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Type 2 Diabetes - Overview

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Title: Type 2 Diabetes - Overview


1
Type 2 Diabetes - Overview
  • Veronica Piziak MD, PhD
  • Endocrinology, Scott White

2
DisclosuresResearch support JJ
  • Objectives
  • Prevalence of diabetes
  • Prevention of diabetes
  • Diagnosis of diabetes
  • Treatment goals
  • Incorporating new medications into practice
  • Inpatient management of diabetes
  • Pump use
  • Hyperosmolar state

3
Type 2 DiabetesDefinition
  • A disorder of glucose, lipid, protein metabolism
    characterized by peripheral insulin resistance,
    inadequate pancreatic insulin secretory response
    and disordered glucagon supression.
  • Risk factors
  • Obesity
  • Heredity
  • Environment

4
The Diabetes Pandemic
5
25
40
6
Relationship Between BMI and Risk of Type 2
Diabetes
93.2
Men Women
54.0
Age-Adjusted Relative Risk
42.1
40.3
27.6
21.3
15.8
8.1
5.0
11.6
4.3
2.9
2.2
6.7
4.4
1.5
1.0
1.0
1.0
Body Mass index (kg/m2)
Chan J et al. Diabetes Care 199417961. Colditz
G et al. Ann Intern Med 1995122481.
7
Obesity Trends Among U.S. Adults 2009
(BMI 30, or 30 lbs. overweight for 5 4
person)
No Data lt10 1014
1519 2024 2529
30
CDC Data 2010
8
County-level Estimates of Diagnosed Diabetes for
Adults aged 20 years United States 2008
Metabolic syndrome
9
NCEP ATP III Working Definition of the
Metabolic Syndrome
?3 of the following
Risk Factor Defining Level Abdominal obesity
(waist circumference) Men
Intramesenteric Fat gt102 cm (gt40 in) Women gt 88
cm (gt35 in) Triglycerides ?150 mg/dL HDL
cholesterol Men lt40
mg/dL Women lt50 mg/dL Blood pressure ?130/?85
mm Hg Fasting glucose ?100 mg/dL
Some male patients may develop multiple
metabolic risk factors when waist circumference
is only marginally increased (eg, 94102 cm
3740 inches). NCEP ATP III. JAMA.
200128524862495.
10
New-onset Diabetes, A CHD Risk Equivalent, as
Correlated With the Number of Characteristics of
the Metabolic Syndrome
No. of MetS risk factors
RR
24.4
With event
7.26
4.50
2.36
1.00
Years
RR Relative risk
Adapted from Sattar N, et al. Circulation.
2003108414-419.
11
Metabolic Syndrome Impact on Cardiovascular
Health
25
P lt 0.001.
Isomaa B et al. Diabetes Care. 200124683-689.
12
Cardiometabolic Risk
Excess Abdominal Adiposity High-Risk Fat
Associated With Inflammatory Markers
Free Fatty
?
?
Acids
(C-Reactive Protein)
(FFAs)
?
Adiponectin
(insulin sensitizer)
Kershaw EE, et al. J Clin Endocrinol Metab.
2004892548-2556. Lee YH, et al. Curr Diab Rep.
2005570-75. Boden G, et al. Eur J Clin Invest.
20023214-23.
13

Modest Weight Loss Prevents Diabetes in
Overweight and Obese Persons With Impaired
Glucose Tolerance
Placebo, Lifestyle, and Metformin Participants
Diabetes Prevention Program Research Group. N
Engl J Med. 2002346393.
14
DPP USA
  • DEVELOPMENT OF DIABETES
  • 29 Placebo group
  • 14 lifestyle change
  • 58 decrease
  • 5 weight loss
  • lt30 fat, 10 saturated fat diet
  • No added sugar
  • 150 minutes/week of exercise
  • THOMPSON NIH
    BULLITEN 8/01

15
Food Plan for Metabolic Syndrome, Prediabetes,
Type 2 Diabetes
  • Caloric restriction is the key
  • Low CHO (6-8) with monounstaurated fats decreases
    insulin resistance
  • High complex CHO and fiber (25 gm) decrease
    insulin resistance
  • Fresh fruits and vegetables are important.
  • Lara-Castro C et al 2004 JCEM894197
  • Meal replacements work!
  • Add 150 minutes of exercise / week

