Insulin therapy: art of initiation and titration

Insulin therapy: art of initiation and titration

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  Insulin Therapy-the ArtOf Initiation and Titration
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  Insulin is thebody’s key to metabolism
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  Characteristics : BASAL :1u/hr between meals,through the night with fasting » To restrict but not eliminate hepatic glucose production which is necessary for cerebral glucose metabolism » Correlate highly with FPG PRANDIAL : 5 to 10 times basal rate, peaks in ½ to 1 hr. returning to base line in 2 to 4 hrs
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  Intiating insulin therapy •In type 1 daibetes – All patients – In some patients like LADA who may be initially responsive to to oral hypoglycemic agents later require insulin
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  Indications for InsulinUse in Type 2 Diabetes Pregnancy (preferably prior to pregnancy) Acute illness requiring hospitalization Perioperative/intensive care unit setting Postmyocardial infarction High-dose glucocorticoid therapy Inability to tolerate or contraindication to oral antiglycemic agents Newly diagnosed type 2 diabetes with significantly elevated blood glucose levels (pts with severe symptoms or DKA) Patient no longer achieving therapeutic goals on combination antiglycemic therapy
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  Advantages of InsulinTherapy • Oldest of the currently available medications, has the most clinical experience • Most effective of the diabetes medications in lowering glycemia – Can decrease any level of elevated HbA1c – No maximum dose of insulin beyond which a therapeutic effect will not occur • Beneficial effects on triglyceride and HDL cholesterol levels. Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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  *Lower extremity amputationor fatal PVD †P < 0.0001; ‡P = 0.035 Error bars = 95% CIs Percentagereductioninrelativerisk correspondingtoa1%fallinHbA1c –50 –45 –40 –35 –30 –25 –20 –15 –10 –5 0 21% Any diabetes-related endpoint 21% Diabetes- related death 14% All cause mortality 14% Myocardial infarction 12% Stroke 43% Peripheral vascular disease* 37% Microvascular disease 19% Cataract extraction Adapted from Stratton IM, et al. UKPDS 35. BMJ 2000;321:405–412. UKPDS: Observational data for a 1% decrease in HbA1c –55 † † † † ‡ † † †
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  0 1 23 4 5 metformin Sus TZDs EXENATIDE INSULIN 9.5%HbA1c 6.5%HbA1c
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  Fears & concerns aboutinsulin therapy
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  Patient Concerns AboutInsulin • Fear of injections(Trypanophobia) • Perceived significance of need for insulin • Worries that insulin could worsen diabetes • Concerns about hypoglycemia • Complexity of regimens 21
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  When to StartInsulin? • Watch for the following signs – Increasing BG levels – Elevated A1C – Unexplained weight loss – Traces of ketonuria – Poor energy level When OHAs are not enough to achieve target glycemic status --
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  …..When Oral MedicationsAre Not Enough – Sleep disturbances – Polydipsia • Next steps – Make a decision to start insulin – Offer patient encouragement, not blame
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  What we havein our pockets? • Basal Insulins (NPH,Lantus) • Bolus Insulins(Human Regular) • Premixed (Human 70/30)
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  Bolous insulins (Mealtimeor prandial) Insulin Type Onset of action Peak of action Duration of action Human regular Short acting 30-60 minutes 2-4 hours 8-10 hours Insulin analogs (Lispro,Aspart, Glulisin) Rapid acting 5-15 minutes 1-2 hours 4-5 hours Inhaled insulin Rapid acting 10-20 minutes 2 hours 6 hours The time course of action of any insulin may vary in different individuals, or at different times in the same individual. Because of this variation, time periods indicated here should be considered general guidelines only.
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  Basal Insulins Insulin TypeOnset of action Peak of action Duration of action NPH Intermediate acting 1-2 hours 5-7 hours 13-18 hours Glargine (Lantus) Aventis Long acting 1-2 hours Relatively flat Upto 24 hours Detemir (Levimir)Novo Long acting 2-4 hours 8-12 hours 16-20 hours The time course of action of any insulin may vary in different individuals, or at different times in the same individual. Because of this variation, time periods indicated here should be considered general guidelines only.
