1.
How Manage Outpatient of Diabetes Mellitus?

2.
1921 – Banting and Best Began to Isolate the “ Internal Secretion of the Pancreas”

5.
1923 Banting and Best Awarded Nobel Prize for Discovery And Use of Insulin in the Treatment of IDDM

6.
Islets of Langerhans  -cell destruction Insulin Deficiency Adipo- cytes Muscle Liver Decreased Glucose Utilization Glucagon Excess Increased Protein Catabolism Increased Ketogenesis Gluconeogenesis IncreasedLipolysis Hyperglycemia Ketoacidosis Polyuria Volume Depletion Ketonuria

8.
Classification of Different Forms of Diabetes Mellitus

9.
Type 1 DM <ul><li>Autoimmune destruction of the pancreatic islet cell </li></ul><ul><li>Hallmark = lymphocytic infiltration of islets </li></ul><ul><li>Progresses over years </li></ul><ul><li>Leads to insulin deficiency </li></ul><ul><li>Later may also be associated with glucagon deficiency </li></ul>

10.
Progression to Type 1 DM Autoimmune destruction “ Diabetes threshold” Honeymoon 100% Islet loss Autoimmune markers (ICA, IAA, GAD

11.
Disease-Free Survival is Shortened with More Numerous Antibodies

12.
EPIDEMIOLOGY <ul><li>Most common metabolic disease in childhood </li></ul><ul><li>Annual incidence 15 new cases per 100,000 in children < 18 yrs </li></ul><ul><li>Frequency increases with increasing age. </li></ul><ul><li>1: 1400 at age 5 yrs </li></ul><ul><li>1: 400 at age 16 yrs </li></ul><ul><li>Males and females equally affected </li></ul><ul><li>No correlation with socioeconomic status </li></ul>

13.
IDDM RISK OF CONCORDANCE <ul><li>Offspring of IDDM parent: </li></ul><ul><li>2-5% overall risk </li></ul><ul><li>Offspring of diabetic mother: </li></ul><ul><li>2% risk </li></ul><ul><li>Offspring of diabetic father: </li></ul><ul><ul><li>5% risk </li></ul></ul>

14.
Type I - IDDM <ul><li>1.9/100,000 school age children </li></ul><ul><li>1/1430@ 5 yr of age </li></ul><ul><li>1/360 @ 16 yr of age </li></ul><ul><li>ID twins </li></ul><ul><ul><li>50% concordance risk </li></ul></ul><ul><li>Dizygotic twins </li></ul><ul><ul><li>20% concordance risk </li></ul></ul><ul><li>Two shared HLA haplotypes </li></ul><ul><li>(DR3 + DR4) </li></ul><ul><ul><li>12-20% risk </li></ul></ul><ul><li>One shared HLA haplotype </li></ul><ul><li>(DR3 or DR4) </li></ul><ul><ul><li>5-7% risk </li></ul></ul><ul><li>No shared HLA haplotypes </li></ul><ul><ul><li>1-2% risk </li></ul></ul><ul><li>HLA DQ(beta) Asp 57 </li></ul><ul><ul><li>virtual protection </li></ul></ul><ul><li>HLA DQ(beta) non-Asp 57 </li></ul><ul><ul><li>100 X increased risk </li></ul></ul>

15.
DIABETES MELLITUS - TYPE I Body Systems Involved <ul><li>GU Urinary frequency </li></ul><ul><li>GI Nausea, vomiting, constipation abdominal pain </li></ul><ul><li>Respiratory Acidosis, Kussmaul breathing </li></ul><ul><li>Cardiovascular Vascular collapse, </li></ul><ul><li>dehydration tachycardia </li></ul><ul><li>CNS Cerebral edema </li></ul><ul><li>Musculoskeletal Glycogen depletion, K loss muscle weakness </li></ul>

16.
DIABETES MELLITUS - TYPE 1 THERAPEUTIC OBJECTIVES <ul><li>Achieve metabolic control </li></ul><ul><li>Maintain normal growth and sexual </li></ul><ul><ul><ul><li>Maturation </li></ul></ul></ul><ul><li>Prevent acute and chronic </li></ul><ul><li> complications </li></ul><ul><li>Prevent ketoacidosis </li></ul>

