Insulin Case Studies AACE 5-20-05[2]

Insulin Therapy Case Studies : 

Insulin Therapy Case Studies Bruce W. Bode, MD, FACE Atlanta Diabetes AssociatesAtlanta, Georgia

Case Studies in Diabetes : 

Case Studies in Diabetes All of these cases are real patients Names have been deleted to protect patient identity In your answers, assume all are new patients to your practice

Case 1: Poorly Controlled Type 2 Diabetes on No Treatment : 

Case 1: Poorly Controlled Type 2 Diabetes on No Treatment 40-year-old African-American male diagnosed with diabetes 6 months ago on admit for MI Current treatment: None for diabetes Current exam: Wt 201 lbs, Ht 69”, BMI 29 A1C 13%, BG 497, Cr 1.3, ketones negative Current complications: Hyperlipidemia, CAD

Case 1: Poorly Controlled Type 2 Diabetes on No Treatment : 

Case 1: Poorly Controlled Type 2 Diabetes on No Treatment What is your goal for glucose? 90 to 130 mg/dL premeal,<180 mg/dL postmeal 80 to 110 mg/dL premeal,<140 mg/dL postmeal 70 to 100 mg/dL premeal,<120 mg/dL postmeal ARS QUESTION

Case 1: Poorly Controlled Type 2 Diabetes on No Treatment : 

Case 1: Poorly Controlled Type 2 Diabetes on No Treatment What is your treatment in addition to diet and exercise? One oral agent Two oral agents Basal insulin Premixed insulin Basal bolus therapy ARS QUESTION

Case 1: Poorly Controlled Type 2 Diabetes on No Treatment : 

Case 1: Poorly Controlled Type 2 Diabetes on No Treatment Patient refused insulin Placed on glimepiride and metformin A1C 6.8% in 3 months; patient quit sweet tea, colas, and orange juice Lesson learned: Do not underestimate the power of diet and exercise

Case 2: Poorly Controlled Type 2 Diabetes on OHA : 

Case 2: Poorly Controlled Type 2 Diabetes on OHA 46-year-old Indian man with diabetes since age 33, on max doses of rosiglitazone, glyburide and metformin; diet balanced; daily exercise Current exam: Wt 167 lbs, Ht 69.5”, BMI 24 A1C 8.0%, Cr 1.1, C-peptide 2.6 ng/mL Current complications: Vitrectomy OD, proteinuria, hyperlipidemia

Case 2: Poorly Controlled Type 2 Diabetes on OHA : 

Case 2: Poorly Controlled Type 2 Diabetes on OHA A1C 8.0%; SMBG 1/d; avg 110 mg/dL fasting; random BG 300 after breakfast What treatment do you recommend? Basal insulin morning (~10 U) Premixed insulin morning (~10 U) Premixed insulin morning and evening (~5 U BID) Bolus insulin with the largest meal (~5 U) Starch blocker or glinide (repaglinide or nateglinide) ARS QUESTION

Case 2: Poorly Controlled Type 2 Diabetes on OHA 4. Bolus insulin with the largest meal (~6 U) : 

Case 2: Poorly Controlled Type 2 Diabetes on OHA 4. Bolus insulin with the largest meal (~6 U)

Case 2: Poorly Controlled Type 2 Diabetes on OHA 4. Bolus insulin with the am and pm meals : 

Case 2: Poorly Controlled Type 2 Diabetes on OHA 4. Bolus insulin with the am and pm meals

Basal/Bolus Treatment Program withRapid-acting and Long-acting Analogs : 

4:00 16:00 20:00 24:00 4:00 Breakfast Lunch Dinner 8:00 12:00 8:00 Time Glargine or Detemir Plasma Insulin Basal/Bolus Treatment Program withRapid-acting and Long-acting Analogs Aspart, Lispro Or Glulisine Aspart, Lispro Or Glulisine Aspart, Lispro Or Glulisine Adapted from Bode B. Medical Management of Type 1 Diabetes. 4th ed. Alexandria, Va: American Diabetes Association; 2004.

