Intentional weight loss is an important component of treatment for overweight patients with type 2 diabetes, but the effects on bone density are not known. We used data from the Look AHEAD trial to determine the impact of an intensive lifestyle weight loss intervention (ILI) compared to diabetes support and education (DSE) on changes in bone mineral density (BMD) over 12 months. Overweight and obese adults with type 2 diabetes were randomly assigned to ILI or DSE. In a sub-study of BMD conducted at 5 of 16 clinical centers, hip, spine and whole body dual x-ray absorptiometry scans were obtained at baseline and one year later on 642 of 739 ILI and 632 of 740 DSE participants. At baseline, mean age was 58.4 years, and average body mass index was 35.2 kg/m2. Total hip BMD T-score was <−2.5 in 1% and <−1.0 in 8%. At one year, weight loss was greater in ILI than DSE (−8.6% versus −0.7%), and glycemic control and fitness were also improved. Bone loss over one year was greater in ILI at the total hip (−1.4% versus −0.4%; p<0.001) and femoral neck (−1.5% versus −0.8%; p=0.009), but change in BMD for the lumbar spine and whole body did not differ between groups. In ILI, bone loss at the total hip was independently associated with weight loss in men and women and with poorer glycemic control in men, but was not associated with changes in fitness. One year of an intensive lifestyle intervention in adults with type 2 diabetes, resulting in weight loss, was associated with a modest increase in hip bone loss despite improved fitness and glycemic control.

Background.

Longevity clusters in families, and parental longevity may be associated with lower risk of chronic diseases in their children. It is unknown if diabetes risk is associated with parental longevity.

Methods.

We evaluated participants in the Diabetes Prevention Program with a parental history questionnaire at study entry. We classified them into five groups: premature death (parental death at age < 50 years), parental longevity (living to at least 80 years), and three intermediate groups (alive by age 49 but dying at age 50–59, 60–69, or 70–79). Those with alive parents and younger than 80 years were excluded. We analyzed separately effects of paternal (n = 2,165) and maternal (n = 1,739) longevity on diabetes incidence and risk after an average follow-up of 3.2 years.

Results.

At baseline, more diabetes risk factors (parental history of diabetes, coronary heart disease, higher body mass index, homeostasis model assessment for insulin resistance, and corrected insulin response) were found in participants whose parents died prematurely. Diabetes incidence was 9.5 cases/100 person-years in the 229 whose fathers died prematurely. In the 618 with paternal longevity, the rate was 6.6 cases/100 person-years (hazard ratio [95% confidence interval] = 0.68 [0.49–0.94]). The rates were 10.7 cases/100 person-years (n = 156) and 7.3 cases/100 person-years (n = 699, hazard ratio = 0.67 [95% confidence interval 0.47–0.95]) for those with maternal premature death or longevity, respectively. Associations with demographic and diabetes risk factors had minimal influence on the reduced risk found in those with paternal (adjusted hazard ratio = 0.78, 95% confidence interval 0.52–1.16) and maternal (adjusted hazard ratio = 0.64, 95% confidence interval 0.41–1.01) longevity.

Conclusion.

Parental longevity is associated with lower diabetes incidence in adults at high risk of type 2 diabetes.

Background

Dopamine (DA) and the DA D2 receptor (D2R) are involved in the rewarding and the conditioned responses to food and drug rewards. Osborne-Mendel (OM) rats are genetically prone and S5B/P rats are genetically resistant to obesity when fed a high-fat diet. We hypothesized that the differential sensitivity of these two rat strains to natural rewards may also be reflected in sensitivity to drugs of abuse. Therefore, we tested whether OM and S5B/P rats showed a differential preference to cocaine using conditioned place preference (CPP). To also evaluate whether there is specific involvement of the D2R in this differential conditioning sensitivity, we then tested whether the D2R agonist bromocriptine (BC) would differentially affect the effects of cocaine in the two strains.

