IDC IDC Diabetes Update: Diabetes Update: Recent Research and Impact Recent Research and Impact on Diabetes Management on Diabetes Management • Type 1 Diabetes Type 1 Diabetes – Post DCCT findings--improving glycemic Post DCCT findings--improving glycemic control and preventing complications control and preventing complications • Type 2 Diabetes Type 2 Diabetes – Impact of the United Kingdom Prospective Impact of the United Kingdom Prospective Diabetes Study on Current Practice Diabetes Study on Current Practice – Relationship between blood glucose, blood Relationship between blood glucose, blood pressure dyslipidemia and complications pressure dyslipidemia and complications • Diabetes in Pregnancy Diabetes in Pregnancy – New screening, diagnostic and treatment New screening, diagnostic and treatment criteria (use of Glyburide) for GDM criteria (use of Glyburide) for GDM
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IDC Diabetes Update: Recent Research and Impact on Diabetes Management Type 1 DiabetesType 1 Diabetes –Post DCCT findings--improving glycemic control and.
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IDCIDC
Diabetes Update: Diabetes Update: Recent Research and Impact Recent Research and Impact
on Diabetes Managementon Diabetes Management
• Type 1 DiabetesType 1 Diabetes– Post DCCT findings--improving glycemic control and Post DCCT findings--improving glycemic control and
preventing complicationspreventing complications
• Type 2 DiabetesType 2 Diabetes– Impact of the United Kingdom Prospective Diabetes Study on Impact of the United Kingdom Prospective Diabetes Study on
Current PracticeCurrent Practice
– Relationship between blood glucose, blood pressure Relationship between blood glucose, blood pressure dyslipidemia and complicationsdyslipidemia and complications
• Diabetes in PregnancyDiabetes in Pregnancy – New screening, diagnostic and treatment criteria (use of New screening, diagnostic and treatment criteria (use of
Glyburide) for GDMGlyburide) for GDM
IDCIDC
Epidemiology of Diabetes Epidemiology of Diabetes Interventions and Complications TrialInterventions and Complications Trial
6-Year Follow-up6-Year Follow-up
1375 SubjectsRecruited
Both original groups are nowtreated with the
goal of HbA1c <7%
710 Conventionally Treated Patients
HbA1c=9.2%
Annual measurements at
28 sites
710 IntensivelyTreated Patients
HbA1c=7.2%
IDCIDC
EDIC:EDIC: Comparison of Baseline and Year 6 HbA1cComparison of Baseline and Year 6 HbA1c
DCCT and EDIC: Conclusions for Type 1 DCCT and EDIC: Conclusions for Type 1 DiabetesDiabetes
• HbA1c <7% because near normal blood glucose HbA1c <7% because near normal blood glucose control prevents the development and progress of control prevents the development and progress of microvascular diseasemicrovascular disease
• Intensive insulin therapies can be utilized as they Intensive insulin therapies can be utilized as they do not increase the risk of macrovascular diseasedo not increase the risk of macrovascular disease
• Any lowering of blood glucose is important since Any lowering of blood glucose is important since there is a continuous relationship between glucose there is a continuous relationship between glucose lowering and reduction in the risk of complicationslowering and reduction in the risk of complications
IDCIDC
Type 2 Diabetes: ControversiesType 2 Diabetes: Controversies
• Does intensive glycemic control in Type 2 diabetes reduce Does intensive glycemic control in Type 2 diabetes reduce micro and macrovascular complications?micro and macrovascular complications?
• Are there advantages or disadvantages to sulfonylureas, Are there advantages or disadvantages to sulfonylureas, insulin or metformin?insulin or metformin?– ? Increased cardiovascular risk with insulin or SU? Increased cardiovascular risk with insulin or SU– Is metformin advantageous in those with obesity?Is metformin advantageous in those with obesity?
• Does aggressive lowering of blood pressure reduce the risk of Does aggressive lowering of blood pressure reduce the risk of secondary complications?secondary complications?
