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Ueda 2016 6-diabetes in special populations - mesbah kamel
1. Diabetes in Special Populations
UEDA Diabetes Mini-Course
Aswan Feb. 2016
INDIVIDUALIZE DIABETES THERAPY
TREATING THE PATIENT NOT THE DISEASE
2.
3. Diabetes in Special Populations
Agenda
1. Diabetes in Childhood and Adolescence + DKA
2. Diabetes in Pregnancy
3. Diabetes in Older People
4. Diabetes in Ramadan
5. Diabetes in Renal Insufficiency
6. Diabetes in Hepatic Insufficiency
4. Diabetes in Childhood and Adolescence
in Under-Resourced Countries
UEDA Diabetes Mini-Course
Aswan Feb. 2016
5.
6. Type1 Diabetes in Childhood and
Adolescence
Most diabetes in children is type 1 diabetes,
resulting in lifelong insulin dependency. Type 2
diabetes can also occur in children (mainly in
adolescents). Other rarer types can also occur, even
in neonates.
Onset can be at any age after the neonatal period,
but it is most common in childhood and
adolescence.
Clinical presentation can vary from non-urgent
presentation to severe presentation with
dehydration, shock and DKA.
7.
8. Newly diagnosed children should be transferred to a
centre that has expertise in paediatric diabetes, if
this is possible.
Treatment of diabetes consists of
lifelong insulin dependency with multiple injections per
day
a healthy eating plan
regular physical activity.
Type1 Diabetes in Childhood and
Adolescence
9. It is increasingly being seen in older children, particularly
adolescents who are overweight and inactive, have a
family history of type 2 diabetes or in those who are of
particular ethnic backgrounds where type 2 diabetes in
adults is more prevalent.
• People with type 2 diabetes produce insulin but the
insulin produced does not work effectively (“insulin
resistance”).
• Type 2 diabetes often responds initially to a healthy
eating plan, appropriate exercise and weight reduction.
• However, metformin is frequently needed (+/- an
insulin sensitizer), and later insulin may be required.
Type2 Diabetes in Childhood and
Adolescence
10. Some forms of diabetes do not neatly fit type 1 or type 2
“atypical diabetes”
Neonatal Diabetes (presenting in the first six months
of life) results from the inheritance of a mutation or
mutations in a single gene (monogenic diabetes). If
this is suspected, genetic testing should be undertaken
because it may influence management.
Monogenic diabetes outside the neonatal period. This
was previously known as MODY – Maturity Onset
Diabetes in the Young. These cases generally have a
strong family history of diabetes.
Diabetes associated with syndromes such as Down
Syndrome, Prader-Willi Syndrome
Other Types of Diabetes in Childhood and
Adolescence
11. Goals of T1DM Management
• Utilize intensive therapy aimed at near-normal BG and
A1C levels
• Prevent diabetic ketoacidosis and severe hypoglycemia
• Achieve the highest quality of life compatible with the
daily demands of diabetes management
• In children, achieve normal growth and physical
development and psychological maturation
• Establish realistic goals adapted to each individual’s
circumstances
12. Treatment goals: Juveniles
(ADA Guidelines)
Plasma blood glucose goal range
(mg/dL)
Before Meals
Bedtime/Overnight
HbA1c Rationale
Toddlers and
Preschoolers
<6 years
100-180 110-200
<8.5%
(>7.5%)
High risk and
vulnerable to
hypoglycemia
School Age
6 to12 years
90-180 100-180 <8%
Risk of
hypoglycemia and
relatively low risk
of complication
before puberty
Adolescents
and Young
Adults
13 to19 years
90-130 90-150 <7.5%
Risk of
hypoglycemia.
Developmental
and psychological
issues
Plasma blood glucose and HbA1c goals by age group
UKDBT00743 – February 2011
Copyright 2005 American Diabetes Association from 21. Diabetes Care, Vol. 28, 2005; 186-212. Reprinted with permission
13. INSULIN TREATMENT
All children with type 1 diabetes and some children with
other forms of diabetes require insulin.
