Download Rapid (lispro, aspart, glulisine)

Outpatient Management, co -morbidities
& complications of Type 1 Diabetes
Mellitus
Prof. Abdulmoein Al-Agha,
Consultant, Pediatric Endocrinologist,
King Abdulaziz University Hospital,
Jeddah, KSA
Available at my website: aagha,kau.edu.sa
Overview
Education
Immunization
Glycemic targets
Psychology
Insulin therapy
Comorbidities
Glucose monitoring
Complications
Nutrition
Hypoglycaemia
Type 1 DM
• Autoimmune
destruction of the
pancreatic islet cell
• Hallmark = lymphocytic
infiltration of islets
• Progresses over months
- years
• Leads to insulin
deficiency initially
• Later may also be
associated with glucagon
deficiency
Goals of T1DM Management
• Utilize intensive therapy aimed at nearnormal BG and A1C levels
• Prevent diabetic ketoacidosis and severe
hypoglycemia
• Achieve the highest quality of life compatible
with the daily demands of diabetes
management
• Achieve normal growth and physical
development and psychological maturation
• Establish realistic goals adapted to each
individual’s circumstances
Education
• Education, from diagnosis onwards, is complex,
touching on a range of issues medical and social
• It is best done by a multidisciplinary team trained in
paediatric diabetes
• Education topics should include:
–
–
–
–
–
–
–
Prevention, detection and treatment of hypoglycaemia
Insulin action and administration
Dosage adjustment
Blood glucose (BG) and Ketone testing
Sick-day management
Prevention of DKA
Nutrition and exercise
Glucose Monitoring
• Self-monitoring of blood glucose is an essential
part of management of type 1 diabetes
• Subcutaneous continuous glucose sensors allow
detection of asymptomatic hypoglycemia and
hyperglycemia
• Subcutaneous continuous glucose sensors may
have a beneficial role in children and adolescents
but evidence is not as strong as in adults
MONITORING STRATEGIES
• Self Blood Glucose Monitoring – 4-6 / day
– Affected by anemia, hemoglobinopathy
• Urine Testing – Ketones - PRN
• Glycosylated Hemoglobin - HbA1 C - quarterly
• Blood lipids - annually
• Thyroid function – annually
• Urine micro albumin – annually
• Dilated fundoscopic – annually
Glycemic Targets
Age
(years)
A1C (%)
FPG / premeal
PG
(mmol/L)
2-hour pc
PG
(mmol/L)
Considerations
<6
<8.0%
6.0-10.0
N/A*
Caution is required to minimize
hypoglycemia because of the
potential association between severe
hypoglycemia and later cognitive
impairment. Consider target of <8.5%
if excessive hypoglycaemia occurs
6-12
≤7.5%
4.0-10.0
N/A
13-18
≤7.0%
4.0-7.0
5.0-10.0
Targets should be graduated to the
child’s age. Consider target of <8.0%
if excessive hypoglycaemia occurs
Appropriate for most adolescents
*Postprandial monitoring is rarely done in young children except for those on pump therapy for whom targets are not available
A1C = Glycated Haemoglobin; FPG = Fasting Plasma Glucose; PG = Plasma Glucose; N/A = Not Available
Continuous Glucose Monitoring
Interstitial Fluid Measurement
Interstitial fluid glucose (G2) is almost always comparable
with blood glucose (G1)
Insulin Therapy
1921
Banting
Best
Insulin was the first discovered (late
1920's) which won the doctor and
medical student who discovered it the
Nobel Prize (Banting and Best)
Banting & Best
Types of Insulin for Use in T1DM
Insulin Type (trade name)
Onset
Peak
Duration
10 - 15 min
10 - 15 min
10 - 15 min
1 - 1.5 h
1 - 1.5 h
1-2h
3-5h
3-5h
3.5 - 4.75 h
30 min
2-3h
6.5 h
1-3h
5-8h
Up to 18 h
90 min
Not
applicable
Up to 24 h
(glargine 24 h,
detemir 16 - 24 h)
Bolus (prandial) Insulins
Rapid-acting insulin analogues (clear):
• Insulin aspart (NovoRapid®)
• Insulin glulisine (Apidra™)
• Insulin lispro (Humalog®)
Short-acting insulins (clear):
• Insulin regular (Humulin®-R)
• Insulin regular (Novolin®geToronto)
Basal Insulins
Intermediate-acting insulins (cloudy):
• Insulin NPH (Humulin®-N)
• Insulin NPH (Novolin®ge NPH)
Long-acting basal insulin analogues
(clear)
• Insulin detemir (Levemir®)
• Insulin glargine (Lantus®)
Pharmacokinetics of Insulin Products
Rapid (lispro, aspart, glulisine)
Insulin
Level
Short (regular)
Intermediate (NPH)
Long (glargine)
Long (detemir)
0
2
4
6
8
10 12 14 16 18 20 22 24
Hours
Adapted from Hirsch I. N Engl J Med. 2005;352:174-183.
