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Sociodemographic and lifestyle-related risk factors for identifying vulnerable groups for type 2 diabetes: a narrative review with emphasis on data from Europe.
Kyrou, I, Tsigos, C, Mavrogianni, C, Cardon, G, Van Stappen, V, Latomme, J, Kivelä, J, Wikström, K, Tsochev, K, Nanasi, A, et al
BMC endocrine disorders. 2020;20(Suppl 1):134
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Type 2 diabetes mellitus (T2DM) results from progressive loss of insulin secretion, which is typically combined with various degrees of insulin resistance. The aim of this study is to provide a comprehensive overview of key sociodemographic and lifestyle-related risk factors for identifying vulnerable groups for T2DM with emphasis on data from Europe. This study is a narrative review which includes 101 publications. Literature shows that prevention of T2DM should be a collaborative effort which mobilizes multiple partners/ stakeholders at a national and international (e.g. European) level. In addition, a holistic approach is becoming increasingly essential in order to put into effect multidimensional public health programs and integrated interventions for effective T2DM prevention which will take into account both traditional and socioeconomic/socioecological factors. Authors conclude that a multidimensional approach for the prevention of T2DM may have a broader impact against the current diabesity epidemic within and across countries in Europe.
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) comprises the vast majority of all diabetes cases in adults, with alarmingly increasing prevalence over the past few decades worldwide. A particularly heavy healthcare burden of diabetes is noted in Europe, where 8.8% of the population aged 20-79 years is estimated to have diabetes according to the International Diabetes Federation. Multiple risk factors are implicated in the pathogenesis of T2DM with complex underlying interplay and intricate gene-environment interactions. Thus, intense research has been focused on studying the role of T2DM risk factors and on identifying vulnerable groups for T2DM in the general population which can then be targeted for prevention interventions. METHODS For this narrative review, we conducted a comprehensive search of the existing literature on T2DM risk factors, focusing on studies in adult cohorts from European countries which were published in English after January 2000. RESULTS Multiple lifestyle-related and sociodemographic factors were identified as related to high T2DM risk, including age, ethnicity, family history, low socioeconomic status, obesity, metabolic syndrome and each of its components, as well as certain unhealthy lifestyle behaviors. As Europe has an increasingly aging population, multiple migrant and ethnic minority groups and significant socioeconomic diversity both within and across different countries, this review focuses not only on modifiable T2DM risk factors, but also on the impact of pertinent demographic and socioeconomic factors. CONCLUSION In addition to other T2DM risk factors, low socioeconomic status can significantly increase the risk for prediabetes and T2DM, but is often overlooked. In multinational and multicultural regions such as Europe, a holistic approach, which will take into account both traditional and socioeconomic/socioecological factors, is becoming increasingly crucial in order to implement multidimensional public health programs and integrated community-based interventions for effective T2DM prevention.
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Effects of Plant-Based Diets on Outcomes Related to Glucose Metabolism: A Systematic Review.
Johannesen, CO, Dale, HF, Jensen, C, Lied, GA
Diabetes, metabolic syndrome and obesity : targets and therapy. 2020;13:2811-2822
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Research indicates that a reduction in the intake of animal products and an increase in plant-based foods have several positive health outcomes. The aim of this study was to evaluate the effect of a plant-based diet on outcomes related to glucose metabolism. This study is a systemic review of nine randomised controlled trials which focused on subjects with overweight/obesity, type 2 diabetes mellitus, or cardiovascular disease. Overall, the results of this study were inconsistent overall. Findings show that: - five of the nine studies (56%) showed that the plant-based intervention significantly improved markers of glycaemic control from baseline to end point. - four studies (44%) showed a significant improvement in markers of glycaemic control in the intervention group that differed from the control intervention. Additionally, they also did not reveal any significant improvements of a plant-based intervention on outcomes related to glucose metabolism. Authors outline that no clear conclusion regarding effects of different plant-based diets can be drawn based on the current findings.
