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Lifestyle Interventions across the Continuum of Type 2 Diabetes:
Reducing the Risks of Diabetes
Marion J. Franz, MS, RD, CDE
Nutrition Concepts by Franz, Inc.
Minneapolis, MN
Abstract
Type 2 diabetes is a progressive disease resulting from defects in insulin action (insulin
resistance), insulin secretion (insulin deficiency), or both. The progressive decline in
beta-cell function requires that medical therapy progress from lifestyle interventions for
prevention of diabetes, to medical nutrition therapy (MNT) alone for diabetes
management, to MNT in combination with glucose-lowering medications that target the
multiple pathophysiologic aspects of diabetes, to MNT with insulin. MNT also
progresses from prevention of obesity or weight gain to improving insulin resistance to
contributing to improved metabolic control of glucose, lipids, and blood pressure.
However, MNT is important throughout the continuum of diabetes and its medical
management. Early diagnosis and aggressive therapy decrease the risk of diabetes-related
complications.
Key Words: lifestyle interventions, medical nutrition therapy, diabetes prevention,
diabetes treatment, weight loss, carbohydrate
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Introduction
Worldwide, the number of persons with diabetes and at risk for diabetes is increasing at
an alarming rate. Over the next decade the number is expected to grow by 25%, which is
largely driven by the rising prevalence of obesity and inactivity (1). Today, more than 1.1
billion adults worldwide are overweight and 312 million are obese (2). In the past 20
years, the rates of obesity have tripled in developing countries that have adopted a
Western lifestyle with the Middle East, Pacific Islands, Southeast Asia, India and China
facing the greatest increase. Consequently, the number of people with diabetes in these
countries is expected to increase from 84 million in 2000 to 200 million by 2010 and to
330 million by 2030 (1). The World Health Organization predicts that in less than a
decade, 60% of the worldwide population with diabetes will be in Asia.
In the United States, 20.8 million people of all ages are reported to have diabetes
(3). Of these, 14.6 million are diagnosed and 6.2 million are undiagnosed. At high risk for
type 2 diabetes are the greater than 41 million people estimated to have pre-diabetes and
the 47 million with metabolic syndrome.
To prevent and treat type 2 diabetes requires that persons at risk for and with
diabetes and health care-providers understand the etiology and progressive nature of the
disease. This understanding will mean that as the disease progresses, treatment and
management, including both nutrition therapy and medications, will also change and
progress. However, throughout the continuum of the disease process, lifestyle
interventions continue to be an essential component of therapy.
The Natural Progression of Type 2 Diabetes
Diabetes is defined as a metabolic disease characterized by hyperglycemia caused
by a deficient response of tissues to insulin or impairment in insulin secretion or both (4).
Pathogenic processes involved in the development of diabetes range from autoimmune
destruction of the β-cells of the pancreas with resultant insulin deficiency—type 1
diabetes—to abnormalities that result in resistance to insulin action and an inadequate
compensatory insulin secretory response—type 2 diabetes. This form of diabetes
frequently goes undiagnosed for many years as hyperglycemia develops gradually and
persons do not notice the classic symptoms of diabetes. It is usually associated with a
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strong genetic predisposition and risk of developing the disease increases with age,
obesity, and lack of physical activity.
Type 2 diabetes is characterized by two major pathophysiological abnormalities:
insulin resistance, which is associated with increased hepatic glucose production and
reduced glucose clearance, and impaired beta cell insulin secretion—both basal and
glucose-stimulated (5). In most individuals who develop diabetes, insulin resistance
begins and progresses many years before the development of diabetes. Impaired beta cell
secretory function, however, must be present before hyperglycemia develops (6).
Impaired insulin secretion has been demonstrated in individuals with impaired fasting
glucose concentrations between 100 and 125 mg/dL and deteriorates further as glucose
concentrations rise above this (7). By the time diabetes develops, the individual has lost
as much as 50% of beta cell function. The rising glucose levels further compromise
insulin secretion and action—known as glucose toxicity.
In type 2 diabetes, the normal biphasic insulin response to glucose characterized
by a rapidly peaking (at ~2 to 3 minutes), short-duration (~10 minutes) initial phase
followed by a delayed, prolonged second phase is altered resulting in postprandial
hyperglycemia (8). The first-phase insulin response in type 2 diabetes is also inadequate
in suppressing alpha-cell glucagon secretion, resulting in glucagon hypersecretion and
increased hepatic glucose production causing or exacerbating postprandial hyperglycemia
(9). The second major metabolic abnormality is characterized by a reduction in the ability
of insulin to act on target tissues—muscle, liver, and fat cells. Fasting hyperglycemia
results from a decrease in the suppressive effect of insulin on hepatic glucose production.
