Type 1 Diabetes Mellitus – insulins Key slides

1. Type 1 Diabetes Mellitus – insulinsKey slides

2. Type 1 vs. type 2 diabetesLambert P, et al. Medicine 2006; 34(2): 47-51Nolan JJ. Medicine 2006; 34(2): 52-56 Features of type 2 diabetes • Usually presents in over-30s (but also seen increasingly in younger people) • Associated with overweight/obesity • Onset is gradual and diagnosis often missed (up to 50% of cases) • Not associated with ketoacidosis, though ketosis can occur • Immune markers in only 10% • Family history is often positive with almost 100% concordance in identical twins • Features of type 1 diabetes • Onset in childhood/adolescence • Lean body habitus • Acute onset of osmotic symptoms • Ketosis-prone • High levels of islet autoantibodies • High prevalence of genetic susceptibility

3. Goals of management • Manage symptoms • Prevent acute and late complications • Improve quality of life • Avoid premature diabetes-associated death • An individualised approach Glycaemic control BP Lipids Lifestyle (e.g. diet & exercise) Patient education Management Microalbuminuria & kidneys Eye care Foot care

4. Approximate pharmacokinetic profiles of human insulin and insulin analoguesHirsch IB. N Engl J Med 2005; 352: 174-83 N.B. Duration of action will vary widely between and within people NPH = neutal protamine hagedorn/isophane insulin

5. Which insulin regimens are used? • Regimen individualised depending on various factors e.g. patient choice and cognitive abilities, age, mealtimes, diet, exercise, shiftwork, target HbA1C, risk or experience of hypoglycaemia, previous control if already on insulin. Three basic regimens NICE. Type 1 diabetes Clinical Guideline 15, 2004 • One, two or three insulin injections/day • Multiple daily injection • Continuous subcutaneous insulin infusion OR

6. Tight control with intensive insulin reduces development and progression of microvascular complicationsDCCT*. N Engl J Med 1993; 329: 977-86 • Multicentre RCT (no of patients =1441) • Insulin treatment: intensive vs. conventional • Mean 6.5 years • Primary outcome: development and progression ofretinopathy (Change >3 steps on fundus photography sustained over 6 months – DOO†) • Secondary outcomes: nephropathy, neuropathy, cardiovascular events, adverse events • Observational follow up of DCCT cohort: EDIC** study (no patients=1375). All patients advised intensive treatment * Diabetes Control and Complications Trial (DCCT) ** Epidemiology of Diabetes Interventions and Complications (EDIC) † Disease oriented outcome, often used as proxy measure for patient outcomes, which may be loss of vision or reduced visual acuity

7. Are insulin analogues better? Rapid-acting analogues • Rapid-acting insulin analogues have only a minor benefit over short-acting soluble insulin in most type 1 diabetes patients (Ô 0.1% HbA1C). • Overall hypoglycaemia: comparable effects with soluble insulin. • Cautious approach until long-term efficacy and safety data. • Expensive, but see NICE. Siebenhofer A, et al. Cochrane 2006, Issue 2 Long-acting analogues • In most studies, glycaemic control (HbA1C) with insulin glargine and detemir appears to be comparable to that achieved with daily or twice daily isophane (NPH) insulin. • The incidence of hypoglycaemia is similar to or slightly less than that of NPH. • Several studies suggest insulin glargine and detemir reduce the incidence of nocturnal hypoglycaemia compared with NPH, but it is unclear whether this is due to the pharmacology or frequency of admin of the basal insulin. • Cautious approach until long-term efficacy and safety data. • Expensive, but see NICE. Warren E, at al Health Technology Assessment 2004; 8(45): 1-72

8. What is the optimum HbA1C threshold?NICE. Type 1 diabetes Clinical Guideline 15, 2004 NICE • Advise adults that HbA1C<7.5%is likely to minimise risk of developing diabetic eye, kidney or nerve damage in long term. • Adults who want to achieve HbA1C down to, or towards, 7.5% should be given all appropriate support in their efforts to do so. • Advise patients with increased arterial risk* that approaching lower HbA1C levels (e.g. 6.5% or lower) may be of benefit to them (and support them). • Don’t pursue tight control without discussing pros and cons if risk/experience of hypoglycaemia or effort to achieve target curtails QoL. • For children and young people, target HbA1C<7.5% without frequent disabling hypoglycaemia. * Identified by ­albumin excretion rate, features of metabolic syndrome, or other arterial risk factors

9. What is a NICE regimen?NICE 2004 Clinical Guideline 15 A • Multiple insulin injections regimens, in adults who prefer them, should be used as part of an integrated package of which education, food and skills training should be integral partsDCCT. N Engl J Med 1993; 329: 977-86 • Twice-daily insulin regimens should be used by those adults who consider number of daily injections an important issue in QoL • Biphasic insulin preparations are often the preparation of choice in this circumstance • Biphasic rapid-acting insulin analogue premixes may give an advantage to those prone to hypoglycaemia at night • Such twice daily regimens may also help: 1. those who find adherence to their agreed lunch- time injection difficult 2. adults with learning difficulties who may require assistance from others D