Notice of update
The DDG clinical practice guidelines are updated regularly during the second half
of the calendar year. Please note that due to the overlap of the deadlines for
the printing version of this clinical practice guideline and the publication of
the 5th edition of the S3 guideline on the treatment of type 1 diabetes in
September 2023, the present clinical practice guideline still refers to the
version from 2018. The current long version of the S3 guideline
(09/2023) can be found at:
https://register.awmf.org/de/leitlinien/detail/057–013
and on the DDG homepage.
Addressees and objectives
Addressees and objectives
This guideline is directed at all people with type 1 diabetes and all occupational
groups that care for people with type 1 diabetes, especially:
-
Registered diabetologists,
-
General practitioners and internists,
-
Doctors working in hospitals (diabetes specialists, anaesthesiologists,
surgeons, radiologists),
-
Nurses/professional caregivers (in the operating theatre
and/or wards or in the field of diagnostics) and
-
Outpatient or inpatient diabetes consultants and other professional groups in
diabetology.
In addition, the guideline is directed at higher-level institutions such as health
insurance companies or medical services.
In preparing and updating these guidelines, the authors pursue the following
objectives of
-
Reducing the rate of diabetes-associated complications and damage. For the
first time, the diagnosis and treatment of lipodystrophies is also
described;
-
Improving the quality of life of people with type 1 diabetes;
-
Contributing to proper care of people with type 1 diabetes in hospital, both
in normal wards and intensive care units. In particular, the implementation
of safe protocols to protect against hypoglycaemia in intravenous insulin
therapy should be supported;
-
Ensuring correct treatment of acute complications and thus reducing the risk
of complications due to treatment;
-
Focus more strongly on proper training of people with type 1 diabetes,
especially in the outpatient sector.
Definition and classification of type 1 diabetes
Definition and classification of type 1 diabetes
Currently, the disease diabetes mellitus is classified into 4 main types (as per
etiological classification) according to the American Diabetes Association (ADA)
[1]:
-
Type 1 diabetes (as a result of autoimmune beta-cell destruction, which
usually leads to absolute insulin deficiency), subform: idiopathic;
-
Type 2 diabetes (due to progressive loss of insulin secretion from the beta
cell, often against the background of insulin resistance);
-
Other specific diabetes types (subtypes A: genetic defects of beta cell
function; B: genetic defects of insulin efficacy; C: exocrine pancreatic
disease, D: diabetes due to endocrinopathies; E: drug or chemical-induced;
F: diabetes resulting from infections; G: rare forms of immune-mediated
diabetes; H: other genetic syndromes occasionally associated with
diabetes);
-
Gestational diabetes (glucose tolerance disorder diagnosed for the first time
in pregnancy with a 75 g oral glucose tolerance test).
Type 1 diabetes occurs primarily in younger years but can also manifest itself in
later life. Even today, when type 1 diabetes is diagnosed, a severe metabolic
derailment in the form of ketoacidosis can be seen in about 15–30%
of cases, reaching as far as loss of consciousness [2].
Within the category type 1 diabetes, 2 subtypes are currently distinguished: the
immune-mediated form and the idiopathic form.
Type 1 diabetes (immune-mediated, autoimmune disease)
Type 1 diabetes is caused by a cell-mediated, chronic autoimmune destruction of
beta cells. The following serological markers are suitable for diagnosing type 1
diabetes [3]
[4]
[5]
[6]
[7]
[8]:
-
Islet cell antibodies (ICA)
-
Insulin autoantibodies (IAA) (for children and adolescents but not for
adults)
-
Autoantibodies against glutamate decarboxylase of the B-cell (GAD65A)
-
Autoantibodies to tyrosine phosphatase (IA-2ª) and
IA-2ß
-
Autoantibodies against the zinc transporter 8 of the B-cell (ZnT8)
Type 1 diabetes is diagnosed when one or more of these autoantibodies are
detected. At least one of these autoantibodies is detectable in
85–90% of patients with stage 3 diagnosis, i. e.
simultaneous hyperglycaemia.
Idiopathic type 1 diabetes
Patients with idiopathic type 1 diabetes have a permanent insulin deficiency,
tend to repeated episodes of ketoacidosis and are autoantibody negative, without
etiopathogenetic classification of autoimmune type 1 diabetes. There is no
association with HLA risk alleles. This form of type 1 diabetes is inherited
with high penetrance, occurs very rarely and is predominantly in patients with
an Asian or African background [9].[1]
Therapy goals
The therapy for type 1 diabetes aims to avoid diabetes-related reductions to the
quality of life. It is also important to achieve for those affected to accept the
disease and be satisfied with the therapy regime.
