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Low Carb High Protein Diets as Management Tool of Insulin Resistance in Patients with Obesity and/or Type 2 Diabetes Mellitus

Authors:
  • Dutch Knowledge of Dietititans on Overweight and Obesity (KDOO)

Abstract

Introduction and Rationale: Low carbohydrate high protein diets have been prescribed from as early as 1797 and are taken seriously by many researchers, although in main stream dietetics and medicine the diet can still be received with skepticism. Insulin resistance (IR) is the result of a cascade of physiological events, starting with hyperphagia leading to a positive energy balance and weight gain. Patients with IR gain weight easily and have trouble losing weight on diets with normal carbohydrate content, because of the highly elevated insulin levels. A diet for patients with IR must therefore tackle this problem to make weight loss possible. In this review the evidence on the diet short and long-term, effects on comorbidities and difference with Mediterranean diet are discussed. Methods: A search was carried out in Pubmed for articles of obesity management, IR, low carb/high protein diets and weight loss combined with comorbidities, several nutrients and the Mediterranean diet between 1995 and July 2017. Outcomes were compared to patient observations from dietary practice in weight loss management. Management: Diagnosis can easily be made by measuring waist circumference. The diet should be low carb/high protein but not provoking ketosis; energy and macro nutrient requirements should be individually assessed. Fat is not low but also not ad libitum, focusing on unsaturated fats. The intake of vitamin D, iodine and magnesium needs to be optimal. Alcohol consumption is not part of first phase of the diet. Exercise (endurance and resistance) is an essential part of the therapy. For patients with type 2 diabetes medication, diet and glucose values need to be meticulously observed. Conclusion: Low carbohydrate/high protein diets should be considered as a serious treatment option for all obese patients with and without comorbidities. They should be administered by specialised dietitians working in a multi-disciplinary team. Keywords: Low carbohydrate/high protein diet; Insulin resistance; Obesity; T2dm; Cvd; Nafld; Dietitian
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Open Access
Copyright: © 2017 Govers E. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Volume: 3.2
Review Article
Low Carb High Protein Diets as Management Tool
of Insulin Resistance in Patients with Obesity and/or
Type 2 Diabetes Mellitus
Elisabeth Govers1,2,3,4*
1Dutch Knowledge Centre for Dietitians, Amsterdam, Netherlands
2Dietetic Network on Obesity, European Federation of Associations of Dietitians, Rotterdam, Netherlands
3Nutrition Working Group, European Association for the Study of Obesity, Rotterdam, Netherlands
4Primary Care dietitian, Amstelring, Amstelveen, Netherlands
Received date: 31 Jul 2017; Accepted date: 26
Aug 2017; Published date: 04 Sep 2017.
Citation: Govers E (2017) Low Carb High Protein
Diets as Management Tool of Insulin Resistance
in Patients with Obesity and/or Type 2 Diabetes
Mellitus. Obes Open Access 3(2): doi http://dx.doi.
org/10.16966/2380-5528.131
Copyright: © 2017 Govers E. This is an open-
access article distributed under the terms of the
Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
*Corresponding author: Elisabeth Govers, the Dutch Knowledge Centre for Dietitians specialised
in the management of obesity, Amsterdam, Netherlands (KDOO), E-mail: e.govers112@upcmail.nl
Introduction
Low carbohydrate high protein diets have been prescribed from as
early as 1797, when Rollo started to treat patients with diabetes that way.
Almost a century later, in 1886, Banting, a British undertaker, introduced
the diet for weight loss. It became immensely popular at that time, when
following a weight loss diet was even called ‘banting. In 1972 Atkins,
among others, reintroduced the diet. A totally revised, evidence based
version appeared in 2010 [1]. Although low carb diets are taken seriously
by many researchers, in main stream dietetics and medicine the diet can
still be received with skepticism. Arguments to doubt the diet are: weight
loss is achieved by energy restriction, not by carbohydrate restriction; how
can a low carb diet dier greatly in macro nutrient content from national
guidelines and still be healthy. Furthermore: the amount of saturated fat
in the diet; possible deciencies in micronutrients, and the sustainability
long term. In this article I shall focus on the importance of the diet in
the world wide battle against obesity and its comorbidities and the
composition of the diet, to answer the question if this diet is healthy and
good for weight loss. Low carb/high protein diet will be compared to the
Mediterranean diet. Finally I will discuss sustainability.
Methods
A search was carried out in PubMed (Pubmed.gov) from 1995 to
July 2017 with the search terms: insulin resistance; insulin resistance
syndrome; obesity; obesity management and weight loss were combined
with search terms: low carbohydrate diets; low carbohydrate/high protein
diets; low carbohydrate/high fat diets ; type 2 diabetes mellitus; cardio
vascular disease; comorbidities; thyroid gland function; non-alcoholic
fatty liver disease; Mediterranean diet; and vitamin D 25-hydroxyvitamin
D; iodine; magnesium; ber and alcohol. e outcomes were compared
to literature I used for previous articles, and to patients observations
from dietitians connected to the Dutch Knowledge Centre for Dietitians
specialized in Overweight and Obesity (KDOO). Preliminary results
have been presented and discussed with peers at the EASO conference
(European Association for the Study of Obesity) in Porto, May 19, 2017.
e Rationale
Insulin resistance (IR) is the result of a cascade of physiological events,
starting with hyperphagia (an abundant intake of carbohydrates and
saturated fats) that leads to a positive energy balance and weight gain. In
this way subcutaneous adipose tissues get overlled, adipose cells enlarge.
Continuous weight gain in individuals leads to fat storage outside fatty
tissues into the abdomen (visceral fat), the muscles and liver. e fat
stored in these locations has a dierent metabolism which is characterized
by hypoxia, an impaired blood ow through the adipose tissue;
metaammation; an inltration of macrophages. Leading to a rise in leptin,
causing constant appetite; a rise in angiotensin, causing hypertension.
ISSN 2380-5528
Abstract
Introduction and Rationale: Low carbohydrate high protein diets have been prescribed from as early as 1797 and are taken seriously by
many researchers, although in main stream dietetics and medicine the diet can still be received with skepticism. Insulin resistance (IR) is the
result of a cascade of physiological events, starting with hyperphagia leading to a positive energy balance and weight gain. Patients with IR gain
weight easily and have trouble losing weight on diets with normal carbohydrate content, because of the highly elevated insulin levels. A diet for
patients with IR must therefore tackle this problem to make weight loss possible. In this review the evidence on the diet short and long-term,
eects on comorbidities and dierence with Mediterranean diet are discussed.
Methods: A search was carried out in Pubmed for articles of obesity management, IR, low carb/high protein diets and weight loss combined
with comorbidities, several nutrients and the Mediterranean diet between 1995 and July 2017. Outcomes were compared to patient observations
from dietary practice in weight loss management.
Management: Diagnosis can easily be made by measuring waist circumference. The diet should be low carb/high protein but not provoking
ketosis; energy and macro nutrient requirements should be individually assessed. Fat is not low but also not ad libitum, focusing on unsaturated
fats. The intake of vitamin D, iodine and magnesium needs to be optimal. Alcohol consumption is not part of rst phase of the diet. Exercise
(endurance and resistance) is an essential part of the therapy. For patients with type 2 diabetes medication, diet and glucose values need to be
meticulously observed.
Conclusion: Low carbohydrate/high protein diets should be considered as a serious treatment option for all obese patients with and without
comorbidities. They should be administered by specialised dietitians working in a multi-disciplinary team.
Keywords: Low carbohydrate/high protein diet; Insulin resistance; Obesity; T2dm; Cvd; Nad; Dietitian
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Citation: Govers E (2017) Low Carb High Protein Diets as Management Tool of Insulin Resistance in Patients with Obesity and/or Type 2 Diabetes
Mellitus. Obes Open Access 3(2): doi http://dx.doi.org/10.16966/2380-5528.131
On the other hand drop in adiponectin, inuencing hyperlipidemia and
insulin resistance; and elevated insulin-sensitizing and anti-inammatory
adipokines. e rise in pro-inammatory cytokines like TNF-α interferes
with insulin receptor signalling, and among many others, IL-6, involved
in glucose and lipid metabolism [2-4]. IR is a pathological condition in
which cells fail to respond normally to the hormone insulin. When the
body produces insulin under conditions of IR, the cells are unable to
use insulin eectively, leading to prolonged high blood sugar values and
further weight gain. Beta cells in the pancreas subsequently increase their
production of insulin, further contributing to a high blood insulin level.
is oen remains undetected and leads to impaired glucose tolerance and
eventually to type 2 diabetes [5,6]. Patients with IR gain weight easily and
have trouble losing weight on diets with a normal carbohydrate content,
because of the highly elevated insulin levels. A diet for patients with IR
must therefore tackle this problem to make weight loss possible [7-9].
