Effects of weight loss during a very low carbohydrate diet on specific adipose tissue depots and insulin sensitivity in older adults with obesity: a randomized clinical trial.

BACKGROUND: Insulin resistance and accumulation of visceral adipose tissue (VAT) and intermuscular adipose tissue (IMAT) place aging adults with obesity at high risk of cardio-metabolic disease. A very low carbohydrate diet (VLCD) may be a means of promoting fat loss from the visceral cavity and skeletal muscle, without compromising lean mass, and improve insulin sensitivity in aging adults with obesity. OBJECTIVE: To determine if a VLCD promotes a greater loss of fat (total, visceral and intermuscular), preserves lean mass, and improves insulin sensitivity compared to a standard CHO-based/low-fat diet (LFD) in older adults with obesity. DESIGN: Thirty-four men and women aged 60-75 years with obesity (body mass index [BMI] 30-40 kg/m2) were randomized to a diet prescription of either a VLCD (< 10:25:> 65% energy from CHO:protein:fat) or LFD diet (55:25:20) for 8 weeks. Body composition by dual-energy X-ray absorptiometry (DXA), fat distribution by magnetic resonance imaging (MRI), insulin sensitivity by euglycemic hyperinsulinemic clamp, and lipids by a fasting blood draw were assessed at baseline and after the intervention. RESULTS: Participants lost an average of 9.7 and 2.0% in total fat following the VLCD and LFD, respectively (p < 0.01). The VLCD group experienced ~ 3-fold greater loss in VAT compared to the LFD group (- 22.8% vs - 1.0%, p < 0.001) and a greater decrease in thigh-IMAT (- 24.4% vs - 1.0%, p < 0.01). The VLCD group also had significantly greater thigh skeletal muscle (SM) at 8 weeks following adjustment for change in total fat mass. Finally, the VLCD had greater increases in insulin sensitivity and HDL-C and decreases in fasting insulin and triglycerides compared to the LFD group. CONCLUSIONS: Weight loss resulting from consumption of a diet lower in CHO and higher in fat may be beneficial for older adults with obesity by depleting adipose tissue depots most strongly implicated in poor metabolic and functional outcomes and by improving insulin sensitivity and the lipid profile. TRIAL REGISTRATION: NCT02760641. Registered 03 May 2016 - Retrospectively registered.

Effects of a carbohydrate-restricted diet on hepatic lipid content in adolescents with non-alcoholic fatty liver disease: A pilot, randomized trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common form of liver disease among adolescents in industrialized countries. While lifestyle intervention remains the hallmark treatment for NAFLD, the most effective dietary strategy to reverse NAFLD in children is unknown. OBJECTIVE: The objective of this study was to determine the effects of a moderately CHO-restricted diet (CRD) vs fat-restricted diet (FRD) in adolescents with NAFLD on reduction in liver fat and insulin resistance. METHODS: Thirty-two children/adolescents (age 9-17) with obesity and NAFLD were randomized to a CRD (<25:25:>50% energy from CHO:protein:fat) or FRD (55:25:20) for 8 weeks. Caloric intakes were calculated to be weight maintaining. Change in hepatic lipid content was measured via magnetic resonance imaging, body composition via dual energy X ray absorptiometry and insulin resistance via a fasting blood sample. RESULTS: Change in hepatic lipid did not differ with diet, but declined significantly (-6.0 ± 4.7%, P < .001 only within the CRD group. We found significantly greater decreases in insulin resistance (HOMA-IR, <.05), abdominal fat mass (P < .01) and body fat mass (P < .01) in response to the CRD vs FRD. CONCLUSION: These findings suggest that consumption of a moderately CHO-restricted diet may result in decreased hepatic lipid as well as improvements in body composition and insulin resistance in adolescents with NAFLD even in the absence of intentional caloric restriction. Larger studies are needed to determine whether a CHO-restricted diet induces change in hepatic lipid independent of change in body fat.

Childhood obesity intervention studies: A narrative review and guide for investigators, authors, editors, reviewers, journalists, and readers to guard against exaggerated effectiveness claims.

Being able to draw accurate conclusions from childhood obesity trials is important to make advances in reversing the obesity epidemic. However, obesity research sometimes is not conducted or reported to appropriate scientific standards. To constructively draw attention to this issue, we present 10 errors that are commonly committed, illustrate each error with examples from the childhood obesity literature, and follow with suggestions on how to avoid these errors. These errors are as follows: using self-reported outcomes and teaching to the test; foregoing control groups and risking regression to the mean creating differences over time; changing the goal posts; ignoring clustering in studies that randomize groups of children; following the forking paths, subsetting, p-hacking, and data dredging; basing conclusions on tests for significant differences from baseline; equating "no statistically significant difference" with "equally effective"; ignoring intervention study results in favor of observational analyses; using one-sided testing for statistical significance; and stating that effects are clinically significant even though they are not statistically significant. We hope that compiling these errors in one article will serve as the beginning of a checklist to support fidelity in conducting, analyzing, and reporting childhood obesity research.

Higher hemoglobin A1C and atherogenic lipoprotein profiles in children and adolescents with type 2 diabetes mellitus.