17.
IDDM: OPTIMIZING GLYCEMIC CONTROL <ul><li>Hypoglycemia: </li></ul><ul><ul><li>May be unaware </li></ul></ul><ul><ul><li>School grades </li></ul></ul><ul><ul><li>Early am symptoms </li></ul></ul><ul><ul><ul><li>Headache </li></ul></ul></ul><ul><ul><ul><li>Nightmares </li></ul></ul></ul><ul><ul><li>Look for at camp </li></ul></ul><ul><li>Reduce dose 10% </li></ul><ul><li>Hyperglycemia: </li></ul><ul><ul><li>Few symptoms </li></ul></ul><ul><ul><li>Nocturia </li></ul></ul><ul><ul><li>Dawn phenomenon </li></ul></ul><ul><ul><li>Adolescent insulin resistance </li></ul></ul><ul><li>Increase dose 10% </li></ul>

18.
Treatment of T1 DM <ul><li>Insulin </li></ul><ul><li>1 u/kg/day – 1.3 u/kg/day in puberty </li></ul><ul><ul><li>Standard 2 – 3 injections (NPH / Reg) / day </li></ul></ul><ul><li>Intensive Therapy </li></ul><ul><ul><li>long acting at bedtime + short acting at meals </li></ul></ul><ul><ul><li>4 – 6 shots / day </li></ul></ul><ul><li>Insulin Pump </li></ul><ul><li>Diet – adequate calories / limit fat / complex CHO </li></ul><ul><li>Exercise </li></ul><ul><li>GOAL – Optimal glycemic control </li></ul>

19.
DIABETES MELLITUS - TYPE 1 MONITORING STRATEGIES <ul><li>Self Blood Glucose Monitoring – 4-6 / day </li></ul><ul><li>Urine Testing – Ketones - PRN </li></ul><ul><li>Glycosylated Hemoglobin - HbA1 C - quarterly </li></ul><ul><li>Blood lipids - annually </li></ul><ul><li>Thyroid function – annually </li></ul><ul><li>Urine microalbumin – quarterly after 5 yr </li></ul><ul><li>Dilated fundoscopic – age 10 yr + 3-5 yr Hx </li></ul>

20.
TYPE I - DIABETES MELLITUS MONITORING STRATEGIES <ul><li>Glycosylated hemoglobin - HbA1c </li></ul><ul><ul><li>Average blood glucose 3-4 months </li></ul></ul><ul><ul><li>Affected by anemia, hemoglobinopathy </li></ul></ul><ul><li>Age dependent target range </li></ul><ul><ul><li>Probably HbA1c < 8% for most </li></ul></ul><ul><ul><li>school age children </li></ul></ul><ul><ul><li>adolescents </li></ul></ul><ul><li>Beware of hypoglycemia (80% risk in DCCT) </li></ul>

21.
Definition of Various Levels of Glycemic Control

22.
DIABETES MELLITUS-TYPE I COMPLICATIONS <ul><li>Acute Chronic </li></ul><ul><li>Hypoglycemia Neuropathy </li></ul><ul><li>Hyperglycemia Retinopathy </li></ul><ul><li>Ketosis Nephropathy </li></ul><ul><li>Ketoacidosis </li></ul>

23.
Hyperglycemia: Microangiopathic complications Hypoglycemia: Neuronal loss Poor school performance seizures

24.
Microangiopathic complications from DM can occur by the time of diagnosis but typically 10 – 15 yr

25.
Nephropathy <ul><li>Diabetes #1 cause of end-stage renal disease (ESRD) </li></ul><ul><li>1 st manifestation = microalbuminuria (low but abnormal, 30 mg/day or 20 µg/min urine albumin) </li></ul><ul><li>Without intervention </li></ul><ul><ul><li>In 80% albumin excretion increases 10–20% / year to overt nephropathy (albumin = 300 mg/24 h or 200 µg/min) over 10–15 yr </li></ul></ul><ul><li>Once nephropathy occurs </li></ul><ul><ul><li>GFR falls over several years (2–20 ml · min -1 · year -1 ). </li></ul></ul><ul><ul><li>ESRD develops </li></ul></ul><ul><ul><li>in 50% of type 1 DM with nephropathy within 10 years </li></ul></ul><ul><ul><li>and in 75% by 20 yr. </li></ul></ul><ul><li>Microalbuminuria is rare with short duration of type 1 DM </li></ul><ul><li>Screening in type 1 DM should begin after 5 yr of disease </li></ul>

