Documente Academic
Documente Profesional
Documente Cultură
Agustin Busta, MD
Assistant Professor Albert Einstein College of Medicine
Association of DM with total life expectancy and life expectancy with and without cardiovascular disease
Women with diabetes had more than double the risk of developing cardiovascular disease and, 2.2 times higher risk of dying among those with CVD, compared with nondiabetic women, Diabetic men, compared with non-diabetic men, had more than double the risk of developing CVD and a 1.7 times higher risk of dying once CVD was present.
Among those age 50 and older, diabetic men lived an average of 7.5 years less than men without diabetes, and diabetes reduced women's life expectancy by an average of 8.2 years. Life expectancy free of cardiovascular disease was reduced by 7.8 years in men and 8.4 years in women with diabetes.
Associations of Diabetes Mellitus with Total Life Expectancy and Life Expectancy with and without Cardiovascular Disease
Diabetic men and women 50y and older lived on average 7.5 & 8.2 years less than their nondiabetic equivalents
OH Franco, et al. Arch Intern Med. 2007;167:1145-1151.
men women
6 5 4 3 2 1 0 <5 %
>7 %
Known diabetes
Hb A1c
DCCT- EDIC
Post ad-hoc analysis shows a decreased of macrovascular complications on patients who received intensive insulin therapy in the DCCT trial.
Epidemiology of Diabetes Interventions and Complications Study (EDIC) Observational study DCCT participants (type 1 diabetes) Looked at risk factors for long-term complications
0.12
Cumulative Incidence
Hemoglobin A1C
10%
8%
6%
P < 0.001
P < 0.001
P = 0.61
DCCT
End of Randomized Treatment
EDIC Year 1
EDIC Year 7
*Diabetes Control and Complications Trial (DCCT) ended and Epidemiology of Diabetes Interventions and Complications (EDIC) began in year 10 (1993). Mean follow-up: 17 years.
DCCT/EDIC Research Group. JAMA. 2002;287:2563-2569. Copyright 2002 American Medical Association. All rights reserved. | Nathan DM, et al. N Engl J Med. 2005;353:2643-2653. Copyright 2005 Massachusetts Medical Society. All rights reserved.
Cont r olling Post pr a ndia l H y pe r glyce m ia Le a ds t o Re gr e ssion of gly ce Ca r ot id At he r oscle r osis in Pa t ie nt s W it h Type 2 D ia be t e s Me llit u s
Re p ag lin id e Gly b u r id e
Post pr a n dial Pe a k
260 220
Post pr a n dial Pe a k
* P = 0 .0 1
0 .0 0 1
0.0 1
Glucose (mg/dL)
* *
Before After
Before After
100
0 60 120 0 Minutes 60 120
Before
After
Before
G l y b u r
After
i d e
Repaglinide
C- II M T Regr e ssion Associa t ed W it h PPG, II L- 6 ,, and CRP C- M T Re gr ession Associat e d W it h PPG, L- 6 and CRP LC-IMT = carotid intima-media thickness; PPG = postprandial glucose; IL-6 = interleukin 6; CRP = C-reactive protein
Esposito K, et al. Circulat ion. 2004;110:214219
Slid e Sou r ce Lipids Online Slide Library www.lipidsonline.org
-10
-5
10
15
Onset
Diagnosis
Pre-diabetes
Adapted from Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789; Nathan DM. NEJM. 2002;347:1342-1349
UKPDS-DM Pancreas
Is a continue state of beta cell function impairment that will lead to an state of complete pancreas exhaustation and lead to pancreatic insulin secretion unsuffiency. Pancreas exhaustion rapidly occurred at rate of 24 % year, and in 10 years majority of patient needs insulin Majority of T2dm will fail to maintain targets withA1c with OAD because pancreas run out of insulin
50 40 30 20 10 0
50 40 30 20 10 0
3 years
6 years
9 years
3 years
6 years
9 years
Between NHANES III and NHANES 1999-2000, percentage of patients treated with drug therapy increased 7.2% Percentage of patients treated with insulin remained constant at ~27%
Adapted from Koro et al, Diabetes Care. 2004; 27(1):17-20
