Diabetes (abridged!)Diabetes (abridged!)

Who needs screening for DM?Who needs screening for DM?

Age >45Age >45Obese – BMI >25Obese – BMI >2511stst degree relative with DM degree relative with DMRacial groups: Racial groups:

– African AmericanAfrican American– Hispanic AmericanHispanic American– Native AmericanNative American– Asian AmericanAsian American– Pacific IslanderPacific Islander

History of GDM – or delivered macrosomic babyHistory of GDM – or delivered macrosomic babyHTNHTNHDL <35, TG>250HDL <35, TG>250Previous “pre-diabetes” or “impaired glucose tolerance” Previous “pre-diabetes” or “impaired glucose tolerance” i.e. Fasting BG 110-126i.e. Fasting BG 110-126

How should you screen?How should you screen?

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

Treatment GoalsTreatment Goals

Pre-prandial glucosePre-prandial glucose80-12080-120

2 hour post prandial glucose2 hour post prandial glucose<160<160

Pre-bed glucosePre-bed glucose100-140100-140

HbA1c <6.5 – 7%HbA1c <6.5 – 7%

InsulinInsulin

Daily insulin production is 24-30 unitsDaily insulin production is 24-30 unitsIn normal people insulin is secreted directly into In normal people insulin is secreted directly into the portal circulationthe portal circulationPatients with Type I DM usually need 0.5-1 Patients with Type I DM usually need 0.5-1 units/Kgunits/KgBut dose depends on diet, stress and exerciseBut dose depends on diet, stress and exerciseStress hormones (Cortisol, GH, Stress hormones (Cortisol, GH, Catecholamines) all increase insulin resistance Catecholamines) all increase insulin resistance and in stressful situations you will need more and in stressful situations you will need more insulin. insulin.

Types of insulinTypes of insulinName Category Time to

onsetTime to peak

Duration effective

Maximum duration

Lispro(Humalog)

Rapid 15 mins 30-90 mins

3-4 h 4-6 h

Aspart (Novolog)

Rapid 15-30 mins

60-90 mins

1-3 h 3-5 h

Regular Short 30-60 mins

2-3 h 3-6 h 6-8 h

NPH Intermediate 2-4 h 6-10 h 10-16 h 14-18h

Glargine (Lantus)

Long 2 h No peak 24 hours 24 hours

Lente Intermediate 3-4 h 6-12 h 12-18 h 16-20 h

Ultralente Long 6-10h 10-16 h 18-20h 20-24 h

Basal/Bolus regimenBasal/Bolus regimen

Basal/Bolus regimenBasal/Bolus regimen– Daily insulin dose consists of a basal insulin to inhibit hepatic Daily insulin dose consists of a basal insulin to inhibit hepatic

glucose production and pre-meal insulin to cover intakeglucose production and pre-meal insulin to cover intake– Typically this is achieved with Lantus QHS and Novolog (aspart) Typically this is achieved with Lantus QHS and Novolog (aspart)

pre meals.pre meals.– Patients on this regimen should either be given a Sliding scale Patients on this regimen should either be given a Sliding scale

instructing them how to cover their premeal accuchecks and how instructing them how to cover their premeal accuchecks and how to “Carb count” OR they need a standard dose of premeal insulin to “Carb count” OR they need a standard dose of premeal insulin which you review when you see them in clinic based on their which you review when you see them in clinic based on their readings. readings.

– 15g carbs = 1 unit of insulin15g carbs = 1 unit of insulin– Requires multiple insulin injections and accuchecks, but Requires multiple insulin injections and accuchecks, but

provides greater flexibility in matching insulin to meal. provides greater flexibility in matching insulin to meal.

