Why We Pump Henry Anhalt, DO, CDE Director, Pediatric Endocrinology and Diabetes Saint Barnabas Medical Center Livingston, NJ
THE PANCREAS THROUGHOUT HISTORY • 1550 BCE-Papyrus describes polyuria and its treatment • 4th century BCE-Ayur Veda of Susruta (India) described sugarcream urine which attracted ants. • 7th century CE-Chinese physician Chen Chuan recorded sweet urine in diabetes • 1869-Langerhans describes islets • 1909-the name insuline is suggested by Jean de Meyer (Brussels) • 1921-Banting and Best-report discovering Insulin used in 1922
BANTING-1891-1941 & BEST-1899-1978 Orthopod who became a physiologist and died in air crash in Newfoundland while on wartime mission Together they isolated insulin and Banting won the Nobel Prize in 1923 knighted in 1934
Prevalence of Diabetes in the US Diagnosed Type 1 Diabetes1.5 Million(1:400-600 children) Diagnosed Type 2 Diabetes14 million Undiagnosed Diabetes6 Million 1.5 million new cases of diabetes were diagnosed in people aged 20 years or older in 2005
Good Glycemic Control (Lower HbA1c) Reduces Incidence of Complications DCCT 9 7% 63% 54% 60% 41%* Kumamoto 9 7% 69% 70% – – UKPDS 8 7% 17-21% 24-33% – 16%* HbA1c Retinopathy Nephropathy Neuropathy Macrovascular disease * not statistically significant DCCT Research Group. N Engl J Med. 1993;329:977-986. Ohkubo Y et al. Diabetes Res Clin Pract. 1995;28:103-117. UKPDS 33: Lancet.1998;352:837-853.
HbA1c and Microvascular Complications Retinopathy 15 13 11 9 7 5 3 1 Nephropathy Relative Risk Neuropathy 7 8 9 10 11 12 HbA1c, % 10
Every 1% HbA1c Increase Above Goal Elevates the Risk of Diabetic Complications +37% Incidence of Diabetes-Related Complications (%) +21% +14% +12% Increase in Any Diabetes-Related Endpoint Increase in Risk of Myocardial Infarction (MI) Increase in Risk of Stroke Increase in Risk of Microvascular Complications Adapted from Stratton et al. BMJ. 2000;321:405-412.
Physiology of Insulin and blood glucose Insulin secretion Basal Insulin Breakfast Lunch Dinner Blood glucose Basal blood glucose
Insulin Preparations Onset ofDuration of ActionPeak Action Humalog/Novalog5 to 15 min 1 to 2 hr 4 to 6 hr Human Regular 30 to 60 min 2 to 4 hr 6 to 10 hr Human NPH 1 to 2 hr 4 to 6 hr 10 to 16 hr Human Lente 1 to 2 hr 4 to 6 hr 10 to 16 hr Human Ultralente 2 to 4 hr Unpredictable <24 hr Lantus 30minutes none 24hr
NPH and regular insulin - 2 injections Bkfst lunch dinner bedtime bkfst
Disadvantages of NPH/ Regular regimen • No flexibility: • Required certain amount of calories a day • Skipped meal - hypoglycemia (peak of NPH) • Exercise - hypoglycemia (excessive glucose use) • At night - hypoglycemia (peak of NPH) • Overeating- hyperglycemia (not enough) • Oversleeping- hyperglycemia(skipped dose)
Results of conventional therapy • Poor control - HbA1C 10% and higher • Fear of hypoglycemia - worsening of control • Inability to exercise - poor fitness • Early development of complications • “OUT OF CONTROL”-Negative reinforcement • “Don’t Do This, Don’t Do That” • Mauriac syndrome - chronic insulin deficiency - stunted growth, hepatomegaly
Some causes of hypoglycemia in toddlers and preschoolers: • Unpredictable food intake and physical activity. • Imprecise administration of low doses of insulin. • Frequent viral infections. • Inability to convey the symptoms of low blood sugar. Adapted from Litton J et al; J Pediatr 2002;141:490-495.
Dr. Arnold Kadish of Los Angeles, California, devised the first insulin pump in the early 1960s. It was worn on the back and was roughly the size of a Marine backpack
Humalog/Novolog versus Regular • Rapid acting insulins: Start in 10min Peak in 1-2h Gone in 3.5-4h • Regular insulin: Starts in 30min Peaks in 3-4h Gone in 6-8h
Benefits of rapid acting insulins • May be given just prior to the meal or after meal in babies • Time of action match rise in sugar caused by most meals • No action left at the time of next meal - no boluses buildups • Less activity at bedtime - less night “low’s” and no need for bedtime snack
WHEN WE STARTED TO DABBLE-THREE SHOTS A DAY Lispro Lispro Insulin Effect NPH NPH B L S HS B Meals
Twice Daily vs. Three Daily Injections Rationale: Avoid Dawn Phenomenon and Somogyi Effect 872 adolescents evaluated over a 3-year period. Either regimen: • Increased insulin dose. • Deterioration of metabolic control. • Increase in BMI. • Females faired worse than males. Adapted from Holl R et al; Eur J Pediatr. 2003 Jan; 162(1): 22-9.
