Slide 1

Insulin therapy Dr. A. R. GOHARIAN Endocrinologist

Slide 2

type 1 diabetes The loss of pancreatic function is a hallmark for the diagnosis of T1DM and is the reason, insulin is a necessary treatment modality for patients with that form of the disease. vol 32, No 2, 2014. clinical Diabetes

Slide 3

Indications of Insulin therapy Most people with type 1 diabetes should be treated with multiple-dose insulin (MDI) injections ( 3 4 injections per day of basal & prandial insulin) or continuous subcutaneous insulin infusion (CSII). [A]

Slide 4

T2 DM Type 2 diabetes is also partially defined by a loss of pancreatic function. At the time of diagnosis of type 2 diabetes, ~ 50% of pancreatic function is already lost.

Slide 5

T2 DM This is a progressive loss that continues throughout treatment, leading to poor glycemic control and its associated complications. The continued decline of -cell function results in the need for medication(s) and eventually exogenous administration of insulin for type 2 diabetes.

Slide 6

T2DM Many patients with type 2 diabetes eventually require and benefit from insulin therapy. The progressive nature of type 2 diabetes and its therapies should be regularly and objectively explained to patients.

Slide 7

T2DM & Insulin A patient centered approach to insulin therapy is essential to ensure optimal outcomes and safety given the varying levels of evidence regarding the use of insulin.

Slide 8

Short-term studies comparing insulins show that a high percentage of people with established type 2 diabetes not well controlled with oral therapies can achieve blood glucose control to target, and without high rates of hypoglycemia.

Slide 9

T2DM & Insulin Insulin products available on the U.S. market include : rapid- short- intermediate-, and long acting products as well as premixed formulations.

Slide 10

Basal Insulin Basal therapy includes long- and intermediate acting insulin products used to mimic physiological insulin secretion in the absence of food.

Slide 11

Bolus Insulin Rapid- and short-acting insulin products constitute bolus therapy, which is used to mimic the secretion of insulin from the pancreas in response to food. ( postprandial )

Slide 12

Insulin delivery There are currently four delivery Options available for insulin administration, including : - subcutaneous injections, - continuous subcutaneous insulin infusion (CSII), - insulin patch pumps, - and intravenous infusion.

Slide 13

ADA Standards of Medical Care in Diabetes2015 Although oral therapy is generally the preferred option for most patients with type 2 diabetes at diagnosis, the progressive loss of -cell function means that insulin replacement therapy will eventually become necessary for many patients.

Slide 14

ADA Standards of Medical Care in Diabetes2015 Multiple factors should be taken into account when assessing diabetes control and, subsequently, considering the initiation and impact of insulin therapy : - the patients A1C level and - self-monitoring of blood glucose (SMBG) records, - in combination with patient interviews.

Slide 15

ADA/EASD 2015 Position Statement The ADA/EASD guidelines support the use of patient specific insulin therapy to achieve a glycemic profile as close to normal as possible while minimizing adverse effects such as weight gain and hypoglycemia.

Slide 16

ADA/EASD 2015 Position Statement In accordance with the ADA standards of care, the ADA/EASD generally recommends oral therapy as first-line treatment for patients newly diagnosed with type 2 diabetes, typically initiating with one agent.

Slide 17

After ~ 3 months of monotherapy, providers may consider a second oral agent, the addition of a glucagon-like peptide-1 (GLP-1) receptor agonist, or the addition of basal insulin if glycemic goals are not attained.

Slide 18

Initiation of Insulin therapy Often, insulin therapy is an adjunct, when mono- or dual therapies do not achieve or maintain desired glucose targets ( generally if a patients A1C is 8.5% on dual oral therapy ). The guidelines note that higher A1C levels often increase the likelihood of requiring the addition of basal insulin to adequately achieve the necessary A1C reduction.

