Myofiber-specific lipidomics unveil differential contributions to insulin sensitivity in individuals of African and European ancestry.

Aims: Individuals of African ancestry (AA) present with lower insulin sensitivity compared to their European counterparts (EA). Studies show ethnic differences in skeletal muscle fiber type (lower type I fibers in AA), muscle fat oxidation capacity (lower in AA), whilst no differences in total skeletal muscle lipids. However, skeletal muscle lipid subtypes have not been examined in this context. We hypothesize that lower insulin sensitivity in AA is due to a greater proportion of type II (non-oxidative) muscle fibers, and that this would result in an ancestry-specific association between muscle lipid subtypes and peripheral insulin sensitivity. To test this hypothesis, we examined the association between insulin sensitivity and muscle lipids in AA and EA adults, and in an animal model of insulin resistance with muscle-specific fiber types. Methods: In this cross-sectional study, muscle biopsies were obtained from individuals with a BMI ranging from normal to overweight with AA (N = 24) and EA (N = 19). Ancestry was assigned via genetic admixture analysis; peripheral insulin sensitivity via hyperinsulinaemic-euglycemic clamp; and myofiber content via myosin heavy chain immunohistochemistry. Further, muscle types with high (soleus) and low (vastus lateralis) type I fiber content were obtained from high-fat diet-induced insulin resistant F1 mice and littermate controls. Insulin sensitivity in mice was assessed via intraperitoneal glucose tolerance test. Mass spectrometry (MS)-based lipidomics was used to measure skeletal muscle lipid. Results: Compared to EA, AA had lower peripheral insulin sensitivity and lower oxidative type 1 myofiber content, with no differences in total skeletal muscle lipid content. Muscles with lower type I fiber content (AA and vastus from mice) showed lower levels of lipids associated with fat oxidation capacity, i.e., cardiolipins, triacylglycerols with low saturation degree and phospholipids, compared to muscles with a higher type 1 fiber content (EA and soleus from mice). Further, we found that muscle diacylglycerol content was inversely associated with insulin sensitivity in EA, who have more type I fiber, whereas no association was found in AA. Similarly, we found that insulin sensitivity in mice was associated with diacylglycerol content in the soleus (high in type I fiber), not in vastus (low in type I fiber).Conclusions; Our data suggest that the lipid contribution to altered insulin sensitivity differs by ethnicity due to myofiber composition, and that this needs to be considered to increase our understanding of underlying mechanisms of altered insulin sensitivity in different ethnic populations.

Association between insulin sensitivity and lean mass loss during weight loss.

OBJECTIVE: The study objective was to assess the relationship between insulin sensitivity and changes in total lean mass (LM) and appendicular LM (ALM) during weight loss. METHODS: Individuals were randomly assigned to either a standard or a moderately reduced carbohydrate diet for 16 weeks. Body composition was assessed using dual-energy x-ray absorptiometry and insulin sensitivity index (SI) using an intravenous glucose tolerance test. Multiple linear regression was used to determine whether baseline SI was predictive of changes in total LM and ALM. RESULTS: Participants (n = 57; baseline BMI 32.1 ± 3.8 kg/m2) lost an average of 6.8 ± 3.2 kg of body weight (p < 0.001), with 1.5 ± 2.6 kg coming from LM (p < 0.05) and 0.5 ± 0.73 kg from ALM (p < 0.05). Multiple regression analysis demonstrated that SI was inversely associated with changes in total LM (kilograms; ß = 0.481, p < 0.001), after adjusting for baseline LM, fat mass, acute insulin response to glucose, and weight loss. Similar results were seen when assessing ALM loss (ß = 0.359, p < 0.05). CONCLUSIONS: Identifying individuals with low insulin sensitivity prior to weight loss interventions may allow for a personalized approach aiming at minimizing LM loss.

Adaptive thermogenesis, at the level of resting energy expenditure, after diet alone or diet plus bariatric surgery.