26.
Retinopathy <ul><li>After 20 yr, nearly all patients with T1 DM and >60% with T2 DM have some retinopathy </li></ul><ul><li>In patients with T1 DM </li></ul><ul><li>3.6% of young-onset patients (aged <30 yr at dx) were legally blind </li></ul><ul><ul><li>86% of blindness was due to diabetic retinopathy </li></ul></ul><ul><li>1.6% of old-onset patients (aged 30 yr at dx) were legally blind. </li></ul><ul><li>Vision-threatening retinopathy almost never occurs with T1 DM in the first 3–5 years of diabetes or before puberty. </li></ul><ul><li>Dilated funduscopic – age 10 yr + 3-5 yr Hx </li></ul>

28.
Typical Split-Dose NPH-REG BID Regimen

29.
BID NPH / REG AM NPH / REG DINNER REG HS NPH

30.
OPC Management Tools <ul><li>School </li></ul><ul><li>Individual treatment plan </li></ul><ul><li>Glucagon </li></ul><ul><li>Administer for severe low BG </li></ul><ul><li>Nutrition </li></ul><ul><li>55% CHO </li></ul><ul><ul><li>Complex CHOs </li></ul></ul><ul><li>30% FAT </li></ul><ul><ul><li>< 10% Saturated </li></ul></ul><ul><li>15% Protein </li></ul>

31.
<ul><li>SICK DAY MANAGEMENT </li></ul><ul><ul><li>NEVER omit your insulin , even if you can't eat. </li></ul></ul><ul><ul><li>Test your blood sugar every 4 hours. If you need help, ask for it! </li></ul></ul><ul><ul><li>If you have T1 DM, test your urine for ketones every 4 hours. </li></ul></ul><ul><ul><li>Drink clear liquids (at least ½ cup / hr), and eat light foods </li></ul></ul><ul><ul><li>Rest. Do not exercise during an illness. </li></ul></ul><ul><ul><li>Call your doctor or diabetes educator if: </li></ul></ul><ul><ul><ul><li>You have an obvious infection </li></ul></ul></ul><ul><ul><ul><li>Your illness lasts longer than 2 days </li></ul></ul></ul><ul><ul><ul><li>You have vomiting or diarrhea more than 8 hours </li></ul></ul></ul><ul><ul><ul><li>Your blood sugar is over 400 mg in two consecutive tests </li></ul></ul></ul><ul><ul><ul><li>All urine tests are positive for large amounts of sugar </li></ul></ul></ul><ul><ul><ul><li>You have moderate to large urine ketones with a blood glucose level over 200 mg for more than 8 hours </li></ul></ul></ul><ul><ul><ul><li>You feel very ill or experience pain </li></ul></ul></ul><ul><ul><ul><li>You have extreme fatigue, shortness of breath, or dizziness </li></ul></ul></ul>

32.
<ul><li>For blood sugar over 150 mg/dl , add 10% of your total daily dose as Regular insulin every 4-6 hours. </li></ul><ul><ul><li>Here is an example: Blood sugar is 210 mg and urine ketones are negative. </li></ul></ul><ul><li>10% of the total dose = 4 units. </li></ul><ul><li>Add 4 units regular insulin to usual dose every 4-6 hours, when blood sugar is over 150 mg. </li></ul><ul><li>Total usual AM dose of insulin </li></ul><ul><li>NPH Regular </li></ul><ul><li>22 units 4 units </li></ul><ul><li>Total usual PM dose of insulin </li></ul><ul><li>NPH Regular </li></ul><ul><li>10 units 4 units </li></ul><ul><li>GRAND TOTAL: </li></ul><ul><li>40 Units </li></ul>

