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DiabetesandPregnancy 000

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Information about DiabetesandPregnancy 000
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Published on February 28, 2008

Author: Tirone

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Diabetes and Pregnancy:  Diabetes and Pregnancy Eric Lind Johnson, M.D. Assistant Medical Director Altru Diabetes Center Assistant Clinical Professor Department of Family and Community Medicine University of North Dakota School of Medicine and Health Sciences Overview of Diabetes in US:  Harris MI. In: Harris MI et al, eds. Diabetes in America. Bethesda, MD: USDHHS-NIH; 1995:DHHS Publication No. (NIH) 95-1468 Gregg EW, et al Diabetes Care 27:2806-2812, 2004 NHANES 2002 (w/2005 projections-NIH) Prevalence: 22 million Americans 1 in every 17 people (>90% type 2 diabetes) In patients with BMI >35, prevalence increased from 4.9% in 1960 to 15.1% in 2000 Incidence: >1 million new cases diagnosed yearly >2000 cases diagnosed each day  Type 2 diabetes in children and adolescents Related to our society’s  Obesity  Age  Growth of ethnic populations with high prevalence  Physical activity Overview of Diabetes in US Total Prevalence of Diabetes in the United States, All Ages, 2005 :  Total Prevalence of Diabetes in the United States, All Ages, 2005 22 million people—7 percent of the population (90%+ have Type 2) Undiagnosed: 6.5 million people 12.8 percent of Native Americans have Diabetes 8.7 percent of all non-Hispanic whites have Diabetes *Diabetes Listed as 6th leading cause of death-NIH Diabetes Mellitus:  Diabetes Mellitus Type 1 Usually younger (can be diagnosed at any age) FBG often >300 Usually ketones in urine and serum Glucosuria Metabolic acidosis on presentation Diagnosis usually preceded by weight loss,polyuria,polydipsia,fatigue Serum C-peptide markedly decreased Positive GAD and anti-islet cell antibodies Natural History of Type 1 Diabetes:  Natural History of Type 1 Diabetes ©2000 International Diabetes Center. All rights reserved Diabetes Mellitus:  Diabetes Mellitus Type 2 -Usually older, but 50% of children/adolescents with DM are Type 2 -Unusual to have markely elevated Fasting Glucose -Ketosis much less common, unless physical stress (surgery, illness) -Glucosuria -Usually obese -May be relatively asymptomatic (fatigue is often presenting complaint) -Often preceeded by a pre-diabetes syndrome (metabolic syndrome, history of gestational diabetes) -May have normal fasting glucose, but abnormal post-prandial glucose -Not antibody positive, often normal C-peptide levels Slide7:  Natural History of Type 2 Diabetes Glucose Relative to normal -10 -5 0 5 10 15 20 25 30 0 100 200 50 150 Post- prandial glucose Fasting glucose Insulin resistance Insulin level Years At risk for diabetes Beta-cell dysfunction 250 R. Bergenstal and D. Kendall, International Diabetes Center mg/dL (%) Diabetes Mellitus:  Diabetes Mellitus Type “1.5” -Mixed features -Usually present like Type 2, but progress to insulin defeciency more rapidly, and may develop Type 1 symptoms months after diagnosis -May be antibody positive, variable C-peptide - ~ 10% of all Type 2 (?) Diagnosis Guidelines:  Category FPG (mg/dL) Normal <100 Impaired Fasting Glucose* (IFG) 100 – 125 Diabetes >126** Not to be confused with impaired glucose tolerance (IGT): 2 h OGTT 75 g at 140–200 mg/dL ** On 2 separate occasions (Diabetes Care 29:Supplement 1, 2006) Diagnosis Guidelines Targets for Glycemic Control Adults :  Targets for Glycemic Control Adults American Diabetes Association. Diabetes Care.2006; 29(supp 1) HbA1c < 7%* Fasting/preprandial glucose 80-120 mg/dL