Presentation on theme: "GESTATIONAL DIABETES MELLITUS - CURRENT CONCEPTS Dr.Vivek Sundaram.MD.DNB.MRCP(UK) Consultant – Internal Medicine,Diabetes & Critical Care Sundaram Hospital,Trichy."— Presentation transcript:
GESTATIONAL DIABETES MELLITUS - CURRENT CONCEPTS Dr.Vivek Sundaram.MD.DNB.MRCP(UK) Consultant – Internal Medicine,Diabetes & Critical Care Sundaram Hospital,Trichy.
Watching TV for 2 hours/day increases Risk of diabetes by 20%....JAMA,June 2011
ARETAEUS(200 A.D.) ….wonderful affliction with melting down of flesh and limbs into urine…..patient never stops making water..……illness is chronic but the patient shortlived
Definition Gestational Diabetes Mellitus (GDM) is defined as - carbohydrate intolerance with recognition or onset during pregnancy, irrespective of the treatment with diet or insulin. The importance of GDM is that two generations are at risk of developing diabetes in the future.
The maternal metabolic adaptation is to maintain the mean FBG of 74.5 ± 11 mg/dl and the PPG peak of ± 16.9mg/dl.1 Compensatory hyperinsulinaemia due to insulin resistance. Failure of beta cells secretion to overcome the insulin resistance leads to GDM.
Diabetes and Pregnancy – Why it is relevant? Hyperglycaemia during pregnancy is associated with high risk of maternal and perinatal morbidity and mortality Diagnosis of GDM identifies women at high risk of future diabetes, offers opportunity of primary prevention Maternal hyperglycaemia is associated with development of type 2 diabetes in the offspring
Pregnancy – diabetogenic condition (metabolic stress test) Unmasks a compensated metabolic abnormality A direct consequence of the altered maternal metabolism stemming from the changing hormonal milieu. GDM………
GDM IGT 2% Agarwal S, Gupta AN. Gestational Diabetes. J Assoc Physicians India 1982;30:203 2% Ramachandran A, et.al., High prevalence of diabetes in an urban population in south India. BMJ 1988;3; 297(6648): s 7.6% Narendra J, Munichoodappa C, et al, Prevalence of glucose intolerance during pregnancy. Int J Diab Dev Countries 1991;11: % Ramachandran A, Snehalatha c, Dharmaraj D, Viswanathan M. Prevalence of glucose intolerance in Asian Indians. Diabetes Care 1992; 15: s 16.6% V Seshiah, V Balaji, Madhuri S Balaji, CB Sanjeevi, A. Green. Gestational Diabetes Mellitus in India. J Assoc Physicians India 2004;52: % Ramachandran A, Snehalatha C, Kapur A, Vijay V, Mohan V,Das AK, Rao PV, Yajnik CS, Prasanna Kumar KM, Nair JD.For the Diabetes Epidemiology Study Group in India (DESI).Diabetologia 2001;44: s GDM prevalence linked to background IGT rates
Pathophysiology Human Placental Lactogen (HPL) – Produced by syncytiotrophoblasts of placenta. – Acts to promote lipolysis increased Free fatty acids contributing to tissue insulin resistance. Estrogen and Progesterone – Interfere with insulin-glucose relationship. Insulinase – Placental product that may play a minor role.
Pathophysiology Normal pregnancy : - - Mild fasting hypoglycemia – increased lipolysis and FFAs become the main fuel substrate for the mother ( Mediated by human placental growth harmone)-accelerated starvation - Postprandial hyperglycemia – insulin resistance aids glucose transfer to the fetus –facilitated anabolism
GDM –POSTPRANDIAL HYPERGLYCEMIA IS MORE RELEVANT Fetal renal thershold for glucose < 110 mg/dl Maternal hyperglycemia (>110 mg/dl) – increased iv glucose load to the fetus producing fetal glycosuria Fetal polyuria - polyhyramnios 20 wks GA – fetus ingests glucose rich amniotic fluid Gut stimulus to insulin secretion is more potent than transient iv hyperglycemia IV + Oral route (glucose) – overfed,fat fetus
Risk Factors Age 35 years Obesity (BMI 30 kg/m 2 ) Family history Previous delivery of a macrosomic infant Member of a high-risk population Polycystic ovarian syndrome Previous abnormal glucose tolerance INDIAN - ETHNICITY
GDM dilemmas Early or late sreening? WHO or ADA criteria One step or twostep? 75 or 100 gm? 1 hour or 2 hour? To treat or not ? Insulin or pills? Early or late delivery? C section or normal? Breast feed or not?