16
When to use metformin for prevention
  • In addition to lifestyle counseling, metformin
    may be considered in those who are at very high
    risk for developing diabetes (combined IFG and
    IGT plus other risk factors such as A1C gt6,
    hypertension, low HDL cholesterol, elevated
    triglycerides, or family history of diabetes in a
    first-degree relative) and who are obese and
    under 60 years of age.
  • ADA practice guidelines 2010

17
Diagnosis of Diabetes
  • A1c may now be used
  • Prediabetes 5.7 - 6.4
  • Diabetes 6.5
  • Laboratory determination, venous sample
  • Not point of care testing
  • ADA practice guidelines 2010

18
Diagnostic Criteria for Diabetes, IFG, and IGT
IFG impaired fasting glucose. American Diabetes
Association. Diabetes Care. 200326(suppl
1)S5-S20.
19
ADA Treatment Goals
FPG/ 90130 mg/dL
PPG lt180 mg/dL
A1C Blood pressure lt 7 lowest possible without hypoglycemia lt 130/lt80 lower if renal disease
LDL HDL Triglycerides lt100 mg/dL, patients with diabetes (70-90) lt70 mg/dL, very highrisk patients with diabetes and CVD gt50 mg/dL, women gt40 men lt 150mg/dl


HDL
Triglycerides lt150 mg/dL
American Diabetes Association. Diabetes Care. 2010
20
ADA RENAL GUIDELINES
  • MICROALBUMIN/CREATININE SPOT URINE ANNUAL
    SCREENING
  • ANNUAL CREATININE
  • ESTIMATE GFR TO CHECK FOR DISEASE
  • www.kidney.org/professionals/kdoqi/gfr_
    calculator.cfm
  • NEED AGE,GENDER,CREATININE,RACE

21
ADA RENAL GUIDELINESESTIMATE GFR ANUALLY
  • STAGE
    ML/MIN
  • 1.RENAL DAMAGE NORMAL OR
  • INCREASED GFR
    /gt90
  • 2.RENAL DAMAGE
  • MILDLY DECREASED GFR
    60-89
  • 3.MODERATELY DECREASED GFR 30-59
  • 4.SEVERELY DECREASED GFR 15-29
  • 5. RENAL FAILURE
    lt15

  • DIALYSIS
  • STAGE 3 OR MORE REFER
  • Diabetes Care 2010 29S22-23

22
STATIN IN DIABETES
  • CONTROL OF
  • LIPIDS LDL lt 100 (lt70)
  • gt Age 40
  • Statins recommended regardless of LDL
  • Reduce the LDL by 30- 40
  • ADA Practice Guidelines Jan 2010 Diabetes Care
  • Statins are contraindicated in pregnancy
  • Aspirin in any diabetic who has had a CV event
    and mengt 50, women gt60 with a risk factor

23
The Goals of Glucose Control
Depend on the patient and the duration
of disease
24
Conventional Monotherapies are Unable to Maintain
Glycemic Control Over Time
United Kingdom Prospective Diabetes Study (UKPDS)

10
Duration of disease
Conventional
9
Insulin
Glibenclamide (glyburide)
8
MET
Median A1C ()
ADA Goal
7
AACE Goal
6
0
0
3
6
9
12
15
Time from randomization (years)
Conventional therapy defined as dietary advice
given at 3-month intervals where FPG was targeted
at best levels feasible in clinical practice. If
FPG exceeded 270 mg/dL, patients were
re-randomized to receive nonintensive MET,
chlorpropamide, glibenclamide, or insulin. If FPG
exceeded 270 mg/dL again, those on SU would have
MET added. If FPG exceeded 270 mg/dL after this,
insulin was substituted. MET metformin SU
sulfonylurea FPG fasting plasma glucose


