’ Health Study database with 75,521 women.  The other was the Zutphen (Netherlands) Elderly Study which examined men 64 and older.  Here’s the primary conclusion of the Zutphen authors verbatim:

Our findings do not support the hypothesis that a high-glycemic index diet unfavorably affects metabolic risk factors or increases risk for CHD [coronary heart disease] in elderly men without a history of diabetes or CHD.

So there’s nothing in the meta-analysis at hand to suggest that high-GI/GL diets promote heart disease in males in the general population.

However, the recent Canadian study in Archives of Internal Medicine found strong evidence linking CHD with high-glycemic index diets.  Although not mentioned in the text of that article, Table 3 on page 664 shows that the association is much stonger in women than in men.  Relative risk for women on a high-glycemic index/load diet was 1.5 (95% confidence interval = 1.29-1.71), and for men the relative risk was 1.06 (95% confidence interval = 0.91-1.20).  See reference below.

Nine of the 37 studies examined the occurrence of type 2 diabetes.  Only one of these studied men only – 42,759 men: the abstract is not available online and the Sydney group does not mention if high-GI or high-GL was positively associated with onset of diabetes in this cohort.  Two of the diabetes studies included both men and women, but the abstracts don’t break down the findings by sex.  [I’m trying to deduce if the major overall findings of this meta-analysis apply to men or not.]

I don’t know anybody willing to change their diet just to avoid the risk of gallstones.  It’s only after they develop symptomatic gallstones that they ask me what they can do about them.  The usual answer is surgery.

The report is well-done and seems free of commercial bias, even though several of the researchers are authors or co-authors of popular books on low-GI eating.

Steve Parker, M.D.


Barclay, Alan W.; Petocz, Peter; McMillan-Price, Joanna; Flood, Victoria M.; Prvan, Tania; Mitchell, Paul; and Brand-Miller, Jennie C.  Glycemic index, glycemic load, and chronic disease risk – a meta-analysis of observational studies [of mostly women].  American Journal of Clinical Nutrition, 87 (2008): 627-637.

Brand-Miller, Jennie, et al.  “The New Glucose Revolution: The Authoritative Guide to the Glycemic Index – The Dietary Solution for Lifelong Health.”  Da Capo Press, 2006.

Mente, Andrew, et al.  A Systematic Review of the Evidence Supporting a Causal Link Between Dietary Factors and Coronary Heart DiseaseArchives of Internal Medicine, 169 (2009): 659-669.


Filed under Causes of Diabetes, Glycemic Index and Load

4 responses to “Glycemic Index and Chronic Disease Risk (Mostly in Women)

  1. Laurel

    Does anyone have a good recipe for Ezekiel bread or Jack Sprat bread? This bread is made from whole grains that have been sprouted, ground and baked. It’s yummy, but I would like to make my own so I can control what goes into each loaf.
    Thanks for any help you can give me. Please email me privately as well as to the blog.

  2. I am very interested in a sugar-free living. I currently have a sweet-tooth, and am finding it difficult to find meal plans, what to eat for snacks, etc. While diabetes is not something that runs in my family, I am still concerned and would like to be smart and take a proactive approach to my health. Any tips or advice?

    • Hi, Augusta. Some people find that if they do something like Atkins Induction Phase for a couple months, the sweet cravings go away or are more manageable. Others substitute artificial sweeteners for real sugar. Tough problem.