1. Diabetes (abridged!)

2. Who needs screening for DM? Age >45 Obese – BMI >25 1 st degree relative with DM Racial groups: –African American –Hispanic American –Native American –Asian American –Pacific Islander History of GDM – or delivered macrosomic baby HTN HDL 250 Previous “pre-diabetes” or “impaired glucose tolerance” i.e. Fasting BG 110-126

3. How should you screen? Fasting plasma glucose is now the recommended test. Oral Glucose Tolerance Testing – measuring glucose 2 hours after 75g glucose load – is no longer necessary HbA1c is used for monitoring but not for screening Need to have two separate readings of fasting glucose >126 Symptoms of DM (polyuria, polydipsia, wt loss) with random glucose >200

4. Treatment Goals Pre-prandial glucose 80-120 2 hour post prandial glucose <160 Pre-bed glucose 100-140 HbA1c <6.5 – 7%

5. Insulin Daily insulin production is 24-30 units In normal people insulin is secreted directly into the portal circulation Patients with Type I DM usually need 0.5-1 units/Kg But dose depends on diet, stress and exercise Stress hormones (Cortisol, GH, Catecholamines) all increase insulin resistance and in stressful situations you will need more insulin.

6. Types of insulin NameCategoryTime to onset Time to peak Duration effective Maximum duration Lispro (Humalog) Rapid15 mins30-90 mins 3-4 h4-6 h Aspart (Novolog) Rapid15-30 mins 60-90 mins 1-3 h3-5 h RegularShort30-60 mins 2-3 h3-6 h6-8 h NPHIntermediate2-4 h6-10 h10-16 h14-18h Glargine (Lantus) Long2 hNo peak24 hours LenteIntermediate3-4 h6-12 h12-18 h16-20 h UltralenteLong6-10h10-16 h18-20h20-24 h

7. Basal/Bolus regimen –Daily insulin dose consists of a basal insulin to inhibit hepatic glucose production and pre-meal insulin to cover intake –Typically this is achieved with Lantus QHS and Novolog (aspart) pre meals. –Patients on this regimen should either be given a Sliding scale instructing them how to cover their premeal accuchecks and how to “Carb count” OR they need a standard dose of premeal insulin which you review when you see them in clinic based on their readings. –15g carbs = 1 unit of insulin –Requires multiple insulin injections and accuchecks, but provides greater flexibility in matching insulin to meal.

8. Other regimens NPH or Lente at bed time and then regular insulin to cover breakfast and dinner, but risk of nocturnal hypoglycemia 70/30 insulin is a mixture of rapid acting and more prolonged acting – can be used in a bid dosing but allows less flexibility with diet

9. Insulin Pump Uses a continuous subcutaneous infusion of Aspart, and the patient programs in boluses to cover meals. Still requires accuchecks, and although there are now continuous glucose recorders the technology does not yet exist to link these up with the pump – but it is coming. Aspart has very predictable absorption – so easier to make the fine adjustments to regimen. Pumps require a very proactive patient – they are not for your non-compliant VA patients.

10. Oral Hypoglycemics ClassDrugsMOAReduction of HbA1c SulphonylureasGlyburide Glipizide Glimerperide Chlorpropamide Insulin secretagogue 1-2% MeglitinidesRepaglinide Nateglinide Insulin secretagogue 0.8-1.5% BiguanidesMetforminDecresed hepatic gluconeogenesis 1-2% ThiazolidinedionePioglitazone Rosiglitazone Insulin Sensitizers0.5-1.3% α-glucosidase inhibitor AcarboseReduces GI absorption of carbohydrate 0.5-1%

11. Sulfonylureas and Meglitinides Stimulate release of insulin in response to glucose Augment insulin levels Meglitinides act rapidly and achieve good post prandial control but are short acting and have to be given with every meal Sulfonylureas are longer acting and given once daily but have risk of hypoglycemia

12. Metformin Stimulates hepatic gluconeogenesis and improves insulin sensitivity Although its effect on glycemic control is not that impressive, it does cause significant reduction in cardiovascular disease Does not cause weight gain Main risk is LACTIC ACIDOSIS –Should be avoided in pts with creatinine >1.4 due to renally excreted. –Hold drug 24-48 hours prior to contrast procedures and do not restart until BUN/Creatinine documented to be normal.

13. Thiazolidinediones Bind to nuclear receptors affecting gene expression and therefore have a long latency requiring 4-12 weeks before they reach efficacy. Beneficial lipid effects. Pioglitazone has greater effect on TG and less LDL lowering than Rosiglitazone. Require LFT monitoring and should be stopped if AST rises Contraindicated in CHF due to fluid retention

14. α-glucosidase inhibitors Reduce the rate of carbohydrate absorption from the gut enabling endogenous insulin to maintain glycemic control. Not absorbed and no weight gain, but severe flatulence.

15. Caveats on oral hypoglycemic Any oral hypoglycemic will only lower HbA1c by 1-2 % They do have additive effects, but if a patients HbA1c is 10 – you will not be able to achieve glycemic control with oral agents alone.