Slide 19

Basal insulins offer simplicity in injection frequency and ease of dose titration but may not be adequate to address postprandial excursions. This is particularly true with further loss of islet -cell function, whence a mealtime + basal regimen will be needed, sometimes with mealtime insulin introduced meal by meal

Slide 20

WHEN SHOULD INSULIN THERAPY BE STARTED? Diabetes Care Volume 37, June 2014

Slide 21

Latent autoimmune diabetes in adults (LADA)

Slide 22

The ADA/EASD guidelines reference certain situations in which immediate initiation of insulin therapy is likely indicated : 1 specifically in patients who exhibit significant symptoms of hyperglycemia 2 - in those who present with drastically elevated plasma glucose levels (i.e., > 300350 mg/dl) or A1C (i.e., 1012%).

Slide 23

immediate initiation of insulin therapy : Some patients may require immediate multiple daily insulin doses rather than a more gradual progression in to insulin therapy.

Slide 24

Initiation of Insulin therapy 3 - When catabolic features, including : weight loss or ketonuria, are present, implementation of insulin therapy is considered mandatory.

Slide 25

Ketoacidosis can be present at the time of diagnosis of type 2 diabetes, especially in the presence of another metabolic stress ( i.e., myocardial infarction or infection or use of antiretroviral therapy). In such situations, immediate use of insulin is recommended and sometimes mandatory.

Slide 26

Insulin is usually needed when diabetes is diagnosed in the context of an acute medical event causing acute metabolic deterioration, or in case of surgery or any other invasive procedure, temporarily or for longer term.

Slide 27

Slide 28

T2DM & Insulin Providers should avoid using insulin as a threat or describing it as a failure or punishment. Basal insulin alone is the most convenient initial insulin regimen, beginning at 10 U or 0.10.2 U/kg, depending on the degree of hyperglycemia.

Slide 29

Basal Insulin & T2DM However, in patients with more severe hyperglycemia (undefined by the guidelines), therapy can begin with larger doses of 0.30.4 units/kg/day.

Slide 30

Glargine & Detemir An advantage of both glargine and detemir is that they have been shown to cause less nocturnal hypoglycemia than NPH.

Slide 31

Glargine & Detemir Comparatively, detemir is associated with slightly less weight gain and a higher average unit requirement when dosing. The main drawback to the long-acting insulins is increased cost. ( Expensive )

Slide 32

Titration Titration is described in the guidelines as the addition of 12 units of basal insulin to the daily dose made once or twice weekly for elevated fasting glucose readings. Or 5 10% of the daily dose

Slide 33

The ADA and EASD suggest : That elevations in postprandial glucose may be a contributing factor to elevated A1C when fasting glucose levels are at goal.

Slide 34

The ADA and EASD Postprandial blood glucose excursions contribute to the majority of elevation in A1C levels that are close to goal. For A1C levels in the range of 7.38.4%, fasting and postprandial glucose levels contribute equally to overall glycemia.

Slide 35

Bolus insulin therapy When basal insulin is not sufficient to maintain glycemic control, bolus insulin therapy with short-acting ( human regular ) or rapid-acting ( aspart, lispro, and glulisine ) insulin just before meals is recommended.

Slide 36

Bolus insulin therapy Rapid-acting insulins offer better postprandial glucose control than regular human insulin, likely because of their pharmacokinetic parameters. Nevertheless, cost considerations still make regular human insulin a viable option in cases in which cost containment is an issue and prandial insulin therapy is required.

Slide 37

When ?? Providers should be aware that when a patients daily dose of basal insulin becomes > 0.5 units/kg/day, the need for intensification with bolus insulin increases. When the total daily dose of basal insulin nears 1 unit/kg/day, the addition of bolus insulin is generally required to achieve glycemic control.

Slide 38

First prandial insulin The guidelines suggest initiating prandial insulin with a single dose just before the meal that contains the largest carbohydrate content of the day. For most patients, this is the evening meal.

Slide 39

Prandial Insulin From there, a second and third injection may be added before the other two meals if they require additional coverage to limit glucose excursions.

Slide 40

Premixed insulin However, some patients, such as those with a history of nonadherence to their diabetes treatment regimen, may not be appropriate candidates for basal - bolus therapy. In such cases, premixed insulin products are available to increase convenience but come with the drawback of reduced flexibility in dosing.

