MIME-Version: 1.0 Content-Type: multipart/related; boundary="----=_NextPart_01C55AE9.252D9030" This document is a Single File Web Page, also known as a Web Archive file. If you are seeing this message, your browser or editor doesn't support Web Archive files. Please download a browser that supports Web Archive, such as Microsoft Internet Explorer. ------=_NextPart_01C55AE9.252D9030 Content-Location: file:///C:/9EC3A292/ADVICE2005slides2.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" ADVICE 2005 Session 2

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Click to edit Master title style<= /div>
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------=_NextPart_01C55AE9.252D9030 Content-Location: file:///C:/9EC3A292/ADVICE2005slides2_files/master08.xml Content-Transfer-Encoding: quoted-printable Content-Type: text/xml; charset="utf-8" ------=_NextPart_01C55AE9.252D9030 Content-Location: file:///C:/9EC3A292/ADVICE2005slides2_files/master02.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii"
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------=_NextPart_01C55AE9.252D9030 Content-Location: file:///C:/9EC3A292/ADVICE2005slides2_files/pres.xml Content-Transfer-Encoding: quoted-printable Content-Type: text/xml; charset="utf-8" ------=_NextPart_01C55AE9.252D9030 Content-Location: file:///C:/9EC3A292/ADVICE2005slides2_files/slide0001.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" ADVICE 2005 Session 2
Promoting Better Health Outcome= s for Your Patients with Diabetes:

A 5-Part Review of Evidence-Ba= sed
Treatment and Education Strateg= ies
Betsy Dokken, NP, CDE
Diabetes Nurse Practitioner
Arizona Health Sci= ences Center
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Session 2
nNatural Progression of Type 2 = Diabetes
n
nGlycemic Control = 1: Focus on early Type 2 Diab= etes
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charset="us-ascii" ADVICE 2005 Session 2
Evidence-Based Medicine
nLevel 1:  Random= ized Controlled Trials
nLevel 2:  Head to Head Trials or Systematic        Review of Cohort Studies
nLevel 3:  Case-C= ontrol Studies
nLevel 4:  Case-series
nLevel 5:  Expert Opinion
------=_NextPart_01C55AE9.252D9030 Content-Location: file:///C:/9EC3A292/ADVICE2005slides2_files/slide0004.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" ADVICE 2005 Session 2
Course Participation
nPlease provide e-ma= il address
nSend to = tskinner@email.arizona.edu
nE-mail questions or comments regarding the course content
nSend a case to discuss
nIf applicable, I wi= ll share via e-mail with other participants
nAvailable at: http://vi= deo.biocom.arizona.edu/video/videolibrary/azte= lemed/ADVICE
------=_NextPart_01C55AE9.252D9030 Content-Location: file:///C:/9EC3A292/ADVICE2005slides2_files/slide0080.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" ADVICE 2005 Session 2
Natural Progression of Type 2 Diabetes = ;
------=_NextPart_01C55AE9.252D9030 Content-Location: file:///C:/9EC3A292/ADVICE2005slides2_files/slide0089.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" ADVICE 2005 Session 2
Normal Regulation of Plasm= a Glucose
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Muscle/fat
insulin response
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Insulin
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Normal
plasma glucose
12
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Glucose enters
peripheral tissues
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Glucose enters
the blood
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Pathogenesis= of Type 2 Diabetes
Two Defects
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Impaired glucose
clearance
&#= 13;
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Hepatic
insulin
resistance
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Muscle/fat
insulin
resistance
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Impaired
insulin
secretion
Hyperglycemia<= /b>
&#= 13;
16
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More gluco= se enters
the blood stream
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Less gluco= se enters
peripheral tissues
Glycosuria &= nbsp;
<= span style=3D'font-size:111%;color:#FFCC00;mso-special-format:lastCR;display:no= ne'>
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ACkAgAAAAJbj/gJVhB+pG+fP4psgMgqtwk5vbngJGIpkZZJio6bgesKtF7uc/NoYfusUv/NNgD9h hjbT1JA5Zs8ZhKJWJirTKulgR0Psk6g1IsTh7Gm6OJdZ6jG7jSAVAAA7 ------=_NextPart_01C55AE9.252D9030 Content-Location: file:///C:/9EC3A292/ADVICE2005slides2_files/slide0081.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" ADVICE 2005 Session 2
Natural History of Type 2 = Diabetes
nAdapted from International Diabetes Center (IDC) Minneapolis, Minnesota
=
=
=
=
=
=
=
<= b>Obesity
=
=
=
<= b>IFG*
=
=
=
<= b>Diabetes
=
=
=
<= b>Uncontrolled Hyperglycemia
=
=
=
<= b>50
=
=
=
<= b>100
=
=
=
<= b>150
=
=
=
<= b>200
=
=
=
<= b>250
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<= b>300
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<= b>350
=
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=
<= b>50
=
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<= b>100
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<= b>150
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<= b>200
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<= b>250
3D"Text
=
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Glucose
(mg/dL)
3D"Text
=
=
=
Relative
Function (%)
=
=
=
<= b>-10
=
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=
<= b>-5
=
=
=
<= b>0
=
=
=
<= b>5
=
=
=
<= b>10
=
=
=
<= b>15
=
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=
<= b>20
=
=
=
<= b>25
=
=
=
<= b>30
=
=
=
Years of Di= abetes
=
=
=
Post-meal Glucose
=
=
=
Fasting G= lucose
=
=
=
Insulin Resistance
=
=
=
Insulin L= evel
=
=
=
b-cell Failure
=
=
=
*= IFG =3D impaired fasting glucose
Sli= de 12. Natural History of Type 2 Diabetes

