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Barbara C. Hansen, PhD Dietary Considerations for Obese Diabetic Subjects Individuals with an upper-body form of obesity show greater associations with higher glucose excursions, exacerbated insulin resistance, increased abnormality of lipoprotein profile, and higher cardiovascular risk. Individuals with obesity and diabetes are at great risk for cardiovascular disease. Weight reduction and improvement in blood glucose control through dietary interventions for the obese person with non-insulin-dependent diabetes mellitus (NIDDM) hold the greatest potential for reducing morbidity and mortality. The relative merits of different weightreduction programs are unclear, but regimens should be nutritionally complete, easy to follow, and include a program for maintaining the reduced weight level. Improvement in insulin action and the possibility of slowing development of clinical nephropathy or endstage renal disease in NIDDM through weight loss have been found. Very low calorie diets, when used with medical supervision, may lead to significant weight loss, improved metabolic status, and even reduction or elimination of the need for oral hypoglycemic agents or insulin; however, further studies are needed to examine possible negative outcomes in people with NIDDM before very low calorie diets can be recommended. The causes of obesity and its connection with diabetes are unclear, but even modest calorie restriction may be beneficial to obese diabetic patients because of the positive effects on blood glucose levels and requirements for insulin and oral antidiabetic agents. Diabetes Care 11:183-88,1988 ietary interventions directed toward weight reduction and improvement in blood glucose control of the obese person with non-insulindependent diabetes mellitus (NIDDM) have the greatest potential for significant positive effect on morbidity and mortality. The potential benefits of weight D DIABETES CARE, VOL. 11, NO. 2, FEBRUARY 1988 reduction for the obese diabetic patient include reduction or elimination of exogenous insulin requirements, an increase in life expectancy, and improved health. The mortality ratio for the patient with diabetes who is 20-30% above average body weight is 2.5-3.3 times higher than for those of normal weight, and the mortality rate is 5.2-7.9 times higher among patients combining diabetes with body weights of >40% above ideal (1). The evidence that reduction of excess body weight can decrease excess mortality was demonstrated in the earlier life insurance statistics of Dublin and Marks (2) and has been reaffirmed in a critical review by Simopoulos and Van Itallie (3). The National Institutes of Health (NIH) Consensus Development Conference on Obesity recently concluded that degree of obesity represents a continuum showing a direct relationship with morbidity and mortality (4). Body mass indices and height-weight tables can be useful, but they do not define obesity. They only provide an indication of what is desirable in terms of mortality. Kissebah et al. (5,6) have further shown that it is not just body fat per se that carries increased risk, but also the location or distribution of that fat. An abdominal, truncal, or upper-body obesity appears to be associated with greater risk than lower-body or peripheral fat distribution (6). Individuals with an upper-body form of obesity, even when present in a mild degree, show greater associations with higher glucose excursions, exacerbated insulin resistance, increased abnormality of the lipoprotein profile, and higher cardiovascular risk. From the Department of Physiology, School of Medicine, University of Maryland, Baltimore, Maryland. Address correspondence and reprint requests to Barbara C. Hansen, PhD, Department of Physiology, School of Medicine, University of Maryland, Baltimore, MD 21201. 183 DIET IN OBESITY The NIH Consensus Development Conference report also supported the association of obesity with increased coronary heart disease, independent of other risk factors. There is no doubt that patients with both obesity and diabetes are at far greater risk than those who are only obese (4). side of the energy balance equation has increased significantly in recent years. The output side is, of course, complicated by any changes in activity or exercise level that may spontaneously occur or may be purposely induced concomitantly with caloric restriction. The role of exercise in body-weight regulation and in weight-loss programs is addressed by Horton in a separate article in this issue. SHOULD WEIGHT REDUCTION IN NIDDM OBESE PATIENTS BE ATTEMPTED? The metabolic improvements achieved by weight reduction in obese diabetic patients are indisputable, but it is equally clear that most attempts to sustain the reduced body weight are doomed to failure (7-9). Before considering how best to achieve body-weight reduction, the pros and cons of making this effort must be carefully considered. First, it is becoming increasingly apparent that obesity is not generally a disease of the gourmand. Probably a very small percentage, generally found only among the severely obese (>100% above normal weight for height and