Prevalence
e prevalence of IR in the obese and overweight population is larger
than is usually estimated and IR is in primary practice oen not considered
as the leading health problem which causes comorbidities. As shown in
the CARDIA study IR is present in 7.7% of Caucasian and 11.9% of black
individuals with a BMI lower than 25/kg/m2 [10]. In obese subjects, these
gures are 33.6% and 41.3% respectively.  e majority of individuals
with obesity develop IR, and may have dyslipidemia, gout, hypertension,
cardiovascular disease or type 2 diabetes, PCOS or other fertility
problems. An estimated 10-25% of obese individuals are the so-called
metabolically healthy. ey have still, for unknown reasons, preserved
their insulin sensitivity [11]. When in obese subjects besides hypertension,
dyslipidemia, IGT and type 2 diabetes non-traditional cardio metabolic
factors like VAT, LM, RMR, RER, TC, LDL, HOMA-IR were considered
the number of comorbidities rose from 13 to 80%. ere were no
signicant dierences between overweight and obese in %fat; VAT; lipids/
GLUC; insulin; leptin; or cortisol. e obese had higher FM, LM, RMR,
and estradiol; males had greater LM, RMR, and TRG (p<0.01); females
had greater %fat, and leptin (p<0.001). No signicant sex dierences were
found in RER, estradiol, insulin, or cortisol levels(p>0.05) [12,13]. To
establish what actual insulin levels in a non- study population are, a family
physician in the Netherlands invited her patients randomly to come to the
practice in a fasting state. She measured the insulin levels at fasting, aer a
breakfast of 60 grams of carbohydrates; 2.5 hours aer breakfast and aer
a lunch with the same amount of carbohydrates. Her data show that even
in young people insulin levels can stay elevated for 2.5 hours aer a meal.
In obese and diabetic subjects the levels were even higher (Table 1) [14].
e levels measured were much higher than published in several studies
[15,16]. Even adolescents can already be insulin resistant [17].
Risk of IR related to Lifestyle and Nutrition
IR is promoted by smoking and a sedentary lifestyle [18-22]. Food
substances that have been linked to the risk of developing IR are: high
carbohydrate diets [23,24]; high content of saturated fat [23]; high intake
of free fatty acids and triglycerides [25]; a low bre content [26]; diets
with a high glycaemic load [27]; take away meals [28,29]; starch, rich in
amylopectin [30]; a low vitamin D status [31,32]; and a high intake of
fructose [33-35] (Table 2). Especially starch is a compound that needs
further examination. Starch in all food products is built up of two
elements: amylose and adiponectin. Products that contain more amylose
are less harmful in relation to developing IR [36,37]. Ideally speaking
starch contains 30% amylose. In many products this is not the case, for
instance in many species of rice, with the exception of brown and basmati
rice. Risotto and sushi rice and other sticky rice species, for example, have
a low amylose content, and therefore eating them on a regular basis adds
to the risk of developing IR. Quinoa is also low in amylose, average 12%.
Many of these products have become popular through websites of foodies
and restaurants. Trendy as well as traditional food styles, rich in starch
with low amylose content, therefore, can lead to promotion of IR in the
general population, especially when consumers have a sedentary lifestyle
and stress, as is common in many in the working force. Large amounts
of fructose, as consumed by many in fruit juices, and in large quantities
of fruit, under the presumption that fruit is healthy and one cannot eat
enough of it, are a risk too. e eects of starch and fructose make clear
that foods that are quite popular among great groups of higher educated
people with a western lifestyle, but also foods that have a place within the
Mediterranean diet, can be harmful if consumed in large quantities on a
regular basis. On the other hand the daily consumption of dairy products
prevents IR. Pereira found that dairy consumption was inversely associated
with the incidence of all IRS components among overweight individuals
Patient A Fasting ½ h. after Break
fast
2 ½ h. After
Break fast
After
Lunch
Glucose mmol/l 4.8 7.0 4.8 6.2
insulin mUl/l 6.5 63.8 6.6 36.8
Patients with normal values after 2 ½ hrs
Patient B Fasting ½ h. after Break
fast
2 ½ h. After
Break fast
After
Lunch
Glucose mmol/l 5.0 7.6 4.8 5.4
insulin mUl/l 5.2 154 8 95
Patient 17 Years. Insulin stays elevated, plus accumulating eect
Patient C Fasting ½ h. after Break
fast
2 ½ h. After
Break fast
After
Lunch
Glucose mmol/l 4.7 6.3 5.2 7.6
insulin mUl/l 6.9 96.6 76.6 180
Patient 45 years. Obese
Patient D Fasting ½ h. after Break
fast
2 ½ h. After
Break fast
After
Lunch
Glucose mmol/l 4.9 7.6 4.8 7.0
insulin mUl/l 10.6 228.3 164.4 282.4
Patient 56 years. High insulin values and high post prandial glucose
(type 2 diabetes)
Patient E Fasting ½ h. after Break
fast
2 ½ h. After
Break fast
After
Lunch
Glucose mmol/l 4.5 14 7.2 9.8
insulin mUl/l 24.1 280 90 160
Table 1: Glucose and Insulin values in at random selected patients.
Patients with normal values of glucose mmol/l; insulin mU/l
Hypertension Elevated oestrogen
Dyslipidemia Fertility problems
Low HDL Low testosterone
Elevated LDL and triglycerides Reduced thyroic gland function
PCOS (policystic ovarian
syndrome) Sleep apnoea
NAFLD (non-alcoholic fatty liver
disease) Gout
Impaired glucose tolerance and
type 2 diabetes
Increased activity of mast cells
in the duodenum
Osteo artritis Vit D deciency
Fatigue Emotional instability
Increased risk of infections
Table 2: Clinical parameters.
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Citation: Govers E (2017) Low Carb High Protein Diets as Management Tool of Insulin Resistance in Patients with Obesity and/or Type 2 Diabetes
Mellitus. Obes Open Access 3(2): doi http://dx.doi.org/10.16966/2380-5528.131
(BMI ≥25 kg/m2 at baseline) [10]. e change of developing IR syndrome
(2 or more components) was 72% lower (odds ratio, 0.28; 95% condence
interval, 0.14-0.58) when overweight individuals consumed ≥35 times
dairy per week compared to those with the lowest consumption: <10 times
per week. Each daily occasion of dairy consumption was associated with
a 21% lower risk of IRS (odds ratio, 0.79; 95% condence interval, 0.70-
0.88). ese associations were similar for blacks and whites and for men
and women. For leaner individuals (BMI <25kg/m2) these associations
were not found. Other dietary factors, including macronutrients and
micronutrients, could not explain the association between dairy intake
and IRS.
Diagnosis in daily practice
It is important for physicians, dietitians, nurse practitioners and other
HP’s to recognise IR at an early stage, because if IR is diagnosed early
appropriate measures can be taken. e presence of metabolic syndrome
is a solid sign of IR: high blood pressure, elevated total cholesterol or
LDL cholesterol, a low HDL cholesterol, and impaired glucose tolerance
are caused by IR; and are in many cases reversible if treatment is started
straight away (Table 3). Less known but easy to establish IR, is the history
of weight loss attempts and relapse a patient has. But, the easiest way to
diagnose IR is measuring the waist circumference. For men a waist of ≥94
cm or 37 inches; and for female a waist ≥88 cm or 34 inches is a clear sign
of IR [38]. Waist circumference is dominant over weight and BMI. e
location of the waist measurement should be just below the lowest rib,
and not halfway the lowest rib and the upper rim of the pelvis, because
this location correlates better with high blood pressure, cholesterol,
IR, impaired glucose tolerance and T2 DM [39], and may therefore be
an easy and cheap diagnostic tool in daily practice, thus avoiding costly
and in primary care impractical measurements like a fasting insulin
level. Han found that even people with a BMI over 23 kg/m2 already had
one comorbidity related to IR [40]. Weighing and measuring the waist
circumference of patients who come in with signs of metabolic syndrome,
even with normal weight is therefore advisable as standard procedure. One
of the pitfalls in taking BMI as diagnostic tool is that people of oriental/
Asian origin have a lower BMI as normal value. For Asian populations,
the suggested BMI categories are as follows: 18.5–23 kg/m2 increasing
but acceptable risk; 23–27.5 kg/m2 increased risk; and ≥27.5 kg/m2 high
risk [41,42]. Cut-o points of waist circumference in Asians were set
by the International Diabetes Federation for South Asians, Chinese and
Japanese on >90 cm for men and >80 cm for women [43]. Because in
Western countries the correct weight and waist cut-o points for patients
of Asian origin are not always used obesity and IR are underestimated in
this population.
Management
e presumption is that anyone can lose weight on any diet that
restricts energy intake [44]. In fact, many patients want to lose weight,
but fail to reach even the point of ≥5% weight loss, similar as we found
in a prospective cohort of 1546 patients (Table 4) [45,46]. is problem
is well known in patients with IGT and type 2 diabetes [47]. Even though
we know that greater weight loss improves long-term maintenance [48]
and metabolic functions, e.g. pancreas function [49]. For years many
health professionals have doubted the motivation of their patients, thus
explaining the low success rates, instead of doubting the eectiveness
of the treatment. But, if the treatment fails, we should attribute that not
only to the patient but also to the therapy. Diet is in weight management
the most signicant conservative treatment option and evidence based
eective [50-54], but not every diet is t for everyone. If patients fail to
lose substantial weight and suer from relapse in many cases, the therapy,
in this case the diet, could be false. Several studies have pointed out that
low carb/high protein diets lead to more substantial weight loss [55-58].