Inhaled Insulin vs Rosiglitazone in DM–2 Patients on Diet Alone : 

Inhaled Insulin vs Rosiglitazone in DM–2 Patients on Diet Alone A1C, % N=69 1.8-kg Weight Gain 0.8-kg Weight Gain P<0.01 N=76 Defronzo R, et al. Accepted for publication. Diabetes Care. 2005.

Insulin Aspart Premeal with Metformin and Rosiglitazone vs Conventional Insulin : 

Insulin Aspart Premeal with Metformin and Rosiglitazone vs Conventional Insulin A1C, % N=16 0.42 U/kg 3-kg Weight Gain 0.67 U/kg 1-kg Weight Gain P=0.03 5 6 7 8 9 10 Insulin Aspart Premeal NPH or 70/30 BID Baseline 6 months Poulsen MK, et al. Diabetes Care. 2003;26:3273-3279.

Starting With Basal Insulin in DM 2 – Advantages : 

Starting With Basal Insulin in DM 2 – Advantages Use when fasting BG >140 mg/dL 1 injection with no mixing Insulin pens for increased acceptance Slow, safe, simple titration Low dosage Effective improvement in glycemic control Limited weight gain

Case 3: Poorly Controlled Type 2 Diabetes on OHA : 

Case 3: Poorly Controlled Type 2 Diabetes on OHA 80-year-old white man with diabetes since age 60, on repaglinide 4 mg TID; hx of CHF Supportive daughter and wife Current exam: Wt 175 lbs, ht 72”, BMI 23.5 A1C 9.2%, Cr 2.7, C-peptide 5.3 ng/mL Current SMBG 2.7 tests/d avg 246 mg/dL: 178 morning, 206 noon, 247 evening, 271 HS

Case 3: Poorly Controlled Type 2 Diabetes on OHA : 

Case 3: Poorly Controlled Type 2 Diabetes on OHA What is your recommendation? 1. Basal insulin 2. Bolus insulin 3. Premixed insulin 4. Basal bolus therapy ARS QUESTION

Case 3: Poorly Controlled Type 2 Diabetes on OHA : 

Case 3: Poorly Controlled Type 2 Diabetes on OHA I chose analog mix 70/30: Patient did well titrated to 24 units morning, 14 units evening with SMBG 4/d Saw RD, weight increased 5 pounds in 1 month with A1C 7.2% at 3 months

Case 3: Poorly Controlled Type 2 Diabetes on OHA 4. Analog Premixed Insulin : 

Case 3: Poorly Controlled Type 2 Diabetes on OHA 4. Analog Premixed Insulin

Insulin Glargine Plus OADs vs Twice-daily Premixed 70/30 Human Insulin : 

Target: FPG 100 mg/dL Subjects (n=364) were randomly assigned to: Insulin glargine once daily + continued OADs Premixed human insulin 70/30 BID Baseline End Point Time (wk) 0 24 Treatment Regimen *Sulfonylurea + metformin OAD=oral antidiabetic drug Janka HU, et al. Diabetes Care. 2005;28:254-259. Insulin Glargine Plus OADs vs Twice-daily Premixed 70/30 Human Insulin OADs*

Insulin Glargine Plus OADs vs Twice-daily Premixed Human Insulin : 

Change in A1C from Baseline to Study End Point* *Intent-to-treat analysis OAD=oral antidiabetic drug Janka HU, et al. Diabetes Care. 2005;28:254-259. P=0.0003 A1C Insulin Glargine Plus OADs vs Twice-daily Premixed Human Insulin Baseline 24 week

Less Hypoglycemia With Glargine Plus OADs vs Twice-daily Premixed 70/30 Human Insulin : 

Documented Hypoglycemic Episodes Per Patient-Year Less Hypoglycemia With Glargine Plus OADs vs Twice-daily Premixed 70/30 Human Insulin Average dose = 28.2 IU with G + OAD vs 64.5 IU with premixed insulin Weight Gain: 1.4 ± 3.4 kg with G + OAD vs 2.1 ± 4.2 kg with pre mixed insulin Janka HU, et al. Diabetes Care. 2005;28:254-259. 4.1 9.9 0 2 4 6 8 10 # of Episodes Per Patient-Year P<0.0001 Insulin Glargine + OAD Premixed

