diabetes management in the outpatient setting
DESCRIPTION
Diabetes Management in the Outpatient Setting. Diagnostic Criteria (before 2010). FPG≥126 mg/dl. Prediabetes (IFG)≥100 mg/dl. 75 gram OGTT 2 hour-value≥200 mg/dl. Prediabetes (IGT)≥140 mg/dl. Random blood glucose≥200 mg/dl + symptoms (polyuria, polydipsia, unexplained weight loss). - PowerPoint PPT PresentationTRANSCRIPT
Diabetes Management in the Outpatient Setting
Diagnostic Criteria(before 2010)
•FPG≥126 mg/dl.•Prediabetes (IFG)≥100 mg/dl.
•75 gram OGTT 2 hour-value≥200 mg/dl.•Prediabetes (IGT)≥140 mg/dl.
•Random blood glucose≥200 mg/dl + symptoms (polyuria, polydipsia, unexplained weight loss).
International Expert Committee Report on the Role of A1C in the Diagnosis of Diabetes
6.5%
THE INTERNATIONAL EXPERT COMMITTEE. Diabetes Care 2009;32:1327
NORMAL IFG or IGT DIABETES
FPG < 100 mg/dl IFG
FPG > 100 - 125 mg/dl
FPG > 126 mg/dl
2-h PG < 140 mg/dl IGT
2-h PG > 140 -
199 mg/dl
2-h PG > 200 mg
Random PG > 200 + symptoms
A1C 5.7% to 6.4% ≥ 6.5%
2010 Diagnosis of Diabetes and Categories of Increased Risk for Diabetes
ADA, Diabetes Care 33: Suppl. 1, S11-S61, 2010
• A1c does not require patients to be fasting.• HbA1c reflects longer-term glycemia than does plasma
glucose.• Relatively unaffected by acute (e.g., stress or illness
related) perturbations in glucose levels.• Currently used to guide management and adjust therapy.• HbA1c laboratory methods are now well standardized and
reliable.
J Clin Endocrinol Metab 93: 2447–2453, 2008Diabetes Care 32 (7):1327-1334, 2009
Main factors in support of using HbA1C as a screening and diagnostic test
• Greater cost• Limited availability of A1C testing in certain
regions of the developing world• Incomplete correlation between A1C and average
glucose • Misleading in patients with anemia and
hemoglobinopathies.
Limitations of the Use of A1C for the Diagnosis of Diabetes
Factors influencing A1c
Recommendation of the International Expert Committee for the diagnosis of diabetes
• Diabetes should be diagnosed when A1C is ≥6.5%• Diagnosis should be confirmed with a repeat A1C test• Confirmation is not required in symptomatic subjects
with plasma glucose levels >200 mg/dl
• If A1C testing is not possible, previously recommended diagnostic methods (e.g., FPG or2HPG, with confirmation) are acceptable.
DIABETES CARE, VOLUME 32, NUMBER 7, JULY 2009
Who To Screen
•No major risk factors, FPG every 3 years beginning at 45 y.o.•Any risk factors, screen earlier and more often:
•Overweight (BMI>25 kg/m2).•First degree relative with T2DM.•High risk ethnic group.•Hypertension (≥140/90 mmHg).•HDL≤35 mg/dl and/or triglycerides≥250 mg/dl.•History of gestational diabetes or delivered baby ≥9lb.•Polycystic ovary syndrome.•History of vascular disease.•Habitual physical inactivity.
Treatment Goals for Type 2 Diabetes
Guidelines for Glycemic, BP, & Lipid Control American Diabetes Assoc. Goals
HbA1C < 7.0% (individualization)
Preprandial glucose 70-130 mg/dL (3.9-7.2 mmol/l)
Postprandial glucose < 180 mg/dL
Blood pressure < 130/80 mmHg
Lipids
LDL: < 100 mg/dL (2.59 mmol/l) < 70 mg/dL (1.81 mmol/l) (with overt CVD)HDL: > 40 mg/dL (1.04 mmol/l) > 50 mg/dL (1.30 mmol/l)TG: < 150 mg/dL (1.69 mmol/l)
ADA. Diabetes Care. 2012;35:S11-63HDL = high-density lipoprotein; LDL = low-density lipoprotein; PG = plasma glucose; TG = triglycerides.
