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Clinical Gems

Our clinical gems come from the top selling medical books, and text books because knowledge is everything when it comes to diabetes.

International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #86: Measuring Insulin Action In Vivo

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It was a challenge to develop a computer model that could account for plasma dynamics in a compact but accurate package. The model was the simplest representation we could devise, which was based upon known physiology, and which could accurately describe moment-by-moment plasma dynamics. The model continues to thrive in that it continues to be the basis for a large number of clinical investigations (∼50 per year) as well as a robust literature related to its mathematical and computer characteristics

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #85: Measuring Insulin Action In Vivo

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Insulin action dynamics: Insulin sensitivity from the clamp is expressed in terms of the steady-state value reached after a period of hyperinsulinemia. A dose–response can be constructed and sensitivity can be expressed as the ED50, that is, the concentration for half-maximal stimulation of Rd as a function of dose. Alternatively, sensitivity can be expressed (as it usually is) as the Rd at a specific dose of insulin, which may be low, intermediate, or a maximum dose. It is often assumed that steady-state rate of glucose uptake is reached by 180 min after onset of the insulin infusion. In fact, steady-state glucose uptake is not reached at 3h. Glucose uptake rate at 3h is only 2/3 the “true” steady-state, which is not achieved until 6h. Certainly, shorter periods (e.g. 120 min) are inadequate to reflect steady-state rates of uptake.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #84: Measuring Insulin Action In Vivo

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The glucose clamp: Rather than using exogenous agents that suppress beta-cell insulin secretion, the glucose clamp uses external feedback control to “open the loop” between insulin secretion and sensitivity. The glucose clamp is a powerful and widely used method to attain a quantitative measure of insulin sensitivity, and has been applied in many hundreds of experimental studies.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #83: Measuring Insulin Action In Vivo

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The heralded isolation of insulin in Toronto in 1921 was followed immediately by treatment of diabetes. It soon became clear that while insulin was effective in regulating the blood glucose levels in most patients, there were some subjects in whom insulin appeared to be ineffective. This lack of insulin effect was termed “insulin resistance” as early as 1925.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #82: Insulin Actions In Vivo: Glucose Metabolism Part 9 of 9

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Oral glucose: At any point in time, the glycemic response to exogenous glucose is the balance between the rate at which glucose appears in the systemic circulation (from oral as well as endogenous sources) and the rate at which glucose is disposed of. Oral glucose appearance in the peripheral circulation depends on: (a) the rate at which the gastric contents are passed on to the small intestine; (b) the rate of intestinal glucose absorption; (c) the extent of gut glucose utilization; (d) the degree of hepatic glucose trapping; and (e) the dynamics of glucose transfer through gut, liver, and posthepatic circulation on to the right heart.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #81: Insulin Actions In Vivo: Glucose Metabolism Part 8 of 9

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Glucose phosphorylation and glucose transport are tightly coupled phenomena. Isoenzymes of HK (HK-I to HK-IV) catalyze the first committed intracellular step of glucose metabolism, the conversion of glucose to G-6-P. HK-I, HK-II, HK-III are single-chain peptides that have a number of properties in common, including a very high affinity for glucose and product inhibition by G-6-P.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #81: Insulin Actions In Vivo: Glucose Metabolism Part 7 of 9

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Cellular, biochemical, and molecular mechanisms of insulin action: The insulin receptor is a glycoprotein consisting of two alpha subunits and two beta subunits linked by disulfide bonds and expresses insulin-stimulated kinase activity directed towards its own tyrosine residues. Insulin receptor phosphorylation of the α subunit, with subsequent activation of insulin receptor tyrosine kinase, represents the first step in the action of insulin on glucose metabolism.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #80: Insulin Actions In Vivo: Glucose Metabolism Part 6 of 9

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Intravenous glucose: In the presence of euglycemia, insulin displays a potent suppressive action on hepatic glucose production, such that portal insulin concentrations of less than 100 mU L−1 abolish glucose entry into the circulation. Figure 14.7 shows a typical time course for endogenous glucose production following an acute increase in plasma insulin to levels of 60 – 70 mU L−1 in a healthy subject.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #79: Insulin Actions In Vivo: Glucose Metabolism Part 5 of 9

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The fed state is the absorptive period between meals. Carbohydrates are normally mixed with lipids and protein in the diet and make up 40 – 60% of the caloric content. Absorption of dietary carbohydrates is influenced by their chemical form (refined sugars or complex carbohydrates) and by other components of food. Furthermore, disposition of dietary carbohydrate is indirectly affected by fats and protein to the extent that these latter (i) compete with glucose as substrates, and (ii) interfere with glucoregulatory hormones by altering insulin secretion.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #78: Insulin Actions In Vivo: Glucose Metabolism Part 4 of 9

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Glucose disposal: In the basal state, steady/near steady-state conditions prevail and whole-body glucose disposal equals endogenous (hepatic) plus renal glucose production. Data on the individual contribution of organs and tissues to total glucose uptake have been obtained in regional catheterization studies. In the case of the splanchnic area, in which glucose uptake and production both occur simultaneously, such data have been derived from the combined use of glucose tracers and indwelling catheters.

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