William T. Donahoo

From instinct to intellect: the challenge of maintaining healthy weight in the modern world.

The global obesity epidemic is being driven in large part by a mismatch between our environment and our metabolism. Human physiology developed to function within an environment where high levels of physical activity were needed in daily life and food was inconsistently available. For most of mankind’s history, physical activity has ‘pulled’ appetite so that the primary challenge to the physiological system for body weight control was to obtain sufficient energy intake to prevent negative energy balance and body energy loss. The current environment is characterized by a situation whereby minimal physical activity is required for daily life and food is abundant, inexpensive, high in energy density and widely available. Within this environment, food intake ‘pushes’ the system, and the challenge to the control system becomes to increase physical activity sufficiently to prevent positive energy balance. There does not appear to be a strong drive to increase physical activity in response to excess energy intake and there appears to be only a weak adaptive increase in resting energy expenditure in response to excess energy intake. In the modern world, the prevailing environment constitutes a constant background pressure that promotes weight gain. We propose that the modern environment has taken body weight control from an instinctual (unconscious) process to one that requires substantial cognitive effort. In the current environment, people who are not devoting substantial conscious effort to managing body weight are probably gaining weight. It is unlikely that we would be able to build the political will to undo our modern lifestyle, to change the environment back to one in which body weight control again becomes instinctual. In order to combat the growing epidemic we should focus our efforts on providing the knowledge, cognitive skills and incentives for controlling body weight and at the same time begin creating a supportive environment to allow better management of body weight.

Variability in energy expenditure and its components

Purpose of reviewTo review factors contributing to variation in total daily energy expenditure and its primary components: (1) resting metabolic rate; (2) diet-induced thermogenesis; and (3) activity thermogenesis, including exercise energy expenditure and nonexercise activity. For each component, the expected magnitude of intra-individual variability is also considered. We also reviewed studies that quantified the variability in 24 h energy expenditure. Recent findingsIn humans, the coefficient of variation in the components of total daily energy expenditure is around 5-8% for resting metabolic rate, 1-2% for exercise energy expenditure, and around 20% for diet-induced thermogenesis. The coefficient of variance for 24 h energy expenditure measured using a room calorimeter for resting metabolic rate is around 5-10%. Thus, these measures are all rather reproducible. Total daily energy expenditure varies several-fold in humans, not due to variation in resting metabolic rate, diet-induced thermogenesis, or exercise thermogenesis, but rather, due to variations in nonexercise activity. A variety of factors impact nonexercise activity, including occupation, environment, education, genetics, age, gender, and body composition, but little is known about the magnitude of effect. SummaryResting metabolic rate, diet-induced thermogenesis, exercise energy expenditure, and 24 h energy expenditure are highly reproducible. Coefficient of variation is smallest for exercise energy expenditure, followed by resting metabolic rate, 24 h energy expenditure, and diet-induced thermogenesis. There is considerable variability in total daily energy expenditure, largely due to variations in nonexercise activity. Although the factors that impact upon nonexercise activity are understood, their contribution to variation in total daily energy expenditure is unclear.

Relation between calcium intake and fat oxidation in adult humans

OBJECTIVE: To determine if total calcium (Ca2+) intake and intake of Ca2+ from dairy sources are related to whole-body fat oxidation.DESIGN: Cross-sectional study.SUBJECTS: A total of 35 (21 m, 14 f) non-obese, healthy adults (mean±s.d., age: 31±6 y; weight: 71.2±12.3 kg; BMI: 23.7±2.9 kg m−2; body fat: 21.4±5.4%).MEASUREMENTS: Daily (24 h) energy expenditure (EE) and macronutrient oxidation using whole-room indirect calorimetry; habitual Ca2+ intake estimated from analysis of 4-day food records; acute Ca2+ intake estimated from measured food intake during a 24-h stay in a room calorimeter.RESULTS: Acute Ca2+ intake (mg· kcal−1) was positively correlated with fat oxidation over 24 h (r=0.38, P=0.03), during sleep (r=0.36, P=0.04), and during light physical activity (r=0.32, P=0.07). Acute Ca2+ intake was inversely correlated with 24-h respiratory quotient (RQ) (r=−0.36, P=0.04) and RQ during sleep (r=−0.31, P=0.07). After adjustment for fat mass, fat-free mass, energy balance, acute fat intake, and habitual fat intake, acute Ca2+ intake explained ∼10% of the variance in 24-h fat oxidation. Habitual Ca2+ intake was not significantly correlated to fat oxidation or RQ. Total Ca2+ intake and Ca2+ intake from dairy sources were similarly correlated with fat oxidation. In backwards stepwise models, total Ca2+ intake was a stronger predictor of 24 h fat oxidation than dairy Ca2+ intake.CONCLUSION: Higher acute Ca2+ intake is associated with higher rates of whole-body fat oxidation. These effects were apparent over 24 h, during sleep and, to a lesser extent, during light physical activity. Calcium intake from dairy sources was not a more important predictor of fat oxidation than total Ca2+ intake.