OBJECTIVE: The objective of this study was to compare the magnitude of adaptive thermogenesis (AT), at the level of resting energy expenditure (REE), after a very low-energy diet alone or combined with Roux-en-Y gastric bypass or sleeve gastrectomy, as well as to investigate the association between AT and changes in appetite. METHODS: A total of 44 participants with severe obesity underwent 10 weeks of a very low-energy diet alone or combined with Roux-en-Y gastric bypass or sleeve gastrectomy. Body weight and composition, REE, subjective appetite feelings, and plasma concentrations of gastrointestinal hormones were measured at baseline and week 11. AT, at the level of REE, was defined as a significantly lower measured versus predicted (using a regression model with baseline data) REE. RESULTS: Participants lost 18.4 ± 3.9 kg of body weight and experienced AT, at the level of REE (-121 ± 188 kcal/day; p < 0.001), with no differences among groups. The larger the AT, at the level of REE, the greater the reduction in fasting ghrelin concentrations and the smaller the reduction in feelings of hunger and desire to eat in the postprandial state. CONCLUSIONS: Weight-loss modality does not seem to modulate the magnitude of AT, at the level of REE. The greater the AT, at the level of REE, the greater the drive to eat following weight loss.

An algorithm to simulate missing data for mixed meal tolerance test response curves.

BACKGROUND: Response curves formed by analyte concentrations measured at sampled time points after consuming a mixed meal are increasingly being used to characterize responses to differing diets. Unfortunately, owing to a variety of reasons, analyte concentrations for some of the time points may be missing. OBJECTIVES: This study aimed to develop an algorithm to estimate the missing values at sampled time points in the analyte response curve to a mixed meal tolerance test (MMTT). METHODS: We developed an algorithm to simulate the missing postprandial concentration values for an MMTT. The algorithm was developed to handle any number of missing values for 2 or less consecutive missing values. The algorithm was tested on MMTT response curve data for glucose and triglyceride measurements in data from 3 different studies with 2119 postprandial MMTT response curves. The algorithm was validated by removing concentration values that were not missing and replacing them with the algorithm simulated values. The AUC error between the actual curve and simulated curves were also calculated. A web-based application was developed to automatically simulate missing values for an uploaded MMTT data set. RESULTS: The algorithm was programmed in Python and the resulting web-based application and a video tutorial were provided. The validation indicated good agreement between actual and simulated values with error increasing for less frequently sampled time points. The study with the mean minimum error of glucose concentrations was 6.2 ± 2.1 mg/dL and study with the mean maximum error of glucose concentrations was 11.3 ± 4.7 mg/dL. Triglycerides had 16.1 ± 6.2 mg/dL mean error. The AUC error was small ranging between 0.01% and 0.28%. CONCLUSIONS: The presented algorithm reconstructs postprandial response curves with estimations of values that are missing.

Expert consensus on nutrition and lower-carbohydrate diets: An evidence- and equity-based approach to dietary guidance.

There is a substantial body of clinical evidence supporting the beneficial effects of lower-carbohydrate dietary patterns on multiple established risk factors associated with insulin resistance and cardiovascular diseases in adult populations. Nutrition and health researchers, clinical practitioners, and stakeholders gathered for, "The Scientific Forum on Nutrition, Wellness, and Lower-Carbohydrate Diets: An Evidence- and Equity-Based Approach to Dietary Guidance" to discuss the evidence base around lower-carbohydrate diets, health outcomes, and dietary guidance. Consensus statements were agreed upon to identify current areas of scientific agreement and spotlight gaps in research, education, and practice to help define and prioritize future pathways. Given the evidence base and considering that most American adults are living with at least one nutrition-related chronic disease, there was consensus that including a lower-carbohydrate dietary pattern as one part of the Dietary Guidelines for Americans could help promote health equity among the general population.

