Ketone bodies: from enemy to friend and guardian angel.

During starvation, fasting, or a diet containing little digestible carbohydrates, the circulating insulin levels are decreased. This promotes lipolysis, and the breakdown of fat becomes the major source of energy. The hepatic energy metabolism is regulated so that under these circumstances, ketone bodies are generated from ß-oxidation of fatty acids and secreted as ancillary fuel, in addition to gluconeogenesis. Increased plasma levels of ketone bodies thus indicate a dietary shortage of carbohydrates. Ketone bodies not only serve as fuel but also promote resistance to oxidative and inflammatory stress, and there is a decrease in anabolic insulin-dependent energy expenditure. It has been suggested that the beneficial non-metabolic actions of ketone bodies on organ functions are mediated by them acting as a ligand to specific cellular targets. We propose here a major role of a different pathway initiated by the induction of oxidative stress in the mitochondria during increased ketolysis. Oxidative stress induced by ketone body metabolism is beneficial in the long term because it initiates an adaptive (hormetic) response characterized by the activation of the master regulators of cell-protective mechanism, nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuins, and AMP-activated kinase. This results in resolving oxidative stress, by the upregulation of anti-oxidative and anti-inflammatory activities, improved mitochondrial function and growth, DNA repair, and autophagy. In the heart, the adaptive response to enhanced ketolysis improves resistance to damage after ischemic insults or to cardiotoxic actions of doxorubicin. Sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors may also exert their cardioprotective action via increasing ketone body levels and ketolysis. We conclude that the increased synthesis and use of ketone bodies as ancillary fuel during periods of deficient food supply and low insulin levels causes oxidative stress in the mitochondria and that the latter initiates a protective (hormetic) response which allows cells to cope with increased oxidative stress and lower energy availability. KEYWORDS: Ketogenic diet, Ketone bodies, Beta hydroxybutyrate, Insulin, Obesity, Type 2 diabetes, Inflammation, Oxidative stress, Cardiovascular disease, SGLT2, Hormesis.

Insulin: too much of a good thing is bad.

BACKGROUND: Insulin shares a limited physiological concentration range with other endocrine hormones. Not only too low, but also too high systemic insulin levels are detrimental for body functions. MAIN BODY: The physiological function and clinical relevance of insulin are usually seen in association with its role in maintaining glucose homeostasis. However, insulin is an anabolic hormone which stimulates a large number of cellular responses. Not only too low, but also excess insulin concentrations are detrimental to the physiological balance. Although the glucoregulatory activity of insulin is mitigated during hyperinsulinemia by dampening the efficiency of insulin signaling ("insulin resistance"), this is not the case for most other hormonal actions of insulin, including the promotion of protein synthesis, de novo lipogenesis, and cell proliferation; the inhibition of lipolysis, of autophagy-dependent cellular turnover, and of nuclear factor E2-related factor-2 (Nrf2)-dependent antioxidative; and other defense mechanisms. Hence, there is no general insulin resistance but selective impairment of insulin signaling which causes less glucose uptake from the blood and reduced activation of endothelial NO synthase (eNOS). Because of the largely unrestricted insulin signaling, hyperinsulinemia increases the risk of obesity, type 2 diabetes, and cardiovascular disease and decreases health span and life expectancy. In epidemiological studies, high-dose insulin therapy is associated with an increased risk of cardiovascular disease. Randomized controlled trials of insulin treatment did not observe any effect on disease risk, but these trials only studied low insulin doses up to 40 IU/day. Proof for a causal link between elevated insulin levels and cardiovascular disease risk comes from Mendelian randomization studies comparing individuals with genetically controlled low or high insulin production. CONCLUSIONS: The detrimental actions of prolonged high insulin concentrations, seen also in cell culture, argue in favor of a lifestyle that limits circadian insulin levels. The health risks associated with hyperinsulinemia may have implications for treatment regimens used in type 2 diabetes.

Cardiorespiratory Fitness and Cardiac Autonomic Function in Diabetes.