Treatment goals
Treatment goals are: rstly to improve insulin sensitivity through 10-
15% weight loss (20-25% in morbid obesity) [59,60]; and loss of ≥10% waist
circumference; secondly to improve comorbidities and blood parameters,
including lowering or stopping medication for comorbidities; thirdly the
increase of fat free mass; improvement of quality of life, sleep and physical
and mental condition, and nally a weight maintenance of 5 years [45,61]
(Table 5). To reach weight maintenance in insulin resistant patients, they
need to understand how their body functions, what is dierent because
of IR and how they can control that. Each kilo of weight loss will improve
comorbidities [62]. A weight loss of >5% is necessary for benecial eects
on HbA1c, lipids, and blood pressure [63].
Energy expenditure
e answer lies in the changed metabolism due to IR [1-4]. e high
insulin production causes more fat storage and prevents weight loss. Each
time a person with IR eats carbohydrates the insulin level goes up to the
levels as shown in Table 1. And, because insulin not only makes it possible
for glucose to enter the cells, but also promotes fat storage, patients
can gain weight by eating carbohydrates in normal quantities. A low
carbohydrate content of around 6 grams per meal does not create release
of insulin. When the insulin levels stay low and there is an energy decit,
fat can be released from the fatty tissue. But, a low carbohydrate diet is
no magical bullet. e normal law of energy expenditure stays intact: if a
patient consumes a diet that is not low enough in calories, or is not close
High carbohydrate diets Diets with high glykemic load
High content of saturated fat High intake of fructose
High intake of free fatty acids Take away meals
High intake of triglycerides Starch rich in amylopectin
Low bre intake Low vitamin D intake
Table 3: Food linked to promotion of insulin resistance.
>5% weight loss
Low energy diet 29,1%
RGV 34,2%
Low fat diet 28,6%
Low carb diet 46,1%
>5% loss of waist circumference
Low energy diet 40%
RGV 38%
Low fat diet 25%
Low carb diet 57%
<3% or no weight loss
Low energy diet 41,7%
RGV 35,9%
Low fat diet 28,8
Low carb diet 28,8%
<3% loss of waist circumference
Low energy diet 37,9%
RGV 35,8%
Low fat diet 62%
Low carb diet 42,8
Table 4: Weight loss after 6 months treatment.
N= 1546; ref. 46; RGV: Dutch Dietary Guidelines for the Healthy
population.
Improvement of insulin sensitivity
10-15% weight loss (20-25% in morbid obesity)
Loss of ≥10% of waist circumference
Improving comorbidities and blood parameters, including lowering or
stopping medication for comorbidities
Increase of fat free mass
Improvement of quality of life and sleep
Improvement of physical and mental condition
Weight maintenance 5 years
Table 5: Treatment goals.
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Citation: Govers E (2017) Low Carb High Protein Diets as Management Tool of Insulin Resistance in Patients with Obesity and/or Type 2 Diabetes
Mellitus. Obes Open Access 3(2): doi http://dx.doi.org/10.16966/2380-5528.131
Exercise is an important part of the treatment. Resistance training
combined with a calorie restriction leads to reduced VLDL cholesterol,
triglycerides, and systolic and diastolic blood pressure [71,72]. Exercise
training added to a calorie restriction leads to better physical functioning
and less loss of muscle [73].
Carbohydrates
A carbohydrate restriction does not need to be lower than 36 grams
per day, spread over 6 moments. 36 grams is the absolute physiological
minimum the brain and erythrocytes need to function. In this way the
pancreas is not forced to produce extra insulin. Since weight loss is
promoted suciently this way, a lower intake of carbohydrates which
would also promote ketosis, is not advisable. Carbohydrate requirement
should be individually calculated. e more obese the patients the
better they feel on a low carbohydrate intake of around 50 grams for a
long period. For example: for many patients a restriction of 75 grams is
a large reduction of the daily intake in carbohydrates (Table 7) [74]. e
challenge lies more in having enough variety in the diet and dealing with
social events and in the workplace than in the restriction itself. Kirk and
colleagues dened moderately low carb as 30-40% of energy, with the
carbohydrate content depending on the energy intake [75]. However, 40%
of a 1600 calorie diets 160 grams, for many women a normal daily intake.
is is de facto not a low carb diet and it will not make a dierence with an
energy restricted diet. erefore it will not have desired results in patients
with IR.
One of the problems connected with obesity is carbohydrate craving.
Some patients with a mild eating disorder have less craving due to a low
enough to the RMR, or less than 600 calories decit of the usual intake,
weight loss will not occur [51,60]. e energy demand should therefore
be individually assessed per patient. And additionally, a diet too low in
protein or fat will prevent weight loss because the diet induced energy
expenditure is too low. A weight loss of 500 grams per week is good. In
the rst phase patients may lose much more, kilos per week, due to the
loss of liquids, which always takes place when people start to eat less
carbohydrates.
Diet and exercise
Weight loss is achieved through a combination of decrease of the
carbohydrate intake and increase of the protein intake (Table 6) [55]. In
the rst phase a strict carbohydrate restriction and high protein intake is
advised for 8 weeks to 3-6 months, dependent on the progress of weight
loss, loss of WC and improvement of comorbidities [55, 62-65]. Diet
induced weight loss leads to better insulin sensitivity and should therefore
be the most important objective in obesity management [66]. e aim is to
bring the high release of insulin down. is also applies to obese patients
with type 2 DM [67-70]. When weight loss results – and improvement of
comorbidities - are suciently achieved the second phase is a less strict
carb restriction, of around 50-100 grams per day, still high protein, for
3-6 months. Good results on low carbohydrate diets can be seen with an
intake of 50-100 grams. An individual assessment of the carbohydrate and
protein intake is necessary to determine the right content of the diet to
make weight loss possible. In the maintenance phase the carbohydrate
level can be elevated till weight loss stops. Sufficient protein intake
stays necessary.
Nutrient Content Quantity
Energy Individually assessed 600 calories decit of usual intake
Protein Individually assessed; large intake of dairy; egg, sh, chicken;
shell sh; moderate red meat; Pulses in phase 2 and 3
At least 1.0 g/kg actual weight up to 1.2 g/kg actual weight, evenly
spread over three meals; comparable to: 30-30-30.
Leucine From protein 3 grams per meal
Carbohydrates 3 phases (Table 7); phase 2 and 3 individually assessed
Phase 1: 36 grams
Phase 2: 50-100 grams
Phase 3: 75-125 grams
Fat Individually assessed Promotion of PUFA and MUFA
Fibre From vegetables, nuts, fruit, pulses; grains Per day: vegetables large portion 2 times; 25 grams of nuts;
1 or 2 servings of fruit
Alcohol Total restriction in phase 1; very modest in phase 2 and 3 Phase 2 and 3: 1 glass of wine twice a week
Vitamin D Suppletion 400-800 IU (10-20 mcg/day)
Iodine Suppletion can be necessary: iodine piccolinate 150 mcg/day
Magnesium Meat, sh, dairy, cheese, vegetables, pulses, potatoes and grains 300 mg/day
Exersize Combination of resistance training and tness 30-60 minutes per day
Table 6: Elements of the low carb/high protein diet.
Phase 1
Weight loss; improvement of comorbidities
Very strong carbohydrate restriction 36 grams; 3 meals & 3 snacks of 6 grams carbohydrates
Minimum duration 8 weeks, or more if IR is severe, up to 6 months.
Phase 2*
Weight loss; improvement of comorbidities
Strong carbohydrate restriction 50-100 grams; 3 meals & 3 snacks 8-16 grams carbohydrates
Duration 6 months to 2 years, dependent on desired weight loss.
Phase 3*
Maintenance phase; stable phase of comorbidities
Moderate carbohydrate restriction 75-125 grams; 3 meals & 3 snacks 8-20 grams carbohydrates. Elevate carbohydrate intake till weight loss stops.
Amount of carbohydrates dependent on weight maintenance.
*carbohydrate content of the diet needs to be assessed individually for each patient
Table 7: Levels of carbohydrate restriction.
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Citation: Govers E (2017) Low Carb High Protein Diets as Management Tool of Insulin Resistance in Patients with Obesity and/or Type 2 Diabetes
Mellitus. Obes Open Access 3(2): doi http://dx.doi.org/10.16966/2380-5528.131
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5
carbohydrate diet, because insulin promotes craving. ey feel more
relaxed and less hungry, and experience more control over their eating
behaviour. An estimate of 30% of obese patients seeking help has a mild
or more severe eating disorder (BED, DSM-5), compared to 2-3% in
the normal population [76]. For patients with severe eating disorders
a carbohydrate restricted diet lower than 100 grams is not a treatment
option. ese patients need to get cognitive behavioural therapy (CBT)
rst. Some of the medication used in the therapy enhances weight loss,
although most therapies for BED do not lead to weight loss [77,78].
Low carb diets for patients with type 2 DM
Low carbohydrate diets are eective to reduce fasting glucose and
HBA1C levels in patients with type 2 diabetes mellitus [79] as well as
to reduce visceral fat [80]. It should be the rst option in patients with
de novo T2DM. Especially in patients that have high glucose values and
HBA1C, or patients that face insulin therapy, and have trouble losing
weight a low carbohydrate/high protein diet works very well. Finally
weight loss is possible and the amount of medication can be lowered.