ACCORD: N Engl J Med 2008; 358(24):2545-59. ADVANCE: N Engl J Med 2008; 358 (24): 2560-72. VADT: J Diabetes Complications 2003; 17 (6): 314-22
Pork
Human** Human** Human** Analog** Human** Human** Human** Analog** Analog** Analog** Analog** Analog** Human** Analog**
Intermediate Acting (Onset 1-4 hrs, duration hrs 18-24)* Human Insulin Novolin N (NPH) (Lilly) Humulin N (NPH) (Lilly) Humulin L (Lente) (Lilly) Purified Insulin NPH Iletin III (Lilly) Long Acting (Onset 4-6 hrs, duration hrs 24-34)* Human Insulin Humulin Ultralente (Lilly) Basal Peakless Insulin Glargine-Lantus (Aventis) Detemir Levemir (Novo Nordisk) Mixed Insulins 70/30 Insulin Novolin 70/30 (Novo Nordisk) Humulin 70/30 (Lilly) Humulin 50/50 (Lilly) Humalog 50/50 Human** Human** Human** Pork
Human**
Analog** Analog**
* Onset and duration are rough estimates. They can vary greatly within the range listed and from person to person ** Human insulin is made by recombinant DNA technology
Insulin (U/mL)
50 25 0
Breakfast
Basal Insulin
Lunch Supper
Nutritional Glucose
Basal Glucose
7 8 9 1011 12 1 2 3 4 5 6 7 8 9 A.M. P.M.
Time of Day
0600
0800
0600
Time of day
B=breakfast; L=lunch; D=dinner
Polonsky KS et al. N Engl J Med. 1988;318:1231-1239
2 3 4
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Hours
Burge MR, Schade DS. Endocrinol Metab Clin North Am. 1997;26:575-598; Barlocco D. Curr Opin Invest Drugs. 2003;4:1240-1244; Danne T et al. Diabetes Care. 2003;26:3087-3092
Treat to Target Study Insulin Glargine vs NPH Insulin Added to Oral Therapy
Study Design
24-wk, multicenter, randomized, parallel, openlabel trial. Compared insulin glargine vs NPH given at HS in type 2 diabetics patients inadequately controlled on 1 or 2 oral agents Insulin dosage adjusted weekly by forced-titration schedule seeking FPG e100 mg/dL Measure achievement of A1C e7% without clinically significant nocturnal hypoglycemia 756 insulin-nave patients,on Glargine =367,on NPH = 389, mean age = 55yr, duration of diabetes = 8-9 yr, baseline A1c= 8.6%, BMI = 32 kg/m2.
Riddle M, Rosenstock J, HOE901/4002 Study Group. Diabetes. 2002;51(suppl 2):A113. Abstract 457-P
2.5
2.3
INITIATE Trial
28-weeks, parallel group randomized study comparing the safety and efficacy of biphasic insulin Aspart mix 70/30 bid vs Glargine qd.
Hypoglycaemia
9.8%
9.7%
4 3.4
P<0.05
( HbA1c
0.7
P<0.01
Final HbA1c 6.9% 7.4%
Glargine.
(40% A1C 7)
Mean (SE) Percentage Change from Baseline to 1 Year in Glycated Hemoglobin, Fasting Plasma Glucose, Postprandial Glucose, and Body Weight (Panel A) and Mean (+SD) Hypoglycemic-Event Rate (Panel B)
Glycated Hemoglobin Level, Hypoglycemia, and Increase in Body Weight at 1 Year and 3 Years
How should I start insulin therapy for my patients with Type 2 diabetes? According to the IDF Global Guideline for Type 2 Diabetes:
Insulin is the most effective way of reducing hyperglycaemia Insulin can be started as a basal insulin alone or with premix insulin Start insulin when glucose control on maximum tablets >7.5 % (HbA1c) Begin at low dose but titrate up rapidly in first month
IDF. Global Guideline for Type 2 Diabetes. 2005
A1c 7% after 2-3 months ? If hypoglycemia occurs, or FBS< 70 mg/dL, reduce HS dose by 4U, or 10% if dose is > 60U
No
Yes
If FBS in target range(70-130mg/dL),check bg before lunch,dinner, and at HS. Depending on bg results,add second injection as below. Can usually begin with ~ 4 U and ajust by 2 U every 3 days until bg is in range
No
Pre-dinner bg out of range. Add NPH insulin at breakfast or rapid acting at lunch
Yes
ADA/EASD Consensus Algorithm 2009
Recheck pre-meals bg levels and if out of range, may need to add another injection. If A1c continues to be out of range,check 2-h postprandial levels and adjust preprandial rapid-acting insulin
How should I advance insulin therapy for people with Type 2 diabetes?
