plans published by Simpson et aI.l9 It can be seen 'that ... in fiber. Plasma lipid concentrations. Because high- carboh
Effect of Dietary Carbohydrate on the Metabolism of Patients with Non-insulin Dependent Diabetes Mellitus Gerald M. Reaven. MD
Although clinical diabetes is usually categorized as a disease of carbohydrate metabolism, it has been apparent for some time that abnormalities of lipoprotein metabolism are common in patients with this syndrome. Defects in lipoprotein metabolism are particularly prevalent in patients with non-insulin dependent diabetes mellitus (NIDDM), and almost certainly play a major role in the accelerated atherogenesis that characterizes patients with NIDDM. Indeed, macroangiopathy, as differentiated from microangiopathy, seems to be primarily responsible for the morbidity and mortality associated with NIDDM. These concerns have led to suggestions that composition of the diabetic diet be changed in order to reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD) by reducing dietary fat and increasing dietary carbohydrate intake.' More recently, the Nutrition Committee of the American Diabetes Association (ADA) has suggested2 that the diabetic diet should also be modified by variations in kind, as well as the amount, of dietary carbohydrate. Although the goal of reducing the risk of ASCVD in patients with NIDDM is exemplary, it is essential that dietary recommendations reduce, not enhance, the likelihood of developing ASCVD in patients with NIDDM. Metabolic Risk Factors Predisposing to ASCVD Increased plasma concentrations of gluDr Reaven is Professor, Department of Medicine, Stanford University School of Medicine and Geriatric Research, Education and Clinical Center, Veterans Administration Medical Center, Palo Alto, CA 94304, USA.
cose, insulin, very-low-density lipoprotein (VLDL) triglyceride (TG), and low-density lipoprotein (LDL) cholesterol have all been implicated as risk factors favoring the development of ASCVD.3-9 More recently, a decrease in high-density lipoprotein (HDL) cholesterol has been defined as an additional risk f a ~ t o r Of .~ the five changes listed above, four-increased plasma glucose, insulin, and VLDL-TG levels, and decreased HDL cholesterol concentrations-are common in patients with NIDDM. Despite this fact, the strategy behind the view that high-carbohydrate low-fat diets will benefit patients with NIDDM is that this intervention will tend to lower LDL cholesterol levels. Since elevated LDL cholesterol levels predispose nondiabetic subjects to ASCVD, this should also be true of patients with NIDDM. On the other hand, it does seem somewhat surprising that the dietary advice has focused entirely on a lipid profile which is not a prominent feature of NIDDM. This is even more surprising to realize in light of evidence that high-carbohydrate low-fat diets may accentuate hyperglycemia, hyperinsulinemia, and hypertriglyceridemia, while lowering plasma HDL cholesterol concentration^.^^‘^^ Thus it seems important to critically evaluate available data on the impact of low-fat high-carbohydrate diets on risk factors for ASCVD in patients with NIDDM. This is the goal of this review. Rationale for Low-fat High-carbohydrate Diets Two lines of reasoning have been advanced in support of a low-fat high-carbohydrate diet in the treatment of NIDDM. One argument is based upon the premise that low-fat high-carbohydrate diets will improve glycemic control NUTRITION REVIEWSNOL. 44, NO. Z/FEBRUARY 1986
65
in patients with diabetes, and the pioneering studies of Himsworth and associates are often cited in support of this point of view.14,15Unfortunately, closer perusal of Himsworth’s studies leads to a somewhat different conclusion. For example, Figure 1 is based on data derived from Himsworth, and the result of these studies in normal subjects require thoughtful interpretation. The most obvious finding is that a verylow-carbohydrate diet (50 g per day) was associated with poor glucose tolerance, and that glucose tolerance markedly improved when carbohydrate intake was raised to 100 g per day. Further improvement in glucose tolerance in these normal subjects was quite modest as dietary carbohydrate was increased from 100 to 300 g per day. Somewhat analogous results in normal subjects and patients with impaired glucose tolerance have been reported by Brunzell et all6 and by Anderson and coll e a g u e ~ In . ~these ~ instances, an increase in carbohydrate intake from approximately 45 percent to 85 percent and 75 percent of total calories led to approximate 10 percent improvements in oral glucose tolerance. Of even greater significance are the results (Figure 2) of clinical studies carried out in patients with diabetes by Himsworth and Kerr.15 In these
140
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100-
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80 60 -
40 -
/’
0
100
200
300
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600
Dietary Carbohydrate (glday)
Figure 1. Relationship between daily carbohydrate intake and ability to dispose of an oral glucose challenge in normal individuals. The change in glucose tolerance due to the variation in dietary carbohydrate intake is expressed relative to the glucose tolerance observed at the lowest level of carbohydrate intake.I4 66
