The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as a predictor of insulin resistance, ß-cell function, and diabetes in Hispanics and African Americans.

OBJECTIVE: The TG/HDL-C ratio is used as a marker of insulin resistance (IR) in Caucasians; however, there is limited data in other ethnic groups. We hypothesized that the TG/HDL-C ratio is associated with IR in Hispanics and African Americans (AA). RESEARCH DESIGN AND METHODS: Data from the Insulin Resistance Atherosclerosis Family Study was examined for associations between TG/HDL-C ratio and IR, ß-cell function and incident diabetes in non-diabetic Hispanics (n = 872, 63% female) and AA (n = 371, 61% female). Insulin sensitivity index (SI) and disposition index (DI) from frequently-sampled intravenous glucose tolerance tests were used as markers of IR and ß-cell function respectively. Incident type 2 diabetes was determined by fasting glucose ≥ 126 mg/dl or initiation of anti-hyperglycemia agents over 5 year follow-up. RESULTS: Higher TG/HDL-C ratio was associated with IR in Hispanic and AA men and women (P < 0.0002), as well as ß-cell function in Hispanic women and AA men and women (P < 0.02). TG/HDL-C predicted incident type 2 diabetes in women (area under the curves 0.703 and 0.795 for Hispanics and AA respectively). CONCLUSIONS: Similar to Caucasians, the TG/HDL-C ratio can be used to identify IR in Hispanics and AA, and may predict type 2 diabetes in women.

The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as a predictor of ß-cell function in African American women.

BACKGROUND: The TG/HDL-C ratio is used as a marker of insulin resistance (IR) in Caucasians. However, there are conflicting data on TG/HDL-C ratio as a predictor of IR in African Americans. Compared to Caucasians, African Americans have lower TG levels and increased insulin levels despite a greater risk for diabetes. We hypothesized that the TG/HDL-C ratio is predictive of IR and/or ß-cell function in African American (AA) women. METHODS: Non-diabetic AA women (n = 41) with a BMI > 25 kg/m(2) underwent frequently sampled intravenous glucose tolerance test (FSIGTT). Insulin sensitivity (SI) and the acute insulin response to glucose (AIRg) were measured using minimal model and ß-cell function was determined by disposition index (DI = S I*AIRg). IR was defined as the lowest tertile of SI (<1.8 × 10(-4)min(-1)/µU/ml) and inadequate ß cell compensation was defined as the lowest tertile of DI (< 900). Data were analyzed using logistic regression models and area under the receiver operating characteristic curve (AUC-ROC). An AUC-ROC > 0.70 was defined as significant discrimination. RESULTS: The mean (± SD) age was 38.5 ± 11.3 years, with BMI of 33.5 ± 6.7 kg/m(2) and fasting glucose of 86.5 ± 10.5 mg/dL. The AUC-ROC for the prediction of DI < 900 was 0.74 indicating that a higher TG/HDL-C ratio was associated with decreased DI. However, the AUC-ROC for prediction of IR or low AIRg (<335 µU/ml) was not significant. CONCLUSION: This study confirmed that the TG/HDL-C ratio is a poor predictor of IR in AA women. However, we did show an inverse association between the TG/HDL-C ratio and ß-cell function, suggesting that this simple tool may effectively identify AA women at risk for DM2.

Multiple Disease Associations in Autoimmune Polyglandular Syndrome Type II.

OBJECTIVE: Autoimmune polyglandular syndrome type II (APS II) is characterized by adrenal insufficiency (Addison's disease), autoimmune thyroid disease, and/or type 1 diabetes mellitus (DM1). Multiple other autoimmune diseases have been associated with APS II. Here we report a case of a patient with APS II who over the course of 10 years developed Addison's disease, hypothyroidism, DM1, Hashimoto's encephalopathy, vitiligo, celiac disease, seronegative arthritis, and ulcerative colitis. This is a particularly aggressive course of APS II, and this combination of autoimmune diseases has not been previously reported. METHODS: A 25-year-old female with a history of ulcerative colitis (UC), celiac disease, and DM1 presented to our institution with mental status changes. She was diagnosed with Hashimoto's encephalopathy and treated with high-dose steroids and intravenous immunoglobulin (IVIG). She recovered well from her encephalopathy but her posthospitalization course was complicated due to the development of Addison's disease, vitiligo, seronegative arthritis, and hypothyroidism. RESULTS: The current understanding of APS II and its autoimmune disease associations are briefly summarized. The association of UC and Hashimoto's encephalopathy with APS II is novel and discussed in detail. CONCLUSION: A case of a patient with APS II with a dramatic development of 8 autoimmune diseases over 10 years is described. The novel APS II developments of Hashimoto's encephalopathy and UC are discussed. This case highlights the potential complexity and severity of the clinical course of APS II.

The inositol phosphatase SHIP-2 down-regulates FcgammaR-mediated phagocytosis in murine macrophages independently of SHIP-1.

FcgammaR-mediated phagocytosis of IgG-coated particles is a complex process involving the activation of multiple signaling enzymes and is regulated by the inositol phosphatases PTEN (phosphatase and tensin homolog deleted on chromosome 10) and SHIP-1 (Src homology [SH2] domain-containing inositol phosphatase). In a recent study we have demonstrated that SHIP-2, an inositol phosphatase with high-level homology to SHIP-1, is involved in FcgammaR signaling. However, it is not known whether SHIP-2 plays a role in modulating phagocytosis. In this study we have analyzed the role of SHIP-2 in FcgammaR-mediated phagocytosis using independent cell models that allow for manipulation of SHIP-2 function without influencing the highly homologous SHIP-1. We present evidence that SHIP-2 translocates to the site of phagocytosis and down-regulates FcgammaR-mediated phagocytosis. Our data indicate that SHIP-2 must contain both the N-terminal SH2 domain and the C-terminal proline-rich domain to mediate its inhibitory effect. The effect of SHIP-2 is independent of SHIP-1, as overexpression of dominant-negative SHIP-2 in SHIP-1-deficient primary macrophages resulted in enhanced phagocytic efficiency. Likewise, specific knockdown of SHIP-2 expression using siRNA resulted in enhanced phagocytosis. Finally, analysis of the molecular mechanism of SHIP-2 down-regulation of phagocytosis revealed that SHIP-2 down-regulates upstream activation of Rac. Thus, we conclude that SHIP-2 is a novel negative regulator of FcgammaR-mediated phagocytosis independent of SHIP-1.