26

supplement to Journal of the association of physicians of india Published on 1st of every month 1st July, 2014 VOL. 62

Consensus Evidence-based Guidelines for Insulin

Therapy in Patients with Type 1 Diabetes Mellitus as
per Indian Clinical Practice
Alok Kanungo*, Ashok Jhingan**, Rakesh Kumar Sahay***, A Muruganathan****,
Ashok Kumar Das*****

Abstract
Type 1 diabetes mellitus (T1DM) is a chronic disease characterised by auto-immune destruction of insulin
producing beta cells of the pancreas. Most cases of T1DM are diagnosed during childhood and adolescence, and
it remains the predominant form of the disease in this population. Early identification and treatment of T1DM
is important in reducing complications of this form of disease. Because individuals with T1DM lack endogenous
insulin production, the current consensus guideline recommends administration of rapid-acting and long-acting
analogues for all patients with T1DM to achieve glycaemic goals and reduce insulin-induced side effects like
weight gain and hypoglycaemia. It also emphasises that effective use of insulin requires an understanding of
various insulin treatment and regimens, sick-day management regarding insulin use, and ability to manage insulin-
induced hypoglycaemia to achieve the individualised treatment goals established between the patient, family and
diabetes care team. The current consensus guideline has been developed by a panel of experts based on the existing
guidelines which aims to provide better clinical practice in the Indian scenario for the management of T1DM.

Introduction
D iabetes mellitus (DM) is a metabolic disease characterised
by high glucose level in the blood. Type 1 diabetes
mellitus (T1DM) is a form of DM that results from autoimmune
destruction of insulin-producing beta cells of the pancreas.1 It
is one of the most common metabolic diseases among children
and every year the number of children developing this form of
diabetes is increasing rapidly.2
Prevalence of T1DM: Global
According to the International Diabetes Federation (IDF),
globally 366 million people are living with DM resulting in a
prevalence rate of 8.3%. Out of 366 million, 70 million people
live in South East Asia (prevalence rate 8.7%) with more than
50% remaining undiagnosed.2 T1DM accounts for 10-12% of all
diabetes cases. It is estimated that 490,000 children worldwide
are living with this disorder of whom 24% and 23% come from
Europe and South-East Asia region respectively. 2 The South-East
Asia region has one of the highest estimates of T1DM cases in
children, with India being home to an estimated 100,000 children
with T1DM. 2 Globally the incidence of T1DM is also rising at 3%
per year affecting not only children but adults. Be they children
or adults, the needs of people with T1DM are different from
those of the majority of people with diabetes and have to be
addressed separately.
Prevalence of T1DM: India
The prevalence of T1DM in India is 10.1-10.6/100,000
population. 3 A recent study in Karnal, Haryana reported
overall prevalence of T1DM to be 10.2/100,000 population
with a higher prevalence in urban population than rural,
and men (11.56/100,000) being more susceptible than women
(8.6/100,000).4 In the 5 to 16 years age group, the prevalence was
*
Kanungo Institute of Diabetes Specialities, Dumduma, Bhubaneshwar,
Odisha; **Dehli Diabetes Research Centre, J-136, Rajouri Garden,
Delhi; ***Department of Endocrinology, Osmania Medical College and
Hospital, Hyderabad; ****A. G. Hospital, 34, K.P.N. Colony, Tirupur;
*****
Department of Medicine, Jawaharlal Institute of Postgraduate
Medical Education and Research, Pondicherry
22.22/100,000, while in the 0-5 years age group, prevalence was
3.82/100,000.4 An epidemiological study conducted in a South
Indian population for a period of four years, indicated that the
prevalence of T1DM in India is increasing.5,6
Burden of T1DM
T1DM places a heavy burden on the affected individual, their
family, the healthcare system, and the society. The increasing
burden of T1DM is accounted by missed diagnoses or inadequate
insulin supply. The costs involved in the care and management
of T1DM is estimated around $14.9 billion (8.6%) that includes
direct medical costs of $10.5 billion and indirect costs (as
measured by loss of productivity) of $4.4 billion.7 The high costs
of treatment among all socioeconomic patient groups will result
in a serious economic burden on patients and society as well.
