Download Dietary Considerations for Obese Diabetic Subjects

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
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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.
ACKNOWLEDGMENTS
The assistance of Alexis Thomas and Robert Haskins
in the preparation of this manuscript is appreciated.
This work was supported in part by NIH Grant DK37717 and the International Health Foundation.
REFERENCES
1. Blackburn GL, Read JL: Benefits of reducing revisited.
Postgrad Med J 60:13-18, 1984
2. Dublin LI, Marks HH: Mortality among insured overweights in recent years. Trans Assoc Life Insur Med Directors 35:235-66, 1951
DIABETES CARE, VOL. 11, NO. 2, FEBRUARY 1988
B.C. HANSEN
3. Simopoulos AP, Van Itallie TB: Body weight, health and
longevity. Ann Intern Med 100:285-95, 1984
4. Burton BT, Foster WR, Hirsch J, Van Itallie TB: Health
implications of obesity: an NIH consensus development 24.
conference. Int j Obes 9:155-69, 1985
5. Kissebah A, Vydelingum N, Murray RW, Evans DJ, Hartz
AJ, Kalkhoff RK, Adams PW: Relation of body fat distri- 25.
bution to metabolic complications of obesity. ) Clin Endocrinol Metab 54:254-60, 1982
6. Kissebah AH, Evans DJ, Peiris A, Wilson CR: Endocrine 26.
characteristics in regional obesities: role of sex steroids.
In Proc Int Symp Metabolic Compile Human Obes. Amsterdam, Elsevier, 1985, p. 115-30
7. Stunkard AJ: Behavioral treatment of obesity—current sta- 27.
tus. Int j Obes 2:237-48, 1978
8. Stunkard AJ, Penick SB: Behavior-modification in the
treatment of obesity—problem of maintaining weight-loss.
Arch Gen Psychiatry 36:801-806, 1979
9. Drenick EJ: The prognosis of conventional treatment in 28.
severe obesity. In Recent Advances in Obesity Research
III. Bjorntorp P, Cairella M, Howard AN, Eds. London,
Libbey, 1981, p. 80-84
10. Keen H, Thomas BJ, Jarrett RJ, Fuller JH: Nutrient in- 29.
take, adiposity, and diabetes in man. Br Med 11:655-58,
1979
11. Tattersall RB, Pyke DA: Diabetes in identical twins. Lan- 30.
cet 2:1120-25, 1972
12. Bouchard C, Sabard R, Despres J, Tremblay A, Leblanc
C: Body composition in adopted and biological siblings.
Hum 8/0/57:61-75, 1985
31.
13. Stunkard AJ, Foch TT, Hrubec Z: A twin study of human
obesity. JAMA 256:51-54, 1986
14. Stunkard AJ, Sorenson TIA, Hanis C, Teasdale TW, Chakraborty R, Schull WJ, Schulsinger F: An adoption study 32.
of human obesity. N Engl I Med 314:193-98, 1986
15. Poehlman E, Despres J, Marcotte M, Trembaly A, Theriault G, Bouchard C: Genotype dependency of adaptation 33.
in adipose tissue metabolism after short-term overfeeding.
Am j Physiol 250:E480-95, 1986
16. Neumann RO: Experimented Beitrage zur Lehre von dem
taglichen Nahrungsbefard des Menschen unter beson- 34.
derer Berucksich tigung der notendigen Eiweissmenge.
Arch Hyg 45:1-87, 1902
17. Clausen JD, Silfen M, Coombs J, Ayers W, Altschul AM:
Relationship of dietary regimens to success, efficiency, 35.
and cost of weight loss. ) Am Diet Assoc 77:249-57,
1980
18. Rosenstock IM: Understanding and enhancing patient
compliance with diabetic regimens. Diabetes Care 8:61016, 1985
36.
19. Wilson GT, Brownell KD: Behavior therapy for obesity:
an evaluation of treatment outcome. Adv Behav Res Ther
3:49-86, 1980
37.
20. Nutzinger DO, Cayiroglu S, Sachs G, Zapotoczky HG:
Emotional problems during weight reduction: advantages
38.
of a combined behavior therapy and antidepressive drug
therapy for obesity. I Behav Ther Exp Psychiatry 16:21721, 1985
21. Burnett KF, Taylor CB, Agras WS: Ambulatory computer39.
assisted therapy for obesity: a new frontier for behavior
therapy. / Consult Clin Psychol 53:698-703, 1985
22. Stunkard AJ: From explanation to action in psychosomatic
40.
