Insulin Resistance and Hyperglycemia

The insulin resistance and hyperglycemia of severe bums has been observed to persist for 1-2 weeks and has been described as pseudodiabetes. Apart from insulin antagonism of endocrine origin some cell membrane defect may be present and increased levels of the antagonist syn-albumin has been found in a significant number of patients recovering from myocardial infarction (VI). 

R.S. Surwit, M.F. Seldin, C.M. Kuhn, C. Cochrane, and M.N. Feinglos, Control of expression of insulin resistance and hyperglycemia by different genetic factors in diabetes C57BL/6J mice, Diabetes, 1991, 40, 82-87. 

Petersen, K.F., Dufour, S., Befroy, D., Lehrke, M., Hendler, R.E, and Shulman, G.I. 2005. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes. 

Insulin resistance and type 2 diabetes Insulin resistance alone will not lead to type 2 diabetes. Rather, type 2 diabetes develops in insulin-resistant individuals who also show impaired p cell function. Insulin resistance and subsequent development of type 2 diabetes is commonly observed in the elderly, and in individuals who are obese, physically inactive, or in women who are pregnant. These patients are unable to sufficiently compensate for insulin resistance with increased insulin release. Figure 25.8 shows the time course for the develpment of hyperglycemia and the destruction of P cells. 

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. 

Vanadium compounds have also been shown to be effective in animal models of insulin resistance and type 2 diabetes. Oral administration of vanadium compounds lowered blood glucose levels to near normal in the ob/ob and db/db mouse and fa/fa rat [149-151], These rodent models are homozygous for the indicated gene and are characterized by obesity, hyperglycemia, and hyperinsulinemia [12]. The ob allele is the gene for leptin, whereas db and fa are the genes for the leptin receptor in the mouse and rat, respectively. Leptin is one of the cytokine hormones that are produced in fat cells and act on receptors in the central nervous system. Its effects involve inhibition of food intake and promotion of energy expenditure [99],... 

Treatment with either vanadium salts or organic complexes of vanadium have decreased plasma insulin levels and improved insulin sensitivity in animal models of both insulin resistance and type 2 diabetes. This work has recently been reviewed [13]. The Zucker Diabetic Fatty (ZDF) rat develops overt hyperglycemia in the presence of hyperinsulinemia followed by [3-cell depletion. This is a type 2 diabetic rat model developed from the Zucker Fatty (fa/fa) rat. In these animals, chronic treatment with vanadium reduced the elevated plasma glucose levels [152,153], The effect in the type 2 models of diabetes can take weeks to develop, whereas the effect in the type 1 models of diabetes are seen within 3 to 4 days. 

Etgen, G.J., Oldham, B.A., Johnson, W.T. et al. (2002) A tailored therapy for the metabolic syndrome the dual peroxisome proliferator-activate receptor-a/y agonist LY465608 ameliorates insulin resistance and diabetic hyperglycemia while improving cardiovascular risk factors in predinical models. Diabetes, 51, 1083-1087. 

Interest in GA arose following findings that have implicated the role of increased activation of GC receptors in the development of MetS symptoms such as central obesity and hyperlipidemia. Overexpression of llp-HSD type 1 (llp-HSDl) in white adipose tissue of mice, for example, resulted in increased intracellular GC level, abdominal obesity, insulin resistance, hypertension, hyperglycemia, and dyslipidemia [47]. 

It has been widely accepted that high-sucrose diets lead to tmdesirable metabolic abnormalities such as hypertension, hyperglycemia, insulin resistance, and dyslipidemia. Several studies have utilized animal models such as rabbits [48], mini-pigs [49], mice [50], and rats [51] fed on high-sucrose diet to examine... 

Facilitates the breakdown of protein in the muscle, leading to increased plasma amino acid levels. Increases activity of enzymes necessary for glucogenesis producing hyperglycemia, which can aggravate diabetes, precipitate latent diabetes, and cause insulin resistance... 

Differential diagnoses include diabetes mellitus and metabolic syndrome because patients with these conditions share several similar characteristics with Cushing s syndrome patients (e.g., obesity, hypertension, hyperlipidemia, hyperglycemia, and insulin resistance). In women, the presentations of hirsutism, menstrual abnormalities, and insulin resistance are similar to those of polycystic ovary syndrome. Cushing s syndrome can be differentiated from these conditions by identifying the classic signs and symptoms of truncal obesity, "moon faces" with facial plethora, a "buffalo hump" and supraclavicular fat pads, red-purple skin striae, and proximal muscle weakness. 

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