AIM: Significant knowledge gaps exist regarding lipoprotein profiles in children with type 2 diabetes mellitus (T2DM). The primary objective was to analyze the type and nature of lipoprotein abnormalities present in children with T2DM and to identify determinants of adverse lipoprotein profiles. The secondary objective was to assess associations with elevated glycated hemoglobin (HbA1C), i.e., <8% vs. ≥8.0% and pediatric dyslipidemias in the setting of T2DM. METHODS: This retrospective chart review included children with T2DM who had undergone lipoprotein analysis and were not on lipid lowering medications (n = 93). RESULTS: The participants (mean age 15.2 ±â€¯2.7y) were 71% female and 78% African American (AA). Adjusted for age, sex, and race, BMI z-score was positively associated with LDL-pattern B (pro-atherogenic profile with small dense LDL particles) (P = 0.01), and negatively associated with total HDL-C (P = 0.0003). HbA1C was robustly positively associated with the LDL-C, apoB and LDL pattern B (all P < 0.001). Patients with an HbA1C >8% had significantly higher total cholesterol (191.4 vs. 158.1 mg/dL, P = 0.0004), LDL-C (117.77 vs. 92.3 mg/dL, P = 0.002), apoB (99.5 vs. 80.9 mg/dL, P = 0.002), non-HDL-C (141.5 vs. 112.5, P = 0.002), and frequency of LDL pattern B (57% vs. 20%, P = 0.0008). CONCLUSION: HbA1C and BMI were associated with adverse lipoprotein profiles, and may represent two major modifiable cardiovascular risk factors in the pediatric T2DM population. Patients with an HbA1C higher than 8.0% had significantly worse atherogenic lipid profile, i.e., higher LDL-C, non-HDL-C, apoB and LDL pattern B, suggesting adequate glycemia may improve adverse lipoprotein profiles.

Dyslipidemia is associated with pediatric nonalcoholic fatty liver disease.

BACKGROUND: With the increasing prevalence of childhood obesity, nonalcoholic fatty liver disease (NAFLD) has emerged as the most common cause of pediatric chronic liver disorder. Factors underlying the pathophysiology of NAFLD remain poorly defined. OBJECTIVE: This study aimed to describe the metabolic characteristics of children with NAFLD differing in race/ethnicity and to test associations between dyslipidemia and NAFLD. METHODS: A retrospective chart review was conducted at a tertiary referral university hospital among 309 children with a diagnosis of NAFLD. RESULTS: Participants (mean age 12.5 ± 3.4 years) were 64% male, 63% white, 23% Hispanic, and 14% black. Hispanic children were diagnosed with NAFLD at a significantly younger age (10.6 ± 3.1 years, P < .0001) and lower body mass index (31.5 ± 6.8 kg/m2, P < .0001) than their white and black counterparts. For the entire cohort, prevalence of systolic hypertension was 41%, diabetes 14%, elevated cholesterol 42%, elevated non-high-density lipoprotein cholesterol (non-HDL-C) 58%, elevated low-density lipoprotein cholesterol 36%, elevated triglycerides (TG) 88%, and low high-density lipoprotein cholesterol 77%. Whites had elevated non-HDL-C, low-density lipoprotein cholesterol, and TG compared to blacks or Hispanics. Serum TG and non-HDL-C were significantly correlated to alanine aminotransferase (r = 0.18, P = .01; r = 0.16, P = .02), respectively, and persisted after adjusting for age and body mass index. CONCLUSION: Cardiometabolic derangements, especially dyslipidemia, are highly prevalent in children with NAFLD and differ based on race/ethnicity. Serum TG and non-HDL-C may play an important role in the pathophysiology of pediatric NAFLD.

Effectiveness of a carbohydrate restricted diet to treat non-alcoholic fatty liver disease in adolescents with obesity: Trial design and methodology.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder among children in the developed world and can progress to cirrhosis, hepatocellular carcinoma, and liver failure. No evidence-based dietary guidelines exist on the most effective diet prescription to treat NAFLD. OBJECTIVE: To compare the effect of a carbohydrate (CHO)-restricted diet vs fat-restricted diet, the current standard of care, on changes in hepatic fat infiltration, body composition, and metabolic health over an 8-week period among overweight and obese children diagnosed with NAFLD. METHODS: In this two-arm, parallel design randomized controlled trial (RCT), 40 participants aged 9 to 18 years were randomized to a CHO restricted diet (<25:>50:25% daily calories from CHO: fat: protein) or control, fat restricted diet (55,20:25% daily calories from CHO: fat: protein). This family-based diet intervention included: (1) a 2-week supply of groceries to feed a four-person household specific to the assigned diet; and (2) extensive education on diet implementation through biweekly, diet-specific group and individualized counseling sessions with participants and one parent or guardian led by a registered dietitian (RD). The primary outcome measure of this study was hepatic lipid, measured using magnetic resonance spectroscopy (MRS). Secondary outcomes included liver transaminases; markers of inflammation (hsCRP, IL-6, TNF-α); body composition; visceral adipose tissue; and insulin resistance. All testing was conducted at baseline and week 8; hepatic transaminases were also measured at weeks 2 and 4. This RCT is registered with ClinicalTrials.gov (ID: NCT02787668).