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
*Corresponding author: Elisabeth Govers, the Dutch Knowledge Centre for Dietitians specialised in the management of obesity, Amsterdam, Netherlands (KDOO), E-mail: email@example.com
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.
Low carbohydrate/high protein diet; Insulin resistance; Obesity; T2dm; Cvd; Nafld; Dietitian
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 . 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 differ greatly in macro nutrient content from national guidelines and still be healthy. Furthermore: the amount of saturated fat in the diet; possible deficiencies 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
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; fiber and alcohol. The 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.
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 overfilled, adipose cells enlarge. Continuous weight gain in individuals leads to fat storage outside fatty tissues into the abdomen (visceral fat), the muscles and liver. The fat stored in these locations has a different metabolism which is characterized by hypoxia, an impaired blood flow through the adipose tissue; metaflammation; an infiltration of macrophages. Leading to a rise in leptin, causing constant appetite; a rise in angiotensin, causing hypertension.
On the other hand drop in adiponectin, influencing hyperlipidemia and insulin resistance; and elevated insulin-sensitizing and anti-inflammatory adipokines. The rise in pro-inflammatory 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 effectively, 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. This often 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].
The prevalence of IR in the obese and overweight population is larger than is usually estimated and IR is in primary practice often 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 . In obese subjects, these figures are 33.6% and 41.3% respectively. Te 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. They have still, for unknown reasons, preserved their insulin sensitivity . 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%. There were no significant differences between overweight and obese in %fat; VAT; lipids/ GLUC; insulin; leptin; or cortisol. The 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 significant sex differences 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, after a breakfast of 60 grams of carbohydrates; 2.5 hours after breakfast and after 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 after a meal. In obese and diabetic subjects the levels were even higher (Table 1) . The levels measured were much higher than published in several studies [15,16]. Even adolescents can already be insulin resistant .
|Patient A||Fasting||½ h. after Break fast||2 ½ h. After Break fast||After Lunch|
|Patients with normal values after 2 ½ hrs|
|Patient B||Fasting||½ h. after Break fast||2 ½ h. After Break fast||After Lunch|
|Patient 17 Years. Insulin stays elevated, plus accumulating effect|
|Patient C||Fasting||½ h. after Break fast||2 ½ h. After Break fast||After Lunch|
|Patient 45 years. Obese|
|Patient D||Fasting||½ h. after Break fast||2 ½ h. After Break fast||After Lunch|
|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|
Table 1: Glucose and Insulin values in at random selected patients.
Patients with normal values of glucose mmol/l; insulin mU/l
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 ; high intake of free fatty acids and triglycerides ; a low fibre content ; diets with a high glycaemic load ; take away meals [28,29]; starch, rich in amylopectin ; 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. The effects 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 (BMI ≥25 kg/m2at baseline) . The change of developing IR syndrome (2 or more components) was 72% lower (odds ratio, 0.28; 95% confidence 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% confidence interval, 0.70- 0.88). These 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.
|► 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 deficiency|
|► Fatigue||► Emotional instability|
|► Increased risk of infections|
Table 2: Clinical parameters.
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. The 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 . Waist circumference is dominant over weight and BMI. The 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 , 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 . 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-off 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 . Because in Western countries the correct weight and waist cut-off points for patients of Asian origin are not always used obesity and IR are underestimated in this population.
|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 fibre intake||Low vitamin D intake|
Table 3: Food linked to promotion of insulin resistance.
The presumption is that anyone can lose weight on any diet that restricts energy intake . 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]. This problem is well known in patients with IGT and type 2 diabetes . Even though we know that greater weight loss improves long-term maintenance  and metabolic functions, e.g. pancreas function . For years many health professionals have doubted the motivation of their patients, thus explaining the low success rates, instead of doubting the effectiveness 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 significant conservative treatment option and evidence based effective [50-54], but not every diet is fit for everyone. If patients fail to lose substantial weight and suffer 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].
|>5% weight loss
||<3% or no weight loss
Table 4: Weight loss after 6 months treatment.
Treatment goals are: firstly 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 finally 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 different because of IR and how they can control that. Each kilo of weight loss will improve comorbidities . A weight loss of >5% is necessary for beneficial effects on HbA1c, lipids, and blood pressure .
Table 5: Treatment goals.
The answer lies in the changed metabolism due to IR [1-4]. The 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 deficit, fat can be released from the fatty tissue. But, a low carbohydrate diet is no magical bullet. The normal law of energy expenditure stays intact: if a patient consumes a diet that is not low enough in calories, or is not close enough to the RMR, or less than 600 calories deficit of the usual intake, weight loss will not occur [51,60]. The 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 first 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) . In the first 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 . The aim is to bring the high release of insulin down. This also applies to obese patients with type 2 DM [67-70]. When weight loss results – and improvement of comorbidities - are sufficiently 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.
|Energy||Individually assessed||600 calories deficit of usual intake|
|Protein||Individually assessed; large intake of dairy; egg, fish, chicken; shell fish; 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, fish, dairy, cheese, vegetables, pulses, potatoes and grains||300 mg/day|
|Exersize||Combination of resistance training and fitness||30-60 minutes per day|
Table 6: Elements of the low carb/high protein diet.
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 .