Methods

OM and S5B/P rats were conditioned with cocaine (5 or 10mg/kg) in one chamber and saline in another for 8 days. Rats were then tested for cocaine preference. The effects of BC (0.5, 1, 5, 10, 20mg/kg) on cocaine preference were then assessed in subsequent test sessions.

Results

OM rats did not show a significant preference for the cocaine-paired chamber on test day. Only the S5B/P rats showed cocaine CPP. Later treatment with only the highest dose of BC resulted in reduced cocaine CPP in S5B/P rats when treated with 5mg/kg cocaine and in OM rats treated with 10mg/kg cocaine.

Conclusion

Our results indicated obesity-resistant S5B rats showed greater cocaine CPP than the obesity-prone OM rats. These findings do not support a theory of common vulnerability for reinforcer preferences (food and cocaine). However, they show that BC reduced cocaine conditioning effects supporting at least a partial regulatory role of D2R in conditioned responses to drugs.

Background

Adults with type 2 diabetes mellitus often have limitations in mobility that increase with age. An intensive lifestyle intervention that produces weight loss and improves fitness could slow the loss of mobility in such patients.

Methods

We randomly assigned 5145 overweight or obese adults between the ages of 45 and 74 years with type 2 diabetes to either an intensive lifestyle intervention or a diabetes support-and-education program; 5016 participants contributed data. We used hidden Markov models to characterize disability states and mixed-effects ordinal logistic regression to estimate the probability of functional decline. The primary outcome was self-reported limitation in mobility, with annual assessments for 4 years.

Results

At year 4, among 2514 adults in the lifestyle-intervention group, 517 (20.6%) had severe disability and 969 (38.5%) had good mobility; the numbers among 2502 participants in the support group were 656 (26.2%) and 798 (31.9%), respectively. The lifestyle-intervention group had a relative reduction of 48% in the risk of loss of mobility, as compared with the support group (odds ratio, 0.52; 95% confidence interval, 0.44 to 0.63; P<0.001). Both weight loss and improved fitness (as assessed on treadmill testing) were significant mediators of this effect (P<0.001 for both variables). Adverse events that were related to the lifestyle intervention included a slightly higher frequency of musculoskeletal symptoms at year 1.

Conclusions

Weight loss and improved fitness slowed the decline in mobility in overweight adults with type 2 diabetes. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT00017953.)

Background

Weight loss reduces energy expenditure, but the contribution of different macronutrients to this change is unclear.

Hypothesis

We tested the hypothesis that macronutrient composition of the diet might affect the partitioning of energy expenditure during weight loss.

Design

A sub-study of 99 participants from the POUNDS LOST trial had total energy expenditure (TEE) measured by doubly labeled water and resting energy expenditure (REE) measured by indirect calorimetry at baseline and repeated at 6 months in 89 participants. Participants were randomly assigned to one of 4 diets with either 15% or 25% protein and 20% or 40% fat.

Results

TEE and REE were positively correlated with each other and with fat free mass and body fat, at baseline and 6 months. The average weight loss of 8.1±0.65 kg (LSmean±SE) reduced TEE by 120±56 kcal/d and REE by 136±18 kcal/d. A greater weight loss at 6 months was associated with a greater decrease in TEE and REE. Participants eating the high fat diet lost significantly more fat free mass (1.52±0.55 kg) than the low fat diet group (p<0.05). Participants eating the low fat diet had significantly higher measures of physical activity than the high fat group.

Conclusion

A greater weight loss was associated with a larger decrease in both TEE and REE. The low fat diet was associated with significant changes in fat free body mass and energy expenditure from physical activity compared to the high fat diet.

Background

Common genetic variants in the IRS1 gene have been recently associated with insulin resistance and hyperinsulinemia. We examined whether the best-associated variant modifies the long-term changes in insulin resistance and body weight in response to weight-loss diets in the Pounds Lost Trial.