The aim is to replace insulin
as physiologically as possible so that blood glucose levels are within
the target range
avoiding hypoglycaemia
Avoiding sustained hyperglycaemia.
Prolonged underinsulinisation results in chronic
hyperglycaemia which increases the risk of stunted growth,
diabetes complications, including diabetic ketoacidosis.
14. Physiologic Multiple Injection Regimens:
The Basal-Bolus Insulin Concept
Basal insulin
Controls glucose production between meals and overnight
Near-constant levels
Usually ~50% of daily needs
Bolus insulin (mealtime or prandial):
Limits hyperglycemia after meals
Immediate rise and sharp peak at 1 hour post-meal
10% to 20% of total daily insulin requirement at each meal
For ideal insulin replacement therapy, each component should
come from a different insulin with a specific profile or via an
insulin pump (with 1 insulin)
Handelsman Y, et al. Endocr Pract. 2011;17(suppl 2):1-53.
15. 4:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
8:0012:008:00
Glargine or
detemir
Plasmainsulin
Basal/Bolus Treatment Program With
Rapid-Acting and Long-Acting Analogs
Bed
Rapid
(lispro,
aspart,
glulisine)
Rapid
(lispro,
aspart,
glulisine)
Rapid
(lispro,
aspart,
glulisine)
21. Management of Acidosis with Insulin
Insulin should
be maintained
until the anion
gap normalizes
Insulin used to
treat the
acidosis, not
the glucose!
