Randomised controlled trial of lifestyle interventions for abdominal obesity in primary health care.

AIM: Assess effects on waist circumference from diet with or without cereal grains and with or without long-term physical exercise. BACKGROUND: Elevated waist circumference is an indicator of increased abdominal fat storage and is accordingly associated with increased cardiovascular mortality. This is likely due to the association between lifestyle-induced changes in waist circumference and cardiovascular risk factors. Reductions in waist circumference may be facilitated by diet without cereal grains combined with long-term physical exercise. METHODS: Two-year randomised controlled trial with factorial trial design in individuals at increased risk of cardiovascular disease with increased waist circumference. Participants were allocated diet based on current Swedish dietary guidelines with or without cereal grains (baseline diet information supported by monthly group sessions) and with or without physical exercise (pedometers and two initial months of weekly structured exercise followed by written prescription of physical activity) or control group. The primary outcome was the change in waist circumference. FINDINGS: The greatest mean intervention group difference in the change in waist circumference among the 73 participants (47 women and 26 men aged 23-79 years) was at one year between participants allocated a diet without cereal grains and no exercise and participants allocated a diet with cereal grains and no exercise [M = -5.3 cm and -0.9 cm, respectively; mean difference = 4.4 cm, 4.0%, 95% CI (0.0%, 8.0%), P = 0.051, Cohen's d = 0.75]. All group comparisons in the change in waist circumference were non-significant despite the greatest group difference being more than double that estimated in the pre-study power calculation. The non-significance was likely caused by too few participants and a greater than expected variability in the change in waist circumference. The greatest mean intervention group difference strengthens the possibility that dietary exclusion of cereal grains could be related to greater reduction in waist circumference.

Inverse association between Paleolithic Diet Fraction and mortality and incidence of cardiometabolic disease in the prospective Malmö Diet and Cancer Study.

PURPOSE: Paleolithic Diet Fraction (PDF) estimates how large a portion of the absolute dietary intake stems from food groups included in the Paleolithic diet. In randomized controlled trials higher PDFs have been associated with healthier levels of cardiometabolic risk markers. Our aim was to build upon these findings by examining associations between PDF and mortality and incidence of cardiometabolic disease in the prospective Malmö Diet and Cancer Study. METHODS: PDF was calculated from an interview-based, modified diet history method, and associations were estimated by using multivariable Cox proportional hazards regression. The examined cohort consisted of 24,104 individuals (44-74 years, 63% women) without previous coronary events, diabetes, or stroke at baseline (1992-1996). A total of 10,092 individuals died during a median follow-up of 18 years. RESULTS: Median PDF was 40% (0-90%). The adjusted hazard ratios (HR) for PDF as a continuous variable (from 0 to 100%) were for risk of death from all causes 0.55 [95% CI 0.45, 0.66], tumor 0.68 [95% CI 0.49, 0.93], cardiovascular 0.55 [95% CI 0.39, 0.78], respiratory 0.44 [95% CI 0.21, 0.90], neurological 0.26 [95% CI 0.11, 0.60], digestive, 0.10 [95% CI 0.03, 0.30], and other diseases 0.64 [95% CI 0.41, 1.00]. The corresponding HR for risk of coronary event was 0.61 [95% 0.43, 0.86], for ischemic stroke it was 0.73 [95% 0.48, 1.09] and for type 2 diabetes it was 0.82 [95% 0.61, 1.10]. CONCLUSION: Observational data suggest an inverse association between PDF and all-cause as well as cause-specific mortality and incidence of cardiometabolic disease.

Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data.

