Inpatient hyperglycemia.ver3 (3)

Management of inpatient
hyperglycaemia in non–critically
ill patients with type 2 diabetes
Under guidance of - Dr. RAJEEV PATNI
Fellow Institute of Endocrinology, Univ of Sydney,
NSW, Australia
Consultant Endocrinologist & Diabetologist
Santokba Durlabhji Memorial Hospital Jaipur
1
Presented by- Dr. MOHAMMAD REHAN
DNB Resident

Overview
• Introduction
• Definition and diagnosis of inpatient hyperglycaemia
• Classification of hyperglycaemia
• Pathogenesis of hyperglycaemia in hospitalized patients
• Glycaemic targets
• Treatment of hyperglycaemia
• Sliding scale vs Basal-bolus
• Insulin regimens
• Insulin therapy in specific clinical situations
• Summary
• Case discussion
2

Introduction
• Diabetes is a major healthcare challenge of the century and is epidemic
worldwide.
• Global prevalence of Diabetes patients- 415 million (41.5 Cr)
• Prevalence in India- 69.2 million (6.92 Cr); expected to cross 100 million mark
by year 2040.
• Hyperglycaemia is common in hospitalized patients
• 12-25% of hospitalized patients have pre-existing diabetes
• 50% of patients admitted to ICU have prediabetes or diabetes
• Of the hospitalized patients, almost a third have significant hyperglycaemia
IDF Diabetes Atlas,7th Edition, 2015. International Diabetes Federation http://www.diabetesatlas.org/
Umpierrez GE, et al. JCEM: January 2012, 97 (1):16–38.
Umpierrez GE. J Clin Endocrinol Metab.2002;87:978–982.
3

Introduction
• Hyperglycaemia is a risk factor for adverse outcomes during acute illness,
surgery or steroid treatment
• Insulin is the mainstay of treatment of hyperglycaemia in hospitalized
patients
• Hyperglycaemia in inpatients is a strong predictor of in-hospital mortality
• Hyperglycaemia has been shown to increase the risk of mortality in
hospitalized patients irrespective of diabetic status
4
IDF Diabetes Atlas,7th Edition, 2015. International Diabetes Federation http://www.diabetesatlas.org/
Umpierrez GE. J Clin Endocrinol Metab.2002;87:978–982.

Definition and diagnosis of inpatient hyperglycaemia
• In-hospital hyperglycaemia is defined as glucose value greater than 7.8
mmol/litre (140 mg/dl)
• Hyperglycaemia occurs not only in patients with known diabetes but also
in those with previously undiagnosed diabetes and others with “stress
hyperglycaemia”
• Stress hyperglycaemia may be defined as hyperglycaemia which may
occur during an acute illness or stress, and that resolves once the illness
improves or stress is over.
RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 5

Classification of hyperglycemia
• Hyperglycaemia in hospitalised patients can be further classified into 3
broad categories1:
Previously diagnosed Existing hyperglycaemia prior to hospitalization
Previously
undiagnosed
At admission:
 Fasting Blood Sugar (F) > 126 mg/dl,
 Random Blood Sugar Level (R) > 200 mg/dl,
 HbA1c > 6.5%
Stress
hyperglycaemia
At admission:
 HbA1c < 5.7%
 During hospitalization: F > 126 mg/dl, R > 200 mg/dl
 Post discharge: Normoglycaemia

Pathogenesis of hyperglycaemia in hospitalized patients
Mehta KC. Chapter 62. Medicine Update. 2005;300–303. Available at
http://www.apiindia.org/medicine_update_2005/chapter_62.pdf
7
 Stress hormones
cortisol, epinephrine  Glucose Production
 Lipolysis
FFAs
FFAs
+
 Glucose Uptake
 Glucose
 Fatty Acids
Illness

Adverse effects of hyperglycaemia
8
Illness
 Glucose
 Fatty Acids
Hemodynamic insult
Electrolyte losses
Oxidative stress
Myocardial injury
Hypercoagulability
Altered immunity
 Wound healing
 Inflammation
 Endothelial function
Mehta KC. Chapter 62. Medicine Update. 2005;300–303. Available at
http://www.apiindia.org/medicine_update_2005/chapter_62.pdf

