In summary, postbinding defects in insulin action primarily are responsible for the insulin resistance in T2DM. Diminished insulin binding, when present, is modest and secondary to downregulation of the insulin receptor by chronic hyperinsulinemia. In type 2 diabetic patients with overt fasting hyperglycemia, a number of postbinding defects have been demonstrated, including reduced insulin receptor tyrosine kinase activity, insulin signal transduction abnormalities, decreased glucose transport, diminished glucose phosphorylation, and impaired glycogen synthase activity. The glycolytic/glucose oxidative pathway is largely intact and, when defects are observed, they appear to be acquired secondary to enhanced FFA/lipid oxidation. From the quantitative standpoint, impaired glycogen synthesis represents the major pathway responsible for the insulin resistance in T2DM, and is present long before the onset of overt diabetes, that is, in normal glucose-tolerant, insulin-resistant prediabetic subjects and in individuals with IGT. The impairment in glycogen synthase activation appears to result from a defect in the ability of insulin to phosphorylate IRS-1, causing a reduced association of the p85 subunit of PI-3 kinase with IRS-1 and decreased activation of the enzyme PI-3 kinase.

How comfortable are you with prescribing a SGLT-2 inhibitor? Follow the link to see how you and your colleagues compare.

A 72-year-old patient arrives in your office complaining of shakiness and sweating before he went to bed the previous night. He doesn’t recall checking his blood glucose level at the time, however he felt better after a glass of milk and a few graham crackers. His current medications are metformin, pioglitazone, and glyburide. Which one of the following medications is the most likely cause of his symptoms?

A. Metformin
B. Pioglitazone
C. Glyburide

A patient who has had type 1 diabetes became pregnant after nearly 20 years of having type 1 diabetes. She reported her OB-GYN referred her to a specialty clinic for high-risk pregnancy, including diabetes in pregnancy. They worked in tandem to ensure her care was carefully managed throughout the stages of her pregnancy.

In this week's Homerun Slides, the general concept of insulin pump therapy and CGM patterns.

Glucose transport: Activation of the insulin signal transduction system in insulin target tissues stimulates glucose transport via a mechanism that involves translocation of a large intracellular pool of glucose transporters (associated with low-density microsomes) to the plasma membrane and their subsequent activation after insertion into the cell membrane.

Reducing HbA1c may be new goal of therapy to prevent coronary artery disease and other subtypes.

Vitamin D shows potential to lower HbA1c, FPG, insulin resistance, and 2-hour post-prandial glucose levels.

Should we lower the A1c to 5.7 for the diagnosis for diabetes and remove prediabetes as a diagnosis, so that we can treat pharmaceutically? Follow the link to share your opinion.

Your patient has been systematically titrating his basal insulin dose for the last 6 months. His daily dose is NPH .90 U/kg/day. Despite his good efforts, you decide it would be prudent to add a prandial insulin dose to his treatment regimen. Which of the following scenarios might lead you to this conclusion?

A. A1C=7.4%, FPG less than 130 mg/dl, PPG greater than 180 mg/dl
B. A1C=7.0%, FPG less than 130 mg/dl, PPG less than 180 mg/dl
C. A1C=7.0%, FPG less than 120mg/dl, PPG less than 160mg/dl
D. A1C=6.8%, FPG less than 120 mg/dl, PPG less than 160 mg/dl

Follow the link for the answer.