RCN Back Pain Conference

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  • DISCUSSION This diagram demonstrates the GLP-1 effects in humans and the role these effects play in normal physiology. Upon the ingestion of food, plasma glucose levels increase postprandially. GLP-1 is secreted from intestinal L cells and provides a stimulus to the β -cells to release insulin in a glucose-dependent manner. When plasma glucose levels return to normal, the action of GLP-1 decreases 1 . GLP-1 also suppresses glucagon levels that are inappropriately elevated in patients with type 2 diabetes 1 . Lower glucagon levels leads to decreased hepatic glucose output 2 . In the stomach, GLP-1 slows the rate of gastric emptying, which reduces the rate at which meal-derived glucose appears in the circulation 3 . In the brain, GLP-1 promotes satiety and reduces appetite, which leads to a feeling of fullness and a reduction in food intake 4,5 . All these actions help maintain overall glucose homeostasis. 1 Nauck MA, et al. Diabetologia 1993;36:741–744 2 Larsson H, et al. Acta Physiol Scand 1997;160:413–422 3 Nauck MA, et al. Diabetologia 1996;39:1546–1553 4 Flint A, et al. J Clin Invest 1998;101:515–520 5 Zander et al. Lancet 2002;359:824–830.
  • Lessons from UKPDS: better control means fewer complications The UKPDS has proven beyond doubt that intensive glycaemic control is strongly associated with significant clinical benefits for patients with type 2 diabetes. In an epidemiological analysis of the UKPDS cohort every 1% decrease in HbA 1C was associated with clinically important reductions in the incidence of diabetes-related death (  21%) myocardial infarction (  14%) microvascular complications (  37%) peripheral vascular disease (  43%) There is no lower limit beyond which reductions in HbA 1C cease to be of benefit. Taking diabetes-related death as an example, this means that:  HbA 1C of 2% delivers a 42% reduction in risk  HbA 1C of 3% delivers a 63% reduction in risk, and so on. Therefore, the greater the reduction in HbA 1C , the greater the protection against complications. Stratton MI Adler AI, Neil AW, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:405-12.
  • RCN Back Pain Conference

    1. 1. When to Start Insulin Doctors and Nurses Working Together Dr Ketan Dhatariya Consultant in Diabetes and Endocrinology Norfolk and Norwich University Hospital NHS Trust
    2. 2. Good Timing!
    3. 3. Why is it the 14 th of November? <ul><li>Fred Banting – one of the co-discoverers of insulin </li></ul><ul><li>Born on 14 th November 1891 </li></ul>
    4. 4. We’re All Trying to Achieve The Same Thing – But Using Different Approaches
    5. 5. Some Definitions <ul><li>Type 1 </li></ul><ul><li>Type 2 </li></ul><ul><li>Others (not mentioned any more) </li></ul>
    6. 6. Two Main Types <ul><li>Type 1 </li></ul><ul><ul><li>Autoimmune destruction of the β cells of the Islets of Langerhans in the pancreas. This leads to an absolute insulin deficiency. Insulin treatment is therefore mandatory </li></ul></ul><ul><ul><li>Previously known as IDDM or juvenile onset diabetes </li></ul></ul>
    7. 7. Two Main Types <ul><li>Type 2 </li></ul><ul><ul><li>Impaired insulin action (insulin resistance) and eventually, impaired insulin secretion as well </li></ul></ul><ul><ul><li>Usually treated with oral medication initially, then may move onto insulin </li></ul></ul><ul><ul><li>Formerly known as NIDDM or maturity onset diabetes </li></ul></ul>
    8. 8. Epidemiology <ul><li>Diabetes currently affects approximately 3 to 4% of the population </li></ul><ul><li>90% of whom have type 2 diabetes </li></ul><ul><li>Lifetime risk of developing diabetes is about 10% </li></ul>
    9. 9. Why is it Important? <ul><li>Poorly controlled diabetes leads to accelerated cardiovascular morbidity and mortality </li></ul><ul><li>A combination of microvascular and macrovascular disease </li></ul>Thom T et al Circulation 2006;113(6):e85-151
    10. 10. Some Good News Health Consumer Power House Euro Consumer Diabetes Index Sept 2008
    11. 11. UKPDS HbA 1c Median Values 0 6 7 8 9 0 3 6 9 12 15 HbA 1c (%) Years from randomisation Conventional Intensive 6.2% upper limit of normal range
    12. 12. Data From 3.3M Danes Schramm TK et al Circulation 2008;117:1945-1954