In order to avoid diabetes-related reductions to the quality of life, the therapy
should be designed in such a way that the risk of severe metabolic disorders (severe
hypoglycaemia and/or severe hyperglycaemia with ketoacidosis or diabetic
coma) is as low as possible. Furthermore, the therapy should be conducted in such a
way as to reduce the risk of developing microangiopathies (retinopathy, nephropathy)
and other diabetes-associated complications (neuropathy, accelerated
macroangiopathy).
A further therapeutic goal in the treatment of type 1 diabetes is to avoid the
development of additional risk factors. This is done by monitoring and, if present,
undergoing proper therapy for blood pressure, lipid profile and obesity-induced
insulin resistance. The documentation in the Diabetes Health Pass (Gesundheitspass)
can be helpful.
|
Recommendations
|
Degree of recommendation
|
|
In adults with type 1 diabetes, an HbA1c value of 7.5%
(≤58 mmol/mol) should be targeted at≤as
long as no problematic hypoglycaemia occurs. [10]
[11]
|
B
|
|
In adults with type 1 diabetes, HbA1c≤6.5%
(≤48 mmol/mol) may also be targeted if there is
a low intrinsic risk of hypoglycaemia (e. g. new onset
of type 1 diabetes, stable low glycaemic variability). [10]
[11]
(strong consensus)
|
0
|
|
In adults with type 1 diabetes, a less tight HbA1c
value<8.5% (69 mmol/mol) should be
sought if therapy safety cannot be guaranteed, if severe
hypoglycaemia has frequently occurred, extensive comorbidities
or advanced macrovascular complications are present. [10]
[11]
(strong consensus)
|
B
|
|
Adults with type 1 diabetes with an HbA1c
value>9% (75 mmol/mol) or higher can be
assumed to have polyuria symptoms and a significantly increased
risk of secondary diseases. Expert consensus (strong
consensus)
|
Statement
|
|
In people with type 1 diabetes and severe hypoglycaemia in recent
months, the HbA1c target should be raised. [12]
[13]
[14]
(strong consensus)
|
B
|
|
In people with type 1 diabetes and low life expectancy
or significant comorbidities, an increase in blood
glucose can be considered with the sole therapeutic
goal of symptom-free treatment. [15]
(strong consensus)
|
0
|
Therapy for type 1 diabetes
Therapy for type 1 diabetes
The type 1 diabetes therapy concept consists of insulin therapy, nutritional
knowledge, training, glucose self-monitoring and psychosocial care.
Insulin therapy
The indication for insulin therapy in type 1 diabetes is permanent and lifelong.
A prerequisite for the substitution of lacking insulin in people with type 1
diabetes is knowledge of the physiological insulin requirement as well as the
pharmacokinetic and pharmacodynamic properties of the insulins used for therapy
([Table 1]). For the planning of insulin
therapy, the following are also important: (a) consideration of how the additive
insulin requirement depends on the dietary intake (prandial insulin always in
addition to basal insulin requirement) and (b) the ratio between basal and
prandial insulin requirement.
Table 1 Types of insulin – efficacy, adverse effects,
interactions and contraindications (with data from [16]).
