Family history of type 2 diabetes, abdominal adipocyte size and markers of the metabolic syndrome.

BACKGROUND/OBJECTIVES: A major risk factor of type 2 diabetes mellitus (T2DM) is a positive family history of diabetes. First degree relatives (FDR) of patients with T2DM are more insulin resistant and are reported to have larger abdominal subcutaneous adipocytes than adults without a family history. Our objectives were to assess whether FDR of T2DM are associated with larger abdominal adipocytes independent of age, sex and abdominal subcutaneous fat and to assess whether a family history of T2DM is also independently related to femoral adipocyte size, as well as visceral fat and fasting plasma triglyceride (TG) concentrations. METHODS: We extracted adipocyte size, body composition, plasma TG and demographic data of non-diabetic research participants of previous studies conducted in our laboratory. We ascertained the family history of T2DM from the electronic medical records. Multivariate regression analysis was used to assess whether FDR of T2DM are more likely to have other risk factors after adjusting for known covariates. RESULTS: Of 604 participants, 148 were FDR of T2DM. Although abdominal and femoral adipocyte size was greater in FDR of T2DM than those without a family history (0.74±0.33 vs 0.63±0.33 µg lipid per cell, P<0.001; 0.81±0.29 vs 0.72±0.33 µg lipid per cell, P=0.01, respectively), this was confounded by FDR of T2DM being older, having greater body mass index and percent body fat. A family history of T2DM was a significant predictor of abdominal adipocyte size after adjustment for age and body fat distribution parameters in females (total R2=0.5, P<0.0001), but not in males. A family history of T2DM was not independently predictive of femoral adipocyte size, visceral fat area or TG. CONCLUSIONS: Female FDR of T2DM have larger abdominal, but not femoral, adipocytes, even after accounting for age and body fat distribution.

Adipose tissue fatty acid storage factors: effects of depot, sex and fat cell size.

BACKGROUND/OBJECTIVES: Patterns of postabsorptive adipose tissue fatty acid storage correlate with sex-specific body fat distribution. Some proteins and enzymes participating in this pathway include CD36 (facilitated transport), acyl-CoA synthetase (ACS; the first step in fat metabolism) and diacylglycerol acetyltransferase (DGAT; the final step of triglyceride synthesis). Our aim was to better define CD36, ACS and DGAT in relation to sex, subcutaneous fat depots and adipocyte size. SUBJECTS/METHODS: Data were collected from studies conducted at Mayo Clinic between 2004 and 2012. Abdominal and femoral subcutaneous fat biopsy samples must have been collected in the postabsorptive state from healthy males and premenopausal females. Body composition was measured with dual-energy X-ray absorptiometry and abdominal computerized tomography scans. Adipocyte size (microscopy), CD36 protein content (enzyme-linked immunosorbent assay) and ACS and DGAT enzyme activities were measured. Data are presented as medians and 25th, 75th quartiles. RESULTS: Males (n=60) and females (n=78) did not differ by age (37; 28, 46 years), body mass index (28.4; 24.6, 32.1 kg m(-)(2)) or abdominal (0.60; 0.45, 0.83 µg lipid per cell) and femoral adipocyte size (0.76; 0.60, 0.94 µg lipid per cell). Femoral ACS and DGAT were greater in females than males when expressed per mg lipid (ACS: 73 vs. 55 pmol/mg lipid/min; DGAT: 5.5 vs. 4.0 pmol/mg lipid/min; P<0.0001 for both) and per 1000 adipocytes (ACS: 59 vs. 39 pmol per min per 1000 adipocytes; DGAT: 4.3 vs 3.1 pmol per min per 1000 adipocytes; P⩽0.0003 for both). There were no differences in abdominal fat storage factors between sexes. ACS and DGAT decreased as a function of adipocyte size (P<0.0001 for both). The decrease in ACS was greater in males and abdominal subcutaneous fat. There were no sex differences in CD36 in either fat depot, nor did it vary across adipocyte size. CONCLUSIONS: Facilitated transport of fatty acids by CD36 under postabsorptive conditions would not be different in those with large vs small adipocytes in either depot of both sexes. However, intracellular trafficking of fatty acids to triglyceride storage by ACS and DGAT may be less efficient in larger adipocytes.

African American women exhibit similar adherence to intervention but lose less weight due to lower energy requirements.