FDA approves Afrezza to treat diabetes
• June 30, 2014 -Millions of people with
type 1 or type 2 diabetes
will have another
treatment option now
that the FDA has
approved an inhaled
insulin, called Afrezza,
the rapid-acting insulin is
taken before each meal
Insulin Therapy
• Insulin is the mainstay of medical
management
• The choice of insulin regimen depends
on many factors:
– Child’s age
– Duration of diabetes
– Family lifestyle
– Socioeconomic factors
– Family, patient, and physician preferences
Everyone has different needs
Insulin regimens
Frequently used regimens
• Two injections daily
mixture of short and intermediate-acting
insulin (before breakfast and before evening
meal)
• Three injections daily
using a mixture of short and intermediate
acting insulin before breakfast & dinner
short-acting insulin alone before Lunch
• Basal-bolus regimen
short-acting insulin 20-30 min before main
meals
intermediate or long-acting insulin at bedtime
• Insulin pump
2 Vs 3 Daily insulin injections profiles
Short acting insulin injection
Breakfast
Lunch
Evening meal
Long Acting
insulin injection
2 x daily
3 x daily
8
10
12
14
16
18
20
22
24
2
4
Time
6
8
Basal/Bolus Treatment Program With RapidActing and Long-Acting Analogs
Plasma insulin
Rapid
(lispro,
aspart,
glulisine)
4:00
Rapid
(lispro,
aspart,
glulisine)
Rapid
(lispro,
aspart,
glulisine)
Glargine or
detemir
8:00
Breakfast
12:00
Lunch
16:00
20:00
Dinner
Bed
24:00
4:00
8:00
Intensive insulin therapy
• What was considered "intensive therapy" in the
DCCT is now considered to be standard therapy for
management of type 1 diabetes
• Intensive insulin therapy (three or more injections
per day or continuous subcutaneous insulin infusion
with an insulin pump) is successful only if the patient
is:
– fully committed to it
– has good understanding of the regimen
– is supported by a health care team with sufficient
expertise to educate the patient and to continuously
monitor his or her progress
Physiologic Multiple Injection Regimens:
The Basal-Bolus Insulin Concept
• Basal insulin
– Controls glucose production between meals and
overnight
– 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
Handelsman Y, et al. Endocr Pract. 2011;17(suppl 2):1-53.