|
Effect
|
|
Onset
|
Maximum
|
Duration
|
Usually used
|
References
|
|
Human insulins
|
|
NPH insulin
|
1–2 h
|
6–7 h
|
14 h
|
2×daily
|
[17]
[18]
|
|
Normal insulin
|
30–60 min
|
3 h
|
8 h
|
0–30 min before meals
|
[19]
|
|
Mixed insulin NPH (70)/Normal (30)
|
30–60 min
|
3–3.5 h
|
14 h
|
Before breakfast and dinner
|
[20]
[21]
|
|
Insulin analogues
|
|
Degludec
|
1–2 h1
|
8–14 h low Maximum
|
>42 h
|
1×daily
|
[22]
[23]
[24]
|
|
Detemir
|
1 h
|
7–9 h
|
19–26 h
|
1 or 2×daily
|
[18]
[25]
[26]
|
|
Glargin U100
|
1 h
|
8–12 h
|
20–27 h
|
1 or 2×daily
|
[25]
[26]
[27]
|
|
Glargin U300
|
1–6 h1
|
12–16 h low Maximum
|
30–32 h
|
1×daily
|
[27]
[28]
|
|
Aspart
|
20–25 min
|
120–150 min
|
4–5 h
|
0–15 min before meals
|
[29]
[30]
|
|
Glulisin
|
20–25 min
|
120–150 min
|
4–5 h
|
0–15 min before meals
|
[19]
|
|
Lispro
|
20–25 min
|
120–150 min
|
4–5 h
|
0–15 min before meals
|
[31]
|
|
Ultra rapid lispro
|
11–13 min
|
120 min
|
4–5 h
|
Immediately before meals
|
[82]
|
|
Faster Aspart
|
15 min
|
120 min
|
4 h
|
Immediately before meals
|
[29]
|
|
Mixed insulin protamine aspart (70)/aspart (30);
protamine lispro (70), lispro (30)
|
20–25 min
|
2–3 h
|
10–14 h
|
0–15 min before breakfast and dinner
|
[30]
[31]
[32]
[33]
|
|
Combination insulin degludec (70)/aspart (30)
|
20–25 min
|
2–3 h
|
>30 h
|
0–15 min before one or before two main meals
|
[34]
[35]
|
1 Under steady state conditions, the time of onset of action
is of low clinical relevance due to the long effect and the flat action
profile. NPH = Neutral protamine Hagedorn.
Individual insulin needs
In principle, the individual insulin requirement of people with type 1
diabetes resulting from an absolute insulin deficiency depends on the
physiological insulin secretion. This occurs both without food intake
(= basal insulin requirement) and after food intake (=
prandial insulin requirement), i. e. discontinuous and pulsatile.
When dosing insulin, it must be taken into account that the absolute insulin
requirement also depends on the individual insulin sensitivity of the
respective patient. The therapeutic insulin requirement can therefore only
be deduced preliminarily based on the insulin secretion of a healthy
person.
Strategies of insulin therapy
Simple and more complex (intensified) strategies are available for insulin
therapy.
Conventional therapy
Conventional therapy is characterized by a binding specification of both the
insulin dose and the sequence and size of the meals (fixed carbohydrate
portions). A blood glucose self-measurement is recommended 3–4 times
daily. As a rule, fixed insulin mixtures are used, which are administered twice
a day for breakfast and dinner and, as far as possible, adapted to the eating
behaviour of the patients. A simple conventional insulin therapy can only be
successful with a fixed diet plan.
In contrast to intensified conventional insulin therapy, this form of insulin
therapy is a subordinate therapy option for people with type 1 diabetes in the
following cases:
-
For people who cannot meet the requirements of an intensified therapy
(due to cognitive impairment, illness or age),
-
For people who decide against intensified therapy after receiving
extensive information on the risks and benefits,
-
For people with a significant problem adhering to long-term
therapies.
Since medium and long-term glycaemic control is crucial for reducing the risk of
diabetes-associated complications, conventional insulin therapy can be
sufficient if the individual HbA1c target values are reached, hypoglycaemia is
avoided, and the quality of life is not restricted by the therapy.
Intensified conventional insulin therapy
The intensified conventional insulin therapy is defined as the administration of
at least three insulin injections per day. Above all, however, it is
characterised by substituting the basal insulin requirement with long-acting
basal insulin and by substituting prandial insulin requirement with rapid-acting
bolus insulin at mealtimes (basal bolus principle). Synonyms of intensified
conventional insulin therapy are functional insulin therapy and flexible insulin
therapy. This therapy can be performed with insulin syringes, insulin pens or
insulin pumps (see recommendations).
Insulin types
There are currently two different groups of insulin available in Germany for
insulin replacement therapy for people with type 1 diabetes: human insulin
and insulin analogues ([Table 1]).
The use of animal insulin can be very necessary for a few people; the
possibility of importing animal insulin is hereby referred to.
|
Recommendations
|
Degree of recommendation
|
|
Human insulins (normal insulin or human insulins with
delayed onset of action) or insulin analogues
(short-acting or long-acting) are to be used for the
therapy of people with type 1 diabetes. [36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
(strong consensus)
|
A
|
|
If strict therapeutic goals are pursued, the use of
short-acting and long-acting insulin analogues is
associated with advantages in terms of reducing HbA1c
and risk of hypoglycaemia as compared to normal insulin.
