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C L I N I C A L F E AT U R E S
Postgraduate Medic ine, Volume 126, Issue 1, January 2014, ISSN 0032-5481, e-ISSN 1941-9260 139ResearchSHARE: www.research-share.com Permissions: [email protected] Reprints: [email protected]
Warning: No duplication rights exist for this journal. Only JTE Multimedia, LLC holds rights to this publication. Please contact the publisher directly with any queries.
Nutritional Management of Type 2 DiabetesMellitus and Obesity and Pharmacologic
Therapies to Facilitate Weight Loss
Marion L. Vetter, MD, RD1,2
Anastassia Amaro, MD2
Sheri Volger, RD, MS2,3
1Center for Weight and EatingDisorders, Department of Psychiatr y,Perelman School of Medicine,
Hospital of the University ofPennsylvania, Philadelphia, PA;2Division of Endocrinology, Diabetes,and Metabolism, Department ofMedicine, Perelman School ofMedicine, Hospital of the Universityof Pennsylvania, Philadelphia, PA;3Wyeth Nutrition at Nestle S.A.,King of Prussia, PA
Correspondence: Mar ion L. Vetter, MD,3535 Market St, Suite 3108,Philadelphia, PA 19104.Tel: 215-360-8965E-mail: [email protected]
DOI: 10.3810/pgm.2014.01.2734
Abstract:Diet plays an integral role in the treatment of type 2 diabetes mellitus (T2DM).
Unfortunately, many patients with T2DM do not have access to a registered dietitian or certied
diabetes educator, and rates of physician counseling about diet remain low. This article pro-
vides an overview of the current recommendations for the nutritional management of T2DM,
which are endorsed by the American Diabetes Association (ADA). Medical nutrition therapy,
which provides a exible and individualized approach to diet, emphasizes the total number
(rather than the type) of carbohydrate consumed. Because fat intake also affects glycemia and
cardiovascular risk, a reduction in daily mono- and polyunsaturated fat intake is recommended
for most patients with T2DM. Weight loss plays an important adjunct role in treating patients
with T2DM, because the majority of individuals with T2DM are overweight or obese. Patient
lifestyle modication, which encompasses diet, physical activity, and behavioral therapy, can
be used to facilitate weight loss in conjunction with several different dietary approaches. These
include low-carbohydrate, low-fat, low-glycemic index, and Mediterranean diets. Studies have
demonstrated that modest weight loss (5%10% of body weight) is associated with signicant
improvements in patient measures of glycemic control, lipids, blood pressure, and other car-
diovascular risk factors. Furthermore, a modest weight loss of as little as 4.5 kg can result in
reducing the glycated hemoglobin level by approximately 0.5%. Pharmacologic agents, when
combined with these approaches, may further augment weight loss. Familiarity with these prin-
ciples can help physicians provide dietary counseling to their patients with T2DM and obesity.
Keywords:medical nutrition therapy; pharmacotherapy; diabetes; obesity
IntroductionObesity affects 35.9% of US adults and dramatically increases the risk of type 2 diabetes
mellitus (T2DM).1,2Currently,two thirds of the 23 million US adults who have T2DM
are obese.3,4In conjunction with dietary management, exercise, and pharmacotherapy,
weight loss plays an integral role in the management of T2DM.
The term medical nutrition therapy(MNT) was introduced by the American Dietetic
Association in 1994 to describe the process of providing individualized nutrition reco-
mmendations to patients that took their lifestyle and treatment goals into account.5
The effectiveness of MNT is well established,68particularly if delivered within
1 year of diagnosis of T2DM.8However, many patients do not have access to a registered
dietitian or a certied diabetes educator. Rates of nutrition counseling from health care
providers also remain low, which makes it particularly challenging for many patients
to receive adequate education about the dietary management of diabetes. 911This
article reviews current nutritional recommendations for the management of T2DM and
obesity, using a case-based approach to illustrate questions that frequently arise during
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140 Postgraduate Medicine , Volume 126, Issue 1, January 2014, ISSN 0032-5481, e-ISSN 1941-9260ResearchSHARE: www.research-share.com Permissions: [email protected] Reprints: [email protected]
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dietary counseling. Given the benecial effects of weight
loss on glycemia, behavioral and pharmacologic therapies
for weight management (and their subsequent effects on
glycemic control) are also briey discussed.
Case StudyA 48-year-old African-American woman named D.B. was
diagnosed with T2DM approximately 2 years ago. She alsohas a history of hypertension and hyperlipidemia, for which
she takes lisinopril 10 mg once daily and simvastatin 40 mg
once daily. She is currently taking metformin 1000 mg twice
daily and sitagliptin 100 mg once daily, but her glycated
hemoglobin (HbA1c
) level is still above target at 8.0%. She
checks her blood sugars once a day (in the morning), but
has been resistant to more frequent monitoring. Her current
weight is 222 lbs and her body mass index is 38.5 kg/m2.