When i= ndividuals have insulin resistance, the normal response of the body is to increase insulin secretion. This hyperinsulinemia maintains normal glucose toleran= ce. When the beta cell begins to fail, in those people who develop diabetes, there first appears post-meal hyperglycemia and subsequently fasting hyperglycemia.

The on= set of diabetes occurs only after a significant decline in beta cell function occurs. There is some controversy about the relative importance of insulin resistance and impaired insulin secretion; however, “essentially all patients who have type 2 diabetes and elevated FPG levels have a defect in insulin secretion.”

Becaus= e the progression of diabetes is inevitable, most patients with type 2 diabetes will require combination therapy to reach an acceptable level of glycemic control.

DeFron= zo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131:281-303.

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file:///C:/9EC3A292/ADVICE2005slides2_files/slide0083.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" ADVICE 2005 Session 2
Characteristics of Early Type 2 Diabetes=
nSecretion of insulin from b= -cells is appx 50% of normal
nHepat= ic glucose production is high&#= 13;
nInsulin resistance is present
ØThis is the pathophysiology most modifiable by lifestyle behavior
------=_NextPart_01C55AE9.252D9030 Content-Location: file:///C:/9EC3A292/ADVICE2005slides2_files/slide0093.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" ADVICE 2005 Session 2
b-cell function
(% = of norm= al by = HOMA)
Adapted from Holman RR= . Diab Res Clin Pract= . 1998;40(suppl):S21-S25;
UKPDS. <= span style=3D'font-family:"Arial Narrow";mso-ascii-font-family:"Arial Narrow"; mso-bidi-font-family:"Times New Roman";color:white'>Diabetes= . 1995;44:1249-1258=
Years
0 <= /div>
20 <= /div>
40 <= /div>
60 <= /div>
80 <= /div>
100 <= /div>
= -10
= -9
= -8
= -7
= -6
= -5
= -4
= -3
= -2
= -1
0 <= /div>
1 <= /div>
2 <= /div>
3 <= /div>
4 <= /div>
5 <= /div>
6 <= /div>
Time of diagnosis
?&#= 13;
HOMA=3Dhomeostasis model assessment
Decline of b-Cell Function in the UKPDS Illustrates Progressive Nature of Di= abetes
Pancreatic function
=3D 50% of normal
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nWhat is the pathophysiologi= cal nature of the progressive b-cell failure?
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Glucose entry
GLUT2 glucose
transporter
Glucokinase
ADP/ATP
Potassium (KATP) channel closes
K+
2+
Calcium channel opens
     SUR 1
Insulin Secr= etion by the b-Cell
Roles of Glucose, K+, and Ca2+
Glucose metabolism
ADP/ATP<= /span>
K+
K+
Ca2+
Ca2+
 Kir 6.2
Insulin secretory granules
2+
Ca2+
Insulin secretion
K+
KATP channel subunits: <= /div>
SUR 1=3Dregulatory subunit;
Kir 6.2=3Dinward rectifying channel=
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b= - cell Failure
nInitial defect in early (first-phase) secretion
<= span style=3D'font-size:125%'>nLater defective b= asal secretion
nAmyloid fibril formation and deposi= tion
<= span style=3D'font-size:125%'>nHyper-proinsuline= mia
<= span style=3D'font-size:125%'>nProgressive hyperglycemia
------=_NextPart_01C55AE9.252D9030 Content-Location: file:///C:/9EC3A292/ADVICE2005slides2_files/slide0168.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" ADVICE 2005 Session 2
A: Normal islets wi= th beta cells (insulin) stained; B: alpha cells (glucagon) stained; C: Delta cells (somatostatin) stained.  Abov= e, right: Top panel: insulin-filled vesicles approaching the intercellular interface during 1st phase secretion. Bottom panel: = insulin-filled vesi= cles during 2nd  phase secretion.
I incl= uded this slide to demonstrate the cells of the……
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