Resistant starch consumption promotes lipid oxidation

BackgroundAlthough the effects of resistant starch (RS) on postprandial glycemia and insulinemia have been extensively studied, little is known about the impact of RS on fat metabolism. This study examines the relationship between the RS content of a meal and postprandial/post-absorbative fat oxidation.Results12 subjects consumed meals containing 0%, 2.7%, 5.4%, and 10.7% RS (as a percentage of total carbohydrate). Blood samples were taken and analyzed for glucose, insulin, triacylglycerol (TAG) and free fatty acid (FFA) concentrations. Respiratory quotient was measured hourly. The 0%, 5.4%, and 10.7% meals contained 50 μCi [1-14C]-triolein with breath samples collected hourly following the meal, and gluteal fat biopsies obtained at 0 and 24 h. RS, regardless of dose, had no effect on fasting or postprandial insulin, glucose, FFA or TAG concentration, nor on meal fat storage. However, data from indirect calorimetry and oxidation of [1-14C]-triolein to 14CO2 showed that addition of 5.4% RS to the diet significantly increased fat oxidation. In fact, postprandial oxidation of [1-14C]-triolein was 23% greater with the 5.4% RS meal than the 0% meal (p = 0.0062).ConclusionsThese data indicate that replacement of 5.4% of total dietary carbohydrate with RS significantly increased post-prandial lipid oxidation and therefore could decrease fat accumulation in the long-term.

The Relationship between Dietary Fat and Fatty Acid Intake and Body Weight, Diabetes, and the Metabolic Syndrome

Research Group 2002; Ornish, 2005]. However, it is impossible to draw final conclusions from these studies in that they do not have a higher fat control group, they often incorporated additional lifestyle interventions, and there is difficulty in maintaining the very low fat diets, which leads to high drop out rates. Despite the findings of post hoc analyses of these trials that show that adherence to a high fiber, low fat diet is the strongest predictor of weight loss and decreased risk of type 2 diabetes (T2DM) [Lindstrom et al., 2006a], unified recommendations are difficult and the public is left with mixed messages [Bravata et al., 2003]. This review will endeavor to provide an update of the literature from 1993 to the present with respect to the role of dietary fat and obesity, metabolic syndrome and diabetes. Data from cross-sectional, prospective cohort and interventional studies will be evaluated, and emerging data on the role of genetic regulation of the response to dietary fat will be presented.

Construction of a Multisite DataLink Using Electronic Health Records for the Identification, Surveillance, Prevention, and Management of Diabetes Mellitus: The SUPREME-DM Project

Introduction Electronic health record (EHR) data enhance opportunities for conducting surveillance of diabetes. The objective of this study was to identify the number of people with diabetes from a diabetes DataLink developed as part of the SUPREME-DM (SUrveillance, PREvention, and ManagEment of Diabetes Mellitus) project, a consortium of 11 integrated health systems that use comprehensive EHR data for research. Methods We identified all members of 11 health care systems who had any enrollment from January 2005 through December 2009. For these members, we searched inpatient and outpatient diagnosis codes, laboratory test results, and pharmaceutical dispensings from January 2000 through December 2009 to create indicator variables that could potentially identify a person with diabetes. Using this information, we estimated the number of people with diabetes and among them, the number of incident cases, defined as indication of diabetes after at least 2 years of continuous health system enrollment. Results The 11 health systems contributed 15,765,529 unique members, of whom 1,085,947 (6.9%) met 1 or more study criteria for diabetes. The nonstandardized proportion meeting study criteria for diabetes ranged from 4.2% to 12.4% across sites. Most members with diabetes (88%) met multiple criteria. Of the members with diabetes, 428,349 (39.4%) were incident cases. Conclusion The SUPREME-DM DataLink is a unique resource that provides an opportunity to conduct comparative effectiveness research, epidemiologic surveillance including longitudinal analyses, and population-based care management studies of people with diabetes. It also provides a useful data source for pragmatic clinical trials of prevention or treatment interventions.

DRUGS CAUSING DYSLIPOPROTEINEMIA

Diuretics and beta-blockers have a strong tendency to affect serum lipids adversely, whereas the peripherally acting alpha-blocking agents consistently result in beneficial effects. Most of the other antihypertensive agents (calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists, and drugs that act centrally) are lipid neutral. The effect of steroid hormones varies with the drug, dose, and route of administration. In general, androgens lower HDL-C and have a variable effect on LDL-C. The effects of progestins vary greatly depending on their androgenicity, and estrogens are beneficial except when hypertriglyceridemia occurs with oral estrogens. Glucocorticoids raise HDL-C and may also increase triglycerides and LDL-C. Retinoids increase triglycerides and LDL-C and also reduce HDL-C. Interferons can cause hypertriglyceridemia. Following organ transplantation, a dyslipidemia often ensues. This is caused in part by the medications used to prevent rejection (glucocorticoids, cyclosporine, and FK-506) and requires close attention and, in some patients, drug therapy to prevent coronary artery disease.