Adapted from UK Prospective Diabetes Study
(UKPDS 34) Group. Lancet. 1998352854865.
25
UKPDSStudy Results Legacy Effect of Early
Glucose Control (Ins/SU Cohort)
After median 8.5 years post-trial follow-up
1997 1997
Aggregate End Point RRR () P value RRR () P value
Any diabetes-related end point 12 0.029 9 0.040
Macrovascular disease 25 0.0099 24 0.001
Myocardial infarction 16 0.052 15 0.014
All-cause mortality 6 0.44 13 0.007
1997
2007
P values were calculated with the use of the
log-rank test. RRRrelative risk reduction
SUsulfonylurea. Diabetes Trials Unit. UKPDS Post
Trial Monitoring. UKPDS 80 Slide Set. Available
at http//www.dtu.ox.ac.uk/index.php?maindoc/ukp
ds/. Accessed 12 September, 2008. Holman RR, et
al. N Engl J Med. 2008359epub ahead of print.
26
Action to Control CardiOvascular Risk in Diabetes
ACCORD Update
  • On February 6, 2008, NHLBI announced they have
    decided to stop the intensive glycemic treatment
    arm of the trial
  • Per DSMB scheduled review
  • Higher incidence of deaths in the intensive
    treatment group (HbA1c lt6.0) vs the standard
    treatment group (HbA1c 7.0 to 7.9)
  • Death rates in both glycemic control groups were
    lower than seen in similar populations in other
    studies

27
ACCORD
  • Adverse events
  • Hypoglycemia no. () I
    S
  • Requiring medical assistance 538 (10.5) 179 (3.5)
    lt0.001
  • Requiring any assistance 830 (16.2) 261 (5.1)
    lt0.001
  • Fluid retention no./total no. () 3541/5053
    (70.1) 3378/5054 (66.8) lt0.001
  • Clinical measures
  • Weight gain gt10 kg since baseline no./total no.
    () 1399/5036 (27.8) 713/5042 (14.1) lt0.001
  • NEJM June 12, 2008 vol. 358 no. 24
  • Effects of Intensive Glucose Lowering in Type 2
    Diabetes

28
Does intensive glucose control prevent death?
  • Meta analysis of data from 5 clinical trials
    involving 27,802 adults with Type 2 diabetes
  • VADT,ACCORD,ADVANCE,UKPDS (2)
  • 5 year risk of MI, Stroke, CHF, CV death, all
    cause mortality
  • No reduction in fatality ,CHF, Stroke
  • Significant increase in hypoglycemia
  • Kelly TN Ann Inter Med 2009151394-403

29
How Low should we go?
  • Early aggressive therapy
  • lt7.0 if possible without hypoglycemia ADA
    Guidelines
  • Goals of therapy
  • Control glucose individual level for
    patient
  • HbA1c 7-7.5 for patients with multiple
  • comorbidities ?? Avoid hypoglycemia!
  • Prevent microvascular complications
  • Prevent macrovascular complications
  • Montori VM, Fernandez-Balsells ann Int Med
    2009150803-808

30
ACCORD BP StudyConclusions
  • Effect of targeting a SBP goal of 120 mm Hg,
    compared to a goal of 140 mm Hg, in patients with
    type 2 diabetes at increased cardiovascular risk.
  • The results provide no conclusive evidence that
    the intensive BP control strategy reduces the
    rate of a composite of major cardiac events
    events in such patients.
  • However stroke was significantly reduced

Cushman W. N Engl J Med. 2010. epub ahead of print
31
INVEST
  • Diabetic patients with SBP not controlled (gt 140
    mm Hg) had the worst outcomes.
  • Tight Control lt 130 mm Hg) of SBP was not
    associated with improved CV outcomes compared
    with Usual Control (130-140 mm Hg)
  • There was increased risk for mortality in the
    Tight Control group which persisted during
    extended follow-up
  • SBP lt 115 mm Hg was associated with an increase
    in risk for mortality