22. Identify and Treat the Precipitating Factor
• Insulin omission – MOST COMMON CAUSE of DKA
• New diagnosis of diabetes
• Infection / Sepsis
• Myocardial infarction
– Small rise in troponin may occur without overt ischemia
– ECG changes may reflect hyperkalemia
• Thyrotoxicosis
• Drugs
23. PREVENTION of DKA / HHS
• Type 1 diabetes
– Education around sick day management
– Continuation of insulin even when not eating
– Frequent monitoring when ill
• Type 2 diabetes
– Education around sick day management
– Frequent monitoring when ill
24. Gestational Diabetes
One of the most challenging aspects of
diabetes practice
Seemingly easy: Practically difficult
Needs a lot of commitment on part of
doctor, patient and family
Success can be achieved if we try
together
25. Definition
Glucose intolerance with onset or first
recognition during pregnancy
Characterized by β-cell function that is
unable to meet the body’s insulin needs
Buchanan, Wiang, Kjos, Watanabe 2007
27. Risk factors for GDM
High risk
Obesity
Age >25ys
Diabetes in 1st degree relative
Previous history of GDM or
glucose intolerance
Previous infant with macrosomia
> 3.5 kg
High risk ethnic group; South
Asian, East Asian, Indigenous
American or Australian, Hispanic
PCOS
Low risk
Age less than 25 years
No previous poor pregnancy
outcomes
No diabetes in 1st degree
relatives
Normal prepregnancy
weight and weight gain
during pregnancy
No history of abnormal
glucose tolerance
Perkins, Dunn, Jagastia, 2007
29. Why diagnose and treat GDM?
No increase in congenital anomalies
Short term risks for the baby
Macrosomia
Neonatal hypoglycemia
Jaundice
Preterm birth
Birth injury
Hypocalcemia/ hypomagnesimia
Respiratory distress syndrome
Long term risks for the baby
Obesity
Type 2 diabetes
30. Recommendations:
Detection and Diagnosis of GDM (1)
Screen for undiagnosed type 2 diabetes
at the first prenatal visit in those with
risk factors, using standard diagnostic criteria
Screen for GDM at 24–28 weeks of gestation in
pregnant women not previously known to have
diabetes
Screen women with GDM for persistent diabetes
at 6–12 weeks postpartum, using OGTT,
nonpregnancy diagnostic criteria
ADA. III. Detection and Diagnosis of GDM. Diabetes Care 2014;37(suppl 1):S18
31. GDM Diagnosis
2 Approaches for Diagnosing Gestational Diabetes Mellitus (GDM)
AACE- and ADA-
recommended
1-step 75-g 2-hour oral glucose tolerance test (OGTT) 1,2
or
ACOG- recommended 2 steps: a 50-g 1-hour glucose challenge test (GCT), followed by
a 100-g 3-hour OGTT (if necessary)3
GDM Diagnostic Criteria for OGTT Testing
75-g 2-hour† 100-g 3-hour*
Fasting plasma glucose
(FPG)
≥92 mg/dL (5.1 mmol/L)2 ≥95 mg/dL (5.3 mmol/L)2
1-hour post-challenge
glucose
≥180 mg/dL (10.0 mmol/L)2 ≥180 mg/dL (10.0 mmol/L)2
2-hour post-challenge
glucose
≥153 mg/dL (8.5 mmol/L2 ≥155 mg/dL (8.6 mmol/L)2
3-hour post-challenge
glucose
≥140 mg/dL (7.8 mmol/L)2
†A positive diagnosis requires that test results satisfy any one of these criteria
*A positive diagnosis requires that ≥2 thresholds are met or exceeded
.1AACE. Endocr Pract. 2011;17(2):1-53.
.2ADA. Diabetes Care. 2013;36(suppl 1):11-66.
.3Committee on Obstetric Practice. ACOG. 2011;504:1-3.
32. Diet
Exercise
Glucose monitoring
Insulin and other medications
Management
33. Dietary Modifications
• Decrease carbohydrate content 40%
• Frequent small feedings
• Small breakfast meals
• Bedtime snacks
• No > 10 hours overnight fast
• NO JUICE
• Adequate calorie intake
34. Exercise improved cardiorespiratory
fitness
Physical activity reduced risk of GDM
Resistance exercise diminished the need
for insulin therapy in overweight
women with GDM
Exercise
37. Need Optimal Glycemic Control in
Pregnancy for Pre-existing Diabetes
• Individualized insulin therapy with
close monitoring
– Bolus insulin: May use aspart or lispro
instead of regular insulin
– Basal insulin: May use detemir or glargine
as alternative to NPH
• Encourage patients to SMBG pre- and
postprandially
Target glucose values
Fasting PG <5.3 mmol/L
1h postprandial PG <7.8 mmol/L
2h postprandial PG <6.7 mmol/L
38. Diabetes in Pregnancy: Hypoglycemia
Pathophysiology
May be related
to fetal
absorption of
glucose from
the maternal
bloodstream
via the
placenta,
particularly
during periods
of maternal
fasting
Risk Factors
History of severe
hypoglycemia
before pregnancy
Impaired
hypoglycemia
awareness
Longer duration of
diabetes
A1C ≤6.5% at first
pregnancy visit
High daily insulin
dosage1
Causes of
Iatrogenic
Hypoglycemia
Administration of
too much insulin or
other anti-
hyperglycemic
medication
Skipping a meal
Exercising more
than usual2,3
Clinical
Consequences
Signs of
hypoglycemia:
anxiety, confusion,
dizziness, headache,
hunger, nausea,
palpitations,
sweating, tremors,
warmth, weakness4
Risks of
hypoglycemia:
coma, traffic
accidents, death1,5
Severe
hypoglycemia can
lead to maternal
seizures or hypoxia
Management
Inform patients of
increased risk of
severe hypoglycemia
during early
pregnancy4
Educate patients
on hypoglycemia
prevention:
Frequent SMBG
Regular meal
timing
Accurate
medication
administration
Careful
management of
exercise
programs4
1. Mathiesen ER, et al. Endocrinol Metab Clin N Am. 2011;40:727-738. 2. Inturrisi M, et al. Endocrinol Metab Clin N Am. 2011;40:703-26.
3. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80. 4. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.