OBJECTIVE: To determine the efficacy and safety of low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Searches of CENTRAL, Medline, Embase, CINAHL, CAB, and grey literature sources from inception to 25 August 2020. STUDY SELECTION: Randomized clinical trials evaluating LCDs (<130 g/day or <26% of a 2000 kcal/day diet) and VLCDs (<10% calories from carbohydrates) for at least 12 weeks in adults with type 2 diabetes were eligible. DATA EXTRACTION: Primary outcomes were remission of diabetes (HbA1c <6.5% or fasting glucose <7.0 mmol/L, with or without the use of diabetes medication), weight loss, HbA1c, fasting glucose, and adverse events. Secondary outcomes included health related quality of life and biochemical laboratory data. All articles and outcomes were independently screened, extracted, and assessed for risk of bias and GRADE certainty of evidence at six and 12 month follow-up. Risk estimates and 95% confidence intervals were calculated using random effects meta-analysis. Outcomes were assessed according to a priori determined minimal important differences to determine clinical importance, and heterogeneity was investigated on the basis of risk of bias and seven a priori subgroups. Any subgroup effects with a statistically significant test of interaction were subjected to a five point credibility checklist. RESULTS: Searches identified 14 759 citations yielding 23 trials (1357 participants), and 40.6% of outcomes were judged to be at low risk of bias. At six months, compared with control diets, LCDs achieved higher rates of diabetes remission (defined as HbA1c <6.5%) (76/133 (57%) v 41/131 (31%); risk difference 0.32, 95% confidence interval 0.17 to 0.47; 8 studies, n=264, I2=58%). Conversely, smaller, non-significant effect sizes occurred when a remission definition of HbA1c <6.5% without medication was used. Subgroup assessments determined as meeting credibility criteria indicated that remission with LCDs markedly decreased in studies that included patients using insulin. At 12 months, data on remission were sparse, ranging from a small effect to a trivial increased risk of diabetes. Large clinically important improvements were seen in weight loss, triglycerides, and insulin sensitivity at six months, which diminished at 12 months. On the basis of subgroup assessments deemed credible, VLCDs were less effective than less restrictive LCDs for weight loss at six months. However, this effect was explained by diet adherence. That is, among highly adherent patients on VLCDs, a clinically important reduction in weight was seen compared with studies with less adherent patients on VLCDs. Participants experienced no significant difference in quality of life at six months but did experience clinically important, but not statistically significant, worsening of quality of life and low density lipoprotein cholesterol at 12 months. Otherwise, no significant or clinically important between group differences were found in terms of adverse events or blood lipids at six and 12 months. CONCLUSIONS: On the basis of moderate to low certainty evidence, patients adhering to an LCD for six months may experience remission of diabetes without adverse consequences. Limitations include continued debate around what constitutes remission of diabetes, as well as the efficacy, safety, and dietary satisfaction of longer term LCDs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020161795.

C-reactive protein in traditional melanesians on Kitava.

BACKGROUND: Population-based levels of the chronic low-grade systemic inflammation biomarker, C-reactive protein (CRP), vary widely among traditional populations, despite their apparent absence of chronic conditions associated with chronic low-grade systemic inflammation, such as type 2 diabetes, metabolic syndrome and cardiovascular disease. We have previously reported an apparent absence of aforementioned conditions amongst the traditional Melanesian horticulturalists of Kitava, Trobriand Islands, Papua New Guinea. Our objective in this study was to clarify associations between chronic low-grade systemic inflammation and chronic cardiometabolic conditions by measuring CRP in a Kitava population sample. For comparison purposes, CRP was also measured in Swedish controls matched for age and gender. METHODS: Fasting levels of serum CRP were measured cross-sectionally in ≥ 40-year-old Kitavans (N = 79) and Swedish controls (N = 83). RESULTS: CRP was lower for Kitavans compared to Swedish controls (Mdn 0.5 mg/L range 0.1-48 mg/L and Mdn 1.1 mg/L range 0.1-33 mg/L, respectively, r = .18 p = .02). Among Kitavans, there were small negative associations between lnCRP for CRP values < 10 and total, low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) cholesterol. Among Swedish controls, associations of lnCRP for CRP values < 10 were medium positive with weight, body mass index, waist circumference, hip circumference and waist-hip ratio and low positive with triglyceride, total cholesterol-HDL cholesterol ratio, triglyceride-HDL cholesterol ratio and serum insulin. CONCLUSIONS: Chronic low-grade systemic inflammation, measured as CRP, was lower among Kitavans compared to Swedish controls, indicating a lower and average cardiovascular risk, respectively, for these populations.

