© 2013 eli lilly and company managing insulin therapy in insulin resistance speaker name and...
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© 2013 Eli Lilly and Company
Managing insulin therapy in Insulin resistance
Speaker name and affiliation
Prescribing information is available on the last slide.
© 2013 Eli Lilly and Company
UKDBT01534 September 2013
Company Confidential © 2012 Eli Lilly and Company© 2013 Eli Lilly and Company
Back to Basics
What are the clinical indications for insulin therapy in Type 2 diabetes?
Types of insulin at initiation
– What are the clinical characteristics of a basal pt – What are the clinical characteristics of a mixture patient– How do you determine regime at initiation– Does one size fit all ??– Initial regime is vital .... Wrong insulin wrong time and place..... May
contribute to insulin resistance.
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Company Confidential © 2012 Eli Lilly and Company© 2013 Eli Lilly and Company
Back to BasicsWhat does insulin do??
Released 1st acute phase lasts a few minutes followed by a sustained second phrase1
Increases glucose uptake at cell level by transporting glucose across cell membrane1
Decreases Glycogenolysis (Glycogen breakdown)
Decreases gluconeogenisis (production of new glucose)
Decreases lipolysis (fat breakdown)
Insulin binds to cell surface receptor
Insulin has many functions primary function is to lower blood glucose level
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1. Bilous R & Donnelly R 2010, 28:Handbook of diabetes
Company Confidential © 2012 Eli Lilly and Company© 2013 Eli Lilly and Company
What is insulin resistance
Defined as early as 19301
Effect on glucose uptake and utilisation that defines insulin resistance1
The development of insulin resistance is seen as the core defect for the development of type 2 diabetes2
Insulin resistance + deficient beta cell function = Type 2 diabetes1
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1. Lebovitz H.E Insulin resistance :definition and consequences: Endocrinology and diabetes 2001 S135 -148 2. Schofield & Sutherland 2012 Disordered insulin secretion in the development of insulin resistance and Type 2 diabetes: Diabetic medicine 2012: 1464
Company Confidential © 2012 Eli Lilly and Company© 2013 Eli Lilly and Company
The underlying defects: Insulin resistance and -cell dysfunction
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5. Ramlo-Halsted BA, et al. Prim Care 1999;26:771–789.
Impaired Insulin Production & Secretion
Insulin Resistance (IR)
- Hyperinsulinaemia - Normal Glucose Tolerance
IR + Declining Insulin Levels + Impaired Glucose Tolerance
- Failure of β-Cell to Adapt to IR
Impaired Responsivenessto Insulin
↑FFA Levels
Sedentary Lifestyle
Diet Obesity
Type 2 Diabetes
Glucotoxicity
-Cell Dysfunction
Genetic Predispositions
Company Confidential © 2012 Eli Lilly and Company© 2013 Eli Lilly and Company
Pathophysiology of type 2 diabetes involves three core defects and multiple organ systems
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Inzucchi SE. JAMA 2002; 287: 360–372
HYPERGLYCAEMIA
Insulinresistance
1. Peripheral tissues1. Peripheral tissuesDecreased
glucose uptakeIncreased lipolysis
2. LiverIncreased
glucose production
2. LiverIncreased
glucose production
Combined islet cell dysfunction and insulin resistance
3. Pancreatic beta cells
Decreased insulin secretion
Pancreatic alpha cellsExcessive
glucagon secretion
3. Pancreatic beta cells
Decreased insulin secretion
Pancreatic alpha cellsExcessive
glucagon secretion
Islet cell dysfunction
Company Confidential © 2012 Eli Lilly and Company© 2013 Eli Lilly and Company
Insulin resistance and insulinhypersecretion precede type 2 diabetes
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Adapted from: Beck-Nielsen H, Groop LC. J Clin Invest 1994; 94: 1714–1721.
Insulin Insulin Macrovascularsecretion resistance disease
- - ++ ++
- +(+) +
+ - + -
+ +
IGT
Impaired glucose
metabolism
Normal glucose metabolism
Type 2 diabetes
Company Confidential © 2012 Eli Lilly and Company© 2013 Eli Lilly and Company
What are the clinical characteristics of an insulin resistant patient?
