Diabetes with insulin resistance

Type 2 diabetes is a heterogeneous and progressive endocrine disorder associated with insulin resistance (impaired insulin action) and defective function of the insulin-secreting (3-cells in the pancreatic islets of Langerhans. These endocrine disorders give rise to widespread metabolic disturbances epitomised by hyperglycaemia. The present classes of antidiabetic agents other than insulin act to either increase insulin secretion, improve insulin action, slow the rate of intestinal... 

The precise mechanism involved in loss of body fat in this disorder however remains speculative but it is likely that autoimmune mechanisms (body defense mechanisms acting against body fat) are involved. Interestingly, in AGL severe insulin resistant diabetes mellitus is a typical clinical feature." Insulin resistance is frequently associated with an increased body weight and fat mass. Therefore, AGL is an interesting and unique knockout model of subcutaneous adipose tissue combined with insulin resistant diabetes mellitus. 

Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, Lee CH, Oh WK, Kim CT, Hohnen-Behrens C, Gosby A, Kraegen EW, James DE, Kim JB. (2006) Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistance states. Diabetes 55 2256-2264. 

Hamilton J, Cummings E, Zdravkovic V, Finegood D, Daneman D. Metformin as an adjunct therapy in adolescents with type 1 diabetes and insulin resistance a randomized controlled trial. Diabetes Care 2003 26(l) 138-43. 

Type 2 diabetes and insulin resistance per se are frequently associated with dyslipidemia (i.e., borderline elevation of LDL cholesterol, elevated triglycerides, and low HDL cholesterol), and a markedly increased incidence of atherosclerotic disease (i.e., coronary, cerebral, and peripheral artery disease). Atherosclerotic cardiovascular disease is... 

Two independent kindreds with insulin-resistant type 2 diabetes in association with novel PPARy mutations were recently described (64). In both cases, the mutations—Val—>Met290 and Pro—>Leu467—were shown to function as dominant-negative proteins when expressed in transfected cells. This compelling story provides further proof of the role of PPARy as a potential regulator of in vivo insulin action. 

For a number of years, there have been suggestions that glucosamine interferes with glucose metabolism in patients with type 2 diabetes, and insulin resistance may occur. This would be a significant risk in older patients, who often have concomitant illnesses. A recent study has demonstrated that oral glucosamine supplementation (1500 mg), in combination with 1200 mg chondroitin per day, did not adversely affect glycemic control when administered to patients with type 2 diabetes. ... 

The effects of thiazide-type diuretics on carbohydrate tolerance cannot be ignored (50). There is a definite relation between diuretic treatment, impaired glucose tolerance, and biochemical diabetes, and a possible relation with insulin resistance (64). It is well estabhshed that the effect of thiazides on blood glucose is dose-related, probably linearly, while the antihjrpertensive effect has httle relation to dose (65-67). There is relatively httle information on the time-course numerous short-term studies have shown that the blood glucose concentration increases in 4-8 weeks (68). The evidence that current low dosages impair glucose tolerance in the long term is not entirely consistent, perhaps because of differences between studies... 

Though it is tempting to attribute the epidemic increase in diabetes in the last two decades to the ubiquitous phthalates, more research remains to be carried before this is proven. The Stahlhut et al. study correlates urinary phthalate metabolite presence with insulin resistance only. The connection to type 2 diabetes has thus been suggested but proof awaits further inquiry. 

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. 

Goodpaster BH, Thaete FL, Kelley BE. Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus. Am J Clin Nutr 2000 71 885-892. 

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