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Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
Diabetes Step Care Approach
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Diabetes Step Care Approach

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  •  -Cell Dysfunction and Insulin Resistance Produce Hyperglycemia in Type 2 Diabetes Dual Impairment Impaired 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 2 Defects Beta cell Insulin resistance
  • 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).
  • Mean duration of DM – 8 yrs
  • ½ w/o and ½ with clinical retinopathy
  • 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.
  • Transcript

    • 1. Diabetes: Step care approach to management Dr. B. K. Iyer
    • 2. Diabetes: classification, diagnosis, management  Classification  Diagnosis  Treatment
    • 3. Diabetes classification – a relook  Classification  Diagnosis  Treatment
    • 4. Classification  Type 1 diabetes  Type 2 diabetes  Other 1. Genetic defects of beta cell function 2. Genetic defects in insulin action 3. Diseases of the exocrine pancreas 4. Endocrinopathies 5. Drug/ chemical - induced 6. Infections 7. Uncommon forms of immune-mediated diabetes 8. Genetic syndromes sometimes associated with diabetes  Gestational diabetes mellitus
    • 5. Type 1 diabetes  Type 1 diabetes is characterized by β-cell destruction, usually leading to absolute insulin deficiency. A. Immune-mediated B. Idiopathic * Diagnosis and Classification of Diabetes Mellitus. ADA 2009.
    • 6. * Atkinson MA and Eisenbarth GS. Lancet 2001;358:221-229. Type 1 diabetes - progression
    • 7. Type 1 diabetes – 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)
    • 8. Type 2 diabetes  Hyperglycemia  Insulin resistance  Relative insulin secretion/ response impairment
    • 9. Type 2 diabetes - causes Hyperglycemia in type 2 diabetes can be due to 2 causes: Pancreas Insulin Resistance Liver Hyperglycemia Islet Cell Degranulation; Reduced Insulin Content Muscle Adipose Tissue Decreased Glucose Transport & Activity (expression) of GLUT4 Increased Lipolysis ↑Glucose Production ↓Glucose Uptake Reduced Plasma Insulin Increased Glucose Output Cell Dysfunction Elevated Plasma FFA
    • 10. Type 2 diabetes & declining β–cell function : UKPDS Dashed line = extrapolation from UKPDS data Lebovitz HE, Diabetes reviews, 1999;7: 139-153
    • 11.  Maturity–onset diabetes of the young (MODY)  6 subtypes:  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 β-cell function
    • 12. Other specific types of diabetes: Genetic defects in insulin action  Type A insulin resistance  Leprechaunism  Rabson- Mendenhall syndrome  Lipoatrophic diabetes  Others
    • 13. *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)  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
    • 14. Gestational DM  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.  10% have circulating islet cell antibodies
    • 15. Diabetes diagnosis  Classification  Diagnosis  Treatment
    • 16. Diagnosis  Diabetes mellitus  Impaired fasting glucose (IFG)  Impaired glucose tolerance (IGT)  Gestational diabetes mellitus (GDM)
    • 17. Diagnosis: Diabetes mellitus  Symptoms of diabetes (polydipsia, polyuria, unexplained weight loss) PLUS a random plasma glucose >200 mg/dL (11.1 mmol/L) or  Fasting plasma glucose > 126 mg/dL (7.0 mmol / L) after overnight (at least 8 hours) fast or  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
    • 18. 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)
    • 19.  Oral glucose tolerance test (OGTT) – glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water  2-h post-load glucose < 140 mg/dl (7.8 mmol/l) = normal  2-h post-load glucose 140 - 199 mg/dl (7.8 – 11.1 mmol/l) = impaired glucose tolerance (IGT) Diagnosis: Impaired glucose tolerance (IGT)
    • 20. Diagnosis: Gestational Diabetes Mellitus (GDM) 1. Unequivocal hyperglycemia (confirmed on a subsequent day) Fasting plasma glucose > 126 mg/dL (7.0 mmol/L) Random plasma glucose >200 mg/dL (11.1 mmol/L) OR 2. Diagnostic OGTT 100-g glucose load 7.81403-h 8.61552-h 10.01801-h 5.395Fasting mmol/lmg/dl
    • 21. Diabetes: management  Classification  Diagnosis  Treatment – drugs in brief
    • 22. Treatment Treatment Lifestyle intervention Hypoglycaemic drugs •Weight loss •Increased exercise Oral hypoglycemic drugs Insulin & insulin analogs Others [incretins, pramlintide] 1.Biguanides 2.Sulfonylureas 3.Meglitinide analogs 4.Thiazolidinediones 5.α-Glucosidase Inhibitors 6.DPP-4 Inhibitors
    • 23. Treatment: Oral Antihyperglycemic Drugs
    • 24. Oral antihyperglycemic drugs: Biguanides  Metformin & Extended- release metformin now available  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
    • 25. Oral antihyperglycemic drugs: Metformin titration 1. Begin with low-dose metformin (500 mg) taken once or twice per day with meals (breakfast and/or dinner). 2. After 5–7 days, if GI side effects have not occurred, advance dose to 850 or 1,000 mg before breakfast and dinner. 3. If GI side effects appear as doses advanced, can decrease to previous lower dose and try to advance dose at a later time. 4. The maximum effective dose is usually 850 mg twice per day, with modestly greater effectiveness with doses up to 3 g per day. GI side effects may limit the dose that can be used. 5. Based on cost considerations, generic metformin is the first choice of therapy. A longer-acting formulation is available in some countries and can be given once per day.
