Standards of care in the Rx of Diabetes:

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Standards of care in the Rx of Diabetes
A practical approach
C.R.Kannan, M.D. Consultant in Endocrinology South
west Medical Associates Las Vegas , Nevada
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Standards of care in Rx of Diabetes
Introduction the scope
Glycemic control Early Insulin therapy
BP control
Lipid control
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Prevention of Complications Delaying progression
of complications
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ADA Standards for Control
Normal lt 6
A1c
Goal lt7
Intervention gt 7
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AACE Standards for Control
Normal lt 6
A1c
Goal gt 6.5
PP less than 140 mg
Intervention gt 7
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Treatment of Type 2 Diabetes
Oral agent failure when 2 consecutive A1c are
above 7
If 2 A1c s gt 7 on MFSU What next?
If 2 A1c s gt 7 on dual Rx
Mono therapy Metformin
Dual therapy Metformin Plus SU
When A1c is gt7 x 2 on monoRX
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Type 2 Diabetics failing on Dual therapy why
do they fail?
Build up of Glucotoxicity
Reversible
Eventual beta cell failure
Type 11/2 Diabetes
Irreversible
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TYPE 2 DIABETES . . . A PROGRESSIVE
DISEASE Progressive Decline of ?-Cell Function
in the UKPDS
100
80
Insulin reserve
60
?-Cell Function ( ?)
40
20
0
?10
?9
?8
?7
?6
?5
?4
?3
?2
?1
0
1
2
3
4
5
6
Years
Adapted from UK Prospective Diabetes Study
(UKPDS) Group. Diabetes. 1995441249-1258.
6-4
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If 2 A1c s gt 7 on MFSU What next?
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The mean A1c decline is no greater than 1.5 so,
this is a consideration if A1c is 7-9
Keep MF SU start Exenatide (byetta)
What is byetta?
GLP 1 analog
What is GLP 1?
Gut hormone INCRETIN
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Exogenous Glucose
satiety
Suppresses glucose production
Delays gastric absorption
Insulin
Glucagon
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When Sulfonylurea Metformin combination fails..
The mean A1c decline is no greater than 1 so,
this is a consideration if A1c is 7-8 weight
loss is an advantage. 2 shots needed
Keep MF SU start Exenatide (byetta)
Insulin therapy
Orals plus One shot ofGlargine
NPH Plus Regular Insulin BID
Basal plus prandial (bolus) Insulin
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MIMICKING NATURE WITH INSULIN THERAPY Insulin
Secretory PatternsBasal vs Mealtime peaks
Basal
Mealtime
120
100
80
?U/mL
60
Plasma insulin
40
Normal
20
0600
1200
1800
2400
0600
Time of Day
What does basal insulin do?
Riddle. Diabetes Care. 199013676-686.
6-18
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NPH or Lente was used in attempt to providebasal
insulin coverage as BID injections
6
5
Peak not 24 hr unpredictable
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Glucose Utilization Rate (mg/kg/h)
3
2
1
0
0
10
20
30
Time (h) After SC Injection
Lepore, et al. Diabetes. 199948(suppl 1)A97.
6-34
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Glargine provides basalbackground insulin to
turn off the switch ofinappropriate
hepaticgluconeogenesis
6
5
4
Glucose Utilization Rate (mg/kg/h)
3
2
1
0
0
10
20
30
Time (h) After SC Injection
6-34
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ADD Bedtime Glargine 15-20 units
Metformin Plus SU Failure
Monitor FBS daily
Increase Glargine by 5 U Q 5 days until FBS lt 160
Continue day time pills
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ADD Bedtime Glargine 15-20 units
Weekly adjustments
Increase Glargine by
Monitor FBS daily
2 U
Increase Glargine by 5 U Q 5 days until FBS lt 160
4 U
6 U
8 U
Continue day time pills
Goal 80-120
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3
Titrating Lantus dose
Every 3 days
2
2 units of Lantus
1
Until the FPG is 100
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Titrating Lantus dose
add1
Unit more every day
Until the FPG is 100 mg!
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Why keep the Sulfonylurea?
Glargine provides only Basal insulin
Secretagogue needed for prandial coverage.
