Upload
bianca-monckton
View
215
Download
1
Tags:
Embed Size (px)
Citation preview
Diabetes:Diagnosis, Classification, Management
Controversies and News
Diabetes:Diagnosis, Classification, Management
Controversies and News
Leonid Poretsky, MD
Chief, Division of Endocrinology and Metabolism
Director, Gerald J. Friedman Diabetes Institute
Gerald J. Friedman Chair in Endocrinology
Professor of Medicine, Albert Einstein College of Medicine
Leonid Poretsky, MD
Chief, Division of Endocrinology and Metabolism
Director, Gerald J. Friedman Diabetes Institute
Gerald J. Friedman Chair in Endocrinology
Professor of Medicine, Albert Einstein College of Medicine
Bianca Alfonso, MD Bianca Alfonso, MD Endocrinology Fellow, Year 1Endocrinology Fellow, Year 1
Marina Krymskaya, ANP, CDE Diabetes Nurse Educator
Jill Gregory Medical Illustrator
Diabetes Care Enhancement InitiativeDiabetes Care Enhancement Initiative Team: Leonid Poretsky, MD; Agustin Busta, MD; Morton Davidson, MD; Marina
Krymskaya, RN, NP; Jason Park, MD; Carmen Schmidt, RN; Daniel Steinberg, MD; Goal: Improvement of diabetes care for both inpatients and outpatients throughout the Beth
Israel System. The first event of the Initiative – Grand Rounds on June 16th, presented by Dr. Silvio E.
Inzucchi,of Yale University: Successful Management of Inpatient Hyperglycemia. The Initiative includes educational and clinical components.
Plan Educational aspects:
To include physicians, nurses, house staff, patients and their significant others; The series of lectures, grand rounds, in-service events to be planned; The “discharge kit” with general and individualized instructions to be developed and piloted; Educational video materials for inpatient TV to be selected/created and used throughout BIMC;
Clinical aspects: review of all existing diabetes protocols for general wards; review of current PRIZM orders; review of current diabetes-related protocols in CCU, MICU, CT ICU, SICU;
Quality Improvement: jointly with GMA, develop program for house staff Open for suggestions. Please direct any comments to Marina Krymskaya at [email protected]
or 212-420-2062
Team: Leonid Poretsky, MD; Agustin Busta, MD; Morton Davidson, MD; Marina Krymskaya, RN, NP; Jason Park, MD; Carmen Schmidt, RN; Daniel Steinberg, MD;
Goal: Improvement of diabetes care for both inpatients and outpatients throughout the Beth Israel System.
The first event of the Initiative – Grand Rounds on June 16th, presented by Dr. Silvio E. Inzucchi,of Yale University: Successful Management of Inpatient Hyperglycemia.
The Initiative includes educational and clinical components. Plan
Educational aspects: To include physicians, nurses, house staff, patients and their significant others; The series of lectures, grand rounds, in-service events to be planned; The “discharge kit” with general and individualized instructions to be developed and piloted; Educational video materials for inpatient TV to be selected/created and used throughout BIMC;
Clinical aspects: review of all existing diabetes protocols for general wards; review of current PRIZM orders; review of current diabetes-related protocols in CCU, MICU, CT ICU, SICU;
Quality Improvement: jointly with GMA, develop program for house staff Open for suggestions. Please direct any comments to Marina Krymskaya at [email protected]
or 212-420-2062
Diabetes:diagnosis, classification, management
Diabetes:diagnosis, classification, management
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
Diabetes:diagnosis, classification, management
Diabetes:diagnosis, classification, management
DefinitionDefinition
Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.*
The name 'diabetes mellitus' derives from:Greek: 'diabetes' – “siphon” or “to pass through”Latin: 'mellitus' – “honeyed” or “sweet”**
* Diagnosis and Classification of Diabetes Mellitus. ADA 2009. ** http://science.jrank.org/pages/2044/Diabetes-Mellitus.html
Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.*
The name 'diabetes mellitus' derives from:Greek: 'diabetes' – “siphon” or “to pass through”Latin: 'mellitus' – “honeyed” or “sweet”**
* Diagnosis and Classification of Diabetes Mellitus. ADA 2009. ** http://science.jrank.org/pages/2044/Diabetes-Mellitus.html
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
Diabetes:diagnosis, classification, management
Diabetes:diagnosis, classification, management
EpidemiologyEpidemiology
20.8 million Americans (7% of US population) About 10% have Type 1 DM 14.6 million diagnosed 6.2 million remain undiagnosed 41 million have pre-diabetes Lifetime risk for developing DM (Type 1 or 2) is 33 % in
males and 39% in females for individuals born in 2000 Up to 45% of newly diagnosed cases of DM in US children
and adolescents are type 2
AACE Diabetes Mellitus Guidelines, Endocr Pract. 2007;13(Suppl 1) 2007
20.8 million Americans (7% of US population) About 10% have Type 1 DM 14.6 million diagnosed 6.2 million remain undiagnosed 41 million have pre-diabetes Lifetime risk for developing DM (Type 1 or 2) is 33 % in
males and 39% in females for individuals born in 2000 Up to 45% of newly diagnosed cases of DM in US children
and adolescents are type 2
AACE Diabetes Mellitus Guidelines, Endocr Pract. 2007;13(Suppl 1) 2007
Diabetes:diagnosis, classification, management
Diabetes:diagnosis, classification, management
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
ClassificationClassification
Type 1 diabetes Type 2 diabetes Other
1. Genetic defects of beta cell function2. Genetic defects in insulin action3. Diseases of the exocrine pancreas4. Endocrinopathies5. Drug/ chemical - induced 6. Infections7. Uncommon forms of immune-mediated diabetes8. Genetic syndromes sometimes associated with diabetes
Gestational diabetes mellitus
Type 1 diabetes Type 2 diabetes Other
1. Genetic defects of beta cell function2. Genetic defects in insulin action3. Diseases of the exocrine pancreas4. Endocrinopathies5. Drug/ chemical - induced 6. Infections7. Uncommon forms of immune-mediated diabetes8. Genetic syndromes sometimes associated with diabetes
Gestational diabetes mellitus
Type 1 diabetesType 1 diabetes
A. Immune-mediated B. Idiopathic
Type 1 diabetes is characterized by β-cell destruction, usually leading to absolute insulin deficiency.*
A. Immune-mediated B. Idiopathic
Type 1 diabetes is characterized by β-cell destruction, usually leading to absolute insulin deficiency.*
* Diagnosis and Classification of Diabetes Mellitus. ADA 2009.* Diagnosis and Classification of Diabetes Mellitus. ADA 2009.
Atkinson MA and Eisenbarth GS. Lancet 2001;358:221-229.
Type 1 diabetes mellitus – immune mediated Type 1 diabetes mellitus – immune mediated Absolute insulin deficiency
Usually due to autoimmune destruction of the pancreatic beta cells
Islet-cell antibodies (ICA) or other autoantibodies (antibodies to glutamic acid decarboxylase [anti-GAD] and anti-insulin)
Absolute insulin deficiency
Usually due to autoimmune destruction of the pancreatic beta cells
Islet-cell antibodies (ICA) or other autoantibodies (antibodies to glutamic acid decarboxylase [anti-GAD] and anti-insulin)
Type 2 diabetesType 2 diabetes
Hyperglycemia
Insulin resistance
Relative impairment in insulin secretion.