Postprandial glucose 100-180 mg/dL Bedtime glucose 100-140 mg/dL *6% for certain individuals Gestational Diabetes:  Gestational Diabetes Occurs in 2-9% of pregnancies Management can include insulin (usually preferred, better efficacy) or sulfonylureas (in very select cases) Diagnosis made on OGTT at 24-28 weeks Dietary management a very important component Only have 8-16 weeks to manage, must be aggressive to avoid complications (i.e. macrosomia) Should be rechecked 6-12 weeks following delivery, and annually thereafter to be screened for Type 2 Diabetes-high risk of developing Type 2 Diabetes Oral Glucose Tolerance Test:  Oral Glucose Tolerance Test Diagnosis of GDM with a 100-g or 75-g glucose load Two or more of the venous plasma concentrations must be met or exceeded for a positive diagnosis. The test should be done in the morning after an overnight fast of between 8 and 14 h and after at least 3 days of unrestricted diet ( 150 g carbohydrate per day) and unlimited physical activity. The subject should remain seated and should not smoke throughout the test. Gestational Diabetes:  Gestational Diabetes Potential complications: Neonatal hypoglycemia (can be severe) Macrosomia Fractures Shoulder dystocia, Nerve palsies (Erb’s C5-6) Pregnancy outcomes can be very poor with HTN/nephropathy Slide14:  Table 32-9   -- COMPARATIVE RATES OF MAJOR MALFORMATIONS IN OFFSPRING OF DIABETIC WOMEN RECEIVING PRECONCEPTIONAL COUNSELING Congenital Malformations Gabbe, Obstetrics: Normal and Problem Pregnancies 2002 Pre-existing Diabetes and Pregnancy:  Pre-existing Diabetes and Pregnancy Slide16:  Perinatal Mortality-Type 1 and Pregnancy Gabbe, Obstetrics: Normal and Problem Pregnancies 2002 Diabetes and Congenital Malformations:  Diabetes and Congenital Malformations Cardiac VSD, transposition of great vessels Anencephaly, Spina Bifida Sacral agenesis or caudal dysplasia Complications associated with polyhydramnios, oligohydramnios (i.e. growth retardation) Other Diabetes and Pregnancy Complications:  Other Diabetes and Pregnancy Complications Fetal demise-once as high as 10-30%, considerably declined in recent years Ohio State University: Diabetes in Pregnancy Program-Congenital anomalies in 10% (1987-93) Diabetes in Early Pregnancy Study 2.1% control vs. 9% in Diabetes Mills, etal NEJM 1988 318 A1C in normal range, 3.4% malformation rate vs. 22% with elevated A1C Miller, et al NEJM 1981 304 Infant Calcium disturbance, hyperbilirubinemia, hypoglycemia, polycythemia Pre-Existing Type 2 Diabetes and Pregnancy:  Pre-Existing Type 2 Diabetes and Pregnancy Pre-conception counseling an important part of routine care for women with pre-existing diabetes (including Diabetes Educator and Dietician (routine for all Diabetes patients) Recommended pre-conception A1C 6.5 or less Insulin dosage may increase dramatically, particularly in 3rd trimester More and more Type 2 patients in child bearing years (diagnosed at younger age) Pre-Existing Type 2 Diabetes and Pregnancy:  Pre-Existing Type 2 Diabetes and Pregnancy Metformin can be used in Type 2 in pregnancy-many of these women have PCOS; Metformin can enhance fertility Metformin usually stopped at 14 weeks; many of these women will be on insulin-often a basal insulin (usually NPH) started first Ongoing research with TZD’s in PCOS and Type 2 DM pregancy (Rezulin had early good results in PCOS before going off the market) Pre-Existing Type 1 Diabetes and Pregnancy:  Pre-Existing Type 1 Diabetes and Pregnancy If doing well on multiple daily injection (i.e. glargine or detemir plus rapid acting aspart or lispro), probably would continue No official indication of any insulin in pregnancy-most experience with NPH and Regular