Glycaemic targets for non-critically ill patients
• Premeal blood glucose (BG) <140 mg/dl
• Postmeal/random BG <180 mg/dl
• BG target <200 mg/dl is reasonable for
• Patients with low life expectancy, terminal illness or increased risk of
hypoglycaemia
• Reassess if BG <100 mg/dl
• Modify if BG <70 mg/dl
Moghissi ES. Diabetes Care 2009 Jun; 32(6): 1119-1131
9

Treating hyperglycaemia in non-critically ill patients
• Insulin is the preferred treatment for hyperglycaemia in non-critically ill
hospitalized patients with diabetes
• For patients with T1DM- basal-bolus
• For T2DM patients who are already on oral agents and have well
controlled glycaemia continue existing therapy

• Indications of using insulin in T2DM
1) Lean individuals or those with severe weight loss
2) Individuals with underlying renal or hepatic disease that precludes oral
drugs
3) Hospitalised or acutely ill individuals
4) Glycemic target not achieved after combination oral therapy
11

Treating hyperglycaemia in non-critically ill patients
• Non-insulin agents
• Generally not preferred because of
• recurrent vomiting, sepsis, enteral/parenteral feeding, pancreatic disorders, renal failure
• Common problems with oral antidiabetic drugs (OADs)
• Sulphonylureas (SUs): prolonged and severe hypoglycaemia if meal is skipped or
oral intake is poor
• Metformin: ↑risk of lactic acidosis
• Thiazolidinediones (TZD): take several weeks for the full effect
• DPP-4 Inhibitors: generally contraindicated in patients with pancreatic disease
• GLP-1 Agonists: cause nausea; best avoided in hospitalised patients
• SGLT2 inhibitors: can predispose to genito-urinary infections
RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication.
Moghissi ES. Diabetes Care 2009 Jun; 32(6): 1119-1131
12

Insulin regimens for treating non-critically ill in-hospital patients
• Insulin is the preferred choice
• Sliding Scale Insulin (SSI) was a common approach in hospital settings
• Problems with SSI
Umpierrez GE. Diabetes Care. 2007;30:2181–2186.
Umpierrez GE. DiabetesCare. 2011;34:256–261.
13
• It is based on the assumption that
insulin resistance is uniform in all
patients
• One dosing formula for all
• Chases glucose values; dosing decided
based on hyperglycaemia after it has
happened
• Under-estimates the total daily insulin
requirement
• Does not differentiate basal and
prandial requirements
• Ineffective glycaemic
control
• ↑Hypoglycaemia risk
• Increased hospital stay

Sliding-Scale regular Insulin (SSI) vs Basal-Bolus (RABBIT-2 Trial)
Umpierrez GE. Diabetes Care 30:2181–2186, 2007 14
Changes in blood glucose concentrations in patients treated
with glargine plus Glulisine (•) and with SSI (○). *P < 0.01; ¶P <
0.05.
Mean blood glucose concentration in subjects who remained with
severe hyperglycemia despite increasing doses of RI per the sliding-
scale protocol (○). Glycemic control rapidly improved after switching
to the basal-bolus insulin regimen (•). P < 0.05.
Treatment with basal insulin & bolus insulin resulted in significant improvement in glycaemic control as compared to sliding-scale
regular insulin (SSI) alone. Use of basal-bolus insulin regimen was safe & associated with a low rate of hypoglycaemic events

Sliding-Scale regular Insulin (SSI) vs Basal-Bolus (RABBIT-2 Surgery Trial)
Umpierrez GE. DiabetesCare. 2011;34:256–261. 15
Changes in blood glucose concentration after the
1st day of treatment with basal-bolus with glargine
once daily plus glulisine before meals (○) and with
SSI 4-times daily (●). *P < 0.001, ŧP = 0.02, †P =
0.01.
Glucose levels before meals and bedtime. Premeal and
bedtime glucose levels were higher throughout the day in the
SSI group (●) compared with basal-bolus regimen (○).
Basal-bolus treatment with glargine once daily plus glulisine before meals improved glycemic control and reduced
hospital complications compared with SSI in general surgery patients

