Lipodystrophy: some comments from Nelson Vergel

Nelson Vergel, long-time AIDS treatment activist and community expert on lipodystrophy, recently posted a good set of guides to understanding this topic:

–D4T and AZT linked to lipoatrophy; some protease inhibitors linked to insulin resistance, which can be related to higher triglycerides and fat cell size in some patients

–exercise helpful for maintaining lean body mass; anabolic steroids for help in regaining normal weight

–supplements like omega-3/fish oil and niacin to help statins and fibrates to lower bad cholesterol (LDL), triglycerides and increasing good cholesterol (HDL)

Also included in the post are reviews of some regimen-switching strategies to counter lipodystrophy.

“Unfortunately,” Nelson concludes, more research is still needed on “lower glycemic index diets, good comparison data of what happens to visceral fat when different protease inhibitors or non-nucleosides are used with Truvada in naives with low and higher CD4 at baseline, diet/exercise combinations, and other supplements like carnitine and others.”

Read the full entry at thebody.com.

“Prevention of Diabetes with Nutritional Supplements”

“Prevention of Diabetes with Nutritional Supplements” is the title of a research project funded in 2007 by the National Center for Complementary and Alternative Medicine (an NIH Center). The researchers at University of California – Davis are investigating alpha lipoic acid and a combination of alpha lipoic acid and the omega-3 fatty acid EPA as means to prevent or delay onset of Type 2 diabetes. The researchers are hypothesizing that the combination of ALA and the omega-3 fatty acid (also known as eicosapentaenoic acid, a component of fish oil supplements) may have effect against insulin resistance associated with adult-onset diabetes, and against impairment of pancreatic function.

See also the NYBC entries on the supplements mentioned in this research:

Arctic Omega fish oil (with EPA)

Alpha Lipoic Acid (sometimes called just “Lipoic Acid”)

CATIE Treatment Update: Chromium supplements for metabolic problems in people with HIV

The Canadian AIDS Treatment Information Exchange (CATIE) website has posted news about a new study of chromium supplements for metabolic abnormalities in people with HIV. Here’s the introduction:

Can chromium supplementation help body shape?

A research team at Toronto General Hospital found a statistical link between low chromium levels in the blood and HIV infection, particularly in HAART users. The Toronto team also noted that some of the symptoms of chromium deficiency are similar to the metabolic problems—higher-than-normal levels of blood sugar and insulin and the weakened effects of insulin—in some HIV positive people. So the team later conducted a double-blind study with a modest dose of chromium vs. placebo in people with HIV infection. Their findings suggest that chromium supplementation may confer some benefit(s) in people with HIV/AIDS (PHAs) in the short-term.

Read the entire article on the CATIE website.

This April/May 2008 post from CATIE follows after news of several other studies regarding chromium supplementation and metabolic complications in people with HIV. In February 2008, for example, the 15th Conference on Retroviruses and Opportunistic Infections in Boston included a report
entitled “Chromium supplementation decreases insulin resistance and trunk fat.”

For more background on this dietary supplement, see the NYBC entry CHROMIUM.

Chromium and glucose tolerance factor

Since there are a number of federally funded research studies dealing with chromium supplementation and blood glucose levels (see other posts under “Chromium” on this blog), we’d be very interested in hearing about the experience of our members in using this product.

Jarrow Chromium GTF
Here’s an extract of the manufacturer’s product description:

Chromium GTF (Jarrow) Each bottle, 100 caps. Each capsule, 200 mcg of chromium (in a food matrix of 100 mg of Saccharomyces cerevisiae nutritional yeast).