Hyperglycemia
Insulin resistance
Relative impairment in insulin secretion.
cell dysfunction and insulin resistance produce hyperglycemia in type 2 diabetes
cell dysfunction and insulin resistance produce hyperglycemia in type 2 diabetes
Pancreas
Insulin Resistance
Liver
HyperglycemiaHyperglycemia
Islet Cell Degranulation;Reduced Insulin Content
Muscle Adipose Tissue
Decreased Glucose Transport & Activity
(expression) of GLUT4
Increased Lipolysis
↑GlucoseProduction
↓GlucoseUptake
ReducedPlasma Insulin
Increased Glucose Output
Cell Dysfunction
Elevated Plasma FFA
Elevated Plasma FFA
Other specific types of diabetes – Genetic defects of beta cell functionOther specific types of diabetes –
Genetic defects of beta cell function
Maturity–onset diabetes of the young (MODY)
6 subtypes
Maturity–onset diabetes of the young (MODY)
6 subtypes
Maturity:Onset diabetes of the young (MODY)
Maturity:Onset diabetes of the young (MODY)
MODY 1 - Mutation in HNF-4-alpha (transcription factor), chromosome 20
MODY 2 - Mutation in glucokinase gene, chromosome 7 MODY 3 - Mutation in HNF-1-alpha (transcription factor),
chromosome 12 (most common form) MODY 4 - Mutation in insulin promoter factor-1 (IPF-1),
chromosome 13 MODY 5 - Mutation in HNF-1-beta, chromosome 17 MODY 6 - Mutation in Neurogenic Differentiation Factor-1
(NEUROD1) , chromosome 2
MODY 1 - Mutation in HNF-4-alpha (transcription factor), chromosome 20
MODY 2 - Mutation in glucokinase gene, chromosome 7 MODY 3 - Mutation in HNF-1-alpha (transcription factor),
chromosome 12 (most common form) MODY 4 - Mutation in insulin promoter factor-1 (IPF-1),
chromosome 13 MODY 5 - Mutation in HNF-1-beta, chromosome 17 MODY 6 - Mutation in Neurogenic Differentiation Factor-1
(NEUROD1) , chromosome 2
Other specific types of diabetes: Genetic defects in insulin actionOther specific types of diabetes: Genetic defects in insulin action
Type A insulin resistance
Leprechaunism
Rabson- Mendenhall syndrome
Lipoatrophic diabetes
Others
Type A insulin resistance
Leprechaunism
Rabson- Mendenhall syndrome
Lipoatrophic diabetes
Others
*A clinical screening tool identifies autoimmune diabetes in adults. Fourlanos S; Perry C; Stein MS; Stankovich J; Harrison LC; Colman PG. Diabetes Care. 2006 May;29(5):970-5
Latent Autoimmune Diabetes in Adults (LADA)
Latent Autoimmune Diabetes in Adults (LADA)
Adult-onset diabetes with circulating islet antibodies but not requiring insulin therapy initially
Adults who should be considered for antibody testing*: age of onset <50 years acute symptoms BMI <25 kg/m2
personal or family history of autoimmune disease
Adult-onset diabetes with circulating islet antibodies but not requiring insulin therapy initially
Adults who should be considered for antibody testing*: age of onset <50 years acute symptoms BMI <25 kg/m2
personal or family history of autoimmune disease
Gestational DMGestational DMDefinition Any degree of impaired glucose tolerance with onset or first
recognition during pregnancy Gestational diabetes (GDM) occurs when pancreatic function
is not sufficient to overcome the insulin resistance created by changes in diabetogenic hormones during pregnancy
Most have impaired glucose tolerance that begins in pregnancy
Some have previous undiagnosed type 2 diabetes mellitus 10% have circulating islet cell antibodies
Definition Any degree of impaired glucose tolerance with onset or first
recognition during pregnancy Gestational diabetes (GDM) occurs when pancreatic function
is not sufficient to overcome the insulin resistance created by changes in diabetogenic hormones during pregnancy
Most have impaired glucose tolerance that begins in pregnancy
Some have previous undiagnosed type 2 diabetes mellitus 10% have circulating islet cell antibodies
Diabetes:diagnosis, classification, management
Diabetes:diagnosis, classification, management
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
DiagnosisDiagnosis
Diabetes mellitus
Impaired fasting glucose (IFG)
Impaired glucose tolerance (IGT)
Gestational diabetes mellitus (GDM)
Diabetes mellitus
Impaired fasting glucose (IFG)
Impaired glucose tolerance (IGT)
Gestational diabetes mellitus (GDM)
Diagnosis: Diabetes mellitusDiagnosis: Diabetes mellitus
1. Symptoms of diabetes (polydipsia, polyuria, unexplained weight loss) PLUS a random plasma glucose >200 mg/dL (11.1 mmol/L)
or2. Fasting plasma glucose > 126 mg/dL (7.0 mmol/L) after overnight
(at least 8 hours) fastor
3. Two-hour plasma glucose> 200mg/dL (11.1 mmol/L) during a standard 75g oral glucose tolerance test
Any of these criteria establishes the diagnosis but needs to be confirmed on a later day
1. Symptoms of diabetes (polydipsia, polyuria, unexplained weight loss) PLUS a random plasma glucose >200 mg/dL (11.1 mmol/L)
or2. Fasting plasma glucose > 126 mg/dL (7.0 mmol/L) after overnight
(at least 8 hours) fastor
3. Two-hour plasma glucose> 200mg/dL (11.1 mmol/L) during a standard 75g oral glucose tolerance test
Any of these criteria establishes the diagnosis but needs to be confirmed on a later day
Diagnosis: Impaired fasting glucose (IFG)Diagnosis: Impaired fasting glucose (IFG)
Fasting plasma glucose (FPG) < 100 mg/dl (5.6 mmol/l) = normal
FPG 100-125 mg/dl (5.6-6.9 mmol/l) = impaired fasting glucose (IFG)
Fasting plasma glucose (FPG) < 100 mg/dl (5.6 mmol/l) = normal
FPG 100-125 mg/dl (5.6-6.9 mmol/l) = impaired fasting glucose (IFG)
Oral glucose tolerance test (OGTT) – glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water
2-h postload glucose < 140 mg/dl (7.8 mmol/l) = normal
2-h postload glucose 140 - 199 mg/dl (7.8 – 11.1 mmol/l) = impaired glucose tolerance (IGT)
Oral glucose tolerance test (OGTT) – glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water
2-h postload glucose < 140 mg/dl (7.8 mmol/l) = normal
2-h postload glucose 140 - 199 mg/dl (7.8 – 11.1 mmol/l) = impaired glucose tolerance (IGT)
Diagnosis: Impaired glucose tolerance (IGT)Diagnosis: Impaired glucose tolerance (IGT)
Diagnosis: Gestational Diabetes Mellitus (GDM)
Diagnosis: Gestational Diabetes Mellitus (GDM)
1. Unequivocal hyperglycemia(confirmed on a subsequent day)
2. Diagnostic OGTT
Fasting plasma glucose > 126 mg/dL > 126 mg/dL (7.0 mmol/L)(7.0 mmol/L)
Random plasma glucose >200 mg/dL Random plasma glucose >200 mg/dL (11.1 mmol/L)(11.1 mmol/L)
OR
100-g glucose load
mg/dl mmol/l
Fasting 95 5.3
1-h 180 10.0
2-h 155 8.6
3-h 140 7.8
Diabetes:diagnosis, classification, management
Diabetes:diagnosis, classification, management
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
TreatmentTreatment
Lifestyle intervention
Hypoglycemic drugs oral hypoglycemic drugs insulin and insulin analogs others (incretins, pramlintide)
Lifestyle intervention