Metabolic adaptation is associated with a greater increase in appetite following weight loss: a longitudinal study.

BACKGROUND: Weight loss is associated with a disproportionate reduction in energy expenditure, along with increases in hunger feelings and ghrelin concentrations. These changes are presumed to be homeostatic mechanisms to counteract the energy deficit. The possibility that these 2 components of the energy balance equation are mechanistically linked has never been examined. OBJECTIVE: This study aimed to determine if the disproportionate reduction in resting metabolic rate (RMR) seen with weight loss is associated with changes in the plasma concentration of gastrointestinal hormones involved in appetite regulation and subjective appetite ratings. METHODS: This was a longitudinal study with repeated measurements. Fifty-six individuals with obesity (body mass index [BMI]: 34.5±0.5 kg/m2; age: 47±1 y; 26 males) underwent an 8 wk low-energy diet, followed by 4 wk of refeeding and weight stabilization. The RMR, respiratory quotient (RQ), body composition, plasma concentrations of ghrelin, glucagon-like peptide 1, peptide YY, cholecystokinin, insulin, and appetite ratings in the fasting and postprandial states were measured at baseline, Wk9 and 13. Metabolic adaptation was defined as significantly lower when measured versus the predicted RMR (pRMR) (from own regression model using baseline data). RESULTS: A 14.2±0.6 kg weight loss was seen at Wk9 and maintained at Wk13. RQ was significantly reduced at Wk9 (0.82±0.06 vs. 0.76±0.05, P< 0.001) but returned to baseline at Wk13. Metabolic adaptation was seen at Wk9, but not Wk13 (-341±58, P <0.001 and -75±72 kJ/d, P = 0.305, respectively). The larger the difference between measured and predicted RMR at both timepoints, the greater the increase in hunger, desire to eat, and composite appetite score (fasting and postprandial at Wk9, postprandial only at Wk13), even after adjusting for weight loss and RQ. CONCLUSION: A larger metabolic adaptation during weight loss is accompanied by a greater drive to eat. This might help explain the interindividual differences in weight loss outcomes to dietary interventions.

The Effects of COVID-19 Virtual Learning on Body Fat and Insulin Resistance in Adolescents with Overweight or Obesity.

(1) Background: COVID-19 virtual learning reduced structural supports for adolescent physical activity and diet, threatening metabolic health, especially in teens with overweight or obesity (OWOB). (2) Methods: Adolescents (N = 14) with OWOB completed fasting blood draws (measuring insulin resistance, IR) and Dual Energy X-Ray Absorptiometry (DXA, measuring total body fat percent, TBF%) pre-COVID-19 and during COVID-19. Changes in TBF% and IR were calculated (1) pre-COVID-19 and (2) from pre-COVID-19 to during COVID-19. Age and body mass index (BMI) percentile-matched data assessed normative changes across similar, non-COVID-19 time periods. Paired t-tests compared TBF% change pre- to during COVID-19 with (1) TBF% change pre-COVID19 and (2) TBF% normative change. Two ANCOVAs compared IR change pre- to during COVID-19 with (1) IR change pre-COVID-19 controlling for BMI z-score and difference in time between assessments and (2) normative change in IR controlling for sex/race. (3) Results: The TBF% change pre-COVID-19 and the normative change were similar. The TBF% increased more (~six percentage points) during COVID-19 compared to normative change (p < 0.01). During COVID-19, IR increased more (~2.5 units) than change pre-COVID-19 (p = 0.03) and increased more (~3.5 units) than normative change (p = 0.01). (4) Conclusions: TBF% and IR increased exponentially during COVID-19 in teens with OWOB compared to pre-COVID-19 and normative changes.

Adipose Tissue Dysfunction in Polycystic Ovary Syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity. METHODS: We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS. RESULTS: Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS. CONCLUSION: AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.

Systemic Inflammation, Endothelial Function, and Risk of Periodontitis in Overweight/Obese Adults.

