Diabetes Mellitus OverviewDiabetes Mellitus Overview

DefinitionDefinition

Disease of abnormal carbohydrate Disease of abnormal carbohydrate metabolism characterized by metabolism characterized by hyperglycemia hyperglycemia

Caused by:Caused by:– Impairment in insulin secretion and/orImpairment in insulin secretion and/or– Peripheral resistance to insulinPeripheral resistance to insulin

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True or FalseTrue or False

Diabetes insipidus is the opposite of Diabetes insipidus is the opposite of diabetes mellitus, in other words, a diabetes mellitus, in other words, a problem of low blood sugar. problem of low blood sugar.

FalseFalse

Diabetes insipidusDiabetes insipidus– Disorder involving the secretion or response Disorder involving the secretion or response

to ADH (antidiuretic hormone)to ADH (antidiuretic hormone)– Causes high-volume urine output and Causes high-volume urine output and

hypernatremiahypernatremia– Not a glucose problemNot a glucose problem

Diabetes MellitusDiabetes Mellitus

Over 7% of U.S. populationOver 7% of U.S. population

14% of health care expenditures14% of health care expenditures

132 billion dollars (2002)132 billion dollars (2002)

Associated with:Associated with:– Higher psychiatric illnessHigher psychiatric illness– Decreased work productivityDecreased work productivity– Increased absenteeismIncreased absenteeism

Diabetes MellitusDiabetes Mellitus

Type 1: destruction of pancreatic beta Type 1: destruction of pancreatic beta cells leading to insulin deficiency (10%)cells leading to insulin deficiency (10%)

Type 2: insulin resistance with varying Type 2: insulin resistance with varying degrees of insulin deficiency (80%)degrees of insulin deficiency (80%)

Gestational: insulin resistance created by Gestational: insulin resistance created by anti-insulin hormones secreted by anti-insulin hormones secreted by placenta during pregnancyplacenta during pregnancy

Other causes: drugs, infectionsOther causes: drugs, infections

Type 1 DMType 1 DM

Autoimmune destruction of insulin-Autoimmune destruction of insulin-producing cells in pancreasproducing cells in pancreas– Islet cell autoantibodiesIslet cell autoantibodies– Glutamic acid decarboxylase antibodiesGlutamic acid decarboxylase antibodies– Anti-insulin antibodiesAnti-insulin antibodies– Associated with other autoimmune diseasesAssociated with other autoimmune diseases

Genetically susceptibleGenetically susceptible

Triggered by environmental agentTriggered by environmental agent

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Diabetes mellitus damages:Diabetes mellitus damages:

A.A. EyesEyes

B.B. KidneyKidney

C.C. NervesNerves

D.D. HeartHeart

E.E. BrainBrain

ComplicationsComplications

MicrovascularMicrovascular– NephropathyNephropathy– NeuropathyNeuropathy– RetinopathyRetinopathy

MacrovascularMacrovascular– Coronary artery diseaseCoronary artery disease– Peripheral vascular diseasePeripheral vascular disease– StrokeStroke

Diabetic nephropathyDiabetic nephropathy

Microalbuminuria > Macroalbuminuria > Microalbuminuria > Macroalbuminuria > Elevated creatinine > End stage renal Elevated creatinine > End stage renal disease > Dialysisdisease > Dialysis

AsymptomaticAsymptomatic

Diabetic neuropathyDiabetic neuropathy

18% have evidence of nerve damage at 18% have evidence of nerve damage at diagnosisdiagnosis

Usually symmetrical, affecting lower Usually symmetrical, affecting lower extremities firstextremities first

Stocking-glove syndromeStocking-glove syndrome

Impaired sensation (pain, light touch, Impaired sensation (pain, light touch, temperature, vibration, proprioception)temperature, vibration, proprioception)

Can feel numb or painfulCan feel numb or painful

Diabetic neuropathyDiabetic neuropathy

Major risk factor for foot ulcersMajor risk factor for foot ulcers

Autonomic neuropathyAutonomic neuropathy– Postural hypotensionPostural hypotension– GastroparesisGastroparesis– Enteropathy (constipation/diarrhea)Enteropathy (constipation/diarrhea)

Diabetic retinopathyDiabetic retinopathy

Most common cause of blindness in Most common cause of blindness in middle-aged peoplemiddle-aged people