Who & When to screen? First booking – Differentiates pre GDM from GDM weeks [ Repeat - GTT] weeks [ Repeat -GTT] UNIVERSAL
How to screen? One Step Approach – Validated in the indian population 2 hrs value >140 mg/dl with 75g oral glucose -GDM ( irrespective of the time last meal was consumed) Definitive test: 75gm 2 hour OGTT ( ADA Criteria) Definitive test: 75gm 2 hour OGTT ( ADA Criteria) If negative rescreen at 24 weeks /32 weeks If negative rescreen at 24 weeks /32 weeks If positive proceed to treatment If positive proceed to treatment
Gestational DM-Revised ADA criteria (2011) 75 g OGTT at wks of gestation Fasting > 92 mg/dl 1 hr >180 mg/dl 2 hr > 153 mg/dl _ _ ANY 1 ABNORMAL VALUE - GDM 100 g OGTT – O,I,2,3 hr values …. 95,180,155,140 …2 abnormal values _
18 Abnormal Plasma Glucose during Pregnancy Occurrence of birth weight of new born > 90 th percentile was continuum as FPG increased from 80 mg/dl and was significant above 90 mg/dl (adjusted odds ratio 2.08 [ 95% CI 1.24 – 3.48], P = 0.005]) V Seshiah, V Balaji, Madhuri S Balaji, A Paneerselvam. Abnormal Fasting Plasma Glucose during Pregnancy. Diabetes Care vol 31 (12): e92, December 2008 The occurrence of macrosomia was continuum as the 2 hr plasma glucose increased from 120 mg/dl ( adjusted odds ratio 3.02 [ 95% CI 1.30 – 7.00], P < 0.05]) Balaji V, Balaji MS, Seshiah V, Mukundan S, Datta M.Diabetes Res Clin Pract Aug;73(2): Abnormal : FPG > 90 & PPG > 120 mg/dl
19 TARGET BLOOD GLUCOSE LEVELS Oded Langer. Maternal glycemic criteria for insulin therapy in GDM. Diabetes care, vol 21 (2), August B Fasting PG 80 mg % 90 mg % PPG 110 mg % 120 mg % Mean PG level 95 mg % 105 mg % V. Seshiah, AK Das, Balaji V, Shashank Joshi, MN Parikh, Sunil Gupta for DIPSI. GDM- Guidelines. JAPI vol 54, 2006, Balaji V, Balaji MS, Seshiah V, Mukundan S, Datta M.Diabetes Res Clin Pract Aug;73(2): Birth weight between 2.5 and 3.5 Kg Vinod K Paul, Ashok K Deorari, Meharban Singh. Management of Low Birth Weight Babies. In: IAP Textbook of Pediatrics. 2nd ed. A. Parthasarathy, editor. Jaypee publications, 2002, p60.
GDM – Fetal Morbidity Macrosomia of the baby CPD – Shoulder Dystocia Intrapartum Trauma – Feto-maternal Neonatal Hypoglycemia Neonatal Hypocalcemia Neonatal Hyperbilirubinemia Respiratory Distress Syndrome (RDS) Polycythemia (secondary) in the new born 20
Maternal Morbidity Hypertension/Preeclampsia and Eclampsia Cesarean delivery; Pre term labour Polyhydramnios – fluid > 2000 ml Post-partum uterine atony Abruptio placenta 40-60% risk of DM (screen 6 wk/6 mths after delivery) 22
Aim To maintain plasma glucose values as to that of non diabetic pregnancy MANAGEMENT
How to treat? Medical nutrition therapy (MNT) Exercise Insulin
MNT 2 wk trial – if uncontrolled switch over to insulin 30 kcal/kg/day for 60 kg BMI>30- 25kcal/kg/day 300 extra calories for 2 & 3 trimester 3 meals & 3 snacks - avoid hypoglycemia 40 – 50% of calories as CHO,25% each as fat and protein
Exercise Women with GDM often need regular, moderate physical activity to help control their blood sugar levels by allowing insulin to work better. Examples include: – Walking – Prenatal aerobics classes – Swimming Keep in mind that it may take 2 to 4 weeks before physical activity has an effect on blood sugar levels.