The network interaction between systemic inflammatory mediators, endothelial cell adhesion function, and adiponectin as mediators of the association between metabolic diseases and periodontitis has not been evaluated. The objective of this study is to assess whether the interaction of baseline serum levels of TNF-α, hs-CRP, ICAM-1, VCAM-1, and adiponectin leads to periodontitis. Five hundred and ninety-seven overweight/obese (overweight: BMI 25 to <30 kg/m2; obese: >30 kg/m2) adults, aged 40-65 years, with complete 3-year follow-up data were included. Generalized structural equation models with negative binomial regression were used to estimate the regression coefficient (ß) for the outcome number of teeth with probing pocket depth (PPD) ≥ 4 mm and bleeding on probing (BOP) at 3-year follow-up for a 1 standard deviation unit increase (Δ = +1SD) in each biomarker. After adjusting for multiple covariates, baseline ICAM-1 and VCAM-1 had significant direct effects on increased log-transformed number of teeth with PPD ≥ 4 mm and BOP (ß: 0.16; 95% CI: 0.02-0.30; ß: 0.15; 95% CI: 0.02-0.30, respectively). Baseline hs-CRP showed a significant indirect effect via ICAM-1 on the log-transformed number of teeth with PPD ≥ 4 mm and BOP (ß: 4.84; 95% CI: 0.27-9.42). Thus, elevated serum ICAM-1 and VCAM-1 have a significant direct effect and increased hs-CRP has a significant indirect effect on the predicted level of periodontitis at the 3-year follow-up among overweight/obese Hispanic adults.

Association between ß-Hydroxybutyrate Plasma Concentrations after Hypocaloric Ketogenic Diets and Changes in Body Composition.

BACKGROUND: Early studies show that ketogenic diets (KDs) lead to preferential loss of fat mass (FM), whereas preserving fat-free mass (FFM). Additionally, animal data support the anticatabolic effects of DL-3-hydroxybutyrate. From our knowledge, a potential association between ß-hydroxybutyrate (ßHB) plasma concentrations and changes in body composition has never been explored. OBJECTIVES: The main aim of this analysis was to determine if ßHB plasma concentrations, following hypocaloric KDs, were associated with FM and FFM changes in men and women with obesity. METHODS: Data from 199 individuals (BMI = 36.6 ± 4.3 kg/m2; age = 43.6 ± 9.8 y; 82 men) were collated from 3 weight loss studies employing common measures of body composition (air displacement plethysmography) and ßHB plasma concentration (ELISA). The association between ßHB and weight, FM and FFM loss (kg), and %FFM loss (%FFML) was investigated with Spearman correlation. Multivariable linear regression was used to determine if ßHB was a significant predictor of the changes in anthropometric variables, after adjusting for confounding factors. RESULTS: ßHB was not associated with FFML (% or kg), but a weak positive association was seen with FM loss (r = 0.182, P = 0.01, n = 199) and a trend with weight loss (r = 0.128, P = 0.072, n = 199). ßHB was a significant predictor of both weight and FM loss (kg), after adjusting for age, sex, baseline BMI, and intervention study. CONCLUSIONS: The magnitude of ketosis is not associated with FFM preservation. However, the higher the level of ketosis, the greater the weight and FM loss. Further studies are needed to confirm these findings and to explore the mechanisms involved. This trial was registered at clinicaltrials.gov identifier as NCT01834859, NCT04051190, NCT02944253.

Associations of renal sinus fat with blood pressure and ectopic fat in a diverse cohort of adults.