As type 2 diabetes progresses, insulin production and secretion progressively decline and
without treatment increasing hyperglycemia ensues. Recently, Monnier et al (10)
suggested that deterioration of glucose homeostasis occurs in a three-step process: 1) loss
of postprandial control; 2) deterioration of glycemic control during the prebreakfast and
postbreakfast periods, referred to as the dawn phenomena; and 3) sustained
hyperglycemia over the nocturnal period resulting in fasting hyperglycemia.
What is essential, however, is effective therapy to lower elevated blood glucose
concentrations as early as possible to prevent the deleterious effects of hyperglycemia.
The progressive loss of beta cell secretory function means that patients with diabetes
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usually require more medication(s) over time to maintain the same level of glycemic
control and that eventually exogenous insulin will be required (11).
The progression of type 2 diabetes and the changes in lifestyle interventions and
medications that must occur over the continuum of prevention and management are
illustrated in Figure 1. Preventing obesity and increasing physical activity is a high
priority for the prevention of diabetes and other chronic diseases. Identifying individuals
at risk and implementing prevention interventions is essential. However, as the disease
progresses appropriate treatment is essential to prevent and manage the long-term
complications of diabetes.
Overweight and Obesity: Halting the Epidemic
Although some obesity researchers suggest that it may not be possible to decrease the
current numbers of overweight and obese persons in the United States, preventing the
increase that has been occurring at an increasing rate is an important goal (12). In
programs designed to increase physical activity and decrease energy intake, the physical
activity goal is to increase the number of steps an individual takes throughout the day by
about 2,000 steps above baseline and the decreased energy intake goal is to eat 100 fewer
calories per day (13).
The hope is that slowing the rising prevalence of obesity will have a positive
impact on slowing the epidemic of diabetes and other chronic diseases. Can this be
accomplished? Thus far, nothing seems to have slowed the increase in both obesity and
diabetes, but there is general agreement in the medical field and government that
something needs to be tried.
Insulin resistance has been assumed to be the common pathogenesis for the
cluster of risk factors that predict diabetes and cardiovascular disease (CVD). However,
an increase in free fatty acids may also be a common denominator, and this requires
obesity, in particular, intra-abdominal obesity, to be present (14). An excess
accumulation of visceral fat around and inside abdominal organs results in an increase in
flux of free fatty acids to the liver causing an increase in insulin resistance, to muscles
impairing insulin-mediated glucose uptake and a potential apoptosis of beta cells.
However, other adipocytes are also metabolically toxic producing inflammatory
cytokines, adipokines and a decrease in adiponectin resulting in an increase in insulin
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resistance and inflammation of blood vessels. These deleterious effects are referred to as
lipotoxicity.
First-line therapy for disease reduction for diabetes and CVD includes stopping
cigarette smoking and reducing glucose, low-density lipoprotein cholesterol, and blood
pressure to recommended goals (15). Medical nutrition therapy includes a reduction of
body weight by 7% to 10% in overweight and obese individuals, an increase in physical
activity to 30 to 60 minutes per day of moderate-intensity physical activity, and
modification of an atherogenic diet, which includes an increase in whole grains and fiber
and a decrease in saturated and trans fatty acids and dietary cholesterol (15,16).
It is often assumed that a high carbohydrate intake contributes to insulin
resistance and to increases in triglyceride concentrations. In general, observational and
intervention studies provide support for the concept that high-carbohydrate diets, at the
very least, do not adversely affect insulin sensitivity and may be beneficial for insulin
sensitivity (17,18). Furthermore, carbohydrate appears to only increase triglyceride levels
when energy intake and weight are constant and carbohydrate intake is ~55% of total
energy intake (19). High intakes of dietary fats, especially saturated and trans fatty acids,
appear to be associated with a decline in insulin sensitivity. Excess energy intake,
regardless of the energy source, and positive energy balance contribute to insulin
resistance through the production of obesity.
Pre-Diabetes: Preventing Diabetes
The increase in diabetes worldwide has made prevention of type 2 diabetes a top priority,
based on the belief that preventing the disease will also prevent its long-term
consequences. Hyperglycemia not sufficient to meet the diagnostic criteria for diabetes is
categorized as either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)
depending on whether it is identified through a fasting plasma glucose or an oral glucose
tolerance test. Recently, IFG and IGT have been officially termed “pre-diabetes”
indicating the relatively high risk for development of diabetes and cardiovascular disease
in these patients (4).