IDCIDC
• Designed in 1976Designed in 1976
• A 20-year, multicenter (23), prospective, A 20-year, multicenter (23), prospective, randomized, interventional trialrandomized, interventional trial
• Recruited 5102 Recruited 5102 newly diagnosednewly diagnosed type 2 type 2 diabetes patientsdiabetes patients– FPG >108 mg/dL (6 mmol/L) on two occasionsFPG >108 mg/dL (6 mmol/L) on two occasions
• Mean duration of follow-up: 11 yearsMean duration of follow-up: 11 years
* These therapies* These therapieswere combined or changedwere combined or changedto maintain targetto maintain target
IDCIDC
UKPDS: Conclusions From Intensive UKPDS: Conclusions From Intensive Glucose Control StudyGlucose Control Study
• Intensive glucose control achieved HbA1c lowering Intensive glucose control achieved HbA1c lowering of ~ 1.0% at 10 yearsof ~ 1.0% at 10 years– Mean Hb A1c Mean Hb A1c 7.9% 7.9% 7.0% 7.0%
• Intensive glucose control Intensive glucose control significantlysignificantly reduced reduced clinical complicationsclinical complications– Reduced microvascular complications by 25%Reduced microvascular complications by 25%
• Glycemic control deteriorated over time regardless Glycemic control deteriorated over time regardless of therapyof therapy
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66
77
88
99
00 33 66 99 1212 1515
Hb
AH
bA 1
c1c (%
)(%
)
Years from randomizationYears from randomization
ConventionalConventional
IntensiveIntensive
6.2% upper limit of normal range6.2% upper limit of normal range
• Intensive therapy for Type 2 diabetesIntensive therapy for Type 2 diabetes– Lowered risk of microvascular complicationsLowered risk of microvascular complications– Sulfonylureas and insulin DO NOT increase Sulfonylureas and insulin DO NOT increase
– Associated with significant increase in weight Associated with significant increase in weight (~6.8 lbs)(~6.8 lbs)
• No evidence of glycemic thresholdNo evidence of glycemic threshold– Benefits of intensive glycemic control outweigh the risk Benefits of intensive glycemic control outweigh the risk
of hypoglycemiaof hypoglycemia
UKPDS: Clinical Observations UKPDS: Clinical Observations Intensive Glucose Control StudyIntensive Glucose Control Study
UKPDS: Conclusions UKPDS: Conclusions Metformin Therapy in Overweight PatientsMetformin Therapy in Overweight Patients
• Metformin therapy may be preferable in Metformin therapy may be preferable in overweight individualsoverweight individuals– Comparable glycemic control Comparable glycemic control – Achieved with limited weight gain and less Achieved with limited weight gain and less
hypoglycemiahypoglycemia
• Potential benefit of metformin on CVD riskPotential benefit of metformin on CVD risk– Lower risk of myocardial infarction in those treated Lower risk of myocardial infarction in those treated
with metformin monotherapywith metformin monotherapy
– Benefit related to treatment of insulin resistance?Benefit related to treatment of insulin resistance?
IDCIDC
Achieving Sustained Glycemic Control Achieving Sustained Glycemic Control in Type 2 Diabetes in Type 2 Diabetes
Treatment Priorities After UKPDSTreatment Priorities After UKPDS
• Type 2 Diabetes - A Progressive DiseaseType 2 Diabetes - A Progressive Disease– Glucose control deteriorated over timeGlucose control deteriorated over time
– Insulin resistance and insulin deficiencyInsulin resistance and insulin deficiency
• Selection of TherapySelection of Therapy– Numerous treatment options availableNumerous treatment options available– Therapy must be selected to “fit” individual patient needs and Therapy must be selected to “fit” individual patient needs and
should change to adapt to disease progressionshould change to adapt to disease progression
IDCIDC
Pathogenesis of Type 2 DiabetesPathogenesis of Type 2 DiabetesInsulin Resistance and Insulin DeficiencyInsulin Resistance and Insulin Deficiency
Saltiel J. Saltiel J. Diabetes. Diabetes. 45:1661-1669, 199645:1661-1669, 1996. . Robertson RP. Robertson RP. Diabetes. 43:1085, 1994.
Tokuyama Y. Tokuyama Y. DiabetesDiabetes 44:1447, 1995. Polonsky KS. 44:1447, 1995. Polonsky KS. N Engl J Med N Engl J Med 1996;334:777.1996;334:777.