5. Hod M. Jovanovic L. Int J Clin Pract. 2010;64(166):47-52.
39. Diabetes in Pregnancy: Hypoglycemia
Treatment
Suspected or
confirmed
hypoglycemia
(blood glucose
<60 mg/dL via
SMBG)
Severe
hypoglycemia
(patient cannot
swallow)
1 mg glucagon
injected
subcutaneously;
request emergency
assistance1
Mild to
moderate
hypoglycemia
(patient can
swallow)
Preferred treatment:
15-20 g glucose1,2
Alternative
treatments include
fast-acting
carbohydrates
(eg, 8 oz nonfat milk,
4 oz juice)1
15-minutes:
recheck
SMBG
Hypoglycemia
resolved
(normal
SMBG
confirmed)
Snack or
meal should
be consumed
to prevent
recurrence1
Hypoglycemia
not resolved
Repeat
treatment
1. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80. 2. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.
42. Objectives
• Establish 7 GDM care and control centres in
7uuniversity hospitals .
• The existing government healthcare centres will
be involved and strengthened to perform GDM
screening and care.
• Reduction of the incidence of future diabetes of
women that diagnosed with GDM and her baby .
• Training of health care providers.
• NGO's women self help groups will be involved
for their effective participation.
• Raising the public awareness.
43. Screening and care
Assiut
GDM care and
control center
Al-Fayoum
GDM care center
Beni-Suif
GDM care center
El-Menia
GDM care
center
Sohag-Nagh
Hammady
GDM care center
44. Diabetes in Pregnancy:
Labor and Delivery
• Counsel women on diabetes management during labor and
delivery1
• During the 4-6 hours prior to delivery, there is increased risk of
transient neonatal hypoglycemia1
• Labor and delivery in women with insulin-dependent type 1
diabetes should be managed by an endocrinologist or a diabetes
specialist1
• Blood glucose levels should be monitored closely during labor to
determine patient’s insulin requirements
– Most women with gestational diabetes mellitus who are receiving insulin
therapy will not require insulin once labor begins1
1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.
45. Diabetes in Pregnancy: Postpartum and
Lactation
• Metformin and glyburide are secreted into breast milk and are
therefore contraindicated during lactation1
• Breastfeeding plus insulin therapy may lead to severe
hypoglycemia1
– Greatest risk is in women with T1DM
– Preventive measures are: reduce basal insulin dosage and/or
carbohydrate intake prior to breastfeeding
• Bovine-based infant formulas are linked to increased risk of T1DM1
– Avoid in offspring of women with a genetic predisposition for diabetes
– Soy-based products are a potential substitute
1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.
48. 2013
≥60…
≤60…
International Diabetes Federation. Managing Older People with Type 2 Diabetes Global Guidelines.
http://www.idf.org/sites/default/files/IDF%20Guideline%20for%20Older%20People.pdf accessed 15-12-2013
2050
≥60…
≤60…
These changes present significant challenges to welfare, pension, and healthcare systems in
both developing and developed nations
49. Factors specific to the management of
diabetes in the elderly:
• Screening and diagnosis .
• Specific complications of type 2 diabetes
in the elderly:
–Risk of hypoglycaemic episodes
–Functional disability
–Depression, cognitive impairment and
other geriatric syndromes, such as
fractures and falls.
50. Managing type 2 diabetes in the elderly
Special considerations
–Clinicians who manage older people with
diabetes require special skills if they wish to
provide high-quality care
–Their approach is influenced by a multitude of
factors, such as the higher frequency of medical
comorbidities, frailty and socioeconomic issues
–Comprehensive geriatric assessment is a
potentially important tool in ensuring that
patients with diabetes receive a multi-
professional assessment of their functional
status and unmet needs. Sinclair A. Diabetes Spectrum. 2006;19(4):229-33.
51. Management goals in the elderly
– The overall goals of diabetes management in older
adults are similar to those in younger adults and
include management of both hyperglycaemia and risk
factors1
– However, in frail, elderly patients with diabetes,
avoidance of hypoglycaemia, hypotension, and drug
interactions due to poly-pharmacy are of even greater
concern than in younger patients with diabetes1,2.
