12.2 Medicine II_Treatment of Hyperglycemia in Type 2 DM_2014A

August 13, 2012

Management of Hyperglycemia in Type 2 DM I. II.

III. IV.

increase in hepatic glucose production, which leads to an increase in blood glucose.  It is known that in DM type two, there are bigger and more Alpha cells and they are not suppressing glucagon as well as normal individuals. In normal individuals, after a meal, blood sugar level goes up and glucagon should be suppressed. Insulin will be released so that your liver will stop from gluconeogenesis and glycogenolysis. In DM type 2, there is decreased insulin and improper suppression of glucagon. Hence, the two reasons for increased glucose release of liver which leads to hyperglycemia, both in fasting and postprandial states.  With decreased secretion of insulin, less glucose is taken up by muscle, adipose tissue, and liver. This leads to post meal hyperglycemia.  There are other systems which are being looked into like kidney, brain and the gut but the most basic is this.

Outline Review: Major Pathophysiologic Defects in T2DM Management of Hyperglycemia in T2DM o UKPDS Prospective Diabetes Study o Steno-2 Study o ADA-EASD Position Statement: A PatientCentered Approach 1. Patient-Centered Approach 2. Background - Epidemiology and healthcare impact - Relationship of Glycemic Control Outcomes - Overview of the Pathogenesis of Type 2 Diabetes 3. Antihyperglycemic Therapy Oral agents and non-insulin injectables (biguanides, SU, TZD, a-glucosidase inhib, DPP-4-I, GLP-1-RA) Insulin Implementation therapy in type 2 DM  Sequential insulin strategies in type 2 DM Variations in antihyperglycemic therapy (avoid weight gain, minimize cost, guidelines for glycemic, BP and lipid control) 4. Other considerations 5. Future directions/ Research Needs Key points Samplex review

{Editor’s note: Please go back to the outline if you feel lost in this trans. We revised the flow of the discussion a bit to make it easier to follow. FOCUS ON THE ADA-EASD position statement since it is the bulk of the lecture. Thank you! }

REVIEW MAJOR PATHOPHYSIOLOGIC DEFECTS IN TYPE 2 DIABETES

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 Major defects: insulin resistance and islet cell dysfunction. In the islet cells of Langerhans there are two cells that are involved in the generation of hyperglycemia: 1. Beta Cell (insulin); 2. Alpha cells (glucagon).  Insulin resistance is increased and insulin secretion is impaired.  Most patients have insulin resistance. Pancreatic β cells increase insulin secretion to compensate for insulin resistance. When β-cell function is impaired, hyperglycemia develops.  By the time diabetes is diagnosed, β-cell function has already decreased substantially and continues to decline over time.  Once insulin secretion is impaired, an imbalance between insulin and glucagon can develop. Elevated glucagon levels lead to an Belisario, Bernabe, Bringas | Bautista XJV

{Editor: Not explained by Dr. Panelo but this picture just illustrates 2 points in the pathophysiology mentioned earlier. The graph on the upper part demonstrates that both postprandial and fasting hyperglycemia is present in uncontrolled diabetes. The lower graph shows that by time of diagnosis of DM, β-cell function has already decreased substantially and continues to decline over time.}

MANAGEMENT OF HYPERGLYCEMIA IN TYPE 2 DIABETES UK PROSPECTIVE DIABETES STUDY (UKPDS) 

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UK Prospective Diabetes Study (UKPDS) was a prospective observational study to determine the relation between exposure to hyperglycemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes who were participants in the UKPDS. 3,642 White, Asian Indian and Afro-Caribbean UKPDS patients who had HbA 1c measured three months after their diabetes diagnosis and with complete data for potential confounders were included in the sub-analysis of relative risk. Page 1 of 13

Reductions in the risk of microvascular and macrovascular complications that might be achieved by lowering HbA 1c by 1% were estimated. UKPDS: Reduced micro- and macrovascular complications for a 1% decrease in HbA1c Any diabetes-related 21 % (P