Type 1 and Type 2 Diabetes in Pediatric Practice

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1 Type 1 and Type 2 Diabetes in Pediatric Practice Chirag R. Kapadia, MD Division of Endocrinology, Phoenix Children s Hospital Clinical Assistant Professor, U of A College of Medicine Presentation outline Pediatric Diabetes Type 1 Diabetes Pathophysiology Type 2 Diabetes Pathophysiology Pathophysiology beyond Insulin Local effects Gut-Brain Signaling Type 1 Diabetes Insulin Treatment Standard Subcutaneous Insulin Regimens Insulin Pumps Type 2 Diabetes Treatment Regimens in Pediatrics Technology and Devices Newer therapies on the horizon for pediatric diabetes Common pharmaceutical and insulin issues 1

2 Type 1 Diabetes Beta Cell Destruction Eisenbarth, GS. Primer: Imunology/Autoimmunity. from Eisenbarth, GS & Lafferty, KJ. (Eds.) Oxford University Press: New York Type I Diabetes: Molecular, Cellular, and Clinical Immunology Type 1 Diabetes Gradual onset Jasinski, JM. Drugs Today 2005, 41(2): 141 2

3 DKA betic-ketoacidosis.html 3

4 Type 2 Diabetes Pathophysiology Type 2 Diabetes Pathophysiology Update in pathofysiology of diabetes: Insulin resistance, β-cell dysfunction, and sustained glycaemic control. Prof. Bernard Charbonnel, Nantes, France, presented at CDMC, oct 08, Brussels In T2DM in children, B-cell defects play a larger role 4

5 T2DM in children: greater severity, beta cell destruction plays a greater role than in adults, and there is a greater chance of needing insulin More than 30% of pediatric Type 2 Diabetes patients may be Antibody positive (Kaufman FR, Endocrinology and Metabolism Clinics - Volume 34, Issue 3 (September 2005) Only 10% can be managed with lifestyle and diet alone Grinstein,Muzumdar,Saenger, DiMartino-Nardi, Horm Res 2003;60: African Americans/Hispanic: 20% need insulin 5 years post-diagnosis The results of a survey of 130 clinical practices of members of the Lawson Wilkins Pediatric Endocrine Society reported in 2000 that 48% of subjects were treated with insulin and 44% with oral agents Gut peptides with influence on appetite, weight, glucose glucagon amylin Modified for presentation 5

6 Diabetes complications (and a note on diagnosis) Type 1 Diabetes Treatment Goals for glucose control vary by age Very young children and infants: Safety first; avoid DKA and severe hypoglycemia Ages 5 to 12: Gradual tightening of control; A1c targets around 8% Greater than 12: A1c target 7%; 6.5% OK if can avoid severe hypoglycemia Glucose variability also found to play a role in macrovascular disease 6

7 Common insulin regimens Intensive management Lantus or Levemir once or twice a day to provide basal rate. Short acting insulin such as Humalog, Novolog, Apidra with meals. Very flexible in terms of meal times/amounts. NPH plus short acting NPH/short acting at breakfast, dinner; NPH at bedtime. Avoid lunch shot; but requires strict dietary adherence. 70/30 or 75/25 twice a day used in T2DM; or used in T1DM patients who have difficulty doing more intensive management or shots, or the uninsured. This regimen can work well in T2DM; in T1DM, it s just a way to get by w/o a disaster. Insulin pumps more on this later 7

8 Insulin side effects I m sure everyone here knows this, but patients don t. Insulin does not cause: Need for dialysis Problems with eyes Nerve problems These are all from poor diabetes control! It does cause: Hypoglycemia Some weight gain Recently in news: Lantus- cancer link. Lantus binds tightly to certain growth factors. Some speculation that it may cause existing cancer cells to grow more quickly. However, risk remains unproven at this time; if it does exist, it is very small; even Sanofi s competitors, when they come to our office, state that they doubt there is much to be worried about. Insulin Emergencies: Hypoglycemia The rule of 15: 15 grams CHO, recheck in 15 minutes, repeat until sugar >80 Glucose tablets 4 tabs 4 to 5 ounces of apple juice, soda, etc. Dizzy, passing out, seizure, can t take PO: Glucose gel rub on buccal mucosa/gums. One tube is 15 grams CHO Cake gel a cheaper version of glucose gel Glucagon: 0.5 mg for <7 years of age, 1.0 mg for >7 years of age. Intramuscular, subcutaneous, or IV 8