– In addition, management of coexisting medical
conditions is important because it influences their
ability to perform self-management2
1.Brown AF, 2003; 51(5):S265-286. 2.Sinclair A. Diabetes Spectrum. 2006;19(4):229-33.
52. Treatment priority of the elderly: prevention
of hypoglycaemia
– The elderly patient with diabetes is often a frail
patient1
– Elderly people with diabetes are also at higher risk for
hypoglycaemia and hypoglycaemia unawareness1,2
– Hypoglycaemia is associated with many adverse
consequences1
The available data suggest that the risks of tight
glycaemic control (and the greatest risk is
hypoglycaemia) exceed the benefits in many elderly
patients1
1. Sinclair A. Diabetes Spectrum.
2006;19(4):229-33.
2. ADA Diabetes Care;2012:35(1):S11-S63
53. EASD/ADA recommendations for managing
hyperglycaemia in the elderly (2012)
– Glycaemic targets for elderly with long-standing or more
complicated disease should be less ambitious than for
younger, healthier individuals
– If lower targets cannot be achieved with simple interventions,
an HbA1c of <7.5–8.0% may be acceptable, transitioning
upward as age increases and capacity for self-care, cognitive,
psychological and economic status, and support systems
decline
– In the aged, the choice of anti-hyperglycaemic agent should
focus on drug safety, especially protecting against
hypoglycaemia, heart failure, renal dysfunction, bone
fractures, and drug–drug interactions. Strategies specifically
minimising the risk of low blood glucose may be preferred
Inzucchi SE, et al. Diabetes Care. 2012;55(56):1577-96.
54. Glucose-lowering algorithm for frail patients with type 2
diabetes mellitus
Sinclair AJ, et al. Diabetes Metab. 2011;37 Suppl 3:S27-38.
3−6 months dietary
and lifestyle advice
Not achieving agreed
glucose targets
Metformin
Metformin + DPP-IV
inhibitor
Metformin + insulin
Metformin contraindicated in
renal/hepatic dysfunction,
respiratory/heart failure,
anorexia, gastrointestinal
disease
Alternative treatments:
DPP-IV inhibitors, or lower risk
sulphonylureas (SU)
Glinides
Further weight loss with a
GLP-1 agonist may have
adverse consequences in a
frail patient
Alternative treatments:
Metformin + lower-risk SU
Metformin + GLP-1 agonist
Frailty associated with
increased hypoglycaemia risk:
caution when using insulin or
sulphonylurea therapy
Alternative
treatments:
Low risk SU +
insulin
Failure to achieve glucose targets
Failure to achieve glucose targets
Frailty criteria:
Care home residency
Significant cognitive decline
Major lower limb mobility
disorder
History of disabling stroke
Recommended glucose
targets:
Fasting glucose range =
7.6−9.0 mmol/l
HbA1c range = 7.6−8.5%
56. Diabetes in the Elderly Checklist
ASSESS for level of functional dependency (frailty)
INDIVIDUALIZE glycemic targets based on the
above (A1C ≤8.5% for frail elderly) but if otherwise
healthy, use the same targets as younger people.
AVOID hypoglycemia in cognitive impairment.
SELECT antihyperglycemic therapy carefully:
Caution with sulfonylureas or thiazolidinediones
Basal analogues instead of NPH or human 30/70
insulin
Premixed insulins instead of mixing insulins separately
GIVE regular diets instead of “diabetic diets” or
nutritional formulas in nursing homes.
2015
Canadian D A Guidelines 2015
58. Fasting Diabetics in figures
• Islam has 1.57 billion adherent according to 2009
demographic studies.
• According to high global prevalence studies among adults
age 20-79 years 6.6% type 2 diabetes.
• According to EPIDIAR Study .
( 12243 patients , 13 Islamic countries ):
43% of patients of type 1 fast during Ramadan.