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  Pre-mixed Insulins Insulin CompositionExamples NPH-Regular 70% NPH 30% Regular Humulin 70/30 Dongsulin 70/30 Mixtard 70/30 Insulin Composition Example Rapid acting aspart (Free and soluble) + Intermediate acting aspart(protaminated- crystallized 30% rapid acting aspart +70 % intermediate acting aspart(IAA) NovoMix 30 Humolog Mix 25 Humolog Mix 50 (25% lispro75%IAA) (50% lispro 50%IAA)
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  The ADA Treatment Algorithmfor the Initiation and Adjustment of Insulin
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  Initiating and AdjustingInsulin Continue regimen; check HbA1c every 3 months If fasting BG in target range, check BG before lunch, dinner, and bed. Depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range) Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin If HbA1c ≤7%... Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg) Check FG and increase dose until in target range. If HbA1c 7%... Hypoglycemia or FG >3.89 mmol/l (70 mg/dl): Reduce bedtime dose by ≥4 units (or 10% if dose >60 units) Pre-lunch BG out of range: add rapid-acting insulin at breakfast Pre-dinner BG out of range: add NPH insulin at breakfast or rapid-acting insulin at lunch Pre-bed BG out of range: add rapid-acting insulin at dinner Continue regimen; check HbA1c every 3 months Target range: 3.89-7.22 mmol/L (70-130 mg/dL) Nathan DM et al. Diabetes Care. 2006;29(8):1963-72. If HbA1c ≤7%... If HbA1c 7%...
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  Step One… Continue regimen;check HbA1c every 3 months If fasting BG in target range, check BG before lunch, dinner, and bed. Depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range) Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin If HbA1c ≤7%... Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg) Check FG and increase dose until in target range. If HbA1c 7%... Hypoglycemia or FG >3.89 mmol/l (70 mg/dl): Reduce bedtime dose by ≥4 units (or 10% if dose >60 units) Pre-lunch BG out of range: add rapid-acting insulin at breakfast Pre-dinner BG out of range: add NPH insulin at breakfast or rapid-acting insulin at lunch Pre-bed BG out of range: add rapid-acting insulin at dinner Continue regimen; check HbA1c every 3 months Target range: 3.89-7.22 mmol/L (70-130 mg/dL) If HbA1c ≤7%... If HbA1c 7%... Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
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  Step One: InitiatingInsulin • Start with either… – Bedtime intermediate-acting insulin or – Bedtime or morning long-acting insulin Insulin regimens should be designed taking lifestyle and meal schedules into account Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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  Step One: InitiatingInsulin, cont’d • Check fasting glucose and increase dose until in target range – Target range: 3.89-7.22 mmol/l (70-130 mg/dl) – Typical dose increase is 2 units every 3 days, but if fasting glucose >10 mmol/l (>180 mg/dl), can increase by large increments (e.g., 4 units every 3 days) Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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  • If hypoglycemiaoccurs or if fasting glucose < 3.89 mmol/l (70 mg/dl)… – Reduce bedtime dose by ≥4 units or 10% if dose >60 units Step One: Initiating Insulin, cont’d Nathan DM et al. Diabetes Care 2006;29(8):1963-72. Reduction in overnight and fasting glucose levels achieved by adding basal insulin may be sufficient to reduce postprandial elevations in glucose during the day and facilitate the achievement of target A1C concentrations. While using basal insulin alone,never stop or reduce ongoing oral therapy
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  • If HbA1cis <7%... – Continue regimen and check HbA1c every 3 months • If HbA1c is ≥7%... – Move to Step Two… After 2-3 Months… Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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  With the additionof basal insulin and titration to target FBG levels, only about 60% of patients with type 2 diabetes are able to achieve A1C goals < 7%.[36] In the remaining patients with A1C levels above goal regardless of adequate fasting glucose levels, postprandial blood glucose levels are likely elevated.
