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.