Presentation on theme: "Diabetes: Diagnosis, Classification, Management Controversies and News"— Presentation transcript:
1 Diabetes: Diagnosis, Classification, Management Controversies and News Bianca Alfonso, MD Endocrinology Fellow, Year 1Marina Krymskaya, ANP, CDE Diabetes Nurse EducatorJill Gregory Medical IllustratorLeonid Poretsky, MDChief, Division of Endocrinology and MetabolismDirector, Gerald J. Friedman Diabetes InstituteGerald J. Friedman Chair in EndocrinologyProfessor of Medicine, Albert Einstein College of Medicine
2 Diabetes 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.PlanEducational 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 staffOpen for suggestions. Please direct any comments to Marina Krymskaya at or
5 DefinitionDiabetes 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.**
7 Epidemiology 20.8 million Americans (7% of US population) About 10% have Type 1 DM14.6 million diagnosed6.2 million remain undiagnosed41 million have pre-diabetesLifetime risk for developing DM (Type 1 or 2) is 33 % in males and 39% in females for individuals born in 2000Up to 45% of newly diagnosed cases of DM in US children and adolescents are type 2AACE Diabetes Mellitus Guidelines, Endocr Pract. 2007;13(Suppl 1) 2007
9 Classification Type 1 diabetes Type 2 diabetes Other Genetic defects of beta cell functionGenetic defects in insulin actionDiseases of the exocrine pancreasEndocrinopathiesDrug/ chemical - inducedInfectionsUncommon forms of immune-mediated diabetesGenetic syndromes sometimes associated with diabetesGestational diabetes mellitus
10 Type 1 diabetes 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.
11 Atkinson MA and Eisenbarth GS. Lancet 2001;358:221-229.
12 Type 1 diabetes mellitus – immune mediated Absolute insulin deficiencyUsually due to autoimmune destruction of the pancreatic beta cellsIslet-cell antibodies (ICA) or other autoantibodies (antibodies to glutamic acid decarboxylase [anti-GAD] and anti-insulin)
13 Type 2 diabetes Hyperglycemia Insulin resistance Relative impairment in insulin secretion.
14 Decreased Glucose Transport & Activity (expression) of GLUT4 cell dysfunction and insulin resistance produce hyperglycemia in type 2 diabetesInsulin ResistanceCell DysfunctionIncreasedLipolysisPancreasLiverElevatedPlasma FFA↓GlucoseUptake↑GlucoseProductionIslet Cell Degranulation; Reduced Insulin Content-Cell Dysfunction and Insulin Resistance Produce Hyperglycemia inType 2 DiabetesDual ImpairmentImpaired insulin action (Insulin Resistance)Impaired insulin secretion (Impaired -cell function)In adipose tissue resistant to the effects of insulin, there is increased lipolysis resulting in elevated level of plasma free fatty acids (FFA). Elevated FFA lead to an increase in hepatic glucose production and decrease in glucose uptake in the muscle.Impaired -cell function and -cell degranulation lead to a reduction in circulating insulin. This reduction in circulating insulin leads to hyperglycemia.Impaired insulin action or insulin resistance results in a decreased response to insulin in insulin sensitive tissues. In the liver, insulin resistance results in an increase in hepatic glucose production.Whether the impairment is to insulin secretion or action, the resulting hyperglycemia has a negative effect on muscle and adipose tissue by decreasing expression of GLUT4 which, in turn, limits glucose transport into insulin-sensitive tissues.Key words:Type 2DefectsBeta cellInsulin resistanceMuscleAdipose TissueIncreased Glucose OutputReducedPlasma InsulinDecreased Glucose Transport & Activity (expression) of GLUT4Hyperglycemia
17 Other specific types of diabetes – Genetic defects of beta cell function Maturity–onset diabetes of the young (MODY)6 subtypes
18 Maturity: Onset diabetes of the young (MODY) MODY 1 - Mutation in HNF-4-alpha (transcription factor), chromosome 20MODY 2 - Mutation in glucokinase gene, chromosome 7MODY 3 - Mutation in HNF-1-alpha (transcription factor), chromosome 12 (most common form)MODY 4 - Mutation in insulin promoter factor-1 (IPF-1), chromosome 13MODY 5 - Mutation in HNF-1-beta, chromosome 17MODY 6 - Mutation in Neurogenic Differentiation Factor-1 (NEUROD1) , chromosome 2
19 Other specific types of diabetes: Genetic defects in insulin action Type A insulin resistanceLeprechaunismRabson- Mendenhall syndromeLipoatrophic diabetesOthers