PURPOSE OF REVIEW: This review summarizes the current knowledge on the relationship of physical activity, exercise, and cardiorespiratory fitness (CRF) with cardiovascular autonomic neuropathy (CAN) based on epidemiological, clinical, and interventional studies. RECENT FINDINGS: The prevalence of CAN increases with age and duration of diabetes. Further risk factors for CAN comprise poor glycemic control, dyslipidemia, abdominal obesity, hypertension, and the presence of diabetic complications. CAN has been also linked to reduced CRF. We recently showed that CRF parameters (e.g., maximal oxidative capacity or oxidative capacity at the anaerobic threshold) are associated with cardiac autonomic function in patients recently diagnosed with type 1 or type 2 diabetes. Exercise interventions have shown that physical activity can increase cardiovagal activity and reduce sympathetic overactivity. In particular, long-term and regularly, but also supervised, performed endurance and high-intense and high-volume exercise improves cardiac autonomic function in patients with type 2 diabetes. By contrast, the evidence in those with type 1 diabetes and also in individuals with prediabetes or metabolic syndrome is weaker. Overall, the studies reviewed herein addressing the question whether favorably modulating the autonomic nervous system may improve CRF during exercise programs support the therapeutic concept to promote physical activity and to achieve physical fitness. However, high-quality exercise interventions, especially in type 1 diabetes and metabolic syndrome including prediabetes, are further required to better understand the relationship between physical activity, fitness, and cardiac autonomic function.

Lowered cutoffs to reduce false positives on the Word Memory Test.

OBJECTIVE: To adjust the decision criterion for the Word Memory Test (WMT, Green, 2003) to minimize the frequency of false positives. METHOD: Archival data were combined into a database (n = 3,210) to examine the best cut score for the WMT. We compared results based on the original scoring rules and those based on adjusted scoring rules using a criterion based on 16 performance validity tests (PVTs) exclusive of the WMT. Cutoffs based on peer-reviewed publications and test manuals were used. The resulting PVT composite was considered the best estimate of validity status. We focused on a specificity of .90 with a false-positive rate of less than .10 across multiple samples. RESULTS: Each examinee was administered the WMT, as well as on average 5.5 (SD = 2.5) other PVTs. Based on the original scoring rules of the WMT, 31.8% of examinees failed. Using a single failure on the criterion PVT (C-PVT), the base rate of failure was 45.9%. When requiring two or more failures on the C-PVT, the failure rate dropped to 22.8%. Applying a contingency analysis (i.e., X2) to the two failures model on the C-PVT measure and using the original rules for the WMT resulted in only 65.3% agreement. However, using our adjusted rules for the WMT, which consisted of relying on only the IR and DR WMT subtest scores with a cutoff of 77.5%, agreement between the adjusted and the C-PVT criterion equaled 80.8%, for an improvement of 12.1% identified. The adjustmeny resulted in a 49.2% reduction in false positives while preserving a sensitivity of 53.6%. The specificity for the new rules was 88.8%, for a false positive rate of 11.2%. CONCLUSIONS: Results supported lowering of the cut score for correct responding from 82.5% to 77.5% correct. We also recommend discontinuing the use of the Consistency subtest score in the determination of WMT failure.

Neuropsychological differential diagnosis of mild traumatic brain injury.

The diagnosis and evaluation of mild traumatic brain injury (mTBI) is reviewed from the perspective of meta-analyses of neuropsychological outcome, showing full recovery from a single, uncomplicated mTBI by 90 days post-trauma. Persons with history of complicated mTBI characterized by day-of-injury computed tomography or magnetic resonance imaging abnormalities, and those who have suffered prior mTBIs may or may not show evidence of complete recovery similar to that experienced by persons suffering a single, uncomplicated mTBI. Persistent post-concussion syndrome (PCS) is considered as a somatoform presentation, influenced by the non-specificity of PCS symptoms which commonly occur in non-TBI samples and co-vary as a function of general life stress, and psychological factors including symptom expectation, depression and anxiety. A model is presented for forensic evaluation of the individual mTBI case, which involves open-ended interview, followed by structured interview, record review, and detailed neuropsychological testing. Differential diagnosis includes consideration of other neurologic and psychiatric disorders, symptom expectation, diagnosis threat, developmental disorders, and malingering.