    • 26. Oral antihyperglycemic drugs: Sulfonylureas  1st generation no longer used: Chlorpropamide Tolbutamide  2nd generation : Glyburide, Glipizide, Glimepiride  enhance insulin secretion  lower HbA1c by 1.5 %  side effects: hypoglycemia, weight gain
    • 27. 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  Repaglinide  Nateglinide  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
    • 28. Oral antihyperglycemic drugs: Thiazolidinediones (TZDs)  Rosiglitazone & Pioglitazone  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
    • 29. Oral antihyperglycemic drugs: -Glucosidase Inhibitors  Acarbose  Miglitol  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
    • 30. Oral antihyperglycemic drugs: DPP-IV inibitors  Sitagliptin : DPP-IV inhibitor  Dipeptidyl peptidase IV (DPP- IV) is a ubiquitous enzyme that deactivates a variety of bioactive peptides, including GIP and GLP-1  Used alone or in combination with metformin or TZDs  Reduces HbA1c by 0.5 – 0.7 %  Side effects: increased rate of respiratory infections, headaches
    • 31. Other antihyperglycemic drugs: Incretins  Glucagon-like peptide 1 (GLP-1) agonist  Exenatide - active ingredient in Exenatide (Byetta) is a synthetic version of a protein present in the saliva of the Gila monster
    • 32. 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 is 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.
    • 33. Other antihyperglycemic drugs: Incretins [Exenatide]  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)
    • 34. 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 Effect
    • 35. Antihyperglycemic drugs: Others  Pramlintide (Symlin)  synthetic analog of amylin  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  ↓ HbA1c by 0.5- 0.7 %  Side effects: nausea, gastro- intestinal symptoms
    • 36. Amylin  Stored in insulin secretory granules in the ß- cells  Co-secreted with insulin  Decreases glucagon  Satiety signal?  Decreases GI motility
    • 37. * 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
    • 38. Summary of antidiabetic interventions as monotherapy Interventions Expected decrease in A1C (%) Advantages Disadvantages Step 1: initial Lifestyle to decrease weight and increase activity 1–2 Low cost, many benefits Fails for most in 1st year Metformin 1.5 Weight neutral, inexpensive GI side effects, rare lactic acidosis Step 2: additional therapy Insulin 1.5–2.5 No dose limit, inexpensive, improved lipid profile Injections, monitoring, hypoglycemia, weight gain Sulfonylureas 1.5 Inexpensive Weight gain, hypoglycemia* TZDs 0.5–1.4 Improved lipid profile Fluid retention, weight gain, expensive Other drugs α-Glucosidase inhibitors 0.5–0.8 Weight neutral Frequent GI side effects, three times/day dosing, expensive Exenatide 0.5–1.0 Weight loss Injections, frequent GI side effects, expensive, little experience Glinides 1–1.5† Short duration Three times/day dosing, expensive Pramlintide 0.5–1.0 Weight loss Injections, three times/day dosing, frequent GI side effects, expensive, little experience
    • 39. Diabetes: management  Classification  Diagnosis  Treatment – goals
    • 40. * 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 diabetes  Key concepts in setting glycemic goals  HbA1c is the primary target for glycemic control  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)*
    • 41. * 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 diabetes  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
    • 42. Glycemic 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 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%
    • 43. Road map to achieve glycaemic goals: Naive to type 2 therapy
    • 44. Diabetes: management  Classification  Diagnosis  Treatment – step care approach
    • 45. 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 Algorithm
    • 46. Algorithm for the metabolic management of type 2 diabetes. Reinforce lifestyle intervention at every visit. *Check A1C every 3 months until <7% and then at least every 6 months. +Although three oral agents can be used, initiation and intensification of insulin therapy is preferred based on effectiveness and expense. ADA Treatment Algorithm
    • 47. 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 Algorithm
    • 48. 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 ref. 71 for more detailed instructions. +Premixed insulins are 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 Algorithm
    • 49. 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 ref. 71 for more detailed instructions. +Premixed insulins are 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 Algorithm
    • 50. Clarifications on the watch list  Insulin therapy in outpatient and inpatient settings  Glycemic control and inpatient outcomes  Does a perfect eating plan exist?  Medical Nutrition Therapy for Diabetes  Review goals and outcomes of Medical Nutrition Therapy [MNT]  Discuss basic recommendations for MNT  Review specific recommendations for patient population groups
    • 51. Road Maps to Achieve Glycemic Control in Type 2 Diabetes Mellitus ACE/AACE Diabetes Road Map Task Force

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