Six clinical trials have compared lifestyle interventions to a control group with
risk reduction for type 2 diabetes ranging from 33% to 67% (20). The two most
frequently cited are the Finnish Prevention Study (11) and the Diabetes Prevention Study
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(DPP) (21), both reporting a risk reduction of 58% from lifestyle interventions compared
to a control group. Both studies emphasized moderate weight loss, a lower energy, low-
fat food intake, and increased physical activity. Structured programs that emphasized
regular contact with study participants were necessary to accomplish the study objectives.
Although intensive lifestyle intervention is the safest, most efficacious, and
usually the least expensive ways to prevent diabetes, several clinical trials have shown
that drugs (i.e., metformin, troglitazone, acarbose, orlistat, rosiglitazone) can also lower
or delay progression from pre-diabetes to diabetes. The efficacy of metformin in
decreasing the incidence of type 2 diabetes was shown in the DPP (21). A study in
women treated for gestational diabetes during their pregnancy using the thiazolidinedione
troglitazone (removed from the market because of concern with hepatotoxicity) reported
a 55% risk reduction (22). Most recently, the Diabetes Reduction Assessment with
Ramipril and Rosiglitazone (DREAM) reported that another thiazolidinedione,
rosiglitazone, combined with a healthful diet and physical activity reduced the risk of
developing diabetes by 60% in people with pre-diabetes compared to placebo (23). The
debate about lifestyle intervention or medication recommendations for prevention has
been whether the intervention-induced reduction is caused by a long-term effect on the
basic pathophysiologic processes leading to diabetes or by masking of incident cases of
diabetes by pharmacologic treatment of dysglycemia. As a result, the DREAM washout
period results, presented at the International Diabetes Federation 19th World Diabetes
Conference, were highly anticipated (24). Hopes by proponents of medication use were
dashed when it was reported that at the end of the washout period, those taking
rosiglitazone progressed to diabetes at the same rate as participants receiving placebo.
The results suggest that rosiglitazone delays progression to diabetes during treatment, but
the effects do not persist when therapy is discontinued. The American Diabetes
Association recently recommended that only metformin be considered as drug therapy for
individuals with pre-diabetes (25). Cost, weight gain, and an increase in heart failure
were concerns related to use of rosiglitazone.
Although medical professionals are often skeptical about the ability of individuals
to make permanent lifestyle changes, support for the role of lifestyle interventions comes
from the recently published seven-year follow-up of participants in the Finnish Diabetes
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Study (26). This is the first study to report that an intensive lifestyle intervention in
people with pre-diabetes results in continued lifestyle changes, which remain even after
the individual lifestyle counseling has stopped. After a median of four years of active
lifestyle intervention, participants still free of diabetes were followed for another three
years, at which time a 43% lower diabetes risk in the intervention group was reported.
Although the 58% risk reduction during the original active trial period was higher,
Tuomilehto reports this was due to statistical facts (27). The cumulative incidences
became higher in both groups, which reduced the ratio, whereas the absolute risk
difference between the original randomization groups remained about the same or even
increased a little. The degree of risk reduction was related to the participants’ success in
achieving the intervention goals of moderate weight loss, reduced intake of total and
saturated fat and increased intake of dietary fiber, and increased physical activity during
the original randomized trial period. In regard to safety of pharmacologic and lifestyle
interventions, lifestyle interventions are safe and promote healthy behaviors that have
multiple health benefits beyond diabetes prevention. The challenge for medical
professionals is how to implement the needed intensive lifestyle intervention programs
into their medical centers and communities.
Diabetes: Achieving Euglycemia
The goal in managing patients with diabetes is to provide each patient with the
opportunity to achieve glucose levels as close to normal as possible without significantly
increasing his or her risk for additional complications such as hypoglycemia, and taking
into account the presence of comorbid conditions, expected longevity of individuals, and
their ability to adhere to therapeutic regimens including lifestyle changes (28). The target
hemoglobin A1c (A1C) value set by the American Diabetes Association is less than 7%
(29), while the American College of Endocrinology recommends a target A1C less than
6.5% (30). Of equal concern are optimal lipid levels and blood pressure goals.
Clinical trials and outcome studies of medical nutrition therapy (MNT) for
diabetes have reported decreases in A1C of ~1% in type 1 diabetes and 1–2% in type 2
diabetes, depending on the duration of diabetes (31). Meta-analysis of studies in
nondiabetic, free-living subjects report that MNT reduces LDL cholesterol by 15–25
mg/dl (32). After initiation of MNT, improvements in glucose and lipids are apparent in
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six weeks to three months. Meta-analysis and expert committees also support the role of
lifestyle modification in treating hypertension (33). Moderate-intensity exercise may lead
to a reduction in A1C value slightly more than 0.5% (34).