Standard of Care-Multifactorial Therapy
•DCCT (1993) and UKPDS (1998) established role for better glycemic control on prevention of microvascular complications. •Studies that improved BP or lipids generally showed lower CAD in type 2 diabetes.•Steno 2 trial (2003) showed a marked lowering of both micro and macrovascular events when all 3 utilized.
•DCCT (1993) and UKPDS (1998) established role for better glycemic control on prevention of microvascular complications. •Studies that improved BP or lipids generally showed lower CAD in type 2 diabetes.•Steno 2 trial (2003) showed a marked lowering of both micro and macrovascular events when all 3 utilized.•Memory effect-longterm micro and macrovascularprotection years after stopping the trial-in DCCT, UKPDS, and Steno 2 trials.
Standard of Care-Multifactorial Therapy
But…then the role of intensive glucose control management came under active debate.
ConclusionsIntensive treatment of glycemia in the ACCORD cohort did not reduce the risk of
composite measures of advanced microvascular outcomesrenal failure: initiation of dialysis or ESRD, or renal transplant, or a rise of
serum creatinine above 3.3 mg/dLretinal photocoagulation or vitrectomy to treat diabetic retinopathy, or development of neuropathy
Intensive therapy delayed the onset of albuminuria and some measures of eye complications and neuropathy
Microvascular benefits of intensive therapy should be weighed against increase in total and CVD-related mortality, increased weight gain, and high risk for severe hypoglycemia
Figure 1 Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print](Adapted with permission from: Ismail-Beigi F, et al. Ann Intern Med 2011;154:554)
++
peripheralglucose uptake
hepatic glucose production
pancreatic insulinsecretion
pancreatic glucagonsecretion
Main Pathophysiological Defects in T2DM
gutcarbohydratedelivery &absorption
incretineffect
HYPERGLYCEMIAHYPERGLYCEMIA
?
Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011
Antihyperglycemic AgentsPlasma glucosePlasma glucose
Major Sites of ActionMajor Sites of Action
Glucosidase Inhibitors Glucosidase Inhibitors
Muscle/Fat Muscle/Fat GI tractGI tract
Carbohydrate AbsorptionCarbohydrate Absorption
Glucose UptakeGlucose Uptake
Liver Liver
Glucose Production Glucose Production
Injected InsulinInjected Insulin
InsulinSecretion InsulinSecretion
Pancreas Pancreas InsulinSecretion InsulinSecretion
Sulfonylureas MeglitinidesSulfonylureas Meglitinides
(-)
(+)(+)
1. Hines SE. Intensive management of type 2 diabetes. Patient Care.April 30, 2000:91-107.2. Kelley DB, ed. Medical Management of Type 2 Diabetes. 4th ed. Alexandria, Va: American Diabetes Association; 1998:56-72.
(-) (-)
(+)
MetforminGlitazonesMetforminGlitazones
Natural History of Type 2 DMPlasmaGlucosePlasmaGlucose
Relative-CellFunction
Relative-CellFunction
Postmeal glucosePostmeal glucose
Fasting glucoseFasting glucose
Insulin resistanceInsulin resistance
Insulin secretionInsulin secretion
126mg/dL126mg/dL
Years of DiabetesYears of Diabetes-20-20 -10-10 00 1010 2020 3030-30-30
DeFronzo RA. Pathogenesis of type 2 diabetes: Implications for metformin. Drugs. 1999;58 (suppl 1):29-30.