Hypoglycemic drugs oral hypoglycemic drugs insulin and insulin analogs others (incretins, pramlintide)
Treatment:Lifestyle Interventions
Treatment:Lifestyle Interventions
Weight loss
Increased exercise
Weight loss
Increased exercise
Treatment:Oral Antihyperglycemic Drugs
Treatment:Oral Antihyperglycemic Drugs
Biguanides Sulfonylureas Meglitinide analogs Thiazolidinediones -Glucosidase Inhibitors DPP-4 Inhibitors
Biguanides Sulfonylureas Meglitinide analogs Thiazolidinediones -Glucosidase Inhibitors DPP-4 Inhibitors
Treatment:Oral Antihyperglycemic Drugs
Treatment:Oral Antihyperglycemic Drugs
Oral antihyperglycemic drugs: Biguanides
Oral antihyperglycemic drugs: Biguanides
Metformin (Glucophage) Extended-release metformin (Glucophage-XR)
decrease hepatic glucose output lower fasting glycemia reduce HbA1c by 1.5% adverse effects: lactic acidosis, gastro-
intestinal disturbances
Metformin (Glucophage) Extended-release metformin (Glucophage-XR)
decrease hepatic glucose output lower fasting glycemia reduce HbA1c by 1.5% adverse effects: lactic acidosis, gastro-
intestinal disturbances
AMPK - adenosine monophosphate-activated protein kinase, ACC - acteyl-CoA carboxylase, SREPB-1 - sterol-
regulatory-element-binding-protein-1. Diagram adapted from Alice Y.Y. Cheng, I. George Fantus, 'Oral antihyperglycemic therapy for type 2 diabetes mellitus' Canadian Medical Association Journal 172(2),2005 pp213-226
Oral antihyperglycemic drugs: MetforminOral antihyperglycemic drugs: Metformin
Treatment:Oral Antihyperglycemic Drugs
Treatment:Oral Antihyperglycemic Drugs
Oral antihyperglycemic drugs: Sulfonylureas
Oral antihyperglycemic drugs: Sulfonylureas
1st generation : Tolbutamide (Orinase), Tolazamide (Tolinase), Acetohexamide (Dymelor), Chlorpropamide (Diabinese)
2nd generation : Glyburide (DiaBeta, Glynase) Glipizide (Glucotrol), Glimepiride (Amaryl)
enhance insulin secretion lower HbA1c by 1.5 % side effects: hypoglycemia, weight gain
1st generation : Tolbutamide (Orinase), Tolazamide (Tolinase), Acetohexamide (Dymelor), Chlorpropamide (Diabinese)
2nd generation : Glyburide (DiaBeta, Glynase) Glipizide (Glucotrol), Glimepiride (Amaryl)
enhance insulin secretion lower HbA1c by 1.5 % side effects: hypoglycemia, weight gain
Treatment:Oral Antihyperglycemic Drugs
Treatment:Oral Antihyperglycemic Drugs
Black C, Donnelly P, McIntyre L et al. Meglitinide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004654.
Oral antihyperglycemic drugs: Meglitinide analogs
Oral antihyperglycemic drugs: Meglitinide analogs
Repaglinide (Prandin) Nateglinide (Starlix)
enhance insulin secretion (early-phase insulin release) lower HbA1c by 0.1- 2.1 % (repaglinide) and by 0.2-
0.6% (nateglinide) side effects: weight gain, hypoglycemia
Repaglinide (Prandin) Nateglinide (Starlix)
enhance insulin secretion (early-phase insulin release) lower HbA1c by 0.1- 2.1 % (repaglinide) and by 0.2-
0.6% (nateglinide) side effects: weight gain, hypoglycemia
Treatment:Oral Antihyperglycemic Drugs
Treatment:Oral Antihyperglycemic Drugs
Oral antihyperglycemic drugs: Thiazolidinediones (TZDs)
Oral antihyperglycemic drugs: Thiazolidinediones (TZDs)
Rosiglitazone (Avandia) Pioglitazone (Actos)
peroxisome proliferator-activated receptor γ modulators (PPAR γ)
insulin sensitizers (increase the sensitivity of muscle, fat and liver to endogenous and exogenous insulin)
lower HbA1c by 0.5 - 1.4 % adverse effects: weight gain, fluid retention
Rosiglitazone (Avandia) Pioglitazone (Actos)
peroxisome proliferator-activated receptor γ modulators (PPAR γ)
insulin sensitizers (increase the sensitivity of muscle, fat and liver to endogenous and exogenous insulin)
lower HbA1c by 0.5 - 1.4 % adverse effects: weight gain, fluid retention
Treatment:Oral Antihyperglycemic Drugs
Treatment:Oral Antihyperglycemic Drugs
Oral antihyperglycemic drugs:-Glucosidase Inhibitors
Oral antihyperglycemic drugs:-Glucosidase Inhibitors
Acarbose (Precose) Miglitol (Glyset)
reduce the rate of digestion of polysaccharides in the proximal small intestine, primarily lowering post-prandial glucose levels
lower HbA1c by 0.5 – 0.8 % side effects: increased gas production and gastro-
intestinal symptoms
Acarbose (Precose) Miglitol (Glyset)
reduce the rate of digestion of polysaccharides in the proximal small intestine, primarily lowering post-prandial glucose levels
lower HbA1c by 0.5 – 0.8 % side effects: increased gas production and gastro-
intestinal symptoms
Oral antihyperglycemic drugs: DPP-IV inibitors
Oral antihyperglycemic drugs: DPP-IV inibitors
Sitagliptin (Januvia) : DPP-IV inhibitor Dipeptidyl peptidase IV (DPP-IV) is a ubiquitous
enzyme that deactivates a variety of bioactive peptides, including GIP and GLP-1
Sitagliptin (Januvia) : DPP-IV inhibitor Dipeptidyl peptidase IV (DPP-IV) is a ubiquitous
enzyme that deactivates a variety of bioactive peptides, including GIP and GLP-1
Oral antihyperglycemic drugs - Sitagliptin (Januvia)
Oral antihyperglycemic drugs - Sitagliptin (Januvia)
Used alone or in combination with metformin or TZDs
Reduces HbA1c by 0.5 – 0.7 %
Side effects: increased rate of respiratory infections, headaches
Used alone or in combination with metformin or TZDs
Reduces HbA1c by 0.5 – 0.7 %
Side effects: increased rate of respiratory infections, headaches
"Januvia" by Byron Rubin"Januvia" by Byron Rubin
Sculpture was installed at the West Point Pennsylvania Merck location.
Sculpture was installed at the West Point Pennsylvania Merck location.
Other antihyperglycemic drugs: Incretins
Other antihyperglycemic drugs: Incretins
Exenatide (Byetta) glucagon-like peptide 1 (GLP-1) agonist
Exenatide (Byetta) glucagon-like peptide 1 (GLP-1) agonist
Antihyperglycemic drugs: Exenatide (Byetta)Antihyperglycemic drugs: Exenatide (Byetta)
Glucagon-like Peptide - 1Glucagon-like Peptide - 1
The majority of GLP-1 producing cells are in the terminal ileum and proximal colon.
GLP-1 levels in the blood increase rapidly after a meal. Half-life being very short, approximately one minute. GLP-1 binding to its G-protein coupled receptor on ß-cells
increases glucose stimulated insulin secretion GLP-1 infused into healthy subjects decreases gastric
emptying, causes a sensation of satiety, and decreases appetite. Effects:
enhances insulin secretion limits postprandial hyperglycemia.
The majority of GLP-1 producing cells are in the terminal ileum and proximal colon.
GLP-1 levels in the blood increase rapidly after a meal. Half-life being very short, approximately one minute. GLP-1 binding to its G-protein coupled receptor on ß-cells
increases glucose stimulated insulin secretion GLP-1 infused into healthy subjects decreases gastric
emptying, causes a sensation of satiety, and decreases appetite. Effects:
enhances insulin secretion limits postprandial hyperglycemia.
