Highly active antiretroviral therapy dysregulates proliferation and differentiation of human pre-adipocytes.

Aim: To investigate the mechanism(s) by which potential effects of multi-drug highly-active antiretroviral therapy contributes to lipodystrophy syndrome.

Methods: Preadipocytes from healthy donors were assessed for proliferation and differentiation in the presence of nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) individually and in combination. Effects on proliferation were assessed with a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay and effects on differentiation were assessed from glycerol-3-phosphate dehydrogenase (GP DH) activity and quantitation of Oil Red O staining for intracellular lipid.

Changes in diabetes medications in the Diabetes and Periodontal Therapy Trial and their effect on hemoglobin A1c (HbA1c).

Objective: Evaluate the effect of medications and medication changes during the Diabetes and Periodontal Therapy Trial (DPTT) on the primary study outcome, namely, change in hemoglobin A1c (HbA1c) at 6months following baseline.

Methods: The DPTT set strict criteria for changes in diabetes medications. Medication change was defined as: change in dose of any 1 oral hypoglycemic agent by more than two-fold, change in dose of insulin of >10% and/or addition or subtraction of an oral hypoglycemic agent, insulin or non-insulin injectable agents.

Systemic Inflammatory Biomarkers and Their Association With Periodontal and Diabetes-Related Factors in the Diabetes and Periodontal Therapy Trial, A Randomized Controlled Trial.

Background: The present study evaluates effects of non-surgical periodontal treatment on serum biomarkers in patients with type 2 diabetes mellitus (t2DM) and chronic periodontitis who participated in the Diabetes and Periodontal Therapy Trial (DPTT); and associations among diabetes markers, serum biomarkers, and periodontal measures in these patients.

Methods: DPTT participants randomized to receive immediate or delayed non-surgical periodontal therapy were evaluated at baseline and 6 months. Serum samples from 475 participants with 6-month data were analyzed for the following biomarkers: 1) high sensitivity C-reactive protein; 2) E-selectin; 3) tumor necrosis factor (TNF)-α; 4) vascular cell adhesion molecule (VCAM); 5) interleukin (IL)-6; 6) IL-8; 7) intercellular adhesion molecule; and 8) IL-10.

An evaluation of recruitment methods utilized for a clinical trial with periodontal and diabetes enrollment criteria: the Diabetes and Periodontal Therapy Trial.

Background: Diabetes and its complications are a major United States public health concern.

Methods: The Diabetes and Periodontal Therapy Trial (DPTT) evaluated whether non-surgical treatment of periodontal disease influenced diabetes management among persons with Type 2 diabetes and periodontitis. The aim of this study was to evaluate DPTT's many recruitment strategies in terms of enrollment success.

Chromium Therapy for Insulin Resistance Associated with HIV-Disease.

Objective: With the advent of highly active anti-retroviral therapy, HIV disease has become a chronic condition, but with a number of metabolic complications including insulin resistance and diabetes mellitus, dyslipidemia and hypertension and an increased incidence of atherosclerosis. The aim of the current study was to test the safety and efficacy of chromium picolinate for HIV- associated insulin resistance.

Materials/methods: The study was a randomized, double-blind, placebo-controlled trial with subjects receiving 500μg of chromium picolinate or placebo twice daily for two months.

The effect of nonsurgical periodontal therapy on hemoglobin A1c levels in persons with type 2 diabetes and chronic periodontitis: a randomized clinical trial.

Importance: Chronic periodontitis, a destructive inflammatory disorder of the supporting structures of the teeth, is prevalent in patients with diabetes. Limited evidence suggests that periodontal therapy may improve glycemic control.

Objective: To determine if nonsurgical periodontal treatment reduces levels of glycated hemoglobin (HbA1c) in persons with type 2 diabetes and moderate to advanced chronic periodontitis.

Peripheral fat loss and decline in adipogenesis in older humans.

Objective: Aging is associated with a redistribution of body fat including a relative loss of subcutaneous peripheral fat. These changes in body fat can have important clinical consequences since they are linked to increased risk of metabolic complications. The causes and mechanisms of loss of peripheral fat associated with aging are not clear.

Rosiglitazone-Mediated Effects on Skeletal Muscle Gene Expression Correlate with Improvements in Insulin Sensitivity in Individuals with HIV-Insulin Resistance.

Rosiglitazone, an agonist of peroxisome proliferator activated receptor (PPARγ), improves insulin sensitivity by increasing insulin-stimulated glucose uptake into muscle tissue. This study was undertaken to assess changes in expression of PPAR-regulated genes in muscle tissue following treatment of HIV-associated insulin resistance with rosiglitazone. Muscle gene expression was assessed in twenty-two seronegative HIV subjects (control), 21 HIV-infected individuals with normal insulin sensitivity (HIV-IS) and 19 HIV-infected individuals with insulin resistance (HIV-IR).

Effect of ritonavir and atazanavir on human subcutaneous preadipocyte proliferation and differentiation.

Protease inhibitors (PIs) have been implicated in the development of HIV-associated lipodystrophy through a reduction in the differentiation of preadipocytes. While atazanavir (ATV) is associated with fewer clinical metabolic abnormalities in the short-term, the effects of long-term exposure are not known. ATV effects on preadipocyte replication or differentiation would indicate the potential for long-term problems.

Feeding acutely stimulates fibrinogen synthesis in healthy young and elderly adults.