Abstract
According to the rising prevalence of obesity and metabolic disorders leading to impaired glucose metabolism, effective strategies to prevent and/or delay the onset of disease are of great need. A plant-based diet has been suggested as an effective lifestyle change that may reduce the degree of obesity and improve outcomes related to glucose metabolism. This systematic review aimed to evaluate the effect of a plant-based diet on outcomes related to glucose metabolism. A literature search was conducted in the database PubMed until January 30, 2020. Randomized controlled trials investigating the effect of a plant-based dietary intervention on outcomes related to glucose metabolism in human subjects compared to an omnivorous diet were eligible for inclusion. Of 65 publications identified, nine trials on subjects with overweight/obesity, type 2 diabetes mellitus, or cardiovascular disease were included. Five studies reported that the plant-based intervention significantly improved markers of glycemic control from baseline to end point, of which four revealed a significant improvement in the intervention group compared to the control intervention. The remaining four studies did not observe a significant effect of a plant-based intervention on outcomes related to glucose metabolism. Our findings suggest that a shift to a plant-based diet may lead to favorable effects on glycemic control in individuals diagnosed with type 2 diabetes mellitus and/or obesity. The data were however somewhat conflicting, and the included trials reported results based on different intervention diets and study populations. Overall, no clear conclusions regarding effects of different plant-based diets can be drawn based on the current findings alone.
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Comparison of Food and Nutrient Intakes between Japanese Dyslipidemic Patients with and without Low-Density Lipoprotein Cholesterol Lowering Drug Therapy: A Cross-Sectional Study.
Kameyama, N, Maruyama, C, Shijo, Y, Umezawa, A, Sato, A, Ayaori, M, Ikewaki, K, Waki, M, Teramoto, T
Journal of atherosclerosis and thrombosis. 2020;27(7):683-694
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Dyslipidaemia is a risk factor for atherosclerotic cardiovascular disease and its treatment is of great public health and clinical importance. The aim of this study was to investigate actual food and nutrient intakes in Japanese patients with dyslipidaemia who had not received dietary counselling. A secondary aim was to compare food and nutrient intakes between patients with and without low-density lipoprotein cholesterol (LDL-C) lowering drug therapy. This is a cross-sectional study of 104 (53 women & 51 men) dyslipidaemic patients with an age range from 30 to 65 years. Results show that most patients consumed excessive amounts of energy, lipids, saturated fatty acids, cholesterol and sodium, while consumption of dietary fibre, EPA and DHA were low, regardless of whether or not they were being treated with LDL-C lowering drugs. Furthermore, food groups showing an independent correlation with LDL-C concentrations differed between patients with and without LDL-C lowering drug therapy. Authors conclude that diet therapy while taking LDL-C lowering drugs, merits further consideration.
Abstract
AIM: We aimed to clarify actual food and nutrient intakes in Japanese patients with dyslipidemia. We also compared food and nutrient intakes between patients with and without low-density lipoprotein cholesterol (LDL-C) lowering drug therapy. METHODS Food and nutrient intakes were assessed employing 3-day weighted dietary records in this cross-sectional study of 104 Japanese outpatients with dyslipidemia, age 30-65 years, not given dietary counseling. Anthropometric and biochemical parameters were measured after an overnight fast. Food and nutrient intakes were compared between patients with versus without LDL-C lowering drug prescriptions. Stepwise multiple regression analysis was performed to identify relationships between the serum LDL-C concentrations and food intakes. RESULTS Of the 104 patients, 43.3% were prescribed LDL-C lowering drugs, primarily statins. Of the total patients, 83% had lipid intakes over 25% of total energy consumption (%E), exceeding the recommendation for dyslipidemia by the Japan Atherosclerosis Society. Similarly, 77% had saturated fatty acid intakes over 7%E, and 88% had cholesterol intakes over 200 mg per day. Dietary fiber consumption was low (<25 g) in 97% of patients. Those taking LDL-C lowering drugs consumed less "meat, poultry and processed meat products" and "cereals", and more "fish", "fruits" and "nuts", than patients not taking these drugs (p<0.05). Food intakes correlating with LDL-C concentrations independently of drug therapy differed between patients taking versus not taking these medications. CONCLUSION Our results support the necessity of diet therapy for patients with dyslipidemia regardless of whether LDL-C lowering drugs are prescribed.The clinical trial registration number: UMIN000022955.