Methods and Results

We genotyped IRS1 rs2943641 in 738 overweight adults (61% were women) who were randomly assigned to one of four diets varying in macronutrient contents for 2 years. We assessed the progress in fasting insulin, insulin resistance (HOMA-IR) and weight loss by genotypes. At 6 months, participants with the risk-conferring CC genotype had greater decreases in insulin (P=0.009), HOMA-IR (P=0.015) and weight loss (P=0.058) than those without this genotype in the highest carbohydrate diet group, while an opposite genotype effect on changes in insulin and HOMA-IR (P≤0.05) was observed in participants assigned to the lowest carbohydrate diet group. No significant differences were observed across genotypes in other 2 diet groups. The tests for genotype by intervention interactions were all significant (P<0.05). At 2 years, the genotype effect on changes in insulin and HOMA-IR remained significant in the highest carbohydrate diet group (P<0.05). The highest carbohydrate diet led to a greater improvement of insulin and HOMA-IR (P for genotype-time interaction≤0.009) in participants with the CC genotype than those without this genotype across 2-year intervention.

Conclusions

Individuals with the IRS1 rs2943641 CC genotype might obtain more benefits in weight loss and improvement of insulin resistance than those without this genotype by choosing a high-carbohydrate and low-fat diet.

OBJECTIVE

To determine contributions of trunk and extremity adiposity to cardiometabolic risk factors (blood pressure, fasting blood glucose, HDL cholesterol, and triglycerides) among white and African American adults.

RESEARCH DESIGN AND METHODS

The sample consisted of 1,129 white women, 779 African American women, 1,012 white men, and 300 African American men.

RESULTS

Higher trunk adiposity was significantly associated with an increased risk of having two or more cardiometabolic risk factors among African American and white men and women. After adjustment for trunk and arm adiposity, higher leg adiposity was significantly associated with a decreased risk of having two or more cardiometabolic risk factors among white men and women and African American women.

CONCLUSIONS

In contrast with adverse risk with high trunk adiposity, high leg adiposity is associated with a decreased risk of having two or more cardiometabolic risk factors in both African American and white adults.

Dopamine (DA) and DA D2 receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and a progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10mg/kg and 20mg/kg) increased the number of active lever presses (10mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation.

OBJECTIVE

Consumption of sugar-sweetened beverages (SSBs), which include soft drinks, fruit drinks, iced tea, and energy and vitamin water drinks has risen across the globe. Regular consumption of SSBs has been associated with weight gain and risk of overweight and obesity, but the role of SSBs in the development of related chronic metabolic diseases, such as metabolic syndrome and type 2 diabetes, has not been quantitatively reviewed.

RESEARCH DESIGN AND METHODS

We searched the MEDLINE database up to May 2010 for prospective cohort studies of SSB intake and risk of metabolic syndrome and type 2 diabetes. We identified 11 studies (three for metabolic syndrome and eight for type 2 diabetes) for inclusion in a random-effects meta-analysis comparing SSB intake in the highest to lowest quantiles in relation to risk of metabolic syndrome and type 2 diabetes.

RESULTS

Based on data from these studies, including 310,819 participants and 15,043 cases of type 2 diabetes, individuals in the highest quantile of SSB intake (most often 1–2 servings/day) had a 26% greater risk of developing type 2 diabetes than those in the lowest quantile (none or <1 serving/month) (relative risk [RR] 1.26 [95% CI 1.12–1.41]). Among studies evaluating metabolic syndrome, including 19,431 participants and 5,803 cases, the pooled RR was 1.20 [1.02–1.42].

CONCLUSIONS

In addition to weight gain, higher consumption of SSBs is associated with development of metabolic syndrome and type 2 diabetes. These data provide empirical evidence that intake of SSBs should be limited to reduce obesity-related risk of chronic metabolic diseases.