Medical Nutrition Therapy. Although there are similarities, MNT for individuals with
diabetes differs in several aspects from the recommendations for prevention, but basic to
both is the recommendation that individuals achieve optimal nutrition through healthful
food choices and a physically active lifestyle (35,36). Although lifestyle interventions
appear superior to medication use for prevention of diabetes, antidiabetes drugs are
nevertheless needed for the next stage in the continuum of diabetes. However, MNT
continues to be important, but as the disease progresses, medications—including insulin
—need to be combined with nutrition therapy.
As individuals move from being primarily insulin resistant to insulin resistant
with insulin deficiency, the therapeutic focus shifts from emphasis on weight loss to
emphasis on glucose, lipid, and blood pressure control (35). Although moderate weight
loss may be beneficial for some individuals, those who are primarily insulin resistant, as
insulin deficiency progresses for many it is often too late for weight loss to improve
glucose control dramatically (37,38). At later stages of the disease when medications—
including insulin—need to be combined with nutrition therapy, prevention of weight gain
often becomes an issue, although glycemic control must take precedence over concern
about weight. Thus far no study has reported weight loss and maintenance for a long
enough time period to know if there are long-term benefits of weight loss on prevention
of diabetes complications. The Look AHEAD (Action for Health in Diabetes) trial is a
12-year multicenter trial examining the effects of weight loss achieved through an
intensive lifestyle program in overweight and obese individuals with type 2 diabetes (39).
The goal is for individuals to lose 7-10% of their body weight and maintain the weight
loss for the duration of the study. Examined will be the effects of weight loss on
cardiovascular disease, diabetes control, myocardial infarction and stroke.
Achieving an ideal body mass index (BMI) has been recommended for people
with diabetes (40). But is this achievable by the majority of persons with or without
diabetes and, if not, should advice be given that is not achievable? To answer the
question about expected weight loss from weight loss interventions, a systematic review
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of randomized clinical trials for weight loss with a minimum duration of one year was
undertaken (41). Eighty studies with a total of 24,698 subjects, primarily completers,
were identified and the data were pooled to determine the mean weight loss from eight
different interventions used in the trials—diet alone, diet and exercise, exercise alone,
meal replacements, very-low-calorie diets, orlistat, sibutramine, and advice alone. A
mean weight loss of 5 to 8.5 kg (5 to 8.7% of baseline weight) was observed in the first
six months from interventions involving a reduced energy intake diet and/or weight loss
medications; weight loss plateaus at approximately six months. In studies extending to 48
months, a mean 3 to 6 kg of weight loss was maintained. Adaptive mechanisms occur
with a reduced energy intake—hormonal regulation (42), adaptive thermogenesis
requirements leading to a decrease in energy expenditure (43), decline in weight-
maintenance energy requirement (44)—to name just a few that appear to prevent the
majority of “dieters” from achieving an ideal BMI.
The data from the studies in the systematic review (41) in which the subjects had
diabetes was then pooled to determine weight loss and affects on A1C levels (Table 1)
(45). Weight loss again plateaus at six months and it appears that weight loss may be
more difficult in people with diabetes as suggested by Wing et al in 1987 (46).
Improvement in glycemic control may be due to the decrease in total energy intake rather
than to weight loss (47,48). The beneficial effects on blood glucose control begin to occur
before much weight loss, suggesting the focus on lifestyle interventions should be on a
reduced energy intake rather than weight loss. Even in persons with diabetes the benefits
of bariatric surgery on blood glucose occur quickly suggesting the improvement is due to
the diversion of nutrients away from the gastrointestinal tract and by delivery of
incompletely digested nutrients to the ileum rather than by the weight loss per se (49).
Persons with diabetes can benefit from comprehensive medical nutrition therapy,
which is individualized based on beta-cell function, pharmacotherapy, and other
metabolic abnormalities; however, it is essential to take into account an individual’s
personal and cultural preferences and willingness and ability to change (35). The
American Diabetes Association (ADA) also recommends that the pleasure of eating
should be maintained by only limiting food choices when indicated by scientific
evidence. Table 2 is a summary of key ADA nutrition recommendations.
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Monitoring carbohydrate is a key strategy in achieving glycemic control. Over 20
studies in subjects with type 1 or type 2 diabetes, ingestion of a variety of starches or
sucrose, both acutely and up to six weeks, produced no significant differences in
glycemic response if the amount of carbohydrate is kept similar (50). This is the basis of
carbohydrate counting, a method of food and meal planning commonly implemented by
persons with diabetes. Doses of insulin and insulin secretagogues can be matched to the
carbohydrate content of the meals (51). By testing pre- and postprandial glucose, glucose
goals can be achieved with a variety of foods. If glucose goals are not being achieved,
medications need to adjusted or added. Many individuals with diabetes also have
dyslipidemia and hypertension, so decreasing saturated and trans fat, cholesterol, and
sodium intake, should also be a priority. These interventions should be implemented as
soon as the diagnosis of diabetes is made in order to prevent or treat the chronic
complications of diabetes.
