German Diabetes Association: Clinical Practice Guidelines Thieme

Therapy of Type 1 Diabetes

Abridged Version of the S3 Guideline (AWMF Register Number: 057–013;
2nd Edition)

Authors
Thomas Haak1, Stefan Gölz2, Andreas Fritsche3, Martin Füchtenbusch4, Thorsten Siegmund5, Elisabeth Schnellbächer6,
Harald H. Klein7, Til Uebel8, Diana Droßel9

Affiliations Bibliography
1 Diabetes Center, Bad Mergentheim, Germany Exp Clin Endocrinol Diabetes
2 Diabetic Practice, Esslingen, Germany DOI 10.1055/a-1624-3340
3 Department of Internal Medicine IV, University Hospital, ISSN 0947-7349
Tübingen, Germany © 2022. Thieme. All rights reserved.
4 Diabetes Center, Munich, Germany Georg Thieme Verlag KG, Rüdigerstraße 14,
5 Diabetes, Hormones and Metabolism Centre, Private 70469 Stuttgart, Germany
Practice at the Isar Hospital, Munich, Germany
6 Birkenfeld, Germany German Diabetes Association: Clinical Practice Guidelines
7 Department of Endocrinology and Diabetes, Medical This is a translation of the DDG clinical practice guideline
Hospital I, Bergmannsheil University Hospitals, Ruhr published in Diabetologie 2021; 16 (Suppl 2): S142–S153
University of Bochum, Bochum, Germany DOI 10.1055/a-1515-8682
8 prima-diab Practice Dres. Uebel, Ittlingen, Germany
Correspondence
9 Eschweiler, Germany
Prof. Dr. med. Thomas Haak
Diabetes Center Mergentheim
Theodor Klotzbücher-Straße 12
97980 Bad Mergentheim
Germany
[email protected]

Addressees and objectives 3. Contribute to the adequate care of people with type 1 diabetes
This guideline is directed at all people with type 1 diabetes and all in hospitals, both in regular and intensive care units. In particu-
occupational groups that care for people with type 1 diabetes, es- lar, the implementation of safe protocols to protect against
pecially: hypoglycaemia in intravenous insulin therapy should be sup-
▪▪ Registered diabetologists, ported;
▪▪ General practitioners and internists, 4. Ensure correct treatment of acute complications and thus
▪▪ Doctors working in hospitals (diabetes specialists, anaesthesi- reduce the risk of complications due to treatment;
ologists, surgeons, radiologists), 5. Reinforce the correct training of people with type 1 diabetes,
▪▪ Nurses/professional caregivers (in the operating theatre and/ especially in the outpatient sector.
or wards or in the field of diagnostics) and
▪▪ Outpatient or inpatient diabetes consultants and other Definition and classification of type 1
professional groups in diabetology.
In addition, the guideline is directed at higher-level institutions diabetes
such as health insurance companies or medical services. Currently, the disease diabetes mellitus is classified into 4 main
In preparing and updating these guidelines, the authors pursue types (as per etiological classification) according to the American
the following objectives: Diabetes Association (ADA) [1]:
1. Reduce the rate of diabetes-associated complications. The diag- 1. Type 1 diabetes (as a result of autoimmune beta-cell destruc-
nosis and treatment of lipodystrophy is also described for the tion, which usually leads to absolute insulin deficiency), sub-
first time; form: idiopathic;
2. Improve the quality of life of people with type 1 diabetes; 2. Type 2 diabetes (due to progressive loss of insulin secretion from
the beta cell, often against the background of insulin resistance);

Haak T et al. Therapy of Type 1 … Exp Clin Endocrinol Diabetes | © 2022. Thieme. All rights reserved.
 German Diabetes Association: Clinical Practice Guidelines Thieme