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 sufficiently this way, a lower intake of carbohydrates which would also promote ketosis, is not advisable. Carbohydrate requirement should be individually calculated. The 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) . The 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 defined moderately low carb as 30-40% of energy, with the carbohydrate content depending on the energy intake . However, 40% of a 1600 calorie diets 160 grams, for many women a normal daily intake. This is de facto not a low carb diet and it will not make a difference with an energy restricted diet. Therefore it will not have desired results in patients with IR.
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.
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.
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.
Table 7: Levels of carbohydrate restriction.
*carbohydrate content of the diet needs to be assessed individually for each patient
One of the problems connected with obesity is carbohydrate craving. Some patients with a mild eating disorder have less craving due to a low carbohydrate diet, because insulin promotes craving. They 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 . For patients with severe eating disorders a carbohydrate restricted diet lower than 100 grams is not a treatment option. These patients need to get cognitive behavioural therapy (CBT) first. 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 effective to reduce fasting glucose and HBA1C levels in patients with type 2 diabetes mellitus  as well as to reduce visceral fat . It should be the first 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. These 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 first, and adjust short working insulin to the amount of carbohydrates in the meal. After 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 after two months to verify insulin need. High glucose values without fever usually mean that the insulin dosage is too high .
The diet should have 1.2-1.5 grams protein per kg present body weight. Krieger calculated the cut-off 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 figure rose to 1.2 grams/kilo . The 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 . 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 . Leucine prevents decrease of muscle and liver tissue; and it is a part of haemoglobin. Leucine containing products, e.g. dairy, eggs, meat, fish and pulses are therefore an essential part of the diet. The effect of protein rich foods is that they enhance thermogenesis. This effect 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, fish, poultry, eggs, nuts, seeds and pulses. A high protein diet leads to significantly higher decrease of fat mass after a year; and better weight maintenance . This study also looked into genetic predisposition and found that carriers of the AA genotype (67% of the population) benefit 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 benefitted from the changed food behaviour of their parents: their biomarkers also improved .
The diet of elderly can be low in protein , 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].
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. The 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 beneficial for type 2 diabetes [92,96- 99]. A systematic review and meta-analysis by Pimpin et al.  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.  found in a meta-analysis that replacing carbohydrates with PUFA (poli-unsaturated fatty acids) leads to significant lowering of glucose, HBA1C, C peptide, and HOMA-IR. PUFA also significantly improved insulin secretion capacity when replacing carbohydrate, saturated fats or mono-unsaturated fatty acids. The 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 transpalmoleic fat was inversely associated with type 2 diabetes .
Omega-3 fatty acids have positive effects 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 effects on hepatic metabolism, oxidative stress, and fibrosis . A systematic review showed omega-3 fatty acids can reduce waist circumference, but have no effect on BMI . Patients with type 2 diabetes who received 520 mg of DHA and EPA had a beneficial effect on waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin ratio, and lipid profile compared to placebo. In both groups no changes in adiponectin were found; whereas resistin, insulin, and HOMA-IR increased in both groups .
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 effects and should be part of the diet, consumed as fatty fish or supplements with fish oil. In a low carb diet there is very little room for products like cookies and biscuits, cake, pie, ice-cream, milkshake and chocolate. This means that a low carb diet automatically is lower in saturated and industrial trans-fat, the latter being defined as a serious risk factor for CVD .
If vitamin D is deficient in the diet and from sunlight, supplementation is advisable with 400 or 800 IU (10-20 mcg). The 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 beneficial. Renzaho found evidence that in ethnic groups links between vitamin D deficiency and obesity-related chronic diseases exist, reporting a statistically significant result with a measurement of obesity, T2DM, CVDs, and the metabolic syndrome. However, the strength of the association varied across ethnic groups . Patients with NAFLD 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 . It is also not clear whether low vitamin D status is a cause or an effect of IR and obesity. Therefore 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 . Mallard found no evidence for a dose-response effect of weight loss on the change in serum 25-hydroxyvitamin D .
A contributing problem in the assessment of vitamin D studies is, that in different 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 deficiency is very common is these regions and is in many cases not actively diagnosed.
The diet should contain sufficient magnesium. Since magnesium rich foods are meat, fish, dairy, cheese, vegetables, pulses, potatoes and grains, a deficiency 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 .
Iodine is a crucial element in thyroid function. Thyroid hormones are involved in the regulation of metabolism, thermogenesis, food intake, and fat oxidation. Iodine can be obtained by eating sea fish and shellfish, 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. The prevalence of overt and subclinical hypothyroidism was high (19.5%). They 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 . 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 . 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. There was an association between obesity (BMI>30 kg/m(2)) and serum TSH levels (P=0.001) . The 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 sufficient iodine intake is a point of concern for many
Fiber is an important element in any diet. In the low carb/high protein diet fiber may not come from bread, or potatoes, the fiber content of the diet is usually that high that patients seldom complain about intestinal problems. Patients on a Western diet often 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 fiber, their intake in fiber 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 fiber. Pulses are advised once a week in the second phase, which is more often than most patients on a Western diet are used to.