medicine: the case of obesity. Psychosom Med 37:195236, 1975
23. Dahms WT, Moltich ME, Bray GA, Greenway FL, Atkin-
DIABETES CARE, V O L . 1 1 , N O . 2, FEBRUARY 1988
son RL, Hamilton K: Treatment of obesity: cost-benefit
assessment of behavioral therapy, placebo, and two anorectic drugs. Am ) Clin Nutr 31:774-78, 1978
Foreyt JP, Goodrick GK, Giotto AM: Limitations of behavioral treatment of obesity: review and analysis. I Behav Med 4:159-74, 1981
Stunkard AJ: Behavioral treatments of obesity: failure to
maintain weight loss. In Behavioral Self-Management. Stuart
RB, Ed. New York, Brunner/Mazel, 1977
Bistrian BR, Blackburn GL, Flatt J-P, Sizer J, Scrimshaw
NS, Sherman M: Nitrogen metabolism and insulin requirements in obese diabetic adults on a protein-sparing
modified fast. Diabetes 25:494-504, 1976
Doar JWH, Thompson ME, Wilde CE, Sewell PFJ: Influence of treatment with diet alone on oral glucose tolerance test and plasma sugar and insulin levels in patients
with maturity-onset diabetes mellitus. Lancet 2:1263-66,
1975
Hadden DR, Montgomery DAD, Skelly RJ, Trimble ER,
Weaver JA, Wilson EA, Buchanan KD: Maturity onset diabetes mellitus: response to intensive dietary management. Br Med J 3:276-78, 1975
Bennett PH, Rushforth NB, Miller M, LeCompte PM: Epidemiologic studies of diabetes in the Pima Indians. Rec
Prog Horm Res 32:333-76, 1976
Rendell M, Ross DA, Drew HM, ZarrielloJ: Endogenous
insulin secretion measured by C-peptide in maturity-onset
diabetes controllable by diet alone. Arch Intern Med
141:1617-22, 1981
Baxter D, Stanton K, Lazarus NR, Keen H: The relation
between insulin and adipocyte insulin receptors during
treatment of human obesity. Eur) Clin Invest 8:361-72,
1978
Stanik S, Marcus R: Insulin secretion improves following
dietary control of plasma glucose in severely hyperglycemic obese patients. Metabolism 29:346-50, 1980
Kosaka K, Kuzuya T, Akanuma Y, Hagura R: Increase in
insulin response after treatment of overt maturity onset
diabetes is independent of the mode of treatment. Diabetologia 18:23-28, 1980
Golay A, Felber JP, Dusmet M, Gomez F, Curchod B,
Jequier E: Effect of weight loss on glucose disposal in
obese and obese diabetic patients. Int) Obes 9:181-90,
1984
Nagulesparan M, Savage PJ, Bennion LJ, Unger RH, Bennett PH: Diminished effect of caloric restriction on control
of hyperglycemia with increasing known duration of type
II diabetes mellitus. / Clin Endocrinol Metab 53:560-68,
1981
Bogardus C, Lillioja S, Mott DM, Hollenbeck C, Reaven
G: Relationship between degree of obesity and in vivo
insulin in man. Am J Physiol 248.E286-91, 1985
Yki-Jarvinen H, Koivisto VA: Effects of body composition
on insulin sensitivity. Diabetes 32:965-69, 1983
Nagulesparan M, Savage PJ, Unger RH, Bennett PH: A
simplified method using somatostatin to assess in vivo
insulin resistance over a range of obesity. Diabetes 28:98083, 1979
Peters EJ, Stuart CA, Prince MJ: Acanthosis nigricans and
obesity: acquired and intrinsic defects in insulin action.
Metabolism 35:807-13, 1986
Savage PJ, Bennion LJ, Bennett PH: Normalization of insulin and glucagon secretion in ketosis-resistant diabetes
mellitus with prolonged diet therapy. J Clin Endocrinol
Metab 49:830-33, 1979
187
DIET IN OBESITY
41. Savage PJ, Bennion LJ, Flock EV, Nagulesparan FM, Molt
D, Roth J, Unger RH, Bennett PH: Diet-induced improvement of abnormalities in insulin and glucagon secretion
and in insulin receptor binding in diabetes mellitus.) Clin
Endocrinol Metab 48:999-1007, 1979
42. Vasquez B, Flock EV, Savage PJ, Nagulesparan M, Bennion LJ, Baird HR, Bennett PH: Sustained reduction of
proteinuria in type 2 (non-insulin dependent) diabetes following diet-induced reduction of hyperglycemia. Diabetologia 26:127-33, 1984
43. Coronas R, Duran S, Gomez P, Romero H, Sastre A: Modified total fasting and obesity: results of a multicentric
study. IntjObes 6:463-71, 1982
44. Kannel WB, Gordon T, Castelli WP: Obesity, lipids, and
glucose tolerance: the Framingham Study. Am J Clin Nutr
32:1238-45, 1979
45. Sugarman HJ, Fairman RP, Baron PL, KwentusJA: Gastric
surgery for respiratory insufficiency of obesity. Chest 90:
81-86, 1986
46. Vaughan RW, Cork RC, Hollander D: The effect of massive weight loss on arterial oxygenation and pulmonary
function tests. Anesthesiology 54:325-28, 1981
47. Reisin E, Abel R, Modan M, Silverberg DS, Eliahou HE,