32
INVESTResults Outcomes Tight Control Group
All Cause Mortality (n2255)
4.5
4.0
3.5
3.0
2.5
Adjusted Hazard Ratios
2.0
1.5
Reference
1.0
0.5
lt110
110 - lt115
115 - lt120
120 - lt125
125 - lt130
Systolic Blood Pressure (mmHg)
Other Significant Variables in Cox Regression
Model
Age, Race, PAD, MI, CHF, US Residency, Renal
Impairment, LVH, TIA/Stroke
Cooper-Dehoff R. ACC 2010. Late-Breaking Clinical
Trials. Atlanta, GA
33
Intensive vs Conventional Glucose Control in
Critically Ill PatientsThe NICE-SUGAR
Investigators
  • 3000 patients completed in each arm, groups well
    matched
  • Methods Within 24 hours after admission to an
    intensive care unit (ICU), adults were randomly
    assigned to undergo either intensive glucose
    control, target blood glucose range of 81 to 108
    mg
  • conventional glucose control, with a target of
    180 mg or less
  • The primary end point as death from any cause
    within 90 days after randomization.
  • 2009 NEJM3601283

34

NICE-SUGAR Study
  • Results A total of 829 patients (27.5) in the
    intensive-control group and 751 (24.9) in the
    conventional-control group died (odds ratio for
    intensive control, 1.14, 95 confidence interval,
    1.02 to 1.28 P0.02).
  • Operative (surgical) patients and nonoperative
    (medical) patients (odds ratio for death in the
    intensive-control group, 1.31 and 1.07,
    respectively P0.10). NS
  • Severe hypoglycemia (blood glucose level, 40 mg
    per deciliter was reported in 206 of 3016
    patients (6.8) in the intensive-control group
    and 15 of 3014 (0.5) in the conventional-control
    group (Plt0.001).
  • There was no significant difference between the
    two treatment groups in the median number of days
    in the ICU (P0.84) or hospital (P0.86) or the
    median number of days of mechanical ventilation
    (P0.56) or renal-replacement therapy (P0.39).
  • Conclusion Blood glucose target of less than 180
    mg resulted in lower mortality than a target of
    81 to 108 mg. On the basis of our results, we do
    not recommend use of the lower target in
    critically ill adults.
  • Check Mayo Clinic Proceedings May 200984400

35
Diabetes Education
  • The basis for adequate diabetes control

36
(No Transcript)
37
(No Transcript)
38
Treating Diabetes Insulin resistance
Beta and Alpha Cell Dysfunction
39
Antidiabetic agents Mechanism of Action
2 Muscle and adipose tissue ?glucose uptake/
?glucose utilization Metformin, TZDs
1 Intestine ? glucose/Fat absorptiondecreased d
igestion of carbohydrate/fat Acarbose/ Xenical,
bile acid binding resin
Insulin resistance
TZDs preserve Beta cell function
Blood glucose
4 Liver hepatic glucose output
Metformin ? HGO

Insulinresistance
3 Pancreas ? insulin secretion Sulfonylureas,
nateglinide
DeFronzo RA. Diabetes. 198837667-687.Lebovitz
HE. In Joslin's Diabetes Mellitus.
1994508-529 Amatruda JM. In Diabetes Mellitus.
1996. DeFronzo RA et al. J Clin Endocrinol Metab.
1991731294-1301. Whitcomb RW et al. In
Diabetes Mellitus. 1996Cavaghan MK et al. J Clin
Invest. 1997100530-537.Ehrmann DA et al. J
Clin Endocrinol Metab. 1997822108-2116
Wolffenbuttel BHR. Eur J Clin Pharmacol.
199345113-116
40
GLP-1 Modes of Action in Humans
  • Stimulates glucose-dependent insulin secretion
  • Suppress glucagon secretion
  • Slows gastric emptying

GLP-1 is secreted from the L-cells in the
intestine
  • Reduces food intake
  • Improves insulin sensitivity

Long term effectsdemonstrated in animals
This in turn
  • Increases beta-cell mass and maintains
    beta-cell efficiency

Drucker DJ. Curr Pharm Des 2001
71399-1412Drucker DJ. Mol Endocrinol 2003
17161-171
41
28-Day Exenatide Treatment in Type 2 Diabetes
Change in A1C at Day 28
Placebo Exenatide BID (bd) Exenatide BID
(bhs) Exenatide TID (bds)
0
Baseline
-0.2
(BYETTA)
-0.4
Mean (SE)Change in A1C ()
-0.6
-0.8