Relative Risk of Progression of Diabetes
Complications by Mean HbA1c: based on DCCT
Data
15
13
Retinopaty
11
9
Nephropaty
7
Neuropathy
5
3
Microalbuminuria
1
6
7
8
9
10
11
Level of Diabetes Control = HbA1c
12
Advantages of intensive insulin therapy
• Gain of 15.3 years of complication free living
compared to conventional therapy
Disadvantages of intensive insulin therapy
• Hypoglycemia
Peaked profiles result in uncontrolled glycaemic excursions
• Injection issues
Variability of absorption from different sites of injection
Patients’ fear of multiple injections
• Weight gain
Hyperglycemia
Microangiopathic
complications
Hypoglycemia
Neuronal loss
Poor school
performance
seizures
Nutrition
• All children with type 1 diabetes should receive
counselling from a registered dietitian
experienced in pediatric diabetes
• Children with diabetes should follow a healthy
diet as recommended for children without
diabetes
• There is no evidence that one form of nutrition
therapy is superior to another in attaining ageappropriate glycaemic targets
Nutrition
• Use of insulin to carbohydrate ratios may be
beneficial but is not required
• The effect of protein and fat on glucose
absorption must also be considered
• Nutrition therapy should be individualized
(based on the child’s nutritional needs, eating
habits, lifestyle, ability, and interest) and must
ensure normal growth and development
without compromising glycaemic control
Hypoglycaemia
• Hypoglycaemia is a major obstacle for children
with type 1 diabetes and can affect their ability
to achieve glycemic targets
• All families should understand the importance of
hypoglycemia (severity and frequency) along
with treatment and follow up strategies
• Frequent use of continuous glucose monitoring
in a clinical care setting may reduce episodes of
hypoglycaemia
Hypoglycaemia
• There is no evidence in children that one insulin
regimen or mode of administration is superior to
another for reducing non-severe hypoglycaemia
• In children, the use of mini-doses of glucagon has
been shown to be useful in the home management
of mild or impending hypoglycemia associated with
inability or refusal to take oral carbohydrate
• Dose = 10 mcg x (years of age)
• Dose range 20 – 150 mcg
Psychological Issues
• For children, and particularly adolescents, there is a
need to identify psychological disorders associated
with diabetes and to intervene early to minimize the
impact over the course of development
• The risks increase exponentially during adolescence
• Children and adolescents with diabetes have
significant risks for psychological problems:
– Depression
– Anxiety
– Eating disorders
– Externalizing disorders
 Children with persistently poor glycemic
control (e.g. A1C >10%) should be assessed by
a specialized pediatric diabetes team for a
comprehensive interdisciplinary assessment
and referred for psychosocial support as
indicated [Grade D, Consensus].
 Intensive family and individualized
psychological interventions aimed at
improving glycemic control should be
considered to improve chronically poor
metabolic control [Grade A, Level 1A].
Autoimmune Thyroid Disease
• Occurs in 15 to 30% of individuals with type 1
diabetes
• Risk for AITD during the first decade of diabetes
is directly related to the presence or absence of
thyroid antibodies
• Hypothyroidism is most likely to develop in girls
at puberty
• Hyperthyroidism also may occur more
frequently in association with type 1 diabetes
than in the general population
Addison’s Disease
• Is rare, even in those with type 1 diabetes
• Targeted screening is required in those with
unexplained recurrent hypoglycaemia and
decreasing insulin requirements
Celiac Disease
• Celiac disease can be identified in 4 - 9% of
children with type 1 diabetes
• 60 to 70% of these children, the disease is
asymptomatic
• There is good evidence that treatment of classic
or atypical celiac disease with a gluten-free diet
improves:
– Intestinal and extra-intestinal symptoms
– Prevents the long-term squeal of untreated disease
• Universal screening for and treatment of
asymptomatic celiac disease remains controversial
Screening for Comorbid Conditions
Condition
Indications for screening
Screening test
Autoimmune thyroid All children with type 1 diabetes Serum TSH level +
thyroperoxidase
disease
antibodies
Frequency
At diagnosis and every
2 years thereafter
Positive thyroid antibodies,
thyroid symptoms or goiter
Serum TSH level +
thyroperoxidase
antibodies
Ever y 6–12 months
Addison’s disease
Unexplained recurrent
hypoglycemia and decreasing
insulin requirements
8 AM serum cortisol
+ serum sodium and
potassium
As clinically indicated
Celiac disease
Recurrent gastrointestinal
Tissue transglutaminase As clinically indicated
symptoms, poor linear growth, + immunoglobulin A levels
poor weight
gain, fatigue, anemia,
unexplained frequent
hypoglycemia or poor metabolic
control
COMPLICATIONS
Acute
Chronic
• Hypoglycemia
Neuropathy
• Hyperglycemia
Retinopathy
• Ketoacidosis
Nephropathy
Diabetes Complications
• Nephropathy, retinopathy, neuropathy and
hypertension are relatively rare in paediatric
diabetes
• Screening efforts should focus most attention
on post-pubertal patients with longer duration
and poorer control of their diabetes
Nephropathy
• Screening for microalbuminuria (MAU) should
be performed annually, commencing at 12
years of age in children with type 1 diabetes
>5 years` duration [Grade D, Consensus].