Management of Hyperglycemia in T2DM
ANTI-HYPERGLYCEMIC THERAPY
•Therapeutic options: Lifestyle
-Weight optimization
-Healthy diet
- Increased activity levelDiabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Management of Hyperglycemia in T2DM
ANTI-HYPERGLYCEMIC THERAPY
• Therapeutic options: Oral agents & non-insulin injectables
- Metformin
- Sulfonylureas
- Thiazolidinediones
- DPP-4 inhibitors
- GLP-1 receptor agonists
- Meglitinides
- -glucosidase inhibitors
- Bile acid sequestrants
- Dopamine-2 agonists
- Amylin mimetics
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
ClassClass MechanismMechanism AdvantagesAdvantages DisadvantagesDisadvantages CostCostBiguanides • Activates AMP-kinase
• Hepatic glucose production
• Extensive experience• No hypoglycemia• Weight neutral• ? CVD
• Gastrointestinal• Lactic acidosis• B-12 deficiency• Contraindications
Low
SUs / Meglitinides
• Closes KATP channels• Insulin secretion
• Extensive experience• Microvasc. risk
• Hypoglycemia• Weight gain• Low durability• ? Ischemic preconditioning
Low
TZDs • PPAR- activator• insulin sensitivity
• No hypoglycemia• Durability• TGs, HDL-C • ? CVD (pio)
• Weight gain• Edema / heart failure• Bone fractures• ? MI (rosi)• ? Bladder ca (pio)
High
-GIs • Inhibits glucosidase• Slows carbohydrate absorption
• No hypoglycemia• Nonsystemic• Post-prandial glucose• ? CVD events
• Gastrointestinal• Dosing frequency• Modest A1c
Mod.
Table 1. Properties of anti-hyperglycemic agents Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
ClassClass MechanismMechanism AdvantagesAdvantages DisadvantagesDisadvantages CostCostDPP-4inhibitors
• Inhibits DPP-4• Increases GLP-1, GIP
• No hypoglycemia• Well tolerated
• Modest A1c • ? Pancreatitis• Urticaria
High
GLP-1 receptor agonists
• Activates GLP-1 R• Insulin, glucagon• gastric emptying• satiety
• Weight loss• No hypoglycemia• ? Beta cell mass• ? CV protection
• GI• ? Pancreatitis• Medullary ca• Injectable
High
Amylin mimetics
• Activates amylin receptor• glucagon• gastric emptying• satiety
• Weight loss• PPG
• GI• Modest A1c • Injectable• Hypo w/ insulin• Dosing frequency
High
Bile acid sequestrants
• Bind bile acids• Hepatic glucose production
• No hypoglycemia• Nonsystemic• Post-prandial glucose• CVD events
• GI• Modest A1c• Dosing frequency
High
Dopamine-2agonists
• Activates DA receptor• Modulates hypothalamic control of metabolism• insulin sensitivity
• No hypoglyemia• ? CVD events
• Modest A1c• Dizziness/syncope• Nausea• Fatigue
High
Table 1. Properties of anti-hyperglycemic agents Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
ClassClass MechanismMechanism AdvantagesAdvantages DisadvantagesDisadvantages CostCostInsulin • Activates insulin
receptor• peripheral glucose uptake
• Universally effective• Unlimited efficacy• Microvascular risk
• Hypoglycemia• Weight gain• ? Mitogenicity• Injectable• Training requirements• “Stigma”
Variable
Table 1. Properties of anti-hyperglycemic agents Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Management of Hyperglycemia in T2DM
ANTI-HYPERGLYCEMIC THERAPY
•Implementation strategies:
-Initial therapy
-Advancing to dual combination therapy
-Advancing to triple combination therapy
-Transitions to & titrations of insulin
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Management of Hyperglycemia in T2DM
Management of Hyperglycemia in T2DM
CONSIDERATIONS•Age•Weight•Sex / racial / ethnic / genetic differences•Comorbidities
-Coronary artery disease-Heart Failure-Chronic kidney disease-Liver dysfunction-Hypoglycemia
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Management of Hyperglycemia in T2DM
CONSIDERATIONS•Age: Older adults
-Reduced life expectancy-Higher CVD burden-Reduced GFR-At risk for adverse events from polypharmacy-More likely to be compromised from hypoglycemia
Less ambitious targetsHbA1c <7.5–8.0% if tighter
targets not easily achievedFocus on drug safety