Oral glucose lowering medication like metformin does not lead to
hypoglycaemia and can be taken in the same amount, till HBA1C and
fasting glucose have diminished to normal values. In many cases patients
can stop to take insulin and sulfonium derivates. ese medicine can
cause hypoglycemia, when not decreased as soon as the patient starts with
the diet. It is suggested to stop or lower 24 hour working insulin rst, and
adjust short working insulin to the amount of carbohydrates in the meal.
Aer 3-4 weeks insulin dosage can be lowered further in small steps per 4
units, similar to the way insulin was started. For better results in terms of
weight loss the basal level of the insulin pump needs to be lowered more
than rapid insulin dosage. Rapid insulin and medium lasting insulin need
to be stopped last and for a short period higher fasting glucose values
should be accepted, because they will diminish when weight loss occurs.
Patient should record three times a week fasting glucose, before lunch,
before dinner and before going to bed. HbA1c should be checked aer two
months to verify insulin need. High glucose values without fever usually
mean that the insulin dosage is too high [81].
Protein
e diet should have 1.2-1.5 grams protein per kg present body weight.
Krieger calculated the cut-o point for ideal protein intake during weight
loss at 1.05 grams per kilo present body weight, although if the diet was
prolonged for more than 12 weeks, this gure rose to 1.2 grams/kilo
[82]. e protein requirement needs to be individually assessed. Protein
should be evenly spread over three meals preferably 30-30-30 grams
per day [83,84]. A high protein diet leads to more satiation and sustains
muscle mass [85]. Each meal should contain 3 grams of the essential
amino acid leucine. Leucine is present in animal protein, dairy products,
nuts, seeds and pulses. Wey protein and casein are in combination
with leucine essential for building and maintaining muscle tissue [86].
Leucine prevents decrease of muscle and liver tissue; and it is a part of
haemoglobin. Leucine containing products, e.g. dairy, eggs, meat, sh and
pulses are therefore an essential part of the diet. e eect of protein rich
foods is that they enhance thermogenesis. is eect is bigger in animal
protein than in proteins from plants. However, a large intake of meats
is not encouraged, preferably the increase in protein intake comes from
dairy, sh, poultry, eggs, nuts, seeds and pulses. A high protein diet leads
to signicantly higher decrease of fat mass aer a year; and better weight
maintenance [87]. is study also looked into genetic predisposition and
found that carriers of the AA genotype (67% of the population) benet
from a high protein diet. A rise of 5% in protein intake and a decrease of
4% in glycaemic index helped maintain weight loss, and promoted even
further weight loss and improvement of biomarkers. Even children of the
DiOGenes study population benetted from the changed food behaviour
of their parents: their biomarkers also improved [88].
e diet of elderly can be low in protein [89], with an average intake of
0.8 gram/kg, which prevents weight loss and is a risk for sarcopenia, a risk
for patients older than 60 years that need to lose weight. For these patients
1.0-1.2 grams of protein per kilo present body weight, evenly spread over
the day, combined with a moderate calorie restriction and resistance
training is advised [90,91].
Fat
In a low carb/high protein diet the intake of fat is not restricted,
although there is no argument for ad libitum consumption. Diets for
weight loss will always be calorie restricted and fat has the highest amount
of calories per gram. So controlled intake of fat is always necessary and fat
needs to be individually calculated. e diet is not low fat however. Lately
the discussion about which kind of fat has been enhanced by several
publications showing evidence that saturated fat may not be the main cause
of CVD [92-95], and may even be benecial for type 2 diabetes [92,96-
99]. A systematic review and meta-analysis by Pimpin et al. [100] suggests
relatively small or neutral overall associations of butter with mortality,
CVD, and diabetes. A 14 grams consumption of butter would give a 4%
risk reduction. Related to the glucose-insulin homeostasis, Imamura et al.
[101] found in a meta-analysis that replacing carbohydrates with PUFA
(poli-unsaturated fatty acids) leads to signicant lowering of glucose,
HBA1C, C peptide, and HOMA-IR. PUFA also signicantly improved
insulin secretion capacity when replacing carbohydrate, saturated fats or
mono-unsaturated fatty acids. e study has limitations due to the small
number of trials for some outcomes and the heterogeneity. Industrial
trans-fat was associated with all-cause mortality of CVD; ruminant trans-
palmoleic fat was inversely associated with type 2 diabetes [92].
Omega-3 fatty acids have positive eects on non-alcoholic fatty
liver disease (NAFLD), which is a disease resulting from abdominal
obesity. DHA (docosahexaenoic acid (22:6 ω -3)) was superior to EPA
(eicosapentaenoic acid (20:5 ω -3)) at attenuating changes in plasma
lipids and hepatic injury as a result of Western diet in mice. It reversed
dietary eects on hepatic metabolism, oxidative stress, and brosis
[102]. A systematic review showed omega-3 fatty acids can reduce waist
circumference, but have no eect on BMI [103]. Patients with type 2
diabetes who received 520 mg of DHA and EPA had a benecial eect
on waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin
ratio, and lipid prole compared to placebo. In both groups no changes
in adiponectin were found; whereas resistin, insulin, and HOMA-IR
increased in both groups [104].
To summarise: fat does not need to be restricted but can also not be
taken at libitum. Unsaturated fats are preferable over saturated fats for all
patients. Omega-3 fatty acids may have positive eects and should be part
of the diet, consumed as fatty sh or supplements with sh oil. In a low
carb diet there is very little room for products like cookies and biscuits,
cake, pie, ice-cream, milkshake and chocolate. is means that a low carb
diet automatically is lower in saturated and industrial trans-fat, the latter
being dened as a serious risk factor for CVD [92].
Vitamins and Minerals
If vitamin D is decient in the diet and from sunlight, supplementation
is advisable with 400 or 800 IU (10-20 mcg). e relationship between
vitamin D 25-hydroxyvitamin D (25[OH]D) and IR, and its comorbidities
is still unclear. Because vitamin D plays a role in lipid and glucose
metabolism, it is to be expected that a good vitamin D status could be
benecial. Renzaho found evidence that in ethnic groups links between
vitamin D deciency and obesity-related chronic diseases exist, reporting
a statistically signicant result with a measurement of obesity, T2DM,
CVDs, and the metabolic syndrome. However, the strength of the
association varied across ethnic groups [105]. Patients with NAFLD
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Citation: Govers E (2017) Low Carb High Protein Diets as Management Tool of Insulin Resistance in Patients with Obesity and/or Type 2 Diabetes
Mellitus. Obes Open Access 3(2): doi http://dx.doi.org/10.16966/2380-5528.131
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6
who received a 25 µg vitamin D supplement or placebo combined with
a hypo caloric diet had reductions in triglycerides, AST, ALT, insulin
and HOMA-IR compared to the placebo group, which meant they had
improvements in lipids, liver enzymes and insulin sensitivity [106]. It is
also not clear whether low vitamin D status is a cause or an eect of IR
and obesity. erefore supplementation for all obese might not be the
ultimate solution for the cure of comorbidities and IR [107,108]. Pannu
carried out a systematic review on vitamin D status, where 18 of 23 trials
that met the criteria reported an increase in vitamin D status with weight
loss, although the increase in 25OHD was smaller than would be expected
from a direct mobilization of stores into the circulation [109]. Mallard
found no evidence for a dose-response eect of weight loss on the change
in serum 25-hydroxyvitamin D [110].
A contributing problem in the assessment of vitamin D studies is, that
in dierent parts of the world synthesis of the vitamin in the human body
is absent during half of the year, between October and March e.g. in de the
moderate climate of Middle and Northern European countries, including
Belgium, Germany, Poland, the United Kingdom, the Netherlands,
Scandinavia and so on. Latent vitamin D deciency is very common is
these regions and is in many cases not actively diagnosed.
e diet should contain sucient magnesium. Since magnesium
rich foods are meat, sh, dairy, cheese, vegetables, pulses, potatoes and
grains, a deciency in a low carb/high protein diet is not to be expected.
Magnesium has a major role in the regulation of blood pressure. Although
not all data are consistent, there is an inverse relationship between
magnesium intake and blood pressure, especially when obtained from
food rather than that obtained via supplements. Moreover magnesium
seems to have a positive role in the prevention of diabetes mellitus, obesity,
and metabolic syndrome [111].
