LOW-GI CARBOHYDRATES AND RISK OF TYPE 2 DIABETES

11.6 LOW-GI CARBOHYDRATES AND RISK OF TYPE 2 DIABETES

11.6.1 E PIDEMIOLOGICAL S TUDIES

In a large cohort of over 65,000 American nurses, the risk of diabetes over a 6-year follow-up was 40% higher in women in the highest fifth than those in the lowest

fifth of the glycemic index and glycemic load, even after adjusting for baseline BMI and cereal fiber intake. 35 In updated analyses with 6 more years of follow-up, 5 more dietary assessments, and 30 more cases, findings remained similar. 50 Dietary fiber per se is important, since products having a higher fiber content have less starch and

a lower glycemic load, but the above associations were independent of and multi- plicative to those of cereal fiber. Among the nurses, women with both a high glycemic

load and low cereal fiber intake were 2.5 times more likely to develop diabetes than those in the respective lower and upper thirds. A similar apparent protective effect

of the low glycemic index and glycemic load was seen in 43,000 American male health professionals. 34 In contrast, despite similar findings of an inverse association of cereal fiber and whole-grain intake, and no association of refined or total carbo- hydrate intake with incident cereal fiber with incident diabetes, no association of

the glycemic index or load was found in a study of 36,000 Iowan women. 51 A possible explanation for the discrepancy may be related to the assessment of diet only at baseline in the Iowan women. Furthermore, although in both studies diabetes was self-reported, the latter study was in women without a medical background, and no confirmation was made of the diagnosis.

Several reviews on the glycemic index and risk of diabetes have recently been published. 39,52–56 Prospective epidemiological studies addressing the association of dietary factors with the metabolic syndrome have not yet been published, and there is an urgent need for controlled randomized studies in these groups of subjects. Large-cohort studies assessing the association of incidence of diabetes mellitus or cardiovascular disease nonetheless suggest that a diet that has a low glycemic index, is high in fiber, or is high in fruit and vegetable intake, may decrease the risk for obesity, type 2 diabetes, or cardiovascular disease and its risk factors.

In theory, low-GI foods may have a preventive effect on the development of type 2 diabetes by influencing the fundamental defects related to insulin resistance

and impaired β-cell function. Furthermore, although evidence is limited and some- what inconsistent, low-GI diets may also promote weight loss (see Chapter 9, this

book), which strikingly influences insulin sensitivity. 57 Indirect evidence for the glycemic index and soluble fiber in the prevention of diabetes is provided by the glucosidase inhibitor acarbose, which delays intestinal absorption of carbohydrates. 58 Acarbose decreases postprandial insulin and glucose responses and improves gly-

Functional Food Carbohydrates

cemic control in diabetic patients. In 1429 individuals with IGT, acarbose has been shown to decrease the risk of diabetes by 25%, which was independent of the small weight loss (0.77 kg) that occurred in the acarbose group.

11.6.2 P OSTPRANDIAL S TUDIES :S ECOND -M EAL E FFECTS

The effect of low-GI foods on glucose and insulin balance has been shown to extend even to the next meal, so that foods eaten during dinner might influence the glycemic

response at breakfast. 59–61 Some low-GI foods eaten at breakfast (e.g., pasta) have been reported to maintain a net increment in blood glucose and insulin at the time

of lunch, thus reducing postprandial glycemia and insulinemia. 62 Recently it has been suggested that dietary fiber content not only slows down glucose absorption,

but perhaps also contributes to the second-meal effect. An evening meal containing low-GI (53) barley meal rich in β-glucan improved glucose tolerance at breakfast,

whereas an evening meal with pasta (GI = 54) did not have this effect. 61 Factors influencing the second-meal effect need to be studied further, but it is clearly

beneficial if low-GI cereal foods are also rich in soluble fiber.

