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Diabetes Update. Part 3 of 3. Division of Endocrinology Department of Medicine Wayne State University Medical School Detroit, Michigan. Insulin Analogs. Analogs are more predictable and more reliable and consistent in action. Less chance of hypoglycemia. Rapid Acting:
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Diabetes Update Part 3 of 3 Division of Endocrinology Department of Medicine Wayne State University Medical School Detroit, Michigan
Insulin Analogs • Analogs are more predictable and more reliable and consistent in action. Less chance of hypoglycemia. • Rapid Acting: -Humalog (Lispro) -Novolog (Aspart) -Apidra (Glulisine) • Long Acting (Basal): - Lantus (Glargine) - Levemir (Detemir) • Mixes: Novolog 70/30 and Humalog 75/25 & 50/50
Dissociation and Absorption of Analogs Peak Time = 40 – 50 min Insulin analogs Subcutaneous tissue Capillarymembrane Peak Time = 80 – 120 min Regularinsulin
Profiles Human Insulin and Analogs Aspart, Lispro, Glulisine (4–5 hr) Regular (6–8 hr) NPH (12–16 hr) Plasma Insulin Levels Glargine/Detemir (~24 hr) 2 4 6 8 12 14 16 18 20 22 24 0 10 Hours Based on Rosenstock J, Wyne K. In: Goldstein BJ, Muller-Wieland D, eds. Textbook of Type 2 Diabetes. 2003: 131-154.
Newer Directions • The role of Dopamine in type 2 Diabetes • The use of constant glucose monitors (CGMS).
Proposed mechanism of action of Bromocriptine in relation to type 2 DM • Diabetes patients may have low morning levels of hypothalamic dopamine, which is thought to lead to hyperglycemia and dyslipidemia • CYCLOSET (special form of bromocriptine) is thought to reset aberrant low morning hypothalamic dopaminergic activity, which may reset neuroendocrine metabolic control Decreased lipolysis in adipose tissue Decreased postprandial hepatic glucose output Decreased insulin resistance
Glucose Fluctuations Are Not Adequately Measured by A1C Mean A1C = 6.7% 400 300 Glucose Concentration (mg/dL) 200 100 0 12 AM 4 AM 8 AM 12 PM 4 PM 8 PM 12 AM Type 1 diabetes, N = 9 24-h CGMS glucose sensor data Data on file, Amylin Pharmaceuticals, Inc.
Indications for I Pro • Insulin –requiring Diabetic Patient who is: 1. Unacceptable HbA1c (not at goal) 2. Unexplained hypoglycemic episodes 3.Unexplained postprandial hyperglycemia. 4.Recurrent DKA 5. Pregnancy. 6. Prior to pump therapy.
Newer Therapies • Newer DDP IV inhibitors. • Newer Insulin: Insulin Degludec which a new long acting insulin given only 3 times a week. • Newer GLP 1 agonists: given once a week. • Newer agents such as inhibitors of renal tubular glucose re absorption. • Newer smart pumps which communicate with CGMS monitors to deliver insulin more physiologically.
Summary • Newer emphasis on post prandial sugars and therapies ot address those. • Newer emphasis on replacing the defective incretin pathway in type 2 DM and hence achieving better glycemic control without hypoglycemia and without weight gain or even some weight loss. • Newer understanding of the role of dopamine in type 2 DM and how to replace that with bromocriptine (centrally acting). • Expanding the use of ambulatory constant glucose monitors • The future is bright and promising!