[43]
[44]
[45]
(strong consensus)
|
Statement
|
Insulin administration
Adequate handling and correct administration of the insulin used are
prerequisites for successful insulin therapy. Information and review must be
a mandatory part of the structured training.
Continuous subcutaneous insulin infusion (CSII)
|
Recommendations
|
Degree of recommendation
|
|
In people with type 1 diabetes, the use of insulin pump
therapy should be examined if the individual therapy goals
are not achieved using intensified insulin therapy. [46]
[47]
[48]
[49]
[50]
(strong consensus)
|
B
|
|
In people with type 1 diabetes, the use of insulin pump
therapy should be checked in cases of frequent hypoglycaemia
or recurrence of severe hypoglycaemia using intensive
insulin therapy. [49]
[51]
(strong consensus)
|
B
|
|
People with type 1 diabetes can be offered insulin pump
therapy in the following constellations:
-
In cases of frequently irregular daily routines,
e. g. shift work, activities with varying
physical activity, problems with the implementation
of classic ICT/syringe therapy (among other
things to improve the quality of life) [52]
[53],
-
In cases of planned pregnancy (begin before
conception) or at the beginning of a pregnancy,
-
For low insulin requirements, expert consensus
class of evidence (CoE) IV,
-
In cases of insufficient glycaemic control using ICT,
e. g. dawn phenomenon.
[54]
[55]
[56]
[57]
[58]
(strong consensus)
|
0
|
|
Prerequisites for the start of insulin pump therapy in people
with type 1 diabetes are:
-
The patient has mastered an intensified insulin
therapy,
-
A qualified diabetology staff with appropriate
experience in the use of insulin pumps is
present,
-
Insulin pump therapy training by a well-trained
training team.
Expert consensus (strong consensus)
|
Statement
|
|
ICT = intensified conventional insulin therapy.
|
The precision of the blood glucose self-monitoring is sufficient for
self-management, even if it is lower compared to laboratory measurements [59]
[60].
|
Recommendations
|
Degree of recommendation
|
|
Self-management using rtCGM or iscCGM (FGM) should be offered
if individual therapy goals are not achieved. Expert
consensus (strong consensus)
|
B
|
|
In order to use the advantages of a rtCGM/iscCGM
system effectively, adequate training and regular diabetic
care by diabetic teams experienced in the use of these
systems are required. Expert consensus (strong
consensus)
|
Statement
|
|
rtCGM = real-time continuous glucose monitoring, iscCGM =
intermittent-scanning continuous glucose monitoring, FGM = flash
glucose monitoring.
|
Nutrition
It is of crucial importance for the therapy of type 1 diabetes that patients are
able to assess the glucose efficacy of their diet in order to adjust the insulin
dosage accordingly. Recommendations on the objectives, content and modalities of
training for type 1 diabetes are given in section 4.4
Training/structured training and treatment programmes.
|
Recommendations
|
Degree of recommendation
|
|
For people with type 1 diabetes, neither a specific form of
nutrition or diet is required, nor are specific diet foods
required. They are subject to the general recommendations on
healthy eating. Expert consensus (strong
consensus)
|
Statement
|
Training/structured training and treatment programmes
In the treatment of type 1 diabetes, patients must – of their own accord
– implement the essential therapeutic measures (insulin substitution
usually several times a day, hypoglycaemia prevention, etc.) in accordance with
their individual therapy goals. The success of therapy and the prognosis of
people with type 1 diabetes therefore depend very much on their ability to treat
themselves [61]
[62]
[63]. The knowledge and skills
required for this are taught in structured patient training courses. The
training measures are intended to enable patients (empowerment or capacity to
self-manage) “ to integrate diabetes into their own lives as best as
possible on the basis of their own decisions, to avoid acute or long-term
negative consequences of diabetes and to maintain their quality of life”
[62].
Forms of diabetes training
Basic training
In basic training and treatment programmes, which should be carried out
as soon as possible after the manifestation of diabetes or the
changeover to a different therapy regime, basic knowledge and skills for
the implementation of diabetes therapy, for informed decision-making and
for coping with the disease are developed together with the patient.
Repeated or supplementary training measures have the primary objective
of supporting patients with type 1 diabetes in the event of difficulties
in implementing therapy in everyday life and of offering concrete
assistance with problems related to diabetes (e. g. lack of
skills, problems in everyday life).