The 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 modified 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 effect as dietary fiber. Consuming it at high doses can lead to flatulence. When isolated resistant starch is used to substitute for flour 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 first acknowledged by the FDA in the USA was almost immediately retrieved with the note ´there is limited credible scientific evidence for a qualified health claim for high-amylose maize resistant starch and reduced risk of type 2 diabetes.
Alcohol is discouraged in the first 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 significantly 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 significantly associated with ER- breast cancer (144 cases) . For colon cancer a relation with age, male sex and high BMI was found. Intakes of grains, meats, proteins, coffee, alcohol, aspirin, fibre, fruits, and vegetables were not associated with colorectal cancer mortality .
The 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]. The ‘poor’ diet of the people of the southern Mediterranean, consisting mainly of 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. The 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 fish and shellfish, 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 fish, red fruit, rape seed oil and local grains as main components.
The greatest difference 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 refined grains in large quantities which demands a stricter approach in reducing carbohydrates. Another difference is the protein content, which is considerably higher in the low carb/high protein diet. The 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 fit in the low carb/high protein diet. By the public the Mediterranean diet is often interpreted differently than the original: replacing fibre 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 . Patino-Alanso examined factors that influenced adherence to the Mediterranean diet. Adherence was lower among individuals younger than 49 years of age. The 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 . Weight loss in both low carb/high protein and Mediterranean diets are beneficial for CVD risk factors .
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 significantly more weight loss short term, but differences with other energy restricted diets have disappeared after 60 months [126-128]. This 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.  evaluated the effect of a long-term (>1 year) consumption of a low carb/high fat diet on lipid profile, 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. The metabolic profiles 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. The HOMA-IR remained below the threshold for diagnosis of insulin resistance . These results were confirmed in a review on short term results (more than 3 months) . Nackers examined a group of obese women and found that fast, moderate and slow weight loss groups differed significantly 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 differed significantly at 18 months (-10.9, -7.1, and -3.7 kg, respectively, p<0.001). No significant group differences were found in weight regain between 6 and 18 months (2.6, 1.8, and 1.3 kg, respectively, p<0.9). The 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 . 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 .
This 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 benefit 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 field that patients benefit best from individual treatment, that, however, needs to be embedded in a multi-disciplinary setting. Montesi et al.  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.
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 multidisciplinary team.
A strength of this study is the thorough approach of all the evidence available on management short and long term effects of low carbohydrate high protein diets on weight loss and comorbidities, as well as the research done on different nutrients. A weakness of the study is that no metaanalysis took place to weigh the evidence.
The author has no conflict of interest.
- Westman EC, Feinman RD, Mavropoulos JC, Vernon MC, Volek JC, et al. (2007) Low-carbohydrate nutrition and metabolism. Am J Clin Nutr 86: 276-284. [Ref.]
- Westman EC, Yancy WS, Mavropoulos JC, Marquart M, McDuffie JR (2008) The effect of a low-carbohydrate, ketogenic diet versus a lowglycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metabo 5: 36. [Ref.]
- Frubeck G, Gomez Ambrosi J, Murazabal FJ, Burrell MA (2001) The adipocyte: a model for integration of endocrine and metabolic signalling in energy metabolism regulation. Am J Physiol Endocrinol Metab 280: E827-E847. [Ref.]
- Goossens GH (2008) The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance. Physiol Behav 94: 206-218. [Ref.]
- Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29: 415-445. [Ref.]
- Carr DB, Utzschneider KM, Boyko EJ, Asberry PJ, Hull RL, et al. (2005) A reduced-fat diet and aerobic exercise in Japanese Americans with impaired glucose tolerance decreases intra-abdominal fat and improves insulin sensitivity but not beta-cell function. Diabetes 54: 340-347. [Ref.]
- Ryan DH, Diabetes Prevention Program Research Group (2003) Diet and exercise in the prevention of diabetes. Int J Clin Pract Suppl 134: 28-35. [Ref.]
- Volek JS, Phinney CE, Forsythe CE, Quann EE, Wood RJ, et al. (2008) Carbohydrate restriction has a more favourable impact on the metabolic syndrome than a low fat diet. Lipids 44: 297-309. [Ref.]
- Govers E (2015) Obesity and Insulin Resistance Are the Central Issues in Prevention of and Care for Comorbidities. Healthcare 3: 408-416. [Ref.]
- Pereira MA, Jacobs DR Jr, Van Horn L, Slattery ML, Kartashov AI, et al. (2002) Dairy consumption, obesity, and the insulin resistance syndrome in young adults: the CARDIA Study. JAMA 287: 2081-2089. [Ref.]
- Bluher M (2010) The distinction of metabolically ‘healthy’ from ‘unhealthy’ obese individuals. Curr Opin Lipidol 21: 38-43. [Ref.]
- Hirsch KR, Smith Ryan AE, Blue MN, Mock MG, Trexler ET, et al. (2016) Metabolic characterization of overweight and obese adults. Phys Sports med 44: 362-372. [Ref.]
- Muller MJ, Lagerpusch M, Enderle J, Schautz B, Heller M, et al. (2012) Beyond the body mass index: tracking body composition in the pathogenesis of obesity and the metabolic syndrome. Obes Rev13: 6-13. [Ref.]
- Govers E, Slof E, Verkoelen H, Ten Hoor Aukema NM, KDOO (2015) Guideline for the Management of Insulin Resistance. Int J Endocrinol Metab Disord 1. [Ref.]
