Acute & Chronic

Complication
of
Diabetes Mellitus
 Diabetic Complication

Acute : Chronic :

Microangiopathy Macroangiopathy

 Hipoglycemia Retinopathy CAD

 Ketoacidosis Nephropathy PVD
 HONK Neuropathy Stroke
Acute Complication
of
Diabetes Mellitus
Hyperglycemic Crisis
Diabetic Ketoacidosis (DKA)
Hyperosmolar hyperglycemic state (HHS)
In critically ill

Hypoglycemia
 DKA consists of the biochemical triad of
ketonaemia (ketosis),
hyperglycaemia, and
acidaemia.

 DKA has been considered to be indicative, or even

diagnostic, of type 1 diabetes, but increasingly there are
cases of ketone-prone type 2 diabetes being
recognised.

However, the initial treatment is the same !

 The true incidence is difficult to establish.

 Population based studies range from 4.6 to 8 episodes per

1,000 patients with diabetes.

 DKA remains a significant clinical problem in spite of

improvements in diabetes care.

 In the USA the prevalence has risen, whilst mortality has

fallen.

 Mortality rates have fallen significantly in the last 20 years

from 7.96% to 0.67.
These are:
• Hypovolaemia
• Marked hyperglycaemia (30 mmol/L or more) without
significant hyperketonaemia (<3 mmol/L) or
acidosis (pH>7.3, bicarbonate >15 mmol/L)
• Osmolality usually 320 mosmol/kg or more

N.B. A mixed picture of HHS and DKA may occur.

 Whilst DKA presents within hours of onset, HHS comes
on over many days, and consequently the dehydration
and metabolic disturbances are more extreme.

 It is uncommon, but has a higher mortality than DKA.

 There are no recent publications from the UK of

mortality in HHS, but reported series suggest mortality
may have improved though remains high at between 15-
20%.
• Infection (20% - 40%) → urinary tract and lung
• CVA
• Myocardial infarction
• Pancreatitis
• Discontinuation of or inadequate insulin therapy
• Drugs (steroids, sympathomimetics, thiazides)
 DKA HHS
Mild Moderate Severe
Plasma glucose (mg/dl) > 250 > 250 > 250 > 600
Arterial pH 7.25–7.30 7.00–7.24 < 7.00 > 7.30
Serum bicarbonate (mEq/l) 15–18 10 to 15 < 10 > 18
Urine ketones (+) (+) (+) Small
Serum keton (+) (+) (+) Small
Effective serum osmolality Variable Variable Variable >320
(mosm/kg)
Anion gap > 10 > 12 >12 Variable
Alteration in sensoria and Alert Alert/drowsy Stupor/coma Stupor/coma
mental

Anion gap : (Na+) - (Cl + HCO3) (mEq/l).

Osmolality : (2Na+ + glucose + urea)
 IV fluid (NS)
 Insulin (Continuous IV drip/im)
 K+
 Bicarbonate (pH < 7)

PRECIPITATING FACTOR(S)
 The ADA Workgroup on Hypoglycemia defined
hypoglycemia in diabetes as “all episodes of abnormally
low plasma glucose concentration that expose the
individual to potential harm ”.

 The cutoff glucose concentration for defining

hypoglycemia is controversial.
 The ADA Workgroup recommended that people with
insulin secretagogue or insulin treated diabetes become
concerned about the possibility of developing
hypoglycemia at a self-monitored (or device estimated)
plasma glucose concentration of ≤ 70 mg/dL (≤ 3.9
mmol/L).
Excessive Error by patient, doctor or pharmacist
dosage

Increased Accelerated absorbtion (exercise, injection into

insulin abdomen, change to human insulin)
bioavailability Insulin antibodies, Renal failure, Honeymoon periode

Increased Counter-regulatory hormon deficiencies (Addison,

insulin Hypopituitarism)
sensitivity Weight loss, physical exercise, postpartum,
menstrual cycle variation
Inadequate Missed, small or delayed meals
carbohydrate Anorexia nervosa, Vomiting (gastroparesis), breast
response feeding, failure to cover exercise

Other factors Exercise, alcohol, drugs

Heller SR. Textbook of Diabetes 1, 2003, p.33.1
WHIPPLE’S
TRIAD

HYPOGLYCEMIA
HYPOGLYCEMIA

Low Plasma Glucose Levels

Principal metabolic effects of counter-regulation
in response to acute hypoglycaemia
Hypoglycaemia

+
+

ACTH

Glucagon Vasopressin Growth Cortisol

hormone

+
 Response to hypoglycemia

90 –
80 – Counter-regulation
70 – Autonomic symptoms
60 –
Neuroglycopenic symptoms
50 –
40 –
Coma
30 –
20 –
10 – Permanent damage
0 – Death

Gerich JE et al. Endocr Rev 1991;12:356-71.