NUTRITION REVIEWSNOL. 44.NO. ~IFEBRUARY1986
30. 20’O:l&p.&&
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Figure 2. Relationship between dietary carbohydrate intake and 24-hour urinary glucose excretion in two patients with “insulin-sensitive’’diabetes (top panel) and two patients with “insulin-insensitive’’ diabetes (lower paneI).l5
investigations of the effect of variations in dietary carbohydrate on glycemic control, Himsworth and Kerr divided patients with diabetes into two categories-“insulin-sensitive” and “insulin-insensitive.” Patients with insulin-sensitive diabetes would be defined as having insulin-dependent diabetes mellitus (IDDM) by today’s criteria,‘* and it can be seen from Figure 2 that urinary glucose excretion did not vary significantly when carbohydrate intake was varied in these subjects. In contrast, glycosuria clearly increased in magnitude when dietary carbohydrate was raised in “insulin-insensitive” patients, ie, higher carbohydrate intake led to a deterioration in glycemic control of patients who would be classified as having NIDDM.18 Thus, historical support for the view that high-carbohydrate diets substantially improve glucose tolerance is far from overwhelming. The second line of reasoning in support of the use of low-fat high-carbohydrate diets in NIDDM is based on the view that amount of dietary fat intake is the major environmental variable leading to an increased risk of ASCVD. In essence, this represents a translation of the general epidemiological argument which holds that an increase in fat consumption is the major cause of ASCVD in the world
at large. This issue has been extensively debated for at least three decades, and it is obviously impossible to review the data relevant to this question in the current context. Instead, an effort will be made to both narrow and broaden the inquiry. More specifically, the metabolic effects of high-carbohydrate low-fat diets will be focused on patients with NIDDM, and, at the same time, consideration of diet-induced changes in metabolic risk factors will not be confined to changes in plasma LDL cholesterol levels. Effects of High-carbohydrate Low-fat Diets on Patients with NIDDM Plasma glucose concentrations. Increasing dietary carbohydrate content from 40 to 61 percent of total caloric intake (with a commensurate reduction in fat intake) is associated with a fall in fasting and postprandial plasma glucose concentrations and glycosylated hemoglobin (9.6 to 8.6 percent) in patients with NIDDM.lg In addition, it has been stated in another study that insulin requirements fall when patients with NIDDM consume comparable diets.20 However, the situation is more complicated than it first appears. For example, in the latter study20 the insulin dose was reduced in concert with introduction of the highcarbohydrate low-fat diet, and the putative benefits might have remained if patients were given more conventional proportions of carbohydrate and fat. In addition, both studies are characterized by being extremely high in fiber, ie, about 50 g/l,OOO kcal. Insight into the nature of these diets can be gained from inspection of Table I, which contains calculations of daily caloric intake derived from the menu plans published by Simpson et aI.l9 It can be seen ‘that wholemeal bread, legumes, and margarine accounted for approximately 82 percent of daily caloric intake. When the fiber content of the high-carbohydrate low-fat diet was lowered to more typical levels in studies by the same workers, overall glucose tolerance was unchanged.21Thus, it is possible that the beneficial effect of high-carbohydrate low-fat diets on plasma glucose levels may only be seen when the diets are also very high in fiber. Plasma lipid concentrations. Because high-
TABLE I Total Caloric Intake = 1920 kcaP Major Dietary Constituents (kcal) Wholemeal bread Haricot beans Margarine Dried peas Butter beans Kidney beans
604.8 379.4 = 178.8 = 143.0 = 136.5 = 136.0 1578.5 kcal, or 82 percent of total
=
=
carbohydrate low-fat diets were used to improve lipid metabolism in NIDDM, it is interesting to note how relatively modest the documented benefits are. For example, highcarbohydrate low-fat diets that are also extremely high in fiber have been shown to reduce total plasma cholesterol levels by about 15 p e r ~ e n t .However, ~ ~ , ~ ~ when the fiber content of the same diets was held to the amount conventionally consumed,21there was no significant fall in either total or LDL cholesterol concentration. Furthermore, plasma VLDL-TG levels increase22and HDL cholesterol levels decrease2’ when high-carbohydrate low-fat diets are not greatly fiber-enriched. In other words, the two most prominent defects in lipoprotein metabolism seen in patients with NIDDM were accentuated when patients ate a high-carbohydrate low-fat diet containing conventional amounts of fiber. Summary. High-carbohydrate low-fat diets can lower both plasma glucose and LDL cholesterol levels in patients with NIDDM. Furthermore, these changes are seen in the absence of an increase in plasma VLDL-TG levels and a fall in plasma HDL cholesterol concentrations. However, the beneficial effects of such a diet appear to depend upon its fiber content. If the high-carbohydratelow-fat diets are not greatly fiber-enriched, the beneficial effect on plasma glucose and LDL cholesterol levels is dissipated, and deleterious effects on plasma VLDL-TG and HDL cholesterol concentrations are seen. Given these data, it is difficult to understand the enthusiasm about high-carbohydrate low-fat diets. NUTRITION REVIEWSNOL. 44, NO. WFEBRUARY 1986