Other regimensOther regimens

NPH or Lente at bed time and then regular NPH or Lente at bed time and then regular insulin to cover breakfast and dinner, but insulin to cover breakfast and dinner, but risk of nocturnal hypoglycemiarisk of nocturnal hypoglycemia

70/30 insulin is a mixture of rapid acting 70/30 insulin is a mixture of rapid acting and more prolonged acting – can be used and more prolonged acting – can be used in a bid dosing but allows less flexibility in a bid dosing but allows less flexibility with dietwith diet

Insulin PumpInsulin Pump

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

Oral HypoglycemicsOral HypoglycemicsClass Drugs MOA Reduction of

HbA1c

Sulphonylureas GlyburideGlipizideGlimerperideChlorpropamide

Insulin secretagogue

1-2%

Meglitinides RepaglinideNateglinide

Insulin secretagogue

0.8-1.5%

Biguanides Metformin Decresed hepatic gluconeogenesis

1-2%

Thiazolidinedione PioglitazoneRosiglitazone

Insulin Sensitizers 0.5-1.3%

α-glucosidase inhibitor

Acarbose Reduces GI absorption of carbohydrate

0.5-1%

Sulfonylureas and MeglitinidesSulfonylureas and Meglitinides

Stimulate release of insulin in response to Stimulate release of insulin in response to glucoseglucose

Augment insulin levelsAugment insulin levels

Meglitinides act rapidly and achieve good Meglitinides act rapidly and achieve good post prandial control but are short acting post prandial control but are short acting and have to be given with every mealand have to be given with every meal

Sulfonylureas are longer acting and given Sulfonylureas are longer acting and given once daily but have risk of hypoglycemiaonce daily but have risk of hypoglycemia

MetforminMetformin

Stimulates hepatic gluconeogenesis and Stimulates hepatic gluconeogenesis and improves insulin sensitivityimproves insulin sensitivityAlthough its effect on glycemic control is not that Although its effect on glycemic control is not that impressive, it does cause significant reduction in impressive, it does cause significant reduction in cardiovascular diseasecardiovascular diseaseDoes not cause weight gainDoes not cause weight gainMain risk is LACTIC ACIDOSISMain risk is LACTIC ACIDOSIS– Should be avoided in pts with creatinine >1.4 due to Should be avoided in pts with creatinine >1.4 due to

renally excreted. renally excreted. – Hold drug 24-48 hours prior to contrast procedures Hold drug 24-48 hours prior to contrast procedures

and do not restart until BUN/Creatinine documented and do not restart until BUN/Creatinine documented to be normal. to be normal.

ThiazolidinedionesThiazolidinediones

Bind to nuclear receptors affecting gene Bind to nuclear receptors affecting gene expression and therefore have a long latency expression and therefore have a long latency requiring 4-12 weeks before they reach efficacy. requiring 4-12 weeks before they reach efficacy.

Beneficial lipid effects. Beneficial lipid effects.

Pioglitazone has greater effect on TG and less Pioglitazone has greater effect on TG and less LDL lowering than Rosiglitazone. LDL lowering than Rosiglitazone.

Require LFT monitoring and should be stopped Require LFT monitoring and should be stopped if AST risesif AST rises

Contraindicated in CHF due to fluid retentionContraindicated in CHF due to fluid retention

αα-glucosidase inhibitors-glucosidase inhibitors

Reduce the rate of carbohydrate Reduce the rate of carbohydrate absorption from the gut enabling absorption from the gut enabling endogenous insulin to maintain glycemic endogenous insulin to maintain glycemic control. control.

Not absorbed and no weight gain, but Not absorbed and no weight gain, but severe flatulence. severe flatulence.

Caveats on oral hypoglycemicCaveats on oral hypoglycemic

Any oral hypoglycemic will only lower Any oral hypoglycemic will only lower HbA1c by 1-2 %HbA1c by 1-2 %

They do have additive effects, but if a They do have additive effects, but if a patients HbA1c is 10 – you will not be able patients HbA1c is 10 – you will not be able to achieve glycemic control with oral to achieve glycemic control with oral agents alone. agents alone.