Central obesity1
Insulin dose >1 unit /kg in weight1
Continued hyperglycaemia despite increasing insulin doses1
Weight gain on insulin therapy1
Hypertension2
Hyperlipidaemia (especially triglycerides) 2
Increased cvd risk2
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1. W Crasto et al Insulin U-500 in severe insulin resistance in type 2diabetes mellitus2. G Reaven; Role of Insulin resistance in human disease (syndrome x): An expanded definition.
Company Confidential © 2012 Eli Lilly and Company© 2013 Eli Lilly and Company
Potential causes of Insulin resistance
Central obesity/ visceral adiposity1
Genetic abnormalities in insulin action cascade1
Decreased physical activity1
Foetal malnutrition1
Exogenous causes1
– Pregnancy– Cushings – Acromegaly– Polycystic ovaries – Smoking2
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1. Lebovitz H.E Insulin resistance :definition and consequences: Endocrinology and diabetes 2001 S135 -1482. Evans & Krentz: 2000:Insulin resistance and beta cell dysfunction as therapeutic targets in Type 2 diabetes Diabetes. Obesity and Metabolism, 3, 2001 , 219-229 2
leading to increase in counter regulatory hormones
Company Confidential © 2012 Eli Lilly and Company© 2013 Eli Lilly and Company
Measuring insulin resistance
HOMA ir All techniques used to measure IR use the relationship between
insulin and glucose uptake and utilisation Homa assessment1
– Steady state beta cell function (expressed % Bcf)– Insulin sensitivity (expressed % sensitvity)
Fasting plasma glucose and fasting plasma insulin
PTS MUST BE OFF EXOGENOUS INSULIN FOR 2 WEEKS
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1. http://www.dtu.ox.ac.uk/homacalculator/
Company Confidential © 2012 Eli Lilly and Company© 2013 Eli Lilly and Company
Monitoring Insulin Resistance
• Record progression of doses, weight gain and HbA1C
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Consider concordance with insulin– Check number of pens or cartridges used
Use of discovery sheets– pre and post prandial monitoring
Date Insulin Type and dose
Units/kg HbA1C weight
Company Confidential © 2012 Eli Lilly and Company© 2013 Eli Lilly and Company
Treatment of Insulin Resistance in Type 2 diabetes
Lifestyle– Exercise
Insulin sensitivity can be improved by exercise independently from weight reduction and changes in body composition1
– Weight Loss– Consider low carb/low GI diet
to reduce post prandial glucose excursions
– Stop smoking
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Pharmacology
– Metformin2
– Reduces effect of insulin resistance
– Acarbose2
– Acts mainly to reduce post prandial glucose excursion
– Thiazolidinediones2
– Increase insulin sensitivity
– GLP1’S2
– Potential for weight loss
– Optimise insulin, ensure current regime targets problem blood glucose areas
– Pump therapy3
1. Matthaei S et al 2000 21: 585-618 2. Bailey C J Treating insulin resistance in type 2 diabetes with metformin and thiazolidinediones 7:675-691; 2005 3. W Crasto et al Insulin U-500 in severe insulin resistance in type 2diabetes mellitus 2009;85: 219-22
Company Confidential © 2012 Eli Lilly and Company© 2013 Eli Lilly and Company
Treatment of Insulin Resistance in Type 2 diabetes cont
Optimise insulin therapy, ensure current regimen targets problem blood glucose areas
Assess pre and post prandial blood glucose levels
Simply increasing current insulin regime may not address poor control or insulin resistance
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Company Confidential © 2012 Eli Lilly and Company© 2013 Eli Lilly and Company
Conclusion
The development of insulin resistance is seen as the core defect for the development of type 2 diabetes
Treatment strategies need to address- Carbohydrate intake and load
- Obesity, lack of physical activity, smoking cessation
- Pharmacological interventions to improve insulin sensitivity
- Optimising insulin therapy
- A consideration of pump therapy
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UKDBT01534 September 2013
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