The immunoregulatory cytokine interleukin 6 (IL-6) directly upregulates production of human immunodeficiency virus (HIV) in acutely as well as in chronically infected cells of monocytic lineage. In addition, IL-6 synergizes with tumor necrosis factor alpha (TNF-alpha) in the induction of latent HIV expression. Unlike TNF-alpha, upregulation of viral expression induced by IL-6 alone does not occur at the transcriptional level and it is not associated with accumulation of HIV RNA. However, when IL-6 and TNF-alpha synergistically stimulate HIV production, accumulation of HIV RNA and increased transcription are observed, indicating that IL-6 affects HIV expression at multiple (transcriptional and post-transcriptional) levels.
Tumor necrosis factor a (TNF-a) is an immunoregulatory cytokine capable of inducing viral expression in cells chronically infected with the human immunodeficiency virus (HIV), such as the promonocytic line U1 and the Tlymphocytic line ACH-2. In the present study, we demonstrate an autocrine mechanism of TNF-a-mediated HIV induction.
Aim: This observational study in patients with type 2 diabetes failing oral agent therapy with or without basal insulin was conducted to assess whether addition and self‐titration of biphasic insulin aspart 70/30 (BIAsp 30) could achieve American Association of Clinical Endocrinologists (AACE)/International Diabetes Federation (IDF) and American Diabetes Association (ADA) glycemic targets (HbA1c≤6.5 and <7%).
Methods: Enrolled patients (n = 100, HbA1c≥7.5 and ≤10%) were ≥18 years of age, had diabetes ≥12 months and had received a stable antidiabetic regimen for at least 3 months [minimum of two oral antidiabetic drugs (OADs) or at least one OAD plus once‐daily basal insulin ≤60 U]. Patients discontinued prior basal insulin and added one injection of BIAsp 30 (12 U or 70–100% of prior basal insulin dose within 15 min of dinner initiation). Patients self‐titrated their BIAsp 30 dose with investigator guidance every 3 or 4 days to achieve pre‐breakfast fasting blood glucose (FBG) of 80–110 mg/dl. At 16 weeks, a pre‐breakfast injection of 6 U of BIAsp 30 was added if week 15 HbA1c exceeded 6.5%; the added dose was titrated to achieve pre‐dinner BG of 80–110 mg/dl. After an additional 16 weeks, 3 U of pre‐lunch BIAsp 30 was added if HbA1c exceeded 6.5%. This added dose was adjusted based on 2‐h post‐lunch BG to achieve postprandial glucose of 100–140 mg/dl. Subjects achieving an HbA1c≤6.5% at 15 and 31 weeks completed the study at weeks 16 and 32 respectively.
Results: Addition of once‐daily BIAsp 30 before dinner enabled 21% of the patients to achieve AACE and IDF targets (HbA1c≤6.5%) and 41% to achieve ADA targets (HbA1c <7%). With two daily injections of BIAsp 30, these glycaemic goals were achieved by 52 and 70% of subjects. With three daily BIAsp 30 injections, 60% of patients achieved HbA1c≤6.5%, and 77% achieved HbA1c <7.0%.
Conclusions: This clinical trial demonstrates that initiation of once‐daily BIAsp 30 to type 2 diabetes patients poorly controlled on various OAD regimens was an effective treatment approach for achieving glycaemic goals. Additional patients safely achieved these goals by increasing the number of BIAsp 30 injections from one to two, and then, if uncontrolled, from two to three doses per day. Eventually, most patients previously uncontrolled on OADs with or without basal insulin were controlled by the addition and vigorous titration of BIAsp 30 to oral agent therapy.
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