Probiotic fruit beverages with different polyphenol profiles attenuated early insulin response.

BACKGROUND: Consumption of polyphenol-rich fruits and vegetables may improve postprandial glucose and insulin levels and hence promote well-being. Previously it has been observed that consumption of bilberry decreases the postprandial insulin demand. The intention with the present study was to compare the impact of different supplements with various polyphenol profiles, on the postprandial glucose and insulin responses in healthy young adults. METHODS: In a randomized, controlled, crossover study the postprandial glycemic and insulin responses were observed in eleven healthy adults after intake of five different beverages containing bilberry (European blueberry), blackcurrant, beetroot, mango and rose hip, respectively; all drinks were enriched with the same composition of fermented oatmeal and probiotics. The control was a glucose drink. The profile and content of the polyphenols in the different beverages were determined by HPLC-DAD analysis. The antioxidative capacity of the different beverages were measured by TEAC and DPPH assays. RESULTS: Beverages containing bilberry, blackcurrant, mango or rose hip significantly attenuated the early postprandial insulin response (0-90 min), but showed no effect on glucose response. Drinks with bilberry or rose hip reduced the insulin response from the very early phase (0-30 min), and had significantly lower insulin index compared with the control. The efficiency of the bilberry and rose hip to decrease early postprandial insulin responses correlated with higher phenolic contents. CONCLUSIONS: Supplements with bilberry, blackcurrant, mango or rose hip in the tested probiotic and oatmeal enriched beverage attenuated early-phase insulin response, but had no effect on the postprandial glycemic response. The improved ability of bilberry and rose hip to lower the very early phase of insulin response seems to be due to a higher phenolic content. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov with number NCT03159065 .

Palaeolithic diet decreases fasting plasma leptin concentrations more than a diabetes diet in patients with type 2 diabetes: a randomised cross-over trial.

BACKGROUND: We have previously shown that a Palaeolithic diet consisting of the typical food groups that our ancestors ate during the Palaeolithic era, improves cardiovascular disease risk factors and glucose control compared to the currently recommended diabetes diet in patients with type 2 diabetes. To elucidate the mechanisms behind these effects, we evaluated fasting plasma concentrations of glucagon, insulin, incretins, ghrelin, C-peptide and adipokines from the same study. METHODS: In a randomised, open-label, cross-over study, 13 patients with type 2 diabetes were randomly assigned to eat a Palaeolithic diet based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts, or a diabetes diet designed in accordance with current diabetes dietary guidelines during two consecutive 3-month periods. The patients were recruited from primary health-care units and included three women and 10 men [age (mean ± SD) 64 ± 6 years; BMI 30 ± 7 kg/m(2); diabetes duration 8 ± 5 years; glycated haemoglobin 6.6 ± 0.6 % (57.3 ± 6 mmol/mol)] with unaltered diabetes treatment and stable body weight for 3 months prior to the start of the study. Outcome variables included fasting plasma concentrations of leptin, adiponectin, adipsin, visfatin, resistin, glucagon, insulin, C-peptide, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 and ghrelin. Dietary intake was evaluated by use of 4-day weighed food records. RESULTS: Seven participants started with the Palaeolithic diet and six with the diabetes diet. The Palaeolithic diet resulted in a large effect size (Cohen's d = -1.26) at lowering fasting plasma leptin levels compared to the diabetes diet [mean difference (95 % CI), -2.3 (-5.1 to 0.4) ng/ml, p = 0.023]. No statistically significant differences between the diets for the other variables, analysed in this study, were observed. CONCLUSIONS: Over a 3-month study period, a Palaeolithic diet resulted in reduced fasting plasma leptin levels, but did not change fasting levels of insulin, C-peptide, glucagon, incretins, ghrelin and adipokines compared to the currently recommended diabetes diet. TRIAL REGISTRATION: ClinicalTrials.gov NCT00435240.