Algorithm driven dose titration basal regimen*
Once daily intermediate or long-acting insulin Begin 10 U or 0.2 U/kg, titrate by 2 U every 3 days using pre-breakfast plasma glucose (PG) until in target range (70-130 mg/dL) HbA1c 7.0% after 3 months Check pre- breakfast, lunch, dinner, and bedtime PG Add rapid-acting insulin to the meal with the highest excursion Begin 4 U and adjust by 2 U every 3 days based on PG change Add additional meal-time injections if HbA1c 7.0% after 3 months
*Insulin regimens should be designed taking lifestyle and meal schedule into account; this algorithm provides a basic guideline for initiation and adjustment of insulin. Regimens with once- or twice-daily premixed insulins are also possible. Inhaled insulin dosing in 1 mg ( 3 U) steps. Nathan DM et al. Diabetes Care. 2006;29:1963-1972
4 3 2 1 0
48%o
1991 92
93
94
95
96
97
98
99 2000 01
Centers for Disease Control 2004.American Diabetes Association. Diabetes Care. 2005;28(suppl 1):S4-S36. 1- American Diabetes Association. Diabetes Care 2008;31:596-615
Umpierrez G et al. J Clin Endocrinol Metabol. 2002, 87:978-982.. Levetan CS et al. Diabetes Care. 1998;21:246-249.. Krinsley JS. Mayo Clin Proc. 2003;78:1471-1478.. Falciglia M et al. 66th ADA Scientific Meeting, 2006.
* *
Patients
20 15 10 5 0
<110 110-<198 198-<250 >250
Mortality
Hospital Complications
N=2471 patients with CAP, Canada
~3x ~2x
~4x
200-249
250-299
>300
Umpierrez GE et al. J Clin Endocrinol Metab. 2002;87:978-982. Bolk J et al. Int J Cardiol. 2001;79:207-214. Williams LS et al. Neurology. 2002;59:67-71. Malmberg K, et al. BMJ. 1997;314:1512. Van den Berghe G et al. N Engl J Med. 2001;345:1359-1367. Capes SE et al. Stroke. 2001;32:2426-2432.
DIGAMI Study
Diabetes, Insulin Glucose Infusion in Acute Myocardial Infarction (1997)
Acute MI With BG > 200 mg/dl Intensive Insulin Treatment IV Insulin For > 24 Hours Four Insulin Injections/Day For > 3 Months Reduced Risk of Mortality By:
28% Over 3.4 Years 51% in Those Not Previous Diagnosed
Follow-Up (y)
MI = myocardial infarction; DIGAMI = Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction. (Short and long term effect of intensive insulin therapy) 44vs33 Malmberg K et al. BMJ. 1997;314:1512-1515.
Intensive Insulin Therapy in Critically Ill Patients: The Leuven SICU Study
Randomized controlled trial: 1548 patients admitted to a surgical ICU, receiving mechanical ventilation. Patients were assigned to receive either:
Conventional therapy: IV insulin only if BG >215 mg/dL
Target BG levels: 180-200 mg/dL Mean daily BG: 153 mg/dL
Intensive therapy: IV insulin if BG >110 mg/dL Target BG levels : 80-110 mg/dL Mean daily BG: 103 mg/dL
Van den Berghe et al. N Engl J Med. 2001;345:1359-1367.