Impact of a Low-Insulin-Stimulating Bread on Weight Development-A Real Life Randomised Controlled Trial.

The impact on body weight development is usually analysed by comparing different diet types. Our approach was to change only one component, namely bread, common to most diets. In a single-centre triple-blind randomised controlled trial the effects of two different breads on body weight were analyzed without further lifestyle modification. Overweight adult volunteers (n = 80) were randomised 1:1 to exchange previously consumed breads for either a rye bread from milled whole grain (control) or a medium-carbohydrate, low-insulin-stimulating bread (intervention). Pre-tests demonstrated that the two bread types strongly differed in the glucose and insulin response elicited, but had similar energy content, texture and taste. The primary endpoint was the estimated treatment difference (ETD) in change of body weight after 3 months of treatment. Whereas body weight remained unchanged in the control group (-0.1 ± 2.0 kg), significant weight reduction was observed in the intervention group (-1.8 ± 2.9 kg), with an ETD of -1.7 ± 0.2 kg (p = 0.007), that was more pronounced in participants ≥ 55 years (-2.6 ± 3.3 kg), paralleled by significant reductions in body mass index and hip circumference. Moreover, in the intervention group, the percentage of participants with significant weight loss (≥1 kg) was twice as high as in the control group (p < 0.001). No other statistically significant changes in clinical or lifestyle parameters were noted. Simply exchanging a common insulinogenic bread for a low-insulin-stimulating bread demonstrates potential to induce weight loss in overweight persons, especially those at older age.

Forced choice test score of p ≤ .20 and failures on ≥ six performance validity tests results in similar Overall Test Battery Means.

Objective: To determine if similar levels of performance on the Overall Test Battery Mean (OTBM) occur at different forced choice test (FCT) p-value score failures. Second, to determine the OTBM levels that are associated with failures at above chance on various performance validity (PVT) tests. Method: OTBMs were computed from archival data obtained from four practices. We calculated each examinee's Estimated Premorbid Global Ability (EPGA) and OTBM. The sample size was 5,103 examinees with 282 (5.5%) of these scoring below chance at p ≤ .20 on at least one FCT. Results: The OTBM associated with a failure at p ≤ .20 was equivalent to the OTBM that was associated with failing 6 or more PVTs at above-chance cutoffs. The mean OTBMs relative to increasingly strict FCT p cutoffs were similar (T scores in the 30s). As expected, there was an inverse relationship between the number of PVTs failed and examinees' OTBMs. Conclusions: The data support the use of p ≤ .20 as the probability level for testing the significance of below chance performance on FCTs. The OTBM can be used to index the influence of invalid performance on outcomes, especially when an examinee scores below chance.

[Diabetes and cardiovascular health literacy in childhood and adolescence - a 12-year follow-up]. / Diabetes- und kardiovaskuläre Gesundheitskompetenz im Kindes- und Jugendalter ­ ein 12-Jahres-Follow-up.

BACKGROUND: The incidence of diabetes mellitus and cardiovascular diseases is increasing worldwide and also in Germany. The aim of the study was to assess the health literacy regarding these diseases in childhood and adolescence. METHODS: Students of the 5th-12th grade (grammar school ("Gymnasium"), secondary school forms ("Realschule" and "Hauptschule")) were interviewed in 2007 (n = 4383) and 2019 (n = 572) about diabetes and secondary complications. In addition, questions about other cardiovascular risk factors were asked in 2019. RESULTS: Diabetes-related questions were answered correctly by 56 % in 2007 as well as 53 % in 2019. Among others, 70 % (2007) as well as 75 % (2019) of the students stated "ate too much sugar" as a cause for type 1 diabetes. Further, questions about major risk factors for heart attack and stroke were answered correctly by only 33 % (for diabetes) and 43 %-53 % (for smoking) of students.Across all questions, a positive association indicated between the rate of correct answers and the educational level of the school institution; however, the differences remained marginal at 5-19 % between Gymnasium and Hauptschule or Realschule at both survey time points. A difference between genders was indicated in 2007 (girls: 59 % vs. boys: 52 %) and 2019 (girls: 56 % vs. boys: 51 %). CONCLUSION: Changes in health literacy regarding diabetes and other cardiovascular risk factors among 5th-12th grade students over the past 12 years could not be observed. The assumed self-infliction of type 1 diabetes may be perceived as discrimination by those affected.