33.
<ul><li>For blood sugar over 150 mg/dl PLUS moderate to large ketones in the urine , add 20% of your total daily dose as Regular insulin every 4-6 hours. </li></ul><ul><ul><li>Example: Blood sugar is 300 mg, urine ketones - positive. </li></ul></ul><ul><li>20% of the total dose = 6 units. </li></ul><ul><li>Add 6 units regular insulin to usual dose every 4-6 hours, when blood sugar is over 150 mg and urine ketones are positive. </li></ul><ul><li>Total usual AM dose of insulin </li></ul><ul><li>NPH Regular </li></ul><ul><li>14 units 2 units </li></ul><ul><li>Total usual PM dose of insulin </li></ul><ul><li>Regular </li></ul><ul><li>4 units </li></ul><ul><li>Total usual bedtime dose of insulin </li></ul><ul><li>NPH </li></ul><ul><li>10 units </li></ul><ul><li>GRAND TOTAL: </li></ul><ul><li>30 Units </li></ul>

34.
The DCCT is a clinical study conducted from 1983 to 1993 by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The study showed that keeping blood glucose levels as close to normal as possible slows the onset and progression of eye, kidney, and nerve diseases caused by diabetes. NEJM 342:381-389, 2000 DCCT Study Findings Lowering blood glucose reduces risk: Eye disease 76% reduced risk Kidney disease 50% reduced risk Nerve disease 60% reduced risk

35.
RS is a 12 yr old female with T1 DM for 6 yrs. A1C = 7.3, insulin dose is AM: 8 Reg / 18 NPH; Dinner: 7Reg; HS: 20 NPH. BGs

36.
Continuous Glucose Monitor - Overnight Unsuspected and Asymptomatic Hypoglycemia – Common up to 85% of episodes are nocturnal

37.
Continuous Glucose Monitoring Device <ul><li>Worn like the pump </li></ul><ul><li>Inserted with similar tubing and catheter </li></ul><ul><li>Records continuously for three days </li></ul><ul><li>Downloaded to your computer </li></ul><ul><li>Data not yet available for patient use </li></ul><ul><li>Chase et al Pediatrics 107: 222 (2001) </li></ul><ul><ul><li>5 patients, 10 – 17 yr old, DM 3.8 – 9.3 yr </li></ul></ul><ul><ul><li>12.8 hypoglycemic episodes / patient / month </li></ul></ul><ul><ul><li>85% asymptomatic nocturnal </li></ul></ul><ul><ul><li>15% symptomatic nocturnal </li></ul></ul>

38.
Continuous Glucose Monitoring in Children with IDDM <ul><li>Majority have unsuspected, nocturnal hypoglycemia </li></ul><ul><li>Current insulin regimens are non-physiologic despite what we teach the residents </li></ul><ul><li>We need to develop new paradigms that incorporate designer insulins and pumps into management strategies for our patients </li></ul>

39.
BG Breakfast Lunch Dinner Insulin

40.
Currrent Insulins <ul><li>NPH </li></ul><ul><li>Precipitated with protamine </li></ul><ul><li>Requires 45 inversions to mix and achieve same bioavailability </li></ul><ul><li>Peak 4 – 10 hr </li></ul><ul><li>Lasts 12-18 hr </li></ul><ul><li>Patient and site variability </li></ul><ul><li>Regular </li></ul><ul><li>Supposed to be “fast” </li></ul><ul><li>Onset is ½ - 1 hr </li></ul><ul><li>Peak 2 – 3 hr </li></ul><ul><li>Lasts 6 – 8 hrs </li></ul><ul><li>Hexamers in bottle delay absorption </li></ul><ul><li>Mis-match meal – insulin results in lows </li></ul>

41.
BID Split-Dose / Mixed NPH / REG <ul><li>Induces fasting hyperinsulinemia and frequent hypoglycemia </li></ul><ul><li>Requires between meal snacks </li></ul><ul><li>Predisposes to obesity </li></ul><ul><li>Can NOT mimic pancreatic ß-cell insulin secretion </li></ul><ul><li>Limited day-to-day variability </li></ul>

42.
“ Designer” Insulins <ul><li>Glargine </li></ul><ul><li>GLY 21 /ARG 31 /ARG 32 </li></ul><ul><li>Ultra-long acting </li></ul><ul><li>No “peak effect” </li></ul><ul><li>Could be used to provide “basal” insulin secretion like pump therapy </li></ul><ul><li>Lispro </li></ul><ul><li>Invert lysine/proline </li></ul><ul><li>Currently in use </li></ul><ul><li>Ultra-short acting </li></ul><ul><li>Onset 15 minutes </li></ul><ul><li>Duration – < 4 hrs </li></ul><ul><li>Excellent for meal bolus, “correction” bolus, bedtime highs, toddlers </li></ul>

