1. review article
Diabetes, Obesity and Metabolism 13: 204–206, 2011.
© 2011 Blackwell Publishing Ltd
article
review
Dietary prescriptions for the overweight patient:
the potential benefits of low-carbohydrate diets
in insulin resistance
M. W. Lee1 & K. Fujioka2
1 Diabetes/Endocrinology, Scripps Clinic, San Diego, CA, USA
2 Diabetes/Endocrinology, Scripps Clinical Research Center, La Jolla, CA, USA
Obesity in the USA continues to be a medical problem of epidemic proportions, affecting one-third of American adults. This increase in
body weight and body mass index (BMI) is a risk factor for insulin resistance; individuals with insulin resistance are at increased risk for the
development of type 2 diabetes and cardiovascular disease. The identification of effective dietary treatments (e.g. low-carbohydrate diet,
low-fat diet) for patient populations with insulin resistance remains controversial. While a variety of dietary approaches will result in weight
and cardiac risk factor reduction, individuals who have been identified as insulin-resistant may derive additional short-term weight loss results
from a low-carbohydrate diet compared to a low-fat diet.
Keywords: dietary intervention, insulin resistance, obesity therapy
Date submitted 30 July 2010; date of first decision 8 September 2010; date of final acceptance 8 October 2010
Introduction Risk factors for insulin resistance include obesity, sedentary
lifestyle, non-Caucasian ethnicity, history of gestational
Obesity in the USA continues to be a medical problem
diabetes or glucose intolerance and a family history of type
of epidemic proportions, affecting one-third of American
2 diabetes, hypertension or cardiovascular disease (Table 1). In
adults [1]. Considerable controversy remains regarding the
addition, an individual is at increased risk for insulin resistance
identification of effective dietary treatments. Low-carbohydrate
if there is already a personal diagnosis of cardiovascular disease,
diets have been shown to have at least comparable safety and
hypertension, polycystic ovarian syndrome, nonalcoholic fatty
efficacy as diets with higher carbohydrate content [2,3]. It is
liver disease or acanthosis nigricans [4].
possible, however, that low-carbohydrate diets are particularly
While insulin resistance can be measured via the
appropriate for patient populations with insulin resistance. In
hyperinsulinemic–euglycaemic clamp technique and the
addition to reviewing the studies that support and contradict
frequently sampled intravenous glucose tolerance test, these
this theory, this article will discuss the concept of insulin
procedures may not be suitable or convenient for most
resistance, its medical consequences and means of identifying
medical practitioners. The homeostasis model assessment of
those with this condition.
insulin resistance (HOMA-IR) can also be used, but requires
the measurement of fasting insulin and glucose values. A
Insulin Resistance predictive model for insulin resistance based only on clinical
measurements (without laboratory studies) has been proposed,
Secreted by the beta cells of the pancreas, insulin is responsible in which an individual is predicted to be insulin resistant if
for the proper metabolism of glucose and fatty acids by liver, (i) BMI is greater than 28.7 kg/m2 , or (ii) BMI is greater than
muscle and adipose tissue. Insulin resistance, with its compen- 27.0 kg/m2 with a family history of diabetes. This model carried
satory hyperinsulinemia, is associated with glucose intolerance, a sensitivity of 78.7% and a specificity of 79.6% [5]. Such a
abnormal uric acid metabolism, dyslipidemia, hypertension, predictive model may be useful for the busy primary care
inflammation and endothelial dysfunction (figure 1). Individu- provider during the assessment of the overweight patient.
als with insulin resistance and compensatory hyperinsulinemia
are thus at increased risk for the development of type 2 diabetes
and cardiovascular disease [4]. Low-Carbohydrate Diets in Insulin
Resistance
Correspondence to: Dr Michael W. Lee, Diabetes/Endocrinology, Scripps Clinic, 12395 El
Camino Real, Ste 317, San Diego 92130, CA, USA. It has been postulated that individual differences in insulin
E-mail: milee@scrippsclinic.com secretion may affect a particular diet’s ability to induce weight

2. DIABETES, OBESITY AND METABOLISM review article
Glucose
Intolerance
Abnormal
Endothelial Uric Acid
Dysfunction Metabolism
Insulin
Resistance
Inflammation Dyslipidemia
Prothrombotic Hemodynamic
Factors Changes
Figure 1. Disease-related consequences of insulin resistance [4].