- McMillan Price J, Petocz P, Atkinson F, O Neill K, Samman S, et al. (2006) Comparing of 4 diets varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults. Arch Intern Med 166: 1466-14674. [Ref.]
- Larsen TM, Dalskov S, Van Baak M, Jebb S, Kafatos A, et al. (2009) The Diogenes Study, The Diet, Obesity and Genes (Diogenes) Dietary Study in eight European countries - a comprehensive design for long-term intervention. Journal compilation © 2009 International Association for the Study of Obesity. Obesity Reviews 11: 76-91. [Ref.]
- Herder C, Schneitler S, Rathmann W, Haastert B, Schneitler H, et al. (2007) Low-grade inflammation, obesity, and insulin resistance in adolescents. J Clin Endocrinol Metab 92: 4569-4574. [Ref.]
- Bajaj M. (2012) Nicotine and Insulin Resistance: When the Smoke Clears. Diabetes 61: 3078-3080. [Ref.]
- Juneja A, Dwivedi S, Srivastava DK, Chandra K (2017) Insulin Resistance in Young Obese Subjects and Its Relation to Smoking (A Pilot Study). Indian J Clin Biochem 32: 99-102. [Ref.]
- Haj Mouhamed D, Ezzaher A, Neffati F, Douki W, Gaha L, et al. (2016) Effect of cigarette smoking on insulin resistance risk. Ann Cardiol Angeiol (Paris) 65: 21-25. [Ref.]
- Lakka TA, Laaksonen DE, Lakka HM, Mannikko N, Niskanen LK, et al. (2003) Sedentary lifestyle, poor cardio respiratory fitness, and the metabolic syndrome. Med Sci Sports Exerc 35: 1279-1286. [Ref.]
- Hamilton MT, Hamilton DG, Zderic TW (2007) Role of low energy expenditure and sitting in obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Diabetes 56: 2655-2667. [Ref.]
- Reaven GM (2002) Diet and synrome X. Curr Atheroscler Rep 2: 503- 507. [Ref.]
- Abasi F, McLaughlin T, Lamendola C, Kim HS, Tanaka A, et al. (2000) High carbohydrate diets, triglyceride-rich lipoproteins, and coronary heart disease risk. Am J Cardiol 85: 45-48. [Ref.]
- Schinner S, Scherbaum WA, Bornstein SR, Barthel A (2005) Molecular mechanisms of insulin resistance. Diabet Med 22: 674-682. [Ref.]
- Ludwig DS, Pereira MA, Kroenke CH, Hilner JE, Van Horn L, et al. (1999) Dietary fiber, weight gain, and cardiovascular risk disease factors in young adults. JAMA 282:1539-1546. [Ref.]
- Liu S, Willett WC, Stampfer MJ, Hu FB, Franz M , et al. (2000) A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women. Am J Clin Nutr 71: 1455-1461. [Ref.]
- Sampey BP, Vanhoose AM, Winfield HM, Freemerman AJ, Muehlbauer MJ, et al. (2011) Cafeteria diet is a robust model of human metabolic syndrome with liver and adipose inflammation: comparison to high-fat diet. Obesity (Silver Spring) 19: 1109-1117. [Ref.]
- Johnson AR, Wilkerson MD, Sampey BP, Troester MA, Hayes DN, et al. (2016) Cafeteria diet-induced obesity causes oxidative damage in white adipose. Biochem Biophys Res Commun 473: 545-550. [Ref.]
- Juliano BO, Perez CM, Komindr S, Banphotkasem S (1989) Properties of Thai cooked rice and noodles differing in glycaemic index in noninsulin-dependent diabetics. Plant Foods Hum Nutr 39: 369-374. [Ref.]
- Chiu KC, Chu A, Go VL, Saad MF (2004) Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 79: 820-825. [Ref.]
- Ou HY1, Karnchanasorn R, Lee LZ, Chiu KC (2011) Interaction of BMI with vitamin D and insulin sensitivity. Eur J Clin Invest 41: 1195-1201. [Ref.]
- Basciano H, Federico L, Adeli K (2005) Basciano. Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab 2: 5. [Ref.]
- Bidwell AJ (2017) Chronic Fructose Ingestion as a Major Health Concern: Is a Sedentary Lifestyle Making It Worse? A Review. Nutrients 9: E549. [Ref.]
- Rayssiguier Y, Gueux E, Nowacki W, Rock E, Mazur A et al. (2006) High fructose consumption combined with low dietary magnesium intake may increase the incidence of the metabolic syndrome by inducing inflammation. Magnes Res 19: 237-243. [Ref.]
- Juliano BO, Perez CM, Komindr S, Banphotkasem S (1989) Properties of Thai cooked rice and noodles differing in glycemic index in noninsulin-dependent diabetics. Plant Foods Hum Nutr 39: 369-374. [Ref.]
- Boers HM, Seijen Ten Hoorn J, Mela DJ (2015) A systematic review of the influence of rice characteristics and processing methods on postprandial glycaemic and insulinaemic responses. Br J Nutr 114: 1035-1045. [Ref.]