Evidence suggest that people with T1DM and those treated with
insulin show six to seven-fold higher direct cost than nondiabetic
people.8 Moreover, reduced life expectancy among people with
T1DM can have significant negative impact on the quality of life
(QoL) of the patient.9
Importance of glycaemic control in management of T1DM
Optimisation of glycaemic control at an early stage of the
disease is a fundamental aspect of care in the management
of T1DM. The association between tight glycaemic control
and reduced risk of microvascular complications in patients
with T1DM was demonstrated in the Diabetes Control and
Complications Trial (DCCT).10 As assessed over 7 years in
DCCT trial, intensive insulin therapy designed to maintain
normal blood glucose levels greatly reduced the development
and progression of retinopathy, microalbuminuria, proteinuria,
neuropathy, cardiovascular events and overall mortality.10
Existing guidelines
Several diabetes organisations around the world including
the American Association of Clinical Endocrinologist (AACE),
American Diabetes Association (ADA), the Canadian Diabetes
Association (CDA), International Diabetes Federation/
International Society for Paediatric and Adolescent Diabetes
(IDF/ISPAD), Indian Society for Paediatric and Adolescent
supplement to Journal of the association of physicians of india Published on 1st of every month 1st July, 2014 VOL. 62 27
Endocrinology (ISPAE), Australasian Paediatric Endocrine
Group (APEG) and National Institute for Health and Clinical
Excellence (NICE) have formulated evidence-based guidelines
for the management of T1DM.11-17
Rationale for the need of India specific guidelines
Several guidelines including ADA, IDF, AACE, NICE, CDA,
ISPAE, and APEG have been published for the management of
T1DM. These organisations provide guidelines for management
of patients with T1DM in their respective regions. However, due
to confounding biases and non-applicability of these guidelines
in the Indian scenario, they cannot be widely used in Indian
clinical practice. The current consensus guideline aims to provide
specific recommendations based on published data for proper
management of T1DM in India.
Methodology
A systematic review of literature from medical databases
was conducted to provide the best possible evidence base for
the recommendations. Existing guidelines, metaanalyses, cross
sectional studies, systematic reviews and key cited articles
related to T1DM were reviewed by a group of doctors and
recommendations relevant to Indian scenario were framed.
The recommendations were discussed at the National Insulin
Summit held in August 2013 by an expert panel of physicians,
endocrinologists and key opinion leaders. At this summit,
recommendations for each section of the guidelines, and overall
recommendations were agreed upon. Where there was little or
no evidence, the committee relied on experience, judgement
and consensus to make their recommendations. The consensus
document was drafted and circulated for further feedback from
the participants and others who could not attend.
Grading system
The current consensus guidelines have been developed in
accordance with the AACE protocol for standardised production
of clinical practice guidelines.11 Recommendations are organised
by topic and are assigned evidence level (EL) ratings on the
basis of the quality of supporting evidence all of which have
also been rated for strength. Recommendations are based on
clinical importance and graded as A (strongly recommend), B
(intermediate), C (weak) and D (not evidence based), those are
coupled by four intuitive levels of evidence: 1,2,3,4. The evidence
levels have been positioned on the basis of available evidence to
be used for grading recommendations as follows.
1: Meta-analysis of randomised controlled trials,
randomised controlled trials
2: Meta-analysis of nonrandomised prospective or
case-controlled trials, nonrandomised controlled trial,
prospective cohort study, retrospective case-control study
3: Cross-sectional study, surveillance study (registries,
surveys; Epidemiologic study, retrospective chart review,
mathematical modelling of database), consecutive case
series, single case reports
4: No evidence (theory, opinion, consensus, review, or
preclinical study)
Management of T1DM
Criteria for diagnosis of T1DM
The diagnosis of T1DM is based on measurements of blood
glucose for age groups < 30 years and the presence and absence of
clinical symptoms including increased thirst and urine volume,
recurrent infections, unexplained weight loss, weakness, pain,
presence of ketones inurine or blood, severe abdominal pain, and
diabetic ketonuria/ ketoacidosis. C-peptide levels and antibody
profiles may be done subsequently to confirm the diagnosis of
T1DM.18,19 The current recommendations for diagnosis are in line
with already published guidelines i.e. AACE, ADA, and CDA.11-13
Recommendations
In individuals < 30 years, the following criteria are
recommended for diagnosis of T1DM: (Grade A; EL 4)11,13,15
- Symptoms of diabetes plus casual plasma glucose
concentration 11.1 mmol/L (200 mg/dL) or
- Fasting plasma glucose (FPG) 7.0 mmol/L (126 mg/
dL) or
- 2-hour postprandial glucose (PPG) 11.1 mmol/L (200
mg/dL) and
- Symptoms of ketonuria/ketoacidosis
Use of glycated haemoglobin (HbA1c) test is not
recommended for the diagnosis of diabetes in childhood
(Grade A; EL 2).12,13,17,20,21
Use of oral glucose tolerance test (OGTT) is not recommended
for the diagnosis of diabetes in childhood (Grade A; EL 4).20
Criteria for screening of T1DM
An individuals risk of developing T1DM can be screened by
presence of glutamic acid decarboxylase autoantibodies (GADA),
pancreatic islet autoantibodies (PIA), insulinoma-associated
(IA-2) autoantibodies, and zinc transporter autoantibodies
(ZnT8).22,23 Screening can also be done by considering family
history of siblings with T1DM with attention to age of onset
and sex, genetic markers, and C-peptide assay.24 ADA guideline
recommends considering referral of relatives of those with T1DM
for antibody testing for risk assessment for T1DM.12 The current
recommendations are in line with the ADA guidelines.