Not to be forgotten is the important role of physical activity and exercise in the
management of diabetes. Low cardiorespiratory fitness and physical inactivity are
independent predictors of all-cause mortality in type 2 diabetes regardless of weight (52)
and even increased BMI did not increase mortality risk in fit men with type 2 diabetes
(53). There is a stepwise relation between fitness and mortality that is evident within all
BMI strata which is independent of body fat percentages.
The ADA recommends at least 150 minutes per week of moderate-intensity
aerobic physical activity, distributed over at least three days and with no more than two
consecutive days without physical activity (54). Resistance training is also effective an
improving glycemia and, in the absence of proliferative retinopathy, people with type 2
diabetes can be encouraged to perform resistance exercise three times a week.
Glucose-Lowering Medications. Pharmacological options before the mid-1990s were
limited to sulfonylureas and insulin. Since that time, new classes of medications have
been introduced into the market that target the mechanisms underlying insulin resistance
and insulin deficiency. Administered as monotherapy, each of the classes of medications
(except alpha-glucosidase inhibitors) results in an approximate 1% to 2% reduction in
A1C compared to placebo in controlled clinical trials (55). Oral agents include insulin
secretagogues (sulfonylureas and glinides), insulin sensitizers (metformin and
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thiazolidinediones), and drugs that delay absorption of carbohydrate from the
gastrointestinal tract (alpha-glucosidase inhibitors).
Two new classes of insulin secretagogues have recently been approved by the
Food and Drug Administration. Exenatide, an injectable drug, is an analogue of exendin
4, a peptide found in the saliva of the Gila monster that has similar actions to glucagon-
like peptide (GLP-1). It inhibits glucagon secretion and stimulates endogenous insulin
secretion through a mechanism that is different from sulfonylureas and is approved for
use in combination with sulfonylureas, metformin, and/or thiazolidinediones (56).
Sitagliptin, an insulin secretagogue, inhibits the enzyme dipeptidyl peptidase type IV
(DPP-IV), which degrades endogenously secreted incretins like GLP-1. This prolongs the
action of the incretins, which enhance insulin secretion in a glucose-dependent manner
and inhibit glucagon secretion (57). This drug is approved as monotherapy or in
combination with metformin or thiazolidinediones.
Insulins. Long- or intermediate-acting insulins (insulin glargine, insulin determir, and
NPH) provide basal insulin needs for persons with diabetes and are administered once or
twice daily. In persons with type 2 diabetes taking glucose-lowering medications, a basal
insulin is often added at night when fasting glucose levels are elevated. In individuals
whose postprandial glucose concentrations are elevated, rapid- or short-acting insulin
(insulin lispro, insulin aspart, insulin glulisine, regular or inhaled insulin) is needed. The
newer insulins provide flexibility and normalization of lifestyle. Persons taking NPH and
regular must eat at specific times in order to prevent hypoglycemia. To get the best effect,
regular insulin needs to be injected at least 30 minutes prior to eating, an inconvenience
for many. Carbohydrate intake on a day-to-day basis also needs to be kept consistent with
respect to time and amount (58). Nocturnal hypoglycemia can also be a problem due to
the peaking of NPH during the night. Use of a rapid-acting insulin prior to each meal
with a long-acting basal insulin, which can be given at night or in the morning, more
closely matches normal physiology helps normalize lifestyle, while decreasing
hypoglycemic episodes (59). Individuals can choose the timing and size of their meals
and adjust their rapid-acting insulin dose based on planned meal (or snack) carbohydrate
content.
Summary
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The etiology of type 2 diabetes involves insulin resistance in muscle, liver and fat tissues;
impaired insulin secretion by the pancreas; elevated glucose production by the liver; and
defective glucagon release. Both glucotoxicity and lipotoxicity exacerbate the primary
defects and accelerate the progression of type 2 diabetes. Therapeutic interventions,
including MNT as monotherapy, MNT combined with glucose-lowering mediations
and/or insulins, correct these abnormalities and reduce glucotoxicity and lipotoxicity.
Progressive beta-cell loss necessitates changes in medical therapy, including
changes in medications, as the disease progresses. The same principle applies to nutrition
therapy. As the disease progresses, changes in MNT must be made. Lifestyle
interventions begin with prevention of obesity and type 2 diabetes. However, as the
disease progresses and the diagnosis of diabetes is made, nutrition therapy interventions
focus on attaining and maintaining treatment goals such as normal glycemia and optimal
lipid and blood pressure goals.