Shift happens: The gender composition in clinical neuropsychology over five decades.

OBJECTIVE: The current study utilizes five decades of data to demonstrate cohort differences in gender representation in governance, speaking at conferences, serving on editorial boards, and in scholarly productivity in clinical neuropsychology. Broadly examining gender disparities across domains of professional attainment helps illuminate the areas in which inequity in clinical neuropsychology is most pronounced and in need of ameliorative resources. METHODS: Data from 1967 to 2017 were coded from publicly available information from the four major professional associations for clinical neuropsychology in the U.S. (i.e. INS, AACN, NAN, & SCN). Gender differences were examined in (1) speaking at a national conference, (2) holding an office in a professional organization, (3) serving on the editorial team for a journal affiliated with a professional organization, and (4) scholarly activity as coded from Google Scholar. RESULTS: The percentage of men in the field significantly declined across time, whereas the percentage of women significantly increased; the number of women exceeded the number of men in approximately 1992. Gender differences in conference speakers, editorial board members, and research citations were greater in the earlier than in more recent cohorts of clinical neuropsychologists but gender inequity in conference speaking and editorial activities is evident in the most recent cohorts. DISCUSSION: Gender differences in conference speakers, editorial board members, and in earning research citations have diminished over time, but early career women still face disadvantages in speaking at conferences and serving on editorial boards. We provide strategies to increase and sustain women's participation in leadership in neuropsychology.

Early and Strong Leptin Reduction Is Predictive for Long-Term Weight Loss during High-Protein, Low-Glycaemic Meal Replacement-A Subanalysis of the Randomised-Controlled ACOORH Trial.

Lifestyle interventions including meal replacement are suitable for prevention and treatment of obesity and type-2-diabetes. Since leptin is involved in weight regulation, we hypothesised that a meal replacement-based lifestyle intervention would reduce leptin levels more effectively than lifestyle intervention alone. In the international, multicentre, randomised-controlled ACOORH-trial (Almased-Concept-against-Overweight-and-Obesity-and-Related- Health-Risk), overweight or obese participants with metabolic syndrome criteria (n = 463) were randomised into two groups and received telemonitoring devices and nutritional advice. The intervention group additionally used a protein-rich, low-glycaemic meal replacement. Data were collected at baseline, after 1, 3, 6, and 12 months. All datasets providing leptin data (n = 427) were included in this predefined subanalysis. Serum leptin levels significantly correlated with sex, body mass index, weight, and fat mass at baseline (p < 0.0001). Stronger leptin reduction has been observed in the intervention compared to the control group with the lowest levels after 1 month of intervention (estimated treatment difference −3.4 µg/L [1.4; 5.4] for females; −2.2 µg/L [1.2; 3.3] for males; p < 0.001 each) and was predictive for stronger reduction of body weight and fat mass (p < 0.001 each) over 12 months. Strongest weight loss was observed after 6 months (−5.9 ± 5.1 kg in females of the intervention group vs. −2.9 ± 4.9 kg in the control group (p < 0.0001); −6.8 ± 5.3 kg vs. −4.1 ± 4.4 kg (p = 0.003) in males) and in those participants with combined leptin and insulin decrease. A meal replacement-based lifestyle intervention effectively reduces leptin which is predictive for long-term weight loss.

