diabetes complications: screening and...

2015 International Diabetes Center

Diabetes Complications: Screening

and Management

Gregg Simonson, PhD

Director, Professional Training and Consulting International Diabetes Center; Adjunct Assistant Professor, University of Minnesota Department of Family Practice

Complications Associated with Diabetes


� CVD death 2–4 times higher

� Stroke risk 2–4 times higher

� Hypertension risk 2–3 times higher (present in 75–80%)

� PAD 2 times higher

� Type 2 diabetes is closely linked to obesity (although in some not obvious due to excess central adiposity, i.e. ‛‛metabolically obese, normal weight” [MONW])

Cardiovascular Disease in Type 2 Diabetes

CDC, National Diabetes Fact Sheet, 2011; ADA Web Site

Progression of Atherosclerosis

Endothelium

Smooth muscle

Extracellular lipid

Fibrous cap


Priorities of Care for Adults with Diabetes

Macrovascular ComplicationsMacrovascular ComplicationsASA, tobacco, ACEI/ARB, statin

© 2015 International Diabetes Center.

Diagnosis–PreventionDx A1C ≥6.5%, fasting glucose ≥126 casual ≥ 200 + symptoms

prevent pre-diabetes (IFG-IGT) & metabolic syndrome

Self-Management Knowledge and SkillMonitoring Medication Problem solving Food plan & nutrition

Risk reduction Living & coping Physical activity

Hemoglobin A1C

Target < 7.0%

SMBG

Pre 70-130 mg/dL

Post <180 mg/dL

(~ 50% of readings)

Blood Pressure

(every visit)

Dx and Rx < 140/90

Annual Lipid Profile

LDL < 100

HDL > 40

Trigs < 150

DM + CVD

LDL < 70

Annual Screening

NephropathyMicroalbumin screening

Calculated GFR

RetinopathyDilated retinal exam

NeuropathyNeuro and foot exam

Sexual health

Hospital care

Foot care

Dental care

Immunizations

Glucose HypertensionLipidsMicrovascularcomplicationsMicrovascularcomplications

Other essentialsOther essentialsof care

?

ADA LDL Cholesterol Targets 2014 vs. 2015

ADA Clinical Practice Recommendations, Diabetes Care 2014; 37

Suppl 1.; ADA Standards of Medical Care. Diab Care 2015; 38 Suppl 1

LDL-C<100 mg/dL

LDL-C<70 mg/dL

LDL-C Goal Diabetes

LDL-C Goal Diabetes + CVD

2014

No target

No target

LDL-C Goal Diabetes

LDL-C Goal Diabetes + CVD

2015


Rationale

� Statin therapy benefits most diabetes patients

� No LDL targets, consistent with 2013 AHA/ACC recommendations

2015 ADA Dyslipidemia Management Recommendations

ADA Standards of Medical Care. Diab Care 2015; 38 Supplement 1

Statins are Expectant Therapy in Diabetes

� Rosuvastatin (Crestor), Atorvastatin (Lipitor), Simvastatin (Zocor), Pravastatin (Pravachol), Lovastatin, Pitavastatin (Livalo), Fluvastatin

� Most powerful LDL lowering agents

– 50% + reduction from baseline

� Increases HDL ~5-15% and lowers triglycerides ~15-25%

� May cause muscle pain (myopathy)

� Associated with modest increased risk for diabetes (10-25%), yet CV benefit outweighs risk

Ridker et al., Lancet. 2012;380:565-571.


1. Individuals with clinical ASCVD (ACS, MI, angina, revascularization, stroke, TIA, PAD)

2. Individuals with LDL-C ≥190 mg/dL

3. Individuals 40-75 years of age with diabetes and LDL-C 70-189 mg/dL

4. Individuals without clinical ASCVD or diabeteswho are 40-75 years of age and LDL-C 70-189 mg/dL and 10 year ASCVD risk ≥ 7.5%

4 Statin Benefit Groups

Stone et al, Circulation 2013: Published Online Stone et al., Circulation. 2013; Nov Online.


Source: S. E. Nissen et al. , JAMA 2004; 291:1071-80.

Can statins reverse atherosclerosis?