The INITIATE study: Analog Mix 70/30 (BID) vs glargine (QD) : 

The INITIATE study: Analog Mix 70/30 (BID) vs glargine (QD) n = 233 Type 2 DM BMI ≤ 40 kg/m2Body weight ≤125 kg HbA1C  8.0% on metformin +/- TZD Glargine OD (10 U, bedtime) + metformin +/- TZD NovoMix® 30, pre-breakfast (5 or 6U) and pre-dinner (5 or 6U) + metformin +/- TZD 4 wk run-in: Stop insulin secretagogues and -glucosidase inhibitors Optimize metformin to ≥1500 mg/day Switch rosiglitazone for 30 mg pioglitazone -4 0 28 (Weeks) Raskin P, et al. Diabetes Care. 2005;28:260-65 Titrate to 80 to 110 mg/dL

Glargine vs Twice-daily Analog mix 70/30 Insulin with Metformin ± Pioglitazone : 

Glargine vs Twice-daily Analog mix 70/30 Insulin with Metformin ± Pioglitazone Change in A1C From Baseline to Study End Point* P <0.01 A1C Baseline 28 week 9.8 9.7 7.4 6.9 5 6 7 8 9 Insulin Glargine + OAD Premixed + OAD 9.8 9.7 Raskin P, et al. Diabetes Care. 2005;28:260-265.

INITIATE8-Pt BG Profiles - Baseline and Wk 28 : 

INITIATE8-Pt BG Profiles - Baseline and Wk 28  BIAsp 70/30 lower BG vs glargine p<0.05+ Glargine lower BG vs BIAsp 70/30, p<0.05 Blood Glucose (mg/dl) Baseline Week 28 BIAsp 30 Glargine + * * * * 50 100 150 200 250 300 350 50 100 150 200 250 300 350 Raskin P, et al. Diabetes Care. 2005;28:260-265.

INITIATE – Rate of Overall Hypoglycemia (events per patient-year) : 

INITIATE – Rate of Overall Hypoglycemia (events per patient-year) Final insulin dose: 78.5 U (0.82 U/kg) for BIAsp 30 and 51.3 U (0.55 U/kg) for Glargine Weight Gain (kg): 5.4 ± 4.8 for BIAsp 30 and 3.5 ± 4.5 for Glargine Raskin P, et al. Diabetes Care. 2005;28:260-265.

Case 4: Poorly Controlled Type 2 Diabetes on Glargine Insulin at HS : 

Case 4: Poorly Controlled Type 2 Diabetes on Glargine Insulin at HS 49-year old-white woman with diabetes since age 37, on glargine insulin at HS for 3 years Current exam: Wt 223 lbs, Ht 65”, BMI 37 A1C 11.6%, Cr 1.2, C-peptide 2.9 ng/mL Current treatment: Repaglinide 4 mg AC, glargine 47 U HS Cannot tolerate metformin or TZD

Case 4: Poorly Controlled Type 2 Diabetes on Glargine Insulin at HS : 

Case 4: Poorly Controlled Type 2 Diabetes on Glargine Insulin at HS Diet history: Not great; a lot of high-fat, high-carb food with sweets Glucose logs: SMBG 1/d; avg >300 mg/dL Activity history: Minimal, married, husband a drug rep

Case 4: Poorly Controlled Type 2 Diabetes on Glargine Insulin at HS : 

Case 4: Poorly Controlled Type 2 Diabetes on Glargine Insulin at HS In addition to diabetes training and management by CDEs, what is the next treatment? Change to analog mix BID Add bolus insulin to largest meal Add bolus insulin to each meal Insulin pump therapy ARS QUESTION

Case 4: Poorly Controlled Type 2 Diabetes on Glargine Insulin at HS : 

Case 4: Poorly Controlled Type 2 Diabetes on Glargine Insulin at HS Sent for intensive management training in MDI and diet Results 3 months later: SMBG 6.5/d = 121 mg/dL A1C 6.5% On aspart AC: 10 U morning, 7 U noon, 7 U evening; glargine 40 U HS

Case 4: Poorly Controlled Type 2 on Lantus : 