- Lean ME, Han TS, Morrison CE (1995) Waist circumference as a measure for indicating need for weight management. BMJ 311: 158-161. [Ref.]
- Millar SR, Perry IJ, Van den Broeck J, Phillips CM (2015) Optimal central obesity measurement site for assessing cardiometabolic and type 2 diabetes risk in middle-aged adults. PLoS One 10: e0129088. [Ref.]
- Han TS, Seidell JC, Currall JE, Morrison CE, Deurenberg P, et al. (1997) The influences of height and age on waist circumference as an index of adiposity in adults. Int J Obes Relat Metab Disord 21: 83-89. [Ref.]
- WHO (2004) Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363: 157–163. [Ref.]
- Deurenberg P, Deurenberg-Yap M (2003) Validity of body composition methods across ethnic population groups. In: Elmadfa I, Anklam E, König JS, eds. Modern aspects of nutrition: present knowledge and future perspectives. Forum Nutr 56: 299–301. [Ref.]
- WHO (2008) Waist Circumference and Waist–Hip Ratio: Report of a WHO Expert Consultation. Geneva, 8–11. [Ref.]
- Avenell A, Brown TJ, McGee MA Campbell MK, Grant AM, et al. (2004) What are the long term benefits of weight reducing diets in adults? A systematic review of randomised controlled trials. J Hum Nutr Diet 17: 317-335. [Ref.]
- Stevens J, Truesdale KP, McClain J E, Cai J (2006) The definition of weight maintenance. Int J Obes 30: 391-399. [Ref.]
- Govers E, Seidell JC, Visser M, Brouwer IA (2014) Weight related health status of patientstreatedby dietitians in primary care practice: first results of a cohort study. BMC Fam Pract 15: 161. [Ref.]
- Wing RR, Marcus MD, Epstein LH, Salata R (1987) Type II diabetic subjects lose less weight than their overweight nondiabetic spouses. Diabetes Care 10: 563-566. [Ref.]
- Astrup A, Rossner S (2000) Lessons from obesity management programmes: greater initial weight loss improves long-term maintenance. Obes Rev 1: 17-91. [Ref.]
- Mazza AD, Pratley RE, Smith SR (2011) Beta-cell preservation…Is weight loss the answer? Rev Diabet Stud 8: 446-453. [Ref.]
- Shaw K, Gennat H, O’Rourke P, Del Mar C (2006) Exercise for overweight or obesity. Cochrane Database Syst Rev: CD003817. [Ref.]
- NICE (2006) Management of obesity: full guidance, March 2006. Clinical guideline: CG189.
- Wood PD, Stefanick ML, Dreon DM, Frey-Hewitt B, Garay SC, et al. (1988) Changes in plasma lipids and lipoproteins in overweight men during weight loss through dieting as compared with exercise. N Eng J Med 319: 1173-1179. [Ref.]
- Anderssen SA, Hjermann I, Urdal P, Torjesen PA, Holme I (1996) Improved carbohydrate metabolism after Physical training and dietary intervention in individuals with the ‘atherothrombogenic syndrome ‘. Oslo Diet and Exercise Study (ODES). A randomized trial. J Intern Med 240: 203-209. [Ref.]
- Pritchard JE, Nowson CA, Wark JD (1997) A worksite program for overweight middle-aged men achieves lesser weight loss with exercise than with dietary change. J Am Diet Assoc 97: 37-42. [Ref.]
- Wycherley TP, Moran LJ, Clifton PM, Noakes M, Brinkworth GD (2012) Effects of energy-restricted high-protein, low-fat compared with standard-protein, low-fat diets: a meta-analysis of randomized controlled trials. Am J ClinNutr 96: 1281-1298. [Ref.]
- Yancy WS, Olsen MK, Guyton JR, Bakst RP, Westman EC (2004) A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med 140: 769-777. [Ref.]
- Volek JS, Sharman MJ, Gómez AL, Judelson DA, Rubin MR, et al. (2004) Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women. Nutr Metab1: 13. [Ref.]
- Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, et al. (2003) A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med 348: 2074-2081. [Ref.]
- Wing RR1, Hill JO (2001) Successful weight loss maintenance. Annu Rev Nutr 21: 323-341. [Ref.]
- Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, et al. (2014) 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation 129: S102-S138. [Ref.]
- Thomas JG, Bond DS, Phelan S, Hill JO, Wing RR (2014) Weight-loss maintenance for 10 years in the National Weight Control Registry. Am J Prev Med 46: 17-23. [Ref.]
- McGrice M, Porter J (2017) The Effect of Low Carbohydrate Diets on Fertility Hormones and Outcomes in Overweight and Obese Women: A Systematic Review. Nutrients 9: 204. [Ref.]
- Konz EC, Anderson JW (2001) Obesity and Disease Management: Effects of Weight Loss on Comorbid Conditions. Obes Res 9 Suppl 4: 326S-334S. [Ref.]
- Nordmann AJ, Nordmann A, Briel M, Keller U, Yancy WS Jr, et al. (2006) Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials. Arch Intern Med 166: 285-293. [Ref.]
- Hu T, Mills KT, Yao L, Demanelis K, Eloustaz M, et al. (2012) Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol 176 Suppl 7: S44-S54. [Ref.]