Intravascular Ultrasound Images at Baseline and Follow-up

Answer: Yes in some patients and stops progression in others.Results of the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study

Combination Therapy for Dyslipidemia

Rationale

�ACCORD trial showed the addition of fenofibrate to statin therapy did not reduce CV events compared to statin therapy alone

�AIM-High trial was stopped early due to lack of CV benefit of adding niacin to statin therapy vs. placebo

ADA Standards of Medical Care. Diab Care 2015; 38 Supplement 1









Hemoglobin A1C

Target < 7.0%

SMBG

Pre 70-130 mg/dL

Post <180 mg/dL

(~ 50% of readings)

Blood Pressure

(every visit)

Dx and Rx < 140/90


LDL < 100

HDL > 40

Trigs < 150

DM + CVD

LDL < 70

Annual Screening


Calculated GFR



Sexual health

Hospital care

Foot care

Dental care

Immunizations



?

Measure

Blood

Pressures

Accurately

What’s wrong with

this picture?


American Diabetes Association HTN Management Recommendations

� Systolic BP treatment target of <140 mmHg

– Lower systolic BP target of <130 mmHg for certain individuals (e.g. younger patients without undue treatment burden)

� Diastolic BP target <80 mmHg

� Treatment recommendations:

– Lifestyle changes including weight loss, DASH diet, reduced sodium, increased physical activity

– ACE inhibitor or ARB as first-line therapy

– Multiple medications often needed to achieve BP target, administer one or more at bedtime

ADA Clinical Practice Recommendations. Diabetes Care, 2014; 37:Suppl.1.

JNC 8 Guidelines are not without controversy

1. Not endorsed by any large professional association (e.g. ACC/AHA)

2. Not all panel members agreed with raising SBP >150 mmHg in

individuals ≥60 years

3. May cause initiation of pharmacotherapy too early in “low risk”

individuals


JNC 8 Recommendations for Individuals with Diabetes

� In individuals ≥18 years, initiate pharmacologic treatment when BP ≥140/90 mmHg and treat to goal BP <140/90 mmHg

� In the general nonblack population initial pharmacotherapy treatment should be:

– Thiazide diuretic

– Calcium channel blocker

– ACE-I or ARB

� In the general black population initial pharmacotherapy treatment should be:

– Thiazide diuretic or calcium channel blocker

James et al. JAMA, 2013; Published Online Dec 18th.

Role of Intensive BP Control in DiabetesResults of the ACCORD BP Study

ACCORD Study Group, N Engl J Med. 2010.

•Average 3.4 antihypertensive medications in intensive vs. 2.2 in standard care

•Serious adverse events occurred 3.3% intensive vs. 1.3% standard care

•What is the appropriate BP target in type 2 diabetes???

119 mmHg

133.5 mmHg


Anti-platelet Agents in Diabetes

� Aspirin 75-162 mg/day in type 1 and type 2 diabetes if 10 yr CHD risk >10%

� Men >50 yrs and

� Women >60 yrs with at least one additional risk factor

� Family history CVD, Hypertension, Smoking, Dyslipidemia, Albuminuria

� Combination with Clopidogrel (Plavix) for up to 1 yr post acute coronary syndrome (ACS)

� Clopidogrel if aspirin contraindicated

ADA Standards of Medical Care. Diabetes Care Volume 38, 2015 Supplement 1.








Hemoglobin A1C

Target < 7.0%

SMBG

Pre 70-130 mg/dL

Post <180 mg/dL

(~ 50% of readings)

Blood Pressure

(every visit)

Dx and Rx < 140/90


LDL < 100

HDL > 40

Trigs < 150

DM + CVD

LDL < 70

Annual Screening


Calculated GFR



Sexual health

Hospital care

Foot care

Dental care

Immunizations



?


Microvascular Complications of Diabetes:From Head to Toe

Eye�Retinopathy�Cataracts�Glaucoma�Visual Impairment

KidneyNephropathy� Microalbuminuria� Macroalbuminuria� Renal insufficiency/failure

Nerves Neuropathy� Peripheral/Central� Autonomic

Complications Risk in Diabetes

0

2

4

6

8

6 7 8 9 10 11 12A1C (%)

Rel

ati

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Ris

k

of

Co

mp

lica

tio

ns

Adapted from: Skyler JS. Endocrinol Metab Clin North Am. 1996 Jun;25(2):243-54.

DCCT Study Group. N Engl J Med 329:977, 1993

UKPDS 35. Stratton IM. BMJ 321:405-412, 2000.