Case 4: Poorly Controlled Type 2 on Lantus

Case 5: Poorly Controlled Type 2 Diabetes on MDI : 

Case 5: Poorly Controlled Type 2 Diabetes on MDI 55-year-old African-American woman with diabetes since age 19; on insulin for 15 years Current exam: Wt 202 lbs, ht 68”, BMI 30 A1C 15.9%, Cr 0.9, C-peptide 5.5 ng/mL Current treatment: Lispro AC: 25 U morning, 15 U noon, 15 U evening; glargine HS: 85 U Metformin 1000 mg BID

Case 5: Poorly Controlled Type 2 DM on MDI : 

Case 5: Poorly Controlled Type 2 DM on MDI

Case 5: Poorly Controlled Type 2 Diabetes on MDI : 

Case 5: Poorly Controlled Type 2 Diabetes on MDI Diet history: Not great; a lot of high-fat food; 3 colas per day since age 10 Glucose logs: SMBG 4/d; average >300 mg/dL Activity history: Sits for elderly disabled people; no formal exercise; supportive, caring son in health care

Case 5: Poorly Controlled Type 2 Diabetes on MDI : 

Case 5: Poorly Controlled Type 2 Diabetes on MDI What treatment now? Gastric bypass Atkins diet Find another doctor Trial with insulin pump therapy ARS QUESTION

Case 5: Poorly Controlled Type 2 Diabetes on MDI : 

Case 5: Poorly Controlled Type 2 Diabetes on MDI Elected for CSII Started at 75% TDD or 110 U/d Basal: 2.0 U/h Bolus: 25 U, 15 U, 15 U Correction bolus: BG –100/15

Case 5: Poorly Controlled Type 2 DM on MDI : 

Case 5: Poorly Controlled Type 2 DM on MDI

Case 5: Poorly Controlled Type 2 Diabetes on MDI : 

Case 5: Poorly Controlled Type 2 Diabetes on MDI Follow-up 3 months postpump start: A1C 9% SMBG 3.1/d

CSII vs MDI in DM 2 Patients : 

Change in scores (raw units) from baseline to endpoint -5 0 5 10 15 20 25 30 35 Convenience Less burden Less hassle Advocacy Preference General satisfaction Flexibility Less life interference Less pain Fewer social limitations MDI CSII CSII vs MDI in DM 2 Patients Testa et al. Diabetes. 2001;50(suppl 2):1781

Smart Pumps Bolus Calculator: Meter-entered : 

Smart Pumps Bolus Calculator: Meter-entered Monitor sends BG value to pump via radio waves – No transcribing error Enter carbohydrate intake into pump “Bolus Wizard” calculates suggested dose Paradigm Link™ Paradigm 715™ ) ) ) ) ) ) ) ) ) ) ) ) ) Paradigm Link® and Paradigm 715® are registered trademarks of Medtronic MiniMed.

Bolus Wizard Set-up Screen : 

Bolus Wizard Set-up Screen Wizard: OnCarb units: CarbCarb ratio: 1BG units: mg/dLSensitivity: 15BG target: 80–100Active insulin time: 5 h

Case 6: New-onset Diabetes : 

Case 6: New-onset Diabetes 45-year-old male lawyer presents with “polys” and weight loss Sees internist who recommends metformin (blood glucose 500, urine ketones small, BMI 26) Patient does some Internet reading and seeks a second opinion from diabetes specialist who was a high school classmate he has not seen for 27 years

Case 6: New-onset Diabetes : 

Case 6: New-onset Diabetes What type of diabetes does he have? Type 1 Type 1.5 LADA Type 2 1, 2, or 3 ARS QUESTION

Case 6: New-onset Diabetes : 

Case 6: New-onset Diabetes What other diagnostic tests do you need? Islet-cell antibody panel (ICA, anti-GAD) Serum C-peptide Insulin level HLA typing ARS QUESTION

LADA: Detection and Impact of GAD Antibodies : 

UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1997;350:1288-1293. Shimada A, et al. Ann N Y Acad Sci. 2003;1005:378-386. LADA: Detection and Impact of GAD Antibodies GAD: glutamic acid decarboxylase Other antibodies ICA, IA2, insulin autoantibodies 7% of patients screened in the Treat to Target Study had GAD antibodies 95% of patients in the UKPDS who were anti-GAD or anti-IC required insulin within 6 years