 Symptoms and Sign of Hypoglycemia
Hypoglycaemia

Signs Symptoms

Neuro-glycopenic Neurogenic

Cognitive impairments Adrenergic: palpitations,

Pallor
Behavioural changes tremor, and anxiety/arousal
Diaphoresis Psychomotor Cholinergic: sweating,
abnormalities hunger, and paresthesia
Seizure
Coma

Cryer PE. Diabetes. 2008;57:3169-76.

 Mild hypoglycemia Severe hypoglycemia

Still can help themselves Need help from others

Does not depend on low blood glucose level

 Symptoms and Sign of Hypoglycemia
Hypoglycaemia

Signs Symptoms

Neuro-glycopenic Neurogenic

Cognitive impairments Adrenergic: palpitations,

Pallor
Behavioural changes tremor, and anxiety/arousal
Diaphoresis Psychomotor abnormalities Cholinergic: sweating, hunger,
Seizure and paresthesia
Coma

Cryer PE. Diabetes. 2008;57:3169-76.

 Criteria for Hypoglycemia
Mild hypoglycemia Severe hypoglycemia

Still can help themselves Need help from others

Does not depend on low blood glucose level

 Management

Mild hypoglycemia Severe hypoglycemia

 Drink sugar solution or glucose tab
15-20 gr,  IV glucose 10-25 gram 1-3
 Wait for 20 min min
 Re-check blood glucose  Or glucagon 1 mg IM/SC
 If blood glucose is not ≥18 mg/dl,
 Re-administered glucose solution
 Unawareness Hypoglycemia
In elderly people receiving insulin or sulphonylureas,
the symptoms of hypoglycemia most commonly
recognized are not specific in nature:

* Transient cerebral ischemia

* Vertebrobasilar insufficiency
* Vasovagal attacks
* Cardiac dysarhythmia

McAulay V, et al. Diabet Med. 2001;18:690-705.

Chronic Complication
of
Diabetes Mellitus
 Diabetes: A malignant vascular disorder

the most frequent cause

Stroke
of new cases of blindness 2-4 x risk for stroke
among adults aged and coronary heart
disease
20 to 74.
Diabetic
Retinopathy

Cardiovascular
disease

Diabetic
Myocardiac infarct
Nephropathy Most common cause
of death in diabetics
Accounts for ~40% of all new
cases of Diabetic
end-stage renal disease
(ESRD).
Neuropathy
Most common cause of
lower limb amputation

National Diabetes Information Clearinghouse. Diabetes Statistics–Complications of Diabetes.

http://www.niddk.nih.gov/health/diabetes/pubs/dmstats/dmstats.htm#comp.
 Insulin resistance, DM and CVD
Diabetes duration (years)
–10 0 10 20
IGT Type 2 diabetes mellitus CVD

Microvascular complications

Macrovascular complications

Insulin Atherosclerosis Advance atherosclerosis CHD

Resistance
On-going Retinopathy Amputations
 HDL
metabolic Nephropathy
 TG Blindness
 Blood Presure
derangement Neuropathy
Blood Glucose
Renal failure
Obesity Hypertension
 Inflammation will Stimulate Atherosclerosis

Monocyte
Vessel lumen
Circulating LDL

Endothelium
Adhesion
molecules
(VCAM-1, ICAM-1) Circulating LDL

Inflammatory mediators
(CRP, CD40/CD40L, Ox-LDL Intima
TNF-α, IL-1, IL-6)
Foam
cell
Macrophage
CD40L=CD40 ligand; TNF-α=tumor necrosis factor-alpha; IL=interleukin; VCAM=vascular cell adhesion molecule;
ICAM=intercellular adhesion molecule.
Cockerill GW et al. Arterioscler Thromb Vasc Biol. 1995;15:1987-1994; Andre P et al. Circulation. 2002;106:896-899; Libby
P. Circulation. 2001;104:365-372; Libby P et al. Circulation. 2002;105:1135-1143; Ross R. N Engl J Med. 1999;340:115-126.
 Risk factors for macroangiopathy diabetics

Hyperglycemia Risk Micro

Factors angiopathy

Dyslipidemia
exagerate/accelerate
Diabetes
Hypertension Risk Macro
Factors angiopathy

Hyperinsulinemia
UKPDS: Reducing HbA1c Associated with
Reduction in Risk of Fatal / Non-Fatal MI
Risk of fatal and non-fatal MI by HbA1c level
10
p<0.0001 n=3,642
# of events=496
Hazard ratio