Iodine is a crucial element in thyroid function. yroid hormones are
involved in the regulation of metabolism, thermogenesis, food intake,
and fat oxidation. Iodine can be obtained by eating sea sh and shellsh,
meats, eggs, dairy, seaweed and iodine containing salt. Obesity and
thyroid function are closely related. In a group of morbidly obese patients,
serum TSH concentration was associated with fasting serum insulin
levels and insulin resistance but not with serum leptin levels, body mass
index (BMI), fat mass, and lean body mass. e prevalence of overt and
subclinical hypothyroidism was high (19.5%). ey had higher levels of
T3, FT3, T4, and TSH than healthy controls, probably the result of the
reset of their central thyrostat at higher level [112]. De Pergola found that
progressive accumulation of abdominal fat is associated with an increase
in both FT3 and TSH serum levels, independently of insulin sensitivity,
metabolic parameters and blood pressure, suggesting that progressive
central fat accumulation is associated with a parallel increase in FT3 levels,
possibly as an adaptive thermogenic phenomenon [113]. At the same
time the control of TSH secretion by free thyroid hormones is possibly
impaired in obesity. Knudsen found a positive association between BMI
and category of serum TSH (P<0.001) and a negative association between
BMI and category of serum free T4 (P<0.001) but not to serum free T3
levels. ere was an association between obesity (BMI>30 kg/m(2))
and serum TSH levels (P=0.001) [114]. e role of leptin as a cross-talk
between the thyroid gland and the fat cells, and it’s role in the genesis of
auto immune thyroid failure is still unclear. Fact is that sucient iodine
intake is a point of concern for many.
Fiber and Resistant Starch
Fiber is an important element in any diet. In the low carb/high protein
diet ber may not come from bread, or potatoes, the ber content
of the diet is usually that high that patients seldom complain about
intestinal problems. Patients on a Western diet oen have a low vegetable
consumption. On a low carb/high protein diet they need to eat vegetables
twice a day, and fruit once a day. Plus the advice is to take a small serving
of nuts, eat pulses once a week and to drink 2 litres per day. When patients
consumed beforehand lots of white bread, white pasta and white rice,
cookies, sweets and fruit juices, all low in ber, their intake in ber has
increased through the diet.
Resistant starch is a carbohydrate that is not digested in the small
intestine. Resistant starch (RS) is a natural compound of foods but can also
be added as manufactured resistant starch. RS1- is in digestible resistant
starch in seeds or legumes and unprocessed whole grains. RS1 from seeds
and legumes/pulses has a place within a low carb/high protein diet. It is
even advisable to give patients daily portions of seeds and nuts because of
the low carbohydrate content, the satiety and the amount of ber. Pulses
are advised once a week in the second phase, which is more oen than
most patients on a Western diet are used to.
e other groups are: RS2 - indigestible due to starch conformation,
as in high amylose corn starch; RS3 - is formed when starch-containing
foods are cooked and cooled, such as pasta; RS4 – starch that has been
chemically modied to resist digestion. RS 1, 2 and 3 are fermented by the
large intestinal microbiota, producing short-chain fatty acids, promoting
butyrate-producing bacteria, creating a has similar physiological eect
as dietary ber. Consuming it at high doses can lead to atulence.
When isolated resistant starch is used to substitute for our in foods,
the glycaemic response of that food is reduced [115,116]. High amylose
resistant corn starch was said to be protective against type 2 diabetes
mellitus. A claim rst acknowledged by the FDA in the USA was almost
immediately retrieved with the note ´there is limited credible scientic
evidence for a qualied health claim for high-amylose maize resistant
starch and reduced risk of type 2 diabetes.
Alcoholic Beverages
Alcohol is discouraged in the rst phase of a low carb/high protein
diet. Alcohol provides calories which will be metabolised before any
other energy source, thus preventing weight loss and lipolysis. Alcoholic
beverages are a source of carbohydrates as well, especially beer and
liqueurs. If patients can refrain from alcohol for several weeks or months,
weight loss can be promoted. In the second phase a glass of wine a couple
of times per week can be taken. Another aspect of alcohol is that daily
consumption is discouraged because of its relation with breast cancer. A
study found nineteen metabolites signicantly associated with oestrogen
receptor positive (ER+) breast cancer (418 cases): 12 alcohol-associated
metabolites, including 7 androgens and α-hydroxyisovalerate (OR: 2.23;
95% CI: 1.50, 3.32); 3 vitamin E (tocopherol) derivatives (e.g., γ-CEHC; OR:
1.80; 95% CI: 1.20, 2.70); butter-associated caprate (10:0) (OR: 1.81; 95%
CI: 1.23, 2.67); and fried food-associated 2-hydroxyoctanoate (OR: 1.46;
95% CI: 1.03, 2.07), meaning that prediagnostic serum concentrations of
metabolites related to alcohol, vitamin E, and animal fats were moderately
strongly associated with ER+ breast cancer risk. No metabolites were
signicantly associated with ER- breast cancer (144 cases) [117]. For colon
cancer a relation with age, male sex and high BMI was found. Intakes of
grains, meats, proteins, coee, alcohol, aspirin, bre, fruits, and vegetables
were not associated with colorectal cancer mortality [118].
Dierence between Mediterranean Diet and Low Carb/
High Protein Diet
e Mediterranean Diet was introduced in 1993 by the Harvard School
of Public Health and WHO Europe, based on the dietary traditions of
Crete, Greece and southern Italy of around 1960. Research had revealed
that the rates of chronic disease among populations in these regions were
among the lowest in the world, and adult life expectancy was among the
highest even though medical services were limited [119,120]. e ‘poor’
diet of the people of the southern Mediterranean, consisting mainly of
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Citation: Govers E (2017) Low Carb High Protein Diets as Management Tool of Insulin Resistance in Patients with Obesity and/or Type 2 Diabetes
Mellitus. Obes Open Access 3(2): doi http://dx.doi.org/10.16966/2380-5528.131
Open Access
7
fruits and vegetables, beans and nuts, healthy grains, fish, olive oil, small
amounts of dairy, and red wine, proved to be much more likely to lead
to lifelong good health than the Western diet [121,122]. Other vital
elements of the Mediterranean lifestyle are daily exercise, sharing meals
with others, and appreciation for the food. e Mediterranean diet in its
original form was the total opposite of ‘modern’ food and drink habits in
industrialized countries, the latter leading to consumption of more meat
and other animal products, fewer fresh fruits and vegetables, and more
processed convenience foods, with large rates of heart disease, obesity,
diabetes, and other chronic diseases as result. In 2008 the Mediterranean
Diet was updated by the addition of herbs and spices, for reasons of both
health and taste, at the same time contributing to the national identities of
various Mediterranean cuisines, as well as the introduction fish and shell
fish on the pyramid to be eaten at least two times per week. A central role
is for plant foods (fruits, vegetables, grains, nuts, legumes, seeds, olives
and olive oil), followed by sh and shellsh, higher in the pyramid are
dairy products (yoghurt and cheese), eggs and chicken, whereas the top
segment contains red meat and sweets. In Scandinavian countries the
Mediterranean diet is interpreted as the Nordic diet; a comparable diet
having local product as fatty sh, red fruit, rape seed oil and local grains
as main components.
e greatest dierence between low carb/high protein and
Mediterranean diet lies in the abstinence from starch in the former:
IR among other factors is caused by long-term consumption of rened
grains in large quantities which demands a stricter approach in reducing
carbohydrates. Another dierence is the protein content, which is
considerably higher in the low carb/high protein diet. e Mediterranean
diet however, is great for weight maintenance in patients with IR or type
2 diabetes mellitus. Almost all products in the Mediterranean diet also
t in the low carb/high protein diet. By the public the Mediterranean
diet is oen interpreted dierently than the original: replacing bre rich
potatoes by large dishes of white pasta with tomato sauce is regarded
as Mediterranean and therefore healthy, as well as daily consumption
of several glasses of wine. Around the Mediterranean sea part of the
population has forgotten about healthy eating: in Croatia for example
the old eating habits have been replaced by a more Western eating style
[123]. Patino-Alanso examined factors that inuenced adherence to the
Mediterranean diet. Adherence was lower among individuals younger
than 49 years of age. e factors associated with improved Mediterranean
diet adherence were female sex, age older than 62 years, moderate alcohol
consumption, and more than 17 metabolic equivalents (METs)/h/wk of
physical exercise. Poorer adherence was associated with males and obesity
[124]. Weight loss in both low carb/high protein and Mediterranean diets
are benecial for CVD risk factors [125].
Long-term Eects of a Low Carb High Protein Diet
One of the problems in low carb-high protein diets is their sustainability.
For how long can patients keep up with the diet. Several researchers found
that low carb-high protein diets lead to signicantly more weight loss short
term, but dierences with other energy restricted diets have disappeared
aer 60 months [126-128]. is was always presented as a problem and
as an argument to refrain from these diets, but in fact it is not. Low carb
diets are designed to help patients lose weight that otherwise would not
have lost substantial amounts of weight, thus improving their health and
postponing or reducing comorbidities. Grieb et al. [129] evaluated the
eect of a long-term (>1 year) consumption of a low carb/high fat diet
on lipid prole, glycaemic control, and cardiovascular disease risk factors
in healthy subjects. Of 31 the dieters enrolled in the study (17 women
and 14 men, aged 51.7 ± 16.6 years), 22 adhered to the diet for more than
3 years. e metabolic proles of most subjects were positive for several
indicators, including relatively low concentrations of triacylglycerols,
high levels of high-density lipoprotein cholesterol (HDL-C), and normal
ratios of low-density lipoprotein cholesterol/HDL-C and total cholesterol/
HDL-C. In most subjects, plasma concentrations of glucose, insulin,
glucagon, cortisol, homocysteine, glycerol, and C-reactive protein were
within reference ranges. e HOMA-IR remained below the threshold
for diagnosis of insulin resistance [129]. ese results were conrmed
in a review on short term results (more than 3 months) [130]. Nackers
examined a group of obese women and found that fast, moderate and
slow weight loss groups diered signicantly in mean weight changes
at 6 months (-13.5, -8.9, and -5.1 kg, respectively, p<0.001), and the fast
and slow groups diered signicantly at 18 months (-10.9, -7.1, and -3.7
kg, respectively, p<0.001). No signicant group dierences were found in
weight regain between 6 and 18 months (2.6, 1.8, and 1.3 kg, respectively,
p<0.9). e fast and moderate groups were 5.1 and 2.7 times more likely
to achieve 10% weight losses at 18 months than the slow group, indicating
short- and long-term advantages to fast initial weight loss. Fast weight
losers obtained greater weight reduction and long-term maintenance, and
were not more susceptible to weight regain than gradual weight losers
[131]. One of the outcomes of the DiOGenes study was that a higher
protein content of an ad libitum diet improves weight loss maintenance in
overweight and obese adults over 12 months [132].