Background: Renal sinus fat (RSF) is an ectopic fat depot shown to be associated with visceral adiposity and hypertension in predominantly white populations. The purpose of this analysis is to investigate RSF and associations between RSF and blood pressure in a cohort of African American (AA) and European American (EA) adults. A secondary purpose was to explore risk factors associated with RSF. Methods: Participants were 116 A A and EA adult men and women. Ectopic fat depots were assessed with MRI: RSF, intraabdominal adipose tissue (IAAT), intermuscular adipose tissue (IMAT), perimuscular adipose tissue (PMAT), and liver fat. Cardiovascular measures included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure, mean arterial pressure, and flow mediated dilation. Matsuda index was calculated for insulin sensitivity. Pearson correlations were used to investigate associations of RSF with cardiovascular measures. Multiple linear regression was used to evaluate contributions of RSF on SBP and DBP and to explore factors associated with RSF. Results: No difference was observed in RSF between AA and EA participants. RSF was positively associated with DBP in AA participants, but this was not independent of age and sex. Age, male sex, and total body fat were positively associated with RSF in AA participants. Insulin sensitivity was inversely and IAAT and PMAT were positively associated with RSF in EA participants. Conclusions: Differential associations of RSF with age, insulin sensitivity, and adipose depots among AA and EA adults suggest unique pathophysiological mechanisms influence RSF deposition, which may contribute to chronic disease etiology and progression.

Associations of atrial natriuretic peptide with measures of insulin and adipose depots.

Low concentrations of natriuretic peptides (NPs) have been associated with greater risk for Type 2 diabetes (T2D). African American individuals (AA) have lower NP levels and are disproportionately burdened by T2D. The purpose of this study was to test the hypothesis that higher post-challenge insulin in AA adults is associated with lower plasma N-terminal pro-atrial natriuretic peptide (NT-proANP). A secondary purpose was to explore associations between NT-proANP and adipose depots. Participants were 112 AA and European American (EA) adult men and women. Measures of insulin were obtained from an oral glucose tolerance test and hyperinsulinemic-euglycemic glucose clamp. Total and regional adipose depots were measured from DXA and MRI. Multiple linear regression analysis was used to assess associations of NT-proANP with measures of insulin and adipose depots. Lower NT-proANP concentrations in AA participants was not independent of 30-min insulin area under the curve (AUC). NT-proANP was inversely associated with 30-min insulin AUC in AA participants, and with fasting insulin and HOMA-IR in EA participants. Thigh subcutaneous adipose tissue and perimuscular adipose tissue were positively associated with NT-proANP in EA participants. Higher post-challenge insulin may contribute to lower ANP concentrations in AA adults.

Association between Fat-Free Mass Loss, Changes in Appetite, and Weight Regain in Individuals with Obesity.

BACKGROUND: The role of fat-free mass loss (FFML) in modulating weight regain in individuals with obesity, as well as the potential mechanisms involved, remain inconsistent. OBJECTIVES: The aim of this study was to determine if % FFML following weight loss (WL) is a predictor of weight regain and to investigate the association between %FFML and changes in appetite markers. METHODS: Seventy individuals with obesity (BMI: 36 ± 4 kg/m2; age: 44 ± 9 y; 29 males) underwent 8 wk of a very low energy diet (550-660 kcal/d), followed by 4 wk of gradual refeeding and weight stabilization and a 9-mo maintenance program (eucaloric diet). The primary outcomes were body weight and body composition (fat mass and fat-free mass). The secondary outcomes were plasma concentrations of ß-hydroxybutyrate (a marker of ketosis) in fasting and appetite-related hormones (ghrelin, glucagon-like peptide 1, peptide YY, and cholecystokinin) and subjective appetite feelings during fasting and every 30 min after a fixed breakfast for 2.5 h. All were measured at baseline, week 9, and 1 y [week 13 in 35 subjects (25 males)]. The association between FFML, weight regain, and changes in appetite was assessed by linear regression. RESULTS: WL at week 9 was 17.5 ± 4.3kg and %FFML 20.4 ± 10.6%. Weight regain at 1 y was 1.7 ± 8.2 kg (8.8 ± 45.0%). After adjusting for WL and fat mass at baseline, %FFML at week 9 was not a significant predictor of weight regain. Similar results were seen at week 13. The greater the %FFML at week 9, but not 13, the smaller the reduction, or greater the increase in basal ghrelin concentration (ß: -3.2; 95% CI: -5.0, -1.1; P = 0.003), even after adjusting for WL and ß-hydroxybutyrate. CONCLUSIONS: %FFML was not a significant predictor of weight regain at 1 y in individuals with obesity. However, a greater %FFML was accompanied by a greater increase in ghrelin secretion under ketogenic conditions, suggesting a link between fat-free mass and appetite regulation. This trial was registered at clinicaltrials.gov as NCT01834859.

