New and simple Ohmic definition of insulin resistance in lean and obese subjects

objective:: Insulin enhances the influx of glucose into cells. However, the relationship between glucose and insulin is complex and insulin sensitivity varies widely with age, ethnicity and obesity. Insulin sensitivity index (IS) has been introduced to determine precisely who is insulin resistant. However, accurate clamp methods to determine IS, such as hyperinsulinemic-euglycemic test, have been complicated, expensive and labor intensive. In this study, we are introducing insulin resistance rather than IS as a simple and accurate method to assess insulin sensitivity in lean and obese subjects. Methods: The plasma concentration of insulin serves as the driving force for the flow of glucose from the extracellular space into the cell. Since flows are proportional to their driving forces, we can utilize an "Ohmic" definition of insulin resistance. Using an electrical analog as a model where plasma glucose concentration is analogous to the current flow, and insulin concentration is analogous to the electromotive force, then an Ohmic definition yields: insulin resistance (IR)=insulin/glucose. The ratio of the two levels (insulin and glucose) may be obtained in the fasting state, or two hours after eating or at any designated time interval after an oral glucose tolerance test (OGIT) or the ratio of the integrals i.e., area under the insulin tolerance curve over the area under the glucose tolerance curve can be defined as insulin resistance. Results: In this study, we measured fasting levels of glucose, insulin and insulin resistance (resistance = insulin/glucose) in a non-diabetic, non-hypertensive population, divided into lean (N=126) and obese (N=62) groups. Body mass index of lean subjects was between 18.5 and 25 and that of obese subjects was >29. Obesity increased insulin levels by 3.5 folds, and insulin resistance by 3.3 folds, without causing hyperglycemia. We also measured glucose and insulin levels and calculated IR at 30 minutes intervals after oral glucose tolerance test (OGIT). At all four points of the OGTT, glucose levels were significantly higher in the obese subjects than in the lean. Similarly, the area under the glucose curve was significantly greater in the obese group (p<0.05). Glucose loading resulted in higher insulin levels at all the time intervals in the obese as compared to the lean. The total hyperinsulinemic response, as represented by the area under the insulin curve, was significantly greater in the obese than the lean. Moreover, the glucose-induced stimulus resulted in a 5-fold peak increase in IR in lean subjects (over fasting level) but only 3.3-fold increase in obese subjects. However, IR in obese group was still twice as high as in lean group. Conclusion: Hyperinsulinemia has become synonymous with insulin resistance because level of blood insulin itself is the most relevant index. But it is certainly more meaningful to take the insulin level relative to the glucose as a reference value, since glucose is both the substrate that insulin affects as well as the primary secretagogue for insulin secretion. In this study, we are reporting increased insulin resistance, measured as Glucose/Insulin, in the normal non-diabetic obese, both in the fasting state and following glucose loading. This subgroup may go on to develop NIDDM, hypertension, or coronary artery disease. Tulane Institutional Fund; Lavin Bernick grant This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.