120 150 180 210 240 270 300Average Glucose

Lowering blood glucose significantly

reduces the risk of microvascular

complications

In both Type 1 and Type 2 diabetes


Source: United States Renal Data System. USRDS 2007 Annual Data Report

Glomerular Filtration Rate (GFR)

� Glomerular Filtration Rate (GFR) is most useful to determine level of kidney impairment

– GFR does not help determine cause of kidney disease

– GFR is rough measure of the number of filtering nephrons

– Cannot be measured directly

– Not recommended for

• Extremes of age (children and elderly)

• Malnutrition

• Severe obesity

• Altered muscle mass (amputee)

Pathways to Complications


Stages of Chronic Kidney Disease (CKD)

Stage eGFR

(ml/min/1.73 m2)

Description Action

1 >90 Normal or higher

GFR w. evidence of

kidney disease

Dx and Rx of co-

morbidities

2 60-89 Mild decrease in

GFR

Monitor progress and

Rx co-morbidities

3

3a

3b

30-59

45-59

30-44

Moderate decrease

in GFR

Monitor progress and

Rx co-morbidities and

consider referral

4 15-29 Severe decrease in

GFR

Pre ESKD, prepare pt.

for dialysis

5 <15 Kidney failure Dialysis or

replacement

Am J Kid Dis 2002 39:S1-266

CKD defined as Stage 3 or higher for 3 months or more

CKD

Bakris, GL Mayo Clin Proc 2011 86:444-456

Screening Recommendations

Nephropathy

� Annual microalbuminuria screen

� Albumin/creatinine (A/C) ratio preferred

� Annual serum creatinine/calculate eGFR

Type 1 Diabetes

� After 5 years duration; annually thereafter

Type 2 Diabetes

� At diagnosis; annually thereafter

American Diabetes Association Clinical Practice Recommendations. Diabetes Care 2011; Suppl 1.


Albuminuria: Definitions

Term ACR (albumin:creatinine ratio)(aka UMAR)

Nephrotic Range Proteinuria > 3,500 mg/g

Macroalbuminuria(New term: “Very High

Albuminuria”)

> 300 mg

Microalbuminuria(New term: “High Albuminuria”)

30-300 mg/g

“Normal” 0-30 mg/g

Increased CV Risk

Increased ESRD risk

• Urine albumin:creatinine ratio

• Confirm with two or more samples over 3-6 months

Diabetic Kidney Disease: Natural Course

NephSAP 2012


Treatment of Diabetic Nephropathy

� Glucose control

� A1C <7% delays onset of albuminuria- individualize target for pt safety

� Smoking cessation

� Low protein diet (0.8 g/kg/day)

� Improves renal function (e.g. slows increase in albumin level, decline in GFR, and occurrence of ESRD)

� Results conflicting, might be considered in patients whose nephropathy is progressing despite optimal glucose and BP control

� ASA/Lipids

� All patients with persistent albuminuria should be Rx with ASA and statins

� Consider ASA and statins in all patients with eGFR <60 ml/min

� Fenofibrate may further reduce albuminuria (ACCORD-LIPID) but can increase serum creatinine

Treatment of Diabetic Nephropathy

Blood pressure control:

� <140/90 mmHg

� Can consider lower target e.g. <130/80 mmHg if significant proteinuria

� Start ACE Inhibitor(ACE-I) or Angiotensin II Receptor

Blocker (ARB) � Baseline creatinine and K+, repeat in 1-2 weeks

� Titrate dose to maximum approved hypertension dose if can be achieved safely

� Monitor A/C ratio to assess response to therapy and progression of disease

� Similar BP control and kidney protection actions

� May need multiple BP medications to reach goal

� UKPDS 30% pts with 3 or more drugs


Scope of Diabetic Retinopathy (DR)

� After 20 years of diabetes-Evidence of retinopathy in almost all patients with type 1 DM, 60-85% with type 2 DM

� Leading cause of new cases of blindness among adults aged 20-74 years

� Detecting and treating diabetic eye disease with laser can reduce the development of severe vision loss by 50-60%