79% of patients of type 2 fast during Ramadan.
• These figures lead to an estimate of more than 50
million people with diabetes fast during Ramadan.
Al Arouj M, Assaad-Khalil S, Buse J, Fahdil I, Fahmy M, Hafez S, Hassanein M, Ibrahim M, Kendall D, Kishawi S,Al-Madini A, Nakhi A, Tayeb K, Thomas A. Recommendations for the Management
of Diabetes During Ramadan. Diabetes Care. August 2010;33:8
59. Diabetes & Ramadan
Fasting is a spiritual issue for which patients make their own
decision after receiving appropriate advice from religious
teachings and from health care providers.
Frequent monitoring of glycemia: is essential multiple times
daily.
Structured education for patients fasting Ramadan is very
important not only during Ramadan but also throughout the
year for better management of diabetes.
This structured education should also extend to those who do
not wish to fast because they often are exposed to the risk of
hypo- and hyperglycemia during Ramadan as a reflection of
social habits encountered during the month.
60. Fasting in Ramadan
Safe Fasting in Ramadan depends on multiple
factors.
These factors classify Diabetics to 4 categories :-
Very High Risk
High Risk
Moderate Risk
Low Risk
The Decision to fasting or not is based on this
categorization.
61. Very high risk
Severe hypoglycemia within the last 3 months prior to Ramadan
Patient with a history of recurrent hypoglycemia
Patients with hypoglycemia unawareness
Patients with sustained poor glycemic control
Ketoacidosis within the last 3 months prior to Ramadan
Type 1 diabetes
Acute illness
Hyperosmolar hyperglycemic coma within the previous 3
months
Patients who perform intense physical labor
Pregnancy
Patients on chronic dialysis
62. High Risk
Patients with moderate hyperglycemia (average
blood glucose between 150 and 300 mg/dl, A1C 7.5–
9.0%)
Patients with renal insufficiency
Patients with advanced macrovascular complications
People living alone that are treated with insulin or
sulfonylureas
Patients living alone
Patients with comorbid conditions that present
additional risk factors
Old age with ill health
63. Moderate risk
Well-controlled patients treated with short-
acting insulin secretagogues such as repaglinide
or nateglinide
Well-controlled patients treated with diet alone,
metformin, or a thiazolidinedione who are
otherwise healthy
Low risk
64. Major risks associated with fasting
in patients with Diabetes
Al Arouj M, Assaad-Khalil S, Buse J, Fahdil I, Fahmy M, Hafez S, Hassanein M, Ibrahim M, Kendall D, Kishawi S,Al-
Madini A, Nakhi A, Tayeb K, Thomas A. Recommendations for the Management of Diabetes During Ramadan.
Diabetes Care. August 2010;33:8
Hypoglycemia
Hyperglycemia
Diabetic Ketoacidosis
Dehydration and thrombosis
65. •The ADA advise that all patients wishing to fast should undertake a
medical assessment with their HCP at least one month before
Ramadan 1
•During Ramadan it is important for the patient to monitor their
condition, specifically looking at 1:
• Patients should be encouraged to schedule a follow-up consultation after Ramadan to discuss any necessary readjustment of
medicine
Treatment
Certain diabetes
medications may
increase risk of
hypoglycaemia
while fasting,
therefore the
treatment regimen
may need to be
altered to ensure
blood sugar levels
are effectively
managed during
Ramadan
Monitoring
Blood sugar
levels should
be monitored
frequently
during the day
FBS 9H after
Sohour
2 hours before
breakfast
2 hours after
breakfast
Whenever Hypo
glycemic
symptoms
Diet
Diet during
Ramadan
should be
healthy and
balanced and
high saturated
fat foods such
as ghee,
sambosas and
pakoras should
be avoided
Exercise
Patients should
try to maintain
usual physical
activity when
fasting, however
it is best to avoid
rigorous
exercise. Regular
Tarawih
(obligatory
prayers) should
be considered as
part of daily
exercise regime
Breaking the fast
Patients should
break their fast
immediately and
seek advice from
their HCP if they
experience any of
the following
symptoms
Hypoglycaemia –
blood glucose less
than 60 mg/dl (3.3
mmol/l)
Hyperglycaemia –
blood glucose
higher than
300mg/dl (16.7
mmol/l)
Al Arouj, et al. Recommendations for the Management of Diabetes During Ramadan. Diabetes Care. 2010;33:8.Date of preparation: January 2012
EX-2012-01-16T15:01:04
16
66. SU are unsuitable and may be used with caution
• It has been suggested that this group of drugs is
unsuitable for use during fasting because of the
inherent risk of hypoglycemia.