sex), truly ingest excessive amounts of food, and, indeed, appear to have a defective regulation system for body weight, control of food intake, and maintenance of energy balance (10). Growing evidence shows that most obese people have relatively stable body weight and, in fact, defend that spontaneously achieved weight against decreases and further increases in body weight. Body weight is regulated rather tightly, but around an elevated level. Thus, the regulatory system appears to be intact and functioning well in most obese people. This stable body weight, which may change gradually throughout adult life, is greatly dependent on genetic background (11-14). Thus, there may be a biological basis for the great difficulty in maintaining a weight loss, which is encountered by most who have been successful in initially losing weight (15). Maintenance of a reduced body weight may require a continual restriction of caloric intake or a semistarvation condition, which may be achievable only in individuals with unusually high motivation—at least until better means of treatment are discovered. Adding to the complexity of the issue of body-weight regulation is the strong evidence that the body, when confronted with a reduced caloric intake, can make profound changes in its own energy efficiency. The efficiency with which calories are used appears to be greater when calories are restricted, thus not always resulting in the rate of weight loss that might have been predicted based on usual intake at the prereduction body weight. This concept, dubbed luxusconsumption by Neumann (16), has received both support and criticism, because the measurements necessary to prove the presence of relatively small adaptations in energy processing are difficult to carry out for the long periods required and with the accuracy needed. Methods are improving, and understanding of the metabolic consequences of caloric restriction is growing. Scientific attention to the output 184 WHAT IS THE BEST WEIGHT-LOSS PROGRAM? Those who take insulin must assure that any dietary changes aimed at weight loss do not simultaneously produce extreme highs or lows in blood glucose. Clearly, any weight-loss program should be undertaken only with careful involvement of the health-care team. Much remains unknown about the relative merits of various weight-reduction regimens, and the optimal method for producing sustained weight loss has yet to be identified. Nevertheless, a number of features should be considered in making a choice among the available approaches. Nutritional balance. The prescribed diet should be nutritionally complete, providing for a variety of foods. The diet should be relatively easy to follow and completely safe, so as to be sustainable for a long period. Most important, it should lead to good eating habits and should not involve high levels of intake of any single food. There is no "magic diet." Level of caloric restriction. Moderate caloric restriction, perhaps a reduction of 500-1000 kcal, may be useful in producing gradual sustained weight loss. Calorie reduction of 25-50% from normal levels will lead to weight loss because this amount of reduction exceeds the body's ability to make thermogenic adaptations. This intake level should, however, be sufficient to allow a balanced, nutritionally complete diet of normal foods (17). Provision for maintenance program. Nearly all dietary weight-loss plans result in at least short-term loss. The greatest difficulty rests in sustaining that loss. At this time, it appears that to stabilize body weight at a reduced level requires the ingestion of at least a mildly restricted caloric level forever. Fewer calories relative to prior caloric intake levels must be taken to maintain the reduced body-weight level. Thus, there must be support for adhering to a long-term modification of previous eating levels and a lifetime commitment to sustaining the reduced weight level. Because physiological or pharmacological treatments aimed at weight loss are not yet available to alter the mechanisms underlying obesity or to move the "setpoint" for body weight, programs that use behavioral modification or behavioral approaches to produce adherence to altered dietary regimens are most commonly recommended. Recent studies have sought to modify health-related attitudes, including health motivation, DIABETES CARE, VOL. 11, NO. 2, FEBRUARY 1988 B.C. HANSEN perceived susceptibility (including acceptance of the diagnosis), perceived severity, perceived benefits and costs, and perceived self-efficacy (18). Successful changes in health attitudes and health behavior may relate to the setting of proximal, rather than distal, goals for weight loss and small, rather than big, changes in intake and weight, but the relative efficacy of these admonitions remains to be determined. Most studies that have attempted to use behavior therapy for obesity have been limited in their interpretation by relatively small sample sizes and generally short- or moderate-duration follow-up periods. Some have involved multifaceted treatment approaches (19,20), whereas others have tested single concepts such as the potential value of computer-assisted