Bernard V. Miller

Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity

Dietary carbohydrate restriction has been purported to cause endocrine adaptations that promote body fat loss more than dietary fat restriction. We selectively restricted dietary carbohydrate versus fat for 6 days following a 5-day baseline diet in 19 adults with obesity confined to a metabolic ward where they exercised daily. Subjects received both isocaloric diets in random order during each of two inpatient stays. Body fat loss was calculated as the difference between daily fat intake and net fat oxidation measured while residing in a metabolic chamber. Whereas carbohydrate restriction led to sustained increases in fat oxidation and loss of 53 ± 6 g/day of body fat, fat oxidation was unchanged by fat restriction, leading to 89 ± 6 g/day of fat loss, and was significantly greater than carbohydrate restriction (p = 0.002). Mathematical model simulations agreed with these data, but predicted that the body acts to minimize body fat differences with prolonged isocaloric diets varying in carbohydrate and fat.

Category-specific integration of homeostatic signals in caudal but not rostral human insula.

Prevailing theories hold that the insula is functionally organized along its caudal-to-rostral axis, with posterior regions coding lower-level sensory information and anterior regions coding higher-level stimulus significance relative to the bodys homeostatic needs. Contrary to predictions of this model, the response of the taste-sensitive region of the caudal, but not rostral, insula to food images was directly related to the bodys homeostatic state as indexed by levels of peripheral glucose.

The Triglyceride/High-Density Lipoprotein Cholesterol Ratio Fails to Predict Insulin Resistance in African-American Women: An Analysis of Jackson Heart Study

BACKGROUNDnCompared to whites, insulin-resistant African Americans have worse outcomes. Screening programs that could identify insulin resistance early enough for intervention to affect outcome often rely on triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels. Racial differences in TG and HDL-C may compromise the efficacy of these programs in African Americans. A recommendation currently exists to use the TG/HDL-C ratio ≥2.0 to predict insulin resistance in African Americans. The validity of this recommendation needs examination. Therefore, our aim was to determine the ability of TG/HDL-C ratio to predict insulin resistance in African Americans.nnnMETHODSnIn 1,903 African Americans [895 men, 1,008 women, age 55u2009±u200912 years, meanu2009±u2009standard deviation (SD), range 35-80 years, body mass index (BMI) 31.0u2009±u20096.4u2009kg/m(2), range 18.5-55u2009kg/m(2)] participating in the Jackson Heart Study, a population-based study of African Americans, Jackson, Mississippi tricounty region, insulin resistance was defined by the upper quartile (≥4.43) of homeostasis model assessment of insulin resistance (HOMA-IR). An area under the receiver operating characteristic curve (AUC-ROC) of >0.70 was required for prediction of insulin resistance by TG/HDL-C. The optimal test cutoff was determined by the Youden index.nnnRESULTSnHOMA-IR was similar in men and women (3.40u2009±u20092.03 vs. 3.80u2009±u20092.46, Pu2009=u20090.60). Women had lower TG (94u2009±u200949 vs. 109u2009±u200965u2009mg/dL Pu2009<u20090.001) and TG/HDL-C (1.9u2009±u20091.4 vs. 2.7u2009±u20092.1, Pu2009<u20090.001). For men, AUC-ROC for prediction of insulin resistance by TG/HDL-C was: 0.77u2009±u20090.01, meanu2009±u2009standard error (SE), with an optimal cutoff of ≥2.5. For women, the AUC-ROC was 0.66u2009±u20090.01, rendering an optimal cutoff indefinable. When women were divided in two groups according to age, 35-50 years and 51-80 years, the results did not change.nnnCONCLUSIONSnIn African-American men, the recommended TG/HDL-C threshold of 2.0 should be adjusted upward to 2.5. In African-American women, TG/HDL-C cannot identify insulin resistance. The Jackson Heart Study can help determine the efficacy of screening programs in African-Americans.