A High-Protein and Low-Glycemic Formula Diet Improves Blood Pressure and Other Hemodynamic Parameters in High-Risk Individuals.

Low-caloric formula diets can improve hemodynamic parameters of patients with type 2 diabetes. We, therefore, hypothesized that persons with overweight or obesity can benefit from a high-protein, low-glycemic but moderate-caloric formula diet. This post-hoc analysis of the Almased Concept against Overweight and Obesity and Related Health Risk- (ACOORH) trial investigated the impact of a lifestyle intervention combined with a formula diet (INT, n = 308) compared to a control group with lifestyle intervention alone (CON, n = 155) on hemodynamic parameters (systolic and diastolic blood pressure (SBP, DBP), resting heart rate (HR), and pulse wave velocity (PWV)) in high-risk individuals with prehypertension or hypertension. INT replaced meals during the first 6 months (1 week: 3 meals/day; 2−4 weeks: 2 meals/day; 5−26 weeks: 1 meal/day). Study duration was 12 months. From the starting cohort, 304 (68.3%, INT: n = 216; CON: n = 101) participants had a complete dataset. Compared to CON, INT significantly reduced more SBP (−7.3 mmHg 95% CI [−9.2; −5.3] vs. −3.3 mmHg [−5.9; −0.8], p < 0.049) and DBP (−3.7 mmHg [−4.9; −2.5] vs. −1.4 mmHg [−3.1; 0.2], p < 0.028) after 12 months. Compared to CON, INT showed a pronounced reduction in resting HR and PWV after 6 months but both lost significance after 12 months. Changes in SBP, DBP, and PWV were significantly associated positively with changes in body weight and fat mass (all p < 0.05) and resting HR correlated positively with fasting insulin (p < 0.001) after 12 months. Combining a lifestyle intervention with a high-protein and low-glycemic formula diet improves hemodynamic parameters to a greater extent than lifestyle intervention alone in high-risk individuals with overweight and obesity.

High-Protein, Low-Glycaemic Meal Replacement Improves Physical Health-Related Quality of Life in High-Risk Persons for Metabolic Syndrome-A Subanalysis of the Randomised-Controlled ACOORH Trial.

While obesity impairs health-related quality of life (HRQOL), lifestyle interventions targeting weight reduction have been effective in improving HRQOL. Therefore, we hypothesised that a meal replacement-based lifestyle intervention, which has been shown to successfully reduce weight, would also improve HRQOL more effectively than a lifestyle intervention alone. In the international, multicenter, randomised-controlled ACOORH-trial (Almased-Concept-against- Overweight-and-Obesity-and-Related-Health-Risk), overweight or obese participants with elevated risk for metabolic syndrome (n = 463) were randomised into two groups. Both groups received telemonitoring devices and nutritional advice. The intervention group additionally used a protein-rich, low-glycaemic meal replacement for 6 months. HRQOL was estimated at baseline, after 3 and 12 months, using the SF-36 questionnaire, and all datasets providing HRQOL data (n = 263) were included in this predefined subanalysis. Stronger improvements in the physical component summary (PCS) were observed in the intervention compared to the control group, peaking after 3 months (estimated treatment difference 2.7 [1.2; 4.2]; p < 0.0001), but also in the long-term. Multiple regression analysis demonstrated that insulin levels and the achieved weight loss were associated with the mental component summary (MCS) after 12 months (p < 0.05). Thus, meal replacement-based lifestyle intervention is not only effective in weight reduction but, concomitantly, in enhancing HRQOL.

Continuous Protein Supplementation Reduces Acute Exercise-Induced Stress Markers in Athletes Performing Marathon.

