Ketosis-prone diabetes is heterogeneous. Its causes could include novel beta-cell functional defects. To characterize such defects, 103 patients with diabetic ketoacidosis were evaluated for beta-cell autoimmunity and human leukocyte antigen (HLA) class II alleles, with longitudinal measurements of beta-cell function and biochemical and clinical parameters. They were classified into four A beta groups, based on the presence of glutamic acid decarboxylase (GAD)65, GAD67, or IA-2 autoantibodies (A+ or A-) and beta-cell functional reserve (beta+ or beta-). The group distribution was: 18 A+beta-, 23 A-beta-, 11 A+beta+, and 51 A-beta+. Collectively, the two beta- groups differed from the two beta+ groups in earlier onset and longer duration of diabetes, lower body mass index, less glycemic improvement, and persistent insulin requirement. HLA class II genotyping showed that the A-beta- group differed from the A+beta- group in having lower frequencies of two alleles strongly associated with autoimmune type 1 diabetes susceptibility: DQA*03 and DQB1*02. Similarly, the A-beta+ group differed from the A+beta+ group in having a lower frequency of DQB1*02. Ketosis-prone diabetes comprises at least four etiologically distinct syndromes separable by autoantibody status, HLA genotype, and beta-cell functional reserve. Novel, nonautoimmune causes of beta-cell dysfunction are likely to underlie the A-beta+ and A-beta- syndromes.

Tuberculosis causes more extensive and life-threatening disease in patients with HIV infection than in immunocompetent persons.

Objective To determine whether adipose tissue functions as a reservoir for HIV-1. Design We examined memory CD4 T cells and HIV DNA in adipose tissue-stromal-vascular-fraction (AT-SVF) of 5 patients (4 ART-treated and 1 untreated). To determine if adipocytes stimulate CD4 T cells and regulate HIV production, primary human adipose cells were co-cultured with HIV-infected CD4 T cells. Methods AT-SVF T cells were studied by flow cytometry, and AT-SVF HIV DNA (Gag and Env) was examined by nested PCR and sequence analyses. CD4 T cell activation and HIV production were measured by flow cytometry and ELISA. Results AT-SVF CD3 T cells were activated (>60% CD69+) memory CD4 and CD8 T cells in uninfected and HIV-infected persons, but the AT-SVF CD4/CD8 ratio was lower in HIV patients. HIV DNA (Gag and Env) was detected in AT-SVF of all 5 patients examined by nested PCR, comparably to other tissues (PBMC, lymph node, or thymus). In co-culture experiments, adipocytes increased CD4 T cell activation and HIV production ∼2-3 fold in synergy with gamma-chain cytokines IL2, IL7, or IL15. These effects were mitigated by neutralizing antibodies against IL6 and integrin-α1β1. Adipocytes also enhanced T cell viability. Conclusions Adipose tissues of ART-treated patients harbor activated memory CD4 T cells and HIV DNA. Adipocytes promote CD4 T cell activation and HIV production in concert with intrinsic adipose factors. Adipose tissue may be an important reservoir for HIV.

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Compared with healthy tuberculin reactors, Mycobacterium tuberculosis-stimulated peripheral blood mononuclear cells from tuberculosis patients had diminished production and mRNA expression of the Th1 cytokines gamma interferon and interleukin 2 (IL-2), with no change in production and mRNA expression for the Th2 cytokines IL-4, IL-10, and IL-13. These results were confirmed by evaluation of T cells and CD4 ؉ cells. At the level of systemic T cells, development of tuberculosis is associated with diminished Th1 but not enhanced Th2 responses.