Presentation on theme: "Www.diabetesclinic.ca 2003 CDA Clinical Practice Guidelines J. Robin Conway M.D. Diabetes Clinic Smiths Falls, ON www.diabetesclinic.ca."— Presentation transcript:
CDA Clinical Practice Guidelines J. Robin Conway M.D. Diabetes Clinic Smiths Falls, ON
Worldwide rates of diabetes mellitus: predictions Prevalence (millions) North America EuropeSoutheas t Asia Year World Health Organization Canadian Diabetes Association, 1998 website.
Frequency of diagnosed and undiagnosed diabetes and IGT, by age (U.S. data - Harris) 2 Million Canadians Have Diabetes Mellitus Harris. Diabetes Care 1993;16:
Haffner Am J Cardiol 1999;84:11J-4J. Framingham study: diabetes and CAD mortality at 20-year follow-up Cardiovascular Disease Risk is Increased 2 to 4 Times
THE BURDEN OF DIABETES 87% of Type 2 Diabetes is managed in Primary Care Diascan Study: 23.5% of patients in our office have diabetes Que screening >2 Risk Factors 79% tested 7% Diabetes 13% IGT or IFG 74% No Treatment Advice Strychar I et al. Cdn J Diab 2003(abs) Leiter et al. Diabetes Care 2000
T2DM in Family Practice 84% of patients had A1c in past year Average A1c 7.9% (goal<7%) 88% had BP check 48% had lipid profiles 28% tested for microalbuminuria 15% had foot exams Harris S et al. Cdn Fam Phys 2003
Cardiovascular Risk Sask Smiths Falls Statin 19.9% 70% ACE 48.9% 91% ASA 23.5% 70% Brown L et al. Cdn J Diab 2003(abs) Nozek L et al. Cdn J Diab 2003(abs) Conway R et al. Cdn J Diab 2003(abs)
Burden of Poor Control - Cost
CDA Guidelines Early Aggressive Screening FPG every 3yrs over age 40 High Risk Groups Relatives of Diabetics Aboriginals & Hispanics PCOS Schizophrenics Dyslipidemia
SCREENING & PREVENTION All individuals should be evaluated annually for Diabetes risk on the basis of history, clinical and demographic criteria. Screening for Diabetes using a fasting plasma glucose should be performed every 3 years for individuals over 40 years of age. More frequent or earlier testing with either a fasting plasma glucose or OGTT in people with additional risk factors for Diabetes,
PREVENTION Pre diabetes OGTT should be considered if BMI>25 and FPG between 5.7 & 7 to identify IGT or Diabetes With IGT a program of lifestyle mod that includes wt loss & exercise to prevent T2D With IGT treatment with Metformin or Acarbose should be considered.
DIAGNOSIS FBS >7 mmol/L + symptoms RBS >11 mmol/L + symptoms PREDIABETES IFG FBS mmol/L IGT 2 hr PC glucose on OGTT If FBS > 5.7 mmol/L do OGTT
Recommended targets for glycemic control* A1C** (%) FPG/preprandial PG (mmol/L) 2-hour postprandial PG (mmol/L) Target for most patients Normal range (considered for patients in whom it can be achieved safely) *Treatment goals and strategies must be tailored to the patient, with consideration given to individual risk factors. Glycemic targets for children 12 years of age and pregnant women differ from these targets. Please refer to Other Relevant Guidelines for further details. **An A1C of 7.0% corresponds to a laboratory value of Where possible, Canadian laboratories should standardize their A1C values to DCCT levels (reference range: to 0.060). However, as many laboratories continue to use a different reference range, the target A1C value should be adjusted based on the specific reference range used by the laboratory that performed the test. As a useful guide: an A1C target of 7.0% refers to a threshold that is approximately 15% above the upper limit of normal. A1C = glycosylated hemoglobin DCCT = Diabetes Control and Complications Trial FPG = fasting plasma glucose PG = plasma glucose
Monitoring A1c every 3 months Self Monitor Glucose, interpret results,alter food choices, physical activity, frequency of testing & medications Type 1 should test at least 3 times a day Type 2 should test at least daily Type 1 in acute illness should test ketones if glucose >14 mmol/L
Exercise 150 minutes of moderate intensity aerobic exercise over 3 nonconsecutive days of the week or if willing 4 hrs/week Encourage resistance exercise 3 times/week
Nutrition Nutrition Counselling Canada Food Guide For PPG control Amnt & source of CHO, Glycemic Index Sucrose to 10% Cal Discuss Alcohol Intensive Insulin do CHO counting
Goals in Diabetes FBS<7, PC<11, A1c<7% BP <130/80 TC/HDL <4, LDL <2.5, Trig <1.5 ACR <2 Male, <2.8 Female
Drugs in Type 2
Need for Combination Therapy in UKPDS % of Patients
Pathophysiology of Type 2 Diabetes Decreased insulin secretion Loss of first-phase insulin secretion Increased insulin resistance, resulting in: –Decreased glucose and fat uptake –Increased free fatty acid release –Increased hepatic glucose output
9 HbA 1c (%) UKPDS: Long-term Glucose Control Years of treatment Conventional Intensive ULN = 6.2% UKPDS Study Group, Lancet, 1998;352:
-cell function (%) ConventionalSulphonylureaMetformin UKPDS 16: Diabetes 1995; 44:1249–1258 Progressive Loss of -cell Function in UKPDS Mean age at baseline 53 yrs.