20 Latent Autoimmune Diabetes in Adults (LADA) Adult-onset diabetes with circulating islet antibodies but not requiring insulin therapy initiallyAdults who should be considered for antibody testing*:age of onset <50 yearsacute symptomsBMI <25 kg/m2personal or family history of autoimmune disease*A clinical screening tool identifies autoimmune diabetes in adults. Fourlanos S; Perry C; Stein MS; Stankovich J; Harrison LC; Colman PG. Diabetes Care May;29(5):970-5
21 Gestational DM Definition Any degree of impaired glucose tolerance with onset or first recognition during pregnancyGestational diabetes (GDM) occurs when pancreatic function is not sufficient to overcome the insulin resistance created by changes in diabetogenic hormones during pregnancyMost have impaired glucose tolerance that begins in pregnancySome have previous undiagnosed type 2 diabetes mellitus10% have circulating islet cell antibodies
24 Diagnosis: Diabetes mellitus Symptoms of diabetes (polydipsia, polyuria, unexplained weight loss) PLUS a random plasma glucose >200 mg/dL (11.1 mmol/L)orFasting plasma glucose > 126 mg/dL (7.0 mmol/L) after overnight (at least 8 hours) fastTwo-hour plasma glucose> 200mg/dL (11.1 mmol/L) during a standard 75g oral glucose tolerance testAny of these criteria establishes the diagnosis but needs to be confirmed on a later day
34 Oral antihyperglycemic drugs: Metformin 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 pp
42 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 levelslower HbA1c by 0.5 – 0.8 %side effects: increased gas production and gastro-intestinal symptoms
43 Oral antihyperglycemic drugs: DPP-IV inibitors Sitagliptin (Januvia) : DPP-IV inhibitorDipeptidyl peptidase IV (DPP-IV) is a ubiquitous enzyme that deactivates a variety of bioactive peptides, including GIP and GLP-1
44 Oral antihyperglycemic drugs - Sitagliptin (Januvia) Used alone or in combination with metformin or TZDsReduces HbA1c by 0.5 – 0.7 %Side effects: increased rate of respiratory infections, headaches
45 "Januvia" by Byron RubinSculpture was installed at the West Point Pennsylvania Merck location.
48 Glucagon-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 secretionGLP-1 infused into healthy subjects decreases gastric emptying, causes a sensation of satiety, and decreases appetite.Effects:enhances insulin secretionlimits postprandial hyperglycemia.
49 Incretin EffectFigure 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
50 Antihyperglycemic drugs: Exenatide (Byetta) active ingredient in Exenatide (Byetta) is a synthetic version of a protein present in the saliva of the Gila monster
51 Antihyperglycemic drugs: Exenatide (Byetta) Added to metformin or sulfonylureas will reduce HbA1c by %Side effects:nausea (dose-depended, declines with time)acute pancreatitis (some necrotizing or hemorrhagic pancreatitis cases reported as well)
53 Antihyperglycemic drugs: Others Pramlintide (Symlin)synthetic analog of amylin
54 Amylin Stored in insulin secretory granules in the ß-cells Co-secreted with insulinDecreases glucagonSatiety signal?Decreases GI motility
55 Antihyperglycemic drugs: Pramlintide (Symlin) Delays gastric emptying, suppresses glucagon secretion, decreases appetiteAssociated with weight loss ( kg over 6 months)Used only in conjunction with insulin treatmentReduces HbA1c by %Side effects: nausea, gastro-intestinal symptoms
57 AVAILABLE INSULIN PREPARATIONS Product (Manufacturer)FormRapid Acting (Onset min, duration hrs 3-4)Insulin AnalogAspart - Novolog (Novo Nordisk)Lispro - Humalog (Lilly)Glulisine – Apidra (Aventis)Analog**Short Acting (Onset hr, duration hrs 5-7)*Human InsulinNovolin R (Rugular) (Novo Nordisk)Humulin R (Regular) (Lilly)Human**Purified InsulinRegular Iletin II (Lilly)PorkIntermediate Acting (Onset 1-4 hrs, duration hrs 18-24)*Novolin N (NPH) (Lilly)Humulin N (NPH) (Lilly)Humulin L (Lente) (Lilly)NPH Iletin III (Lilly)Long Acting (Onset 4-6 hrs, duration hrs 24-34)*Humulin Ultralente (Lilly)Basal Peakless InsulinGlargine-Lantus (Aventis)Detemir – Levemir (Novo Nordisk)Mixed Insulins70/30 InsulinNovolin 70/30 (Novo Nordisk)Humulin 70/30 (Lilly)Humulin 50/50 (Lilly)Humalog 50/50Product (Manufacturer)FormAnalog MixHumalog 75/25 MixNovolog Mix 70/30 (combination of fast and intermediate acting insulin with action similar to that of Humalog 75/25 mix)Analog**Insulin for Special UseBuffered Insulin (for pumps)Humulin BRRefills for Novolin PenNovolin R PenFillNovolin N PenFillNovolin 70/30 PenFillNovolog Mix 70/30 PenFillPrefilled PensNovolin RNovolin NNovolin 70/30NovologNovolog Mix 70/30HumalogHumalog Mix 75/25Humalog Mix 50/50Humulin NApidraHuman*** 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