• Additional studies on the use of sulfonylureas
in patients who fast during Ramadan are
needed before strong recommendations on
their utility can be made.
These agents may be used in Ramadan, though
with caution.
Al Arouj M, Assaad-Khalil S, Buse J, Fahdil I, Fahmy M, Hafez S, Hassanein M, Ibrahim M, Kendall D, Kishawi S,Al-Madini A, Nakhi A, Tayeb K, Thomas A. R
ecommendations for the Management of Diabetes During Ramadan. Diabetes Care. August 2010;33:8
68. Management of type2 DM in Hepatic
patients
• Hepatogenous diabetes has particular clinical characteristics:
• (1) unlike the hereditary type 2 DM, it is less frequently associated
with risk factors such as age, body mass index, and family history of
diabetes;
• (2) it is less frequently associated with retinopathy and cardiovascular
and renal complications;
• (3) it is more frequently associated with hypoglycemic episodes as a
result of impaired liver function .
• The treatment of DM of cirrhotic patients has particular
characteristics that make it different from type 2 DM without liver
disease:
• (1) about half the patients have malnutrition;
• (2) when clinical DM is diagnosed, the patient has advanced liver
69. • As for the management of diabetes in patients with liver disease, lifestyle
modification plays an important role.
• Oral diabetic medications are contraindicated in patients with advanced liver
diseases with associated cirrhosis, ascites, or encephalopathy.
• As for stable liver disease, metformin and thiazolenediones have shown mixed
results, with some showing them to be effective in improving liver transaminases
in addition to histological improvement in steatosis and inflammation. α-
glucosidase inhibitors may be helpful in decreasing hepatic encephalopathy.
• Upregulation of Dipeptidyl peptidase-4 (DPP-4) has been suggested as a possible
pathogenetic mechanism for HCV-related insulin resistance, and treatment with
DPP-4 inhibitors could improve insulin sensitivity in diabetic patients with liver
disease.
• Patients with impaired liver function with associated insulin resistance may need
increased insulin requirements. On the other hand patients with altered liver
metabolism might need decreased insulin requirements.
• Hala etal.Diabetes research February 03, 2014
•
70. DM Management in Hepatic Patients
• Medical therapy for patients with type 2 diabetes and liver disease
may be the same for patients without liver disease.
• Altered drug metabolism is primarily a concern in patients who have
liver failure and associated ascites, coagulopathy, or
encephalopathy. Metformin is an appropriate first-line therapy for
most patients except those with advanced liver disease who have an
increased risk of lactic acidosis.
• Thiazolidinediones enhance insulin sensitivity and may be useful in
patients with NAFLD. However, the current recommendation is to
evaluate ALT levels and other liver function test results and initiate
TZD therapy only if the serum ALT<2.5 times the upper limit of
normal with no evidence of active liver disease.
• Khan R1, Foster GR, Chowdhury TA Postgrad Med. 2012 Jul;124(4):130-7. doi: 10.3810/pgm.2012.07.2574
71. Management of type2 DM in Hepatic
patients
• Other drugs are also appropriate for use in patients with liver disease.
Sulfonylureas are considered safe in patients with hepatic disease, and drugs
with short half-lives, such as glipizide, are often appropriate choices.