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  Continue regimen; check HbA1cevery 3 months If fasting BG in target range, check BG before lunch, dinner, and bed. Depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range) Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin If HbA1c ≤7%... Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg) Check FG and increase dose until in target range. If HbA1c 7%... Hypoglycemia or FG >3.89 mmol/l (70 mg/dl): Reduce bedtime dose by ≥4 units (or 10% if dose >60 units) Pre-lunch BG out of range: add rapid-acting insulin at breakfast Pre-dinner BG out of range: add NPH insulin at breakfast or rapid-acting insulin at lunch Pre-bed BG out of range: add rapid-acting insulin at dinner Continue regimen; check HbA1c every 3 months Target range: 3.89-7.22 mmol/L (70-130 mg/dL) If HbA1c ≤7%... If HbA1c 7%... Step Two… Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
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  Step Two: IntensifyingInsulin If fasting blood glucose levels are in target range but HbA1c ≥7%, check blood glucose before lunch, dinner, and bed and add a second injection: • If pre-lunch blood glucose is out of range, add rapid-acting insulin at breakfast • If pre-dinner blood glucose is out of range, add NPH insulin at breakfast or rapid-acting insulin at lunch • If pre-bed blood glucose is out of range, add rapid-acting insulin at dinner Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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  Making Adjustments • Canusually begin with ~4 units and adjust by 2 units every 3 days until blood glucose is in range Nathan DM et al. Diabetes Care 2006;29(8):1963-72. When number of insulin Injections increase from 1-2 ………..Stop or taper of insulin secretagogues (sulfonylureas).
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  • If HbA1cis <7%... – Continue regimen and check HbA1c every 3 months • If HbA1c is ≥7%... – Move to Step Three… After 2-3 Months… Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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  Nathan DM etal. Diabetes Care. 2006;29(8):1963-72. Continue regimen; check HbA1c every 3 months If fasting BG in target range, check BG before lunch, dinner, and bed. Depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range) Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin If HbA1c ≤7%... Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg) Check FG and increase dose until in target range. If HbA1c 7%... Hypoglycemia or FG >3.89 mmol/l (70 mg/dl): Reduce bedtime dose by ≥4 units (or 10% if dose >60 units) Pre-lunch BG out of range: add rapid-acting insulin at breakfast Pre-dinner BG out of range: add NPH insulin at breakfast or rapid-acting insulin at lunch Pre-bed BG out of range: add rapid-acting insulin at dinner Continue regimen; check HbA1c every 3 months Target range: 3.89-7.22 mmol/L (70-130 mg/dL) If HbA1c ≤7%... If HbA1c 7%... Step Three…
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  Step Three: Further IntensifyingInsulin • Recheck pre-meal blood glucose and if out of range, may need to add a third injection • If HbA1c is still ≥ 7% – Check 2-hr postprandial levels – Adjust preprandial rapid-acting insulin Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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  Premixed Insulin • Notrecommended during dose adjustment • Can be used before breakfast and/or dinner if the proportion of rapid- and intermediate-acting insulin is similar to the fixed proportions available Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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  • Choice ofan insulin regime for initiation of therapy has always been a matter of debate. • There is no universal consensus for the optimal method of starting insulin therapy in patients with type 2 diabetes (T2DM) who do not respond to oral anti-diabetic drugs (OADs). Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR, American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD) Diabetes Care. 2012 Jun; 35(6):1364-79.
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  • While theAmerican Diabetes Association (ADA) and European Association for study of Diabetes (EASD) suggest basal insulin as an initial preferred strategy , the International Diabetes Federation (IDF) recommends both premixed and basal insulin • Many national guidelines, on the other hand, support the use of premixed insulin as a preferred choice for initiation of therapy. Intensive insulin therapy, too, is indicated as initial line of management in a select group of patients
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  • The value74 mg% is taken by calculating PPGE for the diagnostic cut offs for diabetes (200 mg% and 126 mg%). • The value 40 mg% is taken by calculating PPGE for the diagnostic cut offs for prediabetic (impaired glucose tolerance 140 mg%, and impaired fasting glucose 100 mg%). Kalra and Gupta, Diabetes and Metabolic disorders 2015 vol 14:17
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  • Prandial: fastingindex (PFI) = (PPG‐FPG) /FPG • The value 0.6 is taken by calculating PFI for the diagnostic cut offs of diabetes (200 mg%, 126 mg%). • The value 0.4 is taken by calculating PFI for the diagnostic cut offs of prediabetes. Kalra and Gupta, Diabetes and Metabolic disorders 2015 vol 14:17
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  • *The value1.3 is calculated with the diagnostic cut offs of diabetes using FPG (7.8 mmol/l) and HbA1c (6%). • **The value 20 is calculated with the diagnostic cut offs for diabetes using FPG (126 mg%) and currently accepted HbA1c (6.3%) levels. Kalra and Gupta, Diabetes and Metabolic disorders 2015 vol 14:17
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  • Use ofsulfonylureas with insulin regimens ?
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  Thank you