ICU Survival
1548 Patients (mostly OHS pts.) All with BG >200 mg/dl Randomized into two groups
Maintained on IV insulin Conventional group (BG 180-200) Intensive group (BG 80-110)
96
Intensive treatment
92
Conventional treatment, 8%
92 88 84 80 0
88 84 80 0
0 20 40 60 80 100 120 140 160
Conventional treatment
50
100
150
200
250
Reduction (% )
44%
CII
Patients with diabetes Nondiabetic patients
DSWI (%)
2 1 0 87 88 89 90 91 92 Year 93 94 95 96 97
Target blood glucose <150 mg/dL. IV = intravenous; CII = continuous insulin infusion; DSWI = deep sternal wound infection. Furnary AP et al. Ann Thorac Surg. 1999;67:352-362. (prospective 2467)
The current ADA guideline for pre-prandial plasma glucose levels is 90130 mg/dl
AACE- Endocrine Practice 10 (1): 77-82, 2004; AAE Endocrine Practice February 2006; ADA- Diabetes Care 27: 553-591, 2004
Initiate or continue IV insulin infusion as soon as patient comes out from the OR as follows:
Non-Diabetics
Check Finger Stick (FS) and initiate or adjust insulin infusion as per TIER 1 (Green Wheel) if any BG > 200 mg/dL Check FS and initiate or adjust insulin infusion as follows: If FS > 250 mg/dL bolus with 4 units of regular insulin IV and then follow IV Insulin rate as per weight (below) If FS < 250 mg/dL start as per weight (below) If patient < 70 Kg start as per TIER 1 (Green Wheel) If patient > 70 Kg start as per TIER 2 (Yellow Wheel)
Diabetics
DIABETES / HYPERGLYCEMIA DISCHARGE SUMMARY Date: Mr./ Ms. Diabetes Mellitus Type 1 Diabetes Mellitus Type 2 Post-Operative Hyperglycemia Who underwent: Coronary Artery Bypass Grafting Cardiac Valve Surgery Other Post-operatively treatment : Novolog ( Aspart ) Lantus
Important data: HgA1c Serum creatinine Weight Your patients Diabetes/Hyperglycemia discharge plan is as follows: Life style improvement- diet-control only Oral antihyperglycemic medication(s) Glucophage (Metformin) Prandin (Repaglinide) Januvia (DPP-IV Inh ) Sulfonylureas: Other Insulin(s) _____ AST/ALT
LDL-c
_____
Date :
Recommendations:
1) HgA1c goal of 7% or lower 2) You may also refer your patient to the Friedman Diabetes Institute for diabetes education.Friedman Diabetes Israel Medical Center317 East 17th Street, 8th Floor New York, NY 10003 www.frie
Time course of action of any insulin can vary in different people or at different times in the same person; thus, time periods indicated here should be considered general guidelines only. * Dose dependent
1. Mudaliar S et al. Endocrinol Metab Clin North Am. 2001;30:935-982.; 2. Endotext.com
Insulin Order
There are 6 options (order sets) for the initial insulin orders:
1. 2. 3. 4. 5. 6. Patients with type 1 diabetes or type 2 diabetes previously on insulin therapy- patients eating Patients with type 1 diabetes or type 2 diabetes previously on insulin therapy- patients NPO Patients with type 2 diabetes previously on oral agents- insulinnave patients - eating Patients with type 2 diabetes previously on oral agents, insulin-nave patients NPO Patients with newly diagnosed hyperglycemia - patient eating Patients with newly diagnosed hyperglycemia - patient NPO
Patients with type 1 diabetes or type 2 diabetes previously on insulin therapy- patients eating
Order HgbA1C Order hypoglycemia management nest Use Prior Total Daily Dose (TDD) of insulin, whenever possible, if patient was well controlled. If dose is not known or unable to assess control, TDD should be weight-based. TDD (0.4 u/kg)should be split as follows:
Basal: 50% of TDD : Lantus dose should be calculated as 50% of 0.4units/kg (0.2 units/kg) and given immediately upon arrival to the floor. Prandial: Novolog should be calculated as 15% of 0.4units/Kg given before each meal (TID AC) Correction/Supplemental Insulin Scale: Standard (or Low, Medium or High Dose according to risk of hypo or hyperglycemia). Correction Scale is given before meals and is added to Prandial dose. HS Correction Scale may be ordered but separately.