-1.0

-1.2

Intent to treat population (N109) P
lt0.006 BID (bd) breakfast, dinner BID (bs)
breakfast and bedtime TID (bds) breakfast,
dinner, bedtime.
Data from Fineman MS, et al. Diabetes Care 2003
262370-2377
42
Improvement in Cardiovascular Risk Factors with
3.5 Years of Exenatide Treatment (n 151) Change
from Baseline
  • LDL-C (mg/dL) -11.8 2.9 ?0.0001
  • Systolic Blood Pressure (mmHg) -3.5 1.2 -2
    ?0.0001
  • Diastolic Blood Pressure (mmHg) -3.3 0.8 -4
  • HDL-C (mg/dL) 8.5 0.6 24 ?0.0001
  • Triglycerides (mg/dL) -44.4 12.1 -12 0.0003
  • Total Cholesterol (mg/dL) -10.8 3.1 -5 0.0007
  • Weight loss avg 5.3 kg
  • Klonoff DC, et al. Curr Med Res Opin
    200824275-286
  • Nausea main side effect (use 20 minutes before
    meals), pancreatitis possible. Do not use Cr Cl
    lt30 Caution CrCl lt50

43
Liraglutide (Victoza)
  • 0.6 mg / day starting dose
  • Titrate 1.2-1.8 mg / day Multidose pens
  • Reduces postmeal glucose (A1c 1 lower)
  • Nausea most common side effect
  • Associated with pancreatitis in rare instances
  • Use with metformin, sulfonylureas, TZD
  • Weight loss 2 kg/26 weeks
  • Medullary carcinoma in animals

44
GLP-1 Secretion and Inactivation
DPP-4 dipeptidyl peptidase 4 GLP-1
glucagon-like peptide1.Deacon CF, et al.
Diabetes. 1995441126-1131.
45
Sitagliptin Monotherapy (Januvia) Significantly
Lowers FPG and PPG Levels
24-week placebo-adjusted results
FPG
2-Hour PPG
Mean Baseline 170 mg/dL
Mean Baseline 257 mg/dL
Plt0.001
Plt0.001
n 234
n 201
17
Mean Change in 2-Hour PPG, mg/dL
Mean Change in FPG, mg/dL
(95 CI 24, 10)
47
(95 CI 59, 34)
Compared with placebo. Least-squares means
adjusted for prior antihyperglycemic therapy
status and baseline value. Difference from
placebo. CIconfidence interval FPGfasting
plasma glucose PPGpostprandial plasma glucose
(meal challenge test). Aschner P et al. Diabetes
Care. 20062926322637.
46
Sitagliptin Once-Daily DosingProven 24-Hour
Glycemic Control
Patients With Renal Insufficiency, A dosage
adjustment is recommended in patients with
moderate or severe renal insufficiency and in
patients with end-stage renal disease requiring
hemodialysis or peritoneal dialysis.
50 mg once daily 25 mg once daily
Moderate CrCl ?30 to lt50 mL/min (Serum Cr levels mg/dL Men gt1.73.0 Women gt1.52.5) Severe and ESRD CrCl lt30 mL/min (Serum Cr levels mg/dL Men gt3.0 Women gt2.5)
Assessment of renal function is recommended prior
to initiation and periodically thereafter.
can be taken with or without food. Patients
with mild renal insufficiency100 mg once
daily. ESRDend-stage renal disease requiring
hemodialysis or peritoneal dialysis.
47
Saxagliptin (Onglyza)
  • 2.5, 5 mg
  • Lowers A1c about 0.5-1
  • May be used with dose adjustment in renal
    insufficiency
  • No weight loss

48
Bile Acid Binding ResinColesevelam (Welchol)
  • Approved for use in Type 2 diabetes
  • Lowers A1c by 0.8 625 mg x 6/day
  • Add on to metformin
  • May increase triglycerides when used with
    sulfonylurea or insulin.
  • Dont use when triglycerides are gt500
  • Many have GI side effects
  • May cause malabsorption of medications

