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:
-
Reduce the rate of diabetes-associated complications. The diagnosis and
treatment of lipodystrophy is also described for the first time;
-
Improve the quality of life of people with type 1 diabetes;
-
Contribute to the adequate care of people with type 1 diabetes in hospitals,
both in regular and intensive care units. In particular, the implementation
of safe protocols to protect against hypoglycaemia in intravenous insulin
therapy should be supported;
-
Ensure correct treatment of acute complications and thus reduce the risk of
complications due to treatment;
-
Reinforce the correct 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 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 viability).
[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
([Tab. 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.
Tab. 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
|
>42 h
|
1×daily
|
[22], [23], [24]
|
|
|
maximum
|
|
|
|
|
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
|
30–32 h
|
1×daily
|
[27], [28]
|
|
|
maximum
|
|
|
|
|
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]
|
|
Faster Aspart
|
15 min
|
120 min
|
4 h
|
Immediately before meals
|
[29]
|
|
Ultra rapid lispro
|
11–13 min
|
120 min
|
4–5 h
|
Immediately before meals
|
[82]
|
|
Mixed insulin protamine (70)/Aspart (30); protamine
(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
pump pens (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 ([Tab. 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 application
Adequate handling and correct application of the insulin used are
prerequisites for successful insulin therapy. Information and review must be
an integral part of the structured training.
|
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
(EC/EK) 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:
-
Mastery of an intensified insulin therapy on the part
of the patient,
-
The provision of care by a qualified diabetology
staff with appropriate experience in the use of
insulin pumps,
-
Insulin pump therapy training by a well-trained
training team.
Expert consensus (strong consensus)
|
Statement
|
Continuous subcutaneous insulin infusion (CSII)
Blood glucose self-monitoring, rtCGM and iscCGM (FGM)
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
|
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 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, this 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 because of 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 for planning purposes by self-help organisations,
professional associations and also from government organisations, mostly in the
form of checklists. These checklists, 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 ([Tab. 2]).
Tab. 2 Typical symptoms of hypoglycaemia (from [67], [68], [69], [70], [71]).
|
Autonomic symptoms
|
Neuroglycopenic symptoms
|
General discomfort
|
|
Sweating
|
Mental confusion
|
Nausea
|
|
Trembling
|
Rapid, incoherent speech
|
|
|
Cravings
|
Difficulty in finding words
|
|
|
Irritability
|
|
|
Palpitations
|
Seeing double and other visual disorders
|
|
|
Headaches
|
|
|
Anxiety
|
|
|
Sleepiness
|
|
|
Difficulty with dexterity/coordination
|
|
|
Limitation of awareness and action
|
|
|
Unconsciousness
|
|
|
Seizures
|
|
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 for 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) ([Tab. 3]).
Tab. 3 Therapeutic measures in hypoglycaemic people
with type 1 diabetes.
|
Mild hypoglycaemia
|
Severe hypoglycaemia
|
|
Therapy by patients 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 (Warning: Vomiting and
danger of aspiration)
|
50 ml 40% glucose1 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 prevent recurrent hypoglycaemia.
|
|
1 or 100 ml 20% glucose.
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
([Tab. 4]) or a comorbidity is
present. Further laboratory tests are required to confirm the diagnosis.
Tab. 4 Symptoms of diabetic ketoacidosis (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 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.
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
follows the classification by the American Diabetes Association (ADA)
[74] ([Tab. 5]).
Tab. 5 Degrees of severity of diabetic
ketoacidosis.
|
Parameter
|
Degree of severity
|
|
Mild
|
Moderate
|
Severe
|
|
pH
|
<7.3
|
≤7.2
|
≤7.1
|
|
Bicarbonate
|
<270 mg/dl (15 mmol/l)
|
≤180 mg/dl (10 mmol/l)
|
<90 mg/dl (5 mmol/l)
|
Tab. 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
|
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:
|
A
|
-
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)
|
|
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
|
-
Determination of the albumin-creatinine ratio and
calculation of the glomerular filtration rate for
early detection of microalbuminuria and nephropathy.
Expert consensus EK IV as per
[77]
(strong
consensus)
-
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 had
an unfavourable general risk profile; for all other risk
constellations, the screening interval should be one year.
[78]
(strong
consensus)
|
|
-
Medical history and examination for early diagnosis
of neuropathy, at least annually. Expert
consensus as per NVL neuropathy
[79]
(strong
consensus)
-
Medical history and examination for early detection
of foot complications, at least annually. Expert
consensus as per
[80]
(strong
consensus)
-
Examination of the cardiovascular system,
risk-adapted [Expert consensus as per [81].]
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)
|
|
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 Diabetologie 2021; 16 (Suppl 2): S142–S153
DOI 10.1055/a-1515-8682