Proinsulin-to-C-Peptide Ratio as a Marker of ß-Cell Function in African American and European American Adults.

OBJECTIVE: The primary purpose of the current study was to test the hypothesis that the proinsulin-to-C-peptide (PI-to-CP) ratio, as an index of proinsulin secretion, would be higher and associated with indices of ß-cell function in African American adults relative to European American adults without type 2 diabetes. RESEARCH DESIGN AND METHODS: Participants were 114 African American and European American adult men and women. A 2-h oral glucose tolerance test was conducted to measure glucose, insulin, C-peptide, and proinsulin and derive indices of ß-cell response to glucose. The Matsuda index was calculated as a measure of insulin sensitivity. The disposition index (DI), the product of insulin sensitivity and ß-cell response, was calculated for each phase of ß-cell responsivity. Pearson correlations were used to investigate the relationship of the PI-to-CP ratio with each phase of ß-cell response (basal, Φb; dynamic, Φd; static, Φs; total, Φtot), disposition indices (DId, DIs, DItot), and insulin sensitivity. Multiple linear regression analysis was used to evaluate independent contributions of race, BMI, and glucose tolerance status on PI-to-CP levels before and after adjustment for insulin sensitivity. RESULTS: African American participants had higher fasting and 2-h PI-to-CP ratios. The fasting PI-to-CP ratio was positively associated with Φb, and the fasting PI-to-CP ratio and 2-h PI-to-CP ratio were inversely associated with DId and insulin sensitivity only in African American participants. CONCLUSIONS: The PI-to-CP ratio could be useful in identifying African American individuals at highest risk for ß-cell dysfunction and ultimately type 2 diabetes.

Inflammation, Executive Function, and Adiposity in Children With or at Risk for Obesity: A Pilot Study.

OBJECTIVE: Obesity is associated with executive function (EF) deficits across the lifespan. Higher body mass index (BMI), obesity severity, and poorer adherence and weight outcomes in obesity treatment have all been associated with EF deficits. Adult literature has begun to emphasize neuroinflammation in obesity as a possible pathway to later cognitive impairment in EF. However, pediatric obesity literature has yet to establish associations between peripheral inflammation and EF. Thus, the present study examined associations and variability in inflammation, EF, and adiposity in children with or at risk for obesity. Additionally, inflammation was examined as a mediator of the relationship between adiposity and EF. METHODS: Children (N = 39) aged 8-12 years with BMI ≥ 50th percentile were recruited. The NIH Toolbox Cognitive Battery was used to assess performance-based EF. Peripheral inflammation was assessed in fasted sera. Dual-energy X-ray absorptiometry scans were conducted to assess body composition. Linear regression and Hayes' PROCESS Model 4 (Hayes, 2017) were used to evaluate associations between adiposity and inflammation, inflammation and EF, and whether adiposity effects EF through its effect on inflammation. RESULTS: Positive associations were identified between adiposity and inflammation, and negative to null associations were identified between inflammation and EF. Medium indirect effects of adiposity on EF through inflammation were detected. CONCLUSION: Pilot evidence suggests greater adiposity is linked with greater inflammation, which in turn is associated with less EF in some domains. Directionality and causality cannot yet be established, but with replication, findings may inform efforts to target EF in pediatric obesity.