The aim of this study was to determine the changes in endurance performance and metabolic, hormonal, and inflammatory markers induced by endurance stress (marathon race) in a combined strategy of training and dietary protein supplementation. The study was designed as a randomised controlled trial consisting of regular endurance training without and with a daily intake of a soy protein-based supplement over a three-month period in 2 × 15 (10 males and 5 females per group) endurance-trained adults. Body composition (body mass, BMI, and fat mass) was determined, and physical fitness was measured by treadmill ergometry at baseline and after 3 months of intervention; changes in exercise-induced stress and inflammatory markers (CK, myoglobin, interleukin-6, cortisol, and leukocytes) were also determined before and after a marathon competition; eating behaviour was documented before and after intervention by a three-day diet diary. Although no significant influence on endurance performance was observed, the protein supplementation regime reduced the exercise-induced muscle stress response. Furthermore, a protein intake of ≥20% of total energy intake led to a lower-level stress reaction after the marathon race. In conclusion, supplementary protein intake may influence exercise-induced muscle stress reactions by changing cellular metabolism and inflammatory pathways.

The Epidemiological Boehringer Ingelheim Employee Study (Part 3): Association of Elevated Fasting Insulin Levels but Not HOMA-IR With Increased Intima Media Thickness and Arteriosclerosis in Middle-Aged Persons.

Background: Recently published genetic studies have indicated a causal link between elevated insulin levels and cardiovascular disease (CVD) risk. We, therefore, hypothesized that increased fasting insulin levels are also associated with precursors of CVD such as endothelial lesions. Methods: Middle-aged (≥40 years, n = 1,639) employees were followed up for the occurrence of increased intima media thickness (IMT ≥ 1 mm) or plaques in abdominal or cervical arteries (arteriosclerosis). Multivariable logistic regression analyses determined the incidence of increased IMT or arteriosclerosis. Adjusted relative risk (ARR) for increased IMT and arteriosclerosis was calculated by using Mantel-Haenszel analysis. Results: Increased IMT was diagnosed in 238 participants (15 %) and 328 (20 %) developed arteriosclerosis after 5 years of follow-up. Logistic regression analysis identified fasting insulin, BMI and smoking as risk factors for both cardiovascular endpoints (all p < 0.05), whereas age and diastolic blood pressure were risk factors for increased IMT only, and male sex was associated with incident arteriosclerosis only (all p < 0.01). Additional adjustment for BMI change during follow-up did not modify these associations (including fasting insulin), but adjustment for fasting insulin change during follow-up removed BMI as risk factor for both cardiovascular endpoints. Fasting insulin change during follow-up but not BMI change associated with increased IMT and arteriosclerosis (both p < 0.001). ARR analysis indicated that high fasting insulin and BMI added to age and sex as risk factors. Homeostatic model assessment of insulin resistance (HOMA-IR) did not associate with either cardiovascular endpoint in any model and smoking did not increase the risk conferred by high fasting insulin levels. Conclusions: Higher fasting insulin levels and increases in fasting insulin over time are associated with atherogenic progression and supersede BMI as well as HOMA-IR as risk factors.

Effects of a Protein-Rich, Low-Glycaemic Meal Replacement on Changes in Dietary Intake and Body Weight Following a Weight-Management Intervention-The ACOORH Trial.

Although meal replacement can lead to weight reduction, there is uncertainty whether this dietary approach implemented into a lifestyle programme can improve long-term dietary intake. In this subanalysis of the Almased Concept against Overweight and Obesity and Related Health Risk (ACOORH) study (n = 463), participants with metabolic risk factors were randomly assigned to either a meal replacement-based lifestyle intervention group (INT) or a lifestyle intervention control group (CON). This subanalysis relies only on data of participants (n = 119) who returned correctly completed dietary records at baseline, and after 12 and 52 weeks. Both groups were not matched for nutrient composition at baseline. These data were further stratified by sex and also associated with weight change. INT showed a higher increase in protein intake related to the daily energy intake after 12 weeks (+6.37% [4.69; 8.04] vs. +2.48% [0.73; 4.23], p < 0.001) of intervention compared to CON. Fat and carbohydrate intake related to the daily energy intake were more strongly reduced in the INT compared to CON (both p < 0.01). After sex stratification, particularly INT-women increased their total protein intake after 12 (INT: +12.7 g vs. CON: -5.1 g, p = 0.021) and 52 weeks (INT: +5.7 g vs. CON: -16.4 g, p = 0.002) compared to CON. Protein intake was negatively associated with weight change (r = -0.421; p < 0.001) after 12 weeks. The results indicate that a protein-rich dietary strategy with a meal replacement can improve long-term nutritional intake, and was associated with weight loss.