Less ambitious targetsHbA1c <7.5–8.0% if tighter
targets not easily achievedFocus on drug safety
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Management of Hyperglycemia in T2DM
CONSIDERATIONS•Weight
-Majority of T2DM patients overweight / obese-Intensive lifestyle program-Metformin-GLP-1 receptor agonists-? Bariatric surgery-Consider LADA in lean patients
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Management of Hyperglycemia in T2DM
CONSIDERATIONS•Sex/ethnic/racial/genetic differences
-Little is known-MODY & other monogenic forms of diabetes-Latinos: more insulin resistance-East Asians: more beta cell dysfunction-Gender may drive concerns about adverse effects (e.g.,
bone loss from TZDs)
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
T2DM Anti-hyperglycemic Therapy: General RecommendationsDiabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Adapted Recommendations: When Goal is to Avoid Weight GainDiabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Management of Hyperglycemia in T2DM
CONSIDERATIONS•Comorbidities
-Coronary Disease
-Heart Failure
-Renal disease
-Liver dysfunction
-Hypoglycemia
Metformin: CVD benefit (UKPDS) Avoid hypoglycemia ? SUs & ischemic preconditioning ? Pioglitazone & CVD events ? Effects of incretin-based
therapies
Metformin: CVD benefit (UKPDS) Avoid hypoglycemia ? SUs & ischemic preconditioning ? Pioglitazone & CVD events ? Effects of incretin-based
therapies
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Management of Hyperglycemia in T2DM
CONSIDERATIONS•Comorbidities
-Coronary Disease
-Heart Failure
-Renal disease
-Liver dysfunction
-Hypoglycemia
Metformin: May use unless condition is unstable or severe
Avoid TZDs ? Effects of incretin-based
therapies
Metformin: May use unless condition is unstable or severe
Avoid TZDs ? Effects of incretin-based
therapies
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Management of Hyperglycemia in T2DM
CONSIDERATIONS•Comorbidities
-Coronary Disease
-Heart Failure
-Renal disease
-Liver dysfunction
-Hypoglycemia
Increased risk of hypoglycemia Metformin & lactic acidosis
US: stop @SCr ≥ 1.5 (1.4 women)
UK: dose @GFR <45 & stop @GFR <30
Caution with SUs (esp. glyburide) DPP-4-i’s – dose adjust for most Avoid exenatide if GFR <30
Increased risk of hypoglycemia Metformin & lactic acidosis
US: stop @SCr ≥ 1.5 (1.4 women)
UK: dose @GFR <45 & stop @GFR <30
Caution with SUs (esp. glyburide) DPP-4-i’s – dose adjust for most Avoid exenatide if GFR <30
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Management of Hyperglycemia in T2DM
CONSIDERATIONS•Comorbidities
-Coronary Disease
-Heart Failure
-Renal disease
-Liver dysfunction
-Hypoglycemia
Most drugs not tested in advanced liver disease
Pioglitazone may help steatosis Insulin best option if disease
severe
Most drugs not tested in advanced liver disease
Pioglitazone may help steatosis Insulin best option if disease
severe
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Management of Hyperglycemia in T2DM
CONSIDERATIONS•Comorbidities
-Coronary Disease
-Heart Failure
-Renal disease
-Liver dysfunction
-Hypoglycemia Emerging concerns regarding
association with increased mortality
Proper drug selection in the hypoglycemia prone
Emerging concerns regarding association with increased mortality
Proper drug selection in the hypoglycemia prone
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
T2DM Anti-hyperglycemic Therapy: General Recommendations Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Adapted Recommendations: When Goal is to Avoid HypoglycemiaDiabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Adapted Recommendations: When Goal is to Minimize Costs Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Physiologic Insulin Secretion :Basal/Bolus Concept
Breakfast Lunch Supper
Insu
lin(µ
U/m
L)
Glu
cose
(mg
/dL
)
Basal Glucose
150
100
50
07 8 9 1011 12 1 2 3 4 5 6 7 8 9
A.M. P.M.