Digested wheat gluten inhibits binding between leptin and its receptor.

BACKGROUND: Leptin resistance is considered a primary risk factor for obesity. It has been hypothesized that dietary cereal grain protein could cause leptin resistance by preventing leptin from binding to its receptor. Non-degraded dietary wheat protein has been found in human serum at a mean level of 41 ng/mL. Here, we report our findings from testing whether enzymatically digested gluten from wheat prevents leptin from binding to the leptin receptor in vitro. Gluten from wheat was digested with pepsin and trypsin under physiological conditions. Pepsin and trypsin activity was removed from the gluten digest with a 10 kDa spin-filter or by heat treatment at 100°C for 30 min. Binding to the leptin receptor of leptin mixed with gluten digest at a series of concentrations was measured using surface plasmon resonance technology. RESULTS: Binding of the gluten digest to the leptin receptor was not detected. Spin-filtered gluten digest inhibited binding of leptin to the leptin receptor, with 50% inhibition at a gluten digest concentration of ~10 ng/mL. Heat-treated gluten digest did not inhibit leptin binding. CONCLUSIONS: Digested wheat gluten inhibits binding of leptin to the leptin receptor, with half-maximal inhibition at 10 ng/mL. The inhibition is significant at clinically relevant concentrations and could therefore serve as a novel pathway to investigate to understand the molecular basis of leptin resistance, obesity and associated disorders.

A healthy diet with and without cereal grains and dairy products in patients with type 2 diabetes: study protocol for a random-order cross-over pilot study--Alimentation and Diabetes in Lanzarote--ADILAN.

BACKGROUND: Research on the role of nutrition in type 2 diabetes has largely focused on macro/micronutrient composition and dietary fiber intake, while fewer studies have tested the effects of differing food choice. Some observational studies and short-term intervention studies suggest that a food pattern mimicking the diet with which humans evolved positively influences glucose control and associated endocrine systems. Such a food pattern mainly differs from other common healthy food patterns in its absence of cereal grains and dairy products. The primary aim of this pilot study is to determine the effect of two healthy diets with or without cereal grains and dairy products on glucose control, while keeping participants' weight stable and other food parameters, such as macro/micronutrient composition, dietary fiber and glycemic load, the same in both diets. METHODS/DESIGN: We intend to include 15 adult patients with a medical diagnosis of type 2 diabetes mellitus with or without medication and with an increased waist circumference (≥ 80 cm for women and ≥ 94 cm for men) in a random-order cross-over diet intervention study during two periods of four-weeks separated by a six-week washout period. Patients will be instructed to eat two healthy diets according to official dietary guidelines with respect to macro/micronutrient composition and fiber content, but differing in the type of food included, with one diet being without cereal grains and dairy products. Lunch will be served in a hospital kitchen for control of nutrient intake, while the rest of the meals will be eaten at home according to specific directions. The energy content of the diets will be individually adjusted to maintain a stable body weight during the two four-week intervention periods. Primary outcomes will be change in fasting plasma glucagon and fructosamine, while secondary outcomes include change in fasting glucose and glycated hemoglobin, glucose and glucagon response during oral glucose tolerance test, blood lipids, blood pressure, C-reactive protein, body composition, quality of life, subjective experience with the two diets, satiety scores and changes in medication. DISCUSSION: Using these results, we will assess the need to conduct larger and longer studies with similar design. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT01891955 and Spanish Agency of Medication and Sanitary Products (AEMPS) registration code: MFV-ADI-2013-01.