9 Type 2 Diabetes Insulin use Lantus The official ADA guideline does not advocate polypharmacy in terms of oral agents in T2DM. Instead, if metformin alone fails to achieve goals, suggest adding/titrating lantus; add short-acting insulin if this also fails. 70/30 or 75/25 These are widely used in T2DM. It is a mixed insulin, used twice/day. Can be very effective in T2DM, when some insulin production does remain. 9

10 Technology: Insulin Pens Some operate only on full units; others can dispense ½ units. Some have loadable cartridges; others are pre-filled and disposable. Manufacturers moving more and more to prefilled. Many insurance plans require prior authorization for pens Can be very economical in pediatrics, when doses are smaller (3 ml, not 10 ml, in each pen; insulin must be discarded 1 month after opening) Technology Insulin Pumps 10

11 Insulin pump regimens Technology More devices Blood glucose meters Ketone strips, Ketone Meters Test strips, lancets Glucowatch or similar: not indicated in peds CGMS A few patients with needle phobia are using a device called a J-tip: Injects SQ using high-pressure 11

12 So, that s what s in use, right now. But, as they told us in medical school, only 50% of what we tell you will still be valid in a few years. The problem is, we don t know which 50%. So what s coming in Pediatric Diabetes? Let s go back to our enteroendocrine slide Gut peptides with influence on appetite, weight, glucose glucagon amylin Modified for presentation 12

13 GLP-1 Barnett,Drugs Today 2005, 41(9): 563 GLP-1 Receptor Agonist (Exenetide) Stimulates first and later phase insulin release Delays gastric emptying Decreases food intake Indicated as adjuvant to metformin, sulfonylureas, or insulin May eventually have some use in T1DM also Rarely used as monotherapy, though can lower A1c when used this way SEs include nausea (50%, does improve with time, CNS effect), diarrhea (13%), Hypoglycemia when in combo with other drugs (10 to 20%). Sporadic reports of acute pancreatitis with this drug are a concern Not yet in pediatrics (in trial) 13

14 DPP-IV inhibitors DPP-IV hydrolyzes GLP-1 in 2-3 minutes Therefore inhibiting DPP-IV enhances action of endogenous GLP-1 Also it can be given orally, instead of subcutaneously Examples: Sitagliptin, Vildagliptin Also being used in combination with Metformin (example = Januvia) Not yet in pediatrics (in trial, high hopes for T2DM, maybe even in T1DM) Amylin/Amylin Analogues Not yet in pediatrics but hopes for both T1DM and T2DM in peds 14

15 There is more hope for these newer oral agents, even though some old standbys are rarely used in Peds: Sulfonylureas TZD s (TODAY study has been studying use, some potential for more use in future) Acarbose In fact unless it was a teenager who is nearly an adult, I would question using any of these in a pediatric patients Greater focus on long-term complications Statin therapy only Pravastatin approved in pediatrics as of yet Microvascular Kidney disease Generally ACE-Inhibitors are used for early microalbuminuria Blood Pressure Management Generally ACE-Inhibitors are used in diabetic patients 15

16 Common pharmaceutical issues Insulin dose not written specifically sometime this is intentional Insulin vials or pens for use at schools Prior authorization needed for the higher amounts of test strips or other diabetes technology used in Type 1 DM, vs. T2DM Common misunderstandings If your blood sugar is 300, it s because you missed medications or don t take care of your diabetes properly Not always true in Type 1 Diabetes He has Type 1 Diabetes, but I saw him eating that cake. Unbelievable how they don t take care of themselves! In T1DM, you should eat a normal, healthy diet. Occasional not frequent sugary snacks are OK (twice a week) If you have Type 2 diabetes and end up needing insulin, it means you were non-compliant Maybe but maybe not Herbal medications are more natural than Insulin or oral diabetes drugs These drugs are almost all patterned after human hormones 16

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