referred to in diabetes literature as the ginf value. the procedure takes about two hours. through a peripheral vein, insulin is infused at 10–120 mu per m2 per minute. in order to compensate for the insulin infusion, glucose 20% is infused to maintain blood sugar levels between 5 and 5.5 mmol/l. the rate of glucose infusion is determined by checking the blood sugar levels every five to ten minutes. the rate of glucose infusion during the last thirty minutes of the test determines insulin sensitivity. if high levels (7.5 mg/min or higher) are required, the patient is insulin-sensitive. very low levels (4.0 mg/min or lower) indicate that the body is resistant to insulin action. levels between 4.0 and 7.5 mg/min are not definitive, and suggest "impaired glucose tolerance," an early sign of insulin resistance. this basic technique may be enhanced significantly by the use of glucose tracers. glucose may be labeled with either stable or radioactive atoms. commonly used tracers are 3-3h glucose (radioactive), 6,6 2h-glucose (stable) and 1-13c glucose (stable). prior to beginning the hyperinsulinemic period, a 3h tracer infusion enables one to determine the basal rate of glucose production. during the clamp, the plasma tracer concentrations enable the calculation of whole-body insulin-stimulated glucose metabolism, as well as the production of glucose by the body (i.e., endogenous glucose production). modified insulin suppression test another measure of insulin resistance is the modified insulin suppression test developed by gerald reaven at stanford university. the test correlates well with the euglycemic clamp, with less operator-dependent error. this test has been used to advance the large body of research relating to the metabolic syndrome. patients initially receive 25 μg of octreotide (sandostatin) in 5 ml of normal saline over 3 to 5 minutes via intravenous infusion (iv) as an initial bolus, and then, are infused continuously with an intravenous infusion of somatostatin (0.27 μg/m2/min) to suppress endogenous insulin and glucose secretion. next, insulin and 20% glucose are infused at rates of 32 and 267 mg/m2/min, respectively. blood glucose is checked at zero, 30, 60, 90, and 120 minutes, and thereafter, every 10 minutes for the last half-hour of the test. these last four values are averaged to determine the steady-state plasma glucose level (sspg). subjects with an sspg greater than 150 mg/dl are considered to be insulin-resistant. alternatives given the complicated nature of the "clamp" technique (and the potential dangers of hypoglycemia in some patients), alternatives have been sought to simplify the measurement of insulin resistance. the first was the homeostatic model assessment (homa), and more recent methods include the quantitative insulin sensitivity check index (quicki) and spina-gr, a measure for insulin sensitivity. all of these calculated markers employ fasting insulin and glucose levels to calculate insulin resistance, and all correlate reasonably with the results of clamping studies. prevention and management maintaining a healthy body weight and being physically active can help reduce the risk of developing insulin resistance. the primary treatment for insulin resistance is exercise and weight loss. both metformin and thiazolidinediones improve insulin sensitivity. metformin is approved for prediabetes and type 2 diabetes and has become one of the more commonly prescribed medications for insulin resistance. the diabetes prevention program (dpp) showed that exercise and diet were nearly twice as effective as metformin at reducing the risk of progressing to type 2 diabetes. however, the participants in the dpp trial regained about 40% of the weight that they had lost at the end of 2.8 years, resulting in a similar incidence of diabetes development in both the lifestyle intervention and the control arms of the trial. in epidemiological studies, higher levels of physical activity (more than 90 minutes per day) reduce the risk of diabetes by 28%. furthermore, physical training has also generally been seen to be an effective antagonist of insulin resistance in obese or overweight children and adolescents (under the age of 19). as per the 2016 systematic review and meta-analysis conducted by marson et al., aerobic exercise is associated with fasting insulin reduction; however, resistance and combined exercise are not. the authors caution against demeaning the importance of resistance and combined exercise, as this type of training is generally less researched than aerobic training. overall, physical training can be used in both adolescents and adults to prevent the progression of insulin resistance and future possible metabolic and cardiovascular disease. resistant starch from high-amylose corn, amylomaize, has been shown to reduce insulin resistance in healthy individuals, in individuals with insulin resistance, and in individuals with type 2 diabetes. some types of polyunsaturated fatty acids (omega-3) may moderate the progression of insulin resistance into type 2 diabetes, however, omega-3 fatty acids appear to have limited ability to reverse insulin resistance, and they cease to be efficacious once type 2 diabetes is established. history the concept that insulin resistance may be the underlying cause of diabetes mellitus type 2 was first advanced by professor wilhelm falta and published in vienna in 1931, and confirmed as contributory by sir harold percival himsworth of the university college hospital medical centre in london in 1936; however, type 2 diabetes does not occur unless there is concurrent failure of compensatory insulin secretion. adaptive explanations some scholars go as far as to claim that neither insulin resistance, nor obesity really are metabolic disorders per se, but simply adaptive responses to sustained caloric surplus, intended to protect bodily organs from lipotoxicity (unsafe levels of lipids in the bloodstream and tissues): "obesity should therefore not be regarded as a pathology or disease, but rather as the normal, physiologic response to sustained caloric surplus... as a consequence of the high level of lipid accumulation in insulin target tissues including skeletal muscle and liver, it has been suggested that exclusion of glucose from lipid-laden cells is a compensatory defense against further accumulation of lipogenic substrate." other prevailing thoughts that insulin resistance can be an evolutionary adaptation include the thrifty gene hypothesis. this hypothesis raises the point that if there is a genetic component to insulin resistance and type 2 diabetes, these phenotypes should be selected against. yet, there has been an increase in mean insulin resistance in both the normoglycemic population as well as the diabetic population. j.v. neel postulates that originally in times of increased famine in ancient humans' ancestors, genes conferring a mechanism for increased glucose storage would be advantageous. in the modern environment today, however, this is not the case. evidence is contradictory to neel in studies of the pima indians, which indicate that the people with higher insulin sensitives tended to weigh the most and conversely people with insulin resistance tended to weigh less on average in this demographic. modern hypotheses suggest that insulin metabolism is a socio-ecological adaptation with insulin being the means for differentiating energy allocation to various components of the body and insulin sensitivity an adaptation to manipulate where the energy is diverted to. the behavioral switch hypothesis posits that insulin resistance results in two methods to alter reproductive strategies and behavioral methods. the two strategies are coined as “r to k” and “soldier to diplomat.” the r to k strategy involves diverting insulin via placenta to the fetus. this has demonstrated weight gain in the fetus, but not the mother indicating a method of increased parental investment (k strategy). in the “soldier to diplomat” the insensitivity of skeletal muscle to insulin could divert the glucose to the brain, which doesn't require insulin receptors. this has shown increases in cognitive development across various studies.