When given the option of starting an additional antidiabe-
tes medication, she states that she would like to try dietary
modication rst. She acknowledges that she has not reallypaid much attention to her diet in the past and requests
guidance about carbohydrate intake. Specically, she asks
how many grams of carbohydrates should be consumed daily
and whether different types of carbohydrate have differential
effects on her blood glucose values.
Recommendations forMacronutrient Intake for DiabetesCarbohydratesPostprandial glucose levels are primarily determined by the
amount of carbohydrate consumed, rather than the type of
carbohydrate (ie, sugar, starches, or dietary ber).12,13The
Recommended Dietary Allowance for carbohydrates is
130 g/d, which is based on the average minimum amount
of glucose used by the brain.14The median intake of carbo-
hydrates for US adults is 220 to 330 g/d for men and 180 to
230 g/d for women, with a recommended acceptable range
of 45% to 65% of total caloric intake14; a serving of carbohy-
drate is typically 15 g (ie, a slice of bread).15The American
Diabetes Association (ADA) recommends a consistent dis-
tribution of carbohydrates throughout the day, with a target
intake of 45 to 60 g/meal.16
Carbohydrate intake may be monitored by counting
the number of grams of carbohydrate, using carbohydrate
exchanges, or by experience-based estimation.16Although
the Diabetes Control and Complications Trial firmly
established the efcacy of carbohydrate counting in type 1
diabetes mellitus (T1DM),17it is less clear for individuals
with T2DM.
Types of Carbohydrate
Not all types of carbohydrates are fully metabolized to blood
glucose.12Added sugars, including sucrose and high-fructose
corn syrup (HFCS), are digested, absorbed, and fully metabo-
lized in a similar manner to naturally occurring mono- and
disaccharides. In contrast,half of the carbohydrate content
of dietary ber is metabolized to glucose as discussed in a
later section.
Sucrose
Restricted sucrose intake was recommended for many years
on the assumption that sugars are more rapidly digested and
absorbed than starches. However, several randomized trials
have found no difference in the glycemic response when
sucrose is substituted for equal amounts of other types of
carbohydrates in individuals with T1DM or T2DM.1822
Although it is possible to substitute sucrose for other sources
of carbohydrates,12 it is important to emphasize that con-
sumption of sugars, sugary beverages, and prepared foodswith a high sucrose content tend to be high in calories and
low in micronutrients (ie, vitamins, minerals, and trace
elements).
High-Fructose Corn Syrup
High-fructose corn syrup, an articial sweetener that contains
50% fructose and 50% glucose, is typically found in soft
drinks, sauces, salad dressings, and many processed foods.
Fructose, from either sugar or high-fructose corn syrup,
has been implicated in a growing number of health issues
over the past decade.23Several meta-analyses have shown
associations between the consumption of sugar-sweetened
beverages and obesity24,25and an increased risk of diabetes,26
but convincing evidence of a direct link remains lacking.
Most of these effects have been attributed to the increased
caloric intake associated with HFCS-containing foods, rather
than HFCS itself.27
In terms of glycemic effects, HFCS has also been shown
to decrease insulin sensitivity in both animal and human
models.28Unlike sucrose, fructose does not undergo rst-
pass metabolism by the liver.28Instead, fructose is rapidly
metabolized by hepatic fructose kinase C, leading to the
generation of substrates for de novo lipogenesis. Fructose-
induced lipotoxicity (and other alterations in lipid metabo-
lism) are believed to mediate some of the adverse effects of
fructose and HFCS on insulin sensitivity. Although the ADA
neither recommends for or against the use of HFCS, many
foods that contain this additive tend to be calorie-dense and
limited consumption is recommended.27
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Nutritional Management of T2DM and Obesity
Postgraduate Medic ine, Volume 126, Issue 1, January 2014, ISSN 0032-5481, e-ISSN 1941-9260 141ResearchSHARE: www.research-share.com Permissions: [email protected] Reprints: [email protected]
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Dietary Fiber
Dietary ber is not digested by enzymes in the small intestine
and does not contribute to the immediate glucose supply.12
Solublebers, which are derived from whole-grain products
and fruit (pectin), are fermented in the colon and delay the
digestion and absorption of carbohydrates.29,30Insoluble fber
(such as wheat bran) has bulking action and may improve gly-
cemia by decreasing the production of short chain fatty acidsin the colon, which decrease hepatic insulin sensitivity.31
The term net carbohydrateshas been used to account for the
fact that certain carbohydrates are only partially converted
to glucose, whereas others are not converted at all (such as
insoluble ber).25Net carbohydrates can be calculated in food
items that contain5 g of ber/serving by subtracting half
of the total number of grams of dietary ber from the total
number of grams of carbohydrates.12
Several randomized controlled trials (RCTs) have evalu-
ated the effect of varying the amount of dietary ber (while
controlling the total amount of dietary carbohydrate) on gly-cemic control in individuals with metabolic syndrome, T1DM,
and T2DM.3133High-ber diets contain approximately 50 g
per day, as compared with the average daily intake of 15 g for
US adults.32A recent meta-analysis that included 15 studies
reported a nonsignicant mean reduction in fasting blood glu-
cose of 15 mg/dL with a high-ber diet.34High-ber diets also
had very modest effects on HbA1c
, resulting in a mean difference
in HbA1c
reduction of 0.3%, compared with lower ber diets.