Insulin regimens
Insulin regimen for these patients should include three components:
• ‘Basal-bolus’ is the preferred insulin regimen
• Patients who are well controlled on premix insulins can continue premix
Basal insulin • Insulin glargine once daily
• Insulin detemir once or twice daily
• NPH twice daily
Nutritional insulin • Rapid acting analogues or regular insulin
(RI) given subcutaneously before meals
Correctional insulin • Rapid acting analogues or RI given
subcutaneously before meals

Estimating subcutaneous (SC) insulin dose
• Patients on insulin and well controlled at home can be maintained with same regimen with
adjustments
- based on meals, activity, effects of illness and the effects of other medications
17
TDD calculation TDD: 80% of calculated
TDD
For insulin naïve: Total dose as per body
weight
Use 80% of calculated
TDD for starting s/c
insulin
Give:
Basal insulin: 50% of TDD
Bolus insulin: 50% of TDD
Ideal body weight 0.4-0.5 u/kg
Obese 0.5-0.6 u/kg
Lean or renal compromised 0.3-0.4 u/kg
From IV to S/C transition
Calculate the insulin requirement in previous 6 hours of
stable control of BG and multiply by 4 for total amount of
insulin needed in 24 hours or the actual total insulin
requirement in the last 24 hours.

18
Calculation of the dose with correctional factor
Basal dose Correctional bolus (CB)
Glargine Single dose AM/PM Blood glucose (BG) – 100 =
CB
Correction Factor (CF)
CF= 1500/TDD (Regular
insulin)
Or
CF=1800/TDD (Analogue
insulin)
Detemir Given 12 hourly split dose
NPH Given 12 hourly split dose
Degludec Single dose
For basal dose correction:
PM basal: Check FBG for 2 days, ↑2u of basal till FBG 80-120mg%
AM basal: Check pre-dinner for 2 days, ↑2u of basal till BG 90-110mg%
Bolus dose
Total bolus dose ÷ 3 With breakfast, lunch, dinner
For bolus: regular, Aspart, Glulisine, Lispro can be used
1. RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication.

19
Example of calculation
TDD: 30U
-Basal: 15U AM/PM
-Bolus 15U (Regular)
Bolus 5U-5U-5U before each 3 meals
+ Additional correctional bolus for BG not
at target at any meal
Additional Correctional Bolus:
Estimated BG: 250
CF: 1500/30=50
CB = 250 -100 = 150 = 3U
CF 50 50
Total meal dose: 5U+3U = 8 units
1. RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication.
Insulin in renal compromised patients
• Renal compromised patients need a
lower dose of insulin
• Depending on GFR, target goals
may be relaxed
• Targets for renal patients
HbA1c FBGL(mg/dl) 2h PPBSL
(mg/dl)
Normal GFR,
microalbuminuria +
6.5-7 80-120 < 180
Predialysis (Cr.Cl < 10) < 7.5 100-140 < 180
Dialysis 7.5 – 8 100-140 < 200
Post renal transplant 6.5-7 80-120 < 180

Insulin therapy in specific clinical situations
• Peri-operative management
• Stable glycaemic control prior to the elective procedure with HbA1c target of <
8%
• If HbA1c is >9% or BG >200 mg/dl and surgery cannot be postponed → first
achieve blood glucose control prior to procedure
• During surgical procedure, maintain BG levels 140-180mg/dl
• Minor surgical procedures
• Managed without changing the pre-operative anti-hyperglycaemic treatment
regimen
• If patient has uncontrolled hyperglycaemia it needs to be controlled and then
surgery can be planned.