- Vink RG, Roumans NJ, Čajlaković M, Cleutjens JPM, Boekschoten MV, et al. (2017) Diet-induced weight loss decreases adipose tissue oxygen tension with parallel changes in adipose tissue phenotype and insulin sensitivity in overweight humans. Int J Obes (Lond) 41: 722-728. [Ref.]
- Franz MJ, Boucher JL, Rutten-Ramos S, VanWormer JJ (2015) Lifestyle weight-loss intervention outcomes in overweight and obese adults with type 2 diabetes: a systematic review and meta-analysis of randomized clinical trials. J Acad Nutr Diet 115: 1447-1463. [Ref.]
- Feinman RD, Pogozelski WK, Astrup A, Bernstein RK, Fine EJ, et al. (2015) Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition 31: 1-13. [Ref.]
- Ajala O, English P, Pinkney J (2013) Systematic review and metaanalysis of different dietary approaches to the management of type 2 diabetes. Am J Clin Nutr 97: 505-516. [Ref.]
- Westman EC, Yancy WS Jr, Mavropoulos JC, Marquart M, McDuffie JR (2008) The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab (Lond) 5: 36. [Ref.]
- Normandin E, Chmelo E, Lyles MF, Marsh AP, Nicklas BJ (2017) Effect of Resistance Training and Caloric Restriction on the Metabolic Syndrome. Med Sci Sports Exerc 49: 413-419. [Ref.]
- Miller CT, Fraser SF, Levinger I, Straznicky NE, Dixon JB, et al. (2013) The effects of exercise training in addition to energy restriction on functional capacities and body composition in obese adults during weight loss: a systematic review. PLoS One 8: e81692. [Ref.]
- Stefanaki C, Peppa M, Boschiero D, Chrousos GP (2016) Healthy overweight/obese youth: early osteosarcopenic obesity features. Eur J Clin Invest 46: 767-778. [Ref.]
- Wylie-Rosett J, Aebersold K, Conlon B, Isasi CR, Ostrovsky NW (2013) Health effects of low-carbohydrate diets: where should new research go? Curr Diab Rep 13: 271-278. [Ref.]
- Kirk JK, Graves DE, Craven TE, Lipkin EW, Austin M, et al. (2008) Restricted-carbohydrate diets in patients with type 2 diabetes: a metaanalysis. J Am Diet Assoc 108: 91-100. [Ref.]
- de Zwaan M (2001) Binge eating disorder and obesity. Int J Obes Relat Metab Disord 25 Suppl 1: S51-S55. [Ref.]
- Berkman ND, Brownley KA, Peat CM, Lohr KN, Cullen KE, et al. (2015) Management and Outcomes of Binge-Eating Disorder. Comparative Effectiveness Reviews: 160. [Ref.]
- Brownley KA, Berkman ND, Peat CM, Lohr KN, Cullen KE, et al. (2016) Binge-Eating Disorder in Adults: A Systematic Review and Meta-analysis. Ann Intern Med 165: 409-420. [Ref.]
- Vetter ML, Amaro A, Volger S (2014) Nutritional management of type 2 diabetes mellitus and obesity and pharmacologic therapies to facilitate weight loss. Postgrad Med 126: 139-152. [Ref.]
- Miyashita Y, Koide N, Ohtsuka M, Ozaki H, Itoh Y, et al. (2004) Beneficial effect of low carbohydrate in low calorie diets on visceral fat reduction in type 2 diabetic patients with obesity. Diabetes Res Clin Pract 65: 235-241. [Ref.]
- Govers E, Slof E, Verkoelen H, Ten Hoor-Aukema NM, KDOO (2015) Guideline for the Management of Insulin Resistance. Int J Endocrinol Metab Disord 1. [Ref.]
- Krieger JW, Sitren HS, Daniels MJ, Langkamp-Henken B (2006) Effects of variation in protein and carbohydrate intake on body mass and composition during energy restriction: a meta-regression. Am J Clin Nutr 83: 260-274.
- Layman DK, Walker DA (2006) Potential Importance of Leucine in Treatment of Obesity and the Metabolic Syndrome. J Nutr 136: 319S-323S.
- Wall BT, Cermak NM, van Loon LJ (2014) Dietary Protein Considerations to Support Active Aging. Sports Med 44: S185-194.
- Westerterp-Plantenga MS, Nieuwenhuizen A, Tome D, Soenen S, Westerterp KR (2009) Dietary protein, weight loss, and weight maintenance. Annu Rev Nutr 29: 21-41.
- Gögebakan O, Kohl A, Osterhoff MA, van Baak MA, Jebb SA (2011) Effects of weight loss and long-term weight maintenance with diets varying in protein and glycemic index on cardiovascular risk factors: the diet, obesity, and genes (DiOGenes) study: a randomized, controlled trial. Circulation 124: 2829-2838.
- Astrup A, Raben A, Geiker N (2015) The role of higher protein diets in weight control and obesity-related comorbidities. Int J Obes (Lond) 39: 721-726.
- Damsgaard CT, Papadaki A, Jensen SM, Ritz C, Dalskov SM et al. (2013) Higher protein diets consumed ad libitum improve cardiovascular risk markers in children of overweight parents from eight European countries. J Nutr 143: 810-817.