Blindness 25x higher in diabeticsBlindness 25x higher in diabetics

Asymptomatic until late stagesAsymptomatic until late stages

80% of type 2’s have retinopathy at 20y80% of type 2’s have retinopathy at 20y

MechanismsMechanisms– Impaired blood flowImpaired blood flow– Accumulation of sorbitol in retinaAccumulation of sorbitol in retina

Diabetes and the HeartDiabetes and the Heart

Diabetics have:Diabetics have:– Higher rate of heart diseaseHigher rate of heart disease– Greater coronary ischemiaGreater coronary ischemia– Higher chance of MI and silent MIHigher chance of MI and silent MI

CHD risk equivalentCHD risk equivalent– Aggressive LDL goalAggressive LDL goal

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Per ADA, DM (type 2) screening should Per ADA, DM (type 2) screening should begin at what age?begin at what age?

A.A. 2525

B.B. 3535

C.C. 4545

ScreeningScreening

Start at age 45; if normal repeat every 3 Start at age 45; if normal repeat every 3 yearsyearsScreen earlier or more frequently if Screen earlier or more frequently if overweight with additional risk factor overweight with additional risk factor – InactiveInactive– Family history (1Family history (1stst degree relative) degree relative)– HTNHTN– IFG or IGTIFG or IGT– Vascular diseaseVascular disease

DiagnosisDiagnosisAmerican Diabetes AssociationAmerican Diabetes Association

Fasting plasma glucoseFasting plasma glucose

Random glucose with symptomsRandom glucose with symptoms

Oral glucose tolerance testOral glucose tolerance test

Should be confirmed with repeat testing on Should be confirmed with repeat testing on different daydifferent day

DiagnosisDiagnosis

Fasting plasma glucoseFasting plasma glucose

Fasting = no caloric intake for 8 hoursFasting = no caloric intake for 8 hours

Greater than or equal to Greater than or equal to 126126 mg/dl mg/dl

DiagnosisDiagnosis

Random glucose with symptomsRandom glucose with symptoms

Glucose greater than or equal to Glucose greater than or equal to 200200 mg/dl at any timemg/dl at any time

Classic symptoms: polydipsia, polyuria, Classic symptoms: polydipsia, polyuria, weight lossweight loss

DiagnosisDiagnosis

Oral glucose tolerance testOral glucose tolerance test

Glucose greater than or equal to Glucose greater than or equal to 200200 mg/dl two hours after 75g glucose loadmg/dl two hours after 75g glucose load

TreatmentTreatment

Nonpharmacologic (lifestyle)Nonpharmacologic (lifestyle)– Proper dietProper diet– ExerciseExercise– Weight lossWeight loss

Benefits greater to type 2’sBenefits greater to type 2’s

Drug treatmentDrug treatment

InsulinInsulin

- Initial treatment in type 1’s- Initial treatment in type 1’s

- In type 2’s, more commonly used after oral - In type 2’s, more commonly used after oral agents failagents fail

Multiple daily injectionsMultiple daily injections– Lantus + HumalogLantus + Humalog

Continuous infusionContinuous infusion

Adjustments based on HgbA1c and daily Adjustments based on HgbA1c and daily glucose checksglucose checks

Drug treatmentDrug treatment

MetforminMetformin

SulfonylureasSulfonylureas

MeglitinidesMeglitinides

ThiazolidinedionesThiazolidinediones

Alpha-glucosidase inhibitorsAlpha-glucosidase inhibitors

MetforminMetformin

Decreases liver glucose productionDecreases liver glucose production

Improves insulin sensitivityImproves insulin sensitivity

Modest weight reductionModest weight reduction

Avoid in renal insufficiencyAvoid in renal insufficiency

Avoid before IV contrast load or surgical Avoid before IV contrast load or surgical procedure (lactic acidosis)procedure (lactic acidosis)

Start 500mg once daily with dinnerStart 500mg once daily with dinner

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Metformin should be held ___ hours Metformin should be held ___ hours before IV contrast studies.before IV contrast studies.

