Diabetes in Hospitals

Epidemiology and significance of hyperglycaemia in hospitals

The treatment of diabetes in hospitals is playing an increasingly important role due to the growing number of older multimorbid patients with diabetes. Today, every 5th hospital patient in Germany already has diabetes mellitus [1]. This corresponds to about 3 million patients per year who are treated as inpatients with diabetes mellitus. In most cases, diabetes is listed as a “secondary diagnosis”. Patients with diabetes require different treatment pathways in hospital than people without diabetes due to the co-treatment of diabetes-related complications, acute and chronic metabolic decompensation and perioperative management.

It is not uncommon for the initial diagnosis of diabetes to be made during an inpatient stay. Fritsche et al. determined the HbA_1c value in all patients over 18 years of age in all departments in a representative period of 4 weeks in a maximum care hospital [2]. It was found that 3.7% of the patients had previously undetected diabetes. According to the authors, screening for undiagnosed diabetes by determining HbA_1c on admission to hospital is particularly worthwhile for patients aged 50 and over, as the prevalence of diabetes increases significantly at this age.

The American Diabetes Association (ADA) defines hyperglycaemia in hospitalised patients as having a blood glucose level above 140 mg/dl (7.8 mmol/l) . All patients who meet this criterion should have an HbA_1c determination performed.

Recent surveys show that people with diabetes have an average of 1 to 2 days longer length of stay and an approximately 1.5-fold higher mortality rate in hospital. The cause of this is usually a poor metabolic state, which is often not treated appropriately during the inpatient stay. Both hyperglycaemia and hypoglycaemia as well as glucose variability are associated with poorer recovery and an increased rate of complications [1] [4] [5] [6] [7].

Stress hyperglycaemia, which can accompany a serious illness, is associated with a particularly unfavourable prognosis [8] [9]. The influence of increased pro-inflammatory cytokines, catecholamines and other counter-insulin hormones in acute illness result in stress hyperglycaemia. The same glycaemic target values apply to treatment as for diabetes mellitus in hospitals.

The prevalence of hyper- and hypoglycaemic events during an inpatient stay is at least 40% in patients with diabetes and prediabetes [10]. Surgical interventions present an additional special situation, as the procedure itself can release numerous counter-insulin signalling molecules. Perioperative hyperglycaemia is therefore very common in surgical patients (20 to 90%). This in turn is associated with an increased rate of infections and wound healing disorders [11] [12] [13].

Blood glucose target values in the hospital

Preliminary note

Data on the optimal blood glucose target values during inpatient hospitalisation was mainly collected from critically-ill patients in intensive care units. The following recommendations are therefore essentially derived from these results or the recommendations of the ADA [3] or the current recommendations of the Austrian Diabetes Society [10] [11].

Recommended blood glucose target values

1. In the case of elective procedures, blood glucose optimisation should be performed beforehand in all patients with diabetes mellitus. The HbA_1c value should ideally be below 7.0% (53 mmol/mol haemoglobin [Hb]), but at minimum below 8% (64 mmol/mol Hb) [3] [10] [11] [14]. Elective surgical procedures at the time of acute hyperglycaemias above 300 mg/dl (16.7 mmol/l) or HbA_1c values>10% (86 mmol/mol Hb) should be postponed if possible until better metabolic control has been achieved.

2. Already 4 hours before and for the time during the surgical procedures, the blood glucose values should be between 100 and 180 mg/dl (5.6–10.0 mmol/l).

3. A blood glucose target value of 140 to 180 mg/dl (7.8–10.0 mmol/l) should be aimed for in all hospitalised patients – including critically-ill patients in intensive care units.

4. For some patients, lower target values between 100 and 180 mg/dl (5.6–10.0 mmol/l) can also be defined individually but only if the target values are achieved without hypoglycaemia.

5. If the metabolic state is stable and the values are lower than those mentioned above, these do not need to be corrected upwards if there is no tendency toward hypoglycaemia.

6. Hypoglycaemia <70 mg/dl (<3.9 mmol/l) must be avoided. Level 1 hypoglycaemia (<70 mg/dl [<3.9 mmol/l]) should be treated immediately to prevent a deterioration to level 2 and level 3 hypoglycaemia.

7. If the specified target values are not achieved, a diabetes team or a diabetologist must be contacted immediately.

Frequency of blood glucose measurements

1. All patients with diabetes should have their blood glucose and HbA_1c values determined on admission to hospital.

2. Preoperatively, blood glucose should be measured at minimum every 2 to 4 hours during the fasting phase.

3. As a general rule, all hospitalised patients with diabetes should have their blood glucose measured before meals. In patients who are unable to intake food orally, a blood glucose value should be taken every 4–6 hours.

4. During intravenous insulin infusion, blood glucose levels should be determined at intervals of 30 minutes to 2 hours.

5. To assess sufficiently good metabolic control, the time-in-range (TiR) values can also be included with continuous glucose measurement (CGM). According to the ADA, good glucose levels are considered to be within the range of 70 to 180 mg/dl (3.9–10.0 mmol/l) at least 70% of the time and the time below 70 mg/dl (3.9 mmol/l) should be less than 4% [15]. CGM can help to better detect hypoglycaemia and hyperglycaemia and thus also contribute to better glucose management in the hospital. So far, however, CGM has not been approved for therapy decisions in hospitals, so an appropriate number of blood glucose measurements should always be performed in addition.

Insulin therapy: subcutaneous and intravenous

The indication for insulin therapy in type 1 diabetes (T1D) is permanent and lifelong. In type 2 diabetes (T2D), insulin is used in combination with oral antidiabetic drugs and a basal insulin or as multiple-injection therapy with basal and prandial insulin. A prerequisite for the substitution of lacking insulin in people with T1D is knowledge of the physiological insulin requirement as well as the pharmacokinetic and pharmacodynamic properties of the insulins used. Insulin therapy consists of the administration of basal insulin to stabilise blood glucose during fasting phases and prandial insulin to cover carbohydrates in food.

Both human insulins and analogue insulins are used in therapy. Human insulins correspond to human insulin in their amino acid sequence. Analogue insulins act like human insulins, but a change in the molecular structure has resulted in different pharmacokinetics. This leads to more stable blood glucose trends and takes into account the fact that the insulin is not administered physiologically into the bloodstream, but into the subcutaneous tissue.

The insulin preparations listed in [Tab. 1] are used ([Tab. 1]) [16].

Tab. 1 Overview of the various insulin preparations, their onset of action, maximum effect, duration of action and administration. Data according to [16].

	Effect
	Onset	Maximum	Duration	Usually used
Human insulins
NPH insulin	1–2 h	6–7 h	14 h	2×daily
Normal insulin	30–60 min	3 h	8 h	0–30 min before meals
Mixed insulin NPH (70)/Normal (30)	30–60 min	3–3.5 h	14 h	Before breakfast and dinner
Insulin analogues
Degludec	1–2 h1	8–14 h, low maximum	> 42 h	1×daily
Detemir	1 h	7–9 h	19–26 h	1 or 2×daily
Glargin U100	1 h	8–12 h	20–27 h	1 or 2×daily
Glargin U300	1–6 h1	12–16 h, low maximum	30–32 h	1×daily
Aspart	20–25 min	120–150 min	4–5 h	0–15 min before meals
Glulisin	20–25 min	120–150 min	4–5 h	0–15 min before meals
Lispro	20–25 min	120–150 min	4–5 h	0–15 min before meals
Faster Aspart	15 min	120 min	4 h	Immediately before meals
Mixed insulin Aspart-Protamine (70)/Aspart (30); Lispro-Protamine (70), Lispro (30)	20–25 min	2–3 h	10–14 h	0–15 min before breakfast and dinner
Combination insulin Degludec (70)/Aspart (30)	20–25 min	2–3 h	> 30 h	0–15 min before one or before two main meals

NPH, neutral protamine Hagedorn.