Problem-specific training and treatment programmes
These are aimed at patients in special, diabetes-specific problem
situations (e. g. occurrence of secondary diseases, problems
with hypoglycaemia). The indication for a problem-specific training and
treatment programme may be given if the patient has to implement a
specific, new form of therapy in everyday life (e. g. insulin
pump therapy, continuous glucose monitoring), if significant problems
are associated with acute complications (e. g. hypoglycaemia
perception disorder) or in connection with subsequent complications
(e. g. neuropathy, sexual disorders, diabetic foot, nephropathy,
retinopathy, cardiovascular events) or when special situations exist in
everyday life which make the implementation of the therapy more
difficult (e. g. shift work, fasting, psychological problems)
[61]
[64].
Therapy in special situations
Therapy in special situations
Hospital stays
|
Recommendations
|
Degree of recommendation
|
|
The disease type 1 diabetes should be clearly indicated in
the medical record during a hospital stay. Expert
consensus per
[65]
(strong consensus)
|
A
|
|
In all people with type 1 diabetes, an order to monitor blood
glucose must be issued during an inpatient stay. Trained
patients should be able to continue self-management as far
as possible. The blood glucose levels should be accessible
to all treating members of the healthcare team. If no HbA1c
value from the last 3 months is available, it should be
determined. Expert consensus (strong consensus)
|
A
|
|
Hospitalized patients with type 1 diabetes should receive
intensified insulin therapy with basal insulin and bolus
insulin/pump therapy. Expert consensus
per
[11]
(strong
consensus)
|
A
|
|
The administration of fast-acting insulin only for correction
by means of a post injection plan is inferior to such
insulin therapy; for this reason, the administration of
insulin should not exclusively take place in the form of a
post injection plan. Expert consensus per
[11]
(strong
consensus)
|
B
|
Therapy during travel
People with type 1 diabetes are not subject to significant restrictions on travel
activity and destinations solely from having diabetes. Restrictions, if any,
result from secondary illnesses. It is often the case that metabolic parameters
deteriorate during a journey. Consultation before travel and planning of the
trip based on diabetes treatment are useful. There are many well-made
recommendations available by self-help organisations, professional associations
and also from government organisations, mostly in the form of checklists, which,
at least in the case of patients with type 2 diabetes requiring insulin, have
also been verified within studies [66] and
have found their way into most structured patient training courses.
Acute complications
Diabetes-associated emergencies in people with type 1 diabetes are either the result
of insulin deficiency or insulin overdose. Both hypo- and hyperglycaemia can be
life-threatening ([Table 2]).
Table 2 Typical symptoms of hypoglycaemia (with data from [67]
[68]
[69]
[70]
[71])
|
Autonomic symptoms
|
Neuroglycopenic symptoms
|
General discomfort
|
|
Sweating
|
Mental confusion
|
Nausea
|
|
Trembling
|
Rapid, incoherent speech
|
Headaches
|
|
Cravings
|
Difficulty in finding words
|
|
|
Palpitations
|
Irritability
|
|
|
Double vision and other
|
|
|
visual disturbances
|
|
|
Headaches
|
|
|
Anxiety
|
|
|
Sleepiness
|
|
|
Difficulty with dexterity/coordination
|
|
|
Limitation of awareness and action
|
|
|
Unconsciousness
|
|
|
Cramps
|
|
Hypoglycaemia
The prevention of hypoglycaemia is one of the greatest challenges in achieving a
blood glucose level as close as possible to the norm [11]
[67].
Definition/degrees of severity
The current international classification of hypoglycaemia into mild and
severe hypoglycaemia is not based on specific blood glucose values, but
exclusively on the ability to conduct self-therapy [12]
[68]:
-
Mild hypoglycaemia: Hypoglycaemia can be independently treated with
carbohydrate intake by the patients.
-
Severe hypoglycaemia: The patient depends on outside help in treating
the hypoglycaemia (e. g. from relatives or medical
personnel) ([Table 3]).