A.A. 88

B.B. 2424

C.C. 4848

D.D. 9696

SulfonylureasSulfonylureas

Increase insulin releaseIncrease insulin release

Oldest class of oral agentOldest class of oral agent

Higher rate of hypoglycemic complicationsHigher rate of hypoglycemic complications

Starting dosesStarting doses– Glipizide 5mg dailyGlipizide 5mg daily– Glyburide 2.5 to 5mg dailyGlyburide 2.5 to 5mg daily– Glimeperide 1 to 2 mg dailyGlimeperide 1 to 2 mg daily

MeglitinidesMeglitinides

Increase insulin releaseIncrease insulin release

Short-acting, expensiveShort-acting, expensive

Taken with mealsTaken with meals

Starlix, PrandinStarlix, Prandin

ThiazolidinedionesThiazolidinediones

Increases insulin sensitivityIncreases insulin sensitivity

Less effective than metformin and Less effective than metformin and sulfonylureas as monotherapysulfonylureas as monotherapy

Causes weight gain, fluid retentionCauses weight gain, fluid retention

Avoid in heart failureAvoid in heart failure

Alpha-glucosidase inhibitorsAlpha-glucosidase inhibitors

Modifies intestinal absorption of Modifies intestinal absorption of carbohydratecarbohydrate

Less potent than oral agents (0.5-1% A1c Less potent than oral agents (0.5-1% A1c reduction)reduction)

Main side effects: gas, diarrheaMain side effects: gas, diarrhea

Take with mealsTake with meals

Persistent hyperglycemiaPersistent hyperglycemia

Combination therapy (type 2’s)Combination therapy (type 2’s)– 2 or 3 drugs together2 or 3 drugs together– 2 orals then add insulin if needed2 orals then add insulin if needed– No need for sulfonylurea and insulin togetherNo need for sulfonylurea and insulin together

Exenatide (Byetta)Exenatide (Byetta)– Twice daily subcutaneous injectionTwice daily subcutaneous injection– Promotes weight lossPromotes weight loss– GI side effectsGI side effects– Overweight patient gaining weight on oralsOverweight patient gaining weight on orals

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True or FalseTrue or False

Insulin can be inhaled.Insulin can be inhaled.

Persistent hyperglycemiaPersistent hyperglycemia

Inhaled insulinInhaled insulin– Rapid, similar to lispro insulinRapid, similar to lispro insulin– Taken with mealsTaken with meals– Excludes patients with respiratory disordersExcludes patients with respiratory disorders– Long-term effects on lungs not definedLong-term effects on lungs not defined

Long-term careLong-term care

HgbA1c (goal < 7%)HgbA1c (goal < 7%)

7% = 150 (1% change = 30)7% = 150 (1% change = 30)

Glucose targets (frequency 2-4x day)Glucose targets (frequency 2-4x day)– Preprandial (90 to 130)Preprandial (90 to 130)– Postprandial (<180)Postprandial (<180)

Long-term careLong-term care

Routine eye examsRoutine eye exams– Dilated and comprehensive exam shortly after Dilated and comprehensive exam shortly after

diagnosisdiagnosis– Annual exams thereafterAnnual exams thereafter– Ophthalmologist or optometrist recommendedOphthalmologist or optometrist recommended

Long-term careLong-term care

Routine foot examsRoutine foot exams– Detect or monitor vascular/neurologic Detect or monitor vascular/neurologic

complicationscomplications– Visual inspection of feet at each routine visitVisual inspection of feet at each routine visit– Comprehensive exam yearlyComprehensive exam yearly

PulsesPulses

Monofilament testMonofilament test

Long-term careLong-term care

Screen or treat microalbuminuriaScreen or treat microalbuminuria– Dipstick is insensitiveDipstick is insensitive– Spot urine collection measuring albumin to Spot urine collection measuring albumin to

creatinine ratiocreatinine ratio > 30mg/g abnormal> 30mg/g abnormal

ACE-inhibitor or ARB prevents ACE-inhibitor or ARB prevents progression of nephropathyprogression of nephropathy

Long-term careLong-term care

Aggressively treat cardiac risk factorsAggressively treat cardiac risk factors– SmokingSmoking– Hypertension (< 130/80)Hypertension (< 130/80)– Dyslipidemia (LDL < 100)Dyslipidemia (LDL < 100)

Aspirin (81mg) for 1Aspirin (81mg) for 1° CHD prevention for ° CHD prevention for anyone with one risk factoranyone with one risk factor

Acute complicationsAcute complications

Diabetic ketoacidosisDiabetic ketoacidosis– Metabolic acidosis is main concernMetabolic acidosis is main concern

Nonketotic hyperglycemiaNonketotic hyperglycemia– Glucose often > 1000Glucose often > 1000– Neurologic abnormalities frequentNeurologic abnormalities frequent

Precipitating factors: MI, pancreatitis, trauma, Precipitating factors: MI, pancreatitis, trauma, any stress to bodyany stress to bodyTreatment requires IV insulin, hydration, Treatment requires IV insulin, hydration, electrolyte replacementelectrolyte replacement

Questions?