Recommendations
In first degree relatives of T1DM patients, screening for the
presence of pancreatic beta-cell antibodies and an OGTT is
recommended (Grade A; EL 1).13,24,25
Also it is recommended (Grade B; EL 4)12,17
- to measure thyroid stimulating hormone annually
- to consider screening children with T1DM for coeliac
disease and other autoimmune disorders
- to monitor growth and pubertal development
Glycaemic targets
For selecting glycaemic goals, the difficulty in achieving an
optimal HbA1c must be balanced against the disadvantages of
targeting a higher (although more achievable) goal that may
not promote optimal long-term health outcomes. In addition,
benefits of improved glycaemic control in children must be
balanced with careful consideration of the childs unique
vulnerability to hypoglycaemia. To address these unique needs,
ADA has recommended age-specific HbA1c targets for children
[0-6 years, 6-12 years (pre-pubertal), and 13 years (or pubertal)]
to adulthood.12 The current recommendations are in line with
the ADA guidelines.
Recommendations
In individuals with T1DM, age-specific glycaemic goals with
different targets for different time periods (preprandial,
bedtime and overnight) are recommended. The targets are
listed in Table 1 (Grade B; EL 4).12
28 supplement to Journal of the association of physicians of india Published on 1st of every month 1st July, 2014 VOL. 62

Education blood glucose testing, and management of hypoglycaemia.15,18

Diabetes education is the cornerstone of care for children The current recommendations are in line with AACE, ISPAE,
with T1DM to achieve a successful health-related outcome. NICE, and ADA guidelines.
Proper diabetes education for a child and family of a child Recommendations
with T1DM requires educators with a set of skills including It is recommended that patients with T1DM should receive
good communication, compassion, sensitivity, humour, and family-centred diabetes education, and review the outcomes
in-depth knowledge of childhood diabetes.18 Systematic reviews during subsequent visits (Grade A; EL 1).12,15,17,29,30
of educational and psychosocial interventions in diabetes care
It is recommended that patients with T1DM should receive
for children demonstrated small to medium beneficial effects
diabetes education on recognition of hypoglycaemic
on glycaemic control and greater effect on psychological
symptoms, need for lifelong insulin treatment and various
outcomes.26-28 AACE, ISPAE, NICE, and ADA recommend
insulin injection techniques (Grade A; EL 2).31-33
that education should be provided by a team of certified
professionals, including a physician, nurse, dietician, and mental School teacher(s) or nurse(s) should be educated about blood
health professional who are dedicated to communicating basic glucose testing, injection technique and, prompt recognition
diabetes management skills within a context that addresses the and treatment of hypoglycaemia (Grade B; EL 3).12,17,34,35
need for lifelong treatment with insulin, sick day management, Management of T1DM with insulin therapy
Children with T1DM require administration of exogenous
Table 1 : Glycaemic targets and plasma blood glucose for
insulin because of the destruction of their pancreatic islet cells
T1DM by age group
and lack of endogenous insulin production.36 During the first
Plasma blood glucose few weeks after diagnosis, endogenous insulin secretion may
Values range (mg/dL) HbA1c recover for a short period of time. This is often referred to as
(age in Rationale
years ) (Before (Bedtime/ (%) the honeymoon period and calls for tightly controlled blood
meals) overnight) glucose and often a reduction or even complete stop in the
Toddlers insulin administration.37 Management strategies to achieve
High risk and
and near-glycaemic levels in T1DM patients can significantly reduce
100-180 110-200 7.5 to 8.5 vulnerability to
preschoolers the risk of diabetes related complications and improve QoL.38
hypoglycaemia
(0-6) Treatment with insulin remains the core therapy for management
Risk of of T1DM in children and adolescents.17 However, the choice of
Adolescent
hypoglycaemia
and young insulin regimen depends on the individuals needs, beliefs and
90-180 100-180 <8 and relatively
adults
low risk of
life-style. ISPAE guideline recommends a usual dose of insulin
(13-19) between 0.5-1.5 units/kg/day according to the stage of diabetes,
complications
Risk of age and maturation of the child.15
Adolescents hypoglycaemia; Insulin regimens for T1DM
and young Development
90-130 90-150 < 7.5%* Given that a wide variety of insulin formulations and
adults and
(13-19) psychological mixtures are available, insulin therapy should be initiated
issues with an appropriate insulin regimen ranging from once daily
injection to multiple daily injections (MDIs) of short-acting
a lower goal < 7% is reasonable if it can be achieved without excessive
*

hypoglycaemia.