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Impact of a Web-Based Exercise and Nutritional Education Intervention in Patients Who Are Obese With Hypertension: Randomized Wait-List Controlled Trial.
Lisón, JF, Palomar, G, Mensorio, MS, Baños, RM, Cebolla-Martí, A, Botella, C, Benavent-Caballer, V, Rodilla, E
Journal of medical Internet research. 2020;22(4):e14196
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Cardiovascular disease is the leading cause of morbidity and mortality in developed countries. Internet-based interventions are a promising strategy for promoting healthy lifestyle behaviours. The aim of this study was to investigate the short- and long-term efficacy of a self-administered internet-based intervention aimed at promoting lifestyle changes in patients who are obese with hypertension. The study is a randomized wait-list controlled trial which recruited 105 adults with hypertension who were overweight or obese and randomly assigned to either a 3-month internet-based intervention group (n=55) or the wait-list control group (n=50). Results showed a significant decrease in the body mass index, body fat mass and blood glucose (blood sugar) levels at 3 months in the internet-based intervention group. In addition, there was a favourable trend towards a relation to blood pressure, which reached statistical significance at the 12-month follow-up. Authors conclude that simple strategies that can easily be incorporated into daily living in a scalable and cost-effective way can empower patients by educating them about health, thus, increasing their confidence and promoting self-management.
Abstract
BACKGROUND Internet-based interventions are a promising strategy for promoting healthy lifestyle behaviors. These have a tremendous potential for delivering electronic health interventions in scalable and cost-effective ways. There is strong evidence that the use of these programs can lead to weight loss and can lower patients' average blood pressure (BP) levels. So far, few studies have investigated the effects of internet-based programs on patients who are obese with hypertension (HTN). OBJECTIVE The aim of this study is to investigate the short- and long-term efficacy, in terms of body composition and BP parameters, of a self-administered internet-based intervention involving different modules and learning techniques aimed at promoting lifestyle changes (both physical activity and healthy eating) in patients who are obese with HTN. METHODS A randomized wait-list controlled trial design was used. We recruited 105 adults with HTN who were overweight or obese and randomly assigned them to either a 3-month internet-based intervention group (n=55) or the wait-list control group (n=50). We assessed BMI (primary outcome), body fat mass (BFM), systolic (S)BP and diastolic (D)BP, blood glucose and insulin levels, physical activity levels, and functional capacity for aerobic exercise at Time 0 (preintervention) and Time 1 (postintervention). All the patients in the wait-list control group subsequently received the intervention, and a secondary within-group analysis, which also included these participants, was conducted at Time 2 (12-month follow-up). RESULTS A 2-way mixed analysis of covariance showed a significant decrease in BMI, BFM, and blood glucose at 3 months in the internet-based intervention group; the effect size for the BMI and BFM parameters was moderate to large, and there was also a borderline significant trend for DBP and insulin. These results were either maintained or improved upon at Time 2 and showed significant changes for BMI (mean difference -0.4, 95% CI -0.1 to -0.6; P=.005), BFM (mean difference -2.4, 95% CI -1.1 to -3.6; P<.001), DBP (mean difference -1.8, 95% CI -0.2 to -3.3; P=.03), and blood glucose (mean difference -2, 95% CI 0 to -4; P=.04). CONCLUSIONS Implementation of our self-administered internet-based intervention, which involved different learning techniques aimed to promote lifestyle changes, resulted in positive short- and long-term health benefits in patients who are obese with HTN. TRIAL REGISTRATION ClinicalTrials.gov NCT03396302; https://clinicaltrials.gov/ct2/show/NCT03396302.
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Proteomic profiles before and during weight loss: Results from randomized trial of dietary intervention.