Time of Day
Basal Insulin
50
25
0
Prandial Glucose
Prandial Insulin
Suppresses Glucose Production Between Meals & Overnight
Basal 50% of Daily Needs
Management of Hyperglycemia in T2DM
Long (Detemir)
Rapid (Lispro, Aspart, Glulisine)
Hours
Long (Glargine)
0 2 4 6 8 10 12 14 16 18 20 22 24
Short (Regular)
Hours after injection
Insu
lin le
vel
ANTI-HYPERGLYCEMIC THERAPY
Therapeutic options: Insulin
Intermediate (NPH)
Initial calculation of basal dose•BW in kilograms x sensitivity index (0.15 – 0.2 )
Or•Body Weight in pounds x 0.1
From BID NPHTake total NPH dose and decrease by 20% for starting dose
Establishing Basal Requirement for Glargine
•Sequential increase•Increase every 2-3 days by
4 U if FBG>140 mg/dL2 U if FBG=120mg/dL to 140 mg/dLOR
•Mean of am BG after five days•Add to initial Glargine by formula
(Average BG-100)/10•Example: 200 pounds on 20 units glargine q hs, mean am BG is200 on 6th and 7th day
Add (Av BG -100)10 to glargine, (200-100/10)
i.e. increase from 20 to 30 units q hs• 2nd week--average 130 ,increase glargine from 30 to 33
Establishing Basal Requirement for Glargine
•Sequential increase•Increase every 2-3 days by
4 U if FBG>140 mg/dL2 U if FBG=120mg/dL to 140 mg/dLOR
•Mean of am BG after five days•Add to initial Glargine by formula
(Average BG-100)/10•Example: 200 pounds on 20 units glargine q hs, mean am BG is200 on 6th and 7th day
Add (Av BG -100)10 to glargine, (200-100/10)
i.e. increase from 20 to 30 units q hs• 2nd week--average 130 ,increase glargine from 30 to 33
Establishing Basal Requirement for Glargine
Sequential Insulin Strategies in T2DM Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Management of Hyperglycemia in T2DM
ANTI-HYPERGLYCEMIC THERAPY•Glycemic targets
- HbA1c < 7.0% (mean PG 150-160 mg/dl [8.3-8.9 mmol/l])
- Pre-prandial PG <130 mg/dl (7.2 mmol/l)
- Post-prandial PG <180 mg/dl (10.0 mmol/l)
- Individualization is key: Tighter targets (6.0 - 6.5%) - younger, healthier Looser targets (7.5 - 8.0%+) - older, comorbidities,
hypoglycemia prone, etc.
- Avoidance of hypoglycemiaPG = plasma glucose Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Management of Hyperglycemia in T2DM
KEY POINTS
• Glycemic targets & BG-lowering therapies must be individualized.
• Diet, exercise, & education: foundation of any T2DM therapy program
• Unless contraindicated, metformin = optimal 1st-line drug.
•After metformin, data are limited. Combination therapy with 1-2 other oral / injectable agents is reasonable; minimize side effects.
•Ultimately, many patients will require insulin therapy alone / in combination with other agents to maintain BG control.
•All treatment decisions should be made in conjunction with the patient (focus on preferences, needs & values.)
• Comprehensive CV risk reduction - a major focus of therapy.