3. Other specific diabetes types (subtypes A: genetic defects of possible. Furthermore, the therapy should be conducted in such a
beta cell function; B: genetic defects of insulin efficacy; C: exo- way as to reduce the risk of developing microangiopathies (retino­
crine pancreatic disease, D: diabetes due to endocrinopathies; pathy, nephropathy) and other diabetes-associated complications
E: drug or chemical-induced; F: diabetes resulting from infec- (neuropathy, accelerated macroangiopathy).
tions; G: rare forms of immune-mediated diabetes; H: other A further therapeutic goal in the treatment of type 1 diabetes
genetic syndromes occasionally associated with diabetes); is to the development of additional risk factors. This is done by
4. Gestational diabetes (glucose tolerance disorder diagnosed for the monitoring and, if present, undergoing proper therapy for blood
first time in pregnancy with a 75 g oral glucose tolerance test). pressure, lipid profile and obesity-induced insulin resistance. The
documentation in the Diabetes Health Pass (Gesundheitspass) can
Type 1 diabetes occurs primarily in younger years but can also man- be helpful.
ifest itself in later life. Even today, when type 1 diabetes is diag-
nosed, a severe metabolic derailment in the form of ketoacidosis Recommendations Degree of
recommen-
can be seen in about 15–30 % of cases, reaching as far as loss of con-
dation
sciousness [2].
In adults with type 1 diabetes, an HbA1c value of 7.5 % B
Within the category type 1 diabetes, 2 subtypes are currently ( ≤ 58 mmol/mol) should be targeted at ≤ as long as no
distinguished: the immune-mediated form and the idiopathic form. problematic hypoglycaemia occurs. [10–11]
In adults with type 1 diabetes, HbA1c ≤ 6.5 % 0
Type 1 diabetes (immune-mediated, autoimmune ( ≤ 48 mmol/mol) may also be targeted if there is a low
disease) intrinsic risk of hypoglycaemia (e. g. new onset of type 1
diabetes, stable low glycaemic viability). [10, 11]
Type 1 diabetes is caused by a cell-mediated, chronic autoimmune
(strong consensus)
destruction of beta cells. The following serological markers are suit-
In adults with type 1 diabetes, a less tight HbA1c B
able for diagnosing type 1 diabetes [3–8]:
value < 8.5 % (69 mmol/mol) should be sought if therapy
▪▪ Islet cell antibodies (ICA) safety cannot be guaranteed, if severe hypoglycaemia
▪▪ Insulin autoantibodies (IAA) (for children and adolescents but has frequently occurred, extensive comorbidities or
not for adults) advanced macrovascular complications are present.
▪▪ Autoantibodies against glutamate decarboxylase of the B cell [10, 11] (strong consensus)

(GAD65A) Adults with type 1 diabetes with an HbA1c value > 9 % Statement
(75 mmol/mol) or higher can be assumed to have
▪▪ Autoantibodies to tyrosine phosphatase (IA-2ª) and IA-2ß
polyuria symptoms and a significantly increased risk of
▪▪ Autoantibodies against the zinc transporter 8 of the B-cell secondary diseases. Expert consensus (strong
(ZnT8) consensus)
Type 1 diabetes is diagnosed when one or more of these autoanti- In people with type 1 diabetes and severe hypoglycae- B
bodies are detected. At least one of these autoantibodies is detect- mia in recent months, the HbA1c target should be
able in 85–90 % of patients with stage 3 diagnosis, i. e. simultane- raised. [12–14] (strong consensus)
ous hyperglycaemia. In people with type 1 diabetes and low life expectancy 0
or significant comorbidities, an increase in blood
Idiopathic type 1 diabetes glucose can be considered with the sole therapeutic
goal of symptom-free treatment. [15](strong
Patients with idiopathic type 1 diabetes have a permanent insulin consensus)
deficiency, tend to repeated episodes of ketoacidosis and are au-
toantibody negative, without etiopathogenetic classification of au-
toimmune type 1 diabetes. There is no association with HLA risk
alleles. This form of type 1 diabetes is inherited with high pene- Therapy for type 1 diabetes
trance, occurs very rarely and is predominantly in patients with an The type 1 diabetes therapy concept consists of insulin therapy,
Asian or African background [9].1 nutritional knowledge, training, glucose self-monitoring and psy-
chosocial care.