Effects of a low-carbohydrate/high-protein diet on metabolic health in individuals with chronic spinal cord injury: An exploratory analysis of results from a randomized controlled trial.

We explored the impact of a low-carbohydrate/high-protein diet (LC/HP, ~30% energy from protein, 40% energy from carbohydrate) on indices of metabolic function and body composition in individuals with chronic spinal cord injury (SCI). Adults with SCI (≥3 years post-injury, C4-L2, AIS A-D) and insulin resistance or pre-diabetes were randomly assigned to an 8-week iso-caloric LC/HP diet group (n = 11) or control group (n = 14). All LC/HP meals were delivered weekly to participants' homes, and participants in the control group consumed their habitual diet. Each participant underwent an oral glucose tolerance test (OGTT) to assess glucose tolerance, insulin, area under the curve (AUC) for glucose and insulin, Matsuda Index, glucose-stimulated insulin secretion (GSIS), disposition index, and hepatic insulin extraction (HIE). Fasting blood lipid and inflammation were assessed, and body composition was estimated using dual-energy x-ray absorptiometry. A linear mixed model was used to evaluate the main effect of diet, time, and their interaction. Compared to the control group, participants in the LC/HP group had reduced total body fat mass (LC/HP: -5.9%, Control: 0.7%), visceral fat mass (LC/HP: -16.2%, Control: 5.2%), total- (LC/HP: -20.1, Control: 3.7 mg/dl), and LDL-cholesterol (LC/HP: -13.9, Control: 3.1 mg/dl) (pdiet*time < 0.05 for all). Regardless of group, AUCinsulin and peak insulin during the OGTT decreased, and HIE increased over time (ptime < 0.05). A trend for diet*time interaction was observed for glucoseOGTT120min (LC/HP: -20.7, Control: 3.0 mg/dl, pdiet*time  = 0.09) and peak C-peptide (LC/HP: -2.1, Control: 0.0 ng/ml, pdiet*time  = 0.07). HDL-cholesterol, lean body mass, Matsuda Index, fasting glucose, insulin, insulinOGTT120min , AUCglucose , pancreatic beta cell function (GSIS, disposition index), and inflammation (C-reactive protein, IL-6, IL-8, IL-10, TNF-α) did not change over time. In conclusion, our results suggest that individuals with SCI and insulin resistance may adopt an LC/HP diet to improve body composition and lipid profiles. Its impact on glucose metabolism and inflammation remains inconclusive and warrants future investigations.

Association between Fat-Free Mass Loss after Diet and Exercise Interventions and Weight Regain in Women with Overweight.

PURPOSE: This study aimed to determine if percent fat-free mass loss (% FFML) after diet alone, diet plus aerobic, or diet plus resistance exercise is a predictor of weight regain in women with overweight. METHODS: One hundred and forty-one premenopausal women with overweight (body mass index, 28 ± 1 kg·m -2 ; age, 35 ± 6 yr) enrolled in a weight loss program to achieve a body mass index <25 kg·m -2 (diet alone, diet plus resistance, or diet plus aerobic exercise) and were followed for 1 yr. Body weight and composition (with dual-energy x-ray absorptiometry) were measured at baseline, after weight loss, and at 1 yr. RESULTS: Participants lost 12.1 ± 2.6 kg of body weight, 11.3 ± 2.5 kg of fat mass, and 0.5 ± 1.6 kg of fat-free mass during the weight loss intervention, followed by weight regain at 1 yr (6.0 ± 4.4 kg, 51.3% ± 37.8%; P < 0.001 for all). % FFML was -3.6 ± 12.4, and a greater % FFML was associated with more weight regain ( r = -0.216, P = 0.01, n = 141), even after adjusting for the intervention group ( ß = -0.07; 95% confidence interval, -0.13 to -0.01; P = 0.017). CONCLUSIONS: % FFML is a significant predictor of weight regain in premenopausal women with overweight. These results support strategies for conserving fat-free mass during weight loss, such as resistance training. Future research should try to identify the mechanisms, at the level of both appetite and energy expenditure, responsible for this association.