Research on the conceptualization of adherence to treatment has not addressed a key question: Is adherence best defined as being a uni-dimensional or multi-dimensional behavioral construct? The primary aim of this study was to test which of these conceptual models best described adherence to a weight management program. This ancillary study was conducted as a part of the POUNDS LOST trial that tested the efficacy of four dietary macro-nutrient compositions for promoting weight loss. A sample of 811 overweight/obese adults was recruited across two clinical sites, and each participant was randomly assigned to one of four macronutrient prescriptions: (1) Low fat (20% of energy), average protein (15% of energy); (2) High fat (40%), average protein (15%); (3) Low fat (20%), high protein (25%); (4) High fat (40%), high protein (25%). Throughout the first 6 months of the study, a computer tracking system collected data on eight indicators of adherence. Computer tracking data from the initial 6 months of the intervention were analyzed using exploratory and confirmatory analyses. Two factors (accounting for 66% of the variance) were identified and confirmed: (1) behavioral adherence and (2) dietary adherence. Behavioral adherence did not differ across the four interventions, but prescription of a high fat diet (vs. a low fat diet) was found to be associated with higher levels of dietary adherence. The findings of this study indicated that adherence to a weight management program was best conceptualized as being multi-dimensional, with two dimensions: behavioral and dietary adherence.

The primary aim of this study was to test the association of early (first 6 months) adherence related to diet, self-monitoring, and attendance with changes in adiposity and cardiovascular risk factors. This study used data from the 24-month POUNDS LOST trial that tested the efficacy of four dietary macronutrient compositions for short-and long-term weight loss. A computer tracking system was used to record data on eight indicator variables related to adherence. Using canonical correlations at the 6 and 24 month measurement periods, early behavioral adherence was associated with changes in percent weight loss and waist circumference at 6 months (R = 0.52) and 24 months (R = 0.37), but was not associated with cardiovascular disease risk factor levels. Early dietary adherence was associated with changes in insulin at 6 months (R = 0.19), but not at 24 months (R = 0.08, ns). Early dietary adherence was not associated with changes in adiposity.

The worldwide consumption of sucrose, and thus fructose, has risen logarithmically since 1800. Many concerns about the health hazards of calorie-sweetened beverages, including soft drinks and fruit drinks and the fructose they provide, have been voiced over the past 10 years. These concerns are related to higher energy intake, risk of obesity, risk of diabetes, risk of cardiovascular disease, risk of gout in men, and risk of metabolic syndrome. Fructose appears to be responsible for most of the metabolic risks, including high production of lipids, increased thermogenesis, and higher blood pressure associated with sugar or high fructose corn syrup. Some claim that sugar is natural, but natural does not assure safety.

BACKGROUND

Essential hypertension results from the interaction of several genetic and environmental factors. Identification of genetic factors that modulate blood pressure (BP) response to interventions can lead to improved strategies for prevention and control. The purpose of this study was to identify genes that modulate BP response to dietary interventions.

METHODS

We used data and samples collected in two randomized feeding studies to determine the extent to which genetic architecture is associated with the effect on BP of sodium intake and the Dietary approaches to Stop Hypertension (DASH) dietary pattern. Participants in both trials were adults with above-optimal BP or unmedicated stage 1 hypertension. Genomic DNa was typed for several candidate genes.

RESULTS

The effect of sodium intake on BP differed by genotype at the angiotensinogen, β2-adrenergic receptor, and kallikrein loci. The effect of DASH dietary pattern on BP differed by genotype at the β2-adrenergic receptor locus.

CONCLUSIONS

These findings have implications for understanding the mechanism(s) through which diet affects BP, the heterogeneity of these effects, and the extent to which dietary interventions can modulate genetic predisposition.

OBJECTIVE

To measure ghrelin and energy intake in the laboratory after pioglitazone treatment.

RESEARCH DESIGN AND METHODS

This was a parallel, three-arm study with 51 obese diabetic subjects randomized to either 1) pioglitazone plus a portion-controlled diet (Pio+PC), 2) pioglitazone plus American Diabetes Association (ADA) dietary advice (Pio+ADA), or 3) metformin plus ADA advice (Met+ADA). Energy intake and the suppressive response of a meal on ghrelin were measured at weeks 0 and 16. Mixed models tested if changes from week 0 to 16 differed by group.