Therapy goals Insulin therapy

The therapy for type 1 diabetes aims to avoid diabetes-related re- The indication for insulin therapy in type 1 diabetes is permanent
ductions to the quality of life. It is also important to achieve for those and lifelong. A prerequisite for the substitution of lacking insulin in
affected to accept the disease and be satisfied with the therapy re- people with type 1 diabetes is knowledge of the physiological in-
gime. sulin requirement as well as the pharmacokinetic and pharmaco-
In order to avoid diabetes-related reductions to the quality of dynamic properties of the insulins used for therapy (▶Tab. 1). For
life, the therapy should be designed in such a way that the risk of the planning of insulin therapy, the following are also important:
severe metabolic disorders (severe hypoglycaemia and/or severe (a) consideration of how the additive insulin requirement depends
hyperglycaemia with ketoacidosis or diabetic coma) is as low as on the dietary intake (prandial insulin always in addition to basal
insulin requirement) and (b) the ratio between basal and prandial
1 This classification is based on recommendations of the American Diabe- insulin requirement.
tes Association (ADA).

Haak T et al. Therapy of Type 1 … Exp Clin Endocrinol Diabetes | © 2022. Thieme. All rights reserved.
▶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 3h 8h 0–30 min before meals [19]
Mixed insulin NPH (70)/Normal (30) 30–60 min 3–3.5 h 14 h Before breakfast and [20], [21]
dinner
Insulin analogues
Degludec 1–2 h1 8–14 h low > 42 h 1 × daily [22], [23], [24]
maximum
Detemir 1h 7–9 h 19–26 h 1 or 2 × daily [18], [25], [26]
Glargin U100 1h 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 4h Immediately before [29]
meals
Ultra rapid lispro 11–13 min 120 min 4–5 h Immediately before [82]
meals
Mixed insulin protamine (70)/Aspart (30); 20–25 min 2–3 h 10–14 h 0–15 min before [30], [31], [32], [33]
protamine (70), Lispro (30) breakfast and dinner
Combination insulin Degludec (70)/Aspart 20–25 min 2–3 h > 30 h 0–15 min before one [34], [35]
(30) or before two main
meals
1Under 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 contrast to intensified conventional insulin therapy, this form
In principle, the individual insulin requirement of people with type of insulin therapy is a subordinate therapy option for people with
1 diabetes resulting from an absolute insulin deficiency depends type 1 diabetes in the following cases:
on the physiological insulin secretion. This occurs both without ▪▪ For people who cannot meet the requirements of an intensi-
food intake ( = basal insulin requirement) and after food intake fied therapy (due to cognitive impairment, illness or age),
( = prandial insulin requirement), i. e. discontinuous and pulsatile. ▪▪ For people who decide against intensified therapy after
When dosing insulin, it must be taken into account that the abso- receiving extensive information on the risks and benefits,
lute insulin requirement also depends on the individual insulin sen- ▪▪ For people with a significant problem adhering to long-term
sitivity of the respective patient. The therapeutic insulin require- therapies.
ment can therefore only be deduced preliminarily based on the in- Since medium and long-term glycaemic control is crucial for reduc-
sulin secretion of a healthy person. ing the risk of diabetes-associated complications, conventional in-
sulin therapy can be sufficient if the individual HbA1c target values
Strategies of insulin therapy are reached, hypoglycaemia is avoided, and the quality of life is not
Simple and more complex (intensified) strategies are available for restricted by the therapy.
insulin therapy.
Conventional therapy Conventional therapy is characterized by intensified conventional insulin therapy The intensified con-
a binding specification of both the insulin dose and the sequence ventional insulin therapy is defined as the administration of at least
and size of the meals (fixed carbohydrate portions). A blood glu- three insulin injections per day. Above all, however, it is character-
cose self-measurement is recommended 3–4 times daily. As a rule, ised by substituting the basal insulin requirement with long-acting
fixed insulin mixtures are used, which are administered twice a day basal insulin and by substituting prandial insulin requirement with
for breakfast and dinner and, as far as possible, adapted to the eat- rapid-acting bolus insulin at mealtimes (basal bolus principle). Syn-
ing behaviour of the patients. A simple conventional insulin thera- onyms of intensified conventional insulin therapy are functional in-
py can only be successful with a fixed diet plan. sulin therapy and flexible insulin therapy. This therapy can be per-
formed with insulin syringes, insulin pens or insulin pump pens (see
recommendations).