Progression of Type 1 Diabetes : 

Progression of Type 1 Diabetes Adapted from: Atkinson. Lancet. 2002;358:221-229. Age (y) Precipitating Event Beta-cell mass Normal insulin release Glucose normal Overt diabetes No C-peptide present Progressive loss of insulin release C-peptide present Antibody

Case 6: New-onset Diabetes : 

Case 6: New-onset Diabetes Sees me the following morning (BG 514, urine ketones small) I concur with him that he has type 1 diabetes and metformin is not the treatment, insulin is What is your initial treatment? IV insulin Premixed Basal/bolus therapy by MDI Insulin pump therapy ARS QUESTION

Options in Insulin Therapy for Type 1 Diabetes : 

Options in Insulin Therapy for Type 1 Diabetes Current Multiple injections Insulin pump (CSII)

DCCT Absolute Risk of Retinopathy:Conventional vs Intensive Insulin Therapy : 

DCCT Absolute Risk of Retinopathy:Conventional vs Intensive Insulin Therapy At the same A1C level, intensive insulin therapy provides a greater risk reduction of the development of retinopathy DCCT Research Group. Diabetes. 1995;44:968-983. Conventional Therapy Intensive Therapy 0 4 8 12 16 20 24 1 2 3 4 5 6 7 8 9 0 Mean A1C 10% 9% 8% 7% Rate Per 100 Patient-Years Time During Study (y) 0 4 8 12 16 20 24 1 2 3 4 5 6 7 8 9 0 Mean A1C 8% 7% 6% 11% 9% Development of Retinopathy

Does Intensive Insulin Therapy Preserves Beta Cell Function : 

Does Intensive Insulin Therapy Preserves Beta Cell Function Adapted from DCCT Study Group. Ann Intern Med. 1998;128:517-523. 0 1 2 3 4 5 6 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Years Postenrollment Number of evaluated patients in each treatment group Intensive Conventional 0 131 80 53 32 8 2 108 150 63 32 22 3 0 165 Conventional therapy Intensive therapy Patient Probability of Maintaining C-peptide >2.0

Case 6: New-onset Diabetes on CSII – A1C Results : 

Case 6: New-onset Diabetes on CSII – A1C Results A1C

Case 6: New-onset Diabetes on CSII : 

Case 6: New-onset Diabetes on CSII Patient extremely satisfied with his care C-peptide 0.9–0.8 at 1 year, 0.5–0.7 at 3 years Does not understand why everyone is not on CSII with optimal control

Current Pump Therapy Indications : 

Current Pump Therapy Indications Need to normalize blood glucose (BG) A1C >6.5% Glycemic excursions Hypoglycemia or hypoglycemia unawareness Need for a flexible insulin regimen

Summary : 

Summary Insulin remains the most powerful agent we have to control diabetes When used appropriately, near-normal glycemia can be achieved

Insulin Treatment in Type 2 Diabetes : 

Insulin Treatment in Type 2 Diabetes Basal treatment (NPH or glargine) Start 10 U and titrate; will need ~0.5 U/kg; will lower A1C 1.5–2 points Bolus treatment premeal Start at 4–5 U premeal and titrate; will lower A1C 2+ points Premixed therapy Start at 5–6 U BID and titrate; will need ~0.8 U/kg; will lower A1C 2+ points Basal bolus therapy Start at 0.4–0.5 U/kg, 40-50% basal, 20% bolus each meal with supplement = (BG-100) / CF where CF = 1700/TDD

Indications for Basal Bolus Therapy (MDI or Insulin Pump) : 

Indications for Basal Bolus Therapy (MDI or Insulin Pump) All Type 1 DM patients All Type 2 DM patients not at goal (<6.5%) All hospital patients not at goal (<140 mg/dL) All pregnancy patients not at goal (fasting <90 mg/dL; 1-hr PC <120 mg/dL)

Questions : 

Questions For a copy or viewing of these slides, go to: www.adaendo.com