Modan B: Effect of weight loss without salt restriction on
the reduction of blood pressure in overweight hypertensive patients. N Engl) Med 298:1-6, 1978
48. Andrews G, MacMahon SW, Austin A, Byrne DG: Hypertension: comparison of drug and non-drug treatments,
fir Med) 284:1523, 1982
49. Manicardi V, Camellini L, Bellodi G, Coscelli C, Ferrannini E: Evidence for an association of high blood pressure
and hyperinsulinemia in obese man. J Clin Endocrinol
Metab 62:1302-304, 1986
50. Cruse PJ, Foord R: A five year prospective study of 23,649
surgical wounds. Arch Surg 107:206-10, 1973
51. Printen JK, Paulk SC, Mason EE: Acute postoperative wound
complications after gastric surgery for morbid obesity. Am
Surg 41:483-85, 1975
52. Beatty JD, Robinson GV: A prospective analysis of nosocomial wound infection after mastectomy. Arch Surg
118:1421-24, 1983
53. Kozol RA, Fromm D, Ackerman NB, Chung R: Wound
closure in obese patients. Surg Cynecol Obstet 162:44244, 1986
54. Silberberg R: Obesity and osteoarthrosis. In Medical
Complications of Obesity. Mancini M, Lewis B, Contaldo
F, Eds. London, Academic, 1979, p. 301-15
55. Aro S, Leino P: Overweight and musculoskeletal morbidity: a ten-year follow-up. Int I Obes 9:267-75, 1985
56. Hartz AJ, Fischer ME, Bril G, Kelber S, Rupley D Jr, Oken
B, Rimm AA: The association of obesity with joint pain
and osteoarthritis in the HANES data. / Chron Dis 39:31119, 1986
57. Henry RR, Wiest-Kent TA, Scheaffer L, Kolterman OG,
Olefsky JM: Metabolic consequences of very-low-calorie
diet therapy in non-insulin-dependent diabetic and nondiabetic subjects. Diabetes 35:155-64, 1986
188
58. Blackburn GL, Bistrian BR, Flatt JP, Sizer J: Role of a
protein-sparing modified fast in a comprehensive weight
reduction program. In Recent Advances in Obesity Research. Howard A, Ed. London, Newman, 1975, p. 27981
59. Bistrian BR, Blackburn GL, Stanbury JB: Metabolic aspects of a protein-sparing modified fast in the dietary
management of Prader-Willi obesity. N Engl ) Med
296:774-79, 1977
60. Hughes TA, Gwynne JT, Switzer BR, Herbst C, White G:
Effects of caloric restriction and weight loss on glycemic
control, insulin release and resistance, and atherosclerotic risk in obese patients with type II diabetes mellitus.
Am\Medll:l-M,
1984
61. Genuth S: Supplemented fasting in the treatment of obesity and diabetes. Am ) Clin Nutr 32:2579-86, 1979
62. Bogardus C, LaGrange BM, Horton ES, Sims EAH: Comparison of carbohydrate-containing and carbohydrate-restricted hypocaloric diets in the treatment of obesity. /
Clin Invest 68:399-404, 1981
63. Hoffer LJ, Bristian BR, Young VR, Blackburn GL, Matthews DE: Metabolic effects of very low calorie weight
reduction diets. / Clin Invest 73:750-58, 1984
64. Yang MU, Van Itallie TB: Variability in body protein loss
during protracted, severe caloric restriction: role of triiodothyronine and other possible determinants. Am / Clin
Nutr 40:611-22, 1984
65. Phinney SD, Bristrian BR, Kosinski E, Chan DP, Hoffer LJ,
Rolla A, Schachtel B, Blackburn GL: Normal cardiac
rhythm during hypocaloric diets of varying carbohydrate
content. Arch Intern Med 143:2258-61, 1983
66. Fisler JS, Drenick EJ, Blumfield DE, Swenseld ME: Nitrogen economy during very low calorie reducing diets: quality
and quantity of dietary protein. Am J Clin Nutr 35:471 —
86, 1982
67. Amatruda JM, Biddle TL, Patton ML, Lockwood DH: Vigorous supplementation of a hypocaloric diet prevents
cardiac arrhythmias and mineral depletion. Am ) Med
74:1016-22, 1983
68. Rosen JC, Hunt DA, Sims DAH, Bogardus C: Comparison
of carbohydrate-containing and carbohydrate-restricted
hypocaloric diets in the treatment of obesity: effects on
appetite and mood. Am j Clin Nutr 36:464-69, 1982
69. Rosen JC, Gross J, Loew D, Sims EAH: Mood and appetite
during minimal-carbohydrate and carbohydrate-supplemented hypocaloric diets. Am J Clin Nutr 42:371-79,
1985
70. Bennett PH, Knowler WC, Rushforth NB, Hamman RF,
Savage PJ: The role of obesity in the development of diabetes in the Pima Indians. In Diabetes and Obesity, Proc
Int Meet Endocrinol, 5th, 1978. Vague J, Ebling FJG, Eds.
Amsterdam, Excerpta Med., 1978 (Int. Congr. Ser. no. 454)
71. Hansen BC, Bodkin NL: Heterogeneity of insulin responses: phases leading to type 2 (non-insulin dependent)
diabetes mellitus in the rhesus monkey. Diabetologia
29:713-19, 1986
DIABETES CARE, VOL. 11, NO. 2, FEBRUARY 1988