BACKGROUND: African American (AA) women have been shown to lose less weight than Caucasian women in response to behavioral interventions. Our objective was to examine adherence to intervention and metabolic factors that may explain this difference. DESIGN AND SUBJECTS: We examined longitudinal changes in body weight and energy expenditure (EE), and objective assessment of physical activity (PA) and energy intake (EI) during 6 months of a weight-loss intervention program, including prescribed calorie restriction and increased PA in 66 Caucasian and 39 AA severely obese women. Comparisons were also made in 25 Caucasian and 25 AA women matched for initial body weight. RESULTS: The AA women lost 3.6 kg less weight than Caucasian women. Total daily EE (TDEE) and resting metabolic rate (RMR) adjusted for fat free mass (FFM) were significantly lower in the AA women, whereas the decrease in RMR in response to weight loss was greater in Caucasian women. Adherence to the prescribed PA and change in PA in response to intervention were similar in AA and Caucasian women. Prescribed EI (1794±153 and 1806±153 kcal per day) and measured EI during intervention (2591±371 vs 2630±442 kcal per day) were nearly identical in matched AA and Caucasian women. However, the AA women lost significantly less body weight due to lower energy requirements (2924±279 vs 3116±340 kcal per day; P<0.04), resulting in a lower energy deficit (333±210 vs 485±264 kcal per day). CONCLUSION: Adherence to the behavioral intervention was similar in AA and Caucasian women. However, neglecting to account for the lower energy requirements in AA women when calculating the energy prescription resulted in a lower level of calorie restriction and, hence, less body weight loss. Therefore, to achieve similar weight loss in AA women, the prescribed caloric restriction cannot be based on weight alone, but must be lower than in Caucasians, to account for lower energy requirements.

Reduced skeletal muscle oxidative capacity and elevated ceramide but not diacylglycerol content in severe obesity.

OBJECTIVE: The link between a reduced capacity for skeletal muscle mitochondrial fatty acid oxidation (FAO) and lipotoxicity in human insulin resistance has been the subject of intense debate. The objective of this study was to investigate whether reduced FAO is associated with elevated acyl CoA, ceramide, and diacylglycerol (DAG) in severely obese insulin resistant subjects. METHODS: Muscle biopsies were conducted in lean (L, 22.6 ± 0.5 kg/m(2) , n = 8), Class I (CI, 32.1 ± 0.4 kg/m(2) , n = 7) and Class II&III obese (CII&III, 45.6 ± 1.1 kg/m(2) , n = 15) women for acyl CoA, sphingolipid and DAG profiling. Intramyocellular triglyceride (IMTG) content was determined by histology. FAO was assessed by incubating muscle homogenates with [1-C]palmitate and measuring CO2 production. Cardiolipin content was quantified as an index of mitochondrial content. Lipid metabolism proteins, DGAT1, PLIN5, and PNPLA2 were quantified in biopsy samples by western blot. RESULTS: CII&III were more insulin resistant (HOMA-IR: 4.5 ± 0.5 vs. 1.1 ± 0.1, P < 0.001), and had lower FAO (∼58%, P = 0.007) and cardiolipin content (∼31%, P = 0.013) compared to L. IMTG was elevated in CI (P = 0.04) and CII&III (P = 0.04) compared to L. Sphingolipid content was higher in CII&III compared to L (13.6 ± 1.1 vs. 10.3 ± 0.5 pmol/mg, P = 0.031) whereas DAG content was not different among groups. DGAT1 was elevated in CII&III, and PLIN5 was elevated in CI compared to L. CONCLUSIONS: Severe obesity is associated with reduced muscle oxidative capacity and occurs concomitantly with elevated IMTG, ceramide and insulin resistance.

Associations between accelerometer-derived physical activity and regional adiposity in young men and women.

OBJECTIVE: Empirical evidence supports an inverse relationship between physical activity (PA) and adiposity, but studies using detailed measures of both are scarce. The relationship between regional adiposity and accelerometer-derived PA in men and women are described. DESIGN AND METHODS: Cross-sectional analysis included 253 participants from a weight loss study limited to ages 20-45 years and BMI 25-39.9 kg m(-2) . PA data were collected with accelerometers and expressed as total accelerometer counts and average amount of time per day accumulated in different intensity levels [sedentary, light-, and moderate-to-vigorous intensity PA (MVPA)]. Accumulation of time spent above 100 counts was expressed as total active time. Computed tomography (CT) was used to measure abdominal and adipose tissue (AT). Multivariate linear regression analyses were used to assess the relationship between regional adiposity (dependent variable) and the various PA levels (independent variable), and were executed separately for men and women, adjusting for wear time, age, race, education, and BMI. RESULTS: Among males, light activity was inversely associated with total AT (ß = -0.19; P = 0.02) as well as visceral AT (VAT) (ß = -0.30; P = 0.03). Among females sedentary time was positively associated with VAT (ß = 0.11; P = 0.04) and total active time was inversely associated with VAT (ß = -0.12; P = 0.04). CONCLUSIONS: Findings from this study suggest that PA intensity level may influence regional adiposity differently in men and women. Additional research is needed in larger samples to clarify the difference in these associations by sex, create recommendations for the frequency, duration and intensity of PA needed to target fat deposits, and determine if these recommendations should differ by sex.