Key concepts in setting glycaemic goals:
Ideally, capillary glucose measurements should be done 4 times a day
In resource-limited settings capillary blood glucose measurements should
be done at least once/twice weekly, based on physicians discretion
3 a.m. capillary blood glucose monitoring should be done to assess
nocturnal hypoglycaemia
Abbreviations : TIDM: Type 1 diabetes mellitus; HbA1c: Glycated haemoglobin
insulin or rapid-acting insulin analogues before meal, together
with one or more separate daily injections of intermediate-acting
insulin or long-acting insulin analogues.12,13,17 However, ISPAE
guidelines recommend the use of basal-bolus, split-mix regimen
(twice or thrice daily) or premixed insulin for management of
T1DM (Table 2). Our current consensus is in line with the ISPAE
guideline which recommends the use of basal-bolus regimen
as the most preferred regimen. However, in case of concerns of

Table 2 : Insulin therapy regimens for children and adolescents with T1DM.
Common insulin regimens Pre-breakfast Pre-lunch Pre-dinner Bedtime Comments
Basal-bolus regimen (using
Rapid-acting insulin Rapid-acting insulin Rapid-acting insulin Glargine or detemir Preferred regime
analogues)
Basal-bolus regimen (using Preferred if analogues use is
Regular Regular Regular NPH
human insulins) not possible
With resource limitation
Regular or rapid- Regular or rapid-
Split-mix regimen and when there is a concern
acting analogue plus - acting analogue plus -
(2 injections a day) to reduce number of
NPH NPH
injections
Regular or rapid- With above concerns
Split-mix regimen Regular or rapid-
acting analogue plus - NPH and when nocturnal
(3 injections a day) acting analog
NPH hypoglycaemia is an issue
Premix insulins Concern of number of
Premix Premix
(conventional/analogues) injections
Ideal versus minimal as we move down the table; Abbreviations: RAI: Insulin aspart, lispro, glulisine; NPH, neutral protamine Hagedorn.
supplement to Journal of the association of physicians of india Published on 1st of every month 1st July, 2014 VOL. 62 29
hypoglycaemia and number of injections, split-mix regimen or
premixed regimen is recommended.15
Recommendations
In individuals with T1DM, insulin regimens with different
targets for pre-breakfast, pre-lunch, pre-dinner, and bedtime
have been recommended (Table 2).
In individuals with T1DM, use of rapid-acting insulin is
recommended pre-breakfast, pre-lunch, and pre-dinner,
while insulin glargine or detemir is recommended at
bedtime (Grade A; EL 1).15, 39
In case of unavailability of insulin analogues, use of regular
insulin is recommended pre-breakfast, pre-lunch, and
pre-dinner, while neutral protamine Hagedorn (NPH) is
recommended at bedtime (Grade B; EL 2).40
In case of resource limitation and when there is a concern
to reduce number of injections, split-mix regimen (two
injections/day) is recommended pre-breakfast, and pre-
dinner (Grade B; EL 2).41,42
In case of resource limitation when there is a concern for
nocturnal hypoglycaemia, split-mix regimen (two injections/
day) is recommended pre-breakfast, and pre-dinner (Grade
B; EL 4).15
When there is a concern of number of injections,
premix insulin preparations (conventional/analogues) are
recommended pre-breakfast, and pre-dinner (Grade B; EL
3).43
Basal-bolus insulin
Basal-bolus insulin therapy mimics healthy pancreas by
delivering insulin constantly as a basal and when needed as
a bolus component.44 Basal insulin is administered constantly
to keep the blood glucose from fluctuating due to the normal
release of glucose from the liver whereas; bolus insulin mimics
the burst secretions of the pancreas in response to increases in
blood glucose.45 In a basal-bolus therapy in T1DM, the doses
of individual insulin regimens are divided based on target
FPG and HbA1c. In general, basal dose includes 25% to 30%
of the total dose in toddlers and 40% to 50% in older children
given at bedtime while rest of the dose is divided in to three
pre-meals doses given as bolus insulin which limits post-prandial
hyperglycaemia.46
Good glycaemic control
Randomised trials comparing the efficacy of insulin analogues
with human insulin have demonstrated better glycaemic control
with low risk of hypoglycaemia.47-49 Evidence suggest that use
of insulin detemir/insulin aspart provide better glycaemic
control compared to NPH insulin/regular human insulin (RHI)
(HbA1c: 7.88% vs. 8.11%; mean difference: - 0.22%; P < 0.001).49
Moreover, insulin detemir is associated with fewer episodes
of hypoglycaemia compared to NPH insulin (60% vs. 77%; P =
0.049).48 The ISPAE guideline recommends the use of RHI plus