Individuals with T2DM are encouraged to consume a
variety of ber-containing foods, such as legumes, ber-
rich cereals (5 g ber/serving), fruits, vegetables, and
whole grains.16Similar to recommendations for the general
population, the ADA recommends that patients with T2DM
consume 14 g of ber per 1000 kcal.
Case Study (Continued)D.B. also asks whether fat can adversely affect her blood
sugars and whether certain fats are healthier than others.
FatDietary fat and free fatty acids (FAs) are known to impair
insulin sensitivity and to enhance hepatic glucose pro-
duction, which may contribute to the development of
hyperglycemia.35,36These adverse effects are thought to be
mediated through alterations in cell membrane composition,
lipogenic gene expression, and enzyme activity.37Because
individuals with T2DM are at increased risk for coronary
heart disease, the amount and type of fat consumed also has
important implications for cardiovascular risk reduction.38
Effects of Specic Types of Fat on Cardiovascular
Risk Factors and Insulin Sensitivity
Saturated FAs
Saturated FAs, which are found predominantly in animal
products, are one of the principal determinants of low-density
lipoprotein cholesterol (LDL-C) levels. Saturated fats have
also been found to decrease insulin sensitivity.37Given the
known association of saturated fats and cardiovasculardisease in individuals without diabetes mellitus, the ADA
currently recommends that saturated fat be restricted to7%
of total energy intake.16
Trans FAs
Trans FAs, or trans fats, are formed during the process
that converts vegetable oils into semi-solid fats for use in
margarines, commercial cooking, and manufacturing pro-
cesses. Trans fats have been shown to increase both LDL-C
and triglyceride levels and to reduce levels of high-density
lipoprotein cholesterol (HDL-C).39In addition to inducingan atherogenic dyslipidemia, trans FAs may also promote
inammatory cytokines and induce endothelial dysfunction.
Even a low consumption of trans fats (1%3% of total caloric
intake) appears to substantially increase the risk of coronary
heart disease.4042
Few studies have examined the effects of trans fats on
insulin sensitivity, but animal studies suggest that it may
impair adipocyte membrane uidity and insulin sensitivity,
possibly through downregulation of the peroxisome prolifer-
ator-activated receptor-located in adipose tissue.43The ADA
currently recommends minimal intake of trans FAs.16
Polyunsaturated FAs
Polyunsaturated FAs include the omega-3 FAs,which are
found in sh and canola oil, and the omega-6 FAs,which are
found in vegetable oils. A systematic review that included
23 RCTs of omega-3 supplementation (with a mean of 3.5 g/d
in a total of 1075 participants with T2DM), found signicant
reductions in triglyceride levels and very low LDL-C levels
in participants.44Although LDL-cholesterol levels increased
slightly with omega-3 supplementation, the increase was not
signicant in subgroup analyses. Omega-3 supplementation
did not have any effect on fasting glucose, insulin, or HbA1c
levels. In the Outcome Reduction with Initial Glargine Inter-
vention (ORIGIN) trial, a large RCT that included 12 536
patients with prediabetes or T2DM who were at increased
cardiovascular risk, supplementation of omega-3 FAs did not
prevent death or reduce cardiovascular outcomes in patients
compared with placebo.45
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Omega-6 FAs may have benecial effects on insulin
sensitivity. A recent randomized controlled crossover study
(that included 50% of participants with obesity and/or
T2DM) found that an omega-6 polyunsaturated FArich diet
improved insulin sensitivity (as assessed by a euglycemic
clamp) within 5 weeks compared with a diet that was high
in saturated FAs.46The omega-6 FAs are thought to decrease
insulin resistance by acting as a ligand for peroxisomeproliferator-activated receptors.47
Monounsaturated FAs
Oleic acid, which is contained in olive oil, is the predominant
source of monounsaturated fatty acids (MUFAs) in many
diets. A recent meta-analysis found that a high-MUFA intake
improved fasting glucose, triglyceride, total cholesterol, and
HDL-C levels, but not HbA1c
or LDL-C concentrations.48
A further discussion of MUFAs is provided in the section
called Mediterranean Diets.