45.
Glargine / Lispro <ul><li>Avoids fasting hyperinsulinemia and hypoglycemia </li></ul><ul><li>Can mimic pancreatic ß-cell insulin secretion </li></ul><ul><li>36% had hypoglycemia vs 50% on NPH </li></ul>

47.
Insulin Pump Therapy <ul><li>6,500 in 1990 – 46,500 in 1998 </li></ul><ul><li>Uses Lispro Insulin ONLY </li></ul><ul><li>NO DEPOT </li></ul><ul><ul><li>Reduces hypoglycemia </li></ul></ul><ul><ul><li>Shortens time to DKA </li></ul></ul><ul><li>Can mimic pancreatic ß-cell insulin secretion </li></ul><ul><li>Improves life-style variability </li></ul><ul><li>Reduces need for snacks </li></ul>

48.
INSULIN PUMP THERAPY IN CHILDREN <ul><li>First US Attempts: Yale University – 1970s </li></ul><ul><ul><li>Increased short term mortality </li></ul></ul><ul><ul><li>Presumed: unrecognized hypoglycemia </li></ul></ul><ul><ul><li>Abandoned for several years </li></ul></ul><ul><li>Problems: </li></ul><ul><ul><li>Patients selected for poor compliance </li></ul></ul><ul><ul><li>Limited home BG technology </li></ul></ul><ul><ul><li>Regular insulin infused </li></ul></ul>

50.
Contemporary Insulin Pump Therapy in Children <ul><li>Most studies have highly selected patients </li></ul><ul><ul><li>Motivated, educable, adult supervision </li></ul></ul><ul><ul><li>Learn carbohydrate counting, insulin adjustment </li></ul></ul><ul><ul><li>Ideal: intensive Rx with MDI for 3-6 months first </li></ul></ul><ul><li>Lispro Insulin </li></ul><ul><ul><li>No depot to induce hypoglycemia </li></ul></ul><ul><ul><li>No depot to protect from ketoacidosis </li></ul></ul><ul><li>Target glucose range MUST be individualized </li></ul><ul><ul><li>Age appropriate </li></ul></ul><ul><ul><li>Adjusted for day-to-day changes in activity </li></ul></ul><ul><li>Maniatis et al Pediatrics 107:351 (2001) </li></ul><ul><ul><li>CSII in Routine DM Management works for most patients 10 / 17 with A1c > 9 did poorly tended to be male and skipped meal bolus shots </li></ul></ul>

51.
Components

52.
Typical Insulin Calculations <ul><li>BASAL </li></ul><ul><ul><li>Total daily dose – 25% </li></ul></ul><ul><ul><li>½ that is basal </li></ul></ul><ul><ul><li>Divide into equal 24 hr infusion rate </li></ul></ul><ul><li>BASAL </li></ul><ul><ul><li>TDD = 40 units/day </li></ul></ul><ul><ul><li>40 – 25% = 30 units/day </li></ul></ul><ul><ul><li>½ = 15 units basal </li></ul></ul><ul><ul><li>15 / 24 = 0.6 units/hr </li></ul></ul>

53.
Meal and Correction Bolus <ul><li>Meals </li></ul><ul><ul><li>CHO gms/meal </li></ul></ul><ul><ul><li>Divide by CHO factor </li></ul></ul><ul><ul><li>400 / TDD = gm CHO / unit insulin </li></ul></ul><ul><ul><li>400 / 30 = 13 gm CHO / 1 unit insulin </li></ul></ul><ul><li>“ Correction” </li></ul><ul><ul><li>Insulin sensitivity factor = 1500 / TDD </li></ul></ul><ul><ul><li>1500 / 30 = 50 mg/dl drop in BG for 1 unit insulin </li></ul></ul>

