Diabetes Care in the Hospital Setting
- There are numerous considerations regarding hyperglycemia management in diabetic patients who are hospitalized. Formerly guidelines advocated to stop all oral antidiabetic agents in the hospital settings, nevertheless new clinical trials support the effectiveness of oral antidiabetic drugs, solitary or in combination to insulin therapy.
- The following table is a summary of treatment in non-critically ill hospitalized patients with diabetes:
One of the options which has been studied in randomized controlled trials is dipeptidyl peptidase-4 inhibitor. Although metformin use is common, use it with caution due to high risk of lactic acidosis, especially in high risk patients (such as sepsis, hypoxia, renal insufficiency, shock and hepatic failure)
- The following table is a summary of treatment in critically ill hospitalized patients with diabetes:
Continuous insulin infusion specially could be beneficial in hypoglycemia due to steroid use or in solid organ transplant patients. 
Prompt treatment is recommended in patients with myocardial infarction or ischemic stroke due to possible further harm due to hyperglycemia. ALthough intensive treatment is not recommended due to higher chance of hypoglycemia.

# 2016 ADA Standards of Medical Care in Diabetes Guidelines

## Insulin Treatment
- There are some available clinical practice guidelines and systematic reviews that suggest basal-bolus insulin may lower blood sugar more efficient, nevertheless it is more likely to cause hypoglycemia with no change in clinical outcomes. .
Key studies include:
Basal-bolus versus a basal plus correction insulin
Basal-bolus versus sliding scale insulin
Basal-bolus versus basal Plus sliding scale versus sliding scale alone.
Insulin analogues versus human insulin.
Basal-bolus insulin versus sliding scale insulin using the Glucommander eGlycemic Management System.
- Key studies include:
Basal-bolus versus a basal plus correction insulin
Basal-bolus versus sliding scale insulin
Basal-bolus versus basal Plus sliding scale versus sliding scale alone.
Insulin analogues versus human insulin.
Basal-bolus insulin versus sliding scale insulin using the Glucommander eGlycemic Management System.
- Basal-bolus versus a basal plus correction insulin
- Basal-bolus versus sliding scale insulin
- Basal-bolus versus basal Plus sliding scale versus sliding scale alone.
- Insulin analogues versus human insulin.
- Basal-bolus insulin versus sliding scale insulin using the Glucommander eGlycemic Management System.
- A landmark trial done in 2009 demonstrated an increased mortality risk with intensive insulin treatment, specifically in critically ill patients. Chance of hypoglycemia rises with intensive insulin therapy and can further complicate the situation.
- Continuous insulin infusion is recommended for critically ill diabetic patients (such as ICU patients), which should be replaced by subcutaneous insulin when patient is stable.
The following factors should be considered when transition from continuous insulin infusion to subcutaneous insulin is planned:
Patients should have a steady glucose concentration, at least for last 46 hours
Normal anion gap must be achieved (if patient have been presented with DKA, acidosis should have been resolved before transition).
Patients should be hemodynamically stable with out vasopressors
Patients should be on a stable diet
Patients should be on a steady intravenous infusion rate
- The following factors should be considered when transition from continuous insulin infusion to subcutaneous insulin is planned:
Patients should have a steady glucose concentration, at least for last 46 hours
Normal anion gap must be achieved (if patient have been presented with DKA, acidosis should have been resolved before transition).
Patients should be hemodynamically stable with out vasopressors
Patients should be on a stable diet
Patients should be on a steady intravenous infusion rate
- Patients should have a steady glucose concentration, at least for last 46 hours
- Normal anion gap must be achieved (if patient have been presented with DKA, acidosis should have been resolved before transition).
- Patients should be hemodynamically stable with out vasopressors
- Patients should be on a stable diet
- Patients should be on a steady intravenous infusion rate
- Based on a systematic review published in 2021, numerous subcutanoeus insulin regimen have been studied on non-critically ill diabetic patients. The following table is a summary of the afformentioned studies: 
Two-thirds before breakfast and one-third before dinner
Patients in basal-bolus group showed lower rate of general complications such as postoperative wound infection, bacteremia, pneumonia, renal insufficiency and respiratory failure.
Three times a day
Related article didn't provide the absolute numbers 
NPH insulin has been used twise a day. Regular insulin has been used before meals
60% before breakfast and 40% before dinner
Study terminated after interim analysis.
Two-thirds with breakfast and one-third with dinner
- There are numerous data rejecting use of subcutaneous sliding scale insulin in management of inpatient diabetes. However it usage could be accepted in management of stress hyperglycaemia in nondiabetics.
- If home insulin regimen of a patient has been higher than 06 U/kg each day, 20% reduction in general insulin dose should be considered at the time of admission. This effort is recommended to lower the chance of hypoglycemia in poor oral intake.
- Basal-bolus approach has been reported as an effective treatment for hyperglycemia, nevertheless it's usage in patients with mild hyperglycemia (<200 mg/dl) has been warned due to high risk of iatrogenic hypoglycaemia (with rate of 1230% in some studies).
- Another approach of insulin therapy such as basal-plus has been recommended for patients with mild hyperglycemia, surgical patients and low oral intake. The mentioned approach is consisted of a basal dose of insulin (01025 U/kg/day) and corrective insulin doses if hyperglycemia developed (Monitor glucose concentration every 6 hours in NPO patients, and before every meal in others). This approach has been associated with lower risk of hypoglycemia and is recommended in patients with low oral intake or surgical cases.
- Based on a systematic review, universal usage of premixed insulin regimens is not trusted in hospitalized diabetic patients.
- High rate of iatrogenic hypoglycaemia in premixed insulin therapy turned this approach into an untrsuted hyperglycemia treatment in hospitalized diabetic patients. However using premixed insulin therapy in patients taking enteral nutrition have been recommended (there are not enough supporting data). 