insulin glargine or insulin detemir; and rapid-acting analogue
plus insulin glargine or insulin detemir as basal-bolus therapy.15
Among rapid acting analogues, insulin aspart is approved in
children above 2 years of age, insulin lispro above 3 years of age
and insulin glulisine above 4 years of age.50 Among long acting
analogues, both insulin detemir and glargine are approved above
2 years of age.50 The Canadian guideline recommended the use
of rapid-acting insulin analogues in combination with adequate
basal insulin, over RHI to improve HbA1c while minimising the
occurrence of hypoglycaemia.13 ISPAD guideline recommends
insulin glargine/detemir to improve HbA1c and reduce risk of
hypoglycaemia.14 Our current recommendation is in line with
CDA and ISPAD guidelines which recommend use of basal-bolus
regimen using insulin analogues for better glycaemic control.
Recommendations
An intensive insulin regimen (insulin aspart/insulin
detemir) is recommended over RHI/NPH insulin for
improved glycaemic control, reduced risks of nocturnal
hypoglycaemia and less weight gain (Grade A; EL 1).49
Insulin detemir may be recommended over NPH for
effective glycaemic control, more predictable FBG, and
reduced risk of hypoglycaemia (Grade A; EL 1).48
Reduced weight gain
Weight gain accompanying insulin treatment is considered an
inevitable side effect.51 A consistent difference in terms of weight
change was found in a number of Phase III studies of insulin
detemir in T1DM.52-54 Studies evaluating the safety of insulin
detemir either alone or in combination with rapid-acting insulin
over other insulin regimens (NPH) have demonstrated modest
increase or no change in weight.49 Moreover, gain in body weight
was significantly lower after 6 months with insulin detemir than
with NPH ( 0.54 kg difference; P = 0.024).53 Evidence suggests,
that twice daily injection of insulin detemir (morning and dinner
time) produced greater change in mean body weight compared
to that given during morning and bed time (Difference: (IDet
morn+din)-1.3 kg, P < 0.001, (IDet morn+bed)-0.6 kg, P = 0.050).54
In the absence of guidelines on weight change in these patients,
recommendations were framed from the cited articles.
Recommendations
Insulin detemir is recommended over NPH insulin to
minimise weight gain in individuals with T1DM (Grade
A; EL 1).49,52-54
Reduced nocturnal hypoglycaemia
Insulin-induced nocturnal hypoglycaemia is a significant
problem for children and adults. CDA recommends insulin
degludec or insulin glargine as an alternative to NPH to reduce
the risk of daytime and nocturnal hypoglycaemia.13 Reduced
nocturnal hypoglycaemia was seen in T1DM patients using long-
acting insulin. Randomised controlled trials which compared
the use of insulin detemir versus NPH insulin in T1DM patients
showed 26% reduction in the risk of nocturnal hypoglycaemia
(14.71 vs. 17.09, P = 0.005).53,55 Switching patients from basal-
bolus regimen to insulin detemir demonstrated reduction in
episodes of total and nocturnal hypoglycaemia (P < 0.0001 for
all).55 Reduced nocturnal hypoglycaemia was also reported in
trials comparing insulin degludec versus insulin glargine in
patients with T1DM (25% lower with insulin degludec than with
insulin glargine at P = 0.01).56-59 The current consensus is in line
with CDA guidelines.
Recommendations
In T1DM patients with HbA1c 12%, a basal-bolus therapy
with once daily RHI and insulin detemir at bed time may
be recommended over RHI and NPH insulin/insulin
glargine for lower FPG level, less day-to-day variability, less
fluctuation from blood glucose levels, and reduced risk of
nocturnal hypoglycaemia (Grade A; EL 1).53,55,60
In T1DM patients with HbA1c 10%, despite similar
glycaemic control, long-term basal therapy with once
daily insulin degludec mealtime insulin aspart may be
recommended over insulin glargine for reduced risk of
30 supplement to Journal of the association of physicians of india Published on 1st of every month 1st July, 2014 VOL. 62
nocturnal hypoglycaemia (Grade A; EL 1).56-59
Flexible dosing
Option to dose flexibly is important because such option
would allow individuals with T1DM to achieve a better QoL
without compromising glucose control or safety.61 Randomised
controlled trials comparing day-to-day variability in the
glucose-lowering effect and options for more flexible dosing
demonstrated four-times lower day-to-day glycaemic variability
and fewer episodes of hypoglycaemia with insulin degludec
than insulin glargine.61,62 In the absence of guidelines on flexible
dosing in patients with T1DM, recommendations were framed
from the cited articles.