Figarska, SM, Rigdon, J, Ganna, A, Elmståhl, S, Lind, L, Gardner, CD, Ingelsson, E
Scientific reports. 2020;10(1):7913
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Understanding biological substances, or "biomarkers" that are present in the body of individuals with obesity, could lead to personalised dietary recommendations for weight loss. Current research on biomarkers in individuals with obesity who have undergone a weight loss intervention is lacking. This secondary analysis of a randomised control trial study of 609 healthy and obese adults over 6 months, aimed to identify biomarkers associated with obesity, determine any changes with weight loss and if these could be used to make personalised recommendations. 263 biomarkers were tested and the results showed that 102 were associated with body mass index (BMI). 88 were elevated in individuals with a higher BMI. Upon weight loss, a large number of these decreased and a small number increased. The type of diet had no influence on how these biomarkers changed and only one could be used to predict weight loss. It was concluded that many of the biomarkers were connected to BMI and many changed with weight loss, however none of the biomarkers studied could be used to individualise dietary recommendations. This study could be used by healthcare professionals to understand that the role of biomarkers in personalising recommendations is complex and more research may be needed.
Abstract
Inflammatory and cardiovascular biomarkers have been associated with obesity, but little is known about how they change upon dietary intervention and concomitant weight loss. Further, protein biomarkers might be useful for predicting weight loss in overweight and obese individuals. We performed secondary analyses in the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) randomized intervention trial that included healthy 609 adults (18-50 years old) with BMI 28-40 kg/m2, to evaluate associations between circulating protein biomarkers and BMI at baseline, during a weight loss diet intervention, and to assess predictive potential of baseline blood proteins on weight loss. We analyzed 263 plasma proteins at baseline and 6 months into the intervention using the Olink Proteomics CVD II, CVD III and Inflammation arrays. BMI was assessed at baseline, after 3 and 6 months of dietary intervention. At baseline, 102 of the examined inflammatory and cardiovascular biomarkers were associated with BMI (>90% with successful replication in 1,584 overweight/obese individuals from a community-based cohort study) and 130 tracked with weight loss shedding light into the pathophysiology of obesity. However, out of 263 proteins analyzed at baseline, only fibroblast growth factor 21 (FGF-21) predicted weight loss, and none helped individualize dietary assignment.
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Changes in Weight and Nutritional Habits in Adults with Obesity during the "Lockdown" Period Caused by the COVID-19 Virus Emergency.
Pellegrini, M, Ponzo, V, Rosato, R, Scumaci, E, Goitre, I, Benso, A, Belcastro, S, Crespi, C, De Michieli, F, Ghigo, E, et al
Nutrients. 2020;12(7)
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The pandemic of the coronavirus SARS-CoV-2 (COVID-19) has caused significant disruption in everyday lifestyle. The aim if this study was to evaluate the changes in weight and dietary habits in a sample of individuals with obesity attending the Obesity Unit after 1 month of enforced lockdown. This is an observational retrospective study were patients followed a 12-month multidisciplinary weight loss program. Results showed that patients with obesity attending an Obesity Unit in Northern Italy showed a ≈1.5 kg self-reported weight gain after the first month of lockdown. Lower education level, self-reported anxiety/depression, and not paying attention to the healthiness of food choices were significantly associated with weight and body mass index increase. Authors conclude that the adverse mental burden linked to the COVID-19 pandemic might be associated with their increased weight.
Abstract
Our aim is evaluating the changes in weight and dietary habits in a sample of outpatients with obesity after 1 month of enforced lockdown during the COVID-19 pandemic in Northern Italy. In this observational retrospective study, the patients of our Obesity Unit were invited to answer to a 12-question multiple-choice questionnaire relative to weight changes, working activity, exercise, dietary habits, and conditions potentially impacting on nutritional choices. A multivariate regression analysis was performed to evaluate the associations among weight/BMI changes and the analyzed variables. A total of 150 subjects (91.5%) completed the questionnaire. Mean self-reported weight gain was ≈1.5 kg (p < 0.001). Lower exercise, self-reported boredom/solitude, anxiety/depression, enhanced eating, consumption of snacks, unhealthy foods, cereals, and sweets were correlated with a significantly higher weight gain. Multiple regression analyses showed that increased education (inversely, β = -1.15; 95%CI -2.13, -0.17, p = 0.022), self-reported anxiety/depression (β = 1.61; 0.53, 2.69, p = 0.004), and not consuming healthy foods (β = 1.48; 0.19, 2.77, p = 0.026) were significantly associated with increased weight gain. The estimated direct effect of self-reported anxiety/depression on weight was 2.07 kg (1.07, 3.07, p < 0.001). Individuals with obesity significantly gained weight 1 month after the beginning of the quarantine. The adverse mental burden linked to the COVID-19 pandemic was greatly associated with increased weight gain.