Figure 1. Insulin levels following oral vs IV glucose administration in healthy individuals. Despite identical glucose concentrations, plasma insulin levels peaked much earlier and were greater in response to an oral vs IV dose of glucose.
Figure 2. Insulin levels following oral vs IV glucose administration in patients with type 2 diabetes. The markedly reduced early peak of insulin after oral glucose, along with the smaller differences in insulin levels in response to oral and IV glucose doses, illustrate the diminished incretin effect.
Data extrapolated from Perley, et al. @ http://www.byettahcp.com/hcp/hcp_incretin_effect.jsp
Incretin EffectIncretin Effect
Antihyperglycemic drugs:Exenatide (Byetta)
Antihyperglycemic drugs:Exenatide (Byetta)
active ingredient in Exenatide (Byetta) is a synthetic version of a protein present in the saliva of the Gila monster
active ingredient in Exenatide (Byetta) is a synthetic version of a protein present in the saliva of the Gila monster
Antihyperglycemic drugs:Exenatide (Byetta)
Antihyperglycemic drugs:Exenatide (Byetta)
Added to metformin or sulfonylureas will reduce HbA1c by 0.4-0.6 %
Side effects: nausea (dose-depended, declines with time) acute pancreatitis (some necrotizing or hemorrhagic
pancreatitis cases reported as well)
Added to metformin or sulfonylureas will reduce HbA1c by 0.4-0.6 %
Side effects: nausea (dose-depended, declines with time) acute pancreatitis (some necrotizing or hemorrhagic
pancreatitis cases reported as well)
Antihyperglycemic drugs:Exenatide (Byetta)
Antihyperglycemic drugs:Exenatide (Byetta)
Antihyperglycemic drugs: OthersAntihyperglycemic drugs: Others
Pramlintide (Symlin) synthetic analog of amylin
Pramlintide (Symlin) synthetic analog of amylin
AmylinAmylin
Stored in insulin secretory granules in the ß-cells
Co-secreted with insulin Decreases glucagon Satiety signal? Decreases GI motility
Stored in insulin secretory granules in the ß-cells
Co-secreted with insulin Decreases glucagon Satiety signal? Decreases GI motility
Antihyperglycemic drugs:Pramlintide (Symlin)
Antihyperglycemic drugs:Pramlintide (Symlin)
Delays gastric emptying, suppresses glucagon secretion, decreases appetite
Associated with weight loss (1 - 1.5 kg over 6 months)
Used only in conjunction with insulin treatment Reduces HbA1c by 0.5 - 0.7 % Side effects: nausea, gastro-intestinal symptoms
Delays gastric emptying, suppresses glucagon secretion, decreases appetite
Associated with weight loss (1 - 1.5 kg over 6 months)
Used only in conjunction with insulin treatment Reduces HbA1c by 0.5 - 0.7 % Side effects: nausea, gastro-intestinal symptoms
Antihyperglycemic drugs:Pramlintide (Symlin)
Antihyperglycemic drugs:Pramlintide (Symlin)
Product (Manufacturer) Form
Rapid Acting (Onset 15-30 min, duration hrs 3-4)
Insulin Analog
Aspart - Novolog (Novo Nordisk)
Lispro - Humalog (Lilly)
Glulisine – Apidra (Aventis)
Analog**
Analog**
Short Acting (Onset 0.5-1 hr, duration hrs 5-7)*
Human Insulin
Novolin R (Rugular) (Novo Nordisk)
Humulin R (Regular) (Lilly)
Human**
Human**
Purified Insulin
Regular Iletin II (Lilly) Pork
Intermediate Acting (Onset 1-4 hrs, duration hrs 18-24)*
Human Insulin
Novolin N (NPH) (Lilly)
Humulin N (NPH) (Lilly)
Humulin L (Lente) (Lilly)
Human**
Human**
Human**
Purified Insulin
NPH Iletin III (Lilly) Pork
Long Acting (Onset 4-6 hrs, duration hrs 24-34)*
Human Insulin
Humulin Ultralente (Lilly) Human**
Basal Peakless Insulin
Glargine-Lantus (Aventis)
Detemir – Levemir (Novo Nordisk)
Analog**
Analog**
Mixed Insulins
70/30 Insulin
Novolin 70/30 (Novo Nordisk)
Humulin 70/30 (Lilly)
Humulin 50/50 (Lilly)
Humalog 50/50
Human**
Human**
Human**
Analog**
Product (Manufacturer) Form
Analog Mix
Humalog 75/25 Mix
Novolog Mix 70/30 (combination of fast and intermediate acting insulin with action similar to that of Humalog 75/25 mix)
Analog**
Analog**
Insulin for Special Use
Buffered Insulin (for pumps)
Humulin BR
Refills for Novolin Pen
Novolin R PenFill
Novolin N PenFill
Novolin 70/30 PenFill
Novolog Mix 70/30 PenFill
Prefilled Pens
Novolin R
Novolin N
Novolin 70/30
Novolog
Novolog Mix 70/30
Humalog
Humalog Mix 75/25
Humalog Mix 50/50
Humulin N
Apidra
Human**
Human**
Human**
Analog**
Human**
Human**
Human**
Analog**
Analog**
Analog**
Analog**
Analog**
Human**
Analog**
* Onset and duration are rough estimates. They can vary greatly within the range listed and from person to person
** Human insulin is made by recombinant DNA technology
AVAILABLE INSULIN PREPARATIONS
Initiation and adjustment of insulin regimens. Insulin regimens should be designed taking lifestyle and meal schedule into account. The algorithm can only provide basic guidelines for initiation and adjustment of insulin. See reference 90 for more detailed instructions. aPremixed insulins not recommended during adjustment of doses; however, they can be used conveniently, usually before breakfast and/or dinner, if proportion of rapid- and intermediate-acting insulins is similar to the fixed proportions available. bg, blood glucose.
ADA Treatment AlgorithmADA Treatment Algorithm
Diabetes:diagnosis, classification, management
Diabetes:diagnosis, classification, management
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
EvidenceEvidence
ACCORDACCORD
10,251 patients with DM2 Mean age – 62.2 yrs Baseline A1C – 8.1% Intensive glucose
control vs. standard control
Median f/up 3.5 yrs primary outcome:
nonfatal myocardial infarction
nonfatal stroke death from CV causes
10,251 patients with DM2 Mean age – 62.2 yrs Baseline A1C – 8.1% Intensive glucose
control vs. standard control
Median f/up 3.5 yrs primary outcome:
nonfatal myocardial infarction
nonfatal stroke death from CV causes
Intensive Standard RR reduction
A1C 6.4% 7.5%
Primary outcome 6.9% 7.2% 10%
Death from any cause
5.0% 4.0% ↑22%*
Non-fatal MI 3.6% 4.6% 24%*
Severe hypoglycemia
2.7% 1.5%
The Action to Control Cardiovascular Risk in Diabetes Study Group. N Engl J Med 2008;358:2545-2559
* P-value < 0.05
ACCORDACCORD Action to Control Cardiovascular Risk in Diabetes
(ACCORD) trial Designed primarily to examine the effects of
glycemic control, lower than had previously been achieved, on CVD in subjects with long-standing diabetes
10,250 adults (mean age 62 years) with a median diabetes duration of ten years and at high risk for cardiovascular disease (diagnosed with CVD or two risk factors in addition to diabetes)
Intensive treatment group with the aim of achieving A1C of < 6 % or a standard treatment group with a A1C goal of 7.0 to 7.9 %.
Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial
Designed primarily to examine the effects of glycemic control, lower than had previously been achieved, on CVD in subjects with long-standing diabetes
10,250 adults (mean age 62 years) with a median diabetes duration of ten years and at high risk for cardiovascular disease (diagnosed with CVD or two risk factors in addition to diabetes)
Intensive treatment group with the aim of achieving A1C of < 6 % or a standard treatment group with a A1C goal of 7.0 to 7.9 %.
