2. Diabetes Mellitus
Diabetes is a serious chronic disease often accompanied
with many complications.
This disease is an important public health problem that
affected nearly all countries in the world.
The number of diabetic patients was nearly four times
compared to 108 million in 1980
Diabetes and its complications bring to decreasing quality of
life, substantial economic loss to people with diabetes and
their families, and national economies through direct medical
costs, loss time of work and wages
World Health Organization (WHO). Global Report on Diabetes. ISBN 978 92 4 156525 7
(NLM classification: WK 810), 2016
3. Top 10 Countries/Territories of number
Of people with diabetes (20-79 years), 2014
China
India
USA
Brazil
Indonesia
Mexico
Egypt
German
Turkey
Japan
96,2
66,8
25,7
11,6
9,1
9
7,5
7,2
7,2
7,2
Prevalence: 5,55% (adult pop.)
Diabetes In Indonesia.........
2035 Prediction
International Diabetes Federation. IDF Diabetes Atlas, 6th edition: 2013
International Diabetes Federation. IDF Diabetes Atlas, 6th edition: 2014 Update
http://www.idf.org/diabetesatlas
WHO: Global Report on Diabetes, 2016
7
5
Prevalence: 5,55% (adult pop.)
IDF : 14.1 mill in 2035
WHO: > 21.0 mill in 2030
6%/year
2-3 x
2030-2035
World Health Organization estimated higher increased of diabetic patients in Indonesia
from 8.5 million in 2000 to >21.0 million in 2030 (WHO, 2016).
IDF, 2015
4. DiabCare Indonesia 2012
Chronic Complication Profile
22,8%
14,5%
29,1%
12,4%
59,1%
32,4%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Any recorded
cardiovascular
complications
Any recorded renal
complications
Any recorded eye
complications
Any recorded foot
complications
Peripheral
neuropathy
Erectile
dysfunction
n = 1967
Peripheral neuropathy, erectile dysfunction, eye complications, and cardiovascular complications
were most common.
5. Acute Complication
Hyperglycemic Crisis
• Diabetic ketoacidosis (DKA) and hyperosmolar
hyperglycemic state (HHS) are the two most serious acute
metabolic complications of diabetes.
• Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic
state (HHS) are diabetes emergencies with overlapping
features.
• The mortality rate in patients with DKA is <5% in experienced
centers, whereas the mortality rate of patients with HHS still
remains high at ≈11%
Lorber D. Med Clin North Am 79:39 –52, 1995
Kreisberg RA. Crit Care Clin 3:817– 834, 1987
Wachtel TJ. J Gen Int Met 6:495–502, 1991
J. Goguen, J. Gilbert / Can J Diabetes 37:S72 – S76, 2013
6. Pathogenesis of DKA and HHS, stress, infection,
and/or insufficient insulin. ++ Accelerated pathway
Kitabchi AE.
International Text- book of Diabetes Mellitus. 3rd ed Eds. John Wiley & Sons, Chichester, U.K., 2004, p. 1101–1119
Hyperglycemia
Hyperosmolarity
Ketoacidosis
Absolute
Insulin
Deficiency
Relative Insulin
Deficiency
7. What are DKA and HHS?
• DKA and HHS are the most serious acute metabolic
complications of diabetes
Diabetic
Ketoacidosis
(DKA)
o Uncontrolled
hyperglycemia
o Metabolic acidosis
o↑ total body ketone
concentration
Hyperosmolar
Hyperglycemic State
(HHS)
o Severe hyperglycemia
o Hyperosmolality
o Dehydration
o Absence of significant
ketoacidosis
9. Metabolic
indicators
DKA
HHS
Mild DKA Moderate Severe
Serum glucose >250mg/dl >250mg/dl >250mg/dl >600mg/dl
Arterial pH 7.25-7.30 7.00 to <7.24 <7.00 >7.30
Urine ketone Positive Positive Positive Small
Serum ketone Positive Positive Positive Small
Serum
Osmolality†
Variable Variable Variable >320
mOsm/kg
Anion gap‡ >10 >12 >12 Variable
Mental status Alert Alert / drowsy Stupor / coma Stupor / coma
†Effective serum osmolality: 2 [measured Na (mEq/l)] + glucose (mg/dl)/18
‡Anion gap: (Na+) + [(Cl- + HCO3- (mEq/l)]
DKA: diabetic keto acidosis; HHS: hyperglycemic hyperosmoler state
Kitabchi AE, Umpierrez GE, Miles JM, et al, Diabetes Care 32:1335-1343, 2009
Laboratory diagnostic criteria for KAD
and HHS on presentation
10. Assessment of severity
The presence of one or more of the following may
indicate severe DKA and admission to High Care Unit,
insertion of a central line and immediate review
should be considered:
– Blood ketones over 6 mmol/L
– Bicarbonate level below 5 mmol/L
– Venous/arterial pH below 7.1
– Hypokalaemia on admission (under 3.5 mmol/L)
– GCS less than 12 or abnormal AVPU scale
– Oxygen saturation below 92% on air (assuming normal
baseline respiratory function)
– Systolic BP below 90 mmHg
– Pulse over 100 or below 60 bpm
– Anion gap >16 [Anion Gap = (Na+ + K+) – (Cl- + HCO3-) ]