• Acarbose, an α-glucosidase inhibitor, works directly in the gastrointestinal tract
to decrease carbohydrate metabolism and glucose absorption.
• Although the prescribing information for acarbose contains a warning for
patients with liver disease, it appears to be safe and effective in patients with
hepatic encephalopathy and type 2 diabetes.
• Insulin can be used successfully in patients with liver disease, but higher doses
may be required due to increased insulin resistance.Later on with
decompensation insulin metabolism decreased, so therapy with insulin must be
preferably performed in hospitalized patients with close monitoring of blood
glucose levels for development of hypoglycemia
• Jonathan G. Marquess, Pharm.D Pharmacotherapy. 2011;31(12):65S-72S.
72.
73. Russo E, et al. Diabetes Metab Syndr Obes. 2013; 6: 161–170.
79. • Certain drugs, including exenatide, metformin, sitagliptin, and
saxagliptin, are either contraindicated or must be carefully
monitored and their dosages adjusted in patients with
moderate, severe, or end-stage renal disease.
• Glimepiride 1 mg/day may be used cautiously to avoid
hypoglycemia in patients with renal disease, as they are more
sensitive to the glucose-lowering effects of this agent.In
addition, because glimepiride is cleared by the kidneys, the
duration of action of insulin may be extended.
• Insulin have been found to be relatively safe in patients with
renal disease, although the dosages of insulin glargine and
insulin detemir may need to be adjusted.
• Jonathan G. Marquess, Pharm.D.
• Pharmacotherapy. 2011;31(12):65S-72S.
80. Russo E, et al. Diabetes Metab Syndr Obes. 2013; 6: 161–170.
81. SUs=sulfonylureas; T2DM=type 2 diabetes melllitus; *Requiring medical assistance or hospital admission
UK Prospective Diabetes Study Group. Diabetes.1995;44:1249–1258.
Cumulative Incidence of Hypoglycemia in T2DM over 6 Years in UKPDS
45
3.3
76
11.2
0
10
20
30
40
50
60
70
80
Sulfonylurea (n=922)
Insulin (n=689)
Sulfonylurea Insulin Sulfonylurea Insulin
Patients(%)
Any hypoglycema Major hypoglycemia*
HbA1c = 7.1% in all groups
70% increased risk
40% increased risk
82. 25 mg o.d. 12.5 mg o.d. 6.25 mg
o.d.
Sitagliptin1
DPP-4 inhibitors
100 mg o.d. 50 mg o.d. 25 mg o.d.
Saxagliptin2
Alogliptin3
5 mg o.d.Linagliptin4
Vildagliptin5 50 mg o.d.50 mg b.i.d.
Creatinine
clearance
(mL/min)
Serum
creatinine Male
(mg/dL)
Serum
creatinine
Female (mg/dL)
30
3.0
2.5
Mild RI Moderate RI Severe RI
50
1.7
1.5
1. Available at: http://www.merck.com/product/usa/pi_circulars/j/januvia/januvia_pi.pdf; 2. Available at: http://www1.astrazeneca-
us.com/pi/pi_onglyza.pdf#page=1;
3. Available at: http://general.takedapharm.com/content/file.aspx?FileTypeCode=NESINAPI&cacheRandomizer=7236cffb-eb6c-4b0a-ac79-26810425c89e;
4. Available at: http://bidocs.boehringer-
ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Tradjenta/Tradjenta.pdf;
5. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000771/WC500020327.pdf
2.5 or 5 mg o.d. 2.5 mg o.d.
o.d. = once daily
b.i.d.= twice daily
83. New era in management of CKD patients
with diabetes
Better glycemic and blood pressure control
Older oral hypoglycemic agents is either
contraindicated or requires dosage adjustment in CKD
New medications for diabetes have been approved
recently and many can be used safely in patients with CKD
84. Lastly we hope that course will achieve
its goals and help you all in getting the
best of the forthcoming conference
UEDA Board
UEDA Diabetes Mini-Course
Aswan Feb. 2016