Table 1. Risk factors for insulin resistance [4]. weight on the high-carbohydrate/low-fat diet than the low-
carbohydrate/high-fat diet (13.5 vs. 6.8%) [7].
Overweight/obesity
A similar 24-week pilot study showed comparable results.
Sedentary lifestyle Thirty-two overweight adults had insulin values measured
Non-Caucasian ethnicity 30 min after a 75-g oral glucose tolerance test, and were assigned
Family history of type 2 diabetes, hypertension or cardiovascular disease to either a high-glycaemic load diet or a low-glycaemic load
History of gestational diabetes or glucose intolerance diet. The composition of the high-glycaemic load diet was
History of cardiovascular disease, hypertension, polycystic ovarian
60% carbohydrate, 20% protein, 20% fat, 15 g fibre/1000 kcal,
syndrome, nonalcoholic fatty liver disease or acanthosis nigricans
mean estimated daily glycaemic index of 86 and a glycaemic
load of 116 g/1000 kcal. The composition of the low-glycaemic
load diet was 40% carbohydrate, 30% protein, 30% fat, 15 g
loss. In individuals with a high insulin response to glucose, a fibre/1000 kcal, mean estimated daily glycaemic index of 53
high-glycaemic load results in increased postprandial insulin
and a glycaemic load of 45 g/1000 kcal. Subjects with high
levels, favouring fatty acid uptake, inhibition of lipolysis and
insulin secretion lost more weight on a low-glycaemic load
energy storage. High-glycaemic-load diets also result in a lower
diet compared to a high-glycaemic load diet (p = 0.047).
glucose nadir and increases in counterregulatory hormones,
which may cause hunger and overeating [6]. In addition, low-glycaemic load subjects with high insulin
In a 16-week clinical study, 12 insulin-sensitive and 9 secretion lost more weight than low-glycaemic load subjects
insulin-resistant obese women were randomized to either with low insulin secretion (p = 0.027) [8].
a high-carbohydrate/low-fat (60% carbohydrates and 20% In an 18-month clinical trial, 73 obese young adults were
fat) diet or a low-carbohydrate/high-fat (40% carbohydrates randomized to either a low-glycaemic load (40% carbohydrates
and 40% fat) diet. Insulin-resistant women lost 13.4% of and 35% fat) diet or a low-fat (55% carbohydrate and 20% fat)
their initial body weight on the low-carbohydrate/high-fat diet. Serum insulin concentrations at 30 min after a 75-g dose of
plan, compared to 8.5% on the high-carbohydrate/low-fat oral glucose were measured at baseline. For those subjects with
plan. Interestingly, insulin-sensitive women lost more high insulin secretion, the low-glycaemic load diet resulted in
Volume 13 No. 3 March 2011 doi:10.1111/j.1463-1326.2010.01328.x 205

3. review article DIABETES, OBESITY AND METABOLISM
greater weight loss (5.8 vs. 1.2 kg, p = 0.004) than the low-fat in both normal and hypertriglyceridemic subjects [15,16].
diet [9]. It is therefore reasonable for health care practitioners to
Most recently, 45 obese insulin-resistant female subjects were recommend that individuals with insulin resistance avoid low-
randomized to either a low-fat (60% carbohydrate, 20% fat and fat/high-carbohydrate diets, unless there is concurrent weight
20% protein) diet or a low-carbohydrate (45% carbohydrate, loss [4].
35% fat and 20% protein) diet. Both dietary interventions
utilized prepared calorie-controlled meals. After 12 weeks,
the low-fat group lost 7.34 kg, compared to 9.33 kg in the
Conflict of Interest
low-carbohydrate group (p = 0.04) [10]. Dr Lee and Dr Fujioka designed the study, did data collection
In contrast, 31 obese women underwent insulin resistance and analysis. Dr Lee wrote the manuscript. Both the authors
testing (somatostatin/insulin/glucose infusion, as well as have no competing interests.
postprandial insulin measurements) and were placed on a
hypocaloric (1000 kcal deficit) diet composed primarily of
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