Haak T et al. Therapy of Type 1 … Exp Clin Endocrinol Diabetes | © 2022. Thieme. All rights reserved.
 German Diabetes Association: Clinical Practice Guidelines Thieme

Insulin types Continuous subcutaneous insulin infusion (CSII)

There are currently two different groups of insulin available in Ger- Blood glucose self-monitoring, rtCGM and iscCGM
many for insulin replacement therapy for people with type 1 dia- (FGM)
betes: human insulin and insulin analogues (▶Tab. 1). The precision of the blood glucose self-monitoring is sufficient for
The use of animal insulin can be very necessary for a few people; self-management, even if it is lower compared to laboratory meas-
the possibility of importing animal insulin is hereby referred to. urements [59, 60].

Recommendations Degree of
recommenda- Recommendations Degree of
tion recommenda-
Human insulins (normal insulin or human insulins A tion
with delayed onset of action) or insulin analogues Self-management using rtCGM or iscCGM (FGM) B
(short-acting or long-acting) are to be used for the should be offered if individual therapy goals are not
therapy of people with type 1 diabetes. [36–43] achieved. Expert consensus (strong consensus)
(strong consensus) In order to use the advantages of a rtCGM/iscCGM Statement
If strict therapeutic goals are pursued, the use of Statement system effectively, adequate training and regular
short-acting and long-acting insulin analogues is diabetic care by diabetic teams experienced in the
associated with advantages in terms of reducing use of these systems are required. Expert consensus
HbA1c and risk of hypoglycaemia as compared to (strong consensus)
normal insulin. [43–45] (strong consensus)