- Tieland M, Borgonjen-Van den Berg KJ, Van Loon LJ, de Groot LC (2015) Dietary Protein Intake in Dutch Elderly People: A Focus on Protein Sources. Nutrients 7: 9697-9706.
- Verreijen AM, Verlaan S, Engberink MF, Swinkels S, de Vogel-van den Bosch J et al. (2015). A high whey protein-, leucine-, and vitamin D-enriched supplement preserves muscle mass during intentional weight loss in obese older adults: a double-blind randomized controlled trial. Am J ClinNutr 101: 279-286. [Ref.]
- Verreijen AM, Engberink MF, Memelink RG, Plas SE van der,Visser M et al.(2017) Effect of a high protein diet and/or resistance exercise on the preservation of fat free mass during weight loss in overweight and obese older adults: a randomized controlled trial. Nutr J 16: 10. [Ref.]
- de Souza RJ, Mente A, Maroleanu A, Cozma AI, Ha V et al. (2015) Intake of saturated and trans saturated fatty acids and risk of all-cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. BMJ 351: h3978. [Ref.]
- Mozaffarian D, Rimm EB, Herrington DM (2004) Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women. Am J Clin Nutr 80: 1175-1184.
- Chowdhury R, Warnakula S, Kunutsor S, Crowe F, Ward HA et al. (2014) Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. Ann Intern Med 160: 398-406.
- de Oliveira Otto MC, Nettleton JA, Lemaitre RN, Steffen LM, Kromhout D et al. (2013) Biomarkers of dairy fatty acids and risk of cardiovascular disease in the Multi-ethnic Study of Atherosclerosis. J Am Heart Assoc 2: e000092.
- Chen M, Sun Q, Giovannucci E, Mozaffarian D, Manson JE et al. (2014) Dairy consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis. BMC med 12: 215. [Ref.]
- Mozaffarian D, de Oliveira Otto MC, Lemaitre RN, Fretts AM, Hotamisligil G et al. (2013) trans-Palmitoleic acid, other dairy fat biomarkers, and incident diabetes: the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr 97: 854-861.
- Mozaffarian D, Cao H, King IB, Lemaitre RN, Song X et al. (2010) Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. adults: a cohort study. Ann Intern Med 153: 790-799.
- Forouhi NG, Koulman A, Sharp SJ, Imamura F, Kroger Jet al. Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study. Lancet Diabetes Endocrinol 2: 810-818. [Ref.]
- Pimpin L, Wu JH, Haskelberg H, Del Gobbo L, Mozaffarian D (2016) Is Butter Back? A Systematic Review and Meta-Analysis of Butter Consumption and Risk of Cardiovascular Disease, Diabetes, and Total Mortality. PLoS One 11: e0158118.
- Imamura F, Micha R, Wu JHY, de Oliveira Otto M, Otite FO, et al. (2016) Effects of saturated fat, polyunsaturated fat, monounsaturated fat, and carbohydrate on glucose-insulin homeostasis: a systematic review and meta-analysis of randomised controlled feeding trials. PLoS Med 13: e1002087. [Ref.]
- Jump DB, Depner CM, Tripathy S, Lytle KA (2015) Potential for dietary ω-3 fatty acids to prevent nonalcoholic fatty liver disease and reduce the risk of primary liver cancer. AdvNutr 6: 694-702. [Ref.]
- Du S, Jin J, Fang W, Su Q, et al. (2015) Does Fish Oil Have an Anti-Obesity Effect in Overweight/Obese Adults? A Meta-Analysis of Randomized Controlled Trials. PLoS One 10: e0142652. [Ref.]
- Jacobo-Cejudo MG, Valdés-Ramos R, Guadarrama-López AL, Pardo-Morales RV, Martínez-Carrillo BE, et al. (2017) Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers in Type 2 Diabetes Mellitus Patients. Nutrients 9: E573. [Ref.]
- Renzaho AM, Halliday JA, Nowson C (2011). Vitamin D, obesity, and obesity-related chronic disease among ethnic minorities: a systematic review. Nutrition 27: 868-879. [Ref.]
- LorvandAmiri H, Agah S, Mousavi SN, Hosseini AF, Shidfar F (2016) Regression of non-alcoholic fatty liver by vitamin D supplement: a double-blind randomized controlled trial. Arch Iran Med 19: 631-638. [Ref.]
- Al Masri M, Romain AJ, Boegner C, Maimoun L, Mariano-Goulart D, et al. (2017) Vitamin D status is not related to insulin resistance in different phenotypes of moderate obesity. Appl Physiol Nutr Metab 42: 438-442. [Ref.]
- Karelis AD, Rabasa-Lhoret R (2014) Characterization of metabolically healthy but obese individuals: Should we add vitamin D to the puzzle? Diabetes & metabolism 5: 319–321. [Ref.]
- Pannu PK, Zhao Y, Soares MJ (2016) Reductions in body weight and percent fat mass increase the vitamin D status of obese subjects: a systematic review and metaregression analysis. Nutr Res 36: 201-213. [Ref.]
- Mallard SR, Howe AS, Houghton LA (2016) Vitamin D status and weight loss: a systematic review and meta-analysis of randomized and nonrandomized controlled weight-loss trials. Am J Clin Nutr 104: 1151-1159. [Ref.]
