Low serum high density lipoprotein cholesterol level (HDL-C) < 40 mg/dL in men and < 50 mg/dL in women are a significant independent risk factor for cardiovascular disease (CVD), and are often observed in patients with hypertriglyceridemia, obesity, insulin resistance, and diabetes. Patients with marked deficiency of HDL-C (< 20 mg/dL) in the absence of secondary causes are much less common (< 1% of the population). These patients may have homozygous, compound heterozygous, or heterozygous defects involving the apolipoprotein (APO)AI, ABCA1, or lecithin:cholesterol acyl transferase genes, associated with Apo A-I Deficiency, ApoA-I Variants, Tangier Disease, Familial Lecithin:Cholesteryl Ester Acyltransferase Deficiency, and Fish Eye Disease. There is marked variability in laboratory and clinical presentation, and DNA analysis is necessary for diagnosis. These patients can develop premature CVD, neuropathy, kidney failure, neuropathy, hepatosplenomegaly and anemia. Treatment should be directed at optimizing all non-HDL risk factors.

Purpose of review Our purpose was to examine recent advances in our knowledge of high density lipoprotein (HDL) metabolism, composition, function, and coronary heart disease (CHD), as well as marked HDL deficiency states due to mutations at the apolipoprotein (apo) A-I, ATP binding cassette transfer protein A1 (ABCA1), and lecithin cholesterol acyltransferase (LCAT) gene loci. Recent findings It has been documented that apoA-I, myeloperoxidase (MPO), and paraoxonase 1 (PON1) form a complex in HDL that is critical for HDL binding and function. MPO has a negative impact on HDL function, while PON1 has a beneficial effect. Patients that lack apoA-I develop markedly premature CHD. Patients that lack ABCA1 transporter function have only very small discoidal preβ-1 HDL, and develop hepatosplenomegaly, intermittent neuropathy and premature CHD, although significant heterogeneity for these disorders has been reported. Patients with LCAT deficiency have abnormal small discoidal low density lipoproteins and HDL particles, and develop kidney failure. Enzyme replacement therapy is being developed for the latter disorder. Summary Recent data indicates that proteins other than apoA-I and apoA-II such as MPO and PON1 have important effects on HDL function. There has been considerable recent progress made in our understanding of HDL protein content and function.

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 a family history of T2DM is associated with larger abdominal adipocytes independent of age, sex, and abdominal subcutaneous fat and to assess whether FDR 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 a 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/cell, P < 0.001; 0.81 ± 0.29 vs 0.72 ± 0.33 µg lipid/cell, P=0.01, respectively), this was confounded by FDR of T2DM being older, having greater BMI’s 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 FDR of T2DM females have larger abdominal, but not femoral, adipocytes, even after accounting for age and body fat distribution.

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Background: Some previous studies have indicated that a low basal metabolic rate (BMR) is an independent predictor of future weight gain, but low rates of follow-up and highly select populations may limit the ability to generalize the results. Objective: We assessed whether adults with a low BMR gain more weight than do adults with a high BMR who are living in a typical Western environment. Design: We extracted BMR, body-composition, demographic, and laboratory data from electronic databases of 757 volunteers who were participating in our research protocols at the Mayo Clinic between 1995 and 2012. Research study volunteers were always weight stable, had no acute illnesses and no confounding medication use, and were nonsmokers. The top and bottom 15th percentiles of BMR, adjusted for fat-free mass (FFM), fat mass, age, and sex, were identified. Follow-up electronic medical record system data were available for 163 subjects, which allowed us to determine their subsequent weight changes for $3 y (mean: w9.7 y). Results: By definition, the BMR was different in the high-BMR group (2001 6 317 kcal/d; n = 86) than in the low-BMR group (1510 6 222 kcal/d; n = 77), but they were comparable with respect to age, body mass index, FFM, and fat mass. Rates of weight gain were not greater in the bottom BMR group (0.3 6 1.0 kg/y) than in the top BMR group (0.5 6 1.5 kg/y) (P = 0.17). Conclusion: Adults with low BMRs did not gain more weight than did adults with high BMRs, implying that habitual differences in food intake or activity counterbalance variations in BMR as a risk factor for weight gain in a typical Western population.Am J Clin Nutr 2016;104:959-63.

Background With rising prevalence of morbid obesity, the number of bariatric surgeries performed each year has been increasing worldwide. The objective of this meta-analysis was to assess the risk of kidney stones following bariatric surgery. Methods A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through July 2015. Only studies reporting relative risks, odd ratios or hazard ratios (HRs) to compare risk of kidney stones in patients who underwent bariatric surgery versus no surgery were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Results Four studies (One randomized controlled trial and three cohort studies) with 11,348 patients were included in analysis to assess the risk of kidney stones following bariatric surgery. The pooled RR of kidney stones in patients undergoing bariatric surgery was 1.22 (95% CI, 0.63-2.35). The type of bariatric surgery subgroup analysis demonstrated an increased risk of kidney stones in patients following Roux-en-Y gastric bypass (RYGB) with the pooled RR of 1.73 (95% CI, 1.30-2.30) and a decreased risk of kidney stones in patients following restrictive procedures including laparoscopic banding or sleeve gastrectomy with the pooled RR of 0.37 (95% CI, 0.16-0.85). Conclusions Our meta-analysis demonstrates an association between RYGB and increased risk of kidney stones. Restrictive bariatric surgery, on the other hand, may decrease kidney stone risk. Future study with long-term follow-up data is needed to confirm this potential benefit of restrictive bariatric surgery.

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Some studies indicate that basal metabolic rate is greater winter than the summer, suggesting a role for brown fat in human thermogenesis. We examined whether there are clinically meaningful differences in basal metabolic rate under thermoneutral conditions between winter and summer months in inhabitants of Rochester, Minnesota. We collated data from 220 research volunteers studied in the winter (December 1 – February 28) and 214 volunteers studied in the summer (June 1 – August 31), 1995–2012. Basal metabolic rate was measured by indirect calorimetry and body composition by dual-energy X-ray absorptiometry. The effect of season on basal metabolic rate was tested using multivariate regression analysis with basal metabolic rate as the dependent variable and fat free mass, fat mass, age, sex, and season as the independent variables. The groups were comparable with respect to age, body mass index, fat mass and fat free mass. There was no significant difference in basal metabolic rate between winter and summer groups (1667±322 vs 1669±330 kcal/day). Both winter and summer basal metabolic rates were strongly predicted by fat free mass (Pearson’s r=0.75 and r=0.77, respectively, p<0.0001). Using multiple linear regression analysis, basal metabolic rate was significantly, independently predicted by fat free mass, fat mass, age and sex, but not season. We conclude that the lack of seasonal variation of thermoneutral basal metabolic rate between winter and summer suggests that modern, Western populations do not engage thermogenically detectable brown fat activity during periods of living in a cold climate.