Insulin application Nutrition

Adequate handling and correct application of the insulin used are It is of crucial importance for the therapy of type 1 diabetes that patients
prerequisites for successful insulin therapy. Information and review are able to assess the glucose efficacy of their diet in order to adjust the
must be an integral part of the structured training. insulin dosage accordingly. Recommendations on the objectives, con-
tent and modalities of training for type 1 diabetes are given in section
Recommendations Degree of Training/structured training and treatment programmes.
recommen-
dation
In people with type 1 diabetes, the use of insulin pump B Recommendations Degree of
therapy should be examined if the individual therapy recommenda-
goals are not achieved using intensified insulin tion
therapy.[46–50] (strong consensus) For people with type 1 diabetes, neither a specific Statement
In people with type 1 diabetes, the use of insulin pump B form of nutrition or diet is required, nor are specific
therapy should be checked in cases of frequent diet foods required. They are subject to the general
hypoglycaemia or recurrence of severe hypoglycaemia recommendations on healthy eating. Expert consen-
using intensive insulin therapy.[49], [51](strong sus (strong consensus)
consensus)
People with type 1 diabetes can be offered insulin pump 0
therapy in the following constellations:– In cases of Training/structured training and treatment
frequently irregular daily routines, e. g. shift work, programmes
activities with varying physical activity, problems with
the implementation of classic ICT/syringe therapy In the treatment of type 1 diabetes, patients must – of their own ac-
(among other things to improve the quality of life) cord – implement the essential therapeutic measures (insulin sub-
[52, 53], stitution usually several times a day, hypoglycaemia prevention, etc.)
– In cases of planned pregnancy (begin before
in accordance with their individual therapy goals. The success of ther-
conception) or at the beginning of a pregnancy,
– For low insulin requirements, expert consensus (EC/ apy and the prognosis of people with type 1 diabetes therefore de-
EK) IV, pend very much on their ability to treat themselves [61–63]. The
– In cases of insufficient glycaemic control using ICT, knowledge and skills required for this are taught in structured pa-
e. g. dawn phenomenon. tient training courses. The training measures are intended to enable
[54–58] (strong consensus)
patients (empowerment or capacity to self-manage) “… to integrate
Prerequisites for the start of insulin pump therapy in Statement
diabetes into their own lives as best as possible on the basis of their
people with type 1 diabetes are:
– Mastery of an intensified insulin therapy on the part own decisions, to avoid acute or long-term negative consequences
of the patient, of diabetes and to maintain their quality of life” [62].
– The provision of care by a qualified diabetology staff
with appropriate experience in the use of insulin Forms of diabetes training
pumps,
Basic training In basic training and treatment programmes, which
– Insulin pump therapy training by a well-trained
training team. should be carried out as soon as possible after the manifestation of
Expert consensus (strong consensus) diabetes or the changeover to a different therapy regime, basic
knowledge and skills for the implementation of diabetes therapy, for

Haak T et al. Therapy of Type 1 … Exp Clin Endocrinol Diabetes | © 2022. Thieme. All rights reserved.
informed decision-making and for coping with the disease are de- mendations available for planning purposes by self-help organisa-
veloped together with the patient. Repeated or supplementary train- tions, professional associations and also from government organi-
ing measures have the primary objective of supporting patients with sations, mostly in the form of checklists. These checklists, at least
type 1 diabetes in the event of difficulties in implementing therapy in the case of patients with type 2 diabetes requiring insulin, have
in everyday life and of offering concrete assistance with problems also been verified within studies [66] and have found their way into
related to diabetes (e. g. lack of skills, problems in everyday life). most structured patient training courses.