High energy expenditure masks low physical activity in obesity.

OBJECTIVE: To investigate energy expenditure in lean and obese individuals, focusing particularly on physical activity and severely obese individuals. DESIGN: Total daily energy expenditure (TDEE) was assessed using doubly labeled water, resting metabolic rate (RMR) by indirect calorimetry, activity energy expenditure (AEE) by difference and time spent in physical activity by multisensor activity monitors. SUBJECTS: In all, 177 lean, Class I and severely obese individuals (age 31-56 years, body mass index 20-64 kg m(-2)) were analyzed. RESULTS: All components of energy expenditure were elevated in obese individuals. For example, TDEE was 2404±95 kcal per day in lean and 3244±48 kcal per day in Class III obese individuals. After appropriate adjustment, RMR was similar in all groups. Analysis of AEE by body weight and obesity class indicated a lower AEE in obese individuals. Confirming lower physical activity, obese individuals spent less time engaged in moderate-to-vigorous physical activity (2.7±1.3, 1.8±0.6, 2.0±1.4 and 1.2±1.0 h per day in lean, Class I, Class II and Class III individuals) and more time in sedentary behaviors. CONCLUSIONS: There was no indication of metabolic efficiency in even the severely obese, as adjusted RMR was similar across all groups. The higher AEE observed in the obese is consistent with a higher cost of activities due to higher body weight. However, the magnitude of the higher AEE (20-25% higher in obese individuals) is lower than expected (weight approximately 100% higher in Class III individuals). Confirming a lower volume of physical activity in the obese, the total time spent in moderate-to-vigorous physical activity and average daily metabolic equivalent of task level were lower with increasing obesity. These findings demonstrate that high body weight in obese individuals leads to a high TDEE and AEE, which masks the fact that they are less physically active, which can be influenced by duration or intensity of activity, than in lean individuals.

Use of the bougie in simulated difficult intubation. 1. Comparison of the single-use bougie with the fibrescope.

We studied the success rates for tracheal intubation in 64 healthy patients during simulated grade III laryngoscopy after induction of anaesthesia, using either the single-use bougie or oral flexible intubating fibrescope, both in conjunction with conventional Macintosh laryngoscopy. Patients were randomly allocated to either simulated grade IIIa or grade IIIb laryngoscopy, and also to one of the two study devices. Success rates for tracheal intubation (primary outcome measure) and times taken to achieve intubation (secondary outcome measure) were recorded. For the simulated grade IIIa laryngoscopy group, the fibreoptic scope was more successful than the bougie (16/16 successful intubations vs. 8/16; p = 0.02). For the simulated grade IIIb laryngoscopy group, the fibreoptic scope was also more successful than the bougie (8/16 successful intubations vs. 1/16; p = 0.02), but clearly use of the fibreoptic scope was not as successful as it had been in simulated grade IIIa laryngoscopy (p = 0.04). With either device, median (range) total tracheal intubation times for successful attempts with either grade of laryngoscopy were less than 60 s (19-109) and there were no clinically important differences. We conclude that the fibrescope used in conjunction with Macintosh laryngoscopy is a more reliable method of tracheal intubation than the single-use bougie in both types of grade III laryngoscopy. This finding has implications for the management of patients in whom grade III laryngoscopy is encountered unexpectedly after induction of anaesthesia, and also for the management of patients previously known to have grade III view at laryngoscopy.

Use of the bougie in simulated difficult intubation. 2. Comparison of single-use bougie with multiple-use bougie.

We studied the success rates for tracheal intubation in 32 healthy, anaesthetised patients during simulated grade IIIa laryngoscopy, randomised to either the multiple-use or the single-use bougie. Success rates (primary end-point) and times taken (secondary end-point) to achieve tracheal intubation were recorded. The multiple-use bougie was more successful than the single-use one (15/16 successful intubations vs. 9/16; p = 0.03). With either device, median [range] total tracheal intubation times for successful attempts were < 54 [24-84] s and there were no clinically important differences between these times. We conclude that the multiple-use bougie is a more reliable aid to tracheal intubation than the single-use introducer in grade IIIa laryngoscopy.