Continuous subcutaneous Insulin Infusion (Pump) very effective choice in pregnancy Slide22:  *May consider continuing Metformin Until week 14 Slide23:  Novolog now category B (Jan 2007) May consider continuing Metformin to week 14 Slide24:  Glyburide may be considered if Failing MNT, but only in select patients HYPERTENSION AND LIPID MANAGEMENT :  HYPERTENSION AND LIPID MANAGEMENT Medications for Cholesterol discontinued BP: Usually changed to methyldopa Dietician consult (already in place, but to account for dyslipidemia if pre-existing or newly diagnosed) Co-existing conditions/screening:  Co-existing conditions/screening Type 1: Screen for thyroid disease (TSH), celiac disease (10% incidence) Type 2: Screen for thyroid disease (TSH), consider celiac screening (particularly if DM control issues) Treating Gestational Diabetes:  Treating Gestational Diabetes Australian Study: 1000 subjects 10 year study Randomized to ‘routine care’ or ‘intervention’ (dietary advice, blood glucose monitoring, insulin therapy) Intervention group 1% complications Routine group 4 % complications Crowther, et al, NEJM 2005 Vol 352:2477-2486 Diabetes Medications and Pregnancy:  Diabetes Medications and Pregnancy Diabetes Medications Insulins:  Diabetes Medications Insulins Aspart (novolog) B Breatfeed OK(all insulin OK) Aspart protamine (“NPH” of novolog 70/30) C Detemir (levemir) C Glargine (Lantus) C Glulisine (Apidra) C Lispro (Humalog) B Lispro protamine (“:NPH” of humalog) B Inhaled insulin (Exubra) C NPH B Regular B Diabetes Medications- Others:  Diabetes Medications- Others Medication Pregnancy Category Metformin B usually stopped at end of 1st trimester-maintain preg, not for optimal diabetes management. Avandia (rosiglitzaone) C may have future role in PCOS/pregnancy Actos (pioglitazone) C may may have future role in PCOS/pregnancy Byetta (exenatide) C no known role in pregnancy yet Januvia (sitagliptin) C no role in pregnancy yet Glucose-lowering Potential of Diabetes Therapies*:  Glucose-lowering Potential of Diabetes Therapies* Treatment FPG ¯ HbA1c ¯ Sulfonylureas 50-60 mg/dl 1-2% Metformin 50-60 mg/dl 1-2% Metformin/Sulfonylurea 100-120 mg/dl 3-4% a-Glucosidase Inhibitors(Precose) 15-30 mg/dl 0.5-1% Repaglinade(Prandin) 60mg/dl 1.7% Thiazolidinediones 40-60 mg/dl 1-2% Exenatide (Byetta) targets ppd 1-2% Pramlintide (Symlin) targets ppd 1-2% Insulin Unlimited Unlimited *based on package insert data Sulfonylureas:  Sulfonylureas Older Agents- many. Glipizide, Glyburide Newer agents: glipizide GITS (Glucotrol XL) glimeperide (Amaryl) Increase insulin secretion Lower FBS 50-60 mg/dl and HbA1c 1 - 2 % Sulfonylureas:  Sulfonylureas Advantages: well tolerated (skin, GI side effects) once-a-day dosing enhances compliance inexpensive Sulfonylureas:  Sulfonylureas Disadvantages weight gain(less with glimepiride?) Hypoglycemia (particularly in elderly) premature B-cell exhaustion? Caution in liver disease, renal disease Insulin Sensitizers:  Thiazolidinediones pioglitazone (Actos) rosiglitazone (Avandia)  insulin resistance at muscle and other tissues Slow onset of action-4 to 6 weeks- not a great first choice monotherapy in very symptomatic patient Insulin Sensitizers Metformin and TZD’s:  Metformin and TZD’s Similarly efficacious ( HbA1c 1-2%) Non-glycemic benefits improved dyslipidemia lower BP improved blood’thinning’? improved endothelial dysfunction metformin only agent to  cardiac and all cause mortality in UKPDS TZD’s  carotid IMT and coronary stent stenosis Metformin and TZD’s:  Differences between metformin and TZD’s effect on weight cost onset of action side effects ß -cell preservation? Effect on microalbuminuria Metformin and TZD’s Insulin