Insulin therapy edema

Thiazolidinediones may produce fluid retention and edema however, the mechanism by which this occurs is not completely understood. It is known that blood volume increases approximately 10% with these agents, resulting in approximately 6% of patients developing edema. Thus, these drugs are contraindicated in situations in which an increased fluid volume is detrimental, such as heart failure. Fluid retention appears to be dose-related and increases when combined with insulin therapy. 

M/sce/Zaneows-Allergic reactions. Sodium retention and edema may occur, particularly if previously poor metabolic control is improved by intensified insulin therapy. Antibody production. 

In studies in the 1970s peripheral edema developed in 15 of 86 middle-aged insulin-treated patients (112) and between 4 and 10% of intensively treated people with type I diabetes (113). In later studies of patients with type 2 diabetes, 5.4% of 408 patients treated with insulin developed edema compared with 15% of those who received insulin and a glitazone. In a further study edema occurred in 4.8% of patients who used rosiglita-zone alone (114). Insulin can cause edema that can become clinically significant, particularly when it is combined with other therapies that cause edema. 

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. 

Insulin edema is a rare complication, more often seen in the earlier years of insulin therapy (SEDA-11, 364). It is mostly seen when dysregulated patients with progressive weight loss are treated with relatively high amounts of insulin. Reduced sodium excretion (88), sodium reabsorption, and water retention by a possible direct action of insulin on the kidney may be involved (89). The role of aldosterone or of inhibition of the renin-angiotensin-aldosterone system in insulin edema is unclear. Insulin edema is a specific adverse effect, but it can aggravate pulmonary edema, congestive heart failure, and hypertension. Treatment consists of reduction of the insulin dose, after which the edema resolves within 3 days. 

Respiratory effects of hypoglycemia A 19-year-old woman with diabetes developed hypoglycemia with pulmonary edema (59). This has previously been seen as a complication of insulin shock therapy for psychiatric illnesses. 

King KA, Levi VE. Prevalence of edema in patients receiving combination therapy with insulin and thiazolidinedione. Am J Health-Syst Pharm 2004 61 390-3. 

Rare complications are lipoatrophy or hjrpertrophy and insulin edema. Insulin has to be given by injection, with pumps or specific devices for intensive therapy, which all generate specific problems. Other ways of administrating insulin are still experimental. 

Ankle edema occurred in about 5% of patients treated with both rosiglitazone and pioglitazone in some cases, pulmonary edema can develop. Edema was more frequent in insulin combination therapy with either drug (about 15% compared with 5.4-7% with insulin alone). The reasons for fluid retention and peripheral edema with TZDs are multifactorial. The increase in plasma volume may result from a reduction in renal excretion of sodium and an increase in sodium and free water retention. TZDs may also interact synergistically with insulin to cause arterial vasodilatation, leading to sodium reabsorption and an increase in extracellular volume [61,62], In case reports, the edema has not been responsive to diuretics [63,64]. 

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