Type 2 Diabetes is Characterized by Insulin Resistance and Progressive ß-cell Failure 50% of ß-cell function is already lost at diagnosis Elevated PPG occurs before diagnosis Impaired glucose tolerance Years from Diagnosis Beta Cell Function (%) Postprandial hyperglycemia Type 2 diabetes phase I Type 2 diabetes phase II Type 2 diabetes phase III Lebovitz HE. Diabetes Review 1999;7(3): Stages of Type 2 Diabetes in Relationship to ß-cell Function
Impaired Insulin Secretion in Type 2 Diabetes Time 6 am10 am2 pm6 pm10 pm2 am6 am Insulin secretion (pmol/min) 0 Type 2 diabetes healthy Adapted from Polonsky KS et al. N Engl J Med 1996; 334: 777.
Type 2 Diabetes: Underlying Defects Type 2 diabetes Beta-cell function Insulin resistance Other defects: lipolysis release of NEFA hepatic glucose production Adapted from Matthaei et al. Endocrine Reviews 2000;21: Adapted from Frayn. Br J Nutr 2000;83(suppl 1): S71-S77. Pathophysiology
Type 2 Diabetes - Dual Impairment Impaired insulin secretion from pancreatic ß-cells A sluggish and inadequate response to the glucose load imposed by meals Characteristic only of Type 2 diabetes 100% of patients have impaired secretion at diagnosis Approx. 84% have insulin resistance Also associated with other metabolic conditions Insulin Secretion Insulin Resistance Lebovitz HE. Diabetes Review. 1999; 7(3): Polonsky KS, et al. NEJM 1988;318: Bonora E, et al. Diabetes 1998;47:
Issues to be Addressed when Selecting Agents Degree of -cell deficiency Magnitude of insulin resistance Extent of fasting hyperglycemia Magnitude of postprandial hyperglycemia
Epidemiological Evidence Linking PPG with Cardiovascular Disease
CHD Risk and Type 2 Diabetes Haffner SM et al. N Engl J Med 339: , 1998 Db- No diabetes; Db+ Diabetes; MI- No prior MI; MI+ prior MI p<0.001 for prior MI vs. no MI and diabetes vs. no diabetes calculated with Cox proportional-hazards models, adjusted for age and sex MIStrokeCV death
2-hour PPG, Not FPG, Predicted All-cause Mortality Adjusted for age, centre, sex < – –11.0 <7.8 Fasting plasma glucose (mmol/L) 2-hour PPG, 75g OGTT (mmol/L) Hazard ratio Adapted from DECODE Study Group. Lancet 1999;354:617.
Epidemiological Evidence Linking High PPG * with CVD Risk & Mortality DECODE, DECODE, High PPG is associated with increased risk of death, independent of FPG Pacific and Indian Ocean, Pacific and Indian Ocean, High PPG with normal FPG doubles the risk of mortality Funagata Diabetes Study, Funagata Diabetes Study, IGT, but not IFG, is a risk factor for CVD Whitehall, Paris, Helsinki Study 1998 Whitehall, Paris, Helsinki Study Men in upper 2.5% of PPG distribution had significantly higher CHD mortality The Rancho-Bernardo Study, The Rancho-Bernardo Study, PPG more than doubles the risk of fatal CVD and heart disease in older adults Diabetes Intervention Study, Diabetes Intervention Study, PPG (1-hr post-breakfast), but not FPG, is associated with CHD 1 DECODE Study Group. Lancet 1999;354: Shaw JE et al. Diabetologia 1999;42: Tominaga M et al. Diabetes Care 1999;22: Balkau B et al. Diabetes Care 1998;21: Barrett-Connor E et al. Diabetes Care 1998;21: Hanefeld M et al. Diabetologia 1996;39:1577. *2-hour PPG after 75g OGTT, except where indicated
Intervention Studies to Control PPG and its Effect on CV Disease Manzella Type 2 Repaglinide had greater PPG lowering and a significantly greater improvement in endothelial function and a decline in oxidative stress compared to glyburide Esposito Type 2 After 12 months, CIMT regression (decrease of > mm) was observed in 52% of the repaglinide group vs 18% in the glyburide group (p<0.01). Hanefeld Type 2 Acarbose reduced relative risk of myocardial infarction by 64% (p=0.012) and any CV event 35% (p=0.0061) Chiasson IGT Acarbose reduced relative risk of CV events by 49% and new cases of hypertension by 34% compared to placebo 1. Chiasson et al. JAMA 2003; 290: Hanefeld M, et al. Eur Heart J 2004;25(1): Esposito K et al. Circulation 2004; Manzella D et al. Diabetes Care 2005; 28(2): 366.