Metabolic Syndrome Does Not Detect Metabolic Risk in African Men Living in the U.S.

OBJECTIVE Metabolic risk and metabolic syndrome (MetSyn) prevalence were compared in Africans who immigrated to the U.S. and African Americans. If MetSyn were an effective predictor of cardiometabolic risk, then the group with a worse metabolic risk profile would have a higher rate of MetSyn. RESEARCH DESIGN AND METHODS Cross-sectional analyses were performed on 95 men (39 Africans, 56 African Americans, age 38 ± 6 years [mean ± SD]). Glucose tolerance was determined by oral glucose tolerance test, visceral adipose tissue (VAT) was determined by computerized tomography, and MetSyn was determined by the presence of three of five factors: central obesity, hypertriglyceridemia, low levels of HDL cholesterol, hypertension, and fasting hyperglycemia. RESULTS MetSyn prevalence was similar in Africans and African Americans (10 vs. 13%, P = 0.74), but hypertension, glycemia (fasting and 2-h glucose), and VAT were higher in Africans. CONCLUSIONS African immigrants have a worse metabolic profile than African Americans but a similar prevalence of MetSyn. Therefore, MetSyn may underpredict metabolic risk in Africans.

Higher acute insulin response to glucose may determine greater free fatty acid clearance in African-American women.

CONTEXTnObesity and diabetes are more common in African-Americans than whites. Because free fatty acids (FFA) participate in the development of these conditions, studying race differences in the regulation of FFA and glucose by insulin is essential.nnnOBJECTIVEnThe objective of the study was to determine whether race differences exist in glucose and FFA response to insulin.nnnDESIGNnThis was a cross-sectional study.nnnSETTINGnThe study was conducted at a clinical research center.nnnPARTICIPANTSnThirty-four premenopausal women (17 African-Americans, 17 whites) matched for age [36 ± 10 yr (mean ± sd)] and body mass index (30.0 ± 6.7 kg/m²).nnnINTERVENTIONSnInsulin-modified frequently sampled iv glucose tolerance tests were performed with data analyzed by separate minimal models for glucose and FFA.nnnMAIN OUTCOME MEASURESnGlucose measures were insulin sensitivity index (S(I)) and acute insulin response to glucose (AIRg). FFA measures were FFA clearance rate (c(f)).nnnRESULTSnBody mass index was similar but fat mass was higher in African-Americans than whites (P < 0.01). Compared with whites, African-Americans had lower S(I) (3.71 ± 1.55 vs. 5.23 ± 2.74 [×10⁻⁴ min⁻¹/(microunits per milliliter)] (P = 0.05) and higher AIRg (642 ± 379 vs. 263 ± 206 mU/liter⁻¹ · min, P < 0.01). Adjusting for fat mass, African-Americans had higher FFA clearance, c(f) (0.13 ± 0.06 vs. 0.08 ± 0.05 min⁻¹, P < 0.01). After adjusting for AIRg, the race difference in c(f) was no longer present (P = 0.51). For all women, the relationship between c(f) and AIRg was significant (r = 0.64, P < 0.01), but the relationship between c(f) and S(I) was not (r = -0.07, P = 0.71). The same pattern persisted when the two groups were studied separately.nnnCONCLUSIONnAfrican-American women were more insulin resistant than white women, yet they had greater FFA clearance. Acutely higher insulin concentrations in African-American women accounted for higher FFA clearance.