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.

Insulin concentrations

Insulin is available in Germany in insulin pen cartridges, pre-filled pens and vials. Insulin pen cartridges are only available in the concentration U100. This means that there are 100 units of insulin per ml. Insulins in pre-filled pens are currently available in concentrations U100, U200 and U300. Conversions are not necessary, as the insulin units specified on the pen are administered exactly as specified.

Insulin therapy in hospitals

Most hospitalisations of insulin-treated people with diabetes mellitus are not for diabetes control itself but because of comorbidities. Therefore, in non-critically-ill patients with diabetes under insulin therapy, an existing therapy with insulin pen, insulin pump or AID (automated insulin delivery) system should be continued, provided that safe implementation with a balanced metabolic state is ensured and documented [17] [18] [19] [20] [21]. Likewise, patients with their own CGM systems for glucose self-monitoring should continue to use them even under inpatient conditions.

In critically-ill patients who may have impaired subcutaneous insulin absorption, intravenous insulin infusion (for which only fast-acting insulins are used) must be carried out under intensive care conditions. For safety reasons, regular blood glucose checks are absolutely essential.

Adaptation of oral glucose-lowering medication and medication with GLP-1 receptor agonists

In principle, in the case of non-critical illness that led to hospitalisation, an existing antidiabetic medication plan with oral antidiabetic drugs (OAD) or with a GLP-1 receptor agonist (GLP-1RA) can be continued during an inpatient hospital stay or can also be started during a hospital stay when T2D is first diagnosed. Upon hospital admission, an HbA_1c value should be determined in the case of known diabetes mellitus in order to be able to better adapt the therapy if necessary. It should be noted, however, that treatment causing hypoglycaemia must be avoided at all costs in an inpatient setting, and in this context particular attention must be paid to changes in liver and kidney function, which influence the metabolising and elimination of medication. Because of the acute illness that has led to hospitalisation, and which can have a direct influence on the metabolic situation, the possibility of a temporary insulin therapy should be considered, as it can be better controlled according to need and situation. Especially in the case of critically-ill patients, temporary insulin therapy should take place in the hospital. If there are no contraindications to the therapy before hospitalisation, it should ideally be resumed 1–2 days before discharge. Good discharge management with determination of further therapy targets and steps as well as diabetological follow-up care is essential [3] [10].

The following particularities apply to the different substance classes of OADs:

Metformin

Metformin and administration of contrast agents containing iodine

The following procedure is recommended for the administration of iodine-containing contrast agents (does not apply to contrast agents containing gadolinium):

1. Metformin therapy can be continued at an estimated glomerular filtration rate (eGFR)>60 ml/min/1.73 m².

2. For an eGFR 30–59 ml/min/1.73 m²:

• Metformin can continue to be administered for an eGFR ≥ 45 ml/min/1.73 m² with intravenous administration of contrast agents.

• In the case of intraarterial or intravenous administration of contrast agents and an eGFR of 30–44 ml/min/1.73 m², metformin should be paused 48 h before contrast agent administration and only restarted when there is evidence that renal function has not deteriorated.

1. Metformin is not a contraindication for performing necessary examinations in an emergency. To reduce the risk of lactic acidosis, metformin administration should be paused for 48 h after the examination [10] [22] [23].

Metformin and impaired renal function

Metformin can be used in cases of impaired renal function with an eGFR ≥ 30 ml/min/1.73 m² in the absence of other risk factors for lactic acidosis [5]. However, it should be used with an eGFR of 30–45 ml/min/1.73 m² at a reduced dose of no more than 1000 mg daily [10] [24].

Metformin-associated lactic acidosis (MALA)

Estimates of the incidence of metformin-associated lactic acidosis (MALA) range from 3 to 10 events per 100000 patient-years [10] [23] [25].

The exact cause of MALA is not fully understood. A sudden rapid increase in the metformin concentration in the plasma could be the cause, which can lead to increased lactate concentrations, especially in the case of impaired liver function. The pronounced increases in lactate and metformin, which then trigger lactic acidosis, are mainly observed in acute renal failure, sepsis, cardiovascular failure, alcohol intoxication, liver cirrhosis and other hypoxic conditions (e. g. shock).

Especially in the case of abdominal complaints in combination with muscle cramps, the presence of a MALA should be considered. A low pH value in combination with increased lactate concentrations (> 5.0 mmol/l) confirms the diagnosis [10] [26].

Determining the metformin serum concentration can substantiate the suspected diagnosis but does not change the therapeutic procedure. In addition to discontinuing metformin, the focus is on treating the underlying disease. Metformin can be eliminated by haemodialysis. However, the prognosis does not depend on the level of individual metformin concentration. The indication for haemodialysis is based more on concomitant renal failure [10].

Metformin and other diseases

Metformin must be discontinued in the case of severe infections (e. g. pneumonia or urinary tract infection with fever>38.5°C), unstable or decompensated heart failure, acute liver or kidney failure or severe diarrhoea and exsiccosis that have led to hospital admission [3] [10].

Sulfonylureas

Sulfonylureas can induce hypoglycaemia because they stimulate insulin secretion independent of the glucose metabolic state. The risk of hypoglycaemia is particularly high in the case of impaired renal function, as most sulfonylureas are eliminated renal. Sulfonylureas should therefore be used with extreme caution in the inpatient setting, especially as longer peri-interventional or illness-related fasting periods often must be observed during inpatient stays. In any case, dose reductions or a pause of sulfonylurea therapy should be carried out in such a situation. One study showed an increased incidence of hypoglycaemia in the hospital under sulfonylurea therapy compared to matched outpatient controls [10] [27]. In the case of hyperglycaemic metabolic state under existing therapy with sulfonylureas in hospital, a switch to an at minimum temporary insulin therapy is indicated [3] [10]. If liver function is impaired, the risk of hypoglycaemia can be significantly increased due to impaired hepatic gluconeogenesis [10].

SGLT-2 inhibitors

SGLT-2 inhibitors (SGLT-2i) are drugs that, similar to metformin, should be paused in the form of a “sick day rule” in the case of severe infections and severe acute illnesses or longer fasting periods. This is especially true before surgery, during longer fasting periods or even in intercurrent, serious diseases when ketone bodies are present [3] [10] [28] [29] [30]. SGLT2-i have a very low risk of intrinsic hypoglycaemia. A rare but potentially dangerous side effect of SGLT-2i is euglycemic ketoacidosis. This can occur especially in the case of a sudden increase in insulin demand (e. g. in the event of an infection) or an acute deterioration in kidney function. The diagnosis is made by means of a venous blood gas analysis. In the case of clinical symptoms of ketoacidosis and existing therapy with SGLT2-i, this examination must absolutely be carried out, the therapy must be paused immediately if the diagnosis is suspected [3] [10] [30]. In patients with cardiovascular disease (especially heart failure) but also in patients with chronic renal impairment, treatment with an SGLT2-i should not be discontinued due to the favourable endpoint study data (for the substances dapagliflozin and empagliflozin available in Germany) [3] [10] [28] [30].

GLP-1 receptor agonists

GLP-1 receptor agonists (GLP-1 RA) also have a very low intrinsic risk of hypoglycaemia. Positive endpoint data (for the substances liraglutide, dulaglutide and semaglutide available in Germany) indicates that existing GLP-1 RA therapy should not be discontinued, especially in cardiovascular patients or chronic renal dysfunction [3] [10] [30] [31]. Excluded from this are hospital admissions with gastrointestinal causes (e. g. nausea, vomiting, etc.). It should be taken into account that GLP-1 RA can lead to delayed gastric emptying and consequently to gastrointestinal discomfort [10].

