Insulins lipodystrophy

A number of adipose tissue disorders have been reported. These include conditions of lipodystrophy (where adipose tissue is abnormal but not necessarily absent) and lipoatrophy. Examples of lipodystrophy are lipomas, Dercum s disease and insulin lipodystrophy. Lipoatrophy may be partial or total. 

Levandoski, L. A., White, N. H., and Santiago, J. V., 1982, Localized skin reactions to insulin Insulin lipodystrophies and skin reactions to pumped subcutaneous insulin therapy. Diabetes Care 1) 6-10. 

Fig. 32. The 30-year-old male patient with acquired generalized lipodystrophy (AGE) shows lacking lipids in the subcutaneous layer and in the musculature in a Ti-weighted spin-echo image (a) and in a fat selective image (b). Only marrow fat in the tibia and fibula of the patient seems to be not affected by the disease. Comparison between a spectrum from a insulin resistant subject without AGE (c) and the spectrum from the AGE patient (d) reveals that the AGE patient has nearly lacking EMCE and markedly reduced IMCE content.

Unwanted effects. Hypoglycemia results from absolute or relative overdosage (see p. 260). Allergic reactions are rare—locally redness at injection site, atrophy of adipose tissue (lipodystrophy) systemically urticaria, skin rash, anaphylaxis. Insulin resistance can result from binding to inactivating antibodies. A possible local lipohypertrophy can be avoided by alternating injection sites. 

Highly purified (single component) and human Insulins Local insulin allergy, immunologic insulin resistance, injection-site lipodystrophy temporary insulin use (ie, surgery, acute stress type 2 diabetes, gestational diabetes) newly diagnosed diabetic patients. 

The number and size of daily doses, time of administration, and diet and exercise require continuous medical supervision. Dosage adjustment may be necessary when changing types of insulin. Rotate administration sites to prevent lipodystrophy. Do not administer within 1 inch of the same site for 1 month. It may be best to rotate sites within an area rather than rotating areas. 

Lipodystrophy Rarely, administration of insulin subcutaneously can result in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue). 

Somogyi effect, including rebound hyperglycemia with chronically excessive insulin dosages systemicallergic reaction, marked by rash, angioedema, and anaphylaxis lipodystrophy or depression at injection site due to breakdown of adipose tissue lipo-hypertrophy or accumulation of subcutaneous tissue at injection site due to inadequate site rotation Rare... 

Some patients receiving indinavir exhibit nephrolithiasis/urolithiasis including flank pain that may be accompanied by hematuria. The frequency of nephrolithiasis is dependent on the period of treatment with indinavir. Other side effects associated with indinavir include insulin resistance, hyperglycemia, asymptomatic hyperbilirubinemia, HIV lipodystrophy syndrome and skin abnormalities. Indinavir should not be coadministered with drugs that affect the cytochrome P-450 system (CYP3A4). Antacids are not recommended within 2 h of its administration, specifically didano-sine containing an antacid buffer. 

The effects of insulin are modified by various factors. The speed and extent of absorption of insulin depends, for example, on the site of injection (1), the depth of the subcutaneous injection, skin temperature (2), the presence of lipodystrophy, and variation in the extent of inactivation of injected insulin. The disposal of insulin depends on many factors. Exercise and hard work lower the blood glucose and thereby increase the effect of insulin. Infections and obesity reduce its effect. The timing of food intake and the composition of meals are also related to the action of insulin. A thin layer of fat, as sometimes occurs in the upper arm or in the thighs of thin men, can result in intramuscular injection, leading to faster absorption of long-acting insulins. This can reduce the absorption time by half (3). The major factors that affect the fate of injected insulin (and thereby also its risks) are listed in Table 1 (4). 

Lipodystrophy, lipoatrophy, or lipohypcrtrophy can be a consequence of chronic local insulin reactions that can be elicited by less pure as well as by highly purified preparations (140), but such reactions can also develop at sites distant to the injection. 

For therapy of local lumps, extravasation, etc., one should first seek to improve the injection technique. Substitution with highly purified insulin is recommended. Injection with purified insulin into the affected area may speed up resorption of the lumps. Lipodystrophy or lipoa-trophy improve after switching to highly purified human or insulin lispro. Lipohypertrophy, on the other hand, often fails to respond to changes in the insulin regimen (161). Varying the injection site may help, but differences in absorption rate then have to be taken into account. 