RESULTS

The Pio+ADA group had a significantly larger increase (P < 0.05) in energy intake ([adjusted means ± SE] 207 ± 53 kcal) compared with the Pio+PC (50 ± 46 kcal) and Met+ADA (52 ± 49 kcal) groups. Change in restraint and disinhibition (variables associated with eating behavior) mediated weight change. Ghrelin suppression increased in the Pio+ADA group, which gained weight.

CONCLUSIONS

A portion-controlled diet attenuated the increase in energy intake after pioglitazone. Ghrelin responded to weight change not pioglitazone exposure.

Activation of mu opioid receptors (MOR) makes animals hyperphagic and selectively increases their preference for a high fat diet independent of their dietary preference. The orexigenic peptide Agouti Related Peptide (AgRP) also produces hyperphagia and increased the preference for a high fat diet. In this paper, we tested the hypothesis that the effect of MOR on feeding behavior will be attenuated in the absence of the orexigenic peptide AgRP. Immunohistochemical studies demonstrated that MOR are co-localized on AgRP neurons located in the arcuate nucleus. This finding is consistent with a role of MOR in mediating the release of AgRP. Our data also demonstrated that the wild-type (FVB) animals preferred a diet high in fat whereas the AgRP knockout (AgRP KO) mice did not. mRNA expression of MOR in the hypothalamus was not significantly different between AgRP KO mice and their wild-type control. In a dose response experiment, the low dose (0.025μg) of a MOR agonist, DAMGO, increased cumulative food intake in wild-type and AgRP KO mice. The low and middle (0.25μg) dose of DAMGO significantly increased the amount of high fat diet eaten by the wild-type animals, but did not significantly change the amount of high fat diet eaten by the AgRP KO mice. The highest dose of DAMGO (2.5μg) reduced food intake in the control and AgRP KO mice, probably due to somnolence. These data demonstrate that the increased preference for a high fat diet after stimulation of MOR is attenuated in the absence of AgRP, but the increase in food intake (i.e. hyperphagia) is not.

Background

Pioglitazone (Pio) treatment induces weight gain in Type 2 diabetes mellitus (T2DM), which could worsen hepatic lipid accumulation, and alter adiponectin and high-sensitivity C-reactive protein (hs-CRP).

Objective

To compare changes in hepatic lipid, serum adiponectin and hs-CRP in diabetics treated with Pio (with and without weight gain) against metformin (Met) treatment, which produces weight loss.

Design

Fifty-one men and women with T2DM, naive to thiazolidinediones, entered a 16-week, open-label, parallel arm study, where participants were randomized to one of three groups: (1) Pio plus the American Diabetes Association diet (Pio+ADA); (2) Pio plus a portion control weight loss diet (Pio+PC), or (3) metformin plus ADA diet (Met+ADA).

Methods

Hepatic lipid was assessed with abdominal computed tomography (CT) and the serum adiponectin and hs-CRP by enzyme-linked immunosorbent assay at baseline and study end.

Results

Forty-eight subjects completed the study. The Pio+ADA group gained (mean±S.E.M.) 2.15±1.09 kg, while Pio+PC and Met+ADA group lost −2.59±1.25 and −3.21±0.7 kg, respectively. Pio-treated groups (Pio+ADA and Pio+PC) significantly decreased hepatic fat as indicated by increased liver density on CTscan [10.1±2.4: 11.4±1.0 Hounsfield units (HU)], compared with Met+ADA group (−2.4±3.1 HU). The Pio groups demonstrated significantly increased serum adiponectin, (8.6±1.5; 7.4±1.6 μg/ml) independent of weight change, compared to Met+ADA (−0.14±0.6 μgm/ml) group which lost weight. Serum hs-CRP decreased in groups showing weight loss (Pio+PC, −3.1±1.7 mg/l; Met+ADA, −1.5±1.2 mg/l) compared to Pio+ADA (1.8±3.0 mg/l) group that gained weight.

Conclusions

Pio treatment in T2DM significantly reduced hepatic lipid and increased adiponectin independent of weight change, while decreasing hs-CRP with weight loss.