References
1. World Health Organization. Preventing Chronic Diseases: A Vital Investment.
Geneva, Switzerland: WHO Press; 2005.
2. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing
world—a growing challenge. N Engl J Med. 2007;356:213-215.
3. Centers for Disease Control and Prevention. National Diabetes Fact Sheet:
General Information and National Estimates of Diabetes in the United States,
2005. Atlanta, GA: Department of Health and Human Services, Centers for
Disease Control and Prevention; 2005.
4. American Diabetes Association. Diagnosis and classification of diabetes
mellitus (Position Statement). Diabetes Care. 2007;30:S42-S47.
5. DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM: a
balanced overview. Diabetes Care. 1992;15:318-368.
6. Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin
secretory dysfunction and insulin resistance in the pathogenesis of type 2
diabetes. J Clin Invest. 1999;104:787-794.
13
13
7. Gerich JE. Pathogenesis and treatment of type 2 (noninsulin-dependent)
diabetes mellitus (NIDDM). Horm Metab Res. 1996;28:404-412.
8. Brunzell JD, Robertson RP, Lerner RL, et al. Relationships between plasma
glucose levels and insulin secretion during intravenous glucose tolerance tests.
J Clin Endocrinol Metab. 1976;42:222-229.
9. Quddusi S, Vahl TP, Hanson K, Prigeon RL, D’Alessio DA. Differential
effects of acute and extended infusions of glucagon-like peptide-1 on first-
and second-phase insulin secretion in diabetic and nondiabetic humans.
Diabetes Care. 2003;26:791-798.
10. Monnier L, Colette C, Dunseath GJ, Owens DR. The loss of postprandial
glycemic control precedes stepwise deterioration of fasting with worsening
diabetes. Diabetes Care. 2007;30:263-269.
11. Tuomilehto J, Lindström J, Eriksson JG, et al. for the Finnish Diabetes
Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in
lifestyle among subjects with impaired glucose tolerance. N Engl J Med.
2001;344:1343-1350.
12. Dautsch JG. The obesity epidemic: what’s being done? J Am Diet Assoc.
2002;102:638-639.
13. America on the Move. Simple steps to better health. Available at:
www.americaonthemove.org. Accessed April 3, 2007.
14. Katzmarzyk PT, Janssen I, Ross R, et al. The importance of waist
circumference in the definition of metabolic syndrome. Diabetes Care.
2006;29:404-409.
15. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the
metabolic syndrome. An American Heart Association/National Heart, Lung,
and Blood Institute Scientific Statement. Executive Summary. Circulation.
2005;112:2735-2752.
16. Franz MJ. The role of nutrition therapy and dietitians in the management of
the metabolic syndrome. Current Diabetes Reports. 2007;7:60-65.
17. Bessesen DH. The role of carbohydrates in insulin resistance. J Nutr.
2001;131:2782S-2786S.
14
14
18. McClenaghan NH. Determining the relationship between dietary carbohydrate
intake and insulin resistance. Nutr Res Rev. 2005;18:222-240.
19. Garg A, Bantle JP, Henry RR, et al. Effects of varying carbohydrate content
of diet in patients with non-insulin-dependent diabetes mellitus. JAMA.
1994;271:1421-1428.
20. Franz MJ. The evidence is in: lifestyle interventions can prevent diabetes. Am
J Lifestyle Med. 2007;1:113-121.
21. Diabetes Prevention Program Research Group. Reduction in the incidence of
type 2 diabetes with lifestyle intervention or metformin. N Engl J Med.
2002;346:393-403.
22. Buchannan TA, Xiang AH, Peters RK, et al. Preservation of pancreatic beta-
cell function and the prevention of type 2 diabetes by pharmacological
treatment of insulin resistance in high-risk Hispanic women. Diabetes.
2002;51:2796-2803.
23. DREAM (Diabetes Reduction Assessment with Ramipril and Rosiglitazone
Medication) Trial Investigators. Effect of rosiglitazone on the frequency of
diabetes in patients with impaired glucose tolerance or impaired fasting
glucose: a randomized controlled trial. Lancet. 2006;368:1096-1105.
24. Holman RR. Late-breaking trials: DREAM washout period results. Program
and abstracts of the 19th World Diabetes Congress; December 3-7, 2006; Cape
Town, South Africa.
25. Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glucose and
impaired glucose tolerance. Implications for care. (Consensus statement).
Diabetes Care. 2007;30:753-759.
26. Lindström J, Ilanne-Parikka P, Peltonen M, et al. Sustained reduction in the
incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish
Diabetes Prevention Study. Lancet. 2006;369:1673-1679.