Hypoglycaemia

Hypoglycaemia in type 2 diabetes

The prevention of hypoglycaemia is one of the greatest challenges in achieving a blood glucose level as close as possible to normal [3] [32].

Definition/degrees of severity

Hypoglycaemia can be associated with various clinical signs and symptoms ([Tab. 2]). The currently internationally-used classification of hypoglycaemia has been summarised in [Tab. 3] ([Tab. 3]) [33]. Level 1 hypoglycaemia is defined as a blood glucose level of <70 mg/dl (<3.9 mmol/L) but ≥ 54 mg/dl (≥ 3.0 mmol/L). Even if there may be no symptoms due to a hypoglycaemia perception disorder, a blood glucose level of <70 mg/dl (<3.9 mmol/l) is considered an alarm value at which the patient should be made aware. Level 2 hypoglycaemia (defined as a blood glucose level of <54 mg/dL [<3.0 mmol/L]) is the threshold as of which neuroglycopenic and autonomic symptoms occur and immediate action must be taken to correct hypoglycaemia. Level 3 hypoglycaemia is defined as a serious event in which the patient is dependent on outside help (e. g. from relatives or medical staff) as a result of impaired mental and/or physical functions, regardless of the measured blood glucose concentration ([Tab. 4]).

Tab. 2 Typical symptoms of hypoglycaemia.

Autonomic symptoms	Neuroglycopenic symptoms	General discomfort
Sweating	Mental confusion	Nausea
Trembling	Rapid, incoherent speech
Cravings	Difficulty in finding words
Palpitations	Irritability
	Double vision and others
	Visual disturbances
	Headaches
	Anxiety
	Sleepiness
	Difficulty with dexterity/coordination
	Limited awareness and action
	Unconsciousness
	Cramps
	Hemiplegia
	Aphasia

Hypoglycaemia regularly leads to an increase in QTc time in ECGs and to other various cardiac arrhythmias in 50% of patients with T1D.

Tab. 3 Classification of hypoglycaemia. Data according to [33].

Level	Blood glucose/description
Level 1	Glucose level <70 mg/dl (3.9 mmol/l) and>54 mg/dl (3.0 mmol/l)
Level 2	Glucose level <54 mg/dl (3.0 mmol/l)
Level 3	A serious event in which the patient is dependent on outside help as a result of impaired mental and/or physical functions

Tab. 4 Therapeutic measures for hypoglycaemia.

Level 2 hypoglycaemia	Level 3 hypoglycaemia
Therapy by patient possible	Patient is conscious, but therapy is no longer possible by the patient.	If unconscious
		Without IV access	With IV access
20 g carbohydrates (preferably glucose; however, 200 ml fruit juice also possible)	30 g carbohydrates (glucose)	1 mg glucagon IM or SC (e. g. by family, strangers) 3 mg glucagon intranasally as nasal powder (recommended from the age of 4 years) (caveat: risk of vomiting and aspiration)	50 ml 40% glucose 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.

Causes of hypoglycaemia

In people with type 1 diabetes, hypoglycaemia is always the result of an absolute or relative insulin overdose.

Causes for insulin overdose can include:

• Insulin dose is too high, insulin injection at the wrong time, or the wrong injection site is used

• Exogenous glucose intake is decreased (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)

• People with type 1 diabetes and hypoglycaemia perception disorder can be offered specific structured training

Hypoglycaemia in type 2 diabetes

The treatment of severe hypoglycaemia in T2D differs only if the patients are on therapy with sulfonylureas or glinides. In this case, glucose administration and the subsequent increase in blood glucose can stimulate renewed severe insulin secretion and trigger another severe hypoglycaemia. It is therefore imperative for these patients to be monitored in hospital for at least 24 to 72 hours. During this time, a continuous infusion of 5–10% glucose solution should be administered, and ECG monitoring should be performed.

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is a metabolic derangement due to an absolute or relative insulin deficiency and consecutive metabolization of fatty acids. In addition to increasing the glucose concentration in the blood, this also leads to hyperacidity of the blood with a corresponding metabolic acidosis, which in extreme cases can lead to the death of the patient [34]. The cause of DKA can be, for example, the undetected initial manifestation of T1D. Other causes include the interruption of ongoing insulin therapy or acute serious illnesses associated with increased catabolic metabolism and an increased insulin requirement. This is often the case with acute illnesses. Biochemically, ketoacidosis is defined as blood glucose levels above 250 mg/dl (14.0 mmol/L), ketonaemia or ketonuria. The arterial pH value is below 7.35. The degrees of severity are classified as described in [Tab. 5] (Tab. 5)

Tab. 5 Degrees of severity of diabetic ketoacidosis Data according to [35].

Parameters	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)

The symptoms of DKA are not always obvious. Usually, the patient's clinical picture and symptoms are the clinical determining factor, although it is possible for symptoms of DKA to also be very inconspicuous. Patients often notice nausea, vomiting or abdominal pain. More severe DKA is associated with impaired consciousness such as drowsiness and severe DKA can lead to unconsciousness. Only very well-trained patients can recognize a mild form of DKA themselves in good time and treat it adequately. Self-therapy is based on increasing the insulin intake, ensuring hydration and monitoring progress by self-measuring ketones in the urine or blood. In case of doubt and in the case of moderate or severe forms of DKA, admission to an intensive care unit is mandatory. It should be noted that the course of DKA progresses rapidly and that it can be fatal in the absence of treatment. Intensive medical therapy for DKA is primarily aimed at compensating for fluid loss and stabilising the circulation through rehydration ([Tab. 6]).

Tab. 6 Example of an infusion plan for fluid substitution.

Time (h)	Balanced electrolyte solution (ml/h)
1st hour	1000
The next 4 hours	500
The next 8 hours	250
The next 6 hours	166
Assess cardiovascular function after 12 h and adjust fluid administration accordingly

The continuous intravenous insulin infusion leads to an equalisation of the disequilibrium and to a drop in the glucose concentration. It is particularly important that the patient's recompensation takes place slowly, over at least 24 hours:

• In the first 24 hours, do not lower the blood glucose below 250 mg/dl (14 mmol/l) (if necessary, counteract with a 10% glucose solution, do NOT pause insulin).

• Initially lower blood glucose by 50 (to 100) mg/dl (2.8–5.6 mmol/l) per hour until a value of 250 mg/dl (13.9 mmol/l) is reached.

• Low-dose insulin: 0.05 (up to 0.1) I.U./kg body weight (BW) intravenously via a Perfusor.

• (Data on initial insulin bolus is insufficient.)

It is important to pay particular attention to the fact that potassium levels in the blood are stabilised and normalised by adequate substitution ([Tab. 7]).

Tab. 7 Example of an infusion plan to compensate for potassium deficiency.

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
Under 3.5	Additional oral administration of potassium, if necessary

If the procedure is too rushed, there is a risk of cerebral oedema, which is often fatal.

During intensive medical treatment, in addition to diagnosing and eliminating the cause of the decompensation, the following measures must also be taken into account:

• Fluid resuscitation

• Thrombosis prophylaxis with heparin IV/SC

• Bicarbonate administration (possibly at pH <7.0 in critical condition, 50 mmol over 1 h): Target pH with bicarbonate: 7.0

• Avoid using central venous catheter (CVC) and arterial access* due to the risk of exsiccosis-related thrombosis and a high complication rate during the application due to a empty vascular bed

• Gastric tube for gastroparesis/vomiting

• Avoid dangerous therapy complications: cerebral oedema, hypokalaemia

*CVC/gastric tube – benefit not generally confirmed, i. e. use for clinical indications such as cardiac or renal insufficiency, risk of aspiration

In many cases, a readjustment of diabetes medication is necessary.