## Non-Insulin Treatments
- Formerly guidelines advocated to stop all oral antidiabetic agents in the hospital settings of diabetes management, nevertheless some clinical trials support the effectiveness of oral antidiabetic drugs, solitary or in combination to insulin therapy, in some hospitalized individuals. Countries such as England, Israel and India practice the usage of oral antidiabetic agents such as, metformin and sulfonylureas for inpatient diabetic patients.  

### Dipeptidyl Peptidase-4 Inhibitor Medications
- Dipeptidyl peptidase-4 inhibitor medications are effective for glycemic control in mild to moderate hyperglycemia. Moreover dipeptidyl peptidase-4 inhibitors are tolerated very well and there has been low rate of hypoglycemia. It's usage has been recommended alone or in combination with basal insulin in patients with blood glucoselower than 180 mg/dl. 
- There are some evidences about possible effectiveness of sitagliptin in survival of diabetic patients who are infected with COVID-19. Nevertheless due to limitted data more study is required. 

### Glucagon-Like Peptide-1 Analogs
- Studies have shown effectiveness of glucagon-like peptide-1 analogs (such as liraglutide and exenatide) in hospitalized diabetic patients. Based on systematic reviews gastrointestinal side effects have been reported in patients who received glucagon-like peptide-1 analogs.
- Studies show that GLP-1 agonists reduced glycated haemoglobin A1c levels to a greater extent than SGLT-2 inhibitors.
- The following table is summary of various randomized controlled trial and observational studies regards dipeptidyl peptidase-4 inhibitor and glucagon-like peptide-1 analogs use in hospital setting:
Liraglutide has been used subcutaneously with dosage of 06 mg before surgery and 1.2 mg after anesthesia induction.   
Infusion of glucose, insulin and potassium was 30 mintunes before surgery and continued until 4 hours after surgery. 
Exenatide has been used with dose of 5 mg twice a day. 
Liraglutide has been used subcutaneously with dosage of 06 mg on the evening before surgery and 1.2 mg after anesthesia induction.