    13. 13. An (?Uncontroversial) Starting Point <ul><li>People with type 1 diabetes need to be referred to the specialist hospital team at the time of suspected diagnosis </li></ul><ul><li>Many people continue to be followed up in secondary care. </li></ul><ul><ul><li>This depends heavily on the competence and confidence of the primary care team – and the support offered by secondary care </li></ul></ul>
    14. 14. Non-Insulin Hypoglycaemic Agents <ul><li>α glucosidase inhibitors </li></ul><ul><li>Metaglinides </li></ul><ul><li>Metformin </li></ul><ul><li>Sulphonylureas </li></ul><ul><li>Thiazolidindiones </li></ul><ul><li>GLP – 1 analogues </li></ul><ul><li>DPP IV inhibitors </li></ul>
    15. 15. α Glucosidase Inhibitors <ul><li>There is only 1 – acarbose </li></ul><ul><li>Intestinal disaccharidase inhibitor </li></ul><ul><li>Taken one with each meal </li></ul><ul><li>If they don’t eat, no need to take the tablet </li></ul><ul><li>HbA1c reduction of 0.5 - 0.8% </li></ul>
    16. 16. Metaglinides <ul><li>There are 2 – repaglinide and nateglinide </li></ul><ul><li>Work by binding to the sulphonylurea receptor and ‘squeezing’ the β cell to release insulin </li></ul><ul><li>They stimulate first-phase insulin release in a glucose-sensitive manner </li></ul><ul><li>HbA1c reduction of 0.5 - 1.5% </li></ul>
    17. 17. Metformin Derived from the plant known as Goat's Rue, French Lilac, Italian Fitch or Professor-weed ( Galega officinalis )
    18. 18. Metformin <ul><li>First choice oral hypoglycaemic agent for people with type 2 diabetes, regardless of BMI </li></ul><ul><li>Works by decreasing hepatic gluconeogenesis, decreasing gut glucose uptake and increasing peripheral insulin sensitivity </li></ul><ul><li>Metformin does not (or very rarely) give people hypos, because it works by preventing blood glucose levels rising rather than by lowering glucose levels </li></ul><ul><li>HbA1c reduction of 1.0 – 2.0% </li></ul>
    19. 19. Sulphonylureas <ul><li>Have been around since the 1950’s </li></ul><ul><li>Act by binding to the SU receptor causing an influx of Ca 2+ and an exocytosis of insulin containing vesicles </li></ul><ul><li>Use limited to individuals with a BMI < 25 or in whom metformin is contraindicated </li></ul><ul><li>HbA1c reduction of 1.0 – 2.0% </li></ul>
    20. 20. Thiazolidinediones <ul><li>Work by increasing peripheral insulin sensitivity at a nuclear level on peroxisome proliferator-activated receptor γ (PPAR γ ) </li></ul><ul><li>HbA1c reduction of 0.5 - 1.4% </li></ul><ul><li>Several controversies thus use is declining </li></ul><ul><ul><li>Increased CV death rates </li></ul></ul><ul><ul><li>Increased fracture rates </li></ul></ul><ul><ul><li>Increased rates of macular oedema </li></ul></ul>Nissen SE NEJM 2007;356(24):2457-2471 Loke Y et al In press Ryan EH et al Retina 2006; 26(5):562-70
    21. 21. GLP-1 and DPP-IV Nauck MA et al. Diabetologi a 1993;36:741–744; Larsson H et al. Acta Physiol Scand 1997;160:413–422; Nauck MA et al. Diabetologia 1996;39:1546–1553; Flint A et al. J Clin Invest 1998;101:515–520; Zander et al. Lancet 2002;359:824–830. GLP-1 secreted upon the ingestion of food 1.  - cell: Enhances glucose-dependent insulin secretion in the pancreas 3.Liver: reduces hepatic glucose output 2. α - cell: Suppresses postprandial glucagon secretion 4.Stomach: slows the rate of gastric emptying 5.Brain: Promotes satiety and reduces appetite
    22. 22. Their Effects Are Additive HbA 1 C Time
    23. 23. The Goalposts Are Changing <ul><li>HbA 1 C targets are coming down </li></ul><ul><li>The tighter the control, the likelihood of developing complications reduces – to a point </li></ul>
    24. 24. Lessons from UKPDS: Better Control Means Fewer Complications EVERY 1% reduction in HbA 1c REDUCED RISK* 1% Deaths from diabetes Heart attacks Microvascular complications Peripheral vascular disorders UKPDS 35. BMJ 2000;321:405–12 *p<0.0001 – 21% – 14% – 37% – 43%
    25. 25. How Many Guidelines? <ul><li>EASD / ADA </li></ul><ul><ul><li>Nathan et al Diabetes care 22/10/08 epub ahead of publication http://care.diabetesjournals.org/misc/dv08-9025.pdf </li></ul></ul><ul><li>NICE </li></ul><ul><ul><li>http://www.nice.org.uk/nicemedia/pdf/CG66diabetesfullguideline.pdf </li></ul></ul><ul><li>Royal College of Physicians </li></ul><ul><ul><li>http://www.rcplondon.ac.uk/pubs/contents/14f051f1-8fa4-4d0b-9385-9f2e77edc2ca.pdf </li></ul></ul>
    26. 26. Recent ADA / EASD Guidelines Nathan DM et al Diabetes Care 22/10/08 epub online
    27. 27. NICE Advice http://www.nice.org.uk/nicemedia/pdf/CG66diabetesfullguideline.pdf Accessed 9th November 2008