Chromium has been shown to be deficient in populations that consume high carbohydrate diets and especially high in simple sugars. Chromium is an important component in eliciting the glucose tolerance factor (GTF) action upon serum glucose and more importantly enhancing the effectiveness of insulin in glucose disposal into the cell. This makes sense. The more carbs you eat, the more your body will need the chromium to manage them. This could help offset the losses of chromium used up in that effort to take care of the carbs. Of course, this points to another logical step: reduce carb intake!! Check out the glycemic index of the foods you eat and focus on those with lower numbers. This index tells you how rapidly a particular carbohydrate turns into sugar. Check out the URL below for more information on the glycemic index:
http://www.hsph.harvard.edu/nutritionsource/carbohydrates.html

Fish oil, inflammation and metabolic complications in HIV: a clinical trial and related research

We noticed with interest that Dr. Todd T Brown, a Johns Hopkins researcher who has studied body fat changes in people with HIV, has recently started a wide-ranging investigation of fish oil / omega-3 fatty acid supplementation as a way of preventing/treating metabolic complications associated with highly active antiretroviral therapy (HAART). Metabolic complications, including fat wasting, central body fat build-up, insulin resistance, high cholesterol and triglycerides, and bone loss, have been some of the major side effects experienced by people with HIV on medication, so it’s quite interesting to see research that may “connect the dots” and find links between these various problems. 

Furthermore, this is a study that focuses on fish oil / omega-3 fatty acids, which have quite recently gained more respect in US medical circles, especially as a means of preventing/treating cardiovascular disease, but also for a surprising effect on depression. (You can read more about this aspect of fish oil supplementation in the “depression” category on this blog.)

 Here’s the description of Dr. Brown’s research, as provided on the website of NCCAM/NIH, one of the major sponsors of the study:

Abstract: DESCRIPTION (provided by applicant): The overall goal of this proposal is to understand the role of inflammatory cytokines in the metabolic and skeletal abnormalities in HIV disease and to determine whether omega-3 fatty acid supplementation, in the form of fish oil, will alter the pathophysiology of these clinical disorders. Complementary and alternative medicines (CAM) are used widely among HIV-infected patients, often with the hope of preventing or treating complications associated with highly active antiretroviral therapy (HAART). Metabolic abnormalities, including peripheral fat wasting, central adiposity, insulin resistance, and dyslipidemia, and skeletal abnormalities (reduced bone mineral density and high bone turnover), are common in HIV-infected patients on HAART, yet their relationship is unclear. We hypothesize that these metabolic and skeletal abnormalities are related by abnormal inflammatory cytokine expression and that these conditions can be improved with fish oil, a widely-used CAM agent with anti-inflammatory properties. We have the following specific aims: 1) To understand the association between the metabolic and skeletal abnormalities in HIV-infected subjects and their relationship to inflammation, 2) To determine whether treatment with omega-3 fatty acids will have hypotriglyeridemic, anti-inflammatory, and anti-bone resorptive effects in a randomized trial of HIV-infected patients, and 3) To clarify the mechanisms of action of omega-3 fatty acids, namely the effect on lipolysis and bone turnover using stable isotope infusion techniques. To accomplish our specific aims, I intend to do a secondary analysis of data from two cohorts of HIV-infected subjects, and to then perform a randomized trial using a standardized fish oil product. These results will help to define the pathophysiology of the metabolic and skeletal abnormalities in HIV and evaluate the efficacy and potential mechanisms of action of an important complementary treatment […]

(According to the published information, the clinical trial of fish oil is scheduled to run from 2006-2010.)

Note: An interview with Dr. Brown on body fat changes in people with HIV can be found on the website of our friends at www.thebody.com.

New research on Chromium supplemention’s potential in the prevention of Type 2 Diabetes and Coronary Artery Disease

Here’s another federally-funded study of chromium supplementation to counter insulin resistance and potentially help prevent the development of Type 2 Diabetes and Coronary Artery Disease.

