Hyperglycemic Crises and Hypoglycemia

ACUTE COMPLICATION OF
DIABETES MELLITUS
RULLI ROSANDI
Bag. ILMU PENYAKIT DALAM RS.Dr.SAIFUL ANWAR
FAK.KEDOKTERAN UNIV.BRAWIJAYA
MALANG

Learning Objective
To be able to define, recognize and

discriminate
between
diabetic
ketoacidosis and the hyperosmolarhyperglycemic state also hypoglycemia
To
understand
the
basic
pathophysiology of each syndrome
To understand their general treatment
strategies
including
potential
complications from treatment

The Homeostasis

What is DKA and HHS

Two of the most serious acute complications

of diabetes
Diabetic Ketoacidosis : Hyperglycemia,
ketosis,acidemia
Mortality rates :
< 1%

(adult subjects)

>5%
(elderly and in pts with concomitant life
threatening illnesses)

Hyperosmolar Hyperglycemic State :

Hyperosmolarity, Hyperglycemia, dehydration

Mortality rate 5-20 %

Precipitating factors
Infection
Management errors
Medical, surgical or emotional

stress
Drugs
Other factors

Overlapping between

Pathophysiology

Diagnosis
History and physical

examination
Laboratory findings
Differential diagnosis

History and Physical

exam
History of polyuria, polydipsia, weight
dehydration,
change.

weakness,

and

mental

loss,
status

Physical findings : poor skin turgor, kussmaul

respiration (DKA), tachycardia, and hypotension,

mental status change (full alertness to profound
lethargy or coma).
Focal neurologic signs and seizures HHS
Nausea, vomiting, diffuse abdominal pain are

frequent in pts with DKS (>50%) but uncommon

in HHS

Laboratory findings
plasma glucose, serum and urine ketones,

electrolytes (with calculated anion gap),

osmolality, arterial blood gases
blood urea nitrogen/creatinine
urinalysis
complete blood count with differential
electrocardiogram
bacterial cultures of urine, blood, and throat,
etc.
chest X-ray

Diagnostic Criteria

DIABETES CARE, VOLUME 32, NUMBER 7, JULY

Differential Diagnosis

Treatment

Dont Forget to
treat
Precipitating
Factor !

Complications

Aspiration
ARDS
Hypoglycemia
Hypokalemia
Cerebral edema

The major limiting factor to

achieving
intensive glycaemic control for
people with type 2 diabetes
Briscoe VJ, et al. Clin Diab 2006;24:115-121.

How should hypoglycemia be

defined?

Whipples triad:

symptoms consistent with hypoglycemia

a low plasma glucose concentration
relief of those symptoms when the

plasma glucose concentration is raised.

It is not only the nadir glucose

concentration and the duration of

hypoglycemia that may be
inherently dangerous

Hypoglycaemia in type 2
diabetes

Hypoglycaemia symptoms are common in

type 2 diabetes (38% of patients)
Associated with:
Reduced quality of life
Reduced treatment satisfaction
Reduced therapy adherence
More common at HbA1c < 7%
Diabetes, Obesity and Metabolism 2008 Jun;10 Suppl
1:25-32.

Risk factors for

hypoglycaemia
Use of insulin and sulfonylureas

Older people
Irregular eating habits
Exercise
Have lower HbA1c
Periods of fasting e.g. Ramadan
Prior hypoglycemia
Hypoglycemia unawareness
Alcohol

Fear of hypoglycaemia is a
1
burden
for patients
Fear of hypoglycaemia:
Is an additional psychological burden on patients
May limit the aggressiveness of drug therapy
Can decrease adherence to diet
May reduce compliance with therapy

Influences:
Patient health outcomes2
Post-episode lifestyle changes2
Other family members-disrupts domestic life 3

A severe hypoglycaemic event is associated

with a greater fear of hypo in the future 4

Blood glucose awareness training can reduce
levels of fear5
1. Can J Diab. 2005;29:186-192; J Diab Complic 2004;18:60-68;

2. Leiter LA, et al. Can J Diab. 2005;29:186-192; 3. Frier BM et al. IJCP Supplement. 2001;123:3037;

Clinical consequences of
hypoglycaemia
Hospital admissions:
In a prospective study1 of well-controlled

elderly T2D patients, 25% of hospital

admissions for diabetes were for severe
hypos

Increased mortality:
9% in a study2 of severe SU-associated

hypoglycaemia

Road accidents caused by hypos3:

1. Diab Nutr Metab 2004;17(1):23-26.

2. Horm Metab Res Suppl 1985;15:105-111.
3. BMJ 2006;332:812.

45 serious events per month

Oral antidiabetic agents

and hypoglycaemic risk in
type
2 diabetes
Agents with
increased hypoglycaemic potential
Those which enhance insulin secretion/-cell function in non-

glucose dependent manner

Sulfonylureas
Short-acting secretagogues (rapaglinide/nateglinide)

Agents with minimal/low hypoglycaemic risk

Improve insulin resistance
Biguanide-metformin
Thiazolidinediones (pioglitazone/rosiglitazone)

Incretin-based therapies-enhance insulin secretion in glucose-

dependent manner

Incretin enhancers: DPP-IV inhibitors (sitagliptin, vildagliptin,

saxagliptin, alogliptin)

Reduce glucose absorption

Alpha-glucosidase inhibitors (acarbose, voglibose)

Injectable agents and

hypoglycaemic risk in type 2
diabetes
Agents with high hypoglycaemic potential

Human insulin preparations

Regular insulin
NPH insulin
Pre-mixed formulations

Agents with moderate hypoglycaemic

potential

Insulin analogue preparations

Rapid-acting aspart, glulisine, lispro
Long-acting glargine, determir
Amylin analogue pramlintide

Agents with minimal/low hypoglycaemic

potential

Glucagon-like peptide-1 analogue/receptor agonists

Exenatide

Symptoms

Principal metabolic effects of

counter-regulation in
response to hypoglycaemia

Cryer, J Clin Invest 116:147014

Glucose thresholds during

hypoglycaemia

Amiel, Diabetologia, 1998,41

Treatment
If the patient is able to maintain an

airway give oral glucose ideally

in liquid form, e.g. a proprietary
glucose drink.
If patients are unable to take
anything orally then give either
i.m. glucagon or i.v. dextrose.

Treatment

Glucagon.
Give 0.51.0 mg i.m.;
Give i.v. dextrose if there has been no

response after 10 min.

Intravenous dextrose.
Give as 2030 mL of 50 per cent dextrose

into a large forearm vein

Start an i.v. infusion of 10 per cent dextrose
Consider the precipitating cause. If one can be
identified, take steps to avoid further
episodes, e.g.by reducing insulin dose

Treatment
Capillary blood
sample

Established
diagnosis
Oral glucose (liquid)
120 cc

Evaluation

Maintainance
180 200 mg%
10% Dextrose
Dextamethaso
ne

Intramuscular
glucagon 0.5 1 mg
Repeat after 10

Intravenous glucose
20 30 ml 50%
dextrose

Conclusions
Hypoglycaemia is the major factor limiting

intensive control in T2D

Can cause severe morbidity and mortality
and lower health-related quality of life
Patient awareness of the risk of
hypoglycaemia with some antidiabetic
therapies is low
Occurs in a significant proportion of patients
on OADs
Insulin therapy is associated with a
significant incidence of hypoglycaemia