67
Effects of Variation in Kind of Dietary Plasma Glucose Carbohydrate on Patients with NIDDM In addition to variations in the relative 3001 amount of carbohydrate ingested, adjustments -E 2 05 0 1 can also be made in the kind of carbohydrate0 rich foods that patients with NIDDM should be 150 A-A Potato advised to consume. During the past few years 100 r--rRice attention has turned to this question, and has -Spaghetti focused on three issues: 1) the relative ability of carbohydrate-rich foods to raise plasma glu0 60 120 180 cose (glycemic index); 2) the proportion of simTime (min) ple vs complex carbohydrate; and 3) the Figure 4. Plasma glucose concentrations in patients amount of added sucrose that should be incorwith NIDDM following a lunch containing 30 percent porated into the diabetic diet. Surprisingly, of total calories as either potato, rice, spaghetti, or there is not a great deal of data relevant to lentils. The remaining 70 percent of the menu was these issues, rendering a detailed discussion identical.29 impossible. It might be useful to summarize what information is available, as well as point out the areas where our knowledge is deficient. a function of the glucose source. Plasma gluGlycemic index. It has been apparent for cose levels after either 50 g of baked potato or dextrose are similar. On the other hand, the some time that the plasma glucose response glucose responses to 50 g of either corn or rice to a standard carbohydrate load will vary as a function of the specific food i n g e ~ t e d .Ex~ ~ - ~ ~are substantially lower. amples of this phenomenon are the results Based upon these original observations, an effort has been made to measure plasma glushown in Figure 3, which are based upon the cose levels after many different carbohydrateresults of a study from our laboratory which rich foods, and to compare these values to first demonstrated this phenomenon. It is apparent from these data that the plasma glucose plasma glucose levels following a standard response of normal subjects to a series of 50 g oral glucose challenge. With these data, tables have been created that compare the relative oral glucose challenges varied substantially as glycemic responses of many foods, the socalled “glycemic index.”26-28The implication has been that this knowledge will help in planning meals for diabetics which will reduce ---0 Dextrose postprandial hyperglycemia, and the Nutrition Rice Committee of the American Diabetes AssociaPotato ---A Corn tion has supported this view by suggesting that 4 Bread diabetic diets be planned with the glycemic index of foods in mind.2 Unfortunately, there are no experimental data supporting the view that differences in postprandial hyperglycemia occur in patients with NIDDM when carbohydrates with different glycemic indices are incorporated with meals. ---0 Indeed, evidence has been published support1 1 1 I I 120 180 ing the opposite view.29 These data, shown in Time (min) Figure 4, illustrate the postprandial glucose response observed when patients with NIDDM Figure 3. Plasma glucose concentrations in normal ate four test meals, differing only in source of subjects following the ingestion of 50 g carbohydietary carbohydrate. These meals consisted drate as either dextrose, rice, potato, corn, or bread.23 of turkey, white bread, margarine, oil, lettuce,
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NUTRITION REVIEWS/VOL. 44, NO. 2iFEBRUARY 1986
and either potato, rice, lentils, or spaghetti. The last four items comprised 30 percent of the total caloric content of the test meal. Meals were eaten at noon, and the glycemic response over the next 3 hours was measured. It is apparent from the data shown in Figure 4 that postprandial glucose levels were essentially identical in response to meals containing either rice, spaghetti, or lentils as the major source of carbohydrate. Indeed, the only difference noted was that somewhat higher plasma glucose levels were seen following the potatocontaining meal. Based upon available tables,26-28it would have been predicted that the glycemic potency of spaghetti was approximately twice that of lentils. Obviously, these differences in glycemic index of individual foods were not sufficiently potent to exert any discernible effect when they were incorporated with conventional meals. These observations do not negate the fact that differences in glucose levels are seen when individual carbohydrate-rich foods alone are ingested. On the other hand, one can only speculate what data convinced the Nutrition Committee of the ADA of the clinical utility of the glycemic index. Simple vs complex Carbohydrates. Conventional wisdom is that ingestion of simple carbohydrates should be discouraged and complex carbohydrates encouraged in patients with NIDDM. Although this dictum seems to be generally accepted, we are unaware of experimental data which support this position. Indeed, we