Fibrinogen is a positive acute-phase protein and its hepatic synthesis is enhanced following inflammation and injury. However, it is not clear whether fibrinogen synthesis is also responsive to oral nutrients and whether the response to a meal may be affected by age. Our aim in this study was to investigate the acute effect of oral feeding on fibrinogen synthesis in both young and elderly men and women.

Importance of the high-molecular-mass isoform of adiponectin in improved insulin sensitivity with rosiglitazone treatment in HIV disease.

The present study was designed to investigate the relationship of isoforms of adiponectin to insulin sensitivity in subjects with HIV-associated insulin resistance in response to treatment with the thiazolidinedione, rosiglitazone. The two isoforms of adiponectin, HMW (high-molecular-mass) and LMW (low-molecular-mass), were separated by sucrose-gradient-density centrifugation. The amount of adiponectin in gradient fractions was determined by ELISA.

Influence of age on the association of retinol-binding protein 4 with metabolic syndrome.

Objective: The relationships of retinol-binding protein 4 (RBP4) with insulin sensitivity and body fat distribution have been investigated in a few recent studies with conflicting results. This may have been due to differences in ages of the subjects in the different studies. The aim of this study was to investigate whether the association of RBP4 and insulin sensitivity and percent trunk fat are influenced by age.

Endothelial adhesion molecules are associated with inflammation in subjects with HIV disease.

Background: The presence of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1) is associated with elevated risk of cardiovascular disease. Subjects with human immunodeficiency virus (HIV) disease have multiple risk factors for cardiovascular disease, including elevated serum lipid levels, insulin resistance, and elevated levels of ICAM-1 and VCAM-1. This study assessed the variables associated with elevated adhesion molecule levels in this patient population.

Role of recombinant human growth hormone in HIV-associated wasting and cachexia: pathophysiology and rationale for treatment.

Background: Wasting, or cachexia, is a significant, debilitating, and potentially life-threatening complication of HIV infection. It is associated with reduced strength and functional ability, reduced ability to withstand opportunistic infections, and increased risk of mortality. Although the incidence of HIV-associated wasting may have declined since the introduction of highly active antiretroviral therapy (HAART), it continues to be a concern in this patient population.

Limb fat to trunk fat ratio in elderly persons is a strong determinant of insulin resistance and adiponectin levels.

Background: Similar to lipodystrophy syndromes, aging results in increased visceral adiposity with loss of subcutaneous adipose tissue in the extremities. The hypothesis of this study is that the distribution of limb fat to trunk fat (LF/TF) ratio in elderly persons has a stronger correlation than trunk fat alone to insulin resistance and adiponectin levels.

Methods: Thirty-eight elderly participants were divided into an insulin-resistant (IR) group and an insulin-sensitive (IS) group.

Wall suction applied to needle muscle biopsy - a novel technique for increasing sample size.

Background: The needle biopsy technique described by Bergström is the most commonly used technique to obtain samples to assess muscle metabolism. Sampling of muscle, particularly the vastus lateralis, has become an essential tool in biomedical and clinical research. Optimal sample size is critical for availability of tissue for processing.

Retinol-binding protein 4 is associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes.

Background: Adipose tissue is responsible for releasing various adipokines that have been related to insulin resistance. Understanding the relationship of these adipokines to insulin resistance may foster the development of new treatments for diabetes.

Objectives: The primary objective of this study was to determine whether an association between retinol-binding protein 4 (RBP4) and insulin resistance exists in nonobese individuals without a family history or diagnosis of diabetes.

Response of albumin synthesis to oral nutrients in young and elderly subjects.

Background: The synthesis of albumin after oral ingestion of nutrients provides a means of storing amino acids, which can be made available during periods of fasting.

Objective: This study was undertaken to see whether the response of albumin synthesis to the oral intake of nutrients is compromised in elderly subjects.

Design: Albumin synthesis was determined from the incorporation of 43 mg l-[(2)H(5)]phenylalanine/kg body wt.

Chromium picolinate improves insulin sensitivity in obese subjects with polycystic ovary syndrome.

Trivalent chromium (1000 microg), as chromium picolinate, given without change in diet or activity level, caused a 38% mean improvement in glucose disposal rate in five obese subjects with polycystic ovary syndrome who were tested with a euglycemic hyperinsulinemic clamp technique. This suggests that chromium picolinate, an over-the-counter dietary product, may be useful as an insulin sensitizer in the treatment of polycystic ovary syndrome.

The increase in human muscle protein synthesis induced by food intake is similar when assessed with the constant infusion and flooding techniques.

Food intake is accompanied by a stimulation of muscle protein synthesis. However, the reported magnitude of the response differs with different methods of measurement. The aim of this study was to assess whether the response to feeding is dependent on the technique used for measurement when length and amount of feeding are controlled.

Chronic loss of subcutaneous adipose tissue in HIV-associated lipodystrophy may not be associated with accelerated apoptosis.

HIV-associated lipodystrophy (HIV-LD) is characterized by a loss of adipose tissue from the subcutaneous compartment. Previously reported data suggested that this loss of adipose tissue was the result of an increased rate of apoptosis in subcutaneous adipose tissue (SAT). The present study examined the rate of apoptosis in SAT with a sensitive ligase-mediated polymerase chain reaction technique to amplify DNA ladders.