58 ADA Treatment Algorithm 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.
61 ACCORD ↑22%* 10,251 patients with DM2 Mean age – 62.2 yrs Baseline A1C – 8.1%Intensive glucosecontrol vs. standardcontrolMedian f/up 3.5 yrsprimary outcome:nonfatal myocardial infarctionnonfatal strokedeath from CV causesIntensiveStandardRR reductionA1C6.4%7.5%Primary outcome6.9%7.2%10%Death from any cause5.0%4.0%↑22%*Non-fatal MI3.6%4.6%24%*Severe hypoglycemia2.7%1.5%had anatomical evidence of significant atherosclerosis, albuminuria, left ventricular hypertrophy, or at least two additional risk factors for cardiovascular disease (dyslipidemia, hypertension, current status as a smoker, or obesity).* P-value < 0.05The Action to Control Cardiovascular Risk in Diabetes Study Group. N Engl J Med 2008;358:
62 ACCORDAction to Control Cardiovascular Risk in Diabetes (ACCORD) trialDesigned primarily to examine the effects of glycemic control, lower than had previously been achieved, on CVD in subjects with long-standing diabetes10,250 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 %.
63 ACCORDAfter 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 ).* hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P=0.04
64 ACCORDPreliminary 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).
65 The ADVANCE Collaborative Group. N Engl J Med 2008;358:2560-2572 11,140 patients with DM2Mean age – 66 yrsBaseline A1C - 7.5%Intensive glucosecontrol vs. standard controlMedian f/up 5 yrs1º end-points: major macro- and micro vascular eventsIntensiveStandardRR reductionA1C6.5%7.3%Major microvascular9.4%10.9%14% *New/worsening nephropathy4.1%5.2%21%*New onset microalbuminuria23.7%25.7%9% *Major macrovascular10.0%10.6%6%Mean duration of DM – 8 yrs* P-value < 0.05The ADVANCE Collaborative Group. N Engl J Med 2008;358:
66 ADVANCEMean glycated hemoglobin level was lower in the intensive- control group (6.5%) than in the standard-control group (7.3%)Intensive controlreduced 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)
67 ADVANCE 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)
68 ADVANCEIntensive 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
69 DCCT 1441 patients with DM1 Age: 13-39 No history of cardiovascular diseaseIIT vs. conventional IT for 6.5 yrs1º prevention group:RetinopathyNeuropathyNephropathyIntensiveStandardRR reductionA1C7.4%9.1%New retinopathy1.2 per 100 pt-yr4.7 per 100 pt-yr76%*Microalbuminuria2.2 per 100 pt-yr3.4 per 100 pt-yr34%*Clinical neuropathy3.1 per 100 pt-yr9.8 per 100 pt-yr68%*Macrovascular disease0.5 per 100 pt-yr0.8 per 100 pt-yr41%½ w/o and ½ with clinical retinopathy* P-value < 0.05The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:
70 EDIC 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 diseaseIIT vs. conventional IT for 6.5 yrs1º prevention group:RetinopathyNeuropathyNephropathyYear 11th of EDICIntensiveStandardRR reductionA1C7.9%7.8%Microalbuminuria9%17%38%*Cr>2.00%2.0%46%*Progressive retinopathy6%21%75%*Major CV events0.38 per 100 pt-yr0.8% per 100 pt-yr42%*Non-fatal MI CVA, death from CVD112557%*Glycosylated hemoglobin values were measured quarterly and fasting lipid levels, serum creatinine values, and other risk factors for cardiovascular disease were measured annually in a central laboratory. Microalbuminuria and albuminuria were defined by urinary albumin excretion of at least 40 mg in a 24-hour period and of at least 300 mg in a 24-hour period, respectively. Renal disease was defined by the development of a serum creatinine level of at least 2 mg per deciliter (177 µmol per liter) or the need for dialysis or kidney transplantation. Electrocardiograms were obtained and examined annually by readers who were unaware of patients' treatment assignments. During the EDIC follow-up study, the methods used in the DCCT were continued, but glycosylated hemoglobin was measured annually and fasting lipid levels and renal function were measured in alternate years.Epidemiology of diabetes interventions and Complications (EDIC, ) follow-up study
71 EDICGoal : 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 treatmentsEstablished (first time) the role of intensive therapy and chronic glycemia with regard to atherosclerosis(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:
72 United Kingdom Prospective Diabetes Study (UKPDS) 3867 patients with newly diagnosed DM2Randomized to conventional-therapy group (diet alone) or intensive-therapy group: sulfonylurea (chlorpropamide, glibenclamide, glipizide) or insulinMetformin added to sulfonylurea if optimal control not achievedInsulin initiated if combination of oral agents was ineffectiveIntensive 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):