therapy in providing feedback and reinforcement (21,22). Specific learning principles and their potential value in treatment of obesity require much further study (23). Until then, the limitations of behavioral treatment of obesity must be accepted (24). Most obese people will not enter an outpatient treatment program; of those who do, most will not lose significantly; and most who do lose will regain the lost weight (25). WHAT ARE METABOLIC OUTCOMES OF CALORIC RESTRICTION AND SUCCESSFUL WEIGHT REDUCTION? Improved glucose tolerance and a decrease in elevated fasting glucose levels result from weight reduction in both severely obese (26) and moderately obese (27,28) individuals. This improvement in glucose disposal can be observed even when weight loss is modest (29,30). Significant caloric restriction leads to a rapid fall in fasting plasma insulin and postprandial insulin secretion in obese individuals showing initial hyperinsulinemia but leads to a rise in insulin and postprandial insulin secretion for those with hypoinsulinemia, restoring both groups in the direction of normal (31-33). Postabsorptive plasma insulin levels decrease with weight reduction (34). Nagulesparan et al. (35) have, however, shown that the response to dietary therapy was significantly poorer in diabetes of long duration. Fasting plasma glucose levels and insulin responses were less improved, even with similar weight losses, when compared with the effects of dieting on patients recently diagnosed as having diabetes. It is not known whether sustained weight reduction in newly diagnosed diabetic patients can alter the long-term course of the disease. The potential for improvement in insulin action with weight reduction is also suggested by the frequent finding of an at least partial relationship between degree of obesity and insulin action (36-38). In several studies, weight reduction has led to improvement in other measures of insulin action and in other parameters (39). For example, weight reduction has produced an increased insulin sensitivity, which is associated with an increase DIABETES CARE, VOL. 11, NO. 2, FEBRUARY 1988 in the previously subnormal glucose oxidation rates and nonoxidative glucose uptake rates (34). These changes probably result from both increased glucose storage and inhibition of splanchnic glucose output with decrease in weight. The increased lipid oxidation rate associated with the impaired glucose utilization was reduced after weight loss in both individuals with impaired glucose tolerance and those with diabetes (34). Fasting plasma glucagon is decreased and glucagon suppression in response to glucose is enhanced with weight reduction (40,41). Weight reduction also produces a sustained reduction of proteinuria as early as the 1st mo of diet therapy. Such improvement holds the possibility that weight reduction may, therefore, slow the development of clinical nephropathy or end-stage renal disease (42). A reduction of total serum triglycerides occurs with weight reduction (43,44); this is associated with a decrease in elevated low-density lipoprotein and an increase in highdensity lipoprotein (44; Kissebah and Schectman, in this issue). Weight reduction also leads to more general benefits, including improved pulmonary function (45,46); lowering of elevated blood pressure (47-49); reduced risks of surgery (50-53), e.g., fewer wound infections and less pneumonia; and reduced likelihood of arthritic and musculoskeletal problems (54-56). In summary, many physiological functions are improved through weight loss by obese individuals. Thus, the impaired glucose tolerance may be normalized, whereas improvement in diabetic patients may be only partial even with significant weight reduction. Thus, timing of weight loss relative to the progression of the disease may be of critical importance to the long-term prognosis and possibly to the prevention of the development of diabetes. WHICH HYPOCALORIC DIET, IF ANY, IS OPTIMAL FOR OBESE DIABETIC PATIENTS? Because modest caloric restriction results in very slow weight loss, recent studies have examined the possibility of using more marked caloric reduction for relatively short periods. Very low calorie (VLC) diets may be needed to produce more rapid and significant weight reduction, particularly for severely obese individuals or those requiring high doses of insulin. VLC diets generally provide 500-800 kcal/day, contain a high-quality protein, and include vitamin and mineral supplementation. These diets are a considerable improvement over the previous high-protein diets, which produced significant cardiac dysfunction. Although originally tested in obese but otherwise healthy individuals, these VLC diets have now been studied in a small number of NIDDM patients (57) and are reported to be similarly effective and safe in shortterm applications. Further studies are needed to examine possible negative outcomes in people with diabetes 185 DIET IN OBESITY before VLC diets can be recommended. VLC diets may contain either a high proportion of protein, sometimes referred to as the protein-sparing modified fast (26,5860), or may be a more balanced caloric distribution containing