Subjective satiety and other experiences of a Paleolithic diet compared to a diabetes diet in patients with type 2 diabetes.

BACKGROUND: We found marked improvement of glycemic control and several cardiovascular risk factors in patients with type 2 diabetes given advice to follow a Paleolithic diet, as compared to a diabetes diet. We now report findings on subjective ratings of satiety at meal times and participants' other experiences of the two diets from the same study. METHODS: In a randomized cross-over study, 13 patients with type 2 diabetes (3 women and 10 men), were instructed to eat a Paleolithic diet based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts, and a diabetes diet designed in accordance with dietary guidelines, during two consecutive 3-month periods. In parallel with a four-day weighed food record, the participants recorded their subjective rating of satiety. Satiety quotients were calculated as the intra-meal quotient of change in satiety during a meal and consumed energy or weight of food and drink for that specific meal. All participants answered the same three open-ended questions in a survey following each diet: "What thoughts do you have about this diet?", "Describe your positive and negative experiences with this diet" and "How do you think this diet has affected your health?". RESULTS: The participants were equally satiated on both diets. The Paleolithic diet resulted in greater satiety quotients for energy per meal (p = 0.004), energy density per meal (p = 0.01) and glycemic load per meal (p = 0.02). The distribution of positive and negative comments from the survey did not differ between the two diets, and the comments were mostly positive. Among comments relating to recurring topics, there was no difference in distribution between the two diets for comments relating to tastelessness, but there was a trend towards more comments on the Paleolithic diet being satiating and improving blood sugar values, and significantly more comments on weight loss and difficulty adhering to the Paleolithic diet. CONCLUSIONS: A Paleolithic diet is more satiating per calorie than a diabetes diet in patients with type 2 diabetes. The Paleolithic diet was seen as instrumental in weight loss, albeit it was difficult to adhere to.

A paleolithic diet is more satiating per calorie than a mediterranean-like diet in individuals with ischemic heart disease.

BACKGROUND: We found marked improvement of glucose tolerance and lower dietary energy intake in ischemic heart disease (IHD) patients after advice to follow a Paleolithic diet, as compared to a Mediterranean-like diet. We now report findings on subjective ratings of satiety at meals and data on the satiety hormone leptin and the soluble leptin receptor from the same study. METHODS: Twenty-nine male IHD patients with impaired glucose tolerance or diabetes type 2, and waist circumference > 94 cm, were randomized to ad libitum consumption of a Paleolithic diet (n = 14) based on lean meat, fish, fruit, vegetables, root vegetables, eggs, and nuts, or a Mediterranean-like diet (n = 15) based on whole grains, low-fat dairy products, vegetables, fruit, fish, and oils and margarines during 12 weeks. In parallel with a four day weighed food record the participants recorded their subjective rating of satiety. Satiety Quotients were calculated, as the intra-meal quotient of change in satiety during meal and consumed energy or weight of food and drink for that specific meal. Leptin and leptin receptor was measured at baseline and after 6 and 12 weeks. Free leptin index was calculated as the ratio leptin/leptin receptor. RESULTS: The Paleolithic group were as satiated as the Mediterranean group but consumed less energy per day (5.8 MJ/day vs. 7.6 MJ/day, Paleolithic vs. Mediterranean, p = 0.04). Consequently, the quotients of mean change in satiety during meal and mean consumed energy from food and drink were higher in the Paleolithic group (p = 0.03). Also, there was a strong trend for greater Satiety Quotient for energy in the Paleolithic group (p = 0.057). Leptin decreased by 31% in the Paleolithic group and by 18% in the Mediterranean group with a trend for greater relative decrease of leptin in the Paleolithic group. Relative changes in leptin and changes in weight and waist circumference correlated significantly in the Paleolithic group (p < 0.001) but not in the Mediterranean group. Changes in leptin receptor and free leptin index were not significant. CONCLUSIONS: A Paleolithic diet is more satiating per calorie than a Mediterranean-like diet. TRIAL REGISTRATION: ClinicalTrials.gov NCT00419497.

Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study.

BACKGROUND: Our aim was to compare the effects of a Paleolithic ('Old Stone Age') diet and a diabetes diet as generally recommended on risk factors for cardiovascular disease in patients with type 2 diabetes not treated with insulin. METHODS: In a randomized cross-over study, 13 patients with type 2 diabetes, 3 women and 10 men, were instructed to eat a Paleolithic diet based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts; and a Diabetes diet designed in accordance with dietary guidelines during two consecutive 3-month periods. Outcome variables included changes in weight, waist circumference, serum lipids, C-reactive protein, blood pressure, glycated haemoglobin (HbA1c), and areas under the curve for plasma glucose and plasma insulin in the 75 g oral glucose tolerance test. Dietary intake was evaluated by use of 4-day weighed food records. RESULTS: Study participants had on average a diabetes duration of 9 years, a mean HbA1c of 6,6% units by Mono-S standard and were usually treated with metformin alone (3 subjects) or metformin in combination with a sulfonylurea (3 subjects) or a thiazolidinedione (3 subjects). Mean average dose of metformin was 1031 mg per day. Compared to the diabetes diet, the Paleolithic diet resulted in lower mean values of HbA1c (-0.4% units, p = 0.01), triacylglycerol (-0.4 mmol/L, p = 0.003), diastolic blood pressure (-4 mmHg, p = 0.03), weight (-3 kg, p = 0.01), BMI (-1 kg/m2, p = 0.04) and waist circumference (-4 cm, p = 0.02), and higher mean values of high density lipoprotein cholesterol (+0.08 mmol/L, p = 0.03). The Paleolithic diet was mainly lower in cereals and dairy products, and higher in fruits, vegetables, meat and eggs, as compared with the Diabetes diet. Further, the Paleolithic diet was lower in total energy, energy density, carbohydrate, dietary glycemic load, saturated fatty acids and calcium, and higher in unsaturated fatty acids, dietary cholesterol and several vitamins. Dietary GI was slightly lower in the Paleolithic diet (GI = 50) than in the Diabetic diet (GI = 55). CONCLUSION: Over a 3-month study period, a Paleolithic diet improved glycemic control and several cardiovascular risk factors compared to a Diabetes diet in patients with type 2 diabetes.

Coping with recurrent breast cancer: predictors of distressing symptoms and health-related quality of life.

Little is known about how postmenopausal women with recurrent breast cancer cope with distressing symptoms and which factors predict health-related quality of life (HRQOL). In the present study, 56 consecutively enrolled patients completed questionnaires measuring symptom occurrence, coping capacity, coping efforts, and HRQOL at the time of recurrence. Results from this study illustrate that women with recurrent breast cancer suffer from multiple, concurrent, and interrelated symptoms of illness, anxiety, depression, and fatigue. Highly prevalent symptoms are lack of energy, difficulty sleeping, pain, worrying, problems with sexual interest, feeling sad, and dry mouth. The most frequently occurring symptom is problem with sexual interest, and the most severe symptom is worrying. The most distressing symptom experienced is pain. The majority of the women report 10-23 symptoms. Women who experience multiple symptoms also report higher levels of symptom distress. The experience of distressing symptoms is predicted by coping capacity, and the coping efforts experienced predict HRQOL. Patients with lower coping capacity report higher prevalence of symptoms, experience higher levels of distress, and experience worse perceived health, which in turn may decrease their HRQOL. To help women manage recurrent breast cancer, it is important to use multidimensional measurement to identify, evaluate, and treat distressing symptoms, and not assess single symptoms only. Care must be based upon the awareness of critical factors that exacerbate vulnerability to distress, as well as the ability to adapt to a recurrent breast cancer disease.

A Paleolithic diet confers higher insulin sensitivity, lower C-reactive protein and lower blood pressure than a cereal-based diet in domestic pigs.