American Academy of Clinical Neuropsychology (AACN) 2021 consensus statement on validity assessment: Update of the 2009 AACN consensus conference statement on neuropsychological assessment of effort, response bias, and malingering.

Objective: Citation and download data pertaining to the 2009 AACN consensus statement on validity assessment indicated that the topic maintained high interest in subsequent years, during which key terminology evolved and relevant empirical research proliferated. With a general goal of providing current guidance to the clinical neuropsychology community regarding this important topic, the specific update goals were to: identify current key definitions of terms relevant to validity assessment; learn what experts believe should be reaffirmed from the original consensus paper, as well as new consensus points; and incorporate the latest recommendations regarding the use of validity testing, as well as current application of the term 'malingering.' Methods: In the spring of 2019, four of the original 2009 work group chairs and additional experts for each work group were impaneled. A total of 20 individuals shared ideas and writing drafts until reaching consensus on January 21, 2021. Results: Consensus was reached regarding affirmation of prior salient points that continue to garner clinical and scientific support, as well as creation of new points. The resulting consensus statement addresses definitions and differential diagnosis, performance and symptom validity assessment, and research design and statistical issues. Conclusions/Importance: In order to provide bases for diagnoses and interpretations, the current consensus is that all clinical and forensic evaluations must proactively address the degree to which results of neuropsychological and psychological testing are valid. There is a strong and continually-growing evidence-based literature on which practitioners can confidently base their judgments regarding the selection and interpretation of validity measures.

High-Protein, Low-Glycaemic Meal Replacement Decreases Fasting Insulin and Inflammation Markers-A 12-Month Subanalysis of the ACOORH Trial.

Lifestyle interventions, including meal replacement, are effective in the prevention and treatment of type-2-diabetes and obesity. Since insulin is the key weight regulator, we hypothesised that the addition of meal replacement to a lifestyle intervention reduces insulin levels more effectively than lifestyle intervention alone. In the international multicentre randomised controlled ACOORH (Almased Concept against Overweight and Obesity and Related Health Risk) trial, overweight or obese persons who meet the criteria for metabolic syndrome (n = 463) were randomised into two groups. Both groups received nutritional advice focusing on carbohydrate restriction and the use of telemonitoring devices. The intervention group substituted all three main meals per day in week 1, two meals per day in weeks 2-4, and one meal per day in weeks 5-26 with a protein-rich, low-glycaemic meal replacement. Data were collected at baseline and after 1, 3, 6 and 12 months. All datasets providing insulin data (n = 446) were included in this predefined subanalysis. Significantly higher reductions in insulin (-3.3 ± 8.7 µU/mL vs. -1.6 ± 9.8 µU/mL), weight (-6.1 ± 5.2 kg vs. -3.2 ± 4.6 kg), and inflammation markers were observed in the intervention group. Insulin reduction correlated with weight reduction and the highest amount of weight loss (-7.6 ± 4.9 kg) was observed in those participants with an insulin decrease > 2 µU/mL. These results underline the potential for meal replacement-based lifestyle interventions in diabetes prevention, and measurement of insulin levels may serve as an indicator for adherence to carbohydrate restriction.

Meal replacement by formula diet reduces weight more than a lifestyle intervention alone in patients with overweight or obesity and accompanied cardiovascular risk factors-the ACOORH trial.