ProteinDietary protein also plays a role in carbohydrate metabolism.
Amino acids directly contribute to the de novo synthesis of
glucose through gluconeogenesis and also participate in the
recycling of glucose carbon via the glucose-alanine cycle.49
Although specic amino acids, including glycine, leucine,
and arginine, stimulate insulin release, the net impact of
amino acids on glucose homeostasis remains unclear.
Discrepant effects of amino acids on glycemia have been
reported in the literature.50,51
The range of dietary protein intake appropriate for individu-
als with T2DM was recently summarized in a meta-analysis and
a systematic review.52,53Discrepant effects of high-protein diets
(dened as30% of total energy intake) have been reported
on HbA1c
levels, but high-protein diets appear to improve1
cardiovascular risk factor.53The ADA recommends using an
individualized approach with respect to protein intake, with
patient factors such as cardiometabolic risk and renal function to
be taken into consideration.54The ADA recommends reducing
protein intake to between 0.8 to 1.0 g/kg/d during the earlier
stages of chronic kidney disease and to 0.8 g/kg/d in patients
with more advanced renal dysfunction.16
Approaches to Facilitate Weight LossThe Effects of Weight Loss on DiabetesMellitusMost individuals with T2DM are overweight or obese, and
weight reduction is associated with signicant improve-
ments in insulin sensitivity.55Weight loss confers the greatest
benet for individuals with prediabetes56,57or shortly after the
onset of T2DM, when insulin resistance is the predominant
mechanism of impaired glycemia.58Additional defects in
patients with T2DM include inappropriate suppression of
glucagon and a diminished incretin response.59As the dis-
ease progresses and patient -cell function becomes more
impaired, weight loss has a more modest effect on glyce-
mic control.60,61Bariatric surgery studies provide the mostcompelling evidence for this phenomenon. Despite the very
signicant weight loss induced by bariatric procedures, indi-
viduals with longstanding diabetes (5 years in duration),
insulin dependence, body mass index 45 kg/m2, and a
baseline HbA1c
level 7.9% are less likely to experience
diabetes mellitus remission.62,63
Nonetheless, weight loss remains an important compo-
nent in the treatment of longstanding T2DM in patients and
is associated with a signicant reduction in the number of
antidiabetes medications (many of which tend to promote
weight gain) and cardiovascular risk factors.64,65A modestweight loss of 5% to 10% of body weight confers signicant
improvements in glycemic control, lipemia, and blood pres-
sure.65For every 4.5-kg loss in weight, patient HbA1c
levels
may be reduced by 0.5%.66
Macronutrient DistributionThe optimal distribution of dietary macronutrients (ie, carbo-
hydrate, protein, and fat) for the management of diabetes
mellitus and weight loss has not been established.16Isocaloric
diets (ie, equivalent in caloric content) of varying macronutri-
ent composition have been found to induce similar weight
loss (regardless of the distribution of carbohydrates, fat, and
protein),67and no particular dietary approach has been found to
be more efcacious than others in terms of promoting optimal
glycemic control or weight loss in patients.52An energy-
reduced diet should be recommended to facilitate weight loss.