An Evaluation of the Atkins' Diet

Low-carbohydrate (LC) weight-reducing diets are popular choices for self-dieters. Eighteen adults (BMI >/= 25 kg/m(2)) were enrolled in this short-term longitudinal study to evaluate dietary intake and weight on their usual diets and LC diet. Subjects were instructed to follow the first two phases of the diet described in Dr. Atkins New Diet Revolution (2 weeks each). Total daily intake of calories and nutrients were calculated from 3-day food diaries. Body weight was measured at the end of each 2-week diet session. All enrolled subjects completed the study (age = 39.8 +/- 8.1 years, BMI = 36.6 +/- 6.6 kg/m(2)). Mean caloric intakes were 1400 +/- 472 kcal/day (Induction diet) and 1558 +/- 490 kcal/day (Ongoing Weight Loss diet) both p </= 0.001 compared to usual (Baseline diet) 2481 +/- 723 kcal/day. Body weights were 107.4 +/- 24.2 kg, 103.6 +/- 23.0 kg and 102.1 +/- 22.6 kg at the conclusion of the Baseline, Induction, and Ongoing Weight Loss diets, respectively (both p </= 0.001). Decreases in daily caloric intake correlated with weight loss. Pearson correlation coefficients were, r = 0.64 (p </= 0.001) and r = 0.40 (p </= 0.001) for Induction and Ongoing Weight Loss diets versus usual diet. Caloric intake is decreased when otherwise healthy overweight and obese adults self-implement Atkins Induction and Ongoing Weight Loss diets and significantly altered their dietary micronutrient intake. Weight loss can be explained by the self-selected lower caloric intake on The Atkins Diet.

Insulin and extremity muscle mass in overweight and obese women

Background:Obesity disproportionately affects women, especially those of African descent, and is associated with increases in both fat and muscle masses.Objective:Although increased extremity muscle mass may be compensatory to fat mass load, we propose that elevated insulin levels resulting from diminished insulin sensitivity may additionally contribute to extremity muscle mass in overweight or obese women.Methods:The following measurements were performed in 197 non-diabetic women (57% black, 35% white; age 46±11 years (mean±s.d.), body mass index (BMI) range 25.0–57.7u2009kgu2009m−2): dual-energy X-ray absorptiometry for fat and extremity muscle masses; exercise performance by duration and peak oxygen consumption (VO2 peak) during graded treadmill exercise; fasting insulin and, in 183 subjects, insulin sensitivity index (SI) calculated from the minimal model.Results:SI (range 0.5–14.1u2009lu2009mU−1u2009min−1) was negatively, and fasting insulin (range 1.9–35.6u2009μUu2009ml−1) positively associated with extremity muscle mass (both P<0.001), independent of age and height. Sixty-seven percent of women completed 6 months of participation in a weight loss and exercise program: we found a significant association between reduction in fasting insulin and a decrease in extremity muscle mass (P=0.038), independent of reduction in fat mass or improvement in exercise performance by VO2 peak and exercise duration, and without association with change in SI or interaction by race.Conclusions:Hyperinsulinemia in overweight or obese women is associated with increased extremity muscle mass, which is partially reversible with reduction in fasting insulin concentration, consistent with the stimulatory effects of insulin on skeletal muscle.

Bayesian Functional Integral Method for Inferring Continuous Data from Discrete Measurements

Inference of the insulin secretion rate (ISR) from C-peptide measurements as a quantification of pancreatic β-cell function is clinically important in diseases related to reduced insulin sensitivity and insulin action. ISR derived from C-peptide concentration is an example of nonparametric Bayesian model selection where a proposed ISR time-course is considered to be a model. An inferred value of inaccessible continuous variables from discrete observable data is often problematic in biology and medicine, because it is a priori unclear how robust the inference is to the deletion of data points, and a closely related question, how much smoothness or continuity the data actually support. Predictions weighted by the posterior distribution can be cast as functional integrals as used in statistical field theory. Functional integrals are generally difficult to evaluate, especially for nonanalytic constraints such as positivity of the estimated parameters. We propose a computationally tractable method that uses the exact solution of an associated likelihood function as a prior probability distribution for a Markov-chain Monte Carlo evaluation of the posterior for the full model. As a concrete application of our method, we calculate the ISR from actual clinical C-peptide measurements in human subjects with varying degrees of insulin sensitivity. Our method demonstrates the feasibility of functional integral Bayesian model selection as a practical method for such data-driven inference, allowing the data to determine the smoothing timescale and the width of the prior probability distribution on the space of models. In particular, our model comparison method determines the discrete time-step for interpolation of the unobservable continuous variable that is supported by the data. Attempts to go to finer discrete time-steps lead to less likely models.