27. Tuomilehto J. Counterpoint: evidence-based prevention of type 2 diabetes: the
power of lifestyle management. Diabetes Care. 2007;30:435-438.
28. Abrahamson MJ. A 74-year-old woman with diabetes. JAMA. 2007;297:196-
204.
15
15
29. American Diabetes Association. Standards of medical care in diabetes—2007.
Diabetes Care. 2007;30(Suppl 1):S4-S41.
30. The American Association of Clinical Endocrinologists. Medical guidelines
for the management of diabetes mellitus: the AACE system of intensive
diabetes self-management—2002 update. Endocr Pract. 2002;8:1-43.
31. Pastors JG, Franz MJ, Warshaw H, et al. How effective is medical nutrition
therapy in diabetes care? J Am Diet Assoc. 2003;103:827-831.
32. Yu-Poth S, Zhao G, Etherton T, et al. Effects of the National Cholesterol
Education Program’s Step I and Step II dietary intervention programs on
cardiovascular disease risk factors: a meta-analysis. Am J Clin Nutr.
1999;69:632-646.
33. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint
National Committee on Prevention, Detection, Evaluation, and Treatment of
High Blood Pressure: the JNC report. JAMA. 2003;289:2560-2572.
34. Boulé NG, Haddad E, Kenny GP, et al. Effects of exercise on glycemic
control and body mass index in type 2 diabetes mellitus: a meta-analysis of
controlled clinical trials. JAMA. 2001;286:1218-1227.
35. American Diabetes Association. Nutrition recommendations and interventions
for diabetes—2006. A position statement of the American Diabetes
Association. Diabetes Care. 2006;29:2140-2157.
36. Franz MJ, Bantle JP, Beebe CA, et al. Evidence-based nutrition principles and
recommendations for the treatment and prevention of diabetes and related
complications. Technical Review. Diabetes Care. 2002;25:148-198.
37. Wolf AM, Conaway MR, Crowther JQ, et al. Translating lifestyle intervention
to practice in obese patients with type 2 diabetes. Diabetes Care.
2004;27:1570-1576.
38. Franz MJ. The dilemma of weight loss in diabetes. Diabetes Spectrum. 2007;
in press.
39. The Look AHEAD Research Group. The Look AHEAD Study: a description
of the lifestyle intervention and the evidence supporting it. Obesity.
2006;14:737-752.
16
16
40. Mann JI. Nutrition recommendations for the treatment and prevention of type
2 diabetes and the metabolic syndrome: an evidenced-based review. Nutr Rev.
2006;64:422-427.
41. Franz MJ, VanWormer JJ, Crain LA, et al. Weight loss outcomes: a
systematic review and meta-analysis of weight loss clinical trials with a
minimum 1-year follow-up. J Am Diet Assoc. In press.
42. Korner J, Leibel RL. To eat or not to eat—how the gut talks to the brain.
Engl J Med. 2003;349:926-928.
43. Major GC, Doucet E, Trayhurn P, et al. Clinical significance of adaptive
thermogenesis. Int J Obes. 2007;31:201-212.
44. Astrup A, Gotzche PC, van de Verken K, et al. Meta-analysis of resting
metabolic rate in formerly obese subjects. Am J Clin Nutr. 99;69:1117-11122.
45. Franz MJ. Rimonabant: a new weight-loss medication. On the Cutting Edge.
Diabetes Care and Education. 2006;6:19-21.
46. Wing RR, Marcus MD, Epstein LH, Salata R. Type II diabetic subjects lose
less weight than their overweight non-diabetic spouses. Diabetes Care.
1987;10:563-566.
47. Kelley DE, Wing R, Buonocore C, et al. Relative effects of caloric restriction
and weight loss in non-insulin-dependent diabetes mellitus. J Clin Endocrinol
Metab. 1993;77:1287-1293.
48. Wing RR, Koeske R, Epstein LH, et al. Long-term effects of modest weight
loss in type 2 diabetic patients. Arch Intern Med. 1987;147:1749-1753.
49. Guidone C, Manco M, Valera-Mora E, et al. Mechanisms of recovery from
type 2 diabetes after malabsorptive bariatric surgery. Diabetes. 2006;55:2025-
2031.
50. Franz MJ. Carbohydrate and diabetes: is the source or the amount of more
importance. Curr Diab Reports. 2001;1:177-186.
51. The DAFNE Study Group. Training in flexible, intensive insulin management
to enable dietary freedom in people with type 1 diabetes: Dose Adjustment for
Normal Eating (DAFNE) randomised controlled trial. BMJ. 2002;325:746-
752.
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17
52. Wei M, Gibbons LW, Kampert JB, et al. Low cardiorespiratory fitness and
physical activity as predictors of mortality in men with type 2 diabetes. Ann
Intern Med. 2000;132:605-611.
