Insulin resistance syndrome clinical syndromes

Because of the polyfactorial nature of disease states, such as obesity, type 2 diabetes, and Metabolic Syndrome, it is expected that drugs targeting the lipid synthesis and metabolism pathways will be used in the context of combination therapy [7]. Pre-clinical and clinical results to date indicate that pronounced efficacy could be achieved toward the management of associated lipid levels and insulin resistance, and thus, investigation in these areas provides significant promise. 

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). 

Depression and Metabolic Syndrome. Abnormal serum albumin levels and lipid profiles have both been observed in patients with major depression, as well as cardiovascular disease, diabetes mellitus, and end-stage renal disease. Depressive symptoms are very common in patients with these chronic illnesses. Recent clinical data have shown that cardiovascular disease, diabetes mellitus, end-stage renal disease, and obesity are all related to metabolic syndromes [68-74], and especially insulin resistance [75, 76]. However, the data examining major depression without physical illness and insulin resistance are still scarce. In the future, the biological relationship between depression and physical illness needs to be more fully explored. 

Other major points of interest in clinical trials are hyperinsulinaemia and insulin resistance as a common denominator of the metabolic syndrome, hyperinsulinaemia as an independent predictor of coronary heart disease, and the efficacy of new insulin analogues. 

In conclusion, it can be stated, that biguanides, preferably metformin, have been shown in innumerable clinical trials to be highly effective as antihyper-glycaemic drugs. Together with acarbose, they may be the first-choice drug for the treatment of obese hyperinsulinaemic, insulin resistant Type-II diabetics with dietary failure. They help to correct most of the unwanted aspects of the metabolic syndrome, which is felt to contribute most to the high mortality rate of NIDDM patients with heart disease. 

Several genetic mutations have been described in the insuhn receptor and are associated with insulin resistance. Type A insuhn resistance refers to the clinical syndrome of acanthosis nigricans, virilization in women, polycystic ovaries, and hyperinsulinemia. Leprechaunism is a pediatric syndrome with specific facial features and severe insulin resistance due to a defect in the insuhn receptor gene. Lipoatrophic diabetes probably results from postreceptor defects in insulin signaling. 

Diabetes mellitus is the commonest endocrine disorder encountered in clinical practice. It may be defined as a syndrome characterized by hyperglycaemia due to an absolute or relative lack of insulin and/or insulin resistance. 

Table 3. Clinical syndromes associated with insulin resistance.

Insulin resistance is not a disease, but a physiological abnormality that increases the likelihood that one or more of the abnormalities listed in Table 2 will be present. Furthermore, because the abnormalities seen in Table 2 occur more commonly in insulin-resistant individuals, they are at increased risk to develop one or more of the clinical syndromes listed in Table 3. However, the relationship between insulin resistance and the changes seen in Tables 2 and 3 is complicated, and the abnormalities and clinical syndromes listed in these tables can occur in the absence of insulin resistance. It must also be emphasized that insulin-resistant individuals do not necessarily develop any of the clinical syndromes listed in Table 3. 

The focus of this chapter does not permit an extensive discussion of the complex relationship between insulin resistance, compensatory hyperinsulinemia, and the abnormalities and clinical syndromes that makeup the IRS, and reviews of these issues are available [27,28], However, it is important to briefly discuss the relationship between insulin resistance, compensatory hyperinsulinemia, and differential tissue insulin sensitivity in the... 

Thus, although insulin resistance at the level of the muscle and the adipose tissue may be the fundamental abnormality that underlies the IRS, it is the compensatory hyperinsulinemia, preventing the development of type 2 diabetes in insulin-resistant individuals, which is responsible for most, if not all, of the abnormalities and clinical syndromes... 

It is not possible within the confines of this chapter to discuss aU possible therapeutic approaches to the abnormalities and clinical syndromes that comprise the IRS. For example, although type 2 diabetes is one of the clinical syndromes that occur more commonly in insulin-resistant individuals, guidehnes outlining appropriate treatment are readily available, and need not be reviewed here. Instead an attempt will be made to selectively address issues considered to be of particular clinical relevance decisions for inclusion and exclusion that will clearly reflect the biases of the author. 

An enormous amount of new information relevant to the role of insulin resistance in human disease had appeared since the introduction of the concept of Syndrome X, and the abnormalities related to insulin resistance have broadened considerably. At the same time, it has become clear that the adverse clinical outcomes associated with insulin resistance extend far beyond type 2 diabetes and CVD. For example, in addition to type 2 diabetes and CVD, insulin-resistant individuals are at increased risk to develop essential hypertension, PCOS, nonalcoholic fatty liver disease, congestive heart failure. 

The effect of niacin in insulin resistance remains a controversial issue. The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes) and HPS2-THRIVE trial (Treatment of HDL to Reduce the Incidence of Vascular Events) will increase our knowledge about the clinical impact of niacin. 

Vittone, F., Chait, A., Morse, J.S., Fish, B., Brown, B.G., and Zhao, X.Q., 2007. Niacin plus simvastatin reduces coronary stenosis progression among patients with metabolic syndrome despite a modest increase in insulin resistance a subgroup analysis of the HDL-Atherosclerosis Treatment Study (HATS). Journal of Clinical Lipidology. 1 203-210. 

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