49
New 2009 AACE/ACE Algorithm
Lifestyle Modification
A1c 6.57.5
A1c 7.69.0
A1c gt 9.0
Monotherapy
Drug Naive
Under Treatment
Dual Therapy8
Symptoms
No Symptoms
MET TZD2 DPP41 AGI3
MET GLP-1 or DPP41,10 or TZD2
MET SU or Glinide4,5
23 months
MET GLP-1 or DPP41 SU7
MET TZD2 SU7
MET GLP-1 or DPP41 TZDD2
INSULIN Other Agent(s)6
INSULIN Other Agent(s)6
Dual Therapy
MET GLP-1 or DPP41
MET TZD2
MET Glinide or SU5
TZD GLP-1 or DPP41
MET Colesevelam
MET AGI3
23 months
Triple Therapy9
MET GLP-1 or DPP41 TZD2
MET GLP-1 or DPP41 SU7
MET TZD2 SU7
23 months
Triple Therapy
MET GLP-1 or DPP41 TZD2
MET GLP-1 or DPP41 Glinide or SU4,7
23 months
23 months
INSULIN Other Agent(s)6
INSULIN Other Agent(s)6


Rodbard HW, et al .
Endocrine Practice. 200915(6)540-559.
50
Case 1
  • 65 yo female 100 kg type 2 diabetes
  • Stage 3 renal disease, s/p MI
  • HgbA1c 7.5 Fasting glucose 88mg
  • Does she have diabetes?
  • What s the A1c goal?
  • Could you use oral agents?
  • Which oral agents?
  • Would you use insulin? GLP-1 analog?
  • Just use diet and exercise?

51
Case 1 How to treat?
  • Lifestyle statin
  • DPP 4 inhibitors or TZD, sulfonylureas
  • AGI?, nateglinide (Starlix-generic),???
  • What diabetes therapy could we use that might
    decrease the risk of MI?
  • BAR

52
Case 2
  • 48 yo male 99 kg type 2 diabetes for 2 years. On
    no diabetes medication
  • A1c 8.9 Fasting glucose 128 mg
  • Creatinine, SGOT - WNL
  • Would you like more lab values?
  • What would you choose for therapy ?

53
Treating Type 2 Diabetes Insulin
deficiency ? Amylin
deficiency
54
Pancreatic islet morphology structural defects
are evident in type 2 diabetes
End stage type 2 diabetes
Adapted from Rhodes. Science 20053073804
55
Action Profiles of Insulins
Aspart, glulisine, lispro 45 hours
Regular 68 hours
NPH 1216 hours
Detemir 14 hours
Plasma Insulin Levels
Glargine 24 hours
0
2
5
3
4
6
7
8
9
12
13
14
15
16
17
18
19
20
21
22
23
24
1
10
11
Hours
Burge MR, Schade DS. Endocrinol Metab Clin North
Am. 199726575-598 Barlocco D. Curr Opin Invest
Drugs. 200341240-1244 Danne T et al. Diabetes
Care. 2003263087-3092
56
CASE 3
  • 43 year Type 2 diabetes for 10 years
  • Smoker 2 PPD, BP 160/90
  • 100 KG HbA1c 9.9
  • 20 mg glyburide
  • 2000 mg metformin
  • AM 2h noon 2h dinner 2h hs
  • 250 340 270 360 260 320 240
  • Basal Insulin 0.5-2 units/kg/day
  • Continue metformin Stop glyburide ?
  • Stop smoking! Needs 2 BP meds
  • Decrease CHO intake. 6 starches/day

57
Implementing New Titration Strategies With a
Basal Insulin
  • An ADA/EASD consensus algorithm for the
    initiation and adjustment of a basal insulin
    regimen at 10 IU per day is indicated as follows

Start with a long-acting basal insulin, initiated
at 10 IU/day
Check fasting glucose daily and increase dose by
2 IU every 3 days until fasting levels are in
target range (70-130 mg/dL)
  • ADA, American Diabetes Association EASD,
    European Association for the Study of Diabetes.
  • Please see Important Safety Information for
    LANTUS on slides 38-39.
  • Please see accompanying full Prescribing
    Information for LANTUS.
  • Nathan et al. Diabetes Care. 2006291963-1972.