Recommendation
Insulin degludec may be recommended over insulin
glargine for reduced nocturnal confirmed hypoglycaemia
and as an option for more flexible dosing (Grade A; EL 1).61
At steady-state condition, insulin degludec may be
recommended over insulin glargine for more predictable
glucose-lowering effect with low pharmacodynamics
variability and better flexibility (Grade A; EL 1).62
Premixed insulin analogues
Premixed insulin analogues seek to mimic physiologic
endogenous insulin secretion.63 Premixed insulin combines
rapid-acting insulin with NPH basal insulin analogues available
in different ratios where percentage of rapid-acting/regular to
intermediate-acting varies with the formulation. It provides an
option for intensification from once to twice to thrice daily dosing
to achieve glycaemic control with lower risk of hypoglycaemia
and may be used in all stages of disease progression.64Indian
National Consensus Group (INCG) guidelines recommend the
use of premix insulin to achieve glycaemic control in children
and adolescents with T1DM and type 2 diabetes mellitus.65
Evidence suggests that compared to RHI, patients treated with
biphasic insulin aspart-30 achieved long-term glycaemic control
without increased risk of hypoglycaemia.66 Glycaemic targets
set by AACE, ADA, CDA, IDF, NICE, and INCG also include
post-prandial glucose goals. Growing evidence suggests that
reducing PPG is important for achieving glycaemic goals.67
In a randomised trial, biphasic insulin aspart-30 reduced
the postprandial serum glucose area under curve0-4hby 23%
compared with RHI 30 (t = 0) (P < 0.0001) and by 9% compared
with RHI 30 (t = - 30) (P = 0.013).68 Similarly, other studies also
reported improved HbA1c and reduced hypoglycaemic episodes
with no differences in weight change by the use of biphasic
insulin aspart-30 than RHI 30.64,69 The current consensus is in
line with INCG guidelines.
Recommendations
Biphasic insulin aspart-30 is recommended over RHI to
improve long-term HbA1c, minimise glycaemic variability
and risk of hypoglycaemia (Grade A; EL 1).66
In adults with T1DM, biphasic insulin aspart-30 may be
recommended over premixed human insulin 30 to achieve
PPG targets without weight gain (Grade A; EL 1).64,68,69
Avoiding hypoglycaemia with insulin
Hypoglycaemia is a major problem for individuals trying to
achieve glycaemic targets. Hypoglycaemia can be severe and
result in confusion, coma or seizure, anxiety, headache, requiring
the assistance of other individuals.70 Evidence from several
studies has indicated that the risk of hypoglycaemia is high
among patients treated with insulin.71,72 In the DCCT trial, 35%
of patients in the conventional treatment group and 65% in the
intensive treatment group experienced at least 1 episode of severe
hypoglycaemia.73,74 Given the risks, avoidance of insulin-related
hypoglycaemia is important for establishing glycaemic goals
in individuals with T1DM. Canadian guideline recommended
that all individuals with T1DM should be educated about
the complications of insulin-induced therapy.13 The current
consensus is in line with Canadian guidelines.
Recommendations
All individuals with T1DM should be counselled about the
risk and prevention of insulin-induced hypoglycaemia, and
risk factors for severe hypoglycaemia should be identified
and addressed (Grade B; EL 2).75,76
In individuals with hypoglycaemia unawareness, the
following strategies may be used to reduce the risk of
hypoglycaemia and to attempt to regain hypoglycaemia
awareness:
- Continuous glucose monitoring preferably or SMBG,
including periodic assessment during sleeping hours
(Grade B; EL 1).77
- Less stringent glycaemic targets for up to 3 months
(Grade B; EL 2).78,79
- A psycho-educational intervention programme (Grade
B; EL 1).80
Choice of insulin regimen: Multiple daily injections versus
continuous subcutaneous insulin infusion
Continuous subcutaneous insulin infusion (CSII) therapy
or insulin pump therapy is an alternative means of delivering
insulin to patients with T1DM.81 CSII makes use of an external
pump that delivers insulin continuously from a refillable storage
reservoir by means of a subcutaneously placed cannula. The
pump can be programmed to deliver a basal rate of insulin
throughout the day, with higher infusion rates triggered by the
push of a button at meal times.82 This may be a bolus or over
a period of time, and it can also deliver different basal rates of
insulin at different times of the day and night.17 The choice of
pump in very young children should take into account the ability
to deliver a very low basal rate.