Table 3 Therapeutic measures in hypoglycaemic events for
people with type 1 diabetes.
|
Mild hypoglycaemia
|
Severe hypoglycaemia
|
|
Therapy by patient possible
|
Patient is conscious, but therapy is no longer possible
by the patient.
|
If unconscious
|
|
Without IV access (e. g. by
family/others), 3 mg glucagon intranasal as a
nasal powder (recommended as of 4 years of age).
|
With IV access
|
|
20 g carbohydrates (preferably glucose; 200 ml fruit
juice also possible)
|
30 g carbohydrates (glucose)
|
1 mg glucagon IM or SC (Caveat: Vomiting and danger of
aspiration)
|
50 ml 40% glucose1 in bolus IV
|
|
Measure blood glucose after 15 min and repeat therapy if
blood glucose concentration remains low (50–60
mg/dl; 2.8–3.3 mmol/l). After
successful therapy, take a meal or snack to avoid
recurring hypoglycaemia.
|
If no response is received after 5 min of therapy at the
latest, repeat. After successful therapy, take a meal or
snack to avoid recurring hypoglycaemia.
|
1 or 25 ml 40% glucose. IV = intravenous,
IM = intramuscular, SC = subcutaneous.
Causes and symptoms
In people with type 1 diabetes, hypoglycaemia is always the result of an
absolute or relative insulin overdose. Causes for insulin overdose can
include [69]:
-
Insulin dosage is too high, insulin injection at the wrong time, or
the wrong type of insulin is injected
-
Decreased exogenous glucose intake (forgotten meals)
-
Glucose consumption is increased (e. g. after sports)
-
Endogenous glucose production is lowered (for example after alcohol
consumption, in case of renal insufficiency)
-
Insulin sensitivity is increased (during the night, after improved
glycaemic control, after improved physical fitness).
-
Insulin clearance is lowered (for example, in renal
insufficiency).
Treatment of hypoglycaemia
People with type 1 diabetes and hypoglycaemia perception disorder can be
offered specific structured training (see section
“Training/structured training and treatment
programmes”).
Diabetic ketoacidosis
Diabetic ketoacidosis (DKA) is a metabolic derailment due to an absolute or
relative insulin deficiency and consecutive metabolization of fatty acids, which
can occur with or without hyperosmolar diuresis and thus also without massive
hyperglycaemia. Causes of diabetic ketoacidosis:
Diabetic ketoacidosis occurs in clinical routine during:
-
Undetected first manifestation of type 1 diabetes mellitus,
-
Interruption of an ongoing insulin therapy,
-
Interruption of insulin administration during insulin pump therapy,
-
Acute, severe diseases associated with an increased, catabolic
metabolization and increased insulin requirements.
Biochemical definition and suspected diagnosis
Diabetic ketoacidosis is biochemically defined by:
-
Blood glucose>250 mg/dl (13.9 mmol/l)[2] and
-
Ketonemia and/or
-
Ketonuria with arterial pH<7.35 or
-
Venous pH<7.3; serum bicarbonate<270 mg/dl
(15 mmol/l)
The suspected diagnosis of ketoacidosis must be made if persistent
hyperglycaemia>250 mg/dl (13.9 mmol/l) is detected
in combination with ketonuria, in particular if this finding is accompanied
by corresponding clinical symptoms ([Table
4]) or a comorbidity is present. Further laboratory tests are
required to confirm the diagnosis.
Table 4 Symptoms of diabetic ketoacidosis (with data from:
[67]
[72]
[73]).
|
Gastrointestinal Symptoms
|
Loss of appetite, nausea and vomiting, abdominal pain up
to pseudo-peritonitis.
|
|
Symptoms of dehydration
|
Symptoms of dehydration are dry mouth, standing skin
folds, muscle cramps (calves, abdomen), soft bulbi, drop
in blood pressure, polyuria (primary), oliguria
(secondary). The cause is osmotic diuresis due to the
increased blood glucose concentration (up to
100–200 g glucose/day!), which leads to
a significant loss of fluid. This can lead to
microcirculatory disturbances and hyperviscosity with
thrombotic events.
|
|
Respiratory symptoms
|
The clinical characteristic of severe derailment is
metabolic acidosis, with respiratory compensation. To
compensate an acidosis with pH values of 7.1 and less,
the carbon dioxide partial pressure in the blood gas
analysis drops down to 15 mmHg. The deep, laboured or
slightly rapid breathing is called Kussmaul’s
respiration. The exhaled air smells of acetone, the
typical, fruity smell of ketoacidosis.
|
|
Changes in consciousness
|
While the state of consciousness is not restricted in a
mild ketoacidosis, a ketoacidosis of moderate severity
is associated with restrictions of consciousness
(drowsiness). Patients with severe diabetic ketoacidosis
are stuporous or comatose.
|
Symptoms
Laboratory chemical diagnostics
The following laboratory parameters are to be determined initially using
quality-controlled laboratory standards if diabetic ketoacidosis is
suspected: Blood glucose and ketones in urine or blood.