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Type 2 Diabetes Mellitus in Class II and III Obesity: Prevalence, Associated Factors, and Correlation between Glycemic Parameters and Body Mass Index.
Silveira, EA, de Souza Rosa, LP, de Carvalho Santos, ASEA, de Souza Cardoso, CK, Noll, M
International journal of environmental research and public health. 2020;17(11)
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Type 2 diabetes mellitus (T2DM) and obesity are independently known to cause serious health complications, with risks of cardiovascular diseases, higher mortality, low quality of life, and increased public health spending. However, when these diseases occur concurrently, their negative effects on health, health systems, and mortality are even greater. The main aim this study was to investigate the prevalence of T2DM and its associated factors, with an emphasis on biochemical parameters and eating habits, in class II and III obese individuals. The study included 150 class II and III obese individuals from the primary healthcare system of the Brazilian Unified Health System. Results indicate a high prevalence of T2DM (40%) in the studied population, with the associated risks being lower educational level, non-consumption of whole grains, and high insulin resistance. Furthermore, there was no correlation between BMI and glycaemic parameters, that is, an increased BMI did not directly affect a decline in the metabolic condition of T2DM individuals. Authors conclude by emphasising the need to perform further research on T2DM in class II and III obese population.
Abstract
Despite the worldwide growth of class II and III obesity, the factors associated with type 2 diabetes mellitus (T2DM) in these obese individuals are not widely understood. Moreover, no study has investigated these associations in South America. Our study aimed to investigate the prevalence of T2DM and its associated factors, with an emphasis on biochemical parameters and eating habits, in class II and III obese individuals. We also aimed to analyze the correlation between glycemic parameters and body mass index (BMI). Baseline data from a randomized clinical trial (DieTBra Trial) of 150 class II and III obese individuals (BMI > 35 kg/m2) was used. An accelerometer, Food Frequency Questionnaire, and bioimpedance analysis were used to assess physical activity levels, eating habits, and body composition, respectively. Blood was collected after 12 h of fasting. Hierarchical multivariate Poisson regression was performed, and prevalence ratios (PRs) were calculated. Correlations between glycemic parameters (fasting blood glucose, glycosylated hemoglobin, homeostasis model assessment of insulin resistance (HOMA-IR), and insulin) and BMI were also analyzed. The prevalence of T2DM was 40.0% (95% CI, 32.1-48.3), high fasting blood glucose level was 19.33% (95% CI, 13.3-26.6), and high glycosylated hemoglobin was 32.67% (95% CI, 25.2-40.8). Age ≥ 50 years (PR = 3.17, 95% CI, 1.26-7.98) was significantly associated with T2DM; there was a positive linear trend between age and T2DM (p = 0.011). Multivariate analysis showed an association with educational level (PR = 1.49, 1.07-2.09, p = 0.018), nonconsumption of whole grains daily (PR = 1.67, 1.00-2.80, p = 0.049), and high HOMA-IR (PR = 1.54, 1.08-2.18, p = 0.016). We found a high prevalence of T2DM and no significant correlations between BMI and glycemic parameters.
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Effects of A 12-Month Intensive Lifestyle Monitoring Program in Predominantly Overweight/Obese Arab Adults with Prediabetes.
Wani, K, Alfawaz, H, Alnaami, AM, Sabico, S, Khattak, MNK, Al-Attas, O, Alokail, MS, Alharbi, M, Chrousos, G, Kumar, S, et al
Nutrients. 2020;12(2)
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Key determinant factors associated with type 2 diabetes mellitus in the Arab world, aside from the genetic predisposition are obesity, rapid urbanization, and lack of physical activity. The aim of the study was to evaluate the effectiveness of a Diabetes Prevention Programme-based lifestyle modification program focused on overweight/obese Saudi adults with impaired fasting glucose. This study is a 12-month two-arm randomized controlled (1:1) lifestyle intervention. Participants were randomly assigned to receive either an intensive lifestyle modification program or general advice at the time of recruitment. Results showed that participants following the intensive lifestyle modification program had significant changes in body weight, body mass index and glycaemic indices post-intervention. Authors conclude that for Saudi adults with impaired fasting glucose, a self-monitoring-based lifestyle intervention may be a significant tool for weight loss and to reverse to normoglycemia [normal concentration of sugar in the blood].
