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Obesity accounts for 80 85% of the overall risk of developing type 2 diabetes, and underlies the current global spread of the disease However, up to 50% of morbidly obese individuals do not develop type 2 diabetes, while 20% of type 2 diabetic subjects are not obese The risk of type 2 diabetes increases steadily as BMI rises above 24 kg/m2, to an 80-fold increase at BMI 35 kg/m2 Weight gain of over 5 kg in early adult life doubles risk, which also increases with the duration of obesity Central (and especially visceral) obesity is specifically associated with type 2 diabetes, and the risk of high waist circumference synergises with that of high BMI Obesity-associated diabetes risk is higher in certain ethnic groups, such as Pima (Native American) Indians, Black and Asian populations Risk thresholds for both BMI and waist circumference are lower than in Caucasians.



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Higher body fat content in non-Caucasians may contribute Obesity is associated in the metabolic syndrome with insulin resistance, glucose intolerance (including type 2 diabetes), hypertension, gout and pro-inflammatory and pro-coagulant changes Up to 10% of adults in developed countries are affected Fatty liver, glomerulopathy, polycystic ovarian syndrome and sleep apnoea are also associated Obesity induces insulin resistance, which worsens with rising BMI and especially increasing visceral abdominal fat mass Possible mediators include high free fatty acid (FFA) levels generated by overactive lipolysis in fat, and disturbances in adipokines produced by adipose tissue, such as adiponectin and leptin, which both improve insulin sensitivity in peripheral tissues Adiponectin levels fall in obesity, while obese subjects may become resistant to leptin s actions High FFA levels interfere with glucose utilization in muscle and liver (the glucose-fatty acid, or Randle cycle), and with insulin signalling.

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Muscle glucose uptake decreases, while hepatic gluconeogenesis and glucose production are enhanced, thus opposing insulin s glucoselowering actions Ectopic triglyceride deposition occurs in muscle, liver, cells and other tissues in obesity High FFA levels contribute to reduced adiponectin levels and leptin resistance Both adipokines activate AMP kinase, resulting in the clearing of intracellular trigylceride Intracellular triglyceride deposition impairs insulin action and causes various functional abnormalities ( lipotoxicity ), including steatohepatitis, impaired insulin secretion and perhaps heart failure Obesity predisposes to type 2 diabetes by causing both insulin resistance and -cell dysfunction The latter may be due to high FFA levels and intracellular triglyceride deposition, which may lead to -cell apoptosis through oxidative damage and perhaps amyloid formation from aggregated amylin Substantial weight loss, for example following bariatric surgery, may improve or even reverse glucose intolerance, including established type 2 diabetes.

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Obesity and the metabolic syndrome are accompanied by dyslipidaemia, typically with high triglyceride levels throughout the day and low HDL cholesterol Hepatic production of very low density lipoprotein (VLDL) cholesterol (fuelled by high FFA levels) is increased, whereas VLDL clearance by lipoprotein lipase (an insulin-sensitive enzyme) is decreased High triglyceride levels favour the formation of small dense low density lipoprotein (LDL), which is taken up by subendothelial macrophages to form foam cells Small dense high density lipoprotein (HDL) also forms, which is readily catabolized, thus lowering levels of anti-atherogenic HDL cholesterol The dyslipidaemia is therefore atherogenic..

TABLE 20 Continued Product Lipids Intralipid 10% Intralipid 20% Intralipid 10% Intralipid 20% Lipofundin 20% Lipofundin 20% Intralipid 20% Lipofundin 20% Lipofundin 10% Lipofundin 20% Vitamins Vitamin C 500 mg Vitamin B12 1mg B complex B complex Multivitamin MVI Others Albumin 20% Albumin 20% Heparin 1000 U/mL Heparin 5000 U/mL Heparin 5000 U/mL Behring Fujisawa Inc. Crist lia 190.4 235 12* 211.7 732 23* 72 6* 55 15 55 15 15 EMS Bunker Hipolabor Ariston ICN 3443 233* 92 23* 1089 127* 709 65* 588 63* 15 15 15 15 15 Kabi Vitrum Kabi Vitrum Pfrimmer Kabi Pfrimmer Kabi Braun Braun Pharmacia Braun Braun Braun <5 <5 5 7 35 14 30 180 29 6* 34 7* 10 10 11 11 11 11 54 54 15 15 Speci cation Brand Al concentration g/L Reference

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where, as before, w = (w1. . . W N ) ~ Combining (2.18), (2.191, (2.22), and (2.23) shows . that COV(Wm, wn) E[dm(8)d,(8)] = cov (d,(8), d n ( 8 ) ) . Therefore, =

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