Problem-specific training and treatment programmes These

are aimed at patients in special, diabetes-specific problem situations Acute Complications
(e. g. occurrence of secondary diseases, problems with hypoglycae- Diabetes-associated emergencies in people with type 1 diabetes
mia). The indication for a problem-specific training and treatment are either the result of insulin deficiency or insulin overdose. Both
programme may be given if the patient has to implement a specific, hypo- and hyperglycaemia can be life-threatening (▶Tab. 2).
new form of therapy in everyday life (e. g. insulin pump therapy, con-
tinuous glucose monitoring), if significant problems are associated Hypoglycaemia
with acute complications (e. g. hypoglycaemia perception disorder) The prevention of hypoglycaemia is one of the greatest challenges
or in connection with subsequent complications (e. g. neuropathy, in achieving a blood glucose level as close as possible to the norm
sexual disorders, diabetic foot, nephropathy, retinopathy, cardiovas- [11], [67].
cular events) or when special situations exist in everyday life which
make the implementation of the therapy more difficult (e. g. shift Definition/degrees of severity
work, fasting, psychological problems) [61], [64]. 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]:
Therapy in special situations ▪▪ Mild hypoglycaemia: Hypoglycaemia can be independently
treated with carbohydrate intake by the patients.
Hospital stays ▪▪ Severe hypoglycaemia: The patient depends on outside help
Recommendations Degree of in treating the hypoglycaemia (e. g. from relatives or medical
recommen- personnel) (▶Tab. 3).
dation
The disease type 1 diabetes should be clearly indicated A Causes and symptoms
in the medical record during a hospital stay. Expert In people with type 1 diabetes, hypoglycaemia is always the result
consensus per [65] (strong consensus)
of an absolute or relative insulin overdose. Causes for insulin over-
In all people with type 1 diabetes, an order to monitor A
dose can include [69]:
blood glucose must be issued during an inpatient stay.
Trained patients should be able to continue self-man- ▪▪ Insulin dosage is too high, insulin injection at the wrong time,
agement as far as possible. The blood glucose levels or the wrong type of insulin is injected
should be accessible to all treating members of the ▪▪ Decreased exogenous glucose intake (forgotten meals)
healthcare team. If no HbA1c value from the last 3 ▪▪ Glucose consumption is increased (e. g. after sports)
months is available, this should be determined. Expert
consensus (strong consensus)
Hospitalized patients with type 1 diabetes should A ▶Tab. 2 Typical symptoms of hypoglycaemia (from [67], [68], [69], [70],
receive intensified insulin therapy with basal insulin and [71]).
bolus insulin/pump therapy. Expert consensus per [11]
(strong consensus) Autonomic Neuroglycopenic symptoms General
symptoms discomfort
The administration of fast-acting insulin only for B
Sweating Mental confusion Nausea
correction by means of a post injection plan is inferior to
such insulin therapy; for this reason, the administration Trembling Rapid, incoherent speech
of insulin should not exclusively take place in the form of Cravings Difficulty in finding words
a post injection plan. Expert consensus per [11] Irritability
(strong consensus)
Palpitations Seeing double and other visual
disorders
Headaches
Therapy during travel Anxiety
Sleepiness
People with type 1 diabetes are not subject to significant restric-
tions on travel activity and destinations solely because of having Difficulty with dexterity/
coordination
diabetes. Restrictions, if any, result from secondary illnesses. It is
Limitation of awareness and
often the case that metabolic parameters deteriorate during a jour-
action
ney. Consultation before travel and planning of the trip based on
Unconsciousness
diabetes treatment are useful. There are many well-made recom-
Seizures

Haak T et al. Therapy of Type 1 … Exp Clin Endocrinol Diabetes | © 2022. Thieme. All rights reserved.
 German Diabetes Association: Clinical Practice Guidelines Thieme

▶Tab. 3 Therapeutic measures in hypoglycaemic people with type 1 diabetes.

Mild hypoglycaemia Severe hypoglycaemia

Therapy by patients possible Patient is conscious, but If unconscious
therapy is no longer
possible by the patient.
Without IV access (e. g. by family/others), 3 mg With IV access
glucagon intranasal as a nasal powder
(recommended as of 4 years of age).
20 g carbohydrates (preferably glucose; 200 ml 30 g carbohydrates 1 mg glucagon IM or SC (Warning: Vomiting and 50 ml 40 % glucose1
fruit juice also possible) (glucose) danger of aspiration) IV
Measure blood glucose after 15 min and repeat If no response is received after 5 min of therapy
therapy if blood glucose concentration remains at the latest, repeat. After successful therapy,
low (50–60 mg/dl; 2.8–3.3 mmol/l). After take a meal or snack to prevent recurrent
successful therapy, take a meal or snack to avoid hypoglycaemia.
recurring hypoglycaemia.
1 or 100 ml 20 % glucose.

▶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.

▪▪ Endogenous glucose production is lowered (for example after ▪▪ Blood glucose > 250 mg/dl (13.9 mmol/l)2 and
alcohol consumption, in case of renal insufficiency) ▪▪ Ketonemia and/or
▪▪ Insulin sensitivity is increased (during the night, after ▪▪ Ketonuria with arterial pH < 7.35 or Venous pH < 7.3;
improved glycaemic control, after improved physical fitness). ▪▪ serum bicarbonate < 270 mg/dl (15 mmol/l)
▪▪ Insulin clearance is lowered (for example, in renal insufficiency). The suspected diagnosis of ketoacidosis must be made if persis-
tent hyperglycaemia > 250 mg/dl (13.9 mmol/l) is detected in com-
Treatment of hypoglycaemia bination with ketonuria, in particular if this finding is accompanied
People with type 1 diabetes and hypoglycaemia perception disor- by corresponding clinical symptoms (▶ Tab. 4) or a comorbidity is
der can be offered specific structured training (see section “Train- present. Further laboratory tests are required to confirm the diag-
ing/structured training and treatment programmes”). nosis.