Insulin therapy Safe,Effective, time tested Human Insulin preferred Short acting analogues – good option May need short term hospitalization Monitoring fasting, premeals & post meal
CHARLES BEST –FRED BANTING
Fonseca V. Curr Med Res Opin 2003;19:635–641. Insulin secretion defect in diabetes Normal 2 e fase Time (min) ste fase (acute afgifte) Plasma-immunoreactive Insulin (µU/mL) Diabetes Time (min) Plasma-immunoreactive Insulin (µU/mL)
30 Normal insulin physiology is matched by multiple insulin injections Insulin therapy should closely mimic normal insulin physiology Basal needs: Intermediate-/long-acting insulins (NPH, ILPS, detemir, glargine) Bolus needs: Rapid-/short-acting insulins given with meals (lispro, aspart, glulisine, human regular insulin) Meal Expected insulin changes during the day for individuals without diabetes Insulin effect images are theoretical representations and are not derived from clinical trial data.
Insulin Onset Peak Duration Short acting Regular min 2-4 h4-6 h Lispro/aspart 5-15 min 1-2 h 3-4 h Glulisine Intermediate acting NPH1-4 h 4-8 h h Long acting Glargine1-2 h Flat~24 h Detemir 1-4 Flat 12-20
So, Why Modern Insulins ?
Dissociation of Insulins Regular Human Insulin M M10 -8 M Formulation Capillary membrane Analogs M FormulationTransient Peak time 1 hr Peak time 2-4 hr
Presentation titleSlide no 34 Inability of s.c. injected soluble insulin to mimic the physiological pattern Delayed onset of action (30-60 min after injection) i.e. should be injected min prior to a meal Prolonged duration of action (6-8 hrs after injection) Inadequate insulin when in need Insulin when not needed
Presentation title Slide no 35 Date Physiological insulin profile: basal component meal-related peaks Regular insulin fails to match normal insulin peak Fails to match the physiology
Presentation title Slide no 36 Date Physiological insulin profile: basal component meal-related peaks Mixtard fails to re-create the physiological insulin profile Period of unwanted hyperglycemia Period of unwanted hypoglycemia
Presentation titleSlide no 37 Date 30% Protamine-crystallised insulin Soluble insulin analogue Premixed is a suspension of: 30% Soluble human insulin NPH
INSULIN TACTICS Multiple Daily Injections (MDI):NPH + Mealtime Lispro NPH at AM and HS + Lispro ACNPH at HS + Lispro AC Insulin Effect BSLHS B Insulin Effect BSLHS B Lispro NPH Lispro NPH 6- 29
Insulin Regimen If MNT fails after 2 wks of trial initiate Insulin Dose: 0.7, 0.8 and 0.9 u/kg – 1, 2 & 3 trim. Eg. 1 st trim – 64 kg = 0.7 x 64 = 45 units Give 2/3 before BF = 30 units of 30:70 mix Give 1/3 before supper = 15 u of 30:70 mix Increase total dose by 2-4 units based on BG 40
Oral agents -GDM Glibenclamide ( Currently not recommended) Metformin – Select group ( pre GDM/PCOS) ADVANTAGES Easy to take Need far less education Affordable No social stigma Not endorsed by any formal recommendations apart from NICE Guidelines
Original Article Metformin versus Insulin for the Treatment of Gestational Diabetes Janet A. Rowan, M.B., Ch.B., William M. Hague, M.D., Wanzhen Gao, Ph.D., Malcolm R. Battin, M.B., Ch.B., M. Peter Moore, M.B., Ch.B., for the MiG Trial Investigators N E J M.358(19): May 8, 2008
Monitoring HbA1c Levels HbA1c in early pregnancy - differentiates between a pre gestational diabetic and GDM. If the HbA1c level is more than 6%, she is likely to be a pre GDM. HbA1c is useful in monitoring the glucose control during pregnancy, but not for the day to day management. Estimation of fructosamine during pregnancy is less frequently used.
Conclusions Universal screening ideal for our women 2 hour 75 gm screening is cost effective 2 hour 75 gm – GTT ( Definitive test) Diet and exercise provides good control in many Insulin analogues are safe and very effective Oral agents are an alternative – in select situations Postpartum follow-up is an integral part of GDM management
RICHARD S. HOLLIS PRESIDENT ACOG Remember how fortunate we are to be included in the lives of our patients at the most precious times of their lives