Individualization of the macronutrient composition depends on
the metabolic status of the patient (eg, lipid prole and renal
function) or food preferences.16For most patients, the optimal
diet is the one to which individuals have the best adherence.68
Approaches to Weight ManagementLifestyle ModicationPatient lifestyle modication, which encompasses diet, physi-
cal activity, and behavioral therapy, serves as the cornerstone
for any dietary approach to diabetes mellitus and weight
management.69Common techniques include self-monitoring
(keeping records of food intake and physical activity),
modifying cues that elicit unwanted eating (stimulus control),
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problem solving, and relapse prevention. Self-monitoring
increases individuals awareness of their behavior (such as
overeating), the circumstances that trigger the behavior, and
patterns of behavior.70Food records also serve to increase
awareness of the calorie content and portion sizes of com-
monly consumed foods, which may account for the nding
that maintenance of daily food records is associated with
greater initial weight loss.71
Lifestyle modication programs typically induce a weight
loss of 8% to 10% in the rst 6 to 12 months, resulting in
clinically important health benets.71A 5% reduction in body
weight has been associated with a 0.5% decrease in patient
HbA1c
levels.72Unfortunately, most individuals regain one
third of the weight loss during the next year and return to
their baseline weight within 3 to 5 years.73Weight regain
can be minimized by frequent self-monitoring,74as well as
with ongoing contact that is delivered face to face, via the
Internet, or by telephone.75
The Look AHEAD (Action for Health in Diabetes)study, an RCT that included 5145 overweight participants
with T2DM, was designed to assess whether weight reduc-
tion (achieved through lifestyle modication) also reduced
cardiovascular morbidity and mortality.76Participants were
randomly assigned to either of 2 conditions: intensive lifestyle
intervention (ILI), which included group and individual meet-
ings; or diabetes mellitus support and education. In September
2012, the Look AHEAD trial was halted early, with a median
of 9.6 years of follow-up, on the basis of futility.77Although
weight loss was greater in the ILI group than in the support
and education group throughout the study (8.6% vs 0.7% at
1 year; 6.0% vs 3.5% at study end), it did not reduce the rate
of cardiovascular events.78 However, ILI produced greater
reductions in HbA1c
levels and greater initial reductions in
sleep apnea,79urinary incontinence,80and depression,81and
improvements in quality of life,82physical functioning,83and
mobility.84The study will continue as an observational trial to
identify longer-term effects of the intervention.
Case Study (Continued)Several friends and family members have recommended a
variety of diets to D.B., including the South Beach diet, the
Eat Right for Your Blood Type diet, the Scarsdale diet, and
the cabbage soup diet. She asks if 1 of the diets is optimal
to help regulate her blood sugar levels.
Dietary ApproachesA variety of dietary approaches can be used to meet the
recommendations provided above.
Low-Carbohydrate DietsMultiple studies have investigated the effects of a reduced
carbohydrate intake on glycemia, weight, and other meta-
bolic outcomes. However, efforts to compare ndings from
studies have been limited by the lack of a consistent deni-
tion of low-carbohydrate intake. Low-carbohydrate diets
typically include an absolute carbohydrate intake of 50 to
100 g daily,85,86or less than 40% of total calories derivedfrom carbohydrates.87Most low-carbohydrate diets permit
unrestricted intake of fat and calories, although unsaturated
fats are emphasized rather than saturated or trans fats.86
Low-carbohydrate diets are associated with more rapid
and greater short-term weight loss than low-fat diets in both
individuals with and without T2DM.8891However, longer
duration studies (12 months) have consistently shown
that weight loss is not maintained with a low-carbohydrate
diet, and by 12 months weight change is equivocal between
dietary groups.9295Longer term studies (4 years) show
no detrimental effects on cardiovascular risk factors.9698A recent meta-analysis that included 23 RCTs of 6-month
duration or more found that low-carbohydrate and low-fat
diets were equally effective at reducing body weight and
waist circumference.99
Low-carbohydrate diets have also been associated
with short-term improvements in glycemic parameters in
individuals with diabetes mellitus. Two meta-analyses100,101
and a recent ADA systematic review102 reported greater
reductions in HbA1c
levels and lower doses of antidiabetes
medications in individuals with T2DM who were assigned
to a low-carbohydrate diet, compared with conventional
higher carbohydrate diets. However, the benecial effects on
improved glycemic control generally did not persist after 1
year and were likely attributable to weight loss.102Limitations
of these studies include signicant loss to follow-up (many
had completion rates70%), small samples sizes, and sig-
nicant heterogeneity with respect to carbohydrate intake.
The ADA acknowledges that lower carbohydrate diets are
probably effective in the management of T2DM, but cautions
that such diets may eliminate foods that are important sources
of energy, ber, vitamins, and minerals.16,103 Additionally,
the ADA recommends that lipid prole, renal function, and
protein intake (in patients with nephropathy) be monitored
in patients who follow a low-carbohydrate diet.103
Low-Glycemic DietsThe physical properties of food, the rate of intestinal hydro-
lysis, and other dietary factors also affect the glycemic
response.12The glycemic index(GI) is a ranking that was
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developed to compare the postprandial glucose response of
different carbohydrates.104The GI is dened as the incre-
mental increase in plasma glucose (above baseline) that is
observed 2 hours after ingesting a known amount of carbo-
hydrate of an individual food. This value is then compared
with the response to a reference food (glucose or white bread)
containing an equivalent amount of carbohydrate. High-GI
foods, such as highly processed, starchy foods, tend to inducea higher peak glucose level than low-GI foods, which include
lentils, beans, oats, and non-starchy vegetables. Theglycemic
loadis the amount of carbohydrate multiplied by its GI.