58
Case 3
  • Comes into the hospital for CABG
  • What to do about control of diabetes
  • Stop oral agents and injectables except insulin
  • Basal/ bolus insulin therapy
  • Dont stop basal insulin reduce the dose if
    necessary

59
Action Profiles of Insulins
Detemir 14 hours
Plasma Insulin Levels
Glargine 24 hours
0
2
5
3
4
6
7
8
9
12
13
14
15
16
17
18
19
20
21
22
23
24
1
10
11
Hours
Burge MR, Schade DS. Endocrinol Metab Clin North
Am. 199726575-598 Barlocco D. Curr Opin Invest
Drugs. 200341240-1244 Danne T et al. Diabetes
Care. 2003263087-3092
60
What does basal insulin cover?
  • Excessive gluconeogenesis
  • Does this occur in the hospital?
  • Does stress occur in the hospital?
  • Protein and fat intake to some extent

61
Action Profiles of Insulins
Aspart, glulisine, lispro 45 hours
Regular 68 hours
Plasma Insulin Levels
0
2
5
3
4
6
7
8
9
12
13
14
15
16
17
18
19
20
21
22
23
24
1
10
11
Hours
Burge MR, Schade DS. Endocrinol Metab Clin North
Am. 199726575-598 Barlocco D. Curr Opin Invest
Drugs. 200341240-1244 Danne T et al. Diabetes
Care. 2003263087-3092
62
Bolus insulin
  • Meal supplement Mainly covers carbohydrate
  • Helps with protein and fat coverage
  • Correction factor
  • Compensates for insufficient basal insulin or
    insufficient meal supplement
  • If NPO use regular insulin q 6 hours

63
RATE AT WHICH NUTRIENTS CHANGE BLOOD GLUCOSE
CHANGE
Carbohydrate
Protein
FAT
Rate of Change in hours
64
Rapid-Acting AnalogsFaster Dissociation
Tmax 40-50 minutes
Insulin aspart or lispro Regular human insulin
Capillary Membrane
Subcutaneous tissue
Tmax 80 - 120 minutes
65
BOLUS COVERAGE
  • Correction factor
  • Supplemental scale
  • May use anytime
  • Meal times are convenient
  • x units/ y mggt z mg
  • Insulin resistance
  • Type 2 2 4 units/50 mggt150 mg

66
BOLUS INSULIN- GO FIGURE Type 2 Diabetes
  • Meal coverage
  • Counting carbohydrates
  • 1 unit / 5-10 gm CHO
  • Cant count carbs? MD count them and estimate the
    meal supplement

67
Insulin Injection Devices
  • Insulin Pens
  • Faster and easier than syringes
  • Improve patient attitude and adherence
  • Have accurate dosing mechanisms, but inadequate
    resuspension of NPH may be a problem

68
Case of the uncontrollable glucose
  • 52 year Type 2 diabetes
  • 200 kg HbA1c 9.9
  • Stage 2 renal disease
  • 20 mg glyburide, precose 50mg ac
  • 2000 mg metformin, januvia 100mg/day
  • 150 units of Glargine BID
  • AM 2h noon 2h dinner 2h hs
  • 340 440 320 450 320 510 450

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What to do?
  • Meal replacements protein supplements if renal
    function is adequate
  • Bolus insulin how much?
  • 300 basal so 300 bolus
  • Pramlintide 60,120 micrograms before meals, cut
    the bolus dose by ½
  • Consult Endocrinology

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Beta Cell Deficiency in DiabetesInsulin and
Amylin
  • Amylin
  • Reported in 1987
  • 37-amino acid peptide
  • Co-located and co-secreted with insulin from
    pancreatic ß-cells

amylin
insulin
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Insulin and Amylinare Key Partner Hormones
glucagon
gastric emptying

plasma glucose

glucose disposal
Pancreas
insulin
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Pramlintide Synthetic Amylin Analog
  • Specifically engineered to overcome human amylin
    tendency to
  • Aggregate, adhere to surfaces
  • Form insoluble particles and amyloid plaques
  • Potency equal to or greater than human amylin

Pramlintide(25, 28, 29 Pro-h-amylin)
Human amylin
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SYMLIN Boxed Warning
PRAMLINTIDE
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SYMLIN Initiation in Type 2 Diabetes ALSO
DESCRIBED IN MEDICATION GUIDE
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Case of the uncontrollable glucose
  • 56 yo male obese male, A1c 12.8 on
  • Basal insulin 100 units 2 x/day and rapid acting
    insulin 100 units 3 times per day
  • What to do?