• A first morning urine albumin to creatinine
ratio (ACR) has high sensitivity and specificity
for the detection of microalbuminuria (MAU)
• Treatment is indicated only for those
adolescents with persistent microalbuminuria
Retinopathy
• Retinopathy is rare in prepubertal children with
type 1 diabetes and in post pubertal adolescents
with good metabolic control
Age ≥15 yrs +
DM of 5 years
If…. DM 5-10 yrs +
normal eye exam +
good glycemic control
Begin annual screening
Screen every 2 years
Microangiopathic complications from DM can occur
by the time of diagnosis but typically
10 – 15 yr
Neuropathy
• Neuropathy is mostly subclinical in children
• Prospective nerve conduction studies and
autonomic neuropathy assessment studies
have demonstrated increased prevalence of
abnormalities overtime
• Vibration and monofilament testing have
suboptimal sensitivity and specificity in
adolescents
Dyslipidemia
• Children with type 1 diabetes who are
<12 years of age should be screened
for dyslipidemia if they have other risk
factors, such as obesity (BMI >95th
percentile for age and gender) and/or a
family history of dyslipidemia or
premature CVD
Hypertension
• Up to 16% of adolescents with type 1 diabetes
have hypertension
• Screen blood pressure at least twice / year
• Treat according to the guidelines for children
without diabetes
Complication
Indications & intervals for screening
Screening method
Nephropathy
• Yearly screening commencing at 12
years of age in those with duration of
type 1 diabetes ≥ 5 years
• First morning (preferred) or random ACR
• Abnormal ACR requires confirmation at least 1 month
later with a first morning ACR, and if abnormal, followed by
timed, overnight or 24-hour split urine collections for
albumin excretion rate
• Repeated sampling should be done ever y 3–4 months
over a 12-month period to demonstrate persistence
Retinopathy
• Yearly screening commencing at 15 yrs
of age with duration of DM ≥ 5 yrs
• Screening interval can increase to 2 yrs
if good glycemic control, duration of
diabetes < 10 yrs, and no retinopathy at
initial assessment
• 7-standard field, stereoscopic-colour fundus
photography with interpretation by a trained reader (gold
standard); or
• Direct ophthalmoscopy or indirect slit-lamp fundoscopy
through dilated pupil; or
• Digital fundus photography
Neuropathy
• Postpubertal adolescents with poor
metabolic control should be screened
yearly after 5 years’ duration of DM
• Question and examine for symptoms of numbness, pain,
cramps and paresthesia, as well as sensation, vibration
sense, light touch & ankle reflexes
Dyslipidemia
• Delay screening post-diabetes diagnosis
until metabolic control has stabilized
• Screen at ≥12 years of age or <12 years
of age with BMI > 95th percentile, family
history of hyperlipidemia or premature
CVD
• Screen all children with type 1
diabetes at least twice a year
• Fasting total cholesterol, high-density lipoprotein
cholesterol, triglycerides, calculated low-density
lipoprotein cholesterol
Hyper tension
• Use appropriate cuff size