Valenta LJ, Elias AN. Insulin-induced lipodystrophy in diabetic patients resolved by treatment with human insulin. Ann Intern Med 1985 102(6) 790-1. 

A 29-year-old woman with raised insulin concentrations during therapy had lipodystrophy and high insulin antibody titers with high binding capacity and high affinity (21). 

Insulin antibodies are rarely found in patients with lipodystrophy. 

Usui H, Makino H, Shikata K, Sugimoto T, Wada J, Yamana J, Matsuda M, Yoneda M, Koshima I. A case of congenital generalized lipodystrophy with lipoatrophic diabetes developing anti-insulin antibodies. Diabet Med 2002 19(9) 794-5. 

In 30 patients with lipodystrophy associated with HAART rosiglitazone 8 mg/day for 24 weeks had no effect on body weight, subcutaneous or intra-abdominal fat, total body fat, anthropometry, or serum leptin concentrations (84). However, it reduced percentage liver fat and serum insulin concentrations and normalized liver function tests. During the first 12 weeks serum triglycerides rose from 3.5 to 6.5 mmol/1 and serum cholesterol from 6.0 to 7.8 mmol/1. The results on insulin resistance and lipid profiles were opposite to those found in a comparable study with pioglitazone (83). 

Dyslipidemia is a common accompaniment of the lipodystrophy syndrome observed in HIV-infected patients. This syndrome presents as a combination of peripheral lipoatrophy and the metabolic syndrome (central adiposity, insulin resistance, and dyslipidemia). The term lipodystrophy syndrome was first used in two case reports to describe a clinical picture of subcutaneous fat wasting in the face and limbs of HIV infected patients treated with indinavir, reminiscent of the rare congenital lipodystrophy syndromes (138,139). In addition, benign symmetric lipomatoses on the trunk and neck were described. A systematic study of this syndrome in the Australian HIV cohort showed co-existence of peripheral lipoatrophy with abdominal visceral obesity, dyslipidemia, and insulin resistance in HIV-infected patients with or without treatment with protease inhibitors (140). 

Soon after the introduction of highly active antiretroviral combination treatments (HAART), lipodystrophy was associated with the use of protease inhibitors, and several reports have confirmed that a syndrome of peripheral lipodystrophy, central adiposity, breast hypertrophy in women, hyperlipidemia, and insulin resistance with hyperglycemia is an adverse event associated with the use of potent combination antiretroviral therapy, particularly including HIV-1 protease inhibitors (982-987). 

Lipodystrophy, a syndrome characterized by fat redistribution, hyperglycemia/insulin resistance, and dyslipidemia, can be associated with long-term HIV infection or with highly active antiretroviral therapy (HAART). In 1035 patients, those who took stavudine were 1.35 times more likely to report lipodystrophy (1076). However, the study was retrospective, and other factors unrelated to specific drug therapy may have had a greater effect on the adjusted odds ratio. 

Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, Cooper DA. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998 12 F51-8. 

Rudich A, Ben-Romano R, Etzion S, Bashan N. Cellular mechanisms of insulin resistance, lipodystrophy and atherosclerosis induced by HIV protease inhibitors. Acta Physiol Scand. 2005 183 75-88. 

Lipodystrophy can also result from insulin therapy and is characterized by atrophy of subcutaneous fat. Insulin edema is manifested by a generalized retention of fluid. Insulin resistance arises when there is an excess insulin requirement that exceeds 200 units per day. 

Adverse effects observed with insulin Note lipodystrophy is a local atrophy or hypertrophy of subcutaneous fatty tissue at the site of injections. 

Figure 22.7. Effect of DHA on serum levels of adipocytokines and insulin in diet-induced lipodystrophy model mice.

Nagao, K., Inoue, N., Ujino, Y., Higa, K., Shirouchi, B., Wang, Y. M., and Yanagita, T. 2008. Effect of leptin infusion on insulin sensitivity and lipid metabolism in diet-induced lipodystrophy model mice. Lipids Health Dis., 7, 8. 

Shimomura, I., Hammer, R. E., Richardson, J. A., Ikemoto, S., Bashmakov, Y., Goldstein, J. L., and Brown, M. S. 1998. Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-lc in adipose tissue model for congenital generalized lipodystrophy. Genes Dev., 12, 3182-3194. 

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