    28. 28. RCP Management of Type 2 diabetes – May 2008 Accessed 9.11.08 http://www.rcplondon.ac.uk/pubs/contents/14f051f1-8fa4-4d0b-9385-9f2e77edc2ca.pdf
    29. 29. Tighter Control <ul><li>This means that oral agents alone may not be sufficient and that insulin needs to be added </li></ul>
    30. 30. Consider the Following Scenarios <ul><li>60 year old, CVA, blind, dense hemiplegia, lives in a nursing home, fully dependent </li></ul><ul><li>80 year old, plays golf daily, travels the world extensively with their 60 year old partner looking for ‘excitement’ </li></ul><ul><li>QOF is not ‘situation specific’ </li></ul>
    31. 31. Insulin <ul><li>Should be started when the HbA 1 C is ≥ 7.5% on maximal oral hypoglycaemics </li></ul><ul><li>Pregnancy </li></ul><ul><li>Steroids </li></ul><ul><li>Intercurrent illness </li></ul>
    32. 32. Now You’ve made Your Decision <ul><li>A few questions </li></ul><ul><ul><li>Which insulin? </li></ul></ul><ul><ul><li>What dose? </li></ul></ul><ul><ul><li>What regime? </li></ul></ul><ul><ul><li>What do I do with the tablets? </li></ul></ul><ul><li>Should I address their weight first?? </li></ul>
    33. 33. Insulins <ul><li>Soluble (short acting) </li></ul><ul><li>NPH (intermediate) </li></ul><ul><li>Once daily </li></ul><ul><li>Mixtures </li></ul><ul><li>Insulin analogues – ultra short, long and mixtures </li></ul>
    34. 34. EASD / ADA Recommendations <ul><li>Start with once daily basal insulin </li></ul><ul><ul><li>Which type of insulin depends on when BG levels are highest </li></ul></ul><ul><li>If there are no contraindications – stay on night time insulin, with day time metformin or SU’s </li></ul><ul><li>Keep regularly increasing the dose until the fasting blood glucose is less than 7.0 mmol/L </li></ul>Holman RR et al N Engl J Med 2007;357:1716-1730 Bretzel RG et al Lancet 2008;371:1073-1084; Nathan DM et al Diabetes Care 22/10/2008; epub Riddle MC Endocrine and Metabolic Clinics of North America 2005;34:77-98; Pala L et al Diabetes Res Clin Pract 2007;78:132-135
    35. 35. Other Options <ul><li>Twice daily mixtures are commonly used but may be associated with greater weight gain than once daily injections </li></ul><ul><li>Three times daily mixtures are also common on the continent </li></ul><ul><li>In people who have unpredictable lifestyles, a basal bolus regime may be appropriate </li></ul>
    36. 36. ADA/EASD Insulin Initiation Guidelines Nathan DM et al Diabetes Care 22/10/08 epub online
    37. 37. There are Other Algorithms <ul><li>At:Lantus – starting at 10 IU / day </li></ul>Davies M et al Diabetes Care 2005;28:1282-1288
    38. 38. Potential Implications <ul><li>Driving </li></ul><ul><li>Insurance </li></ul>
    39. 39. Recent Data <ul><li>ACCORD (Action to Control Cardiovascular Risk in Diabetes) </li></ul><ul><li>ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) </li></ul><ul><li>VADT (Veteran’s Administration Diabetes Trial) </li></ul>NEJM 2008;358(24):2545-2559 NEJM 2008;358(24):2560-2572 Duckworth WC et al Diabetes Care 2001;24:942-945
    40. 40. Tighter Glycaemic Control Does NOT Influence Outcomes <ul><li>Getting HbA1C to less that 7.0% added no benefit </li></ul><ul><li>In ACCORD it lead to a higher mortality rate </li></ul><ul><li>Lots of reasons – including better risk factor management </li></ul>
    41. 41. Increased Use of Adjunctive Agents Charlton J et al Diabetes Care 2008;31(8):1761-1766
    42. 42. Things That Make the Most Difference <ul><li>Smoking OR 2.87 </li></ul><ul><li>Raised ApoB/ApoA1 ratio OR 3.25 </li></ul><ul><li>History of hypertension OR 1.91 </li></ul><ul><li>Diabetes OR 2.37 </li></ul><ul><li>Abdominal obesity OR 1.12 </li></ul><ul><li>Psychosocial factors OR 2.67 </li></ul><ul><li>Daily fruit and veg intake OR 0.7 </li></ul><ul><li>Regular alcohol consumption OR 0.9 </li></ul><ul><li>Regular physical activity OR 0.86 </li></ul>Yusuf et al Lancet 2004 364:937-952
    43. 43. In Summary <ul><li>There are a lot of medications to try first </li></ul><ul><li>Weight loss is a cornerstone to delaying insulin </li></ul><ul><li>To ensure the best outcomes for your patients with diabetes </li></ul><ul><ul><li>Be Aggressive! </li></ul></ul><ul><ul><li>Treat Early! </li></ul></ul><ul><li>Being on insulin is not ‘failure’ </li></ul>
    44. 44. Thank you for your attention

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