Saturday , October 21 2017
Home / Resources / Clinical Gems

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 #95: Metabolomics: Applications in Type 2 Diabetes Mellitus and Insulin Resistance Part 1

DeFronzoCover

Type 2 diabetes mellitus (T2DM) is not simply a disorder of blood sugar control, but a condition in which multiple biochemical pathways are impacted. An illustrative example of this is the elevated blood ketone body concentration typical of T2DM, which can progress to diabetic ketoacidosis if insulin action and/or availability deteriorates.The elevations of ketone bodies and the acetone accumulation (with associated “sweet breath odor”) of severe or poorly controlled diabetes are indicative of abnormal fatty acid homeostasis and specifically, high lipolysis and hepatic beta-oxidation.

Read More »

International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #94: Lipid and Lipoprotein Metabolism, Hypolipidemic Agents, and Therapeutic Goals Part 6

DeFronzoCover

Nicotinic acid (niacin) has been used for more than 50 years to lower LDL-C and TGs, and increase the level of HDL-C. Indeed, niacin is the most potent HDL-C-raising pharmacologic agent available. Of note, we still, at this late time in the life of niacin, do not have definitive evidence regarding its mechanism(s) at the molecular level.

Read More »

International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #93: Lipid and Lipoprotein Metabolism, Hypolipidemic Agents, and Therapeutic Goals Part 5

DeFronzoCover

Diet and lifestyle modification: Appropriate lifestyle interventions involving diet and exercise can lead to weight loss, and since obesity is a major contributor to the IR and T2DM, weight loss should provide significant benefits to individuals with these problems. The Diabetes Prevention Program demonstrated that a 6% weight loss and the addition of two hours of exercise per week was associated with a 58% reduction in the incidence of new T2DM in a group with IGT. Similar results were obtained in the Finnish Diabetes Prevention Study using similar interventions.

Read More »

International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #92: Lipid and Lipoprotein Metabolism, Hypolipidemic Agents, and Therapeutic Goals Part 4

DeFronzoCover

Therapeutic approaches to the dyslipidemia of insulin resistance and type 2 diabetes mellitus -- Key points: The rationale for treating the diabetic dyslipidemia is clear, it is associated with significantly increased risk of cardiovascular events.Weight loss, exercise, and diet modifications are key to successful treatment of all of the lipid abnormalities in patients with T2DM. Statins are the mainstay of therapy—they lower LDL cholesterol up to 50%, lower triglycerides about 15–25%, and have minimal effects of HDL cholesterol levels.

Read More »

International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #90: Lipid and Lipoprotein Metabolism, Hypolipidemic Agents, and Therapeutic Goals Part 2

DeFronzoCover

Lipoprotein metabolism in normal individuals and in type 2 diabetes mellitus: Triglyceride levels in blood are regulated by the size and number of VLDL secreted from the liver and the efficiency with which triglycerides are cleared from the plasma by lipoprotein lipases. In T2DM, greater numbers of larger, more triglyceride-enriched VLDL are secreted from the liver and lipoprotein lipase activity may be modestly reduced; both lead to increased levels of triglyceride in the blood. HDL cholesterol levels are reduced for several reasons, including increased transfer of that cholesterol to very low- and low-density lipoprotein, in exchange for their triglyceride, by cholesterol ester transfer protein. LDL particles lose some of their cholesterol to VLDL via the same exchange mechanism, which generate smaller, denser, LDL.

Read More »

International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #89: Lipid and Lipoprotein Metabolism, Hypolipidemic Agents, and Therapeutic Goals Part 1

DeFronzoCover

Any discussion of lipid and lipoprotein metabolism in diabetes mellitus, especially type 2 diabetes mellitus (T2DM), must consider the role of insulin resistance (IR). IR plays a central role in the abnormal lipid and lipoprotein metabolism of T2DM [1] as evidenced by the characteristic set of lipid and lipoprotein abnormalities accompanying IR, even in the absence of frank hyperglycemia or abnormal glucose tolerance. Individuals with IR have low plasma levels of HDL-C and elevations in plasma triglyceride (TG) levels compared with levels seen in individuals who have normal insulin sensitivity. There is also an increase in the proportion of low-density lipoprotein (LDL) particles that are small, dense, and cholesterol ester-poor. I

Read More »

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

DeFronzoCover

The wonders of lactate: Very recently, our laboratory has made a major improvement in the use of the minimal model to assess insulin sensitivity and evaluate its importance in metabolic control. During the FSIGT, as it is practiced, there is initially a large increase in glucose concentration, due to the glucose injection, there is an endogenous finite insulin response in normal individuals, and the insulin is then increased again at 20 min after the exogenous insulin injection. We considered the question of the fate of the injected glucose before the secondary insulin injection. In the absence of a large increase in insulin, much of the glucose is disposed by an insulin-independent mechanism, a process we termed “glucose effectiveness.”

Read More »

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

DeFronzoCover

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

Read More »

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

DeFronzoCover

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.

Read More »

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

DeFronzoCover

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.

Read More »