Time Action Curves:  Insulin Time Action Curves 0 20 40 60 80 100 120 140 0 2 4 6 8 10 12 14 16 Insulin Effect Hours 18 20 adapted from R. Bergenstal, IDC Twice-Daily Split-Mixed Regimens:  Twice-Daily Split-Mixed Regimens Regular NPH B D L HS B Endogenous insulin Dawn phenomenon Hyperglycemia Adapted with permission from Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy. New York, NY: Marcel Dekker Inc.; 2002:87 Basal-Bolus Insulin Therapy: Detemir or Glargine at HS and Mealtime Aspart, Lispro, or Glulisine:  Insulin aspart , lispro, glulisine detemir or glargine Basal-Bolus Insulin Therapy: Detemir or Glargine at HS and Mealtime Aspart, Lispro, or Glulisine B D L HS Insulin Effect Adapted with permission from Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy. New York, NY: Marcel Dekker Inc.; 2002:87 Insulin analogues:  Insulin analogues Rapid acting analogues insulin aspart (Novolog) (First rapid acting insulin indicated for CSII-pumps) Lispro (Humalog) glulisine (Apidra) Rapid dissociation facilitates absorption Onset 15 min, peaks 1 hr, duration 3-4 hrs Less variability in time-to-peak, and duration with dose changes Improves postprandial hyperglycemia Insulin analogues:  Reduces postprandial blood glucose Reduced hypoglycemia for most patients More convenient for patients Clinical Pearls may substitute for Reg in any regimen use smaller dose, at least initially snacks are usually not needed test 2 hrs after injection to adjust dose Insulin analogues Insulin analogues:  Long acting analogues insulin detemir (Levemir) insulin glargine (Lantus) Neutral isoelectric point slows dissociation(Glargine) “Peakless” insulins lasting 18- 24 hours or more Replaces NPH and Ultralente as basal insulin Can’t be mixed in same syringe as other insulins Insulin analogues Slide45:  Novo Flexpen-Novolog, Novolog 70/30, Levemir Slide46:  Opticlick Pen Lantus, Apidra Humalog, Humalog 75/25, Humalog 50/50:  Humalog, Humalog 75/25, Humalog 50/50 Paradigm® 522 Pump*:  Paradigm® 522 Pump* Easy to use, Customizable • Safety at its core Clear Purple Smoke Blue *722-300Units Using the Bolus Wizard™ Calculator with the Paradigm Link™ Monitor:  Using the Bolus Wizard™ Calculator with the Paradigm Link™ Monitor Monitor sends BG value to pump via radio waves You enter in your carbohydrate intake “Bolus Wizard” feature calculates a suggested insulin dose based upon your personal settings, including correction factor Paradigm Link™ Paradigm 522™ ) ) ) ) ) ) ) ) ) ) ) ) ) New and Future Technology:  New and Future Technology Guardian RT Sensor-Available in Select markets Sensor Augmented Pump Slide51:  522 system Case #1:  Case #1 30 y/o white female Known Type 2 DM on no anti-diabetic agents or insulin Previous successful pregnancy 2 years ago on insulin, male infant 7lbs 11 oz. (3.5 kg) No known infertility history Now at 11 weeks, referred by primary provider A1C 3 weeks prior to consult 5.8, but some AM glucose elevations prior into 130’s Now what???? Remember this is Type 2, not gestational Case #1:  Case #1 In general, glucose guidelines are that for GDM, but difficult to do over 9 months as opposed to 8 or 9 weeks Fasting 60-90, post-prandial <120, A1C would likely be <6 No assisted hypoglycemia (more difficult with NPH) Now what??? Case #1:  Case #1 Patient had already been started on NPH 10 units at HS, and was told to titrate upwards 2-3 units every 3 or 4 nights until fastings <90 with no significant hypoglycemia Patient required BID NPH by 16 weeks, then R was started in evening with largest meal (along with NPH), eventually on BID NPH/R, although evening NPH moved to HS at approx week 25 to improve fasting glucose A1C not over 6.2 during pregancy