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How do you tell if the Sulfonylurea is working?
By checking day time post meal BGs
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If the fastings are good, but yet the day time
glucose levels are un-controlled...
Not Glucotoxicity
Beta cell exhaustion
Candidate for basal and some type of pre meal
insulin
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Common errors in Lantus therapy
1. Not titrating the dose to goal of 100-110
average fasting glucose
2. Not providing a secretagogue
3. Not attaining adequate post prandial
control
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Treatment of Type 2 Diabetes
A1c lt 9 Add TZD or Byetta
A1c gt 9 Add Glargine
Advancing Rx I shot of basal I prandial with
largest meal using Lispro or Aspart
2 A1c s gt 7 on dual Rx
Mono therapy Metformin
Dual therapy Metformin Plus SU
Basal Bolus Rx
When A1c is gt7 x 2 on monoRX
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3
BP control
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24
32
44
37
34
47
56
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(No Transcript)
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ACE INHIBITORS
Testing for Microalbumin
ARBs
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For comparable BP control, does A2 receptor
blockade provide extra renal protection for Type
2 Diabetics?
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Two trials linking a disease spectrum
IDNT Study of irbesartan to assess its
protective effects in hypertensive patients with
type 2 diabetes and proteinuria
IRMA 2 Study of irbesartan to assess its
effect on slowing of the progression to overt
nephropathy in hypertensive patients with type 2
diabetes and microalbuminuria
25-33 RR
22-28 RR
Death
Parving H-H, et al. N Engl J Med
2001345870-878. Lewis EJ et al. N Engl J Med
2001345851-860.
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BP gt 130/80
Start ACE /ARB and titrate upward to maximum dose
NO
YES
Goal of 130/80
Add HCT
Continue ACE or ARB
Goal of 130/80
YES
NO
Continue ACE or ARB HCT
Add CCB Non DHP
Cont ACE or ARB HCT CCB
Goal of 130/80
YES
NO
Beta or Alpha Blocker
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4
Lipid control
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Ideal Lipid Targets for Diabetics
LDL Target lt 100 mg
Triglyceride Target lt 150 mg
HDL Target gt 40 mg
2 trials have shown benefits of LDL lowering in
diabetics- 4S, CARE
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LDL of lt 70 mg recommended
Very High Risk group Patients with CAD
PLUS one of four
- Diabetes - Multiple risk factors
- The Metabolic Syndrome - Acute
Coronary Syndrome
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LDL of lt 100 mg
Statins
Fibrate gemfibrozil fenofibrate
Triglycerides of lt 150
HDL of gt 50 in women gt 40 in men
Niacin
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Primary prevention trials in patients with
diabetes
CARDS
HPS
Secondary prevention trials in patients who are
very high risk
PROVE IT
REVERSAL
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Colhoun H, Betteridge DJ, Durrington P et
al Effectivenness of lipid lowering for the
primary prevention of major cardiovascular events
in diabetes Lancet. 2004 364 685-696
Collaborative Atorvastatin Diabetes Study
CARDS
Patients
2838 patients with diabetes
No hx of CAD or CVA Age gt
40 years LDL lt 160 mg TG
lt 600 mg and at least one of
the following
Hypertension Retinopathy
Albuminuria Smoking
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Followed for 4 years
Atorvastatin 10 mg
Acute coronary events
placebo
Stroke
revasculariazation
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LDL less than 100 mg 80 in Atorva group
less than 30 in
placebo
Lipid lowering in Atorva vs Placebo
26 lower
40 lower
1 higher
21 lower
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Outcomes in CARDS
36 P lt 0.001
31 P lt 0.001
48 P lt 0.02
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Conclusion 37 reduction decline in major
events regardless of baseline LDL level

First large scale trial for primary prevention in
patients with DM 2
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Lancet 2003 361 2005-2116
The Heart Protection Study- Diabetes Subset
Patients
5963 patients with diabetes
Type 1 or 2 Age gt 40
years LDL lt 116 No prior
hx of CAD
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Patients
5963 patients with diabetes
Type 1 or 2 Age gt 40
years LDL lt 116 No prior
hx of CAD
Randomized
Followed for 4 years
Primary end points
Simvastatin 40
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placebo