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) and will predict type 2 diabetes. RESEARCH DESIGN AND METHODS:A multiethnic cohort from the Insulin Resistance Atherosclerosis Family Study was examined to investigate associations between TG/HDL-C ratio and IR, β-cell function and incident diabetes. The cohort included non-diabetic Hispanics (n=872, 63% female) and AA (n=371, 61% female) followed for 5 years. Insulin sensitivity index (S I ) and disposition index (DI) from frequently-sampled intravenous glucose tolerance tests were used as markers of IR and β-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 insulin resistance in both Hispanic and AA men and women (P <0.0002). It was also associated with β-cell function in Hispanic women

FcγR-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 FcγR 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 FcγR-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 FcγR-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 FcγR-mediated phagocytosis independent of SHIP-1. (Blood. 2006;107:813-820)

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A 65-year-old man was referred to our clinic for management of type 1 diabetes. He was diagnosed with type 1 diabetes at age 18 years and has developed nonproliferative diabetic retinopathy and albuminuria. His insulin regimen consisted of insulin glargine 8 units in the morning and 6 units in the evening and insulin aspart with meals (6 units with breakfast, 6 units with lunch, 8 units with dinner, and a correction factor of 1:50 >150 mg/dL; 8.3 mmol/L). He also had a past medical history of depression, hypertension, hyperlipidemia, and coronary artery disease (CAD). His family history was significant for a father with CAD. He denied any tobacco, alcohol, or illicit drug use. At the time of consultation, his weight was 100 kg. He was afebrile, blood pressure was elevated at 152/86 mmHg, and pulse was 68. His physical exam was unremarkable. His most recent hemoglobin A1c (HbA1c) was 8.4%.