Diabetic ketoacidosis Symptoms

Diabetic ketoacidosis (DKA) is a metabolic derailment due to an Laboratory chemical diagnostics The following laboratory pa-
absolute or relative insulin deficiency and consecutive metaboliza- rameters are to be determined initially using quality-controlled lab-
tion of fatty acids, which can occur with or without hyperosmolar oratory standards if diabetic ketoacidosis is suspected: Blood glu-
diuresis and thus also without massive hyperglycaemia. Causes of cose and ketones in urine or blood.
diabetic ketoacidosis:
Diabetic ketoacidosis occurs in clinical routine during: If these values are pathological, an arterial or venous blood gas
▪▪ Undetected first manifestation of type 1 diabetes mellitus, test should be carried out and potassium levels, serum creatinine,
▪▪ Interruption of an ongoing insulin therapy,
▪▪ Interruption of insulin administration during insulin pump
therapy,
▪▪ Acute, severe diseases associated with an increased, catabolic
2 The presence of diabetic ketoacidosis is defined by different international
blood glucose limit values. The limit value of 250 mg/dl (13.9 mmol/l) is
metabolization and increased insulin requirements.
based on the consensus of the author group. Since the clinical effects of
high blood glucose levels can vary strongly, blood glucose levels should
Biochemical definition and suspected diagnosis be assessed on the basis of the clinical picture. A single blood glucose
Diabetic ketoacidosis is biochemically defined by: measurement of more than 250 mg/dl (13.9 mmol/l) without corre-
sponding accompanying parameters is not yet a ketoacidosis.