Compared with traditional delivery of insulin preparations
by MDIs, delivery of insulin via CSII reduces the frequency
and number of injection allowing for greater flexibility and
accurate dosing. 83 AACE, ADA, ISPAE, APEG, NICE, and
Scottish Intercollegiate Guidelines Network (SIGN) guidelines
recommend the use of CSII in T1DM patients who are unable
to achieve optimal glycaemic control with MDI.11,12,15-17,84 On the
other hand, CDA guideline advocates the use of insulin aspart
or insulin lispro over RHI in patients using CSII for improving
glycaemic control and reducing hypoglycaemia.13
Beneficial use of insulin pump therapy over MDI in terms of
improved glycaemic control, improved QoL, and reduced risks of
hypoglycaemia have been reported in childrens with T1DM.85-91
Currently in India, insulin pumps are usually not reimbursable
or covered by insurance, and the patient needs to buy the
pump and also the consumables, both of which are currently
expensive.92 The current consensus is in line with AACE, ADA,
ISPAE, APEG, NICE, and SIGN guidelines.
Recommendations
CSII may be recommended over MDI for better glycaemic
control, improved quality of life, reduced insulin dose and
risk of hypoglycaemia (Grade A; EL 1).85-90
supplement to Journal of the association of physicians of india Published on 1st of every month 1st July, 2014 VOL. 62 31

Table 3 : Comparison of recommendations from current consensus guidelines and existing guidelines
Criteria Consensus guideline AACE ADA ISPAD NICE CDA ISPAE
Glycaemic targets, HbA1c%
Age < 6 years < 8.5 < 8.5 < 8.5
Age: 6-12 years <8 < 6.5 <8 6.2-7.5 6.5-7.5 < 8.0 6.5
Age: 13-19 y < 7.5 < 7.5 7.0
FPG, mmol/L 7.0 6.1 3.9-7.2 5.1-6.5 4.0-8.0 4.0-7.0 -
PPG, mmol/L 11.1 < 7.7 < 10.0 7.6-9.0 < 10.0 5-10.0 -
First-and
Criteria for Relatives of Regular screening
First degree relative Family history of second-degree
screening for those with - - for long-term
has T1DM T1DM relatives of those
T1DM T1DM complications
with T1DM
Thyroid disease; PIA-2/GAD Thyroid disease;
Thyroid disease;
Screening of coeliac disease; autoantibodies; Same as ISPAD; Coeliac disease;
Thyroid disease; coeliac disease;
non-glycaemic monitoring growth profiling vitamin B12 retinopathy; Same as ISPAD
coeliac disease rest same as
parameters and pubertal immunity and deficiency microalbuminuria;
AACE
development genetic markers blood pressure
Education to patients
Diabetes
and family for Education for Education Education for
Education on Education to education
insulin therapy and children and for insulin diabetes self-
diabetes self- child and family for insulin
injection techniques; adolescents for treatment; management;
Diabetes management about diabetes use, risk of
caution against the insulin therapy, monitoring and insulin pump
education at the time of self-management hypoglycaemia
use of alternative self-monitoring care by a nurse, treatment by a
diagnosis to by health care and self-
therapies; sick of blood glucose, pharmacist or diabetic educator
patients providers management of
day management; hypoglycaemia dietician and a dietician
diabetes
hypoglycaemia
Rapid-acting
bolus insulin
NPH at bedtime;
Insulin glargine/ analogues, in Insulin glargine/
rapid-acting
detemir/NPH at combination detemir/NPH
insulin analogues
bedtime and regular Rapid-acting with adequate at bedtime and
MDI of basal are given at
insulin/rapid-acting analogues basal insulin to regular insulin/
insulin and mealtimes or
analogue/regular immediately minimise the rapid-acting
prandial NPH insulin;
Insulin human insulin/ before meals; occurrence of analogue/regular
insulin; insulin Same as AACE long-acting
therapy regular plus NPH insulin glargine/ hypoglycaemia; human insulin/
analogues if insulin analogues
at pre-breakfast/ detemir: most long-acting regular plus NPH
hypoglycaemia is administered
pre-lunch/pre-dinner commonly given insulin at pre-breakfast/
is a problem when nocturnal
to reduce glycaemic twice daily analogues pre-lunch/pre-
hypoglycaemia
control and improve (detemir, dinner
is a problem on
health related QoL glargine) to
NPH
reduce nocturnal
hypoglycaemia
Insulin pumps
Recommends
CSII over MDI for Rapid-acting to pump regular
CSII when MDI
better glycaemic CSII for better insulin insulin or rapid-
CSII for fails and those
control, improved glycaemic analogues acting analogue