Investigator: Dr. UMESH MASHARANI, Univ. of California at San Francisco

Sponsor: NCCAM/National Institutes of Health

Abstract: DESCRIPTION (provided by applicant): Background: Chromium is an essential nutrient for the maintenance of normal glucose tolerance. While studies of chromium supplementation in patients with type 2 diabetes (T2D) have indicated that this agent lowers glucose and insulin levels, its cellular mechanism of action is not welt understood. Studies both in humans and in cell culture suggest that chromium enhances the insulin signaling pathway. We propose, therefore, to study chromium’s effects on insulin-stimulated glucose uptake in a well characterized population of non-obese, non-diabetic subjects with insulin resistantance. This population is ideal for an analysis of the effects of chromium on insulin action, because they are as insulin resistant as T2D patients but do not have the important confounder of hyperglycemia. Because these insulin resistant subjects are at risk for the development of T2D, the Metabolic Syndrome, and coronary artery disease (CAD), a demonstration of the beneficial effects of chromium on insulin action could ultimately have important public health consequences. Hypotheses: (1) Chromium will improve insulin sensitivity in a general population of non-obese, insulin-resistant, non-diabetic subjects; and (2) The improvement of insulin action by chromium is due to its effects on the major components of the insulin signling pathway (insulin receptor, IRS proteins, PI 3-kinase, PKB/AKT and GLUT4); and/ or regulators of the insulin signaling pathway (PTP 1B, PC-1, IKK, NF-KappaB and PKC) Methods: The insulin sensitivity of 180 subjects will be initially estimated by homeostasis model assessment. The most insulin resistant subjects will then be randomized to 16 weeks of therapy with either chromium or placebo. To quantitate chromium-induced improvements in both in insulin sensitivity and the insulin signaling pathway, euglycemic hyperinsulinemic clamps with muscle biopsies will be performed before and after treament. Anticipated Results and Significance: We believe these studies will (1) confirm the beneficial effect of chromium on insulin sensitvity; (2) further our understanding of the molecular mechanisms of chromium action; and (3) form a basis for a larger project examining the long term efficacy of chromium in preventing the developement of T2D and CAD.

Novel Therapy for Glucose Intolerance in HIV Disease (Chromium picolinate)

This research is being funded by NCCAM, the federal government’s chief dietary supplement research agency. It builds on past knowledge about the role of an inexpensive dietary supplement, chromium, for management of diabetes (insulin resistance/glucose intolerance). This research study is directed especially to the case of people with HIV on multi-drug regimens, who experience insulin resistance/glucose intolerance at a high rate. 

——

Investigator: Dr. Marie C Gelato, State University of New York at Stony Brook 

Abstract: DESCRIPTION (provided by applicant): Multi-drug regimens in HIV disease are associated with an incidence of insulin resistance of at least 50%. Insulin resistance is associated with the development of dyslipidemia, type 2 diabetes, and hypertension. This constellation of metabolic abnormalities is known to cause accelerated atherosclerosis in patients with type 2 diabetes. The current guidelines from the American Diabetes Association and the American College of Endocrinologists recommends screening for glucose intolerance and treatment for patients at high risk of diabetes. This proposal seeks to establish a treatment option for insulin resistance / glucose intolerance in HIV/AIDS prior to the transition to overt diabetes. Chromium picolinate is a dietary supplement that has been shown to improve insulin sensitivity in patients with type 2 diabetes mellitus and, in a preliminary study, in HIV+ patients. This dietary supplement has a wide margin of safety and may provide substantial therapeutic benefit without serious side-effects. This proposal will test the hypothesis that chromium picolinate improves insulin-stimulated glucose uptake by increasing the insulin receptor-mediated tyrosine phosphorylation of insulin receptor substrate-1, resulting in increased activity of phosphatidylinositol 3-kinase. The hypothesis will be addressed in two specific aims. Specific Aim 1 will assess quantitative improvements in insulin-mediated glucose disposal in a double-blind, placebo-controlled study of chromium supplementation with 1000 microgram (19.2 mu/mol) of chromium as chromium picolinate, over a two month course of therapy of subjects with glucose intolerance (defined with an oral glucose tolerance test, OGTT). Both safety and efficacy (improved glucose disposal with a hyperinsulineminc, euglycemic clamp and insulin secretion, OGTT) will be evaluated. The cellular mechanism for improved insulin sensitivity with chromium supplementation will be determined in Specific Aim 2 by assessing the effect of chromium supplementation on the insulin-stimulated activity of insulin receptor substrate-1-associated phosphatidylinositol 3-kinase in biopsies of adipose tissue. Thus, this research will document the therapeutic benefit of chromium supplementation for insulin resistance / glucose intolerance in HIV disease and will provide a mechanistic framework to explain how chromium supplementation enhances insulin action.