55.
RS typical insulin pump Rx TDD = 40 units / day <ul><li>Basal </li></ul><ul><li>40 – 25% = 30 </li></ul><ul><li>30 / 2 = 15 units/day </li></ul><ul><li>15/24 = 0.6 units/hr </li></ul><ul><li>Breakfast BG = 180 </li></ul><ul><li>Meal plan calls for 60 gm CHO </li></ul><ul><li>Meal Bolus </li></ul><ul><ul><li>400 / 30 = 13 gm CHO / unit insulin </li></ul></ul><ul><ul><li>60 gm / 13 = 4.6 units </li></ul></ul><ul><li>Correction Bolus </li></ul><ul><ul><li>1500 / 30 = 50 mg/dl drop / unit insulin </li></ul></ul><ul><ul><li>180 – 120 (target) = 60 </li></ul></ul><ul><ul><li>60 / 50 = 1.2 units </li></ul></ul><ul><li>Pre-Breakfast dose </li></ul><ul><ul><li>= 4.6 + 1.2 = 5.8 units </li></ul></ul>

56.
PUMP THERAPY IN CHILDREN PRO AND CON <ul><li>PROs </li></ul><ul><ul><li>Mimic pancreatic secretion </li></ul></ul><ul><ul><li>Adjustable to lifestyle </li></ul></ul><ul><ul><li>Accurate dosing </li></ul></ul><ul><ul><ul><li>(syringe is +/- 52%) </li></ul></ul></ul><ul><ul><li>Lower insulin levels </li></ul></ul><ul><ul><li>Hypoglycemia </li></ul></ul><ul><ul><ul><li>(Risks are lower than with MDI dosing) </li></ul></ul></ul><ul><li>CONs </li></ul><ul><ul><li>No depot </li></ul></ul><ul><ul><ul><li>ketoacidosis can begin in 2-4 hours </li></ul></ul></ul><ul><ul><li>Expense - $6,000 </li></ul></ul><ul><ul><li>Motivated, educated family and patient </li></ul></ul><ul><ul><li>Labor intensive </li></ul></ul><ul><ul><ul><li>start-up takes about 1 month </li></ul></ul></ul>

57.
DIABETES MELLITUS CLASSIFICATION <ul><li>Type 1 (IDDM) </li></ul><ul><ul><li>Typical symptoms - glycosuria, ketonemia </li></ul></ul><ul><ul><li>Random Plasma Glucose > 200 mg/dl </li></ul></ul><ul><ul><li>Fasting plasma glucose > 127 mg/dl </li></ul></ul><ul><li>Type 2 (NIDDM) </li></ul><ul><ul><li>Typical symptoms </li></ul></ul><ul><ul><li>Fasting plasma glucose > 127 mg/dl </li></ul></ul><ul><ul><li>2 hr post prandial glucose > 200 mg/dl </li></ul></ul>

58.
Different Forms of MODY

59.
Type 2 Diabetes Mellitus in Children <ul><li>Historically - Incidence 8-10% of children with DM </li></ul><ul><li>PIMA Indians 1960s </li></ul><ul><ul><li>Positive F-Hx </li></ul></ul><ul><ul><li>Obesity related </li></ul></ul><ul><ul><li>Increased Insulin and C-peptide </li></ul></ul><ul><ul><li>First US population with T2-DM > T1-DM </li></ul></ul><ul><ul><li>5% incidence 15-19 yr old vs 0.33% T1-DM </li></ul></ul>New Cases/100,000/yr (San Diego, LA, Cincinnati)

60.
TYPE 2 DM IN CHILDREN <ul><li>Among 10 – 19 yr olds in the US </li></ul><ul><li>T2 DM accounts for 33% of all new cases </li></ul><ul><ul><li>African Americans – 42% </li></ul></ul><ul><ul><li>Caucasians – 10% </li></ul></ul>

61.
Obesity Acanthosis Nigricans Adolescence

63.
T2 DM vs T1 DM T2 - DM T1 - DM Polyuria/dypsia + + Ketonuria + / - + / - DKA + / - + / - Autoimmunity + / - + Initial insulin Often required Required Honeymoon + + Worse @ illness + +

64.
T2 DM vs T1 DM T2 DM T1 DM Obesity 95% > 85%tile Not Common + Family Hx T2 72 – 85% Not Common Acanthosis Nigricans 60 – 86% 7% all school aged children Maternal Gestational DM + Not Common IUGR + Not common