achieving near- receiving the
CSII QoL, less insulin control and Same as AACE (aspart or lispro) for providing
normal levels of treatment have the
dose; greater reduce risk of for intensive good glycaemic
blood glucose commitment and
convenience, no hypoglycaemia diabetes control with low
competence to use
hypoglycaemia management hypoglycaemia
the therapy
and better QoL
Abbreviations: AACE: American Association of Clinical Endocrinologist; ADA: American Diabetes Association; CDA: Canadian Diabetes Association; IDF:
International Diabetes Federation; ISPAE: Indian Society for Paediatric and Adolescent Endocrinology; ISPAD: International Society for Paediatric and Adolescent
Diabetes; NICE: National Institute for Health and Clinical Excellence; GIA: Glutamic acid decarboxylase; PIA: Pancreatic islet antigen; CSII: Continuous subcutaneous
insulin infusion; MDI: Multiple daily injections; QoL: quality of life; NPH, neutral protamine Hagedorn

In preschool-age children with T1DM, CSII is recommended
over MDI for higher treatment satisfaction and improved
QoL (Grade A; EL 1).91
Switching from multiple injection therapy to insulin
pump therapy may be recommended in patients who are
adequately educated, motivated and can afford pump
therapy (Grade A; EL 1).92-95
In toddlers and younger children, CSII may be recommended
over MDI (Grade A; EL 1).96
Monitoring of glycaemic control: continuous glucose
monitoring
Continuous glucose monitoring (CGM) provides the patient
with not only a real-time notification of interstitial blood glucose
values but also sounds auditory alerts for extreme changes in
blood glucose values, particularly nocturnal hypoglycaemia in
patients with T1DM.97 CGM, together with intensive insulin
therapy is recommended for better glycaemic control in T1DM
patients 25 years.12 The Endocrine Society recommends the
use of CGM at 8 years of age for anyone with T1DM.97 ISPAE
guideline recommends the use of CGM for measuring interstitial
32 supplement to Journal of the association of physicians of india Published on 1st of every month 1st July, 2014 VOL. 62
fluid glucose.15 NICE and AACE guideline recommends the
use of CGM in children and adolescents with T1DM who have
persistent problems with hypoglycaemia unawareness or
repeated hypoglycaemia or hyperglycaemia.11,17 CGM has been
shown to be helpful in adults with diabetes and offers potential
to improve care for children with T1DM beyond what can be
achieved with self-monitoring blood glucose (SMBG) alone.
With the availability of CGM devices, it is anticipated that
decreased HbA1c goals may be achieved more safely, allowing
further decreases in target HbA1c levels and improved outlooks
for childrens with T1DM.98 A meta-analysis of six trials which
compared the clinical effectiveness of real time CGM with SMBG
in T1DM patients demonstrated overall mean difference in
HbA1c of 0.30% (95% confidence interval: 0.43% to 0.17%) (
3.0, 4.3 to 1.7 mmoL/moL) and reduced overall area under the
curve of hypoglycaemia 0.28 ( 0.46 to 0.09), corresponding
to a reduction in median exposure to hypoglycaemia of 23% for
CGM compared with SMBG.99 The current consensus is in line
with ISPAE, NICE, and AACE guidelines.
Recommendations
CGM is recommended over SMBG for improved glycaemic
control and reduced risk of hypoglycaemia (Grade A; EL
1).12,99,100
Summary
Patients with T1DM require lifelong treatment with insulin.
Management of T1DM involves systematic evaluation of
glycaemic status, setting of glycaemic target and providing
therapeutic interventions. The advent of new rapid-acting insulin
analogues like aspart and ultra-long acting insulin degludec
provide better therapeutic options to achieve glycaemic goals
without the risk of hypoglycaemia. The current consensus
guideline was developed based on the best clinical observations
for management of T1DM from exiting guidelines and protocols
(Table 3). With a focus on high quality evidence it is hoped that
the adoption of the current guideline in Indian medical practice
will help in delivering better healthcare to patients with T1DM.
Acknowledgements
The authors thank Jeevan Scientific Technology Limited,
Hyderabad, India, for writing assistance in the development of
this manuscript.
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