Discussion
is review shows that there is a rationale for prescribing low
carbohydrate/high protein diets to patients for weight loss, and for
improvement of diabetes management. And, although these diets
have been in the commercial domain for most of the time, they should
be administered by dietitians because intake of macro nutrients and
energy expenditure need to be individually assessed. Another argument
for professional handling of these diets in patient care is, that most
obese patients in health care have comorbidities, not seldom more
than one, that also need to be taken into account. Patients that benet
from a low carbohydrate/high protein diet in many cases are vigorous
carbohydrate consumers and need thorough guidance to help them
along. A last argument for specialised dietetic care is that obese patients
have a troubled relation between food and emotional balance, stress and
nutritional knowledge. It is in this complicated eld that patients benet
best from individual treatment, that, however, needs to be embedded in a
multi-disciplinary setting. Montesi et al. [133] argue that a non-physician
lifestyle counsellor would be an asset to an obesity team. I should advocate
that we need the highest quality health professionals, because of the
complex disease obesity is. I would further emphasize that we need to
train dietitians, physicians, nurses, psychologists and physiotherapists in
obesity management. We have a dietary approach that works and should
be given to more patients, to make them able to lose weight and sustain
it. We also need environmental and psychological approaches that can
support patients in their lifelong dealing with this chronic disease.
Conclusion
Low carbohydrate/high protein diets should be considered as a serious
treatment option for all obese patients with and without comorbidities.
ey should be administered by specialised dietitians working in a multi-
disciplinary team.
Strengths and Weaknesses
A strength of this study is the thorough approach of all the evidence
available on management short and long term eects of low carbohydrate
high protein diets on weight loss and comorbidities, as well as the research
done on dierent nutrients. A weakness of the study is that no meta-
analysis took place to weigh the evidence.
Conict of Interest
e author has no conict of interest.
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Citation: Govers E (2017) Low Carb High Protein Diets as Management Tool of Insulin Resistance in Patients with Obesity and/or Type 2 Diabetes
Mellitus. Obes Open Access 3(2): doi http://dx.doi.org/10.16966/2380-5528.131
Open Access
8
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... During recent years low carbohydrate diets have become more popular, because of their effect on weight loss, improvement of HbA1c and on the reduction or end of medication [9,10,14,15]. Low carbohydrate diets can vary from a ≤ 10 energy % (20-50 grams) Very Low Carbohydrate Ketogenic Diet to a ≤ 26 energy % (70-120 grams) Low Carbohydrate Diet (LCD) per day [16]. A restriction of less than 50 grams per day is effective on the short term [16,11]. ...
... Low carbohydrate diets can vary from a ≤ 10 energy % (20-50 grams) Very Low Carbohydrate Ketogenic Diet to a ≤ 26 energy % (70-120 grams) Low Carbohydrate Diet (LCD) per day [16]. A restriction of less than 50 grams per day is effective on the short term [16,11]. Until now studies have compared the effects of low carb and moderate carb diets on weight loss and HbA1c [13], but the difference between Very Low Carbohydrate Ketogenic Diet and LCD has not been fully established. ...
... During recent years low carbohydrate diets have become more popular, because of their effect on weight loss, improvement of HbA1c and on the reduction or end of medication [9,10,14,15]. Low carbohydrate diets can vary from a ≤ 10 energy % (20-50 grams) Very Low Carbohydrate Ketogenic Diet to a ≤ 26 energy % (70-120 grams) Low Carbohydrate Diet (LCD) per day [16]. A restriction of less than 50 grams per day is effective on the short term [16,11]. ...
... Low carbohydrate diets can vary from a ≤ 10 energy % (20-50 grams) Very Low Carbohydrate Ketogenic Diet to a ≤ 26 energy % (70-120 grams) Low Carbohydrate Diet (LCD) per day [16]. A restriction of less than 50 grams per day is effective on the short term [16,11]. Until now studies have compared the effects of low carb and moderate carb diets on weight loss and HbA1c [13], but the difference between Very Low Carbohydrate Ketogenic Diet and LCD has not been fully established. ...
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Background: More than a million people in the Netherlands suffer from type 2 diabetes mellitus; 80 percent is overweight or obese. Weight loss through diet is important; low carb diets are increasingly popular in diabetes management. Objective: From preliminary results we concluded that the 6 × 6 dieet® (a very low carbohydrate ketogenic diet) was more effective in patients with type 2 diabetes and overweight or obesity than other diets. To prove its effectivity, we compared the 6 × 6 dieet® (6 × 6) to a moderate Low Carb Diet (LCD) and an Energy-Restricted Diabetes diet (ERD). Design: A retrospective three-arm study in dietitian practices to reduce weight; HBA1C; and use of medication in overweight/obese adults with type 2 diabetes on 6 × 6 (VLCKD); a 50-100 grams/day LCD; an energy restricted diabetes diet at 3, 6 and 12 months. Results: Data of 344 (n=110; 123; 111 in each study arm) patients from 16 practices were analyzed. More weight loss was seen in patients on 6 × 6, both at a 3, 6, and 12 months follow-up than in patients on LCD or ERD (all p-values <0.05). A total of 34.5% of patients on 6 × 6 turned their HbA1c levels to a value <43 mmol/mol after 12-months follow-up which was a higher proportion than in the LCD study arm (p=0.14) and the ERD study arm (p<0.01). The percentage of patients that stopped or reduced their use of Metformin, SU derivatives or Insulin was larger in the 6 × 6 study arm than in the LCD ad ERD study arms, reaching statistical significance when comparing 6 × 6 with ERD. Conclusions: 6 × 6 was more effective than LCD or ERD in overweight or obese patients with type 2 diabetes regarding weight loss, remission of type 2 diabetes, HbA1c-levels, and the reduction of diabetes medication. Keywords: BMI; Low carbohydrate diet; DMT2 2; HbA1c; VLCKD; 6 × 6; Insulin; Metformin; Sulfoneum derivatives; Weight loss; Diet; Dietitian; Duration of treatment; Primary care
... In conclusion, the ECPPE could effectively inhibit the tested bacteria even in low carbohydrate concentrations and high protein, fat, and fibre concentrations. Such characteristics in food model systems may suit the investigation of ECPPE efficacy in actual food systems containing low carbohydrate and high protein-based media such as meat, poultry, and dairy Figure 2: Chromatogram of ethanol extract of Carica papaya peel products, high fat-content products such as mayonnaise, butter, and margarine, and high fibre food such as legumes, lettuce and barley (Govers, 2017). ...
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This study investigated anti-bacterial activities, chemical composition, and extract efficacy of Carica papaya peel (CPPE) var. Sekaki/Hong Kong. Nine green solvents were used to extract the Carica papaya peel, and the extracts were subjected to anti-bacterial tests and assays against 14 bacteria. The most potent extract was then subjected to phenolic and flavonoid assays, gas chromatography-mass spectrometry (GC/MS) analysis, and efficacy study on food model systems. All CPPEs showed anti-bacterial activities, and pentane extract had moderate to high anti-bacterial activities against all 14 bacteria. Ethanol extract of Carica papaya peel (ECPPE) inhibited C. perfringens, L. monocytogenes, B. subtilis, V. parahaemolyticus, and V. vulnificus with a minimum inhibitory concentration (MIC) of 1.563 mg/ml; therefore, the ECPPE was selected as the most potent extract. The total phenolic (TPC) and flavonoid contents (TFC) of the CPPEs ranged between 6.20 to 58.75 mg GAE/g DW and 1.35-29.09 mg QE/g DW, respectively. Palmitic acid, linoleic acid, β-sitosterol, and stigmasterol in ECPPE may be potential anti-bacterial compounds that render anti-bacterial activities. This study evaluated the ECPPE effectiveness on carbohydrate, protein, fat, and fibre model systems via optical density measurement against C. perfringens, L. monocytogenes, B. subtilis, V. parahaemolyticus, and V. vulnificus. The result showed that the ECPPE could effectively inhibit the tested bacteria in low carbohydrate and high protein, fat, and fibre food model systems.