After 3.5 years, the intensive arm was halted due to a higher number of total deaths: 257 deaths in subjects assigned to intensive therapy versus 203 deaths in patients assigned to standard treatment group.*
The primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) occurred in 352 and 371 patients in the intensive and standard therapy groups, respectively (HR 0.90, 95% CI 0.78-1.04).
After 3.5 years, the intensive arm was halted due to a higher number of total deaths: 257 deaths in subjects assigned to intensive therapy versus 203 deaths in patients assigned to standard treatment group.*
The primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) occurred in 352 and 371 patients in the intensive and standard therapy groups, respectively (HR 0.90, 95% CI 0.78-1.04).
* hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P=0.04* hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P=0.04
ACCORDACCORD
Preliminary information : extensive analyses have not identified a specific cause for the excess mortality in the intensive treatment group.
Subjects in the intensive group rapidly achieved target A1C values and experienced a greater number of severe hypoglycemic events (annualized rate of 3.1 versus 1.0 percent) and more weight gain (mean 3.5 versus 0.4 kg at three years) than the standard group (median A1C 7.5 percent).
Preliminary information : extensive analyses have not identified a specific cause for the excess mortality in the intensive treatment group.
Subjects in the intensive group rapidly achieved target A1C values and experienced a greater number of severe hypoglycemic events (annualized rate of 3.1 versus 1.0 percent) and more weight gain (mean 3.5 versus 0.4 kg at three years) than the standard group (median A1C 7.5 percent).
ACCORDACCORD
ADVANCEADVANCE
11,140 patients with DM2
Mean age – 66 yrs Baseline A1C - 7.5% Intensive glucose
control vs. standard control
Median f/up 5 yrs 1º end-points: major
macro- and micro vascular events
11,140 patients with DM2
Mean age – 66 yrs Baseline A1C - 7.5% Intensive glucose
control vs. standard control
Median f/up 5 yrs 1º end-points: major
macro- and micro vascular events
Intensive Standard RR reduction
A1C 6.5% 7.3%
Major microvascular 9.4% 10.9% 14% *
New/worsening nephropathy
4.1% 5.2% 21%*
New onset microalbuminuria
23.7% 25.7% 9% *
Major macrovascular
10.0% 10.6% 6%
The ADVANCE Collaborative Group. N Engl J Med 2008;358:2560-2572
* P-value < 0.05
ADVANCEADVANCE
Mean glycated hemoglobin level was lower in the intensive- control group (6.5%) than in the standard-control group (7.3%)
Intensive control reduced the incidence of combined major macrovascular and
microvascular events (18.1% vs 20.0% with standard control; hazard ratio 0.90, 95% confidence interval (CI), 0.82 to 0.98; p=0.01)
reduced the incidence of major microvascular events (9.4% vs 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; p=0.01)
This occurred primarily because of a reduction in the incidence of the nephropathy (4.1% vs 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; p=0.006) with NO effect on retinopathy (p=0.50)
Mean glycated hemoglobin level was lower in the intensive- control group (6.5%) than in the standard-control group (7.3%)
Intensive control reduced the incidence of combined major macrovascular and
microvascular events (18.1% vs 20.0% with standard control; hazard ratio 0.90, 95% confidence interval (CI), 0.82 to 0.98; p=0.01)
reduced the incidence of major microvascular events (9.4% vs 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; p=0.01)
This occurred primarily because of a reduction in the incidence of the nephropathy (4.1% vs 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; p=0.006) with NO effect on retinopathy (p=0.50)
NO significant effects of the type of glucose control for: major macrovascular events (hazard ratio with
intensive control 0.94; 95% CI, 0.84 to 1.06; p=0.32) death from CV causes (hazard ratio with intensive
control 0.88; 95% CI, 0.74 to 1.04; p=0.12) death from any cause (hazard ratio with intensive
control 0.93; 95% CI, 0.83 to 1.06; p=0.28)
NO significant effects of the type of glucose control for: major macrovascular events (hazard ratio with
intensive control 0.94; 95% CI, 0.84 to 1.06; p=0.32) death from CV causes (hazard ratio with intensive
control 0.88; 95% CI, 0.74 to 1.04; p=0.12) death from any cause (hazard ratio with intensive
control 0.93; 95% CI, 0.83 to 1.06; p=0.28)
ADVANCEADVANCE
ADVANCEADVANCE
Intensive control that resulted in HbA1c of 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy
Intensive control that resulted in HbA1c of 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy
The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-986
* P-value < 0.05
DCCTDCCT
1441 patients with DM1 Age: 13-39 No history of
cardiovascular disease IIT vs. conventional IT
for 6.5 yrs 1º prevention group:
Retinopathy Neuropathy Nephropathy
1441 patients with DM1 Age: 13-39 No history of
cardiovascular disease IIT vs. conventional IT
for 6.5 yrs 1º prevention group:
Retinopathy Neuropathy Nephropathy
Intensive Standard RR reduction
A1C 7.4% 9.1%New retinopathy 1.2 per 100
pt-yr4.7 per 100 pt-yr
76%*
Microalbuminuria 2.2 per 100 pt-yr
3.4 per 100 pt-yr
34%*
Clinical neuropathy 3.1 per 100 pt-yr
9.8 per 100 pt-yr
68%*
Macrovascular disease
0.5 per 100 pt-yr
0.8 per 100 pt-yr
41%
93% of DCCT patients f/up for additional 11 yrs
At the end of the DCCT: the conventional-treatment
group intensive treatment (all participants returned totheir own health careproviders for diabetes care)
No hx of cardiovascular disease IIT vs. conventional IT for 6.5
yrs 1º prevention group:
Retinopathy Neuropathy Nephropathy
93% of DCCT patients f/up for additional 11 yrs
At the end of the DCCT: the conventional-treatment
group intensive treatment (all participants returned totheir own health careproviders for diabetes care)
No hx of cardiovascular disease IIT vs. conventional IT for 6.5
yrs 1º prevention group:
Retinopathy Neuropathy Nephropathy
Year 11th of EDIC Intensive Standard RR reduction
A1C 7.9% 7.8%
Microalbuminuria 9% 17% 38%*
Cr>2.0 0% 2.0% 46%*
Progressive retinopathy
6% 21% 75%*
Major CV events 0.38 per 100 pt-yr
0.8% per 100 pt-yr
42%*
Non-fatal MI CVA, death from CVD
11 25 57%*
Epidemiology of diabetes interventions and Complications (EDIC, 1994- 2006) follow-up study
EDICEDIC
(DCCT/EDIC Research Group. Epidemiology of Diabetes Interventions and Complications (EDIC). Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort. Diabetes Care 1999; 22: 99- 111.
EDICEDIC Goal : examine the longer term effects of the original
DCCT interventions (applied to cardiovascular, retinal and renal complications)
Discovered the long term “imprinting” effects (metabolic memory) of the previous intensive and standard treatments
Established (first time) the role of intensive therapy and chronic glycemia with regard to atherosclerosis
Goal : examine the longer term effects of the original DCCT interventions (applied to cardiovascular, retinal and renal complications)
Discovered the long term “imprinting” effects (metabolic memory) of the previous intensive and standard treatments
Established (first time) the role of intensive therapy and chronic glycemia with regard to atherosclerosis
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998 Sep 12;352(9131):837-53.