Hyperglycaemic hyperosmolar syndrome

Hyperglycaemic hyperosmolar syndrome (HHS) differs from DKA in that there is no significant hyperketonaemia (<54 mg/dl (3 mmol/l)), there is usually a much more pronounced hyperglycaemia (> 540 mg/dl (30 mmol/l)) and there is a pronounced life-threatening hypovolaemia and hyperosmolarity (serum osmolarity 320 mosmol/kg or more). A mix of HHS and DKA is possible. HHS is more common in people with T2D, but is also present in T1D. It requires monitoring in the intensive care unit. Compared to DKA, ketonuria and ketonaemia are absent or mild (serum hydroxybutyrate 1 ± 0.2 mmol/l, pH>7.3), while hyperglycaemia (> 600 mg/dl (33.3 mmol/l)) and hyperosmolarity (> 320 mOsm/kg) are more pronounced [29] [35].

The therapy targets of the HHS are: normalisation of osmolarity, replacement of low fluid and electrolytes and normalisation of blood glucose, as well as prevention of thromboembolic complications, cerebral oedema, and central pontine myelinolysis.

The therapy of HHS differs from the therapy of DKA in that in the absence of ketonaemia (<18 mg/dl (1 mmol/l)), no insulin should be administered at first. Volume replacement with balanced full electrolyte solution alone usually results in a slow reduction in blood glucose. An even slower hypotonic fluid replacement with 0.45% saline solution should only be considered if the osmolarity does not decrease despite an adequate positive volume balance. The sodium concentration should not fall faster than 180 mg/dl (10 mmol/l) in 24 hours. Blood glucose should not fall by more than 90 mg/dl (5 mmol/l) per hour. If the blood glucose no longer falls due to IV fluid administration or in the presence of ketonemia>18 mg/dl (1 mmol/l), an insulin infusion of 0.05 IU/kg body weight(BW)/h should be started [35]. The potassium substitution corresponds to that of DKA [36] [37].

Perioperative diabetes management

Perioperative mortality is increased by up to 50% in people with diabetes as a result of existing secondary and concomitant diseases as well as acute metabolic changes [26]. Acute hazards include hypoglycaemia resulting from preoperative fasting phases or administration of glucose-lowering drugs, hyperglycaemia due to post-aggression metabolism caused by counter-insulin hormones, and DKA due to non-administration of insulin or stress [38]. In addition, cardiovascular instability and gastroparesis as a result of autonomic diabetic neuropathy of infections and wound healing disorders, among other things, cause the perioperative increased risk [39]. To avoid possible risks and complications, a standardised procedure for the perioperative treatment of people with diabetes should be documented in writing in every hospital and care should be provided by nursing staff trained in diabetes. In addition, people with diabetes should be involved in the surgical planning at an early stage. Preoperative anaesthesiology appointments (premedication appointments) should also be performed at an early stage to identify high-risk patients with existing cardiovascular disease, autonomic neuropathy or chronic renal insufficiency [40].

Elevated preoperative HbA_1c values are associated with unfavourable surgical results [41]. On the other hand, a good HbA_1c value is associated with an improved surgical outcome [42]. For this reason, the preoperative HbA_1c level to be aimed for in elective procedures is <8.0% (64 mmol/mol Hb). Perioperatively, starting 4 hours before surgery, the blood glucose target range is 100–180 mg/dl (5.6–10.0 mmol/l), while avoiding hypo- and hyperglycaemia [3]. Accordingly, in the presence of elevated blood glucose levels>300 mg/dl (16.7 mmol/l), elective surgery should be performed at a later date in order to achieve better blood glucose values beforehand. On the other hand, stricter blood glucose targets do not improve the operating result and are associated with an increased risk of hypoglycaemia [43]. The period of fasting from food should be as short as possible. Subcutaneous insulin administration on the day of surgery should only be carried out for minor and short procedures, as the absorption of subcutaneously administered insulin is uncertain, especially in the case of major surgery with fluid shifts and possible haemodynamic problems. In the case of planned short fasting periods (no more than one skipped meal), it is possible to modify the previous diabetes medication with regular monitoring of blood glucose ([Tab. 8]). On the other hand, perioperative stabilisation of the metabolism in the case of major or prolonged surgery is usually only possible through the individual and needs-based supply of insulin and glucose.

Tab. 8 Recommendations for short surgical procedures. Data according to [3] [40].

	Patients with type 1 diabetes/type 2 diabetes, treated with insulin	Patients with type 2 diabetes with lifestyle-modifying measures/OAD
Preoperative	The day before: Insulin as usual	Discontinue SGLT-2 inhibitors 3–4 days before surgery and discontinue metformin on the day of surgery at the latest. Discontinue all other OADs after the last meal
On the day of surgery	Continue previous basal insulin therapy, if necessary situational correction with rapid-acting insulin
On the ward	7:00 a.m. Blood glucose monitoring. Rapid-acting insulin administered subcutaneously according to the correction scheme	7:00 a.m. Blood glucose monitoring. Rapid-acting insulin administered subcutaneously according to the correction scheme
In the operating room or on the ward	Blood glucose checks hourly and SC/IV administration of rapid-acting insulin according to the correction scheme: 10:00 a.m.; 1:00 p.m.; 5:00 p.m.	Blood glucose checks hourly and SC/IV administration of rapid-acting insulin according to the correction scheme: 10:00 a.m.; 1:00 p.m.; 5:00 p.m.
If no food intake is possible in the evening	Continue basal insulin therapy. Blood glucose checks and SC/IV administration of rapid-acting insulin according to the correction scheme at each: 10:00 p.m.; 3:00 a.m. Resume patient's prior therapy the following day	Blood glucose checks and SC/IV administration of rapid-acting insulin according to the correction scheme at each: 10:00 p.m.; 3:00 a.m. Resume patient's prior therapy the following day
If food intake is possible in the evening	Resume patient's prior therapy	Resume patient's prior therapy. Metformin is not resumed until after 48 h if renal function is stable and within the approval for metformin

IV: intravenous, a.m., Ante meridiem; OAD: oral antidiabetic therapy, OP: operation, SC: subcutaneous, SGLT-2: sodium dependent glucose co-transporter 2, p.m.: Post meridiem

Diabetes management during bowel preparation for colonoscopy

Diabetes is an independent risk factor for inadequate bowel preparation [44] with slow intestinal transit and delayed gastric emptying as possible causes [45]. Adverse effects of inadequate bowel preparation include less detectability of (pre)neoplastic lesions, longer procedure duration, and higher risk of adverse events [46]. Therefore, a detailed information discussion should be held about preparatory measures and the need to consistently follow the recommendations to achieve a good preparation result. In addition, people with diabetes should receive written dietary recommendations for the three to four days before the colonoscopy (low-fibre, carbohydrate-balanced diet), including dietary measures for the treatment of mild hypoglycaemia while continuing the colon lavage [47]. In addition, there is an increased risk of metabolic derailments for people with diabetes such as hypoglycaemia, DKA and lactic acidosis, fluid and electrolyte imbalances, and acute renal failure during bowel preparation [48]. Therefore, it is necessary to adjust the glucose-lowering medication ([Tab. 9]) [49]. All oral glucose-lowering medications should be omitted while the people with diabetes consume clear liquids. In addition, sulfonylureas should be discontinued one day before the colonoscopy and, due to the risk of ketoacidosis, SGLT2-i should be discontinued three days before the colonoscopy. To avoid fluid or electrolyte shifts, it is important to ensure an adequate fluid and calorie intake. If the blood glucose level falls below 90 mg/dl (5 mmol/L), additional glucose should be supplied in liquid form. Sugar-free drinks or jellies should be avoided as long as the blood glucose level does not exceed 180 mg/dl (10 mmol/l) [52]. If an SGLT2-i has not been discontinued in time, blood ketone levels should be measured. If ketone levels are below 1.0 mmol/L and the patient is clinically stable, the colonoscopy may be performed. In the case of ketosis without metabolic acidosis (base excess [BE]>–5), continuation of colonoscopy may be considered, with periprocedural insulin and glucose infusions to reduce the risk of ketoacidosis. In the case of ketosis with metabolic acidosis (BE <–5), postponing the procedure is urgently recommended and an adjustment of therapy is indicated [51]. If no solid food is consumed, short-acting insulin should be discontinued. Corrections should only be made for blood glucose levels of more than 200 mg/dl (11 mmol/l). The dose of basal insulin should be reduced depending on the diabetes type. Blood glucose checks are recommended at least every four hours. In particular, patients with T1D must have the opportunity to consult their diabetes team.