- Champagne CM (2008) Magnesium in hypertension, cardiovascular disease, metabolic syndrome, and other conditions: a review. Nutr Clin Pract 23: 142-151. [Ref.]
- Michalaki MA, Vagenakis AG, Leonardou AS, Argentou MN, Habeos IG, et al. (2006) Thyroid function in humans with morbid obesity. Thyroid 16: 73–78. [Ref.]
- De Pergola G, Ciampolillo A, Paolotti S, Trerotoli P, Giorgino R (2007) Free triiodothyronine and thyroid stimulating hormone are directly associated with waist circumference, independently of insulin resistance, metabolic parameters and blood pressure in overweight and obese women. Clin Endocrinol 67: 265–269. [Ref.]
- Knudsen N, Laurberg P, Rasmussen LB, Bülow I, Perrild H, et al. (2005) Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab 90: 4019-4024. [Ref.]
- Ashwar BA, Gani A, Shah A, Wani IA, Masoodi FA (2015) Preparation, health benefits and applications of resistant starch - a review. StarchStärke 68: 287-301. [Ref.]
- Lockyer S, Nugent AP (2017) Health effects of resistant starch. Nutrition Bulletin 42: 1–32. [Ref.]
- Playdon MC, Ziegler RG, Sampson JN, Stolzenberg-Solomon R, Thompson HJ, et al. (2017) Nutritional metabolomics and breast cancer risk in a prospective study. Am J Clin Nutr 106: 637-649. [Ref.]
- Shaukat A, Dostal A, Menk J, Church TR (2017) BMI Is a Risk Factor for Colorectal Cancer Mortality Dig Dis Sci 21. doi: 10.1007/s10620- 017-4682-z. [Ref.]
- Keys A (1997) Coronary heart disease in seven countries 1970. Nutrition 13: 250-252. [Ref.]
- Keys A (1980) Seven Countries: A multivariate analysis of death and coronary heart disease. Harvard University Press, London, UK. [Ref.]
- Kushi LH, Lenart EB, Willett WC (1995) Health implications of Mediterranean diets in light of contemporary knowledge. 1. Plant foods and dairy products. Am J Clin Nutr 61: 1407S-1415S. [Ref.]
- Kushi LH, Lenart EB, Willett WC (1995) Health implications of Mediterranean diets in light of contemporary knowledge. 2. Meat, wine, fats, and oils. Am J Clin Nutr 61: 1416S-1427S. [Ref.]
- Kolcic I, Relja A, Gelemanovic A, Miljkovic A, Boban K, et al. (2016) Mediterranean diet in the southern Croatia - does it still exist? Croat Med J 57: 415-424. [Ref.]
- Patino-Alonso MC, Recio-Rodriguez JI, Belio JF, Colominas-Garrido R, Lema-Bartolome J, et al. (2014) Factors associated with adherence to the Mediterranean diet in the adult population. J Acad Nutr Diet 114: 583-589. [Ref.]
- Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, et al. (2008) Weight loss with a low carbohydrate, Mediterranean, or low fat diet. N Engl J Med 359: 229-241. [Ref.]
- Anderson JW, Konz EC, Frederich RC, Wood CL (2001) Long term weight-loss maintenance: a meta-analysis of US studies. Am J Clin Nutr 74: 579-584. [Ref.]
- Avenell A, Brown TJ, McGee MA, Campbell MK, Grant AM, et al. (2004) What are the long term benefits of weight reducing diets in adults? A systematic reviw of randomized controlled trials. J Hum Nutr Diet 17: 317-335. [Ref.]
- Nordmann AJ, Nordmann A, Briel M, Keller U, Yancy WS jr, et al. (2006) Effects of low-carbohydrate versus low-fat diets on weight loss and cardiovascular risk factors. Arch Int Med 66: 285-293. [Ref.]
- Grieb P, Klapcinska B, Smol E, Pilis T, Pilis W, et al. (2008) Longterm consumption of a carbohydrate restricted diet does not induce deleterious metabolic effects. Nutr Res 28: 825-833. [Ref.]
- Santos FL, Esteves SS, da Costa Pereira A, Yancy Jr WS, Nunes JPL (2012) Systematic review and meta-analysis of clinical trials of the effects of low carbohydrate diets on cardiovascular risk factors. Obes rev 13: 1048-1066. [Ref.]
- Nackers LM, Ross KM, Perri MG (2010) The Association Between Rate of Initial Weight Loss and Long-Term Success in Obesity Treatment: Does Slow and Steady Win the Race? Int J Behav Med 17: 161-167. [Ref.]
- Aller EE, Larsen TM, Claus H, Lindroos AK, Kafatos A, et al. (2014) Weight loss maintenance in overweight subjects on ad libitum diets with high or low protein content and glycemic index: the DIOGENES trial 12-month results. Int J Obes (Lond) 38: 1511-1517. [Ref.]
- Montesi L, El Ghoch M, BrodosiL, Calugi S, Marchesini G, et al. (2016) Long-term weight loss maintenance for obesity: a multidisciplinary approach. Diabetes Metab Syndr Obes 9: 37-46. [Ref.]
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Article Type: Review Article
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 openaccess 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.