Lipodystrophy causes

In combination with other antiretroviral agents, stavudine has caused fatal lactic acidosis in some patients. It is also associated with motor weakness in which case it should be discontinued. Peripheral neuropathy is the most common toxicity associated with stavudine, which is more prevalent at high doses (4mg/kg per day). Neuropathy in these patients generally is associated with numbness, tingling or pain in feet or hands. Patients treated with the combination of stavudine and didanosine may also exhibit liver function abnormalities (hepatic steatosis) and pancreatitis. It may also be associated with the etiology of HIV lipodystrophy syndrome. 

The adverse effects of saquinavir are mild but predominantly they are related to GI discomfort including abdominal discomfort, nausea, diarrhea and vomiting. Lipodystrophy may result from its long-term use. Rarely, saquinavir causes confusion, weakness, ataxia, seizures, headache and liver abnormalities. 

Peripheral lipodystrophy in patients is characterized by fat wasting of the face, limbs, buttocks, and upper trunk, while central adiposity can cause an increase in belly size ( Crix-belly or protease pouch ) and an increase in the dorsocervical fat pad, creating the appearance of a buffalo hump (988-990). These effects may be related to a glucocorticoid-like action. The increase in belly size is... 

Insulin, administered subcutaneously, may cause either lipoatrophy or lipohypertrophy. Lipoatrophy is the breakdown of adipose tissue at the insulin injection site causing a depression in the skin at the injection site and occasionally at distant sites also. It may be the result of an immune response or the use of less than pure insulin. Some findings suggest that total lipodystrophy syndrome results from the inflammatory destructive process of adipose tissue (Yanagawa et al., 1990). Injection of human or purified porcine insulin into the site over a 2-4-week period may result in subcutaneous fat accumulation. 

The two forms of lipodystrophy, though less common today in people with diabetes, still occur. Lipohypertrophy is caused by many injections into the same injection site. Due to insulin s anabolic actions, a raised fat mass is present at the injection site with resultant variable insulin absorption. Lipoatrophy, in contrast, is thought to be due to insulin antibodies, with destruction of fat at the site of injection. Injection away from the site with more purified insuhn is recommended, though several reports of lipoatrophy with lispro have been reported. 

Adverse effects of protease inhibitors are similar to those seen with reverse transcriptase inhibitors. In addition, this group of drugs causes metabolic disturbances, particularly insulin resistance and hyperglycaemia, and fat redistribution leading to raised plasma lipid levels, which increases the risk of heart disease. These effects are collectively known as lipodystrophy syndrome, which appears to be similar to what happens with long-term corticosteroid use. 

Ritonavir induces its own metabolism, and gradual dose escalation over the first 2 weeks may minimize early intolerance. When ritonavir is used as the sole protease inhibitor, it should be initiated at 300 mg every 12 hours and escalated gradually to 600 mg every 12 hours by day 14 of therapy. Ritonavir causes dose-dependent elevations in serum total cholesterol and triglycerides, as well as other signs of lipodystrophy, and could increase the long-term risk of atherosclerosis in some patients. 

Atazanavir Atazanavir is a peptide protease inhibitor that is active against both HlV-1 and HlV-2. Absorption is increased by food and it is recommended that the drug be administered with a meal. Absorption may be pH dependent, because proton pump inhibitors substantially reduce drug concentration after oral dosing. Like indinavir, atazanavir frequently causes unconjugated hyperbilirubinemia. The drug may be less likely than other HIV protease inhibitors to cause lipodystrophy. 

In particular in mice, the rapid loss of adipose tissue is repeatedly reported in combination with an increase in liver weight and lipid content, or even liver steatosis (7, 11—13). These effects appear to be due to the development of lipodystrophy the loss of functional adipose tissue. As dietary fat cannot be taken up by the adipose tissue, the burden shifts to other tissues such as liver and muscle. A study by Tsuboyama-Kasaoka et al. reported that CLA intake did not cause the extreme adipose tissue loss or increased hepatic lipids in mice supplemented with CLA in a high fat (34%) diet (14). This indicates that the lipodystrophy effects are not caused by CLA directly but by the ablated or dysfunctional adipose tissue. 

The link between hyperinsulinemia and the extreme adipose tissue loss in lean mice models is further demonstrated by a more recent study by Tsuboyoma-Kasaoka et al. (14). The authors reported that a level of 1% CLA in a diet with 34% fat resulted in a more moderate fat decrease in mice compared to 1% CLA in lower fat diets. The insulin resistance found in mice fed CLA in low fat diets was no longer observed in mice fed the high-fat diet. These results indicate that the effects on insulin levels in mice treated with CLA in a low-fat diet were not a CLA-specific effect, but were caused by the development of lipodystrophy. As discussed by Nadler and Attie (28), both obesity and lipodystrophy in mice are associated with a fatty liver, intramuscular fat deposition, increased plasma concentration of insulin, and insulin resistance. In both conditions, there is no functional adipose tissue and the lipogenic burden shifts from the adipose tissue to non-adipose tissue, mainly liver and muscle. 

Lipodystrophy is a feature of treatment with antiretroviral drugs, particularly protease inhibitors and nucleoside reverse transcriptase inhibitors. It has been attributed to inhibition of mitochondrial DNA polymerase y [53 ]. It is associated with other metabolic alterations, such as lactic acidosis, dyslipide-mia, and insulin resistance, and may in turn be associated with an increase in the longterm risk of cardiovascular diseases [54, 55 ]. It causes loss of fat from the face and limbs and can be accompanied by accumulation of fat in the trunk and the back of the neck. It affects up to 50% of the patients taking highly active antiretroviral drug treatment (HAART). 

Stavudine The patterns of change in body fat and metabolism caused by stavudine have been studied in 42 South African subjects [59 J. At baseline, those who went on to develop lipodystrophy were fatter and had greater skinfold thickness and higher insulin concentrations than those who never developed lipodystrophy. Triglyceride and cholesterol concentrations increased in both groups, but in those who developed lipodystrophy blood lactate and glucose concentrations increased more and insulin concentrations increased less. 

In addition to reducing adipose tissue mass, the tl0cl2 CLA isomer has been linked to increased insuhn resistance in men who have symptoms of the metabolic syndrome. A CLA mixture also appeared to cause hyperinsulinemia in C57BL/6J mice that was accompanied by severe adipose tissue ablation and decreased leptin levels. The effects of the CLA mixture on adipose tissue depletion were reversed by continuous leptin infusion. In a follow-up study, decreasing the amount of a CLA mixture from 1 to 0.1 g/100 g diet, while increasing the amoimt of total fat in the diet from 4 to 34 g/100 g diet, did not lead to lipodystrophy, while fat mass was modestly reduced. Insuhn resistance was present in the group fed the 1 g CLA/100 g diet, but not present in the 0.1 g CLA/100 g diet group. 

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