... In conclusion, the ECPPE could effectively inhibit the tested bacteria even in low carbohydrate concentrations and high protein, fat, and fibre concentrations. Such characteristics in food model systems may suit the investigation of ECPPE efficacy in actual food systems containing low carbohydrate and high protein-based media such as meat, poultry, and dairy Figure 2: Chromatogram of ethanol extract of Carica papaya peel products, high fat-content products such as mayonnaise, butter, and margarine, and high fibre food such as legumes, lettuce and barley (Govers, 2017). ...
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This study investigated anti-bacterial activities, chemical composition, and extract efficacy of Carica papaya peel (CPPE) var. Sekaki/Hong Kong. Nine green solvents were used to extract the Carica papaya peel, and the extracts were subjected to anti-bacterial tests and assays against 14 bacteria. The most potent extract was then subjected to phenolic and flavonoid assays, gas chromatography-mass spectrometry (GC/MS) analysis, and efficacy study on food model systems. All CPPEs showed anti-bacterial activities, and pentane extract had moderate to high anti-bacterial activities against all 14 bacteria. Ethanol extract of Carica papaya peel (ECPPE) inhibited C. perfringens, L. monocytogenes, B. subtilis, V. parahaemolyticus, and V. vulnificus with a minimum inhibitory concentration (MIC) of 1.563 mg/ml; therefore, the ECPPE was selected as the most potent extract. The total phenolic (TPC) and flavonoid contents (TFC) of the CPPEs ranged between 6.20 to 58.75 mg GAE/g DW and 1.35-29.09 mg QE/g DW, respectively. Palmitic acid, linoleic acid, β-sitosterol, and stigmasterol in ECPPE may be potential anti-bacterial compounds that render anti-bacterial activities. This study evaluated the ECPPE effectiveness on carbohydrate, protein, fat, and fibre model systems via optical density measurement against C. perfringens, L. monocytogenes, B. subtilis, V. parahaemolyticus, and V. vulnificus. The result showed that the ECPPE could effectively inhibit the tested bacteria in low carbohydrate and high protein, fat, and fibre food model systems.
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This study investigated antibacterial activities, chemical composition and extract efficacy of Carica papaya peel (CPPE) var. Sekaki/ Hong Kong. Nine green solvents were used to extract the Carica papaya peel, and the extracts were subjected to antibacterial tests and assays against 14 bacteria. The most potent extract was then subjected to phenolic and flavonoid assays, gas chromatography-mass spectrometry (GC/MS) analysis, and efficacy study on food model systems. All CPPEs showed antibacterial activities, and pentane extract had moderate to clear inhibitions against all 14 bacteria. Ethanol extract of Carica papaya peel (ECPPE) inhibited C. perfringens, L. monocytogenes, B. subtilis, V. parahaemolyticus , and V. vulnificus with a minimum inhibitory concentration (MIC) of 1.563 mg/ml; therefore, the ECPPE was selected as the most potent extract. The total phenolic (TPC) and flavonoid contents (TFC) of the CPPEs ranged between 6.20 to 58.75 mg GAE/g DW and 1.35–29.09 mg QE/g DW, respectively. Palmitic acid, linoleic acid, β-sitosterol and stigmasterol in ECPPE may be potential antibacterial compounds that render antibacterial activities. The ECPPE could effectively inhibit the tested bacteria in low carbohydrate and high protein, fat, and fibre food model systems, which may suit the investigation of ECPPE efficacy in meat, poultry and dairy products, high fat-content products such as mayonnaise, butter and margarine and high fibre food such as legumes, lettuce and barley.
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Background: The relationship between dietary and lifestyle risk factors and long-term mortality from colorectal cancer is poorly understood. Several factors, such as obesity, intakes of red meat, and use of aspirin, have been reported to be associated with risk of colorectal cancer mortality, though these findings have not been replicated in all studies to date. Methods: In the Minnesota Colon Cancer Control Study, 46,551 participants 50-80 years old were randomly assigned to usual care (control) or annual or biennial screening by fecal occult blood testing. Colon cancer mortality was assessed after 30 years of follow-up. Dietary intake and lifestyle risk factors were assessed by questionnaire at baseline. Results: Age [hazard ratio (HR) 1.09; 95% CI 1.07, -1.11], male sex (HR 1.25; 95% CI 1.01, 1.57), and higher body mass index (BMI) (HR 1.03; 95% CI 1.00-1.05) increased the risk of CRC mortality, while undergoing screening for CRC was associated with a reduced risk of colorectal cancer mortality (HR 0.76; 95% CI 0.61-0.94 and 0.67; 95% CI 0.53-0.83 for biennial and annual screening, respectively). Intakes of grains, meats, proteins, coffee, alcohol, aspirin, fiber, fruits, and vegetables were not associated with colorectal cancer mortality. Conclusions: Our study confirms the relationship between BMI and long-term colorectal cancer mortality. Modulation of BMI may reduce risk of CRC mortality.
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(1) Background: Medical interventions including assisted reproductive technologies have improved fertility outcomes for many sub-fertile couples. Increasing research interest has investigated the effect of low carbohydrate diets, with or without energy restriction. We aimed to systematically review the published literature to determine the extent to which low carbohydrate diets can affect fertility outcomes; (2) Methods: The review protocol was registered prospectively with Prospective Register for Systematic Reviews (registration number CRD42016042669) and followed Preferred Reporting Items For Systematic Reviews and Meta-Analyses guidelines. Infertile women were the population of interest, the intervention was low carbohydrate diets (less than 45% total energy from carbohydrates), compared to usual diet (with or without co-treatments). Four databases were searched from date of commencement until April 2016; a supplementary Google scholar search was also undertaken. Title and abstract, then full text review, were undertaken independently and in duplicate. Reference lists of included studies and relevant systematic reviews were checked to ensure that all relevant studies were identified for inclusion. Quality assessment was undertaken independently by both authors using the Quality Criteria Checklist for Primary Research. Outcome measures were improved fertility outcomes defined by an improvement in reproductive hormones, ovulation rates and/or pregnancy rates; (3) Results: Seven studies fulfilled the inclusion criteria and were included in the evidence synthesis. Interventions were diverse and included a combination of low carbohydrate diets with energy deficit or other co-treatments. Study quality was rated as positive for six studies, suggesting a low risk of bias, with one study rated as neutral. Of the six studies which reported changes in reproductive hormones, five reported significant improvements post intervention; (4) Conclusion: The findings of these studies suggest that low carbohydrate diets warrant further research to determine their effect. These randomised controlled trials should consider the effect of carbohydrates (with or without energy deficit) on hormonal and fertility outcomes.
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Background Intentional weight loss in obese older adults is a risk factor for accelerated muscle mass loss. We investigated whether a high protein diet and/or resistance exercise preserves fat free mass (FFM) during weight loss in overweight and obese older adults. Methods We included 100 overweight and obese adults (55–80 year) in a randomized controlled trial (RCT) with a 2 × 2 factorial design and intention-to-treat analysis. During a 10-week weight loss program all subjects followed a hypocaloric diet. Subjects were randomly allocated to either a high protein (1.3 g/kg body weight) or normal protein diet (0.8 g/kg), with or without a resistance exercise program 3 times/week. FFM was assessed by air displacement plethysmography. ResultsAt baseline, mean (±SD) BMI was 32 ± 4 kg/m2. During intervention, protein intake was 1.13 ± 0.35 g/kg in the high protein groups vs. 0.98 ± 0.29 in the normal protein groups, which reflects a 16.3 ± 5.2 g/d higher protein intake in the high protein groups. Both high protein diet and exercise did not significantly affect change in body weight, FFM and fat mass (FM). No significant protein*exercise interaction effect was observed for FFM. However, within-group analysis showed that high protein in combination with exercise significantly increased FFM (+0.6 ± 1.3 kg, p = 0.011). ConclusionA high protein diet, though lower than targeted, did not significantly affect changes in FFM during modest weight loss in older overweight and obese adults. There was no significant interaction between the high protein diet and resistance exercise for change in FFM. However, only the group with the combined intervention of high protein diet and resistance exercise significantly increased in FFM. Trial registrationDutch Trial Register, number NTR4556, date 05-01-2014.
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Background/objectives: Low plasma 25-hydroxy-vitamin D (25OHD) and high levels of parathyroid hormone (PTH) are associated with obesity and could play a role in the occurrence of its complications such as insulin resistance. The objective of the study was to evaluate whether the relationship between 25OHD status and phosphocalcic parameters differ between metabolically healthy obese (MHO) and insulin-resistant obese (IRO). Subjects/methods: Cross-sectional study including 158 consecutive adults (121 females) with obesity (BMI 35.15±2.8 kg/m2), age 43.21±13.6 years. Serum 25OHD, calcemia, phosphatemia, PTH, plasma lipids, fasting plasma glucose, insulin levels and body composition were measured. Results: Participants were classified as MHO (n = 65) or IRO (n = 93) based on HOMA-IR value. IRO patients had higher BMI (p = 0.001), waist circumference (p = 0.03), and trunk fat mass (p = 0.007) than MHO patients. Mean HbA1c (p = 0.03), triglycerides (p = 0.02), and hsCRP (p = 0.04) plasmatic levels were increased in the IRO group. No between-groups difference was found on 25OHD, PTH, calcium or phosphorus plasmatic levels. Regarding predictive factors of 25OHD, only age predicted 25OHD level among IRO participants while no factors were identified in MHO. No predictive factors of PTH plasmatic level were identified in IRO and MHO groups. Conclusions: Although MHO and IRO patients have different metabolic profiles, we did not detect any difference regarding either 25OHD or PTH. IR was not a predictive factor of vitamin D status. Our results confirm the absence of link between vitamin D status and IR in moderate obesity.