73 United Kingdom Prospective Diabetes Study (UKPDS) Drugs added to conventional group if symptoms of hyperglycemia or FPG>270 mg/dlGoal of therapy: FPG<108 mg/dlMicrovascular and Macrovascular complications examined
74 UKPDS: results 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
75 UKPDS: results No reduction in macrovascular disease More hypoglycemic episodes and weight gain in the intensive therapy group
76 10 year follow-up of intensive glucose control in type 2 diabetes United Kingdom Prospective Diabetes Study (UKPDS) patients in conventional or intensive therapyPost-trial monitor – 3277 patients followed up:first 5 years: annual UKPDS clinic visits (no attempts to maintain previously assigned therapy)years 6 – 10: annual questionnaires10 year follow-up of intensive glucose control in type 2 diabetes. R Holman et al. NEJM 2008;359:
77 10 year follow-up of intensive glucose control in type 2 diabetes ResultsHbA1c: differences between groups in were lost after the first yearSulfonylurea-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)10 year follow-up of intensive glucose control in type 2 diabetes. R Holman et al. NEJM 2008;359:
78 Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes 1791 military veterans with suboptimal response to therapy for type 2 DMmean age: 60.4 yearsMean number of years since diagnosis with diabetes: 11.540% had already had one CV event2 groupsintensive glucose controlstandard glucose controlGoal: absolute reduction of 1.5 percentage points in HbA1c in intensive treatment group compared to the standard treatmentPrimary outcome: time from randomization to first major CV eventGlucose Control and Vascular Complications in Veterans with Type 2 Diabetes. Duckworth W et al. NEJM 2009;360:
79 Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes Follow-up: 5.6 yearsPrimary 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)
80 Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes ResultsNO 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 complicationsNote! Correction: progression of microalbuminuria favors intensive therapy group (9.1% vs % in a standard group, P=0.04).** N ENGL J MED 361;10, September 3, 2009
81 Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes 160 patients with type 2 diabetes mellitus and persistent microalbuminuriaIntensive, target-driven treatmentConventional multifactorial treatmentTargets:- 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.Followed for a mean of 5.5 yearsEffect 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 Feb 7;358(6):
82 Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes: End points Primary end point:time to death from any causeSecondary end points:death from cardiovascular causesa 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)Tertiary end points:incident diabetic nephropathydevelopment or progression of diabetic retinopathy or neuropathy
83 Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes: Results Intensive group24 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)
84 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 groupLower risk of cardiovascular events (HR 0.41; 95% CI, 0.25 to ; p<0.001) vs conventional treatment group1 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
85 Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes Meta-analysisSearchespublished literature,FDA website,GlaxoSmithKline clinical trial registryInclusion criteriastudy duration > 24 weeks,use of a control group not receiving rosiglitazone,availability of outcome data for myocardial infarction and death from cardiovascular causesIncluded: 42 trials (out of 116 potentially relevant trials)Tabulated all occurrences of myocardial infarction and death from any cardiovascular causesMean age of subjects: 56 yearsMean 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:
86 Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes ResultsMyocardial 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)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:
87 Double-blind, randomized, controlled clinical trial Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy ADOPT - A Diabetes Outcome Progression TrialEvaluate rosiglitazone, metformin and glyburide as initial treatment for recently diagnosed type 2 diabetesDouble-blind, randomized, controlled clinical trial4360 patients enrolledMedian treatment time: 4.0 yearsGlycemic durability of rosiglitazone, metformin, or glyburide monotherapy. S E Kahn et al. NEJM 2006;355:
88 Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy OutcomesPrimary outcome: time to monotherapy failure (FPG> 180 mg/dl) for rosiglitazone, as compared to metformin or glyburideSecondary outcomes: FPG levels, glycated hemoglobin, insulin sensitivity, and beta-cell function
89 Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy Results5 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 groupRosiglitazone 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
90 Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) DesignTo evaluate long-term impact of rosiglitazone on cardiovascular outcomes and blood glucose control, compared to the conventional medications metformin and sulfonylureas338 centers in 23 countries,5.5 years durationrandomized 4447 people with type 2 diabetes who were already taking metformin or sulfonylurea alone
91 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 alone1. Add-on rosiglitazone2. Combination of metformin and sulfonylureaGoal: HbA1c: 7.0 or lessIf HbA1c >8.5Add a third oral glucose-lowering agentAdd insulin
92 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 rosiglitazoneRosiglitazone was shown to be superior in controlling blood glucose than older metformin and sulfonylurea therapiesFound a double risk for heart failureFound an increased risk of arm and lower leg fractures in women
93 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) combined2368 people with stable heart disease and type 2 diabetes5 years average follow upA Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease.The BARI 2D Study Group. NEJM, 360:
94 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
95 Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) study No increase in heart attacks was observed in the rosiglitazone groupPrompt 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
97 Glycemic goals: non-pregnant adults with diabetes HbA1c < 7.0%Preprandial capillary plasma glucose mg/dl ( mmol/l)Peak postprandial capillary plasma glucose < 180 mg/dl (< 10.0 mmol/l)*Key concepts in setting glycemic goalsHbA1c is the primary target for glycemic controlGoals should be individualized based on:duration of diabetesage/life expectancycomorbid conditionsknown CVD or advanced microvascular complicationshypoglycemia unawarenessindividual patient considerationsMore or less stringent glycemic goals may be appropriate for individual patientsPostprandial glucose may be targeted if HbA1c goals are not met despite reaching preprandial glucose 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.
98 Glycemic goals - pregnant adults with diabetes Women with GDMMaternal capillary glucose concentrations:preprandial:≤95 mg/dl (5.3 mmol/l) and either1-h postmeal: ≤140 mg/dl (7.8 mmol/l)Women with preexisting diabetes who become pregnantMaternal capillary glucose concentrations:premeal, bedtime, and overnight: 60-99mg/dlPeak postprandial: mg/dlHbA1c <6.0%
101 ADA Treatment Algorithm 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.
102 Coming AttractionsInsulin therapy in outpatient and inpatient settingsGlycemic control and inpatient outcomesAgustin Busta,MDAssistant ProfessorAlbert Einstein College of Medicine2009
103 Coming AttractionsMedical Nutrition Therapy for Diabetes Does a perfect eating plan exist? Jennifer Regester, RD, CDN
104 Coming Attractions Medical Nutrition Therapy Review goals and outcomes of MNTDiscuss basic recommendations for MNTReview specific recommendations for patient population groups
105 Coming Attractions “What Do I Eat?” Discuss lifestyle changes including diet and exerciseReview basic nutrition recommendations and how to give nutrition adviceProvide follow-up resources
106 Coming Attractions Diabetes Technology Update Glucose Monitoring Systems- Glucose Meters- CGMSInsulin Delivery Modes- Syringes- Insulin Pens- Jet Injectors- Insulin PumpsMarina Krymskaya, ANP, CDEIn the last few decades, there has been much progress in diabetes management. Due to technological advancements, patients whose lives are affected by diabetes are able to take advantage of more comfortable methods in checking their glucose and administering insulin.
107 (Answer: detect sugar) Coming AttractionsWhat do these pictures have in common?Glucose monitoring systems have come a long way. In the past, ants were utilized to detect diabetes. High concentration of sugar spilled into the urine would attract these insects. So, we can call it the ANTcient method. Currently, there are faster and more effective methods, which include continuous wireless transmission of the blood glucose readings from the sensor on the skin to the portable receiver. The quality of this modern technology has significantly improved diabetes management.(Answer: detect sugar)