Background

Osborne-Mendel (OM) rats are prone to obesity when fed a high fat diet, while S5B/Pl (S5B) rats are resistant to diet-induced obesity when fed the same diet. OM rats have a decreased satiation response to fatty acids infused in the gastrointestinal tract, compared to S5B rats. One possible explanation is that OM rats are less sensitive to the satiating hormone, glucagon-like peptide 1 (GLP-1). GLP-1 is produced in the small intestine and is released in response to a meal. The current experiments examined the role of GLP-1 in OM and S5B rats.

Methods

Experiment 1 examined preproglucagon mRNA expression in the ileum of OM and S5B rats fed a high fat (55% kcal) or low fat (10% kcal) diet. Experiment 2 investigated the effects of a 2h high fat meal following a 24h fast in OM and S5B rats on circulating GLP-1 (active) levels. Experiment 3 examined the effects of Exendin-4 (GLP-1 receptor agonist) administration on the intake of a high fat or a low fat diet in OM and S5B rats.

Results

Preproglucagon mRNA levels were increased in the ileum of OM rats compared to S5B rats and were increased by high fat diet in OM and S5B rats. OM and S5B rats exhibited a similar meal-initiated increase in circulating GLP-1 (active) levels. Exendin-4 dose-dependently decreased food intake to a greater extent in S5B rats, compared to OM rats. The intake of low fat diet, compared to the intake of high fat diet, was more sensitive to the effects of Exendin-4 in these strains.

Conclusions

These results suggest that though OM and S5B rats have similar preproglucagon mRNA expression in the ileum and circulating GLP-1 levels, OM rats are less sensitive to the satiating effects of GLP-1. Therefore, dysregulation of the GLP-1 system may be a mechanism through which OM rats overeat and gain weight.

Adiposity is more prevalent among individuals with a predominance of small, dense LDL (pattern B) than among those with larger LDL (pattern A). We tested for differences in resting energy expenditure (REE) and respiratory quotient (RQ) in overweight men with pattern A (n=36) or pattern B (n=60). Men consumed a standardized isoenergetic diet for 3 weeks after which a ~9 kg weight loss was induced by caloric deficit for 9 weeks, followed by 4 weeks of weight stabilization. REE and RQ were measured by indirect calorimetry before and after weight loss. Results were analyzed separately in pattern B men who converted to pattern A (B→A; n=35) and those who did not (B→B; n=25). At baseline, B→B men had higher trunk fat, triacylglycerol (TG) and insulin concentrations, HOMA-IR and smaller LDL particles compared to B→A men and baseline pattern A men who remained pattern A (A→A; n=35). REE normalized to fat-free mass did not change after weight loss. RQ decreased in A→A men, increased in B→A men and did not change significantly in B→B men after weight loss. Calculated fat oxidation rates paralleled the RQ results. Baseline plasma TG concentrations were positively correlated with RQ and inversely correlated with the magnitude of weight loss achieved for a given prescribed energy reduction in the entire study population. Pattern B men who converted to pattern A with weight loss may have an underlying impairment in fat oxidation that predisposes to both dyslipidemia and an impaired ability to achieve weight loss by energy restriction.

PURPOSE

To demonstrate how principal components analysis can be used to describe patterns of weight changes in response to an intensive lifestyle intervention

METHODS

Principal components analysis was applied to monthly percent weight changes measured on 2,485 individuals enrolled in the lifestyle arm of the Action for Health in Diabetes (Look AHEAD) clinical trial. These individuals were 45–75 years of age, with Type 2 diabetes and body mass indices >25 kg/m2. Associations between baseline characteristics and weight loss patterns were described using analyses of variance.

RESULTS

Three components collectively accounted for 97.0% of total intra-subject variance: a gradually decelerating weight loss (88.8%), early versus late weight loss (6.6%), and a mid-year trough (1.6%). In agreement with previous reports, each of the baseline characteristics we examined had statistically significant relationships with weight loss patterns. As examples, males tended to have a steeper trajectory of percent weight loss and to lose weight more quickly than women. Individuals with higher HbA1c tended to have a flatter trajectory of percent weight loss and to have mid-year troughs in weight loss compared to those with lower HbA1c.