65.
Pathophysiology of T2 DM Multifactorial Disease <ul><li>Genetic </li></ul><ul><li>Twin studies </li></ul><ul><ul><li>50 – 90% concordance </li></ul></ul><ul><li>PIMA Indians </li></ul><ul><ul><li>AD Single gene 4q </li></ul></ul><ul><li>Mexican-Americans </li></ul><ul><ul><li>Susceptibility locus 2 </li></ul></ul><ul><li>Insulin resistance </li></ul><ul><ul><li>African Americans 30% less insulin sensitive than Caucasians </li></ul></ul><ul><li>Environment </li></ul><ul><li>Insulin Resistance </li></ul><ul><ul><li>Obesity </li></ul></ul><ul><ul><li>Inactivity </li></ul></ul><ul><ul><li>High fat CHO diet </li></ul></ul><ul><ul><li>Mean age of onset = 13 yr </li></ul></ul><ul><ul><li>30% higher insulin requirement in puberty </li></ul></ul><ul><li>Decline in insulin </li></ul><ul><ul><li>“ glucose toxicity” </li></ul></ul><ul><li>IUGR </li></ul><ul><ul><li>Impaired insulin sensitivity high insulin levels reduced GLUT-1 transporter </li></ul></ul>

66.
Diagnosis of T1 vs T2 DM <ul><li>Obese Adolescent </li></ul><ul><li>High risk ethnic group </li></ul><ul><li>C-Peptide + Insulin </li></ul><ul><ul><li>Elevated = T2 DM </li></ul></ul><ul><ul><li>Not-Elevated </li></ul></ul><ul><ul><li>Immune Markers </li></ul></ul><ul><li>Thin Adolescent </li></ul><ul><li>Pre-adolescent </li></ul><ul><li>Low risk ethnic group </li></ul><ul><li>Immune Markers </li></ul><ul><ul><li>Positive = T1 DM </li></ul></ul><ul><ul><li>Negative </li></ul></ul><ul><ul><li>C-Peptide and Insulin </li></ul></ul>

67.
CO is a 9 yr 6 mo male with “IDDM” for 3 yr <ul><li>Dx hyperglycemia no DKA </li></ul><ul><li>No hospital admits since </li></ul><ul><li>Rx insulin: </li></ul><ul><ul><li>24 units / 56.7 kg </li></ul></ul><ul><ul><li>AM 3 R / 9 N </li></ul></ul><ul><ul><li>PM 5 R / 7 N </li></ul></ul><ul><li>A1C = 6.5 </li></ul><ul><li>BGs </li></ul><ul><ul><li>AM 146 – 143 </li></ul></ul><ul><ul><li>Noon 94 – 116 </li></ul></ul><ul><ul><li>PM 106 - 167 </li></ul></ul><ul><li>African American </li></ul><ul><li>Obesity </li></ul><ul><li>Acanthosis </li></ul><ul><li>Family history T2 DM </li></ul><ul><li>Type I or Type II? </li></ul><ul><li>Should he be Rx with </li></ul><ul><ul><li>Insulin? </li></ul></ul><ul><ul><li>Metformin? </li></ul></ul><ul><ul><li>Both? </li></ul></ul>

68.
Treatment of T2 DM in Children <ul><li>Decreased caloric intake </li></ul><ul><li>Decreased insulin resistance </li></ul><ul><li>Screen for microangiopathic complications </li></ul><ul><li>Drug Treatment </li></ul><ul><li>Insulin </li></ul><ul><ul><li>Only approved drug for use in children </li></ul></ul><ul><li>Metformin </li></ul><ul><ul><li>Biguanide </li></ul></ul><ul><ul><li>Suppresses hepatic glucose production </li></ul></ul>

69.
Therapy of T2 DM in Children <ul><li>Reduce calories – weight loss </li></ul><ul><ul><li>NOT T1 DM diet with high complex CHO </li></ul></ul><ul><li>No Between meal snacks </li></ul><ul><ul><li>NOT T1 DM where hypoglycemia is frequent </li></ul></ul><ul><li>Reduce CHO intake </li></ul><ul><li>Reduce fat intake </li></ul><ul><li>Exercise – increase healthy life style </li></ul><ul><li>NOT USUALLY EFFECTIVE </li></ul><ul><li>Drug treatment early </li></ul>