At risk for DiabetesAt risk for Diabetes
normal
IDCIDC
Confirmation of the Natural History of Confirmation of the Natural History of Type 2 Diabetes: Type 2 Diabetes: UKPDSUKPDS
66
77
88
99
00 33 66 99 1212 1515
Hb
AH
bA 1
c1c (
%)
(%)
ConventionalConventional
IntensiveIntensive
• Increasingly intensive Increasingly intensive therapies were required therapies were required to maintain glucose to maintain glucose control over timecontrol over time
• Multi-drug therapy or Multi-drug therapy or multi-dose insulin was multi-dose insulin was required in a majority of required in a majority of patients to maintain patients to maintain glucose control glucose control
UKPDS:UKPDS: Risk Factors for Coronary Risk Factors for Coronary Artery Disease in Type 2 DiabetesArtery Disease in Type 2 Diabetes
Identified 5 major risk factors for CAD:Identified 5 major risk factors for CAD:DyslipidemiaDyslipidemia
(High LDL, Low HDL)(High LDL, Low HDL)
HyperglycemiaHyperglycemia
HypertensionHypertension
SmokingSmoking
Turner, RC et al.Turner, RC et al. BMJBMJ 316:823-8, 1998 316:823-8, 1998
IDCIDC
UKPDS: Intensive Blood Pressure Control UKPDS: Intensive Blood Pressure Control in Type 2 Diabetesin Type 2 Diabetes
Goals: to determine whether:Goals: to determine whether:
1.1. Tight blood pressure control policy can reduce Tight blood pressure control policy can reduce morbidity and mortality in Type 2 diabetic morbidity and mortality in Type 2 diabetic patientspatients
2.2. ACE inhibitor (captopril) or Beta-blocker ACE inhibitor (captopril) or Beta-blocker (atenolol) is advantageous in reducing the risk (atenolol) is advantageous in reducing the risk of development of clinical complicationsof development of clinical complications
IDCIDC
Treatment OutcomesTreatment Outcomes
StartStart FinishFinish
Less tight control: 160/94 mm Hg 154/87 mm HgLess tight control: 160/94 mm Hg 154/87 mm Hg
Tight control:Tight control: 161/94 mm Hg 144/82 mm Hg 161/94 mm Hg 144/82 mm Hg
Average difference: ---- Average difference: ---- 10/5 mm Hg 10/5 mm Hg
UKPDS: UKPDS: Intensive Blood Pressure Control StudyIntensive Blood Pressure Control Study
*Tight vs less tight control.*Tight vs less tight control.
IDCIDC
UKPDS: Treatment of HypertensionUKPDS: Treatment of Hypertension
• ACE inhibitor ACE inhibitor (captopril)(captopril) and beta-blocker and beta-blocker (atenolol)(atenolol) were equally effective in reducing the were equally effective in reducing the risk of secondary complicationsrisk of secondary complications
• Continuous relationship between systolic BP Continuous relationship between systolic BP and diabetes related complications above 130 and diabetes related complications above 130 mm Hgmm Hg
IDCIDC
Type 2 Diabetes:Type 2 Diabetes: Potential Benefit of Combined Blood Pressure and Potential Benefit of Combined Blood Pressure and
Glucose Control (UKPDS)Glucose Control (UKPDS)
0
24
68
1012
1
2
3
4
HbA1cHbA1c
BPBP
Micro and Macrovascular Micro and Macrovascular Complications RiskComplications Risk
Implications of UKPDSImplications of UKPDSPriorities of CarePriorities of Care
• Intensive glycemic control in Type 2 diabetesIntensive glycemic control in Type 2 diabetes– ESSENTIAL to reduce risk of microvascular diseaseESSENTIAL to reduce risk of microvascular disease
– DOES NOT increase risk of macrovascular diseaseDOES NOT increase risk of macrovascular disease
– Continuous relationship of glucose with complicationsContinuous relationship of glucose with complications
• Macrovascular disease preventionMacrovascular disease prevention – Requires treatment of cardiovascular risk factors Requires treatment of cardiovascular risk factors
including hypertension and dyslipidemiaincluding hypertension and dyslipidemia
IDCIDC
Diabetes Self Management SkillsDiabetes Self Management SkillsMedical Nutrition Therapy Medical Nutrition Therapy && Activity Plan Activity Plan
GuidelinesGuidelines• All women by the 26th gestational weekAll women by the 26th gestational week
• At risk women at first pre-natal visit: At risk women at first pre-natal visit: age, multi-parity, previous GDM, genetic, age, multi-parity, previous GDM, genetic, obesityobesity
GuidelinesGuidelines• All women by the 26th gestational weekAll women by the 26th gestational week
• At risk women at first pre-natal visit: At risk women at first pre-natal visit: age, multi-parity, previous GDM, genetic, age, multi-parity, previous GDM, genetic, obesityobesity
• All pregnant women should be screenedAll pregnant women should be screened
• Tight glycemic controlTight glycemic control
IDCIDC
Diabetes Update: Recent Research Diabetes Update: Recent Research and Impact on Careand Impact on Care
• Type 1:Type 1:
– Blood glucose control directly related to development Blood glucose control directly related to development of both micro and macrovascular complicationsof both micro and macrovascular complications
• Type 2:Type 2:
– Blood glucose control directly related to development Blood glucose control directly related to development of both micro and macrovascular complicationsof both micro and macrovascular complications
• Gestational Diabetes:Gestational Diabetes:
– Adverse perinatal outcome associated with blood Adverse perinatal outcome associated with blood glucose control; target prevention of development of glucose control; target prevention of development of type 2 diabetestype 2 diabetes