Use of the GI in clinical practice remains controversial. The
GI of foods can be substantially altered by the presence of other
macronutrients in the meal or by cooking methods.12Moreover,
the GI for any particular food is subject to signicant variation,
both within and between individuals.105These factors limit the
applicability of the GI in the real-world setting.
Studies that have investigated the effects of low- versus
high-GI diets on indices of glycemic control have reporteddiscrepant ndings. A recent Cochrane review that included
402 individuals with T1DM and T2DM reported signi-
cant improvements in glycemic control on a low-GI diet,
as compared with a high-GI diet.106 Low-glycemic diets
resulted in a mean pooled HbA1c
level reduction of 0.5%.
However, many of the studies included in the systematic
review were short term, ranging from 4 to 6 months, and
included small numbers of participants. More recently,
Jenkins and colleagues107 found, in a 6-month RCT that
compared a low-glycemic-index diet and a high-ber cereal
diet among 210 participants with T2DM, that HbA1clevels
were signicantly decreased in the low-glycemic group
compared with the high-cereal ber group (0.5% vs 0.2%;
P0.001), even after controlling for change in body weight.
High-density lipoprotein cholesterol also increased in the
low-glycemic-index group, whereas it decreased in the
high-cereal ber group (P=0.005). Two relatively long-term
studies found no difference in weight loss or HbA1c
levels
at 12 months between participants with T2DM assigned to
a low-glycemic diet versus an ADA diet,108or to diets of
varying carbohydrate content.94
Fat-Restricted DietsLow-fat diets, which contain 30% of calories from fat,
have been conventionally endorsed as a dietary strategy for
the management of T2DM (and have often served as the
control group in many of the dietary studies reviewed in this
article). Low-fat diets, in combination with caloric reduction,
can induce weight loss and may help to reduce CVD risk
in individuals with T2DM.109 In a systematic review that
included 5 studies evaluating low-fat diets versus moderate-fat
or low-carbohydrate diets (although not necessarily mutually
exclusive) in individuals with T2DM, greater weight loss
was achieved in general in the low-fat groups.110Although
the patient level of HbA1c
was reported in some studies, the
improvements were very slight, and the quality of the trials
included were judged to be at high risk of being biased. Manyof the included studies were limited by small sample size,
heterogeneity in fat intake, and differences in fat quality.
Mediterranean DietsMediterranean diets emphasize the moderate consumption
of fats (30%40% of daily energy intake, primarily from
MUFAs such as olive oil), legumes, fruits, vegetables, nuts,
whole grains, sh, and moderate consumption of wine.
Many studies have demonstrated that a Mediterranean diet
pattern has benecial effects on cardiovascular health,111113
and recent research has focused on its effect on diabetesmellitus.
Several RCTs have investigated the effects of a Mediter-
ranean diet, as compared with other commonly used diets, on
glycemic parameters in participants with T2DM.96,114116In
the Prevencin con Dieta Mediterrnea (PREDIMED) study,
Estruch and colleagues114randomly assigned 772 participants
at high risk for cardiovascular disease (including 421 with
T2DM) to 1 of 2 Mediterranean diets (supplemented with
either 1 L/week of virgin olive oil or 30 g/d of tree nuts) or to
a low-fat diet for 3 months. Compared with the low-fat diet,
the Mediterranean diets were associated with greater reduc-
tions in fasting glucose and lipid levels, insulin resistance,
blood pressure, and inammatory markers.
Longer duration studies have also shown a sustained ben-
et on glycemic control. Esposito and colleagues116randomly
assigned 215 participants with newly diagnosed T2DM to
a Mediterranean or low-fat diet for 52 weeks. Signicant
reductions in fasting glucose and HbA1c
levels were observed
in the Mediterranean group compared with the low-fat group
(21 mg/dL and 0.6%, respectively). Similarly, Shai and
colleagues96 reported a higher decrease in fasting plasma
glucose in a subsample of participants with diabetes mellitus
who followed a Mediterranean diet compared with patients
following a low-carbohydrate or low-fat diet.
A recent meta-analysis that included a total of 20 RCTs
(total of 3073 individuals with T2DM) found that low-
carbohydrate, low-GI, Mediterranean, and high-protein diets
were effective in improving glycemic indices and various
markers of cardiovascular risk in individuals with T2DM.
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Per the most recent ADA guidelines, any of these approaches
may effectively enhance glycemic control and weight loss in
patients over the short term (2 years).103
Case Study (Continued)D.B. asks whether any supplements would be helpful in
regulating her blood sugars. She also mentions that she has
heard that cinnamon has some glucose-lowering effects.