National Diabetes Fact Sheet, US 2011

Bressler etal. NEJM 2011: 365; 1520-1526

Non-Proliferative DR Diabetic Macular Edema Proliferative DR

Microvascular damage• Chronic, occurring over years

• Typically no significant vision loss,

but progresses to DME and/or PDR

• Similar damage occurs in other

end-organ vascular beds

Swelling in central retina• Accounts for most vision loss

• Clinically significant ME (CSME)

involves or threatens the fovea

• Co-exists with any level of DR

End stage• Neovascularization of retina

• High risk of severe visual loss

Classification of Diabetic Retinopathy

More common

Less severeLess common

More severe


Normal RetinaEarly Nonproliferative

Retinopathy

Proliferative Retinopathy

Optic nerve

Macula

Hard exudates

Hemorrhage

Neovascularization


American Academy of OphthalmologyRecommended Eye Examination Schedule for Patients with Diabetes Mellitus

• 40-50% do not receive recommended eye care (NCQA, 2009)

• Joslin study of patient self-awareness of DR (ARVO, 2011; n=3100)

• 93% of patients with DR and 63% with vision-threatening DR were unaware they had any DR

• 83% with vision-threatening DR had no scheduled follow-up eye exam

Diabetes Type Recommended Time

For First Examination

Recommended

Follow-up

Type 1 3-5 years after diagnosis Yearly

Type 2 At time of diagnosis Yearly

American Academy of Ophthalmology Retina Panel. Preferred Practice Pattern® Guidelines.

ARVO = The Association for Research in Vision and Ophthalmology ; NCQA = National Committee for Quality Assurance.

Retinopathy: What We Know & What We Are Learning

We Know – The following are critical:• Regular eye check ups

• Glucose control

• Blood pressure control

• Smoking cessation

• Laser treatment gold-standard Rx for PDR

• ASA safe in DR

• Women planning or pregnant should have prompt eye exam with follow-up

We Are Learning:• ACE/ARB’s may slow progression of retinopathy

• Fenofibrate may slow progression of retinopathy (30-40%) -FIELD and ACCORD-EYE

• VEGF inhibitors with prompt or deferred laser gold-standard Rx for diabetic macular edema (DME)


Classifications of Diabetic Neuropathy

� Diabetic Peripheral Neuropathy (DPN)

� Diabetic Autonomic Neuropathy (DAN)

– Cardiac

– Gastrointestinal (gastroparesis)

– Genitourinary (bladder and sexual dysfunction)

– Sudomotor and metabolic (hypoglycemia unawareness)

� Focal

– Cranial (i.e. Bell’s Palsy)

– Truncal /Limb Plexopathy or Mononeuropathy (i.e “foot drop”)

– Diabetic Amyotrophy or Lumbosacral Radiculopathy

– Nerve Entrapment syndromes (i.e. Carpal Tunnel)

Autonomic Nervous system


Signs and Symptoms ofDiabetic Peripheral Neuropathy

Symptoms

� Numbness or loss of sensation (asleep or “bunched up sock under toes” sensation)

� Prickling/Tingling

� Pain (aching, burning, lancinating)

� Unusual sensitivity or tenderness when feet are touched (allodynia)

Signs

� Diminished vibratory perception

� Decreased knee and ankle reflexes

� Reduced protective sensation such as pressure, hot and cold, pain

� Diminished ability to sense position of toes and feet

Peripheral and Symmetric Stocking Glove Distribution

Symptoms and signs progress from distal to proximal over time

Treatment of Painful Peripheral Neuropathy

Staged Diabetes Management, 5th edition Revised, Quick Guide, pages 7-18.


The Foot Examination

Careful inspection

� Skin, shoes, shape of foot

Vascular integrity

� Pulses

� Capillary refill

� Ankle-Brachial Pressure Index (ABI, if indicated)

Neurological examination and function

� Light touch (5.07/ 10g monofilament)

� Vibratory sensation (128-Hz tuning fork)

� Reflexes

Source: Staged Diabetes Management, 5th edition, Quick Guide, pages 7-26.

Standards of Care at Diagnosis & Annually

Foot Ulcer


Source: Staged Diabetes Managemen,t 4th edition, Quick Guide, pages 7-27.

Neurological ExamVibratory Sensation

<10 seconds of

feeling vibration

between patient

and HCP

considered normal

Source: Staged Diabetes Management, 5th edition, Quick Guide, pages 7-28.

Neurological ExamProtective Sensation

� 10g monofilament

� 4 locations on foot

� Apply at 90 degrees with enough pressure to bend filament (10 grams) for 1-2 seconds

Locations on the foot

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