• For morning procedures:
• The day prior to procedure→ take full dose of medications- insulin and OADs at
dinner
• Patient remains nil by mouth until the procedure is complete in the morning
• Usual dose of insulin and/or OADs with breakfast by mid-morning.
• If procedure is delayed & BG are above target (>180 mg/dl) →start insulin
infusion
• Subcutaneous (S.C.) correction short acting insulin dose if facility for infusion is
not available

• For patients who are not on insulin (on OADs or GLP-1 analogues)
• All OADs and GLP-1 analogues
• continued on the day prior to procedure
• omitted on the morning of procedure
• resumed once the patients resume their diet
• Metformin
• Need not be discontinued unless there is renal, cardiac and hepatic
impairment
• For procedures requiring radio-contrast administration
• discontinue metformin 24 hours prior to the procedure.
• restart after confirming normal renal function after 48 hours.

Management of hyperglycaemia during obstetrics
procedures, C-Section and vaginal delivery
• Day care obstetric procedures (cervical cerclage, amniocentesis) do not require more
than 6-8 hours of overnight fasting
• Maintain BG between 70-140 mg/dl during and immediately after the procedure.
Intrapartum glucose management
• Uncontrolled maternal hyperglycaemia during the labour → foetal hyperinsulinism
and neonatal hypoglycaemia
• Maternal BG target during delivery - 70 to 140 mg/dl
• Separate insulin and glucose infusions
• Start insulin infusion at 0.5 -1 U/hr
• 5% Dextrose or dextrose normal saline [DNS] - 80-125 ml/h.

Glycaemic management during caesarean section
and induction of labour
• A planned caesarean section should be posted early in the morning
• Usual dose of OADs and night-time insulin the day prior to surgery
• Withhold OADs and insulins on surgery day
• If procedure is delayed and light breakfast is allowed by obstetrician, give half the
dose of intermediate insulin S.C.
• Maintain BG levels between 70-140 mg/dl by glucose infusion
24RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication.

Patients receiving enteral nutrition
• Hyperglycaemia is a common complication of enteral feedings
• Enteral formulas with low carbohydrate & modified fat content should be used if
possible
• Treat persistent hyperglycemia with insulin
• Insulin regimens
• once-daily glargine insulin
• premixed human 70/30 insulin every 8 hours
• combination of NPH every 12 hours and RI every 6 hours
• Starting TDD of insulin 0.3-0.6 U/kg
• adjusted daily based on glucose response and the amount of correctional insulin that was
required the previous day
• Add 80% of correctional insulin to the long- or intermediate-acting insulin next day

Sample insulin requirement calculation for a patient on enteral feeding
Sample: Insulin dose calculation for 80kg patient with a BMI of 24kg/m2 on continuous
enteral feeding
Step 1. TDD calculation
TDD=0.4x80 (0.4units/kg body weight x body weight) = 32 units
Step 2. Insulin dose based on type of insulin
Insulin glargine/degludec 32 units subcutaneously daily
Insulin NPH 16 units subcutaneously twice daily
Step 3. Correctional scale estimation
Low correctional scale insulin is most appropriate for patients requiring an
estimated TDD of 32 units. Order correction dose every 4 hours with rapid
acting analogues and every 6 hours with RI.
26RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication.

Patients receiving total parenteral nutrition (TPN)
• Hyperglycaemia occurs commonly with total parenteral nutrition (TPN)
• For mild hyperglycaemia add RI to TPN 0.1 units for every gram of carbohydrate
• If glucose remains, adjust insulin dose in TPN daily by adding 80% of the previous
day’s correctional insulin
• If BG are very high use IV insulin
• Once stable IV rate is determined extrapolate it to 24 hr TDD with 75% of this
added to TPN.