-
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Figure 5. Mean (+SEM) plasma glucose concentrations in patients with NIDDM before and after meals containing variable proportions of complex and simple carbohydrate^.^'
TABLE II Urinary Glucose Excretion in Response to Variations in Proportion of Complex to Simple Carbohydrate (CHO)= Ratio of Complex to Simple CHO 80120 50150 20180
Urinary Glucose (giday [mean +SEMI) 25.1 ? 9.1 12.2 ? 4.5 9.7 2 3.3
have recently published evidence that postprandial hyperglycemia and glycosuria were reduced when patients with NIDDM consumed mixed meals in which the ratio of complex to simple carbohydrates was decreased from 80/20 to 20/80.30 The results of these studies are summarized in Figure 5. These data indicate that day-long postprandial plasma glucose levels were highest when patients with NIDDM consumed diets in which the ratio of complex to simple carbohydrate was also highest (80/20), and lowest when the ratio of complex to simple carbohydrates was the lowest (20/80). Furthermore, the data in Table II indicate that 24 hour urinary glucose excretion was highest when the complex to simple carbohydrate ratio was 80/20, and fell progressively as the ratio of complex to simple carbohydrate was reduced from 80/20 to 20180. It should be emphasized that these changes in ratio of complex to simple carbohydrates was accomplished by varying the relative quantities of naturally occurring carbohydrate foods. In other words, the proportion of simple carbohydrate in the diet was increased by incorporating foods like fruit to the menus, not by adding refined sugar to the meals. Therefore, it is essential that these results not be misinterpreted; the data are only applicable to situations involving naturally occurring carbohydrate-rich foods. However, the distinction between naturally occurring and added dietary carbohydrate is rarely made, and these data illustrate that simply telling patients with NIDDM to decrease their consumption of simple carbohydrates and increase intake of complex carbohydrates may do more harm than good. Added dietary sucrose. Until recently, patients with diabetes have been encouraged to NUTRITION REVIEWSNOL. 44, NO. 2/FEBRUARY 1986
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avoid adding sucrose to their diets. However, this point of view seems to be changing, and recent dietary recommendations have indicated that modest amounts of sucrose may be incorporated into menus for diabetics.2 The justification for this change in dietary advice appears to be based upon studies in which the plasma glucose response to single meals was not accentuated when sucrose was incorporated into that meal.31Unfortunately, this study only addressed the acute metabolic effects of added sucrose on plasma glucose excursions, and provided no information on the impact upon lipid metabolism of adding sucrose to these meals. This is particularly surprising because studies in normal individual^^^^^* and patients with h y p e r t r i g l y ~ e r i d e m i a have ~~~~~ shown that added dietary sucrose can both increase VLDL-TG and reduce HDL cholesterol concentration. Since these are the major defects in lipoprotein metabolism seen in patients with NIDDM, one wonders why patients with NIDDM are now being told that it is acceptable to incorporate moderate amounts of refined simple carbohydrate (sucrose) into their diets2 Based upon these concerns, we recently carried out two studies to evaluate the effects of variations in dietary sucrose on various aspects of carbohydrate and lipid metabolism in patients with NIDDM. One study compared two diets-one conforming to current ADA recommendations regarding fat and carbohydrate content, as well as containing a modest amount of added sucrose, and another closely corresponding to what we believe to be a more prudent diet for patients with NIDDM. Both diets contained 20 percent of total calories as protein, 146 mgi1,OOO kcal of cholesterol, and had a polyunsaturated/saturated fat ratio of 1.3. The two diets differed in that one contained (as percent of total calories) 20 percent fat and 60 percent carbohydrate, of which 10 percent was sucrose. The alternative diet contained 40 percent fat and 40 percent carbohydrate, with no added sucrose (total sucrose intake ca 3 percent of daily caloric intake). Each diet was consumed for 2 weeks, and the order of the diets was randomized. Fasting and postprandial plasma glucose, insulin, and triglyceride concentrations follow70
NUTRtTtON REVtEWSNOL. 44, NO. 2/FEBRUARY 1986
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Figure 6. Plasma glucose, insulin, and triglyceride concentrations before and after meals in patients with NIDDM. The 40 percent CHO diet contained no added sucrose, whereas 10 percent of total calories in the 60 percent CHO diet consisted of added sucrose.
ing 2 weeks on the two diets are seen in Figure 6. Although fasting plasma glucose and insulin concentrations did not vary as a function of diet, fasting plama triglyceride concentrations were significantly increased (p