protein, carbohydrate, and fat in varying ratios. Both have been shown to be effective, but it is unclear whether there are relative advantages or disadvantages to differing proportions of food sources (61). Equicaloric VLC diets containing moderate or minimal carbohydrate with higher or lower protein levels have been compared. Carbohydrate-containing diets may provide for better maintenance of muscle glycogen and sustained exercise tolerance compared with a minimum-carbohydrate diet (62). It has been shown that a diet supplemented with carbohydrate reduces the amount of ketosis. Adverse effects due to ketogenesis may thus be minimized by the use of a hypocaloric diet that contains carbohydrate. On the other hand, diets providing higher protein levels may provide for better nitrogen balance despite low caloric intakes (63). Other researchers have been unable to find differences in protein loss with higher or lower protein levels (64,65). Concern remains about prolonged use of VLC diets that can result in significant endogenous protein metabolism. Many factors undoubtedly interact to determine the amount of body protein loss with caloric restriction, e.g., initial total lean body mass, degree of caloric reduction, dietary protein quality and quantity, and possibly, level of circulating hormones and substrates. Great individual variability in nitrogen loss (66) primarily associated with initial lean body mass (57) has been observed. At least a portion of the nitrogen loss may be appropriate because obese people have increased lean body mass. A proportionate loss of body fat and protein may be functional in the dieting individual for relatively short periods of caloric restriction. In a recent study, a diabetic group showed no greater loss of lean tissue than a nondiabetic group (57). It must be emphasized that VLC diets require vitamin and mineral supplementation to meet the recommended daily allowances (67). Potassium supplementation is particularly important (59). These VLC diets, when used with medical supervision, lead to both significant weight loss and improved metabolic status. In NIDDM, the need for oral hypoglycemic agents or insulin may be reduced or eliminated (26). It is essential that patients be carefully monitored during the first few days of a VLC diet to ensure appropriate adjustments in insulin dose. Glucose and lipid levels may be normalized and fat appears to be lost in increasing proportion as the diet is sustained. Recent studies have addressed the question of whether one or another of these hypocaloric diets has a greater effect on reducing appetite or on elevating mood. Comparison of an 800-kcal (58% protein, 42% fat, by weight) to a 1000-kcal (42% protein, 30% fat, 28% carbohydrate) diet showed both decrease in appetite and elevation of psychological well-being regardless of the composition of the diet (68,69). The differences in sub- 186 strate distribution appear to have no measurable effect on either appetite or mood that would produce an advantage for one diet over the other. The effects of long-term VLC diets in diabetic individuals require further study; however, nothing to date suggests that any unique problems have been or will be encountered in obese diabetic patients compared with obese nondiabetic groups. Much is yet to be learned about the importance of the timing of weight reduction in relation to the onset of diabetes and the long-term effects of sustained caloric reduction and/or weight normalization on the progression and severity of diabetes. There are no results of long-term studies of weight reduction in NIDDM patients when the weight-reduction process was initiated in the earliest phases of the disease. Thus, evidence that long-term prevention and/or alteration of the course of the disease can be the result of significant weight reduction followed by a weight-maintaining program is yet to be developed. Evidence suggests, however, that the effect of weight reduction on severe NIDDM may be less than in mild or early diabetes (35). Thus, it appears that the earliest possible treatment of obesity may have the greatest potentially beneficial effect (70). The possible effects of weight reduction before the onset of clinically diagnosed diabetes, e.g., at a point when an individual is normoinsulinemic but shows evidence of 3-cell hyperresponsiveness or at a point where the individual is hyperinsulinemic but not yet hyperglycemic (71), remain to be determined. Obesity remains an enigma, as does the obesity-diabetes connection. Only through better understanding of the mechanisms underlying these problems can obesity be effectively treated. Meanwhile, the difficult choices on how hard to press patients toward caloric restriction and weight loss must be made, noting that even moderate success will be, most often, only temporary. Although normalization of body weight is a desirable goal, it is clear that even modest caloric restriction may be beneficial because of the positive effects on blood glucose and requirements for insulin and oral antidiabetic agents. 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Diabetologia 29:713-19, 1986 DIABETES CARE, VOL. 11, NO. 2, FEBRUARY 1988