### SGLT2 Inhibitors
- SGLT2 inhibitors are the current treatment of choice among other oral antidiabetic drugs especially for diabetes type 2 patients with concurrent heart failure or diabetic nephropathy. It's use has been related to lower rate of readmission, death within 60 days and heart failure. Nevertheless it's routine use in hospital setting is not recommended.
- Frequent euglycaemic diabetic ketoacidosis, mostly in patients with poor oral intake and genitourinary infections have been made worry regards SGLT2 inhibitors use for diabetic inpatients. Fungal infections are the common responsible microorganisms for genitourinary infections of these patients.
- Based on a meta-analysis by Palmer et al., SGLT-2 inhibitors and GLP-1 receptor agonists, together for the treatment of DM type 2, reduce mortality, non-fatal myocardial infarction, and serious hyperglycemia, and renal failure.
- Based on a systematic review empagliflozin use has not shown any improvement compared to the placebo groups, in the following Characteristics:
Dyspnea
Brain natriuretic peptide level
Hospitalization period
Response to diuretics
- Dyspnea
- Brain natriuretic peptide level
- Hospitalization period
- Response to diuretics

### Metformin
- Use metformin with caution in hospitalized patients especially if renal or hepatic failure, sepsis and shock is present due to high chance of lactic acidosis. To prevent such an adverse effect, patients with GFR in range of 3045 mL/min per 173 m2 should recieve lower doses of metformin. Furthermore metformin must be discontinued in patients with GFR lower than 30 ml/min per 173 m2.
- Metformin should be discontinued prior to iodinated contrast imaging if eGFR <60 mL/min per 173 m2, history of hepatic disease, acute heart failure, alcoholism or received intra-arterial contrast medium.
- Compared to other oral antidiabetic agents, metformin showed higher rate of gastrointestinal adverse effects in the hospitalized patients.

### Sulfonylureas
- Frequent hypoglycemic events have been reported in sulfonylureas usage in the hospital setting, hence experts don't recommend it for treatment of diabetic inpatients. Facrors such as old age, renal insufficiency and concurrent insulin use have been related to higher risk of hypoglycemia. Although UK recommendations proposed it's effectiveness in mangement of hyperglycemia due to glucocorticoid use.

### Thiazolidinediones
- Late onset of action and risk of heart failure (due to water retention) turned thiazolidinediones into an ineffective treatment in hospital settings.

## Specific Circumstances
The following are some management considerations that are recommended in hospitalized diabetic patients with specific circumstances.

### Medical Nutrition Therapy
- Use low glucose content formulas in diabetic patients who are receiving nutritional therapy to avoid hyperglycemia. 
- There are some studies that demonstrate the effectiveness of adding short acting insulins into the parenteral bag, compared to usage of solitary subcutaneous insulin. 
- If laboratory evaluations show constant hyperglycemia in diabetic or non-diabetic patients usage of basal-bolus insulin is recommended.
- UK guidelines advocate use of 70/30 mixed insulin in diabetic patients in hospital who are receiving nutrition therapy. 
- When medical nutritional therapy paused infusion of 10% dextrose at rate of 50 ml/hr is recommended.
- Closed loop insulin therapy has been proposed by a randomised trial done in 2019 as a possible treatment in hospitalized diabetic patients on nutrition therapy. 

### Concurrent Glucocorticoid Use
- Frequent hyperglycemia has been reported in hospitalized patients who are taking glucocorticoids.
- Management of glucocorticoid induced hyperglycemia, in order to achieve the glycemic goal, is much harder in diabetic patients who were receiving home insulin.
- Based on an observational study done on patients who were recieving high dose dexamethasone with 2 glucose concentration higher than 250 mg/dL, multiple dose insulin therapy was an effective treatment. Insulin therapy in the aforementioned study initiated at 112 U/kg per day with 1/4 basal and 3/4 prandial distribution. In the case of hyperglycemic patients without diabetes who are taking glucocorticoids, isophane insulin in the morning could be a possible treatment. 
- Based on a systematic review done in 2020, usage of insulin twice a day with a total dose of 03 u/kg/day has been recommended. Recommendations divided this dose to 2/3 in the morning and 1/3 in the evening.
- It is recommended to adjust insulin dose based on the glucocorticoid dosage and oral intake. 
- Dexamethasone discontinuation can be followed by a rapid decrease in insulin requirement, hence insulin dose reduction is necessary.
- Sulfonylurea is not an effective treatment in diabetic patients who are on glucorticoids.