Chromium, Antioxidants, andSupplementsOxidative stress is involved in the pathogenesis of both cardio-
vascular disease and diabetes123 and the protective role of
certain supplements and antioxidants has garnered considerable
interest. Selected supplements are reviewed in Table 1.
Given the lack of clear evidence and the fact that a
balanced diet provides adequate levels of essential vitamins
and minerals, both the ADA and the American Heart Associa-
tion (AHA) recommend against routine supplementation of
antioxidants or the use of herbal products.12,122
Case Study (Continued)Initially, D.B. is very motivated and records her food intake
and activities daily. She also reduces her portion sizes and tries
to make better food choices. She loses 10 lbs (4.5% weight
loss) during the next 3 months and her HbA1c
level decreases
Table 1. Effects of Selected Supplements on Glycemic Control in Patients With T2DM
Supplement Purported effects Evidence Limitations of studies Recommendations
for use
Chromium
picolinate117May potentiate the action
of insulin by augmenting its
signaling pathway
Systematic review (7 studies) found
no signicant effect of chromium
supplementation on HbA1clevels
(WMD 0.33%; 95%
CI; 0.72 to 0.06)
Considerable heterogeneity
in study populations and in
the range of chromium dose/
formulation; short duration
of studies
Not recommended
by the ADA
Zinc118 May play a role in insulin
sensitivity via the induction
of the P13K/AKT pathway
(mediator of insulin signaling
and glucose disposal)
Meta-analysis (8 studies; N =408)
reported a trend toward signicant
reduction in HbA1clevels (0.64%;
P=0.072)
Considerable heterogeneity in
study populations and in the
range of zinc dose/formulation;
confounding effects of other
concomitant medications; short
duration of studies
Not recommended
by the ADA
Vitamin D119 May stimulate postprandial
insulin release
Systematic review and meta-analysis
(4 studies; N =233) found no signicant
change in HbA1clevels with vitamin D
supplementation
Considerable heterogeneity in
study populations and in the
range of vitamin D dose/
formulation; small sample sizes;
loss to follow-up
Not recommended
by the ADA
Vitamin E120 May have a protective effect
on islet -cells by reducing
cytotoxicity mediated by
cytokines and their products
and possibly by enhancing
insulin action
Systematic review (8 RCTs; N =418)
found no benecial effect of vitamin E
supplementation on HbA1clevels
(WMD 0.17%; 95% CI; 0.49 to 0.16)
Considerable heterogeneity
in study populations, duration
of T2DM, level of glycemic
control, and antioxidant status;
small sample sizes; confounding
effects of concomitant
medications noted
Not recommended
by the ADA
Cinnamon121 Cinnamaldehydeamay exert
insulinotropic effects
Systematic review and meta-analysis
(10 RCTs; N =543) found no
signicant effect of cinnamon on
HbA1clevels; cinnamon was associated
with signicant reductions in total
cholesterol, LDL-C, triglyceride, and
FPG levels (WMD 25 mg/dl;
95% CI 40.5 to 8.7 mg/dL)
Considerable heterogeneity
in study populations and in
the range of cinnamon dose/
formulation; short duration
of studies
Not recommended
by the ADA
Fenugreek122 May delay gastric emptying
and slow CHO absorption;
glucose transport may be
inhibited because of ber
content
Meta-analysis (4 RCTs; N =51) found
benecial effects on FPG and PPGbConsiderable heterogeneity
in study populations; generally
poor quality studies with very
small sample size
Not recommended
by the ADA
aActive ingredient in cinnamon.bPooled estimates were not provided.
Abbreviations:ADA, American Diabetes Association; CHO, carbohydrate; FPG, fasting plasma glucose; HbA1c, glycated hemoglobin; PPG, postprandial glucose; RCT,
randomized clinical trial; T2DM, type 2 diabetes mellitus; WMD, weighted mean difference.
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Table2.(Continued)
Nonproprietary
drugname
(proprietary
name)
Doseand
dosing
recommendations
Effectsonweight
Corresponding
changeinHbA1c
levels
Sideeffects
Contraindications
(absoluteandrelative)
FDA
recommendations
forweightlossuse
GLP-1receptor
agonists(Byetta,
Bydureon,Victoza)
Exenatide(immediate
release):510ginjected
subcutaneouslyBID
Exenatide(extended
release):2mgonceperwk
Liraglutid
e:0.61.8mg
injectedsubcutaneouslyQD
(trialsinv
estigatingliraglutide
totreatobesityhaveused
3.0mgQ
D)
2.0kgplacebo-
subtractedweight
lossinstudies
rangingfrom
2052wks(pooled
estimatesoftrials
ofexenatideand
liraglutide)136
0.6%1.2%reduction
fromtrialsof
exenatideand
liraglutide137
Nausea
Hypoglycemiawith
concomitantuseof
otherhypoglycemia
agents
Insomnia
Drymouth
Constipation
Pancreatitis
Usewithcautionincombinationwith
glucose-loweringagentsand/orinsulin.