If these values are pathological, an arterial or venous blood gas test
should be carried out and potassium levels, serum creatinine, blood
count and C-reactive protein (CRP) determined, as they have a decisive
effect on the therapeutic regime. For outpatients, an urgent transfer to
hospital must be arranged. If infections are suspected, bacterial
cultures (e. g. blood, urine, pharynx) should be initiated.
Table 5 Severity of diabetic ketoacidosis.
|
Parameter
|
Degree of severity
|
|
Mild
|
Moderate
|
Severe
|
|
pH
|
<7.3
|
≤7.2
|
≤7.1
|
|
Bicarbonate
|
<270 mg/dl
|
≤180 mg/
|
<90 mg/dl
|
|
(15 mmol/l)
|
10 mmol/l)
|
(5 mmol/l)
|
An extended diagnosis is to be carried out within the framework of causal
research and depending on the comorbid diseases.
Severity of diabetic ketoacidosis
The classification of diabetic ketoacidosis into 3 degrees of severity is
based on the classification of the American Diabetes Association (ADA) [74] ([Table
5]).
Table 6 Example of an infusion plan for the replacement of
liquid and to compensate for the potassium deficiency.
|
Infusion solution
|
Quantity and period
|
|
0.9% NaCl 1000 ml
|
1000 ml over the next 1 h
|
|
0.9% NaCl 1000 ml with potassium chloride
|
1000 ml over the next 2 h
|
|
0.9% NaCl 1000 ml with potassium chloride
|
1000 ml over the next 2 h
|
|
0.9% NaCl 1000 ml with potassium chloride
|
1000 ml over the next 4 h
|
|
0.9% NaCl 1000 ml with potassium chloride
|
1000 ml over the next 4 h
|
|
0.9% NaCl 1000 ml with potassium chloride
|
1000 ml over the next 6 h
|
|
Potassium levels in the first 24 h (mmol/l)
|
Potassium administration per 1000 ml infusion solution
(mEq/l)
|
|
Higher than 5.5
|
No administration
|
|
3.5–5.5
|
40
|
|
<3.5
|
Additional oral administration of potassium, if
necessary
|
|
Infusion solution
|
Quantity and period
|
After 12 h, the cardiovascular situation is to be assessed and the
liquid replacement adjusted accordingly. The S3 guideline
“Intravascular Volume Therapy in Adults” (AWMF Reg.
No. 001–020) recommends that balanced crystalloid solutions
should be used for volume replacement in ICU patients.
|
Recommendations
|
Degree of recommendation
|
|
People with type 1 diabetes and clinical suspicion of
moderate or severe diabetic ketoacidosis should be
admitted to hospital immediately. They should be treated
in the hospital on the basis of a detailed written
treatment plan. [75]
(strong consensus)
|
A
|
|
The monitoring of people with type 1 diabetes who are
being treated for diabetic ketoacidosis should be
carried out under intensive medical conditions. During
the treatment of severe ketoacidosis, clinical
evaluation and monitoring should be performed at least
every hour. Expert consensus as per
[67]
(strong
consensus)
|
A
|
|
Diabetic ketoacidosis should be treated according to the
following therapy principles:
-
Circulation stabilization with initial volume of
1 l of isotonic solution (0.9% NaCl) in
the first hour ([Table 6]);
-
Then, additional liquids and electrolytes equal
depending on age, height, weight and possible
concomitant diseases (total fluid intake can be up
to 6 l/24 h and more for a patient
weighing 70 kg);
-
Potassium replacement already in the standard
range depending on the severity of the
ketoacidosis by administering 40 mEq/L
potassium chloride per 1000 ml NaCl 0.9%,
example see below;
-
Slow normalization of blood glucose using
low-dose insulin; intravenous insulin
administration via perfusor (0.05–0.1
U/kg body weight/h IV).
–
-
Compensation of acidosis and ketosis (addition
of bicarbonate only at pH<7.0 and then up
to a correction of 7.1);
-
Avoidance of therapy complications
(hypokalaemia, cerebral oedema);
-
Diagnosis and therapy of the triggering causes
of DKA.