Weight Loss Programs May Have Beneficial or Adverse Effects on Fat Mass and Insulin Sensitivity in Overweight and Obese Black Women.

ObjectiveWeight loss interventions have produced little change in insulin sensitivity in black women, but mean data may obscure metabolic benefit to some and adverse effects for others. Accordingly, we analyzed insulin sensitivity relative to fat mass change following a weight loss program.Design and MethodsFifty-four black women (BMI range 25.9 to 54.7xa0kg/m2) completed the 6-month program that included nutrition information and worksite exercise facilities. Fat mass was measured by dual-energy X-ray absorptiometry, and insulin sensitivity index (SI) was calculated from an insulin-modified intravenous glucose tolerance test using the minimal model.ResultsBaseline SI (range 0.74 to 7.58xa0l/mU−1•min−1) was inversely associated with fat mass (ru2009= −0.516, pu2009<u20090.001), independent of age. On average, subjects lost fat mass (baseline 40.8u2009±u200912.4 to 39.4u2009±u200912.6xa0kg [meanu2009±u2009SD], Pu2009<u20090.01), but 17 women (32xa0%) actually gained fat mass. SI for the group was unchanged (baseline 3.3u2009±u20091.7 to 3.2u2009±u20091.6, Pu2009=u20090.67). However, the tertile with greatest fat mass loss (−3.6xa0kg, range −10.7 to −1.7xa0kg) improved insulin sensitivity (SI +0.3u2009±u20091.2), whereas the tertile with net fat mass gain (+0.9xa0kg, range −0.1 to +3.8xa0kg) had reduced insulin sensitivity (SI −0.7u2009±u20091.3) from baseline values (Pu2009<u20090.05 by ANOVA).ConclusionsBlack women in a weight loss program who lose fat mass may have improved insulin sensitivity, but fat mass gain with diminished sensitivity is common. Additional support for participants who fail to achieve fat mass loss early in an intervention may be required for success.

Quantitation of Human Whole-Body Synthesis-Secretion Rates of Docosahexaenoic Acid and Eicosapentaenoate Acid from Circulating Unesterified α-Linolenic Acid at Steady State

The rate at which dietary α-linolenic acid (ALA) is desaturated and elongated to its longer-chain n-3 polyunsaturated fatty acid (PUFA) in humans is not agreed upon. In this study, we applied a methodology developed using rodents to investigate the whole-body, presumably hepatic, synthesis-secretion rates of esterified n-3 PUFA from circulating unesterified ALA in 2 healthy overweight women after 10 weeks of low-linoleate diet exposure. During continuous iv infusion of d5-ALA, 17 arterial blood samples were collected from each subject at -10, 0, 10, 20, 40, 60, 80, 100, 120, 150, 180, and 210 min, and at 4, 5, 6, 7, and 8 h after beginning infusion. Plasma esterified d5-n-3 PUFA concentrations were plotted against the infusion time and fit to a sigmoidal curve using nonlinear regression. These curves were used to estimate kinetic parameters using a kinetic analysis developed using rodents. Calculated synthesis-secretion rates of esterified eicosapentaenoate, n-3 docosapentaenoate, docosahexaenoic acid, tetracosapentaenate, and tetracosahexaenoate from circulating unesterified ALA were 2.1 and 2.7; 1.7 and 5.3; 0.47 and 0.27; 0.30 and 0.30; and 0.32 and 0.27 mg/day for subjects S01 and S02, respectively. This study provides new estimates of whole-body synthesis-secretion rates of esterified longer-chain n-3 PUFA from circulating unesterified ALA in human subjects. This method now can be extended to study factors that regulate human whole-body PUFA synthesis-secretion in health and disease.