CONCLUSIONS

Principal components analysis provided a coherent description of characteristic patterns of weight changes and is a useful vehicle for identifying their correlates and potentially for predicting weight control outcomes.

Objective

To identify differences in amount and distribution of fat and lean soft tissue in subjects with and without type 2 diabetes and to determine whether any differences are affected by race/ethnicity or sex.

Design

Overweight and obese (body mass index, BMI≥25 kg/m2) Black, White and Hispanic men (490) and women (825) with type 2 diabetes ([mean±SD] age 58.5±6.6; BMI 35.3±5.3) who had a baseline dual energy x-ray absorptiometry whole body scan at the time of enrollment in the Look Ahead clinical trial, and 242 healthy controls, 91 males and 151 females (age 55.3±8.6 y, BMI 30.7±4.2 kg/m2) who were participating in unrelated research and were scanned on the same densitometers.

Results

Adjusted for covariates, total fat mass was smaller in persons with type 2 diabetes than in controls (−1.4±0.3[SE]; 34.5 vs 35.8 kg, p<0.001) while trunk fat was larger (1.3±0.2[SE]; 19.9 vs 18.6 kg, p<0.001) and leg fat was smaller (−1.5±0.2[SE]; 10.7 vs 12.3 kg, p<0.001). The arms of subjects with type 2 diabetes did not have significantly less fat compared to controls. Adjusted trunk lean mass was larger in type 2 diabetes by 0.6 kg (28.4 vs 27.8 kg, p<0.001) while leg lean was smaller by 0.5 kg (18.1 vs 18.6 kg, p<0.001).

Conclusions

Type 2 diabetes is associated with less total fat, leg fat and leg lean mass and more truncal fat and lean mass than controls. The physiological processes producing these deviations in tissue distribution and their metabolic significance warrant further investigation.

(ClinicalTrials.gov number, NCT00017953)

OBJECTIVE

We hypothesized that, compared with obese subjects, patients with type 2 diabetes have a lower total adipocyte number with fewer small adipocytes.

RESEARCH DESIGN AND METHODS

Abdominal subcutaneous adipose tissue was obtained from lean and obese subjects with or without type 2 diabetes matched for BMI. Adipocyte size was measured by osmium fixation and sizing/counting in a Coulter counter. Adipocyte size and number subdistributions (small, medium, large, and very large) were determined.

RESULTS

Compared with obese subjects, type 2 diabetic patients had larger mean adipocyte size and 67% bigger very large adipocytes; the total adipocyte number was lower, but the fraction of small adipocytes was increased by 27%.

CONCLUSIONS

Total adipocyte cellularity is lower in type 2 diabetic subjects than in obese subjects. We found no evidence for depletion of small adipocytes in patients with type 2 diabetes. This suggests the presence of a defect in early maturation of adipocytes in patients with type 2 diabetes.

Background

Dietary studies designed to lower urinary albumin excretion rate (AER) typically reduce protein by increasing lower protein plant foods and reducing higher protein animal products.

Study Design

We evaluated AER while increasing protein intake in the Dietary Approaches to Stop Hypertension (DASH) Trial (randomized, parallel group, 8 week controlled feeding).

Setting & Participants

378 individuals without diabetes with prehypertension or stage I hypertension.

Intervention

The DASH diet, 18% energy from protein, emphasizes, among other features, lowfat dairy products; and the fruit/vegetable (FV) and Control diets, each with 15% energy from protein.

Outcome

AER

Measurements

We measured AER by immunoassay and covariates at baseline and after 8 weeks.