Expert consensus as per
[76]
(strong consensus)
|
A
|
|
IV = intravenous, DKA = diabetic ketoacidosis.
|
People with type 1 diabetes significantly underestimate the danger of
ketoacidosis, as it is rather rare compared to the acute complication in the
form of hypoglycaemia. Often, training on the subject of ketoacidosis took
place a while ago and patients do not always remember how they can treat
ketoacidosis themselves. Therefore, at regular intervals during check-ups,
the topic should be addressed of recognizing ketoacidosis and treating it in
a timely manner. It would be recommended to develop an evaluated short
training module or other form of easily accessible information on
ketoacidosis (e. g. a smartphone app). Patients should always
remember that ketoacidosis is a dangerous medical situation and, in case of
doubt, immediate medical assistance should be sought through the emergency
medical services.
Control of diabetes-associated secondary diseases and associated risk
factors
|
Recommendations
|
Degree of recommendation
|
|
For diagnosing lipohypertrophy, an inspection of the
injection sites and palpation of the skin should be carried
out at least once a year, and quarterly in the case of
abnormalities and in particular in the case of inexplicably
fluctuating glucose values. Expert consensus (strong
consensus)
|
B
|
|
From the age of 11 or after a diabetes duration of 5 years,
people with type 1 diabetes without known
diabetes-associated secondary diseases or comorbidities
should undergo the following early detection examinations on
a regular basis:
|
B
|
|
a)
|
Determination of the albumin-creatinine ratio and calculation
of the glomerular filtration rate for early detection of
microalbuminuria and nephropathy. Expert consensus CoE IV
as per
[77]
(strong consensus)
|
|
b)
|
An ophthalmological retinal screening using mydriatic fundus
photography
|
|
I.
|
If no diabetic retinal changes are detected, the screening
interval should be two years for known low risk (=
no ophthalmological risk and no general risk).
|
|
II.
|
If the ophthalmologist does not know the general risk
factors, he should treat the patient as if the patient has
an unfavourable general risk profile; for all other risk
constellations, the screening interval should be one year.
[78]
(strong
consensus)
|
|
c)
|
Medical history and examination for early diagnosis of
neuropathy, at least annually. Expert consensus as per
NVL neuropathy
[79]
(strong consensus)
|
|
d)
|
Medical history and examination for early detection of foot
complications, at least annually. Expert consensus as per
[80]
(strong
consensus)
|
|
e)
|
Examination of the cardiovascular system, risk-adapted
Expert consensus as per
[81]
(strong
consensus) In addition to a physical examination,
this includes the determination of biochemical parameters
for cardiovascular risk factors, such as blood pressure
measurement, determination of blood lipids for the early
detection of lipid metabolism disorders.
|
|
Expert consensus (strong consensus)
|
|
CoE = class of evidence, NVL = Nationale Versorgungsleitlinie (National
Healthcare Guideline).
|
Guideline information
The evidence-based guideline was prepared on behalf of the German Diabetes
Society/Deutsche Diabetes Gesellschaft (DDG). President of the DDG at this
point in time was Prof. Dr. med. Dirk Müller-Wieland (2017-2019). The
guideline is valid from March 2018 until March 2023.
Expert group appointed by the DDG Board
-
Prof. Dr. Thomas Haak, Bad Mergentheim (Coordinator)
-
Dr. Stefan Gölz, Esslingen
-
Prof. Dr. Andreas Fritsche, Tübingen
-
PD Dr. Martin Füchtenbusch, Munich
-
Dr. Thorsten Siegmund, Munich
Representatives of other organisations who voted on the recommendations and
commented on the content of the guideline:
-
Elisabeth Schnellbächer; Association of Diabetes Consultants and
Training Occupations in Germany/Verband der Diabetesberatungs-und
Schulungsberufe Deutschlands, Birkenfeld
-
Prof. Dr. Horst H. Klein, German Society for Internal
Medicine/Deutsche Gesellschaft für Innere Medizin,
Bochum
-
Dr. Til Uebel, German Society for General and Family
Medicine/Deutsche Gesellschaft für Allgemein- und
Familienmedizin, Ittlingen
-
Diana Droßel, German Diabetes Aid – People with
Diabetes/Deutsche Diabetes Hilfe – Menschen mit Diabetes,
Eschweiler
German Diabetes Association: Clinical Practice Guidelines This is a translation
of the DDG clinical practice guideline published in Diabetol Stoffwechs 2023; 18
(Suppl 2): S136–S147. doi: 10.1055/a-2075-9984