Metabolic adaptation after combined resistance and aerobic exercise training in older women.

OBJECTIVE: This study investigated whether combined aerobic and resistance training in older women leads to metabolic adaptation. METHODS: A total of 80 women (64 White individuals; BMI: 30.0 [4.4] kg/m2 ; age: 64.8 [3.5] years) followed 32 weeks of aerobic and resistance training. Body weight/composition (dual-energy X-ray absorptiometry) and resting metabolic rate (RMR; indirect calorimetry) were measured at baseline, week 16, and week 32. Metabolic adaptation was defined as significantly lower measured versus predicted RMR. A regression model to predict metabolic adaptation was developed that included race, age, baseline fat-free mass, RMR and respiratory quotient, and changes in net submaximal oxygen consumption after different tasks. RESULTS: There was significant metabolic adaptation at week 16 (-59 [136] kcal/d, p = 0.002), following a 640-kcal/wk energy loss (-0.7 [2.6] kg of weight loss). In 53 women with complete data, metabolic adaptation was seen both at week 16 (-64 [129] kcal/d, p = 0.001) and at week 32 (-94 [127] kcal/d, p < 0.001). Metabolic adaptation at week 16 was predicted by race, age, baseline fat-free mass, RMR and respiratory quotient, and change in net oxygen consumption of walking (R2 adjusted = 0.90, p < 0.001). Similar results were seen at week 32. CONCLUSIONS: In older women with overweight and obesity, a minimal energy deficit induced by aerobic and resistance exercise is associated with metabolic adaptation at the level of RMR.

Genetic European Ancestry and Incident Diabetes in Black Individuals: Insights From the SPRINT Trial.

BACKGROUND: Black individuals have high incident diabetes risk, despite having paradoxically lower triglyceride and higher HDL (high-density lipoprotein) cholesterol levels. The basis of this is poorly understood. We evaluated the participants of SPRINT (Systolic Blood Pressure Intervention Trial) to assess the association of estimated European genetic ancestry with the risk of incident diabetes in self-identified Black individuals. METHODS: Self-identified non-Hispanic Black SPRINT participants free of diabetes at baseline were included. Black participants were stratified into tertiles (T1-T3) of European ancestry proportions estimated using 106 biallelic ancestry informative genetic markers. The multivariable-adjusted association of European ancestry proportion with indices of baseline metabolic syndrome (ie, fasting plasma glucose, triglycerides, HDL cholesterol, body mass index, and blood pressure) was assessed. Multivariable-adjusted Cox regression determined the risk of incident diabetes (fasting plasma glucose ≥126 mg/dL or self-reported diabetes treatment) across tertiles of European ancestry proportion. RESULTS: Among 2466 Black SPRINT participants, a higher European ancestry proportion was independently associated with higher baseline triglyceride and lower HDL cholesterol levels (P<0.001 for both). European ancestry proportion was not associated with baseline fasting plasma glucose, body mass index, and blood pressure (P>0.05). Compared with the first tertile, those in the second (hazard ratio, 0.64 [95% CI, 0.45-0.90]) and third tertiles (hazard ratio, 0.61 [95% CI, 0.44-0.89]) of the European ancestry proportion had a lower risk of incident diabetes. A 5% point higher European ancestry was associated with a 29% lower risk of incident diabetes (hazard ratio, 0.71 [95% CI, 0.55-0.93]). There was no evidence of a differential association between the European ancestry proportion tertiles and incident diabetes between those randomized to intensive versus standard blood pressure treatment. CONCLUSIONS: The higher risk of incident diabetes in Black individuals may have genetic determinants in addition to adverse social factors. Further research may help understand the interplay between biological and social determinants of cardiometabolic health in Black individuals. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.