1 14% decrease per 1%

reduction in HbA1c
0.5
5% 6% 7% 8% 9% 10%
Updated mean HbA1c concentration
MI, myocardial infarction. Reference category (HR 1.0) is HbA1c <6% with log linear scales. P value reflects
contribution of glycemia to multivariate model. Data adjusted for age at diagnosis of diabetes, sex, ethnic
group, smoking, presence of albuminuria, systolic blood pressure, HDL-C, and triglycerides.
Stratton IM et al. BMJ 2000;321(7258):405-12.
 Lessons from UKPDS: better control
means fewer complications
EVERY 1% REDUCED RISK*
reduction in HBA1C

Deaths from diabetes

Heart attacks

1% Microvascular complications

Peripheral vascular disorders

*p<0.0001
UKPDS 35, BMJ 2000; 321: 405-12
Early Diagnosis of Chronic
Complication
 Retinopathy
• It’s recommended to perform a routine-
retinal check up each year
• Methods:
– direct opthalmoscope
– indirect opthalmoscope with slit-lam bio-
microscope
– retinal photography
• Early referral
 Nephropathy

• Started with microalbuminuria, macroalbuminuria,

decrease in renal filtration rate which ends in renal
failure
• Early detection of microalbuminuria is required,
followed by referring to a more experienced
physician
• If GFR<30 it’s recommended to consult to the
nephrologists (kidney specialist)
Natural History of Renal Measures Impairment
in Diabetic Kidney Disease
 Screening for Diabetic Nephropathy

Test When Normal Range

Blood Each office visit <130/80 mm/Hg

Pressure1

Urinary Type 2: Annually <30 mg/day

Albumin1 beginning at diagnosis <20 g/min
Type 1: Annually, 5-years <30 g/mgcreatinine
post-diagnosis

American Diabetes Association: Nephropathy in Diabetes (Position Statement).

Diabetes Care 27 (Suppl.1): S79-S83, 2004
 Definitions of abnormalities in
albumin excretion

Category Spot collection 24-h collection Timed collection

(µg/mg creatinine) (mg/24 h) (µg/min)

Normal < 30 < 30 < 20

Microalbuminuria 30 – 299 30 – 299 20 – 199

Clinical albuminuria ≥ 300 ≥ 300 ≥ 300

Because of variabilityin urinary albumin excretion, two of three specimens collected within a 3-to-6 month
period should be abnormal before considering a patient to have crossed one of these diagnostic threshold.
Exercise within 24 h, infection, fever, congestive heart failure, marked hyperglycemia, marked
hypertension, pyuria, and hematuria may elevate urinary albumin excretion over baseline values.
NEUROPATI
DIABETIK
• Diffuse Neuropathy
1. Distal symmetrical sensorimotor polyneuropathy
2. Autonomic Neuropathy
Sudomotor neuropathy
Cardiovascular autonomic neuropathy
Gastrointestinal neuropathy
Genitourinary neuropathy
3. Symmetric proximal lower limb motor neuropathy

• Focal Neuropathy
1. Cranial neuropathy
2. Radiculopathy/ plexopathy
3. Entrapment neuropathy

Thomas, 1997
• Sensoric Neuropathy
• Autonomic Neuropathy
• Motoric Neuropathy

Thomas PK. International Textbook of Diabetes Mellitus, 2004

Diabetic Foot
Risk Factors

Peripheral
Neuropathy Arterial
Disease

Foot
Trauma
Deformity
 Pathophysiology of diabetic foot
Diabetes Mellitus

Neuropathy Trauma Vascular Disease

MOTOR SENSORY AUTONOMIC MICROVASCULAR MACROVASCULAR

Weakness
Atrophy Anhidrosis dry Structural Structural
skin capillary BM atherosclerosis
Deformity Loss of thickening
Abnormal Protective Occlusive
Stress Sensation narrowing
Functional AV
High Plantar
Shunting
Pressure Sympathetic
Ischemia
Callus Tone
Formation

Structural
Impaired Response
Deformity Ischemia
Cheiroarthropathy to Infection

Amputation Diabetic Foot Ulcer Amputation

Diabetic Foot Disorders: A Clinical Practice Guideline (2006 Revision)

Foot Care
• For all patients with diabetes, perform an annual comprehensive foot
examination to identify risk factors predictive of ulcers and amputations
• Inspection
• Assessment of foot pulses
• Test for loss of protective sensation: 10-g monofilament plus
testing any one of
• Vibration using 128-Hz tuning fork
• Pinprick sensation
• Ankle reflexes
• Vibration perception threshold

ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S47

Diabetic foot care
 Chronic complication’s
treatment and management
• Glycemic control
• Blood pressure control
• Lipid control
• Others : healthy lifestyle and diet scheduling
• Some distinctive methods:
– Retinopathy with photo coagulation
– Nephropathy with dialysis: hemodialysis or peritonial
– CHD with stent installment
– Peripheral vascular disease with metabolic and
infection control, foot rest
– Neuropathy symptomatis