BACKGROUND: A Paleolithic diet has been suggested to be more in concordance with human evolutionary legacy than a cereal based diet. This might explain the lower incidence among hunter-gatherers of diseases of affluence such as type 2 diabetes, obesity and cardiovascular disease. The aim of this study was to experimentally study the long-term effect of a Paleolithic diet on risk factors for these diseases in domestic pigs. We examined glucose tolerance, post-challenge insulin response, plasma C-reactive protein and blood pressure after 15 months on Paleolithic diet in comparison with a cereal based swine feed. METHODS: Upon weaning twenty-four piglets were randomly allocated either to cereal based swine feed (Cereal group) or cereal free Paleolithic diet consisting of vegetables, fruit, meat and a small amount of tubers (Paleolithic group). At 17 months of age an intravenous glucose tolerance test was performed and pancreas specimens were collected for immunohistochemistry. Group comparisons of continuous variables were made by use of the t-test. P < 0.05 was chosen for statistical significance. Simple and multivariate correlations were evaluated by use of linear regression analysis. RESULTS: At the end of the study the Paleolithic group weighed 22% less and had 43% lower subcutaneous fat thickness at mid sternum. No significant difference was seen in fasting glucose between groups. Dynamic insulin sensitivity was significantly higher (p = 0.004) and the insulin response was significantly lower in the Paleolithic group (p = 0.001). The geometric mean of C-reactive protein was 82% lower (p = 0.0007) and intra-arterial diastolic blood pressure was 13% lower in the Paleolithic group (p = 0.007). In evaluations of multivariate correlations, diet emerged as the strongest explanatory variable for the variations in dynamic insulin sensitivity, insulin response, C-reactive protein and diastolic blood pressure when compared to other relevant variables such as weight and subcutaneous fat thickness at mid sternum. There was no obvious immunohistochemical difference in pancreatic islets between the groups, but leukocytes were clearly more frequent in sampled pancreas from the Cereal group. CONCLUSION: This study in domestic pigs suggests that a Paleolithic diet conferred higher insulin sensitivity, lower C-reactive protein and lower blood pressure when compared to a cereal based diet.

Agrarian diet and diseases of affluence--do evolutionary novel dietary lectins cause leptin resistance?

BACKGROUND: The global pattern of varying prevalence of diseases of affluence, such as obesity, cardiovascular disease and diabetes, suggests that some environmental factor specific to agrarian societies could initiate these diseases. PRESENTATION OF THE HYPOTHESIS: We propose that a cereal-based diet could be such an environmental factor. Through previous studies in archaeology and molecular evolution we conclude that humans and the human leptin system are not specifically adapted to a cereal-based diet, and that leptin resistance associated with diseases of affluence could be a sign of insufficient adaptation to such a diet. We further propose lectins as a cereal constituent with sufficient properties to cause leptin resistance, either through effects on metabolism central to the proper functions of the leptin system, and/or directly through binding to human leptin or human leptin receptor, thereby affecting the function. TESTING THE HYPOTHESIS: Dietary interventions should compare effects of agrarian and non-agrarian diets on incidence of diseases of affluence, related risk factors and leptin resistance. A non-significant (p = 0.10) increase of cardiovascular mortality was noted in patients advised to eat more whole-grain cereals. Our lab conducted a study on 24 domestic pigs in which a cereal-free hunter-gatherer diet promoted significantly higher insulin sensitivity, lower diastolic blood pressure and lower C-reactive protein as compared to a cereal-based swine feed. Testing should also evaluate the effects of grass lectins on the leptin system in vivo by diet interventions, and in vitro in various leptin and leptin receptor models. Our group currently conducts such studies. IMPLICATIONS OF THE HYPOTHESIS: If an agrarian diet initiates diseases of affluence it should be possible to identify the responsible constituents and modify or remove them so as to make an agrarian diet healthier.