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This is a job for
  • U 500 insulin
  • Regular insulin that contains 500 units/cc
  • Basal insulin
  • Use before meals and at bedtime
  • Starting dose total daily dose/5/4 for single
    dose
  • (500 units U 100)/5 100 100/4 each dose

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The insulin patch may really be a pump
  •  
  • .

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Insulin Pumps
  • Who needs them?
  • Difficult to control glucose
  • Variable blood sugars in the night
  • Who can have them?
  • Those with adequate insurance coverage

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Pump problems leading to hospitalization
  • Most common
  • Patient doesnt monitor
  • Glucose drops slowly without producing symptoms
    Severe hypoglycemia and death may result
  • Insertion set malfunctions glucose rises DKA
    results without symptoms
  • Patient doesnt change insertion set and site
    becomes infected hospitalization for IV
    antibiotics

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Pump use in the hospital
  • Should the patient continue the pump?
  • Not critically ill
  • A1c lt 8.0
  • Able to show, basal rates, insulin to carb ratio,
    correction factor
  • Capable of supplying data to pump and giving
    bolus doses
  • OK continue

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Pump in Hospital?
  • Patient can not use pump
  • Find the total basal dose.
  • Substitute basal insulin same dose
  • If eating, the insulin to carb ratio is
    frequently the same
  • Start with the same correction factor and adjust
    as necessary

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Hyperosmolar state
  • Serum glucose elevated (600) frequently greater
    than 800 mg/dL.
  • Serum osmolality usually greater than 320 mOsm/L
  • Characterized by severe dehydration
  • BUN and creatinine usually elevated
  • Metabolic acidosis not usually present
  • Altered mental state

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Hyperosmolar state
  • Generally does not occur in patients who monitor
    their glucose values
  • Usually in those with poorly controlled diabetes
  • Usually occurs in patients on oral agents
  • Usually in conjunction with comorbid conditions,
    diuretics
  • Look for MI, rhabdomyolysis, infection
  • Mortality 20 (comorbid condition)

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Hyperosmolar StateTherapy
  • 1-2 L of isotonic saline in the first 2 hours. A
    higher initial volume may be necessary in
    patients with severe volume depletion.
  • Slower initial rates may be appropriate in
    patients with significant cardiac or renal
    disease. Caution should be taken to not correct
    hypernatremia too quickly, as this could lead to
    cerebral edema.
  • After the initial bolus, some clinicians
    recommend changing to half-normal saline, while
    others continue with isotonic saline. Either
    fluid likely will replenish intravascular volume
    and correct hyperosmolarity a good standard is
    to switch to half-normal saline once blood
    pressure and urine output are adequate.
  • Once serum glucose drops to 250 mg/dL, the
    patient must receive dextrose in the intravenous
    fluid. This may decrease the risk of developing
    cerebral edema.1

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Hyperosmolar State Therapy
  • Initiate insulin therapy as soon as possible
  • Most patients respond to fluids alone,with
    significant glucose lowering, however,
    intravenous insulin in dosages similar to those
    used in DKA can facilitate correction of
    hyperglycemia.
  • Insulin used without concomitant vigorous fluid
    replacement increases risk of shock.

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Intestinal liner EndoBarrier
  • Inserted into the small intestine just below the
    pylorus 60 cm in length prevents absorption of
    nutrients
  • Type 2 diabetes who received the EndoBarrier
    System experienced a reduction in HbA1c of gt2.4
    points at week 28, placebo group who reduction of
    .8 points at week 28.
  • 12 weeks 39 excess weight lost
  • Schouten et al Ann Surg on line October 2,2009

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Endo barrier
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