New Long Acting Insulin (Glargine Insulin) • Lantus is a new type of long acting insulin that has no peaks • Mimics physiological insulin (basal)
INSULIN TACTICSThe Basal/Bolus Insulin Concept • Basal Insulin • Insulin requirement to suppress hepatic glucose production between meals • Bolus Insulin (prandial) • Insulin requirement to maintain normal glucose disposal after eating • Insulin:CHO Ratio = 500/(total starting dose) • Correction Factor = 1500/(total starting dose) • Correction factor in young children = 1800/(total starting dose)
LANTUS AND NOVOLOG-”POOR MANS PUMP” Lispro Lispro Lispro Insulin Effect lANTUS B L S HS B Meals
Nine Preschool Patients Meticulously Cared For With MDI Switched To CSII: Mean A1c 9.5% reduced to 7.9%. • Severe hypoglycemic events 0.52 per month reduced to 0.09 per month. • Increased parental confidence and independence. • All refused to relinquish pump at completion of study. Adapted from Litton J et al; J Pediatr 2002;141:490-495.
Better Control and Less Hypoglycemia in Young Children HbA1c Hypoglycemia Litton J., J Pediatr 2002;141:490-495.
Glycemic Memory: Sustained Beneficial Effect Of Prior Intensive Therapy 195 patients between the ages of 13 and 17 in DCCT: • Decreased worsening of retinopathy by 74% (p < 0.001). • Decreased progression to proliferative or severe non-proliferative retinopathy by 78% (p < 0.007). Adapted from White, N et al, J Pediatr. 2001 Dec; 139(6): 804-12.
Glycemic Memory: Sustained Beneficial Effect Of Prior Intensive Therapy 195 patients between the ages of 13 and 17 in DCCT: • Relative risk of hypoglycemia < 1 among prior intensive group. • Prevalence of microalbuminuria 48% less. It is vital to achieve the best glycemic control early in the course in diabetes during adolescence and childhood. Adapted from White, N et al, J Pediatr. 2001 Dec; 139(6): 804-12.
“ Less than optimal glycemic control during the early years of diabetes has a lasting detrimental effect on the development and progression of complications, even after better glycemic control is established later in the course of the disease.” Adapted from White, N et al, J Pediatr. 2001 Dec; 139(6): 804-12.
From Preschool to Prom 161 patients with type 1 diabetes: • 26 ages 1 to 6 • 76 ages 7 to 11 • 59 ages 12 to 18 98% remained on CSII Reduced hypoglycemia (events/year) • Age 1 to 6: 0.42 to 0.19 • Age 7 to 11: 0.33 to 0.22 • Age 12 to 18: 0.33 to 0.27 Mean HbA1c levels Adapted from Ahern J et al; Pediatr Diabetes. 2002 Mar;3(1): 10-5.
I WAS A NON-BELEIVER • TOO HARD/TIME CONSUMING • I WAS UNINFORMED ON HOW TO USE THEM • NOT FOR THE VERY YOUNG OR THE UNMOTIVATED • ONLY AFTER HONEYMOON • YOU HAVE TO TEST FOR ME TO PUT YOU ON PUMP • YOU WILL SUFFER PSYCHOLOGICALLY
Purpose and Method of Study • Purpose: compare two algorithms of management for newly diagnosed kids with diabetes in our clinic. • Method: A study of HbA1c level and total daily insulin dose in 2 groups of patients with new onset diabetes type 1 at diagnosis, 6 months, and 12th months after diagnosis.
Hypothesis • Our hypothesis are: • Patients on pump have better control of their blood glucose level • Better control allows extension of the “honey moon” period
Treatment algorithm Group 1 (number of patients = 24) Treatment algorithm Group 2 (number of patients = 11) All patients with new onset diabetes were discharged within 3-5 days. All patients with new onset diabetes were discharged within 24 hours. Patients and parents were taught within 3 to 5 days in-hospital how to manage diabetes by pediatric endocrinology team. Patients and parents were taught within first 24 hours in-hospital how to manage diabetes by pediatric endocrinology team. Patients were started on Humalog and NPH in the hospital after correction of diabetic ketoacidosis. Patients were started on Humalog and Lantus after correction of diabetic ketoacidosis and regiment was continued for the first 1-2 weeks. CSII was started within first 14 days after diagnosis. A pediatric endocrinologist was available 24 hours a day 7 days a week to support insulin dose adjustment and education over the phone for the patients and parents. A pediatric endocrinologist was available 24 hours a day 7 days a week to support insulin dose adjustment and education over the phone for the patients and parents. Treatment Algorithm Algorithm #1 Algorithm #2
Conclusion: • Intensive teaching, 24 hour support, and CSII within 2 weeks of diagnosis improved patient’s HbA1c levels and decreased total daily dosage of insulin over traditional therapy. • CSII was beneficial for newly diagnosed diabetes patients at the onset of disease.
Typical Criteria Only motivated patients only patients who showed good compliance on previous regimen Adults and children > 6y old My Criteria Any patient who is willing to start and has abilities to learn May improve compliance Any age adults and children of any age (independent users 7-80 y old) Particularly “non-compliant” patients Candidates for pump therapy