Tab. 9 Adjusting glucose-lowering therapy during bowel preparation for colonoscopy. Data according to [50] [51].

Type of treatment	The day before the colonoscopy	The day of the colonoscopy
Sulfonylureas and SGLT-2 inhibitors	Pause (caveat: pause SGLT2 inhibitors 3 days before colonoscopy)	Only take after resuming regular meals.
Metformin, acarbose, DPP4 inhibitors, glitazones, GLP-1 receptor agonists	Take as long as solid food is consumed.	Only administer after resuming regular meals.
Basal insulin and mixed insulin	Administer usual dose up to 24 hours before colonoscopy. In the 24 hours before the colonoscopy: Type 1 diabetes: Reduce to 50–80% of the usual dose (consultation with diabetes team) Type 2 diabetes: Reduce to 50% of the usual dose	Type 1 diabetes: Reduce morning basal insulin to 50–80% (consultation with diabetes team) Type 2 diabetes: Do not inject until regular meals have been resumed.
Rapid-acting insulin	Continue the usual dose as long as solid food is consumed. After that, if the blood glucose level is more than 200 mg/dl (11 mmol/l), only give corrections as the patient does in other fasting situations.	Only administer after resuming regular meals.
Insulin pump	If no more solid food is consumed, reduce basal insulin. Type 1 diabetes:Reduce to 50–80% of the usual dose (consultation with diabetes team) Type 2 diabetes: Reduce to 50% of the usual dose	Maintain reduced dose until regular meals are resumed. Leave the insulin pump switched on during the colonoscopy. Intravenous glucose should be administered if necessary. Return to usual dose when regular meals are resumed.

Glucocorticoid therapy

Glucocorticoids (GC) can lead to hyperglycaemia via an increase in insulin resistance on the one hand and via beta cell dysfunction on the other [10] [53].

Up to 86% of patients treated with systemic GC therapy during a hospital stay with exhibit symptoms of hyperglycaemia [10] [53]. The following risk factors have been identified for hyperglycaemic decompensation [55]:

• Age>65 years,

• Increased BMI,

• Positive family history for diabetes mellitus,

• High GC dose.

There is also a proven association between the occurrence of GC-associated hyperglycaemia and an unfavourable outcome [10] [56] [57].

Shorter-acting GCs such as prednisolone are characterised by a maximum effect after approximately 4–8 hours. Due to the pharmacokinetics of such a therapy option, treatment with an NPH insulin is recommended ([Tab. 10]) [58].

Tab. 10 Possible NPH insulin dosing depending on the prednisolone equivalent dose. Data according to [10].

Equivalence dose to prednisolone [mg/d]	Body weight-adjusted insulin dose (IU/kg BW)
10	0.1
20	0.2
30	0.3
> 40	0.4

I.U., International Units; BW, body weight; NPH, neutral protamine Hagedorn.

Longer-acting basal insulin analogues (insulin degludec, insulin glargine) are practical for therapy with longer-acting GCs such as dexamethasone or for multiple daily doses of a GC. At higher GC doses, additional prandial insulin doses are sometimes necessary according to a plasma glucose-adapted dosing schedule. In the case of diabetes that has already been treated with insulin in advance, the insulin requirement increases by at least about 20% under GC therapy. Further insulin dose adjustments under regular blood glucose monitoring are essential [10].

Blood glucose control with parenteral nutrition

In parenteral nutrition, the patient is continuously administered a relatively large amount of glucose intravenously. Diseases that make parenteral nutrition necessary often lead to insulin resistance, which is why high blood glucose levels are frequently observed during parenteral nutrition, even in patients without known diabetes. Optimal blood glucose control with parenteral nutrition is achieved with a continuous intravenous insulin infusion. If this is not an option, it is possible to add a normal insulin directly to the parenteral nutrition bag.

Tab. 11 Correction scheme in the context of parenteral nutrition.

Blood glucose (mg/dl) [mmol/l]	<180 [<10]	180–220 [10–12.2]	221–260 [12.3–14.4]	261–300 [14.5–16.7]	> 300 [>16.7]
Rapid-acting analogue insulin (I.U.)	0	2	4	6	8

Specific procedure [3] [59]

• Blood glucose target range in patients with parenteral nutrition: 140–180 mg/dl (7.8–10.0 mmol/l).

• A daily blood glucose profile must always be determined when starting parenteral nutrition in patients already receiving treatment. The start of insulin therapy is indicated in the case of repeatedly elevated blood glucose levels>180 mg/dl (10 mmol/l).

• If patients have already been treated with an intravenous insulin infusion in an intensive care unit, the amount of insulin infused over the last 24-hour period can be added directly to the parenteral nutrition bag.

• For patients for whom the amount of required insulin is not known, the following amount of normal insulin can initially be added directly to the bag, depending on the measured blood glucose (~ 0.5–1 I.U. normal insulin/10 g carbohydrates).

• Blood glucose is then measured every 4 hours and, if blood glucose values exceed 180 mg/dl (10.0 mmol/l), corrected by subcutaneous administration of rapid-acting analogue insulin according to the values shown in [Tab. 11] ([Tab. 11]).

• Measures for blood glucose <80 mg/dl (4.4 mmol/l): additional intravenous administration of 250 ml of 10% glucose solution over 1 hour, hourly blood glucose tests until blood glucose>120 mg/dl (6.7 mmol/l); with the next parenteral nutrition bag, reduction of the amount of insulin added by 30%.

• Measures if blood glucose is 80–120 mg/dl (4.4–6.7 mmol/l) twice in 24 hours: reduce the amount of insulin added by 20% with the next parenteral nutrition bag.

• The insulin dose added to the bag per day must be adjusted daily. The amount (sum of the units) of subcutaneously-administered insulin required per 24 hours to adjust the blood glucose to the target range can be added as normal insulin to the next bag in addition to the amount added the day before.

• Parenteral nutrition to which insulin has been added must never be stopped suddenly, as this can provoke hypoglycaemia. Instead, a slow reduction in the infusion rate, a switch to intravenous glucose infusion and oral nutrition should take place before parenteral nutrition is stopped.