11. POCT
• Point-of-care testing allows patient diagnoses in
the physician’s office, an ambulance, the home, the
field, or in the hospital
• Empowering clinicians to make decisions at the
“point-of-care” has the potential to significantly
impact health care delivery and to address the
challenges of health disparities
• Portable diagnostic and monitoring devices for
point-of-care testing is needed
NIH
12. Management Principles of
Hyperglycemic Crisis
Fluid replacement
Electrolyte correction
Acid-base balance control
Hyperglycemic control
Precipitating factors elimination
Avoid treatment complications
14. How should insulin be delivered?
American Association of Clinical Endocrinologists
and American Diabetes Association
Consensus statement on
inpatient glycemic control
Use of insulin infusion protocols with
demonstrated safety and efficacy, resulting in low
rates of occurrence of hypoglycemia, is highly
recommended.
Endocrine Practice Vol 15 No. 4 May/June 2009
16. Insulin dose and timing
• If significant ketonaemia is present (3β-hydroxy
butyrate is more than 1 mmol/L) this indicates
relative hypoinsulinaemia and insulin should be
started at time zero.
• If significant ketonaemia is not present (3β-hydroxy
butyrate is less than 1 mmol/L) do NOT start insulin.
Joint British Diabetes Societies Inpatient Care Group , 2012 (HHS)
17. Insulin dose and timing
• Fluid replacement alone with 0.9% sodium
chloride solution will result in falling blood
glucose and because most patients with HHS
are insulin sensitive there is a risk of lowering
the osmolality precipitously.
• Insulin treatment prior to adequate fluid
replacement may result in cardiovascular
collapse as water moves out of the
intravascular space, with a resulting decline in
intravascular volume (a consequence of insulin-
mediated glucose uptake and a diuresis from
urinary glucose excretion)
If significant ketonaemia is not present (3β-hydroxy butyrate
is less than 1 mmol/L) do NOT start insulin.
Joint British Diabetes Societies Inpatient Care Group , 2012 (HHS)
18. Dose of Insulin infusion
DKA
• It may be necessary to
estimate the weight of the
patient
• A fixed rate intra venous
insulin infusion calculated
on 0.1 units/kg BW/hour
infusion is recommended
• A fall of glucose at a rate
of up to 3 mmol/L (54
mg/dL ) per hour is ideal
HHS
• It may be necessary to
estimate the weight of the
patient
• A fixed rate intravenous
insulin infusion calculated
on 0.05 units/kg BW per
hour infusion is
recommended
• A fall of glucose at a rate of
up to 5 mmol/L (90 mg/dL )
per hour is ideal
Joint British Diabetes Societies Inpatient Care Group 2010 (KAD), 2012 (HHS)
19. Treatment goal
1. Replace fluid and electrolyte losses
2. Normalize the osmolality (HHS)
3. Normalize blood glucose
4. Normalize blood pH (DKA)
5. Other goals include prevention of:
1. Control precipitating factors
2. Arterial or venous thrombosis (HHS)
3. Other potential complications e.g. cerebral edema
4. Foot ulceration
NHS – Joint British Diabetes Societies Inpatient Care Group, 2012
20. Can rapid acting analog insulins be administered
intravenously?
68 Subjects with DKA
IV Insulin Glulisine (n=34)
0.1 U/kg/hr until BD <250
mg/dl then 0.05 u/kg/hr until
resolution of DKA
IV Regular insulin (n=34)
0.1 U/kg/hr until BD <250
mg/dl then 0.05 u/kg/hr until
resolution of DKA
Umpierrez GE et al. Diabetes Care. 2009;32:1164–1169
Transition to SQ
Total daily dose 0.6 U/kg/day
Given 1/2 as glargine OD, and
1/2 as glulisine before meals
Transition to SQ
Total daily dose 0.6 U/kg/day
Given 2/3 as NPH, and 1/3 as
regular insulin twice daily
Analogues
vs
Regular
Insulin
21. Umpierrez GE et al. Diabetes Care. 2009;32:1164–1169
Analogues
vs
Regular
Insulin
The rate of decline of blood glucose concentration; duration of treatment; amount of
insulin; and changes in acid base parameters were not significantly different between
patients treated with regular insulin (black circle) and glulisine (white circle).