BACKGROUND: As formula diets have demonstrated to be effective in reducing weight, we hypothesised that in patients with overweight or obesity and accompanied cardiovascular risk factors, combining a liquid formula diet with a lifestyle intervention is superior in reducing weight and improving cardiovascular risk factors than lifestyle intervention alone. METHODS: In this multicenter RCT 463 participants with overweight or obesity (BMI: 27-35 kg/m²; at least one additional co-morbidity of the metabolic syndrome) were randomised (1:2) into either a control group with lifestyle intervention only (CON, n = 155) or a lifestyle intervention group including a liquid meal replacement (INT, n = 308). Both groups used telemonitoring devices (scales and pedometers), received information on healthy diet and were instructed to increase physical activity. Telemonitoring devices automatically transferred data into a personalised online portal and acquired data were discussed. INT obtained a liquid meal replacement substituting three meals/day (~1200 kcal) within the first week. During weeks 2-4, participants replaced two meals/day and during weeks 5-26 only one meal/day was substituted (1300-1500 kcal/day). Follow-up was conducted after 52 weeks. Intention-to-treat analyses were performed. Primary outcome was weight change. Secondary outcomes comprised changes in cardiometabolic risk factors including body composition and laboratory parameters. RESULTS: From the starting cohort 360 (78%, INT: n = 244; CON: n = 116) and 317 (68%, INT: n = 216; CON: n = 101) participants completed the 26-weeks intervention phase and the 52-weeks follow-up. The estimated treatment difference (ETD) between both groups was -3.2 kg [-4.0; -2.5] (P < 0.001) after 12 weeks and -1.8 kg [-2.8; -0.8] (P < 0.001) after 52 weeks. CONCLUSIONS: A low-intensity lifestyle intervention combined with a liquid meal replacement is superior regarding weight reduction and improvement of cardiovascular risk factors than lifestyle intervention alone.

Weight Reduction by the Low-Insulin-Method-A Randomized Controlled Trial.

Continuous high insulin levels are associated with weight gain and lead to cardiometabolic diseases. Therefore, we have developed the Low-Insulin-Method and integrated it into the multi-component, occupational healthcare program SHAPE-AND-MOTION-Medical-Accompanied-Slimming (SAMMAS) to reduce daily insulin levels for long-term weight reduction in overweight or obesity. Employees were randomized into a starting intervention group (SI, n = 15) or waiting list control group (WL, n = 15). SAMMAS consisted of group-based seminars, low-carbohydrate nutrition including formula diet, continuous glucose monitoring, telemetric monitoring, and telemedical coaching. Both groups received telemetric devices at baseline. Intention-to-treat analyses were performed after 12, 26, and 52 weeks. The estimated treatment difference in weight reduction after 12 weeks, which is the primary endpoint of the study, showed a pronounced effect in favour of SI (-6.3 kg with (95% confidence interval) (-7.4; -4.5) (p < 0.001)) after 12 weeks. Furthermore, SI improved fasting blood glucose, HbA1c, quality of life, fasting insulin, blood pressure, and eating behaviour (all p < 0.05) in the within-group analysis, while WL did not. After 26 and 52 weeks, weight reduction could be maintained in the whole group (both groups together) by -6.7 kg (-9.5; -3.8) (p < 0.001) and -6.1 kg (-9.2; -2.7) (p < 0.01). SAMMAS supports clinically relevant weight reduction and long-term weight loss maintenance in individuals with overweight or obesity.

Premorbid estimates of neuropsychological functioning for diverse groups.

One of the basic tasks performed by a neuropsychologist is to identify the difference between current performance and the premorbid expected performance. Baseline expected performance for Intellectually Impaired (n = 21), Developmentally Delayed (n = 40), Attention Deficit Disorder (n = 98), Learning Disability (n = 42), and "Normal" groups (n = 75) were developed along with a demographically corrected prediction of premorbid functioning and a word reading based prediction of premorbid functioning. We utilized a subset of this data pool for development (n = 107) and validation (n = 108) of premorbid functioning estimates. Findings show that a combination of three methods (baseline, demographic, and reading) were superior to any individual method. The effect size (Cohen's d) calculations show that differences in the prediction of domain level performances were small and likely not clinically meaningful, indicating that the premorbid estimates would be usable as a prediction of expected performance at the domain level. However, the motor domains were not well predicted.