Slide 41

Premixed insulin Generally, such products are dosed twice daily, before the morning and evening meals.

Slide 42

AACE guidelines Current AACE guidelines recommend initiation of insulin therapy for patients whose A1C level is > 9% and those who have not achieved their glycemic targets with combination oral therapy.

Slide 43

However, the 2013 AACE algorithm and consensus statement offer expanded recommendations, including a discussion on the initiation of insulin in patients with an A1C as low as 7.5%, as an adjunct to other therapies. Current opinion

Slide 44

AACE advocates for tighter glycemic control, with a fasting blood glucose target of 70110 mg/dl and a postprandial target of < 140 mg/dl.

Slide 45

AACE also favors long-acting basal insulin to target fasting glucose as the initial insulin therapy in most situations, with glargine or detemir preferred for the same reasons discussed previously.

Slide 46

AACE Basal Insulin : For those with an A1C > 8%, a higher weight - based dose of 0.20.3 units/kg/day is recommended, as opposed to the standard 0.10.2 units/kg/day.

Slide 47

AACE Titration of Basal Insulin is based on fasting blood glucose levels, - with 4 U added for FPG > 180 mg/dl, - 2 U added of 140 < FPG < 180 mg/dl, and - 1 U added for 110 < FPG < 139 mg/dl.

Slide 48

The AACE guidelines recommend : Specific dosing instructions for prandial insulin, initiating at 5 units before a meal, representing ~ 7% of the basal insulin dose, although the guidelines do not identify a specific meal.

Slide 49

AACE The 2015 algorithm and consensus statement also support a basal-bolus regimen for patients with symptomatic hyperglycemia and an A1C level > 10%. Ideally, a full basal - bolus regimen is preferred.

Slide 50

AACE For patients with a total daily dose of 0.30.5 units/kg/day, 50% of that dose should constitute the prandial insulin analog when initiated.

Slide 51

AACE When a rapid-acting analog is used, the prandial dose should be increased by 10% for postprandial glucose levels > 180 mg/dl.

Slide 52

When adjusting the dose of premixed insulin, AACE recommends that providers ; Consider predinner glucose levels for doses administered before breakfast and fasting glucose levels for adjustment of the predinner dose. The updated algorithm discusses a specific increase of 10% of the total daily dose based on fasting or premeal readings > 180 mg/dl.

Slide 53

Slide 54

Slide 55

Slide 56

Slide 57

Slide 58

Slide 59

Slide 60

Slide 61

Slide 62

Insulin Preparations Current insulin preparations are generated by recombinant DNA technology and consist of the amino acid sequence of human insulin or variations thereof. In the United States, most insulin is formulated as U-100 (100 units/mL).

Slide 63

AIME Human insulin has been formulated with distinctive pharmacokinetics or genetically modified to more closely mimic physiologic insulin secretion. Insulins can be classified as : - short-acting Or - long-acting

Slide 64

Properties of Insulin Preparations NovoMix 30 Lansulin 70/30

Slide 65

Slide 66

Slide 67

Aspart Insulin

Slide 68

Slide 69

Slide 70

Insulin Lispro

Slide 71

Slide 72

The rapid-acting insulin analogues should be injected 5 to 15 minutes before a meal. However, in infants or in older adults with dementia who both have unpredictable eating patterns, rapid-acting analogues can be administered after the meal without excessive deterioration of glycemic control

Slide 73

These insulin analogues are rapidly absorbed ( 30 minutes) after subcutaneous injection, peak at 1 hour, and have a shorter duration of action (3 to 4 hours) than regular insulin. Furthermore, the intraindividual variability in time to maximum serum insulin concentration is clinically significantly less for rapid-acting insulin analogues than for regular human insulin preparations

Slide 74

Slide 75

Slide 76

Slide 77

Detemir

Slide 78

Slide 79

Slide 80

Slide 81

Slide 82

Slide 83

Slide 84

Slide 85

Slide 86

Slide 87

Slide 88

Slide 89

140/90

Slide 90