22. Glargine-Glulisine was associated with a lower rate of
hypoglycemia than NPH / regular insulin
Subcutaneous insulin therapy
Glargine /
glulisine
NPH /
regular
Patients with BG <70 mg/dl (%) 5 (15) 14 (41) *
Episodes of BG <70 mg/dl 8 26 †
Patients with BG <40 mg/dl, n (%) 1 (3) 2 (6)
Episodes of BG <40 mg/dl 1 2
Umpierrez GE et al. Diabetes Care. 2009;32:1164–1169
* P=0.03, † P=0.019
Analogues
vs
Regular
Insulin
A transition to SQ glargine and glulisine after resolution of DKA
resulted in similar glycemic control but in a lower rate of
hypoglycemia than with NPH and regular insulin
23. Glulisine, lispro and RHI have similar effects on suppression of
endogenous glucose production, Glucose uptake, Free fatty
acid, glycerol and lactate levels, providing evidence for similar
end-organ metabolic effects.
Horvath K et al. Diabetes, Obesity and Metabolism, 10, 2008, 484–491
Analogues
vs
Regular
insulin
24. Conversion to subcutaneous insulin
• Convert back to an appropriate subcutaneous
regime when biochemically stable (blood ketones
less than 0.3, pH over 7.3)
• and the patient is ready and able to eat.
1. Restarting subcutaneous insulin for patients
already established on insulin
2. Calculating subcutaneous insulin dose in
insulin-naïve patients
25. Restarting subcutaneous insulin for patients
already established on insulin
• Previous regimen should generally be re-started
• With all regimens the intravenous insulin infusion should
not be discontinued for at least 30 to 60 minutes after the
administration of the subcutaneous dose
• The prandial insulin should be injected with the meal and
the intravenous insulin and fluids discontinued 30 minutes
later.
• If the patient was previously on a basal insulin (long acting
insulin analogue such as Glargine ), this should have been
continued during intravenous insulin infusion delivery and
thus the only action should be to restart their normal short
acting insulin at the next meal.
26. Calculating subcutaneous insulin dose in
insulin-naïve patients
• The Total Daily Dose can be calculated by multiplying the
patient's weight (in kg) by 0.5 to 0.75 units.
• Use 0.75 units/kg for those thought to be more insulin
resistant i.e. teens, obese.
• Give 50% of total dose with the evening meal in the form of
long acting insulin (basal insulin)
• and divide 50% remaining dose in the form of rapid/short-
acting insulin (prandial insulin) divided equally between pre-
breakfast, pre-lunch and pre-evening meal.
27. Precipitating factors
• INFECTION
• Discontinuation of or inadequate insulin therapy
• Pancreatitis
• Myocardial infarction
• Cerebrovascular accident
• Drugs (corticosteroids, thiazides,
sympathomimetic agents, antipsychotic drugs)
• Eating disorders
• Hyperthyroidism
• Compromised access to water
Kitabchi AE, Umpierrez GE et al. Diabetes Care, Volume 32, Number 7, July 2009
Fowler M. Clinical Diabetes, Volume 27, Number 1, 2009
28. Prevention of recurrences
• Hyperglycemic emergencies are usually can be prevented
by better access to medical care, proper education, and
effective communication with a health care provider during
an intercurrent illness
• Patients should be educated on how to manage their
diabetes during stress or infection; this “sick-day
management”:
– Never omitting insulin, preventing dehydration and hypoglycemia,
monitoring blood glucose frequently, testing for ketosis,
administering supplemental rapid-acting insulin doses as needed,
treating underlying triggers early and aggressively
– Having frequent contact with their diabetes health care team to
evaluate their acute condition (Wilson JF, 2010).
– Patient education and 24-hour access to care are cornerstones of
preventive therapy (Toeller M, 1999).
Wilson JF. Ann Intern Med 152: C1-14, 2010
Toeller M, Buyken aE, Heitkamp g, et al. Horm Metab Res 31: 680-685, 1999
29. Summary
• Diabetic ketoacidosis (DKA) and hyperosmolar
hyperglycemic state (HHS) are the two most serious acute
metabolic complications of diabetes.
• First step: Intravenous access and initial investigations
(ABC)
• Restoration of circulating volume
• Analogue insulins (e.g. glulisine) may be used for IV infusion
• Nomalize blood glucose by IV-insulin infusion.
• When patient is able to eat, initiate SC multidose insulin
regimen. With all regimens the intravenous insulin infusion
should not be discontinued for at least 30 to 60 minutes
after the administration of the subcutaneous dose
• Control precipitating factors
• Prevent the recurrent by patients/family education