Abstract
This 12-month, randomized, controlled lifestyle intervention study was aimed at assessing the effectiveness of a lifestyle intervention in terms of (1) the reduction of at least 5% of body weight compared to baseline and (2) the percentage of participants in which fasting blood glucose (FBG) normalizes (<5.6 mmol/L) post-intervention, in predominantly overweight/obese Saudi adults with impaired fasting glucose. A total of 300 Saudi adults with prediabetes at baseline (FBG 5.6-6.9 mmol/L) were enrolled to receive either general advice (GA) or a rigorous, self-monitored, lifestyle modification program (intervention group, IG) for 12 months, focused on food choices, physical activity, and weight loss. Anthropometric and biochemical estimations were analyzed at baseline, 6, and 12 months. At baseline, 136/150 in the GA group (90.7%) and 127/150 in the IG group (84.7%) were either overweight or obese. A total of 14% (n = 21) of the subjects in the IG arm discontinued, compared to 8% (n = 12) in the GA arm. Data from completers (92% (n = 138) and 86% (n= 129) participants in GA and IG arms, respectively) were considered for the final analysis. Post-intervention, 37.2% (n = 48) of participants in the IG group had ≥5% weight reduction, as compared to 12.3% (n = 17) in the GA group (p < 0.01). Similarly, the percentage of participants who normalized their FBG post-intervention was 46.5% (n = 60) in the IG group compared to 21.7% (n = 30) in the GA group (p < 0.01). A 12-month Diabetes Prevention Program (DPP)-styled intensive lifestyle program translated effectively in decreasing weight and improving fasting glucose compared to the GA group in predominantly overweight/obese Saudi adults with prediabetes, suggesting that in the case of guided intervention programs, people are willing to participate and possibly change a sedentary lifestyle.
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A Snack Formulated with Ingredients to Slow Carbohydrate Digestion and Absorption Reduces the Glycemic Response in Humans: A Randomized Controlled Trial.
Rebello, CJ, Johnson, WD, Pan, Y, Larrivee, S, Zhang, D, Nisbet, M, Johnson, J, Chu, Y, Greenway, FL
Journal of medicinal food. 2020;23(1):21-28
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The rate, extent, and location of carbohydrate digestion and absorption are factors that influence metabolic outcomes. The aim of this study was to investigate the effect of a savoury snack (Test-snack) on the glycaemic response [changes in blood glucose after consuming a carbohydrate-containing food] in humans. The study is randomized, controlled crossover trial which enrolled twenty subjects, aged between 18 and 60 years. Each subject was randomly assigned to one of six unique orders for receiving the three interventions. Results show that the Test-snack formulated with ingredients and processes to slow carbohydrate digestion lowered the glycaemic response compared to the Control-snack. Furthermore, slowing of starch digestion influences subjective appetite ratings independent of the glycaemic response. Authors conclude that foods designed to slow starch digestion can help consumers meet their need to moderate the postprandial [after a meal] glycaemic response.
Abstract
This study compared the effect of a snack with ingredients to slow carbohydrate digestion (Test-snack) on postprandial blood glucose and insulin concentrations and subjective appetite ratings. We hypothesized that Test-snack would lower glucose and insulin responses and reduce appetite compared with a Control-snack. Overweight or obese subjects (n = 17) completed a randomized crossover study. Glucose, insulin, and appetite ratings were measured before consuming each snack or white bread (Bread) and over a period of 4 h. Subjects received Test-snack, Control-snack, or Bread in random order at least a week apart. The a priori primary outcome was the glucose response, and the secondary outcomes were appetite ratings and insulin responses. Mixed effects statistical models were used to perform analysis of variance in terms of the area under curve (AUC) and at specific time points. The 2-h AUC for glucose was significantly lower with Test-snack compared to Control-snack and Bread (AUC and 95% confidence intervals: Test = 2186.43 [1783.36-2589.51]; Control = 3293.75 [2893.97-3693.54]; Bread = 2800.28 [2405.79-3194.77] mg/dL · min). Four-hour AUC for glucose, and insulin, followed a similar pattern except that Test-snack did not differ from Bread. The glucose concentrations peaked at 45 min under all three conditions, but Test-snack elicited a lower response than Control-snack and Bread (P < .01). Test increased fullness and satisfaction and reduced hunger and prospective intake compared to Bread (P < .02), but was not significantly different from Control-snack. Ingredients that slow carbohydrate digestion in a snack reduce the postprandial glucose and insulin responses compared to a product without these ingredients.
