Complications and ScreeningBy Renee E. Amori, MD FACE

Acute◦ Diabetic Ketoacidosis (DKA)◦ Hyperglycemic Hyperosmolar Non-Ketotic states

(HHNK) Chronic

◦ Microvascular complications◦ Macrovascular complications

Diabetic Ketoacidosis (DKA) Hyperglycemic, Hyperosmolar Non-Ketotic

States (HHNK) This section only introduces the concepts Specific treatments for these conditions will

be reviewed during your critical care rotations

Hyperglycemia: ◦ increased gluconeogenesis, glycogenolysis◦ decreased glucose utilization

Ketonemia: ◦ Lack of insulin (insulinopenia) stimulates

breakdown of fats to free fatty acids to make ketones

Acidemia: ◦ ketone acids exceed the buffering capacity of

the system◦ blood pH drops

Where is typically just enough insulin to prevent lipolysis and ketogenesis

But there’s not quite enough insulin for appropriate utilization of glucose at a cellular level

High glucose levels increase the osmolarity of the blood

From Kitabchi et al “Hyperglycemic Crisis in the Adult Patient with Diabetes: a consensus statement from the American Diabetes Association.” Diabetes Care 2006; 29(12): 2739-2748.

DKA – typically seen in patients with type 1 diabetes

HHNK– seen in patients with type 2 diabetes BUT:

◦ There is a subset of type 2 patients who can develop DKA

◦ These are Ketosis-prone type 2

DKADKAAgeAge Usually <40Usually <40

DurationDurationOf SxOf Sx Usually <2daysUsually <2daysGlucoseGlucoseUsually <600mg/dL Usually <600mg/dL

pHpH LowLowHCO3HCO3 LowLowKetonesKetones At least 4+At least 4+SOsmSOsm Usually <330Usually <330

HHNKHHNKUsually >40Usually >40

Usually >2 daysUsually >2 daysUsually Usually

>600mg/dL>600mg/dL

NormalNormalNormalNormal<2+<2+Usually >330Usually >330

Generally there is a decompensation that results in the hyperglycemic emergency

Common factors (include, but are not limited to):◦ Infection◦ Myocardial Infarction◦ Stroke◦ New onset of diabetes◦ Medication non-compliance

These patients are volume depleted and need fluids

ICU management with IV insulin and hourly glucose checks is safest◦ Monitoring of electrolytes including potassium

and phosphate Correct glucose at 50-70 mg/DL per hour

◦ Rapid correction can lead to cerebral edema

The result of chronic, uncontrolled glucose◦ Microvascular complications

Triopathy: retinopathy, nephropathy, neuropathy◦ Macrovascular complications

Leading to disability and ultimately death

Diabetes Mellitus is the leading cause of blindness in the USA

Intensive glycemic control:◦ decreases risk of developing retinopathy◦ slows progression of existing disease*see DCCT and UKPDS trial data

Screen with a dilated fundus examination annually

Type 1: screening should begin 5 years after diagnosis

Type 2: screening should begin at the time of diagnosis

Eye disease correlates with duration of diabetes!

Non-Proliferative Diabetic Retinopathy (NPDR)◦ Includes microaneurysms◦ More advanced – “cotton wool” spots

Proliferative Diabetic Retinopathy (PDR)◦ Vitreous hemorrhage, neovascularization

Diabetic Macular Edema◦ Is a manifestation of NPDR

Glycemic control At the discretion of Ophthalmology, it can

include:◦ Photocoagulation of the retina

Ex: using argon laser◦ Vitrectomy◦ Intraocular anti-vascular endothelial growth factor

(VEGF) injection Bevacizumab (Avastin) or other agents

Cataracts – ◦ more common in diabetes◦ occur earlier than in people without diabetes

Cranial Neuropathies◦ Palsies of CN III, IV or VI can occur

Diabetic Nephropathy is the most common cause of ESRD in the USA.