53. Church TS, Cheng YJ, Earnest CP, et al. Exercise capacity and body
composition as predictors of mortality among men with diabetes. Diabetes
Care. 2004;27:83-88.
54. Sigal RJ, Kenny GP, Wasserman DH, Castaneda-Sceppa C. Physical
activity/exercise and type 2 diabetes. Technical Review. Diabetes Care.
2004;27:2518-2539.
55. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes. JAMA.
2002;287:360-372.
56. Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (exedin-4)
on glycemic control over 30 weeks in patients with type 2 diabetes treated
with metformin and a sulfonylurea. Diabetes Care. 2005;28:1083-1091.
57. Aschner P, Kipnes MS, Lunceford JK, et al. Effect of the dipeptidyl
peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in
patients with type 2 diabetes. Diabetes Care. 2006;29:2632-2637.
58. Wolever TMS, Hamad S, Chiasson J-L, et al. Day-to-day consistency in
amount and source of carbohydrate intake associated with improved glucose
control in type 1 diabetes. J Amer Coll Nutr. 1999;18:242-247.
59. Rosenstock J, Dailey G, Massi-Benedetti M, et al. Reduced hypoglycemia risk
with insulin glargine: a meta-analysis comparing insulin glargine with human
NPH insulin in type 2 diabetes. Diabetes Care. 2005;28:950-955.
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Table 1. Weight Changes in Persons with Type 2 Diabetes Compared to Weight
Changes in Persons without Diabetes and Effect of Weight Loss in Persons with
Diabetes on Hemoglobin A1c (A1C) Levels.
Interventions Weight Change in
Subjects with Type 2
Diabetes
12-mo A1C
Change
12-mo Weight
Change in Subjects
Without Diabetes
6-mo 12-mo
Weight Loss Diet
(n=532)
-2.4 kg -2.6 kg -0.4% -4.6 to -7.6 kg
Orlistat 120 mg tid
(n=574)
-5.0 kg -5.1 kg -0.8% -8.2 kg
Sibutramine 15-20
mg (n=152)
-7.5 kg -7.2 kg -0.4% -8.2 kg
Rimonabant 20 mg
(n-355) *
-5.9 kg -6.0 kg -0.6% -8.5 kg
*New drug that blocks endocannabinoid receptors thus reducing appetite, the brain’s
craving for flavorful foods and for nicotine.
Adapted from reference 45.
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Table 2. Key American Diabetes Association Macronutrient and Micronutrient
Nutrition Recommendations
Grade * Nutrition Recommendations
Carbohydrate
B
Expert consensus
A
B
A
•A food pattern that includes carbohydrate from fruits,
vegetables, whole grains, legumes, and low-fat milk is
encouraged for good health.
•Low-carbohydrate diets (<130 g/day) are not
recommended in the management of diabetes.
•Monitoring carbohydrate remains a key strategy in
achieving glycemic control.
•The use of the glycemic index and load may provide a
modest additional benefit.
•Sucrose-containing foods can be substituted for other
carbohydrates in the meal plan.
Protein
Expert consensus
A
•For persons with normal renal function, there is
insufficient evidence to suggest that usual protein intake (15-
20% of energy) should be modified.
•Ingested protein does not increase glucose concentrations
but does increase acute insulin responses.
Fat
A
Expert consensus
Expert consensus
•Limit saturated fat to <7% of total calories.
•Intake of trans fat should be minimized.
•Lower dietary cholesterol to <200 mg/day.
Micronutrients
A
A
•There is no clear evidence of benefit from vitamin and
mineral supplementation in people with diabetes who do not
have underlying deficiencies.
•Routine supplementation with antioxidants is not
advised because of lack of efficacy and concern related to
long-term safety.
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20
Expert consensus •Benefit from chromium supplementation has not been
clearly demonstrated and is not recommended.
Alcohol
Expert consensus
Expert consensus
B
•If adults choose to use alcohol, daily intake should be limited
to a moderate amount (one drink per day or less for women
and two drinks per day or less for men).
•In individuals using insulin or insulin secretagogues, alcohol
should be consumed with food to prevent hypoglycemia.
•Moderate alcohol consumption has no acute effect on glucose
and insulin levels.
* Grade is based on the American Diabetes Association evidence-grading system.
Adapted from reference 35.
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Figure 1. Type 2 Diabetes: A
Progressive Disease
Lifestyle
Interventions
Medical Nutrition
Therapy Alone or
With Glucose-
Lowering Meds
Medical Nutrition Therapy
Glucose-Lowering Meds
Insulin
Lifestyle
Meds
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