Haak T et al. Therapy of Type 1 … Exp Clin Endocrinol Diabetes | © 2022. Thieme. All rights reserved.
blood count and C-reactive protein determined, as they have a de- be addressed of recognizing ketoacidosis and treating it in a time-
cisive effect on the therapeutic regime. For outpatients, an urgent ly manner. It would be recommended to develop an evaluated short
transfer to hospital must be arranged. If infections are suspected, training module or other form of easily accessible information on
bacterial cultures (e. g. blood, urine, pharynx) should be initiated. ketoacidosis (e. g. a smartphone app). Patients should always re-
An extended diagnosis is to be carried out within the framework member that ketoacidosis is a dangerous medical situation and, in
of causal research and depending on the comorbid diseases. case of doubt, immediate medical assistance should be sought
through the emergency medical services.
Severity of diabetic ketoacidosis
The classification of diabetic ketoacidosis into 3 degrees of sever- Control of diabetes-associated secondary diseases
ity follows the classification by the American Diabetes Association and associated risk factors
(ADA) [74] (▶Tab. 5).
People with type 1 diabetes significantly underestimate the dan-
Recommendations Degree of
ger of ketoacidosis, as it is rather rare compared to the acute com-
recommen-
plication in the form of hypoglycaemia. Often, training on the sub- dation
ject of ketoacidosis took place a while ago and patients do not al- For diagnosing lipohypertrophy, an inspection of the B
ways remember how they can treat ketoacidosis themselves. injection sites and palpation of the skin should be
Therefore, at regular intervals during check-ups, the topic should 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
Recommendations Degree of
consensus (strong consensus)
recom-
mendation From the age of 11 or after a diabetes duration of 5 B
years, people with type 1 diabetes without known
People with type 1 diabetes and clinical suspicion of A
diabetes-associated secondary diseases or comorbidi-
moderate or severe diabetic ketoacidosis should be
ties should undergo the following early detection exam-
admitted to hospital immediately.They should be treated
inations on a regular basis:
in the hospital on the basis of a detailed written
treatment plan. [75] (strong consensus) a. Determination of the albumin-creatinine ratio and
calculation of the glomerular filtration rate for early
The monitoring of people with type 1 diabetes who are A
detection of microalbuminuria and nephropathy. Expert
being treated for diabetic ketoacidosis should be carried
consensus EK IV as per [77] (strong consensus)
out under intensive medical conditions.During the
b. An ophthalmological retinal screening using
treatment of severe ketoacidosis, clinical evaluation and
mydriatic fundus photography
monitoring should be performed at least every hour.
Expert consensus as per [67] (strong consensus) I. If no diabetic retinal changes are
detected, the screening interval should
Diabetic ketoacidosis should be treated according to the A
be two years for known low risk ( = no
following therapy principles:
ophthalmological risk and no general
– Circulation stabilization with initial volume of 1 l of risk).
isotonic solution (0.9 % NaCl) in the first hour (▶ Table 6);
II. If the ophthalmologist does not know the
Then, additional liquids and electrolytes equal depending
general risk factors, he should treat the
on age, height, weight and possible concomitant diseases
patient as if the patient had an unfavour-
(total fluid intake can be up to 6 l/24 h and more for a
able general risk profile; for all other risk
patient weighing 70 kg);
constellations, the screening interval
– Potassium replacement already in the standard range
should be one year. [78] (strong
depending on the severity of the ketoacidosis by
consensus)
administering 40 mEq/L potassium chloride per 1000 ml
NaCl 0.9 %, example see below; a. Medical history and examination for early diagnosis
– Slow normalization of blood glucose using low-dose of neuropathy, at least annually. Expert consensus as
insulin; intravenous insulin administration via perfusor per NVL neuropathy [79] (strong consensus)
(0.05–0.1 U/kg body weight/h IV). b. Medical history and examination for early detection
– Compensation of acidosis and ketosis (addition of of foot complications, at least annually. Expert
bicarbonate only at pH < 7.0 and then up to a correction consensus as per [80] (strong consensus)
of 7.1); c. Examination of the cardiovascular system,
– Avoidance of therapy complications (hypokalaemia, risk-adapted [Expert consensus as per [81].]
cerebral oedema); In addition to a physical examination, this includes the
– Diagnosis and therapy of the triggering causes of DKA. determination of biochemical parameters for
Expert consensus as per [76] (strong consensus) cardiovascular risk factors, such as blood pressure
measurement, determination of blood lipids for the
early detection of lipid metabolism disorders. Expert
▶Tab. 5 Degrees of severity of diabetic ketoacidosis. consensus (strong consensus)

Parameter Degree of severity

Mild Moderate Severe
pH < 7.3 ≤ 7.2 ≤ 7.1
Bicarbonate < 270 mg/dl ≤ 180 mg/dl (10 < 90 mg/dl (5
(15 mmol/l) mmol/l) mmol/l)

Haak T et al. Therapy of Type 1 … Exp Clin Endocrinol Diabetes | © 2022. Thieme. All rights reserved.
 German Diabetes Association: Clinical Practice Guidelines Thieme

▶Tab. 6 Example of an infusion plan for the replacement of liquid and to Conflicts of Interest
compensate for the potassium deficiency
An overview of the conflicts of interest can be found in the guideline
Infusion solution Quantity and period
report at: https://www.awmf.org/uploads/tx_szleitlinien/057-013m_
0.9 % NaCl 1000 ml 1000 ml over the next 1 h S3-Therapie-Typ-1-Diabetes_2018-04.pdf.
0.9 % NaCl 1000 ml with 1000 ml over the next 2 h
potassium chloride
0.9 % NaCl 1000 ml with 1000 ml over the next 2 h
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