11.6.3 M EDIUM - TO L ONG -T ERM S TUDIES

In a study by Frost et al., 63 women were randomly assigned to consume high- or low-GI diets for 3 weeks. Insulin resistance measured in vivo with a short insulin tolerance test and in cultured adipocytes was greater in women consuming the high-

GI diet. The adverse effects of the high-GI diet appeared to be due to an increased production of free fatty acids in the late postprandial state. In a study by Kiens and Richter, 64 an increase in insulin resistance was not found in seven healthy, lean young men after the subjects had consumed a high-GI diet. It should be noted, however, that subjects were quite healthy and had normal insulin sensitivity, underscoring the concept that metabolic effects of GI are difficult to observe in the healthy population.

A recent crossover study involving 11 overweight subjects showed that insulin sensitivity measured by the euglycemic hyperinsulinemic clamp improved after sub- jects consumed a whole-grain diet, compared with a refined-grain diet, for 6 weeks,

independent of body weight. 65 In another uncontrolled study by the same group, 66

a 4-week low-glycemic diet also decreased an insulin sensitivity index calculated from an oral glucose tolerance test, but the glucose area under the curve only tended to decrease. In contrast, this group 67 found no effect on fasting glucose or insulin concentrations of a 12-week dietary intervention decreasing the GI of the diet (71 vs. 81) in 55 individuals participating in a randomized controlled trial.

Hypothetically, β-cell failure may be induced by high-GI foods by repeated postprandial hyperinsulinemia, leading to overstimulation and exhaustion of the β- cells. 68,69 In a crossover study of six healthy adults, Jenkins et al. 70 found that a low- GI diet containing mainly intact whole grains reduced C-peptide concentrations, a crude measure of insulin secretion, about 32% compared with a high-GI diet con- taining primarily refined-grain products. Recently, we showed that long-term inges- tion of rye bread in elderly women enhanced the acute insulin response to an

The Role of Carbohydrates

intravenous glucose tolerance test, 71 which could be a novel mechanism for the effects of low GI on glucose and insulin. In this regard, it is interesting to address the recent carefully conducted study on six healthy men by Schenk et al., 72 who showed by the stable-isotope technique that the low GI of high-fiber breakfast cereals, compared with high-GI breakfast cereals, was not due to lower systemic appearance of glucose, but instead to earlier disappearance of glucose, which was mainly due to early hyperinsulinemia. These

findings support the study by Juntunen et al. 71 and suggest that one of the hitherto unanticipated mechanisms of foods with a low GI and high in whole grain may be

to enhance the first phase of insulin secretion. Because the loss of the first phase of the insulin response to glucose is one of the early pathogenetic abnormalities in the

development of type 2 diabetes, the potential importance of dietary modification is further strengthened and new developmental avenues are opened.

Low-GI foods may also have relevance with fuel oxidation. Postprandial rises in glucose and insulin concentrations increase carbohydrate oxidation and decrease fatty acid oxidation, but during later postprandial phases, increased release of coun- terregulatory hormones restores euglycemia and elevates free fatty acid (FFA) levels. Increased availability and oxidation of fatty acids may, in turn, decrease carbohydrate

oxidation. 54 Recently, Wolever and Mehling 73 randomly assigned 24 subjects with IGT to a high-carbohydrate + high-GI, high-carbohydrate + low-GI, low-carbohy- drate, or high-monounsaturated-fatty-acid (MUFA) diet for 4 months. Postprandial glucose levels were reduced by the same amount with high-GI and -MUFA diets,

compared to the low-GI diet, but curiously, HbA 1c increased with the MUFA diet. The changes in FFA levels were not significant between the groups, but fasting

insulin levels fell in high-GI and -MUFA groups. Weight changes were small, but significantly more weight was actually lost with the high-GI diet than with the other

two diets, challenging the weight-controlling effects of a low-GI diet. In summary, there are still methodological problems to be worked out for the glycemic index. Prospective epidemiological evidence supporting a role of the glycemic index is mainly limited to two cohort studies, although these are con- vincing in that they are both large and have repeated updating of dietary informa- tion. Medium- to long-term trial evidence is limited and conflicting. There is clearly a need for randomized, controlled, multicenter intervention studies com- paring the effects of conventional and low-GI diets and fat-modified diets on insulin and glucose metabolism.