United Kingdom Prospective Diabetes Study (UKPDS)
United Kingdom Prospective Diabetes Study (UKPDS)
3867 patients with newly diagnosed DM2 Randomized to conventional-therapy group (diet
alone) or intensive-therapy group: sulfonylurea (chlorpropamide, glibenclamide, glipizide) or insulin
Metformin added to sulfonylurea if optimal control not achieved
Insulin initiated if combination of oral agents was ineffective
3867 patients with newly diagnosed DM2 Randomized to conventional-therapy group (diet
alone) or intensive-therapy group: sulfonylurea (chlorpropamide, glibenclamide, glipizide) or insulin
Metformin added to sulfonylurea if optimal control not achieved
Insulin initiated if combination of oral agents was ineffective
United Kingdom Prospective Diabetes Study (UKPDS)
United Kingdom Prospective Diabetes Study (UKPDS)
Drugs added to conventional group if symptoms of hyperglycemia or FPG>270 mg/dl
Goal of therapy: FPG<108 mg/dl
Microvascular and Macrovascular complications examined
Drugs added to conventional group if symptoms of hyperglycemia or FPG>270 mg/dl
Goal of therapy: FPG<108 mg/dl
Microvascular and Macrovascular complications examined
11 percent reduction in A1C ( 7.0% vs. 7.9%)
25 percent risk reduction in microvascular disease (P = 0.001) defined as renal failure,
death from renal failure, retinal photocoagulation, or vitreous hemorrhage
11 percent reduction in A1C ( 7.0% vs. 7.9%)
25 percent risk reduction in microvascular disease (P = 0.001) defined as renal failure,
death from renal failure, retinal photocoagulation, or vitreous hemorrhage
UKPDS: resultsUKPDS: results
UKPDS: resultsUKPDS: results
No reduction in macrovascular disease
More hypoglycemic episodes and weight gain in the intensive therapy group
No reduction in macrovascular disease
More hypoglycemic episodes and weight gain in the intensive therapy group
10 year follow-up of intensive glucose control in type 2 diabetes. R Holman et al. 10 year follow-up of intensive glucose control in type 2 diabetes. R Holman et al. NEJMNEJM 2008;359:1577-89 2008;359:1577-89
10 year follow-up of intensive glucose control in type 2 diabetes
10 year follow-up of intensive glucose control in type 2 diabetes
United Kingdom Prospective Diabetes Study (UKPDS)- 4209 patients in conventional or intensive therapy
Post-trial monitor – 3277 patients followed up: first 5 years: annual UKPDS clinic visits (no
attempts to maintain previously assigned therapy) years 6 – 10: annual questionnaires
United Kingdom Prospective Diabetes Study (UKPDS)- 4209 patients in conventional or intensive therapy
Post-trial monitor – 3277 patients followed up: first 5 years: annual UKPDS clinic visits (no
attempts to maintain previously assigned therapy) years 6 – 10: annual questionnaires
10 year follow-up of intensive glucose control in type 2 diabetes. R Holman et al. 10 year follow-up of intensive glucose control in type 2 diabetes. R Holman et al. NEJMNEJM 2008;359:1577-89 2008;359:1577-89
10 year follow-up of intensive glucose control in type 2 diabetes
10 year follow-up of intensive glucose control in type 2 diabetes
Results HbA1c: differences between groups in were lost after the first year Sulfonylurea-insulin group:
any diabetes-related end point- relative risk reduction persisted at 10 years (9%, p=0.04)
microvascular disease - relative risk reduction persisted at 10 years (24%, p=0.001)
myocardial infarction - risk reduction emerged over time (15%, p=0.01) death from any cause - risk reduction emerged over time (13%, p=0.007)
Metformin group: any diabetes-related end point - significant risk reductions persisted (21%,
p=0.010) myocardial infarction - significant risk reductions persisted (33%, p=0.005) death from any cause - significant risk reductions persisted (27%, p=0.002)
Results HbA1c: differences between groups in were lost after the first year Sulfonylurea-insulin group:
any diabetes-related end point- relative risk reduction persisted at 10 years (9%, p=0.04)
microvascular disease - relative risk reduction persisted at 10 years (24%, p=0.001)
myocardial infarction - risk reduction emerged over time (15%, p=0.01) death from any cause - risk reduction emerged over time (13%, p=0.007)
Metformin group: any diabetes-related end point - significant risk reductions persisted (21%,
p=0.010) myocardial infarction - significant risk reductions persisted (33%, p=0.005) death from any cause - significant risk reductions persisted (27%, p=0.002)
Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes. Duckworth W et al. NEJM 2009;360:129-139
Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes
Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes
1791 military veterans with suboptimal response to therapy for type 2 DM
mean age: 60.4 years Mean number of years since diagnosis with diabetes: 11.5 40% had already had one CV event 2 groups
intensive glucose control standard glucose control
Goal: absolute reduction of 1.5 percentage points in HbA1c in intensive treatment group compared to the standard treatment
Primary outcome: time from randomization to first major CV event
1791 military veterans with suboptimal response to therapy for type 2 DM
mean age: 60.4 years Mean number of years since diagnosis with diabetes: 11.5 40% had already had one CV event 2 groups
intensive glucose control standard glucose control
Goal: absolute reduction of 1.5 percentage points in HbA1c in intensive treatment group compared to the standard treatment
Primary outcome: time from randomization to first major CV event
Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes
Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes
Follow-up: 5.6 years Primary outcome occurred in 264 patients in the standard
treatment group vs 235 patients in the intensive therapy group (HR: 0.88; 95%CI, 0.74 to 1.05; p=0.14)
Median glycated hemoglobin levels were 8.4% in the standard therapy group vs 6.9% in the intensive-treatment group.
Rate of adverse events were 17.6% in the standard therapy group and 24.1% in the intensive therapy group (p=0.05).
Hypoglycemia (most common side effect) occurred significantly more in the intensive treatment group than in the standard treatment group (p<0.001)
Follow-up: 5.6 years Primary outcome occurred in 264 patients in the standard
treatment group vs 235 patients in the intensive therapy group (HR: 0.88; 95%CI, 0.74 to 1.05; p=0.14)
Median glycated hemoglobin levels were 8.4% in the standard therapy group vs 6.9% in the intensive-treatment group.
Rate of adverse events were 17.6% in the standard therapy group and 24.1% in the intensive therapy group (p=0.05).
Hypoglycemia (most common side effect) occurred significantly more in the intensive treatment group than in the standard treatment group (p<0.001)
Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes
Results• NO significant difference between the 2 groups
in any component of the primary outcome (the time from randomization to a major CV event) or in the rate of death from any cause.
• NO difference between the 2 groups was observed for microvascular complications
• Note! Correction: progression of microalbuminuria favors intensive therapy group (9.1% vs. 13.8 % in a standard group, P=0.04).*
* N ENGL J MED 361;10, September 3, 2009
Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes
Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes
Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes.Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes. Gæde P, M.D., D.M.Sc., Lund-Andersen H, M.D., D.M.Sc.,
Parving H, M.D., D.M.Sc., and Pedersen O, M.D., D.M.Sc. N Engl J Med. 2008 Feb 7;358(6):580-91.
160 patients with type 2 diabetes mellitus and persistent microalbuminuria 160 patients with type 2 diabetes mellitus and persistent microalbuminuria
Intensive, target-driven treatment Conventional multifactorial treatment
Followed for a mean of 5.5 years
Targets: - HbA1c < 6.5% - fasting serum total cholesterol < 175 mg/dl (4.5 mmol/l)- fasting serum triglyceride < 150 mg/dl (1.7 mmol per liter)- blood pressure: systolic <130 mm Hg, diastolic < 80 mm Hg.
Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes: End points
Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes: End points
1. Primary end point: time to death from any cause
2. Secondary end points: death from cardiovascular causes a composite of cardiovascular disease events (death from
cardiovascular causes, nonfatal stroke, nonfatal myocardial infarction, coronary-artery bypass grafting, percutaneous coronary intervention or revascularization for peripheral atherosclerotic arterial disease, and amputation because of ischemia)
3. Tertiary end points: incident diabetic nephropathy development or progression of diabetic retinopathy or neuropathy
Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes: Results
Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes: Results
Intensive group
24 patients died (30%) vs 40 patients (50%) in the conventional treatment group (hazard ratio for death in the intensive group vs conventional group: 0.54; 95% confidence interval, 0.32 to 0.89; p=0.02)
Intensive group
24 patients died (30%) vs 40 patients (50%) in the conventional treatment group (hazard ratio for death in the intensive group vs conventional group: 0.54; 95% confidence interval, 0.32 to 0.89; p=0.02)
Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes: Results
Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes: Results
Lower risk of death from cardiovascular causes (HR 0.43; 95% CI, 0.19 to 0.94; p=0.04) compared to conventional treatment group
Lower risk of cardiovascular events (HR 0.41; 95% CI, 0.25 to 0.0.67; p<0.001) vs conventional treatment group
1 patient had progression to end-stage renal disease vs 6 patients in the conventional treatment group (p=0.04)
Fewer patients required retinal photocoagulation (relative risk, 0.45; 95% CI, 0.23 to 0.86; p=0.02) compared to the other group
Lower risk of death from cardiovascular causes (HR 0.43; 95% CI, 0.19 to 0.94; p=0.04) compared to conventional treatment group
Lower risk of cardiovascular events (HR 0.41; 95% CI, 0.25 to 0.0.67; p<0.001) vs conventional treatment group
1 patient had progression to end-stage renal disease vs 6 patients in the conventional treatment group (p=0.04)
Fewer patients required retinal photocoagulation (relative risk, 0.45; 95% CI, 0.23 to 0.86; p=0.02) compared to the other group
S.E. Nissen, M.D., and K. Wolski, M.P.H. Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes. NEJM 2007; 356:2457-2471
Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular CausesEffect of Rosiglitazone on the Risk of Myocardial
Infarction and Death from Cardiovascular Causes Meta-analysis Searches
published literature, FDA website, GlaxoSmithKline clinical trial registry
Inclusion criteria study duration > 24 weeks, use of a control group not receiving rosiglitazone, availability of outcome data for myocardial infarction and death from
cardiovascular causes Included: 42 trials (out of 116 potentially relevant trials) Tabulated all occurrences of myocardial infarction and death
from any cardiovascular causes Mean age of subjects: 56 years Mean baseline HbA1c: 8.2%
Meta-analysis Searches
published literature, FDA website, GlaxoSmithKline clinical trial registry
Inclusion criteria study duration > 24 weeks, use of a control group not receiving rosiglitazone, availability of outcome data for myocardial infarction and death from
cardiovascular causes Included: 42 trials (out of 116 potentially relevant trials) Tabulated all occurrences of myocardial infarction and death
from any cardiovascular causes Mean age of subjects: 56 years Mean baseline HbA1c: 8.2%
S.E. Nissen, M.D., and K. Wolski, M.P.H. Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes. NEJM 2007; 356:2457-2471
Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular CausesEffect of Rosiglitazone on the Risk of Myocardial
Infarction and Death from Cardiovascular Causes
Results Myocardial infarction: OR=1.43 in the
rosiglitazone group compared with the control group (95% CI, 1.03 to 1.98; p=0.03)
Death from cardiovascular causes: OR=1.64 in the rosiglitazone group compared with the control group (95% CI, 0.98 to 2.74; p=0.06)
Results Myocardial infarction: OR=1.43 in the
rosiglitazone group compared with the control group (95% CI, 1.03 to 1.98; p=0.03)
Death from cardiovascular causes: OR=1.64 in the rosiglitazone group compared with the control group (95% CI, 0.98 to 2.74; p=0.06)
Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. S E Kahn et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. S E Kahn et al. NEJMNEJM 2006;355:2427-43 2006;355:2427-43
Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy
ADOPT - A Diabetes Outcome Progression Trial
Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy
ADOPT - A Diabetes Outcome Progression Trial
Evaluate rosiglitazone, metformin and glyburide as initial treatment for recently diagnosed type 2 diabetes
Double-blind, randomized, controlled clinical trial 4360 patients enrolled Median treatment time: 4.0 years
Evaluate rosiglitazone, metformin and glyburide as initial treatment for recently diagnosed type 2 diabetes
Double-blind, randomized, controlled clinical trial 4360 patients enrolled Median treatment time: 4.0 years
Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy
Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy
Outcomes Primary outcome: time to monotherapy failure (FPG> 180
mg/dl) for rosiglitazone, as compared to metformin or glyburide
Secondary outcomes: FPG levels, glycated hemoglobin, insulin sensitivity, and beta-cell function
Outcomes Primary outcome: time to monotherapy failure (FPG> 180
mg/dl) for rosiglitazone, as compared to metformin or glyburide
Secondary outcomes: FPG levels, glycated hemoglobin, insulin sensitivity, and beta-cell function
Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy
Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy
Results 5 years cumulative incidence of monotherapy failure: 15%
with rosiglitazone, 21% with metformin, 34% with glyburide. This represents a risk reduction of 32% for rosiglitazone as compared with metformin and 64% as compared with glyburide (p<0.01 for both)
Risk of cardiovascular (CV) events: glyburide was associated with lower CV risk than rosiglitazone (p<0.05) and risk was similar between the rosiglitazone group and metformin group
Rosiglitazone was associated with more weight gain and edema than either glyburide or metformin; less hypoglycemia than glyburide and less GI effects than metformin (p<0.001 for all)
Rosiglitazone was associated with a higher rate of fractures in women
Results 5 years cumulative incidence of monotherapy failure: 15%
with rosiglitazone, 21% with metformin, 34% with glyburide. This represents a risk reduction of 32% for rosiglitazone as compared with metformin and 64% as compared with glyburide (p<0.01 for both)
Risk of cardiovascular (CV) events: glyburide was associated with lower CV risk than rosiglitazone (p<0.05) and risk was similar between the rosiglitazone group and metformin group
Rosiglitazone was associated with more weight gain and edema than either glyburide or metformin; less hypoglycemia than glyburide and less GI effects than metformin (p<0.001 for all)
Rosiglitazone was associated with a higher rate of fractures in women
Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD)
Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD)
Design To evaluate long-term impact of rosiglitazone on
cardiovascular outcomes and blood glucose control, compared to the conventional medications metformin and sulfonylureas
338 centers in 23 countries, 5.5 years duration randomized 4447 people with type 2 diabetes who
were already taking metformin or sulfonylurea alone
Design To evaluate long-term impact of rosiglitazone on
cardiovascular outcomes and blood glucose control, compared to the conventional medications metformin and sulfonylureas
338 centers in 23 countries, 5.5 years duration randomized 4447 people with type 2 diabetes who
were already taking metformin or sulfonylurea alone
Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD)
Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD)
4447 people with type 2 diabetes with mean HbA1c: 7.9%, who were already taking metformin or sulfonylurea alone
4447 people with type 2 diabetes with mean HbA1c: 7.9%, who were already taking metformin or sulfonylurea alone
1. Add-on rosiglitazone 2. Combination of metformin and sulfonylurea
Goal: HbA1c: 7.0 or less
If HbA1c >8.5
Add a third oral glucose-lowering agent Add insulin
Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD)
Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD)
On the composite outcomes of cardiovascular death, stroke and heart attack the result was slightly but not statistically significant in favor of rosiglitazone
Rosiglitazone was shown to be superior in controlling blood glucose than older metformin and sulfonylurea therapies
Found a double risk for heart failure Found an increased risk of arm and lower leg
fractures in women
On the composite outcomes of cardiovascular death, stroke and heart attack the result was slightly but not statistically significant in favor of rosiglitazone
Rosiglitazone was shown to be superior in controlling blood glucose than older metformin and sulfonylurea therapies
Found a double risk for heart failure Found an increased risk of arm and lower leg
fractures in women
A Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease.The BARI 2D Study Group. NEJM, 360:2503-2515
Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) study
Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) study
Evaluated the cardiovascular treatment approach compared to a diabetes control approach in persons with type 2 diabetes and stable coronary artery disease to reduce deaths or deaths and cardiovascular events (MI, stroke) combined
2368 people with stable heart disease and type 2 diabetes
5 years average follow up
Evaluated the cardiovascular treatment approach compared to a diabetes control approach in persons with type 2 diabetes and stable coronary artery disease to reduce deaths or deaths and cardiovascular events (MI, stroke) combined
2368 people with stable heart disease and type 2 diabetes
5 years average follow up
Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) study
Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) study
Prompt bypass surgery or angioplasty does NOT lower mortality risk compared to drug therapy in people with type 2 diabetes and stable heart disease.