Women With Gestational Diabetes Mellitus Randomized to a Higher–Complex Carbohydrate/Low-Fat Diet Manifest Lower Adipose Tissue Insulin Resistance, Inflammation, Glucose, and Free Fatty Acids: A Pilot Study

OBJECTIVE Diet therapy in gestational diabetes mellitus (GDM) has focused on carbohydrate restriction but is poorly substantiated. In this pilot randomized clinical trial, we challenged the conventional low-carbohydrate/higher-fat (LC/CONV) diet, hypothesizing that a higher–complex carbohydrate/lower-fat (CHOICE) diet would improve maternal insulin resistance (IR), adipose tissue (AT) lipolysis, and infant adiposity. RESEARCH DESIGN AND METHODS At 31 weeks, 12 diet-controlled overweight/obese women with GDM were randomized to an isocaloric LC/CONV (40% carbohydrate/45% fat/15% protein; n = 6) or CHOICE (60%/25%/15%; n = 6) diet. All meals were provided. AT was biopsied at 37 weeks. RESULTS After ∼7 weeks, fasting glucose (P = 0.03) and free fatty acids (P = 0.06) decreased on CHOICE, whereas fasting glucose increased on LC/CONV (P = 0.03). Insulin suppression of AT lipolysis was improved on CHOICE versus LC/CONV (56 vs. 31%, P = 0.005), consistent with improved IR. AT expression of multiple proinflammatory genes was lower on CHOICE (P < 0.01). Infant adiposity trended lower with CHOICE (10.1 ± 1.4 vs. 12.6 ± 2%, respectively). CONCLUSIONS A CHOICE diet may improve maternal IR and infant adiposity, challenging recommendations for a LC/CONV diet.

A Higher-Complex Carbohydrate Diet in Gestational Diabetes Mellitus Achieves Glucose Targets and Lowers Postprandial Lipids: A Randomized Crossover Study

OBJECTIVE The conventional diet approach to gestational diabetes mellitus (GDM) advocates carbohydrate restriction, resulting in higher fat (HF), also a substrate for fetal fat accretion and associated with maternal insulin resistance. Consequently, there is no consensus about the ideal GDM diet. We hypothesized that, compared with a conventional, lower-carbohydrate/HF diet (40% carbohydrate/45% fat/15% protein), consumption of a higher-complex carbohydrate (HCC)/lower-fat (LF) Choosing Healthy Options in Carbohydrate Energy (CHOICE) diet (60/25/15%) would result in 24-h glucose area under the curve (AUC) profiles within therapeutic targets and lower postprandial lipids. RESEARCH DESIGN AND METHODS Using a randomized, crossover design, we provided 16 GDM women (BMI 34 ± 1 kg/m2) with two 3-day isocaloric diets at 31 ± 0.5 weeks (washout between diets) and performed continuous glucose monitoring. On day 4 of each diet, we determined postprandial (5 h) glucose, insulin, triglycerides (TGs), and free fatty acids (FFAs) following a controlled breakfast meal. RESULTS There were no between-diet differences for fasting or mean nocturnal glucose, but 24-h AUC was slightly higher (∼6%) on the HCC/LF CHOICE diet (P = 0.02). The continuous glucose monitoring system (CGMS) revealed modestly higher 1- and 2-h postprandial glucose on CHOICE (1 h, 115 ± 2 vs. 107 ± 3 mg/dL, P ≤ 0.01; 2 h, 106 ± 3 vs. 97 ± 3 mg/dL, P = 0.001) but well below current targets. After breakfast, 5-h glucose and insulin AUCs were slightly higher (P < 0.05), TG AUC was no different, but the FFA AUC was significantly lower (∼19%; P ≤ 0.01) on the CHOICE diet. CONCLUSIONS This highly controlled study randomizing isocaloric diets and using a CGMS is the first to show that liberalizing complex carbohydrates and reducing fat still achieved glycemia below current treatment targets and lower postprandial FFAs. This diet strategy may have important implications for preventing macrosomia.

Dietary fat increases energy intake across the range of typical consumption in the United States.

Objective: The fat content of a diet has been shown to affect total energy intake, but controlled feeding trials have only compared very high (40% of total calories) fat diets with very low (20% of total calories) fat diets. This study was designed to measure accurately the voluntary food and energy intake over a range of typical intake for dietary fat.