Factors influencing nephropathy include:◦ genetics/race◦ hypertensive control◦ glycemic control

1. Hyperfiltration2. “Silent Stage”3. Microalbuminuria: 30-300mg in 24hrs4. Macroalbuminuria: >300mg in 24hrs5. Uremia

Annual assessment of urine albumin excretion◦ Multiple ways to screen:

spot urine microalbumin –to– creatinine ratio (must order BOTH) OR

24hr urine collection (more burdensome)◦ Make sure abnormal values are repeated before

labeling someone with nephropathy Measure serum creatinine at least once

per year in adults A simple urinalysis is not sufficient to

screen

When to screen? Type 1: screening should begin 5 years

after diagnosis Type 2: screening should begin at the time

of diagnosis

Glycemic control Hypertensive control Modification of the renin-angiotensis-

aldosterone system (RAAS)

From Williams’ Textbook of Endocrinology. 12th edition

Important in mediating renal damage in diabetes

ACE Inhibitors (ACEI) Angiotensin Receptor Blockers (ARBs) Both have been used to confer renal

protection in diabetes related kidney disease, and control BP

ACEI vs placebo/no treatment ◦ Significant reduction in the risk of ESRD

( Analysis 1.4 (10 studies, 6819 patients): RR 0.60, 95% CI 0.39 to 0.93)

 AIIRA [ARB] vs placebo/no treatment ◦ Significant reduction in the risk of ESRD

( Analysis 2.4 (3 studies, 3251 patients): RR 0.78, 95% CI 0.67 to 0.91)

Strippoli GF et al. “Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease” Cochran Database Syst Rev. 2006 Oct 18;(4):CD006257

ACEI vs. placebo/no treatment ◦ Significantly reduced the risk of progression from

micro- to macroalbuminuria ◦ ( Analysis 1.5 (17 studies, 2036 patients): RR 0.45,

95% CI 0.29 to 0.69).  AIIRA [ARB] vs. placebo/no treatment

◦ Significant reduction in risk of progression from micro- to macroalbuminuria

◦ ( Analysis 2.5 (3 studies, 761 patients): RR 0.49, 95% CI 0.32 to 0.75)

Strippoli GF et al. “Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease” Cochran Database Syst Rev. 2006 Oct 18;(4):CD006257

Many types of neuropathies can occur Diabetic Sensorimotor Peripheral

Neuropathy Acute mononeuropathies Autonomic neuropathies

Type 1: screening should begin 5 years after diagnosis

Type 2: screening should begin at the time of diagnosis

Ask for symptoms at each visit and examine feet for ulcers, calluses and deformities◦ Offer Podiatry evaluation

Screen by examining sensory function in the feet & ankle reflexes

Use 1 or more to assess sensory function: ◦ Pinprick◦ Temperature◦ vibration perception (using a 128-Hz tuning fork)◦ pressure sensation (using a 10-g monofilament)

Screening is challenging Neuropathy of the GI tract (gastroparesis)

◦ Often misunderstood Neuropathy of the cardiac system

◦ Resting HR >100 is concerning for cardiac neuropathy

Neuropathy of the bladder

Coronary Artery Disease Peripheral Arterial Disease Cerebrovascular disease

Heart Disease and Stroke are the leading cause of death among people with diabetes

In patients with heart disease, people with diabetes have a mortality rate 2-4x higher than people without diabetes

Risk of stroke is also 2-4x higher with diabetes

Very common, especially in people who also smoke cigarettes

Symptoms suggestive of claudication should be screened

Can order Ankle-Brachial Index to screen◦ Can be ordered through the Drexel Vascular Lab

(219 8th Floor, 215-762-5510)◦ Compares BPs in arms to those in legs

Risk of lower extremity amputation in people with diabetes is markedly higher than in those without diabetes

The vast majority of lower extremity amputations are preceded by ulcerations

Higher A1c is associated with increased risk of limb loss, based on meta-analysis◦ Adler et al. Diabetologia 2010; 53(5): 840-849

Poor glyceic control Peripheral sensory neuropathy Arterial insufficiency Foot deformity and callus Obesity Impaired vision Impaired wound healing Improper footwear History of foot ulcer or lower

extremity amputation

Daily inspection of the feet Inspection of the feet at office visits Proper footwear (supportive shoes etc…) Prompt treatment of any injury