Diabetes technology (insulin pumps, continuous glucose monitoring, closed-loop systems)

Approximately 30–40% of patients with T1D use insulin pumps and glucose sensors. More and more insulin-treated patients with T2D are also using glucose sensors. Given their increasing popularity, the number of people with diabetes who are hospitalised and who use such a device will increase. The use of CGM in the hospital can improve blood glucose levels while avoiding hypoglycaemia, potentially increasing the time spent in the target range, and reducing the adverse consequences of out-of-target blood glucose levels [60]. Insulin-treated people with diabetes who are hospitalised for non-critical illness and are already using CGM should therefore continue their CGM in addition to the bedside capillary glucose measurements required for confirmation [61] [62] However, the relationship between glucose levels, time-in-range and clinical outcome is still unclear [63] so that the current focus is on avoiding hypoglycaemia and, as a second therapy target, avoiding relevant hyperglycaemia. At present, CGM data cannot be linked directly to the electronic patient file. For this reason, after patients with diabetes have given their permission, this data must be forwarded to the diabetes team in another form, such as by downloading the glucose values. Given the risk of inaccuracies during an acute illness, capillary glucose measurements should be taken twice a day, regardless of whether the device needs to be calibrated. Capillary glucose measurements are also required for other reasons: when there are discrepancies between the CGM data and existing symptoms, to confirm hypoglycaemia, to ensure that hypoglycaemia is back under control, or to confirm accuracy before continuing CGM use (e. g. after surgery) [64]. According to the manufacturer's instructions, CGM devices should not be used on any part of the body with generalised oedema or skin infections. During surgeries or operations, the sensor must be attached to the contralateral side. If patients with diabetes are unable to handle the CGM themselves and the nursing staff are also unable to work with the device, capillary glucose measurements should be carried out. During this time, the CGM sensor can remain on the patient. However, the sensor should be removed if it is foreseeable that the patients with diabetes will not be able to care for themselves over a longer period of time. The measurement accuracy of CGM can be impaired as a result of reduced tissue perfusion, hypotension, hypothermia, hypoxia and the use of vasopressors [65]. Therefore, CGM is currently contraindicated for use in critically ill patients with diabetes and should not be used in the ICU. Interference can also occur following the administration of certain medications, such as paracetamol, maltose, ascorbic acid, dopamine, mannitol, heparin, uric acid, hydroxyurea and salicylic acid [66]. According to the manufacturer, no CGM device currently allows exposure to X-rays, computer tomography (CT), magnetic resonance imaging (MRI), diathermy, radiotherapy, or other types of radiation. However, shielding the CGM devices can counteract undesirable events in the event of radiation exposure [67]. During MRI examinations, however, CGM devices must be removed. The CGM device can remain in place during minor procedures without sedation as well as during childbirth (including a caesarean delivery) but should not be placed in the immediate vicinity of either the surgical site or a diathermy pad. During cardiac arrest, CGM devices should be removed for possible external cardioversion.

International professional societies advocate the safe continuation of insulin pump therapy (CSII, continuous subcutaneous insulin infusion) in hospitals for patients with diabetes who can take care of themselves [3] [68]. Observational studies in adults with T1D found no difference in mean blood glucose levels between those who continued CSII and those who switched to intensified conventional insulin therapy (ICT) [69] [70]. However, insulin pump users appear to be less frequently affected by severe hyperglycaemia and hypoglycaemia [70]. In addition, people with diabetes often express a desire to continue CSII and thus maintain their independence in diabetes management, and express great satisfaction when this is possible [71]. In the context of a hospital admission, it must be decided on a case-by-case basis whether patients with diabetes can continue to use their insulin pump safely. The most important criteria for the continuation of the CSII include: (1) The patients are clinically stable, willing, and able to take care of themselves, and (2) the treating physician is familiar with CSII, the admitting hospital has appropriate guidelines/guidance on the use of CSII, as well as a trained diabetes team for inpatient treatment. Shortly after admission, the diabetes team should be involved to assist the patients with diabetes with insulin adjustment and pump adjustment, as well as coordination of further treatment after hospital discharge. If, on the other hand, the patients with diabetes are unable or unwilling to operate the insulin pump, they cannot safely work with the pump settings, qualified care is not immediately available, or other contraindications are present, the insulin pump should be removed and, depending on the severity of the disease, subcutaneous ICT or intravenous insulin infusion should be started [72]. Given the high cost of insulin pumps, all devices that are removed should be labelled and stored in a safe place. A hospital cannot be expected to provide all the necessary accessories because each model of equipment has different components. Therefore, the patients with diabetes or their family must be able to provide the necessary pump accessories such as infusion sets and insulin reservoirs. If this is not possible, CSII therapy must be interrupted during the hospital stay. Patients with diabetes should be made aware of the different blood glucose targets in hospital as they are likely to be different from outpatient targets. In the case of minor surgical procedures with a short fasting period, the CSII can be continued during the procedure, provided that certain criteria are met. These include technical requirements, such as the possibility of not placing the pump close by during the planned procedure. It is also important for the patient to be able to communicate with the treatment teams as well as the for the multidisciplinary team to agree that the continued use of the CSII is suitable [72]. CSII can also be continued in most births (including elective caesarean deliveries) [73]. It is necessary to remove the insulin pump before an MRI, but this is not necessary for conventional X-rays. Pump manufacturers also advise removing the pump before a CT scan. However, the pump can also be covered with a radiation apron [74]. For positron emission tomography (PET), the pump must be switched off at least 1 hour before the examination (no bolus insulin <4 hours before). The pumps can be suspended for up to an hour at a time without the need for an alternative insulin. However, when the pump is reconnected, a correction bolus may be required.

Data on the practical use and safety of hybrid closed-loop systems in hospitals is still very limited, but small randomised studies [75] and case series [76] indicate good efficacy and safe use. In people with diabetes who are doing well and are only undergoing a short procedure or examination, it may be appropriate to continue to control blood glucose through the hybrid closed-loop system. On the other hand, the insulin requirement can change rapidly from day to day in people with more severely impairments. For this reason, the algorithms should be deactivated and switched to manual control. This allows patients with diabetes, with the support of their diabetes team, to adjust the insulin pump settings, including the blood glucose target range, carbohydrate factors and basal rates [74]. Other difficult scenarios for hybrid closed-loop systems in hospitals are drugs such as GCs, which can cause pronounced insulin resistance with subsequent hyperglycaemia, nausea and vomiting, and parenteral or enteral nutrition via a nasogastric tube or percutaneous endoscopic gastrostomy (PEG) [67]. The algorithms should also be deactivated in these situations. [54]

German Diabetes Association: Clinical Practice Guidelines

This is a translation of the DDG clinical practice guideline published in Diabetologie 2024; 19 (Suppl 2): S437–S4506.DOI: 10.1055/a-2312-1160

Conflict of interest

K. Müssig: none.
As co-author, B. Gallwitz declares the following potential conflicts of interest in the last 3 years: Advisory boards/consultant activities: AstraZeneca, Bayer Vital, Boehringer Ingelheim, Eli Lilly & Co., Merck Sharp & Dohme, Novo Nordisk; lecture fees: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly & Co., Merck Sharp & Dohme, Novo Nordisk. Company shares: none.
As co-author, T. Haak declares the following potential conflicts of interest in the last 3 years: Advisory boards/consultant activities: MSD, Astra-Zeneca, Roche, Abbott; lecturing activities: Diabetes Academy Bad Mergentheim e.V., Abbott. Research project/implementation of clinical trials: Boehringer Ingelheim, Principal Investigator, AstraZeneca, Abbott REPLACE study. As co-author, M. Kellerer declares the following potential conflicts of interest: Research Support (RCT): AstraZeneca, Lilly, Novo Nordisk. Membership in advisory bodies: Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Merck Sharp & Dohme, Novo Nordisk, Sanofi. Lecture fees: Bayer, Boehringer Ingelheim, BMS, Novartis, Merck Sharp & Dohme, Novo Nordisk.
As co-author, E. Siegel declares the following potential conflicts of interest in the last 3 years: Advisory boards/consultant activities: Boehringer Ingelheim, Eli Lilly & Co., Novo Nordisk; Nevro; Lecturing activities: AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., Novo Nordisk. Company shares: none.