CASE STUDY 2
• A 50-year-old man with diabetes (BMI = 30.2 kg/m2) is admitted for
pneumonia treatment with a RBG level of 300 mg/dL and an HbA1c level
of 10.8 %; OADs are discontinued, and blood glucose testing is ordered
before meals and at bedtime.
31
How will you initiate insulin therapy in
this non-critical care setting

Initiating Insulin Therapy
• Calculated total daily dose (TDD) of insulin:
• 0.6 U/kg × 90kg = 54 U
• Basal dose = 50% of TDD at bedtime
– 50% of 54 U = 27 U basal insulin at bedtime
• Total bolus dose = 50% of TDD evenly distributed 1/3 at each meal
– 27 U÷3 meals = 9 U rapid-/short-acting insulin before each meal (t.i.d.)
• Give additional rapid-/short-acting insulin as per standard supplemental
(correction) insulin schedule
32

Components to be integrated in the discharge plan
• Medications at discharge are based on HbA1c
• Previously diagnosed,
• HbA1c < 8% - continue pre-hospitalisation treatment
• HbA1c > 8% - treatment needs to be intensified
• Addition of another oral antidiabetic medication
• Intensification of the doses of pre-existing medications (or insulin)
• Initiation of basal insulin for patients not on insulin
• HbA1c is not available
• with fair glycaemic control - pre-admission anti-diabetic medication continued
• with poor glycaemic control - pre-admission medications to be titrated
Bogun M. Clinical Therapeutics/Vol 35, Number 5, 2013. http://www.ncbi.nlm.nih.gov/pubmed/23688537
42

Components to be integrated in the discharge plan
• Previously undiagnosed,
• HbA1c 6.5% -7% - life style modification, follow up and monotherapy with an oral glucose
lowering agent may be considered
• HbA1c > 7 % - OHA and / or insulin if indicated
• Stress hyperglycaemia,
• HbA1c < 5.7% - follow up recommended
• HbA1c 5.7%–6.4% - treated as per recommendations for prediabetes
• Follow up: within 15 days of discharge with the specialist and / or
primary care physician.
Bogun M. Clinical Therapeutics/Vol 35, Number 5, 2013. http://www.ncbi.nlm.nih.gov/pubmed/23688537
43

Case study
44
Mr RKS, a 45-year-old male patient, is a known case of type 2 diabetes for five years.
There is no history of hypertension, coronary artery disease, or any other complications of diabetes. He
has been on treatment with glimepiride 4 mg daily, metformin (extended release) 2 grams daily, and
atorvastatin 10mgs daily.
He developed acute pain abdomen and recurrent vomiting for 24 hours for which he was hospitalised.
He was diagnosed with acute renal colic. His blood glucose at the time of admission was 275 mg/dl
and his HbA1C was 8.3%. He is haemodynamically stable. His renal functions were normal. He was
initiated on conservative treatment with anti-emetics and painkillers.
You have been asked to take care of his hyperglycaemia.

45
How will you manage and outline broad management
options

46
Type 2
diabetes
patient
• Hospitalised in non-critical care setting
• With uncontrolled glycaemia prior to
admission
• On oral agents prior to admission
• Able to accept orally

• Guidelines for management of hyperglycaemia in such a patient involves:
• Initiating regular glucose monitoring.
• Stop oral agents.
• Calculating total daily requirement of insulin.
• Giving 40% of the dose as insulin glargine subcutaneously or 20% of the dose as
NPH subcutaneously, given twice daily.
• Dividing 40% of the calculated dose equally in three doses of rapid acting insulin,
given before meals.
• Adding correction bolus based on pre-meal BG values.
• BG monitoring before meals, at bedtime, in fasting state, whenever
hypoglycaemia is suspected.
47

• Targeting fasting BG at 110-140 and other glucose values at 140-180mg/dl.
• Modifying basal insulin dose based on fasting BG/ fasting and before dinner BG.
• Modifying bolus dose of insulin by adding correctional doses used on previous
day to the calculated bolus doses.
• Once improved and accepting normal meals, basal insulin may be continued,
bolus insulin can be stopped and oral agents added, and patient can be
discharged on basal plus oral therapy for hyperglycaemia with advice:
• to monitor BG regularly
• how to interpret BG values
• to watch for hypoglycaemia
• to make adjustments based on BG monitoring
• to come for follow up after 1-2 weeks.
48

Insulin
The Most Powerful Agent We Have to Control
Glucose
• Oldest of the currently available medications
• Most clinical experience available
• Most effective agent for lowering glycemia
• No maximum dose beyond which therapeutic effect will not occur
• Beneficial effects on triglyceride and HDL cholesterol levels
Nathan DM, Buse JB, Davidson MB, et al. Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus
Algorithm for the Initiation and Adjustment of Therapy. Diabetes Care, Volume 32, Number 1, January 2009