No difference in mortality risk between drugs that reduce insulin resistance and drugs that provide insulin
Prompt bypass surgery or angioplasty does NOT lower mortality risk compared to drug therapy in people with type 2 diabetes and stable heart disease.
No difference in mortality risk between drugs that reduce insulin resistance and drugs that provide insulin
Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) study
Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) study
No increase in heart attacks was observed in the rosiglitazone group
Prompt CABG had significantly better outcomes when compared to medical treatment alone when CV events were considered in addition to death (non-fatal MI)
Among the subgroup of patients pre-identified as candidates for CABG, the subgroup that received prompt surgery had fewer heart attacks or strokes compared to those receiving intensive medical therapy alone
No increase in heart attacks was observed in the rosiglitazone group
Prompt CABG had significantly better outcomes when compared to medical treatment alone when CV events were considered in addition to death (non-fatal MI)
Among the subgroup of patients pre-identified as candidates for CABG, the subgroup that received prompt surgery had fewer heart attacks or strokes compared to those receiving intensive medical therapy alone
Diabetes:diagnosis, classification, management
Diabetes:diagnosis, classification, management
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
Definition Epidemiology Classification Diagnosis Treatment Evidence Treatment goals
* Postprandial measurements should be made 1-2 h after the beginning of the meal, generally peak levels in patients with diabetes.
Standards of Medical Care in Diabetes–2009. ADA Position Statement. Diabetes Care;32:S13-S61.
Glycemic goals: non-pregnant adults with diabetesGlycemic goals: non-pregnant adults with diabetes HbA1c < 7.0% Preprandial capillary plasma glucose 70-130 mg/dl (3.9-7.2 mmol/l) Peak postprandial capillary plasma glucose < 180 mg/dl (< 10.0 mmol/l)* Key concepts in setting glycemic goals HbA1c is the primary target for glycemic control Goals should be individualized based on:
duration of diabetes age/life expectancy comorbid conditions known CVD or advanced microvascular complications hypoglycemia unawareness individual patient considerations
More or less stringent glycemic goals may be appropriate for individual patients
Postprandial glucose may be targeted if HbA1c goals are not met despite reaching preprandial glucose goals
HbA1c < 7.0% Preprandial capillary plasma glucose 70-130 mg/dl (3.9-7.2 mmol/l) Peak postprandial capillary plasma glucose < 180 mg/dl (< 10.0 mmol/l)* Key concepts in setting glycemic goals HbA1c is the primary target for glycemic control Goals should be individualized based on:
duration of diabetes age/life expectancy comorbid conditions known CVD or advanced microvascular complications hypoglycemia unawareness individual patient considerations
More or less stringent glycemic goals may be appropriate for individual patients
Postprandial glucose may be targeted if HbA1c goals are not met despite reaching preprandial glucose goals
Glycemic goals - pregnant adults with diabetesGlycemic goals - pregnant adults with diabetes
Women with GDM
Maternal capillary glucose concentrations:
preprandial:≤95 mg/dl (5.3 mmol/l) and either
1-h postmeal: ≤140 mg/dl (7.8 mmol/l)
Women with GDM
Maternal capillary glucose concentrations:
preprandial:≤95 mg/dl (5.3 mmol/l) and either
1-h postmeal: ≤140 mg/dl (7.8 mmol/l)
Women with preexisting diabetes who become pregnant
Maternal capillary glucose concentrations:
premeal, bedtime, and overnight: 60-99mg/dl
Peak postprandial: 100-129 mg/dl
HbA1c <6.0%
Women with preexisting diabetes who become pregnant
Maternal capillary glucose concentrations:
premeal, bedtime, and overnight: 60-99mg/dl
Peak postprandial: 100-129 mg/dl
HbA1c <6.0%
Road Maps to Achieve Glycemic Control
In Type 2 Diabetes Mellitus
ACE/AACE Diabetes Road Map Task Force
ChairpersonsPaul S. Jellinger, MD, MACE, Co-Chair
Jaime A. Davidson, MD, FACE, Co-Chair
Task Force MembersLawrence Blonde, MD, FACP, FACE
Daniel Einhorn, MD, FACP, FACE
George Grunberger, MD, FACP, FACE
Yehuda Handelsman, MD, FACP, FACE
Richard Hellman, MD, FACP, FACE
Harold Lebovitz, MD, FACE
Philip Levy, MD, FACE
Victor L. Roberts, MD, MBA, FACP, FACE
© 2008 AACE. All rights reserved. No portion of the Roadmap may be altered, reproducedor distributed in any form without the express permission of AACE.
Revision April 2008
www.medscape.com/viewarticle/559463
Algorithm for the metabolic management of type 2 diabetes; Reinforce lifestyle interventions at every visit and check A1C every 3 months until A1C is <7% and then at least every 6 months. The interventions should be changed if A1C is ≥7%. a)Sulfonylureas other than glybenclamide (glyburide) or chlorpropamide. b)Insufficient clinical use to be confident regarding safety.
ADA Treatment AlgorithmADA Treatment Algorithm
Coming Attractions
• Insulin therapy in outpatient and inpatient settings
• Glycemic control and inpatient outcomes
Agustin Busta,MDAssistant ProfessorAlbert Einstein College of Medicine2009
Medical Nutrition Therapy for DiabetesDoes a perfect eating plan exist?
Jennifer Regester, RD, CDN
Medical Nutrition Therapy for DiabetesDoes a perfect eating plan exist?
Jennifer Regester, RD, CDN
Coming Attractions
Medical Nutrition Therapy
Review goals and outcomes of MNT Discuss basic recommendations for MNT Review specific recommendations for patient
population groups
Medical Nutrition Therapy
Review goals and outcomes of MNT Discuss basic recommendations for MNT Review specific recommendations for patient
population groups
Coming Attractions
“What Do I Eat?”
Discuss lifestyle changes including diet and exercise
Review basic nutrition recommendations and how to give nutrition advice
Provide follow-up resources
“What Do I Eat?”
Discuss lifestyle changes including diet and exercise
Review basic nutrition recommendations and how to give nutrition advice
Provide follow-up resources
Coming Attractions
Diabetes Technology Update Glucose Monitoring Systems - Glucose Meters
- CGMS Insulin Delivery Modes - Syringes
- Insulin Pens
- Jet Injectors
- Insulin Pumps
Marina Krymskaya, ANP, CDE
Diabetes Technology Update Glucose Monitoring Systems - Glucose Meters
- CGMS Insulin Delivery Modes - Syringes
- Insulin Pens
- Jet Injectors
- Insulin Pumps
Marina Krymskaya, ANP, CDE
Coming Attractions
Coming Attractions
What do these pictures have in common?