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Inpatient hyperglycemia.ver3 (3)

This document provides a comprehensive overview of the management of inpatient hyperglycaemia in non-critically ill patients with type 2 diabetes, highlighting the prevalence of diabetes and hyperglycaemia in hospitalized patients. It discusses glycaemic targets, treatment options such as insulin regimens, and specific clinical situations requiring tailored approaches. The document emphasizes the significance of insulin therapy and presents detailed guidelines for managing hyperglycaemia in various contexts, including surgical procedures and enteral feeding.

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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, et al. JCEM: January 2012, 97 (1):16–38. 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. Umpierrez GE, et al. JCEM: January 2012, 97 (1):16–38. 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: RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 6 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 Umpierrez GE, et al. JCEM: January 2012, 97 (1):16–38. 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 RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 10
• 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 RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 16 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 RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 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. RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 20
Insulin therapy in specific clinical situations • 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 RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 21
Insulin therapy in specific clinical situations • 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. RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 22
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. RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 23
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 RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 25
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. RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 27
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 RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 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. RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 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
Thank you 62

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Inpatient hyperglycemia.ver3 (3)

  • 1.
    Management of inpatient hyperglycaemiain 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
  • 2.
    Overview • Introduction • Definitionand 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
  • 3.
    Introduction • Diabetes isa 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
  • 4.
    Introduction • Hyperglycaemia isa 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, et al. JCEM: January 2012, 97 (1):16–38. Umpierrez GE. J Clin Endocrinol Metab.2002;87:978–982.
  • 5.
    Definition and diagnosisof 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. Umpierrez GE, et al. JCEM: January 2012, 97 (1):16–38. RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 5
  • 6.
    Classification of hyperglycemia •Hyperglycaemia in hospitalised patients can be further classified into 3 broad categories1: RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 6 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
  • 7.
    Pathogenesis of hyperglycaemiain 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
  • 8.
    Adverse effects ofhyperglycaemia 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
  • 9.
    Glycaemic targets fornon-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 Umpierrez GE, et al. JCEM: January 2012, 97 (1):16–38. Moghissi ES. Diabetes Care 2009 Jun; 32(6): 1119-1131 9
  • 10.
    Treating hyperglycaemia innon-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 RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 10
  • 11.
    • Indications ofusing 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
  • 12.
    Treating hyperglycaemia innon-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
  • 13.
    Insulin regimens fortreating 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
  • 14.
    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
  • 15.
    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
  • 16.
    Insulin regimens Insulin regimenfor these patients should include three components: • ‘Basal-bolus’ is the preferred insulin regimen • Patients who are well controlled on premix insulins can continue premix RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 16 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
  • 17.
    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 RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 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.
    18 Calculation of thedose 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.
    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
  • 20.
    Insulin therapy inspecific 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. RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 20
  • 21.
    Insulin therapy inspecific clinical situations • 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 RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 21
  • 22.
    Insulin therapy inspecific clinical situations • 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. RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 22
  • 23.
    Management of hyperglycaemiaduring 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. RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 23
  • 24.
    Glycaemic management duringcaesarean 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.
  • 25.
    Patients receiving enteralnutrition • 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 RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 25
  • 26.
    Sample insulin requirementcalculation 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.
  • 27.
    Patients receiving totalparenteral 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. RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. 27
  • 28.
    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
  • 29.
    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
  • 30.
    Components to beintegrated 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 RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. Bogun M. Clinical Therapeutics/Vol 35, Number 5, 2013. http://www.ncbi.nlm.nih.gov/pubmed/23688537 42
  • 31.
    Components to beintegrated 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. RSSDI Recommendations for “In Hospital Management of Hyperglycemia in Indian Patients”. 2016, under publication. Bogun M. Clinical Therapeutics/Vol 35, Number 5, 2013. http://www.ncbi.nlm.nih.gov/pubmed/23688537 43
  • 32.
    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.
  • 33.
    45 How will youmanage and outline broad management options
  • 34.
    46 Type 2 diabetes patient • Hospitalisedin non-critical care setting • With uncontrolled glycaemia prior to admission • On oral agents prior to admission • Able to accept orally
  • 35.
    • Guidelines formanagement 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
  • 36.
    • Targeting fastingBG 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
  • 37.
    Insulin The Most PowerfulAgent 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
  • 38.
    Polonsky, N EnglJ Med 1996; 334: 777-783 Normal Insulin Secretion
  • 39.
    Main Types ofInsulin 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
  • 40.
    Comparison of HumanInsulins/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
  • 41.
    Comparison of HumanInsulins/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
  • 42.
    4:00 16:00 20:0024:00 4:00 Breakfast Lunch Dinner 8:0012:008:00 Time Plasmainsulin Ideal Basal/Bolus Insulin Absorption Pattern
  • 43.
    Need for Rapid-actingInsulin Analogs • Mimic physiologic insulin profile (1st and 2nd Phase) • Administration at mealtime (no waiting) • Improved postprandial glycemic control • Lower risk of late hypoglycemia
  • 44.
    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
  • 45.
    4:00 16:00 20:0024:00 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
  • 46.
    Premix Analogs • Havebeen 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
  • 47.
    Insulin Analogs • Providemore 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
  • 48.
    Key Advantages ofBasal 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
  • 49.
    Summary: Benefits ofUsing 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
  • 50.