Results

Baseline AER had geometric mean ± standard error 4.0 ± 0.2 mg/24hr. Among 285 participants with baseline AER<7 mg/24hr, AER was unchanged by diet treatment (geometric mean 2.5 ± 0.2 mg/24hr in Control, 3.0 ± 0.2 mg/24hr in FV, 2.8 ± 0.2 mg/24hr in DASH). In contrast, among 93 participants with baseline AER ≥7 mg/24hr, end of feeding AER was lower in FV (6.6 ± 1.0 mg/24hr) than in Control (11.4 ± 1.8 mg/24hr (p=0.01) or DASH (11.7 ± 1.6 mg/24hr p = 0.005). The DASH and control diets were not different (p=0.9).

Limitations

Long term AER change not studied.

Conclusions

Reduction in AER after 8 weeks occurred only in those with high normal baseline AER in FV, in a pattern distinct from blood pressure reduction. The DASH diet did not increase AER despite 3% increase in energy from protein.

Pyrogultamylated arginine-phenylalanineamide peptide (QRFP) is strongly conserved across species and is a member of the family of RFamide-related peptides, with the motif Arg-Phe-NH2 at the C-terminal end. The precursor peptide for QRFP generates a 26-amino acid peptide (QRFP-26) and a 43-amino acid peptide (QRFP-43), both of which bind to the G protein-coupled receptor, GPR103. Recently, QRFP has been characterized in rats, mice and humans and has been reported to have orexigenic properties. In rodents, prepro-QRFP mRNA is expressed in localized regions of the mediobasal hypothalamus, a region implicated in feeding behavior. Increased intake of a high fat diet contributes to increased weight gain and obesity. Therefore, the current experiments investigated the effects of QRFP administration in rats and the effects of a high fat diet on prepro-QRFP mRNA and GPR103 receptor mRNA levels. Intracerebroventricular administration of QRFP-26 (3.0nM, 5.0nM) and QRFP-43 (1.0nM, 3.0nM) dose-dependently increased 1h, 2h, and 4h cumulative intake of high fat (55% fat), but not low fat (10% fat) diet. In Experiment 2, hypothalamic prepro-QRFP mRNA levels and GPR103 receptor mRNA levels were measured in rats fed a high fat or a low fat diet for 21 days. Prepro-QRFP mRNA was significantly increased in the ventromedial nucleus/arcuate nucleus of the hypothalamus of rats fed a high fat diet compared to those fed a low fat diet, while GPR103 mRNA levels were unchanged. These findings suggest that QRFP is a regulator of dietary fat intake and is influenced by the intake of a high fat diet.

BACKGROUND

The possible advantage for weight loss of a diet that emphasizes protein, fat, or carbohydrates has not been established, and there are few studies that extend beyond 1 year.

METHODS

We randomly assigned 811 overweight adults to one of four diets; the targeted percentages of energy derived from fat, protein, and carbohydrates in the four diets were 20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%. The diets consisted of similar foods and met guidelines for cardiovascular health. The participants were offered group and individual instructional sessions for 2 years. The primary outcome was the change in body weight after 2 years in two-by-two factorial comparisons of low fat versus high fat and average protein versus high protein and in the comparison of highest and lowest carbohydrate content.

RESULTS

At 6 months, participants assigned to each diet had lost an average of 6 kg, which represented 7% of their initial weight; they began to regain weight after 12 months. By 2 years, weight loss remained similar in those who were assigned to a diet with 15% protein and those assigned to a diet with 25% protein (3.0 and 3.6 kg, respectively); in those assigned to a diet with 20% fat and those assigned to a diet with 40% fat (3.3 kg for both groups); and in those assigned to a diet with 65% carbohydrates and those assigned to a diet with 35% carbohydrates (2.9 and 3.4 kg, respectively) (P>0.20 for all comparisons). Among the 80% of participants who completed the trial, the average weight loss was 4 kg; 14 to 15% of the participants had a reduction of at least 10% of their initial body weight. Satiety, hunger, satisfaction with the diet, and attendance at group sessions were similar for all diets; attendance was strongly associated with weight loss (0.2 kg per session attended). The diets improved lipid-related risk factors and fasting insulin levels.

CONCLUSIONS

Reduced-calorie diets result in clinically meaningful weight loss regardless of which macronutrients they emphasize.