• References

• 1 Eckert AJ, Fritsche A, Icks A. et al. Common procedures and conditions leading to inpatient hospital admissions in adults with and without diabetes from 2015 to 2019 in Germany. Wien Klin Wochenschr 2023; 135: 325-335
• 2 Kufeldt J, Kovarova M, Adolph M. et al. Prevalence and Distribution of Diabetes Mellitus in a Maximum Care Hospital: Urgent Need for HbA_1c-Screening. Exp Clin Endocrinol Diabetes 2018; 126: 123-129
• 3 ElSayed NA, Aleppo G, Aroda VR. et al. Diabetes Care in the Hospital: Standards of Care in Diabetes –2023. Diabetes Care 2023; 46: 267-278
• 4 Brunkhorst FM, Engel C, Bloos F. et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008; 358: 125-139
• 5 Finfer S, Chittock DR, Su SY. NICE-SUGAR Study Investigators et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360: 1283-1297
• 6 Chang S, Xu M, Wang Y. et al. Acute Glycemic Variability and Early Outcomes After Cardiac Surgery: A Meta-Analysis. Horm Metab Res 2023; 55: 771-780
• 7 Barmanray RD, Cheuk N, Fourlanos S. In-hospital hyperglycemia but not diabetes mellitus alone is associated with increased in-hospital mortality in community-acquired pneumonia (CAP): a systematic review and meta-analysis of observational studies prior to COVID-19. BMJ Open Diabetes Res Care 2022; 10: e002880
• 8 Dungan KM, Braithwaite SS, Preiser JC. Stress hyperglycaemia. Lancet 2009; 373: 1798-1807
• 9 Li L, Zhao M, Zhang Z. et al. Prognostic significance of the stress hyperglycemia ratio in critically ill patients. Cardiovasc Diabetol 2023; 22: 275-284
• 10 Mader JK, Brix JM, Aberer F. et al. Diabetesmanagement im Krankenhaus (Update 2023) [Hospital diabetes management (Update 2023)]. Wien Klin Wochenschr. 2023; 135: 242-255
• 11 Kietaibl AT, Huber J, Clodi M. et al. Positionspapier:Operation und Diabetes mellitus. Wien Klin Wochenschr 2023; 135: 256-271
• 12 Zhang Y, Zheng QJ, Wang S. et al. Diabetes mellitus is associated with increased risk of surgical site infections: a meta-analysis of prospective cohort studies. Am J Infect Control 2015; 43: 810-815
• 13 Martin ET, Kaye KS, Knott C. et al. Diabetes and risk of surgical site infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol 2016; 37: 88-99
• 14 Tao X, Matur AV, Palmisciano P. Preoperative HbA_1c and Postoperative Outcomes in Spine Surgery: A Systematic Review and Meta-Analysis. Spine (Phila Pa 1976) 2023; 48: 1155-1165
• 15 ElSayed NA, Aleppo G, Aroda VR. et al. 6. Glycemic Targets: Standards of Care in Diabetes-2023. Diabetes Care 2023; 46: S97-S110
• 16 Lipska KJ, Hirsch IB, Riddle MC. Human Insulin for Type 2 Diabetes: An Effective, Less-Expensive Option. JAMA 2017; 318: 23-24
• 17 Baker M, Musselman ME, Rogers R. et al. Practical implementation of remote continuous glucose monitoring in hospitalized patients with diabetes. Am J Health Syst Pharm 2022; 79: 452-458
• 18 Davies MJ, Aroda VR, Collins BS. et al. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2022; 45: 2753-2786
• 19 Galindo RJ, Aleppo G, Klonoff DC. et al. Implementation of Continuous Glucose Monitoring in the Hospital: Emergent Considerations for Remote Glucose Monitoring During the COVID-19 Pandemic. J Diabetes Sci Technol 2020; 14: 822-832
• 20 Longo RR, Elias H, Khan M. et al. Use and Accuracy of Inpatient CGM During the COVID-19 Pandemic: An Observational Study of General Medicine and ICU Patients. J Diabetes Sci Technol 2022; 16: 1136-1143
• 21 Wright JJ, Williams AJ, Friedman SB. et al. Accuracy of Continuous Glucose Monitors for Inpatient Diabetes Management. J Diabetes Sci Technol 2022;
• 22 Stacul F, van der Molen AJ, Reimer P. et al. Contrast induced nephropathy: updated ESUR Contrast Media Safety Committee guidelines. Eur Radiol 2011; 2: 2527-2541
• 23 Deutsche Diabetesgesellschaft. Positionspapier der Deutschen Diabetes Gesellschaft zur Therapie des Diabetes mellitus im Krankenhaus. 2018. Retrieved from (Accessed: 24.06.2024) https://www.ddg.info/politik/stellungnahmen/krankenhaus
• 24 Perkovic V, Agarwal R, Fioretto P. et al. Management of patients with diabetes and CKD: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int 2016; 90: 1175-1183
• 25 Lalau JD, Kajbaf F, Protti A. et al. Metformin-associated lactic acidosis (MALA): Moving towards a new paradigm. Diabetes Obes Metab 2017; 19: 1502-1512
• 26 Frisch A, Chandra P, Smiley D. et al. Prevalence and clinical outcome of hyperglycemia in the perioperative period in noncardiac surgery. Diabetes Care 2010; 33: 1783-1788
• 27 Deusenberry CM, Coley KC, Korytkowski MT. et al. Hypoglycemia in hospitalized patients treated with sulfonylureas. Pharmacotherapy 2012; 32: 613-617
• 28 Zinman B, Wanner C, Lachin JM. et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015; 373: 2117-2128
• 29 Umpierrez G, Korytkowski M. Diabetic emergencies – ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia. Nat Rev Endocrinol 2016; 12: 222-232
• 30 Landgraf R, Aberle J, Birkenfeld AL. et al. Therapy of Type 2 Diabetes. Exp Clin Endocrinol Diabetes 2022; 130: S80-S112
• 31 Marso SP, Daniels GH, Brown-Frandsen K. et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375: 311-322
• 32 Haak T, Gölz S, Fritsche A. et al. Therapie des Typ-1-Diabetes. Kurzfassung der S3-Leitlinie (AWMF-Registernummer: 057-013; 2. Auflage). Diabetol Stoffwechs 2023; 18: S136-S147
• 33 American Diabetes Association Professional Practice Committee. 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47: S111-S125
• 34 Diabetes Canada Clinical Practice Guidelines Expert Committee. Goguen J, Gilbert J. Hyperglycemic Emergencies in Adults. Can J Diabetes 2018; 42: S109-S114
• 35 Kitabchi AE, Umpierrez GE, Miles JM. et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009; 32: 1335-1343
• 36 Nyenwe EA, Kitabchi AE. Evidence-based management of hyperglycemic emergencies in diabetes mellitus. Diabetes Res Clin Pract 2011; 94: 340-351
• 37 Joint British Diabetes Societies for inpatient care. The management of the hyperosmolar hyperglycaemic state (HHS) in adults with diabetes: August 2012. 2012. Retrieved from (Accessed: 24.06.2024) http://www.diabetologists-abcd.org.uk/JBDS/JBDS_IP_HHS_Adults.pdf
• 38 Galway U, Chahar P, Schmidt MT. et al. Perioperative challenges in management of diabetic patients undergoing non-cardiac surgery. World J Diabetes 2021; 12: 1255-1266
• 39 Tao LS, Mackenzie CR, Charlson ME. Predictors of postoperative complications in the patient with diabetes mellitus. J Diabetes Complications 2008; 22: 24-28
• 40 Gallwitz B. Diabetes im Krankenhaus: Perioperative Einstellung der Patienten. Dtsch Arztebl 2019; 116
• 41 Halkos ME, Lattouf OM, Puskas JD. et al. Elevated preoperative hemoglobin A1c level is associated with reduced long-term survival after coronary artery bypass surgery. Ann Thorac Surg 2008; 86: 1431-1437