Polonsky, N Engl J Med 1996; 334: 777-783
Normal Insulin Secretion

Main Types of Insulin Analogs
• Rapid Acting Analogs- For providing
prandial/mealtime/bolus doses
• Basal Insulin Analogs- For providing basal levels of
insulin during interprandial and nocturnal periods
• Premix Insulin Analogs- providing both prandial and
basal insulin in single injection

Comparison of Human Insulins/Analogs
Insulin Onset of Duration of
Preparations Action Peak Action
Regular 30-60 min 2-4 h 6-10 h
NPH/lente 1-2 h 4-8 h 10-20 h
Ultralente 2-4 h Unpredictable 16-20 h
Lispro/Aspart 5-15 min 1-2 h 4-6 h
Glargine 1-2 h Flat ~24 h
Detemir 1 – 2 h 3 – 9 h 17 – 23 h

Comparison of Human Insulins/Analogs
Hours
Regular 6-10 hours
NPH 12–20 hours
Lispro/Aspart 4–6 hours
 BASAL INSULINS
Detemir ~ 6-23 hours (dose dependant)
Glargine ~ 20-26 hours
 BOLUS INSULINS

4:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
8:0012:008:00
Time
Plasmainsulin
Ideal Basal/Bolus Insulin
Absorption Pattern

Need for Rapid-acting Insulin Analogs
• Mimic physiologic insulin profile (1st and 2nd Phase)
• Administration at mealtime (no waiting)
• Improved postprandial glycemic control
• Lower risk of late hypoglycemia

Limitations of NPH, Lente,
and Ultralente
• Do not mimic basal insulin profile
• Variable absorption
• Pronounced peaks
• Less than 24-hour duration of action
• Cause unpredictable hypoglycemia
• Major factor limiting insulin adjustments

4:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
8:0012:008:00
Time
Basal Insulin
lispro lispro lispro
Plasmainsulin
Long-acting Insulin Analogs with Rapid Acting Analogs
Provide Ideal Basal Bolus Insulin Profile

Premix Analogs
• Have been shown to be effective for
achieving glycemic control and they may
also decrease the risk for hypoglycemia
• Specially beneficial in patients with
inconsistent mealtimes and lifestyles and in
those whose adherence to treatment may
be enhanced by a simple treatment
regimen

Insulin Analogs
• Provide more closer physiological insulin delivery
• Greater convenience due to flexible timing of injections
• Provide almost identical or better long term glycemic control
• Associated with somewhat lower episodes of hypoglycemia
• May be more weight friendly
• Long-term studies awaited on cancer risk
• Complete data still lacking on use during pregnancy
• No information on benefits in late complications

Key Advantages of Basal Insulin Analogs
• Once daily injection in significant number of subjects
• Appears to be more effective than NPH in real life over several years
• Has less weight gain than premix in BOT
• Have better efficacy/hypoglycaemia ratio than NPH
• Reduces the risk of hypoglycaemia compared to NPH when initiating
insulin in all patient types, including the elderly
• Associated with less risk of nocturnal hypoglycaemia than NPH
• Has a significantly better QoL compared with NPH

Summary: Benefits of Using Premix Insulin Analogs
• Convenient- Easy initiation and same insulin can be intensified
• Effective-
• Better A1c control than long-acting analogs and other agents as shown in several meta-analysis
• Twice-daily regimens provides almost similar glycemic control as an intense regimen of multiple
daily injections (MDI)
• No mixing errors- By combining the insulins themselves, patients can encounter problems
with mixing technique and inaccurate dosing ratios, potentially reducing the effectiveness of
the short-acting insulin.
• Less detailing required- Basal bolus regimen requires patients to remember multiple types of
pens and doses
• Mealtime flexibility with Premix Analogs- Premixed insulin analogs provide quick absorption
and rapid PPG-lowering effects provide potential for improved glycemic control

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