Case #2:  Case #2 30 y/o white female with Type 1 of 20 years duration On insulin pump with Novolog Complicated early by morning sickness (pump very helpful with temporary basals, other advanced features) A1C 5.8 Blood glucose log downloaded from pump showed values 49-273, lows usually overnight or early AM Case #2:  Case #2 Type 1 goals ideally that of GDM, but much more difficult to achieve Lack of insulin resistance, coupled with glucagon dysfunction, as well as amylin dysfunction, contributes to variability Pumps are ideal in pregnancy, underutilized Case #2:  Case #2 Glucose log: 8am noon 6pm 10pm 65 99 121 104 83 154 91 180 100 132 161 108 Case #2:  Case #2 Glucose log (expanded): 8am 10am noon 3pm 6pm 9pm 10pm 65 212 99 132 121 246 104 83 280 154 196 91 172 180 100 183 132 152 161 309 108 Out of control? Case #2:  Case #2 Basal insulin rates steadily increased over time with advancing pregnancy and insulin resistance Bolus insulin more aggressive immediately: was 2units/15 gm CHO, increased to 3 units/15gm CHO (eventually was on 4.5 units/15 gm CHO Total insulin by end of pregnancy was >120 units C-section week 35 (LGA). Healthy male infant, 8lbs, 1 oz. Max A1C in pregnancy was 6.5 Case #3:  Case #3 32 y/o white female Type 2 of 3 years duration On Metformin 500 mg BID and Detemir insulin (Levemir) 22 units BID Blood glucose 1-2x day, 80’s-210’s Did not come in for pre-conception couseling, but had been seen 4 months prior A1C at time of pregnancy diagnosis 5.5 Now what?? Case #3:  Case #3 Kept on Metformin until week 14, then Metformin stopped No previous pregnancy or infertility Levemir continued and titrated as patient doing well. Novolog added at meals 2 units 15gm/CHO Now what??? Case #3:  Case #3 Patient progressed well until 30 weeks Titrating Levemir became problematic (any change takes 3 days to realize-long halflife) Continued Novolog with meals Changed to NPH BID, quicker titration (can do daily if desired) Closer monitoring for overnight hypoglycemia-1 or 2 3am blood glucose/week Inpatient Diabetes Management:  Inpatient Diabetes Management Diabetes Educator and Dietician consult-Diabetes needs/program changes within hours of delivery of infant. Need to account for breast feeding (giving away calories) Continued pump or insulin drip most appropriate for patients on insulin, particularly more than one injection daily. Supplemental subcutaneous may be appropriate for well controlled GDM for a short period of time (24 hours or less) Often return to previous pre-pregnancy program within hours or days of delivery Summary:  Summary Generally, all pregnant patients with any form of Diabetes will do well on insulin when indicated Many new pen and pump devices make this much easier than syringe/vial Treating Diabetes effectively in pregnancy can improve outcomes Generally, oral agents are limited to Metformin in the first trimester in pre-existing Type 2, and glyburide in select gestational patients Suggested Readings/Resources:  Suggested Readings/Resources WWW. Diabetes.org American Diabetes Association website. Includes annually updated clinical practice guidelines and official ADA journals Obstetrics: Normal and Problem Pregnancies. Gabbe, 4th ed., 2002 Jovanovic-Peterson L. (Ed.): Medical Management of Pregnancy Complicated by Diabetes. 3rd ed. Alexandria, VA, American Diabetes Association, 2000 Diabetes Care 27:S88-S90, 2004 Position Statement. GDM Acknowledgements:  Acknowledgements Dr. Bob Beattie, Chair, Department of Family and Community Medicine Melissa Gardner, Department of Family and Community Medicine Dr. James D. Brosseau, Medical Director, Altru Diabetes Center

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