• 42 Dronge AS, Perkal MF, Kancir S. et al. Long-term glycemic control and postoperative infectious complications. Arch Surg 2006; 141: 375-380
• 43 Buchleitner AM, Martínez-Alonso M, Hernández M. et al. Perioperative glycaemic control for diabetic patients undergoing surgery. Cochrane Database Syst Rev 2012; 9: CD007315
• 44 Mahmood S, Farooqui SM, Madhoun MF. Predictors of inadequate bowel preparation for colonoscopy: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2018; 30: 819-826
• 45 Piper MS, Saad RJ. Diabetes Mellitus and the Colon. Curr Treat Options Gastroenterol 2017; 15: 460-474
• 46 Johnson DA, Barkun AN, Cohen LB. et al. Optimizing adequacy of bowel cleansing for colonoscopy: recommendations from the US multi-society task force on colorectal cancer. Gastroenterology 2014; 147: 903-924
• 47 Adamek HE, Bergmann L, Müssig K. Koloskopievorbereitung bei Patienten mit Diabetes mellitus: Entwicklung einer Handlungsempfehlung. Z Gastroenterol 2022; 60: 784-789
• 48 Lewandowski K, Rydzewska G, Ledwoń TK. Preparation for endoscopic examinations in patients with diabetes and hypoglycaemia. Prz Gastroenterol 2021; 16: 297-305
• 49 Müssig K, Adamek HE. Adjustment of Anti-Hyperglycaemic Agents During Bowel Preparation for Colonoscopy in Patients with Diabetes. Exp Clin Endocrinol Diabetes 2022; 130: 627-632
• 50 Hochberg I, Segol O, Shental R. et al. Antihyperglycemic therapy during colonoscopy preparation: A review and suggestions for practical recommendations. United European Gastroenterol J 2019; 7: 735-740
• 51 Australian Diabetes Society. Alert update September 2020. Periprocedural Diabetic Ketoacidosis (DKA) with SGLT2 Inhibitor Use. Retrieved from (Accessed: 24.06.2024) https://diabetessociety.com.au/downloads/20201015%20ADS_DKA_SGLT2i_Alert_update_Sept_2020.pdf
• 52 Australian Diabetes Society. Peri-operative diabetes management guidelines. Retrieved from (Accessed: 24.06.2024) https://diabetessociety.com.au/documents/PerioperativeDiabetesManagementGuidelinesFINALCleanJuly2012.pdf
• 53 van Raalte DH, Diamant M. Steroid diabetes: from mechanism to treatment?. Neth J Med 2014; 72: 62-72
• 54 Tamez-Pérez HE, Quintanilla-Flores DL, Rodríguez-Gutiérrez R. et al. Steroid hyperglycemia: Prevalence, early detection and therapeutic recommendations: A narrative review. World J Diabetes 2015; 6: 1073-1081
• 55 Katsuyama T, Sada KE, Namba S. et al. Risk factors for the development of glucocorticoid-induced diabetes mellitus. Diabetes Res Clin Pract 2015; 108: 273-279
• 56 Stauber MN, Aberer F, Oulhaj A. et al. Early Hyperglycemia after Initiation of Glucocorticoid Therapy Predicts Adverse Outcome in Patients with Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant 2017; 23: 1186-1192
• 57 Hjelmesaeth J, Hartmann A, Leivestad T. et al. The impact of early-diagnosed new-onset post-transplantation diabetes mellitus on survival and major cardiac events. Kidney Int 2006; 69: 588-595
• 58 Clore JN, Thurby-Hay L. Glucocorticoid-induced hyperglycemia. Endocr Pract 2009; 15: 469-474
• 59 Gosmanov AR, Umpierrez GE. Management of hyperglycemia during enteral and parenteral nutrition therapy. Curr Diab Rep 2013; 13: 155-162
• 60 Clubbs Coldron B, Coates V, Khamis A. et al. Use of continuous glucose monitoring in non-ICU hospital settings for people with diabetes: a scoping review of emerging benefits and issues. J Diabetes Sci Technol 2023; 17: 467-473
• 61 Korytkowski MT, Muniyappa R, Antinori-Lent K. et al. Management of hyperglycemia in hospitalized adult patients in non-critical care settings: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2022; 107: 2101-2128
• 62 Dillmann C, Amoura L, Fall Mostaine F. et al. Feasibility of real-time continuous glucose monitoring telemetry system in an inpatient diabetes unit: a pilot study. J Diabetes Sci Technol 2022; 16: 955-961
• 63 Ehrhardt N, Hirsch IB. The impact of COVID-19 on CGM use in the hospital. Diabetes Care 2020; 43: 2628-2630
• 64 Avari P, Lumb A, Flanagan D. et al. Continuous Glucose Monitoring Within Hospital: A Scoping Review and Summary of Guidelines From the Joint British Diabetes Societies for Inpatient Care. J Diabetes Sci Technol 2023; 17: 611-624
• 65 Wallia A, Umpierrez GE, Rushakoff RJ. et al. Consensus statement on inpatient use of continuous glucose monitoring. J Diabetes Sci Technol 2017; 11: 1036-1044
• 66 Inoue S, Egi M, Kotani J. et al. Accuracy of blood-glucose measurements using glucose meters and arterial blood gas analyzers in critically ill adult patients: systematic review. Crit Care 2013; 17: R48
• 67 Galindo RJ, Umpierrez GE, Rushakoff RJ. et al. Continuous glucose monitors and automated insulin dosing systems in the hospital consensus guideline. J Diabetes Sci Technol 2020; 14: 1035-1064
• 68 Flanagan D, Dhatariya K, Kilvert A. Joint British Diabetes Societies (JBDS) for Inpatient Care group and Guidelines writing group. Self-management of diabetes in hospital: a guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care group. Diabet Med 2018; 35: 992-996
• 69 Kannan S, Satra A, Calogeras E. et al. Insulin pump patient characteristics and glucose control in the hospitalized setting. J Diabetes Sci Technol 2014; 8: 473-478
• 70 Cook CB, Beer KA, Seifert KM. et al. Transitioning insulin pump therapy from the outpatient to the inpatient setting: a review of 6 years’ experience with 253 cases. J Diabetes Sci Technol 2012; 6: 995-1002
• 71 Noschese ML, DiNardo MM, Donihi AC. et al. Patient outcomes after implementation of a protocol for inpatient insulin pump therapy. Endocr Pract 2009; 15: 415-424
• 72 Avari P, Lumb A, Flanagan D. et al. Insulin Pumps and Hybrid Close Loop Systems Within Hospital: A Scoping Review and Practical Guidance From the Joint British Diabetes Societies for Inpatient Care. J Diabetes Sci Technol 2023; 17: 625-634
• 73 Dashora U, Levy N, Dhatariya K. et al. Managing hyperglycaemia during antenatal steroid administration, labour and birth in pregnant women with diabetes-an updated guideline from the Joint British Diabetes Society for Inpatient Care. Diabet Med 2022; 39: e14744
• 74 Yeh T, Yeung M, Mendelsohn Curanaj FA. Managing patients with insulin pumps and continuous glucose monitors in the hospital: to wear or not to wear. Curr Diab Rep 2021; 21: 7
• 75 Bally L, Thabit H, Hartnell S. et al. Closed-loop insulin delivery for glycemic control in noncritical care. N Engl J Med 2018; 379: 547-556
• 76 Atif Z, Halstrom A, Peragallo-Dittko V. et al. Efficacy of hybrid closedloop insulin delivery system in a hospital setting: a case series. AACE Clin Case Rep 2021; 7: 184-188

Publication History

Article published online:
12 May 2025