Sites of Action of Currently Available Therapeutic Options GLUCOSE ABSORPTION GLUCOSE PRODUCTION Biguanides Thiazolidinediones MUSCLE PERIPHERAL GLUCOSE UPTAKE Thiazolidinediones (Biguanides) PANCREAS INSULIN SECRETION Sulfonylureas Meglitinides Insulin ADIPOSE TISSUE LIVER Alpha-glucosidase inhibitors INTESTINE Sonnenberg, Kotchen Curr Opin Nephrol Hypertens 1998;7:551-5.
Combination Antihyperglycemic Therapy Addition, rather than substitution recommended Agents from other classes should be added –Diff sites of action –Diff MOA
Normal Blood Glucose Normal Insulin Years Timeline for Therapy in Type 2 Diabetes IGT Diabete s Avg Dx 6.5 yrs Fasting Blood Glucose Postprandial Blood Glucose Insulin Resistance Endogenous Insulin Modified from graphic developed by the IDC Lifestyle Lifestyle Metformin/Thiazolidinediones Secretagogues Insulin
Canadian Diabetes Association 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada Canadian Diabetes Association 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada
Individualized Treatment Metformin for overweight patients If control not achieved add another agent If A1c >9 start with 2 agents Consider early insulin for hyperglycemia Bedtime intermediate insulin (NPH)
Pharmacotherapy Treat the Predominant problem Each Drug will lower A1c 1-1.5% (Acarbose & Orlistat 0-5%) Start with Metformin in Obese or High FBS Combination therapy if A1c >9% Early Insulin if decompensated Consider TZD
Clinical assessment and initiation of nutrition and physical activity Mild to moderate hyperglycemia (A1C <9.0%) Overweight (BMI 25 kg/m 2 ) Non-overweight (BMI 25 kg/m 2 ) Biguanide alone or in combination with 1 of: insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor 1 or 2 antihyperglycemic agents from different classes biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor Add a drug from a different class or Use insulin alone or in combination with: biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitor Marked hyperglycemia (A1C 9.0%) 2 antihyperglycemic agents from different classes biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor Basal and/or preprandial insulin Add an oral antihyperglycemic agent from a different class of insulin* Intensify insulin regimen or add biguanide insulin secretagogue** insulin sensitizer* alpha-glucosidase inhibitor If not at target L I F E S T Y L E Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months
L I F E S T Y L E Add a drug from a different class or Use insulin alone or in combination with: biguanide insulin secretagogue insulin sensitizer* alpha-glucosidase inhibitor Overweight (BMI 25 kg/m 2 ) Mild to moderate hyperglycemia (A1C <9.0%) Timely adjustments to and/or additions of oral antihyperglycemic agents and/or insulin should be made to attain target A1C within 6 to 12 months Biguanide alone or in combination with 1 of: insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor If not at target * When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin is currently not an approved indication in Canada.
Attributes of Meglitinides Gluconorm (repaglinide) Starlix (nateglinide) Increases early-phase insulin release Physiologic response to meals (rapid onset and elimination) Significant improvement in key blood glucose parameters (PPG, FPG, and HbA 1c ) Low risk of hypoglycemia Weight neutral
Hypoglycemia: Why is it Important? Annually, about % of patients on oral agents have hypoglycemia Under-recognized and under-reported Substantial impact: – Social embarrassment – Emotional toll – found dead in bed – Work restrictions (e.g. operating machinery) – Devastating to elderly patients
Adding Repaglinide to Restore Mealtime Insulin Secretion If repaglinide is 1 st line or A1C <8%, start 0.5 mg with meals Double the dose every week until target achieved Maximum mealtime dose (4mg); Maximum daily dose (16mg) If A1C 8% 1 mg or 2 mg with meals GlucoNorm ® Product Monograph, Novo Nordisk Canada Inc., 2005.
4:0016:0020:0024:004:00 BreakfastLunchDinner 8:00 12:008:00 Time Glargine or Detemir Plasma insulin Basal/Bolus Treatment Program with Rapid-acting and Long-acting Analogs LisproLisproLispro AspartAspartAspart or