FamilyorpersonalhistoryofCcellthyroid
tumors(ie,medullarythyroidcancer)
orMEN-2
Approvedfor
thetreatment
ofT2DM
Pramlintide
(Symlin)
120150
ginjected
23timesdaily(higher
dosesusedinstudiesforthe
treatmen
tofobesity)
2.2kgplacebo-
subtractedweight
lossinstudies
rangingfrom
1652wksin
patientswithDM
whoconcurrently
receivedinsulin138
0.3%reduction138
Nausea
Hypoglycemia
(especiallyinpatients
treatedconcurrently
withinsulin)
Usewithcautionincombinationwith
glucose-loweringagentsand/orinsulin
Approvedfor
thetreatment
ofT2DM
SGLT-2inhibitors
Canag
lioz
in
(Invokana)
100
300
mg
QD
be
fore
rst
meal
23kgplacebo-
subtractedweight
lossin26-wk
monotherapytrial139
0.70%0.95%
reduction140
Hyperkalemia
Genitourinaryinfection
Absenceo
flong-t
erm
efcacyan
dsafety
data
Discontinuecanag
lioz
inife
GFRis
persistently4
5mL/min/1.73m2
Approvedfor
thetreatment
ofT2DM
Abbreviations:
BID
,tw
ice
da
ily;
BP,b
loo
dpressure;
Cr,creatin
ine;
DM
,diabetesme
llitus;eG
FR
,est
imate
dg
lomeru
lar
ltrationrate;
GLP
-1,g
lucag
on-l
ikepepti
de-1
;MAOI,monoam
ineox
idase
inhibitor;
MEN
-2,m
ultipleen
docrine
neoplasia-2;OTC,overthecounter;Q
D,oncedaily;SSRI,selectiveserotoninreuptakeinhibitor;SGLT-2,sodium-glucosecotransporter-2;TID,3timesdaily;T2DM,type2diabetesmellitus.
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Nutritional Management of T2DM and Obesity
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by 0.4%. However, D.B. soon tires of daily monitoring and
stops recording her food intake. During the next month, she
regains 5 lbs. When D.B. returns for follow-up, she asks if
she would be a candidate for weight loss medication.
Pharmacotherapy for Weight LossWeight loss, which plays an integral role in diabetes mellitus
management, has profound effects on insulin sensitivity. Inorder to maximize initial weight lost and minimize weight
regain in patients, pharmacotherapy can be used in combi-
nation with continued lifestyle modication. Health care
providers should also be mindful of the potential weight
effects when selecting pharmacologic treatments for diabetes
mellitus.124Several agents, including glucagon-like peptide-1,
mimetics, and sodium glucose cotransporter 2 inhibitors,
promote weight loss. In contrast, sulfonylureas, meglitinides,
thiazolidinediones, and insulin tend to induce weight gain.
A more detailed discussion of the weight effects of the various
classes of antidiabetes medications is beyond the scope ofthis article, but is discussed elsewhere.124
At present, only 3 medicationsorlistat, phentermine/
topiramate, and lorcaserinare approved by the US Food
and Drug Administration (FDA) for long-term weight loss
(Table 2). All of these medications, when combined with life-
style modication, induced losses of approximately 5% to 10%
of initial patient body weight in 1- to 2-year trials.125128These
losses were associated with signicant improvements in seve-
ral metabolic outcomes and CVD risk factors in patients.
ConclusionMedical nutrition therapy is an integral component in the
management of diabetes mellitus. Current nutrition recom-
mendations favor a exible and individualized approach, with
an emphasis on the total number of carbohydrates consumed.
Weight loss plays an important adjunct role, and studies
have demonstrated that modest weight loss (5%10% of
body weight) is associated with signicant improvements in
glycemic and lipid parameters, decreased insulin resistance,
and reduced blood pressure. Optimal macronutrient distribu-
tion and dietary patterns for the management of T2DM and
obesity have not been established, and low-carbohydrate,
low-fat, Mediterranean, or low-GI diets may be effective.
Behavioral modication, with or without pharmacotherapy,
can be used to facilitate weight loss in patients.
Conict of Interest Statement
Marion L. Vetter, MD, RD, has been employed by Bristol-
Myers Squibb in research on pharmacotherapy for patients
with diabetes mellitus. Anastassia Amaro, MD, and Sheri
Volger, RD, MS, have no conicts of interest to disclose.
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