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Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease.
Smith, GI, Shankaran, M, Yoshino, M, Schweitzer, GG, Chondronikola, M, Beals, JW, Okunade, AL, Patterson, BW, Nyangau, E, Field, T, et al
The Journal of clinical investigation. 2020;130(3):1453-1460
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Non-alcoholic fatty liver disease (NAFLD) is a common complication of obesity and is associated with multiorgan insulin resistance, dyslipidaemia and an increased risk of diabetes and coronary heart disease. The aims of this study were to (a) determine hepatic de novo lipogenesis (DNL) [the liver’s biochemical process of synthesising fatty acids] in 3 distinct cohorts, (b) determine the relationships among hepatic DNL and intrahepatic [within the liver] triglyceride (IHTG) content, and (c) determine the effect of moderate (10%) weight loss. This study is a cross-sectional study which included a total of 67 men and women (mean age: 39 ± 1 years; 14 men and 53 women). Results highlight the importance of DNL in the pathogenesis of hepatic steatosis [build up of fats in the liver] and suggest that increases in daily 24-hour plasma glucose and insulin concentrations are major drivers of increased DNL in individuals with obesity and NAFLD. Additionally, moderate (10%) weight loss caused a marked decrease in both hepatic DNL and IHTG content. Authors conclude that increases in circulating glucose and insulin promote hepatic DNL in individuals with NAFLD. Whereas an improvement in insulin sensitivity and a decrease in hepatic DNL, are potentially important contributors to the decline in IHTG content associated with moderate weight loss.
Abstract
BACKGROUNDAn increase in intrahepatic triglyceride (IHTG) is the hallmark feature of nonalcoholic fatty liver disease (NAFLD) and is decreased by weight loss. Hepatic de novo lipogenesis (DNL) contributes to steatosis in individuals with NAFLD. The physiological factors that stimulate hepatic DNL and the effect of weight loss on hepatic DNL are not clear.METHODSHepatic DNL, 24-hour integrated plasma insulin and glucose concentrations, and both liver and whole-body insulin sensitivity were determined in individuals who were lean (n = 14), obese with normal IHTG content (n = 26), or obese with NAFLD (n = 27). Hepatic DNL was assessed using the deuterated water method corrected for the potential confounding contribution of adipose tissue DNL. Liver and whole-body insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp procedure in conjunction with glucose tracer infusion. Six subjects in the obese-NAFLD group were also evaluated before and after a diet-induced weight loss of 10%.RESULTSThe contribution of hepatic DNL to IHTG-palmitate was 11%, 19%, and 38% in the lean, obese, and obese-NAFLD groups, respectively. Hepatic DNL was inversely correlated with hepatic and whole-body insulin sensitivity, but directly correlated with 24-hour plasma glucose and insulin concentrations. Weight loss decreased IHTG content, in conjunction with a decrease in hepatic DNL and 24-hour plasma glucose and insulin concentrations.CONCLUSIONSThese data suggest hepatic DNL is an important regulator of IHTG content and that increases in circulating glucose and insulin stimulate hepatic DNL in individuals with NAFLD. Weight loss decreased IHTG content, at least in part, by decreasing hepatic DNL.TRIAL REGISTRATIONClinicalTrials.gov NCT02706262.FUNDINGThis study was supported by NIH grants DK56341 (Nutrition Obesity Research Center), DK20579 (Diabetes Research Center), DK52574 (Digestive Disease Research Center), and RR024992 (Clinical and Translational Science Award), and by grants from the Academy of Nutrition and Dietetics Foundation, the College of Natural Resources of UCB, and the Pershing Square Foundation.