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Aim To assess the adherence to the Mediterranean diet in the population of Dalmatia in southern Croatia. Methods A cross-sectional study was performed within the 10 001 Dalmatians cohort, encompassing 2768 participants from Korčula and Vis islands and the City of Split, who were recruited during 2011-2014. Using the data obtained from food frequency questionnaire we calculated the Mediterranean Diet Serving Score (MDSS). Multivariate logistic regression was used to identify the characteristics associated with the adherence to the Mediterranean diet, with age, sex, place of residence, education attainment, smoking, and physical activity as covariates. Results The median MDSS score was 11 out of 24 points (interquartile range 8-13), with the highest score recorded on the island of Vis. Participants reported a dietary pattern that had high compliance with the Mediterranean diet guidelines for consumption of cereals (87% met the criteria), potatoes (73%), olive oil (69%), and fish (61%), moderate for consumption of fruit (54%) and vegetables (31%), and low for consumption of nuts (6%). Overall, only 23% of the participants were classified as being adherent to the Mediterranean diet, with a particularly low percentage among younger participants (12%) compared to the older ones (34%). Men were less likely to show good adherence (odds ratio 0.52, 95% confidence interval 0.42-0.65). Conclusion This study revealed rather poor compliance with the current recommendations on the Mediterranean diet composition in the population of Dalmatia. Public health intervention is especially needed in younger age groups and in men, who show the greatest departure from traditional Mediterranean diet and lifestyle.
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Background: The epidemiologic evidence for associations between dietary factors and breast cancer is weak and etiologic mechanisms are often unclear. Exploring the role of dietary biomarkers with metabolomics can potentially facilitate objective dietary characterization, mitigate errors related to self-reported diet, agnostically test metabolic pathways, and identify mechanistic mediators. Objective: The aim of this study was to evaluate associations of diet-related metabolites with the risk of breast cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Design: We examined prediagnostic serum concentrations of dietrelated metabolites in a nested case-control study in 621 postmenopausal invasive breast cancer cases and 621 matched controls in the multicenter PLCO cohort. We calculated partial Pearson correlations between 617 metabolites and 55 foods, food groups, and vitamin supplements on the basis of the 2015 Dietary Guidelines for Americans and derived from a 137-item self-administered foodfrequency questionnaire. Diet-related metabolites (P-correlation < 1.47 × 10⁻⁶) were evaluated in breast cancer analyses. ORs for the 90th compared with the 10th percentile were calculated by using conditional logistic regression, with body mass index, physical inactivity, other breast cancer risk factors, and caloric intake controlled for (false discovery rate <0.2). Results: Of 113 diet-related metabolites, 3 were associated with overall breast cancer risk (621 cases): Caprate (10:0), a saturated fatty acid (OR: 1.77; 95% CI = 1.28, 2.43); γ-carboxyethyl hydrochroman (γ-CEHC), a Vitamin E (γ-tocopherol) derivative (OR: 1.64; 95% CI: 1.18, 2.28); and 4-androsten-3β,17β-diol-monosulfate (1), an androgen (OR: 1.61; 95% CI: 1.20, 2.16). Nineteen metabolites were significantly associated with estrogen receptor (ER)-positive (ER⁺) breast cancer (418 cases): 12 alcohol-associated metabolites, including 7 androgens and a-hydroxyisovalerate (OR: 2.23; 95% CI: 1.50, 3.32); 3 Vitamin E (tocopherol) derivatives (e.g., γ-CEHC; OR: 1.80; 95% CI: 1.20, 2.70); butter-associated caprate (10:0) (OR: 1.81; 95% CI: 1.23, 2.67); and fried food-associated 2-hydroxyoctanoate (OR: 1.46; 95% CI: 1.03, 2.07). No metabolites were significantly associated with ER-negative breast cancer (144 cases). Conclusions: Prediagnostic serum concentrations of metabolites related to alcohol, Vitamin E, and animal fats were moderately strongly associated with ER⁺ breast cancer risk. Our findings show how nutritional metabolomics might identify diet-related exposures that modulate cancer risk.
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Background/objectives: Although adipose tissue (AT) hypoxia is present in rodent models of obesity, evidence for this in humans is limited. Here, we investigated the effects of diet-induced weight loss on abdominal subcutaneous AT oxygen tension (pO2), AT blood flow (ATBF), AT capillary density, AT morphology and transcriptome, systemic inflammatory markers, and insulin sensitivity in humans. Subjects/methods: Fifteen overweight and obese individuals underwent a dietary intervention (DI), consisting of a 5-week very-low-calorie diet (VLCD, 500 kcal/d) (WL), and a subsequent 4-week weight stable diet (WS). Body composition, AT pO2 (optochemical monitoring), ATBF ((133)Xe wash-out), and whole-body insulin sensitivity were determined, and AT biopsies were collected at baseline, end of WL (week 5), and end of WS (week 9). Results: Body weight, body fat percentage, and adipocyte size decreased significantly during the DI period. The DI markedly decreased AT pO2 and improved insulin sensitivity, but did not alter ATBF. Finally, the DI increased AT gene expression of pathways related to mitochondrial biogenesis and non-mitochondrial oxygen consumption. Conclusions: VLCD-induced weight loss markedly decreases abdominal subcutaneous AT pO2, which is paralleled by a reduction in adipocyte size, increased AT gene expression of mitochondrial biogenesis markers and non-mitochondrial oxygen consumption pathways, and improved whole-body insulin sensitivity in humans.International Journal of Obesity accepted article preview online, 09 February 2017. doi:10.1038/ijo.2017.38.
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The merits of a fibre-rich diet are well documented. Resistant starch (RS) is a form of starch that resists digestion in the small intestine and, as such, is classified as a type of dietary fibre. RS can be categorised as one of five types (RS1–5), some of which occur naturally in foods such as bananas, potatoes, grains and legumes and some of which are produced or modified commercially, and incorporated into food products. This review describes human evidence on the health effects of RS consumption, with the aim of identifying any benefits of RS-rich foods and RS as a functional ingredient. The reduced glycaemic response consistently reported with RS consumption, when compared with digestible carbohydrate, has resulted in an approved European Union health claim. Thus, RS-rich foods may be particularly useful for managing diabetes. There appears to be little impact of RS on other metabolic markers, such as blood pressure and plasma lipids, though data are comparatively limited. Promising results on markers of gut health suggest that further research may lead to the classification of RS as a prebiotic. Microbial fermentation of RS in the large intestine to produce short-chain fatty acids likely underpins some of its biological effects, including increasing satiety. However, effects on appetite have not resulted in notable changes in bodyweight after long-term consumption. Emerging research suggests potential for RS as an ingredient in oral rehydration solutions and in the treatment of chronic kidney disease. Overall, RS possesses positive properties as a healthy food component.
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Objectives: Traditional evaluations of metabolic health may overlook underlying dysfunction in individuals who show no signs of insulin resistance or dyslipidemia. The purpose of this study was to characterize metabolic health in overweight and obese adults using traditional and non-traditional cardiometabolic variables. A secondary purpose was to evaluate differences between overweight/obese and male/female cohorts, respectively. Methods: Forty-nine overweight and obese adults (Mean ± SD; Age=35.0 ± 8.9 yrs; Body mass index=33.6 ± 5.2 kg·m⁻²; Percent body fat [%fat]=40.0 ± 7.3%) were characterized. Body composition (fat mass [FM], lean mass [LM], %fat) was calculated using a 4-compartment model; visceral adipose tissue (VAT) was quantified using B-mode ultrasound. Resting metabolic rate (RMR) and respiratory exchange ratio (RER) were evaluated using indirect calorimetry. Fasted blood and saliva samples were analyzed for total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides (TRG), glucose (GLUC), insulin, leptin, estradiol, and cortisol. Results: The prevalence of individuals with two or more cardiometabolic risk factors increased from 13%, using traditional risk factors (GLUC, TRG, HDL), to 80% when non-traditional metabolic factors (VAT, LM, RMR, RER, TC, LDL, HOMA-IR) were considered. Between overweight/obese, there were no significant differences in %fat (p=0.146), VAT (p=0.959), RER (p=0.493), lipids/GLUC (p>0.05), insulin (p=0.143), leptin (p=0.053), or cortisol (p=0.063); obese had higher FM, LM, RMR, and estradiol (p<0.001). Males had greater LM, RMR, and TRG (p<0.01); females had greater %fat, and leptin (p<0.001). There were no significant sex differences in RER, estradiol, insulin, or cortisol (p>0.05). Conclusions: Evaluating metabolic health beyond BMI and traditional cardiometabolic risk factors can give significant insights into metabolic status. Due to high variability in metabolic health in overweight and obese adults and inherent sex differences, implementation of body composition and visceral fat measures in the clinical setting can improve early identification and approaches to disease prevention.