Patients with type 1 diabetes or type 2 diabetes previously on insulin therapy- patients eating
Approximate dose for a 70 kg patient 0.4 u/kg x 70 kg= 28 units a) Lantus 15 units SC Q 24hr (Q HS) b) Novolog 5 units SC Q AC before Breakfast, before Lunch and Before Dinner c) Correction/Supplement Insulin (Novolog) Scale before meals TID AC (Pick Standard, Low Dose, Medium Dose or High Dose)
Patients with type 1 diabetes or type 2 diabetes previously on insulin therapy- patients NPO
Order HgbA1C Order hypoglycemia management nest Use Prior Total Daily Dose (TDD) of insulin, whenever possible, if patient was well controlled. If dose is not known or unable to assess control, TDD should be weight-based. TDD should be split as follows:
Basal: 50% of TDD : Lantus dose should be calculated as 50% of 0.4 units/kg (0.2 units/kg) and given immediately upon arrival on the unit. Prandial: None Correction/Supplemental Insulin Scale: Standard Scale should be given q4-6 hours
Patients with type 1 diabetes or type 2 diabetes previously on insulin therapy- patients NPO Approximate dose for a 70 kg patient : 0.4 u/kg x 70 kg = 28 units a) Lantus 15 units SC Q 24hr (Q HS) b) Correction/Supplement Insulin (Novolog) scale (Standard) Q 4h c) D5 1/2NS at 100 cc/hr
Patients with type 2 diabetes previously on oral agents, insulin-nave - patients eating
Order HgbA1C Order hypoglycemia management nest Total Daily Dose (TDD) (0.3u/kg)of insulin should be weightbased; insulin should be dosed as follows:
Basal: 50% of TDD: Lantus dose should be calculated as 50% of 0.3 units/kg (0.15 units/kg) and given immediately upon arrival on the unit. Prandial: Novolog should be calculated as 15% of 0.3 units/kg and given before each meal (TID AC). Correction/Supplemental Insulin Scale: Standard (or Low, Medium or High Dose according to risk of hypo or hyperglycemia). Correction Scale is given before meals and is added to Prandial dose. HS Correction Scale may be ordered but separately.
Patients with type 2 diabetes previously on oral agents- insulin-nave patients - eating
Approximate dose for a 70 kg patient: 0.3 u/kg x 70 kg = 21 units a) Lantus 10 units SC Q 24hr (Q HS) b) Novolog 3 units SC Q AC before Breakfast, before Lunch and Before Dinner c) Correction/Supplement Insulin (Novolog) Scale before meals TID AC (Pick Standard, Low Dose, Medium Dose or High Dose)
Patients with type 2 diabetes previously on oral agents, insulin-nave - patients NPO
Order HgbA1C Order hypoglycemia management nest Total Daily Dose (TDD) of insulin should be weight-based; insulin should be dosed as follows:
Basal: Lantus dose should be calculated as 0.1 U/kg and given immediately upon arrival to the floor. Prandial: None Correction/Supplemental Insulin Scale: Standard Scale should be given q4-6hours.
Patients with type 2 diabetes previously on oral agents, insulin-nave - patients NPO Approximate: 0.1 u/kg x70 kg = 7 units a) Lantus 7 units SC Q 24hr (Q HS) b) Correction/Supplement Insulin (Novolog) scale (Standard) Q 4h c) D5 1/2NS at 100 cc/hr
Patients with newly diagnosed hyperglycemia patient NPO Approximate: Correction/Supplement Insulin (Novolog) scale (Standard) Q 4h
Hypoglycemia
Treatment of Hypoglycemia Patient alert : 15-30 gm of carbs ( 8 onz of juice, 2 crackers=10 carbs , glucose tablets) Non alert patient : 1 amp D50 or 1 mg glucagon IM (repeat q 15 min ) RULE OF THUMB : 15 gm of carbs will increased glucose levels 25-50 mg/dL Do Not Hold Insulin When BG Normal