### Preoperative State
- Appropriate glycemic control is critical in surgical patients since high glucose concentration is related to higher rates of complications. 
- Basal-bolus insulin treatment has been effective in patients with diabetes type 2 in the preoperative period. 
- Simillarly basal plus insulin treatment approach is effective in patients with diabetes type 2 in the preoperative period, hence it could be an alternative for basal-bolus insulin treatment.
- Reports of some studies support the effectiveness of glucagon-like peptide 1 receptor agonists for glycemic control of diabetic patients in peroperative state. 
- SGLT2 inhibitors is recommended by The US Food and Drug Administration (FDA) to be discontinued 3-4 days before surgery in order to reduce the risk of euglycaemic diabetic ketoacidosis in patients. 
- Dipeptidyl peptidase-4 inhibitor is not an effective treatment in diabetic patients in preoperative period. 

## Hospital Technologies

### Continuous Glucose Monitoring
- More than just checking glucose continuously, this devices give us trends and patterns in order to better study hyperglycemia and hypoglycemia events.
- 2 approved systemes by Food and Drug Administration (FDA) are GlucoScout and OptiScanner 5000, which intemittently collect venous blood samples (central or peripheral veins). 
- The Abbott Freestyle Libre flash glucose is another system in continuous glucose monitoring which collects blood samples intermitently and alarm when high glucose concentration is detected.
- Real time continuous glucose monitoring is used in Dexcom and Medtronic devices which are recommended as an effective approach for management of diabetic patients in hospital.
- Senseonics Eversense is an implanted device which could be used for 5-6 months.
- Apart from all the benefits of continuous glucose monitoring there are some concerns regarding the accuracy of glucose measures due to physiologic changes (such as vasoconstriction, severe dehydration, hypoxemia and rapid changes in blood glucose levels due to diabetic ketoacidosis) or interaction by some agents. Agents that can possibly interact with glucose reading are salicylic acid, paracetamol (doses higher than 4 grams per day) and ascorbic acid.

### Continuous Subcutaneous Insulin Pumps
- Rate of hyperglycemia and hypoglycemia is reduced with use of continuous subcutaneous insulin infusion pumps such as standalone insulin pumps.
- The following are some of the contraindications of continuous subcutaneous insulin pumps:
Hyperglycemia crisis
Absence of trained medical provider
Low level of consciousness (excluding short-term anaesthesia)
Incapability of patients to maintain an appropriate pump setting
Incapability of patients to manage their diabetes
Absence of required supplies
- Hyperglycemia crisis
- Absence of trained medical provider
- Low level of consciousness (excluding short-term anaesthesia)
- Incapability of patients to maintain an appropriate pump setting
- Incapability of patients to manage their diabetes
- Absence of required supplies
- Pumps should be removed during some investigations such as MRI. 

### Closed Loop Insulin Delivery System
- Closed loop system is a combination of continuous glucose monitoring and subcutaneous insulin pumps, which is also known as artificial pancreas system.
- Medtronic 670G, Diabeloop and Tandem Control-IQ are 3 currently commercially available systems that are commonly used by patients with diabetes type 1.
- A trial evaluated the effect of closed loop system on patients with diabetes type 2 reported better glycemic control, compared with the control group (p<00011). 
- Another study investigated the effectiveness of this method on diabetic patients with end stage renal disease which demonstrated better glycemic control.