gestational diabetes mellitus - current concepts
DESCRIPTION
Dr.Vivek Sundaram.MD.DNB.MRCP(UK) Consultant – Internal Medicine,Diabetes & Critical Care Sundaram Hospital,Trichy. GESTATIONAL DIABETES MELLITUS - CURRENT CONCEPTS. Watching TV for 2 hours/day increases Risk of diabetes by 20%....JAMA,June 2011. ARETAEUS(200 A.D.) - PowerPoint PPT PresentationTRANSCRIPT
GESTATIONAL DIABETES MELLITUS -GESTATIONAL DIABETES MELLITUS - CURRENT CONCEPTS 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 108.7 ± 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?
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 IGT2%
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):587-90
1980s
7.6%Narendra J, Munichoodappa C, et al, Prevalence of glucose intolerance during pregnancy. Int J Diab Dev Countries 1991;11:2-4
8.2%Ramachandran A, Snehalatha c, Dharmaraj D, Viswanathan M. Prevalence of glucose intolerance in Asian Indians. Diabetes Care 1992; 15:1348-55
1990s
16.6%V Seshiah, V Balaji, Madhuri S Balaji, CB Sanjeevi, A. Green. Gestational Diabetes Mellitus in India. J Assoc Physicians India 2004;52:707
14.5%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;44:1094-1101.
2000s
GDM prevalence linked to background IGT rates
FREINKEL HYPOTHESIS
Uterine After Birth
Maternal
DM
placenta
A.AFatCHO
At Birth
Macrosomia
Hypoglycemia
Fetus
Amniotic Fluid Insulin
Obesity
Metabolic syndrome
CVD
IGT/DM
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
Risk Factors
Age 35 years
Obesity (BMI 30 kg/m2)
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
24-28 weeks [ Repeat - GTT]
32 -34 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 testDefinitive test: 75gm 2 hour OGTT ( ADA Criteria): 75gm 2 hour OGTT ( ADA Criteria)
If negative rescreen at 24 weeks /32 weeksIf negative rescreen at 24 weeks /32 weeks
If positive proceed to treatmentIf positive proceed to treatment
Gestational DM-Revised ADA criteria (2011)
75 g OGTT at 24-28 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 > 90th 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. 2006 Aug;73(2):223-4.
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 1998. B91-98.
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, 622-28
Balaji V, Balaji MS, Seshiah V, Mukundan S, Datta M.Diabetes Res Clin Pract. 2006 Aug;73(2):223-4.
Birth weight between 2.5 and 3.5 KgVinod 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 born2020
Fetal Morbidity
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)
2222
AimAim To maintain plasma glucose To maintain plasma glucose
values as to that of non values as to that of non diabetic pregnancydiabetic 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 BANTINGCHARLES BEST –FRED BANTING
Fonseca V. Curr Med Res Opin 2003;19:635–641.
Insulin secretion defect in diabetes
-30 0 30 60 90 120
Normal
2e fase
Time (min)
120
100
80
60
40
20
0
1ste fase(acute afgifte)
Plasma-immunoreactiveInsulin (µU/mL)
-30 0 30 60 90 120
Diabetes
120
100
80
60
40
20
0
Time (min)
Plasma-immunoreactiveInsulin (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 Meal 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 30-60 min 2-4 h 4-6 h
Lispro/aspart 5-15 min 1-2 h 3-4 h
Glulisine
Intermediate acting
NPH 1-4 h 4-8 h 10-20 h
Long acting
Glargine 1-2 h Flat ~24 h
Detemir 1-4 Flat 12-20
So, Why Modern Insulins ?
Dissociation of Insulins
Regular Human Insulin
10-3 M 10-3 M 10-5 M 10-8 M
Formulation
Capillary membraneAnalogs
10-3 M 10-3 M 10-3 M
FormulationTransient
Peak time1 hr
Peak time2-4 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 30-60 min prior to a meal
Prolonged duration of action (6-8 hrs after injection)
Inadequate insulin when in need
Insulin when not needed
Presentation titleSlide no
35Date
• Physiological insulin profile:basal componentmeal-related peaks
• Regular insulin fails to match normal insulin peak
Fails to match the physiology
Presentation titleSlide no
36Date
• 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-crystallisedinsulin
Soluble insulin analogue
Premixed is a suspension of:
30% Solublehuman insulin
NPH
INSULIN TACTICS
Twice-daily Split-mixed Regimens
RegularNPH
B SL HS
Insu
lin E
ffect
B
6-23
INSULIN TACTICS
Multiple Daily Injections (MDI):NPH + Mealtime Lispro
NPH at AM and HS + Lispro AC NPH at HS + Lispro AC
Insu
lin E
ffect
B SL HS B
Insu
lin E
ffect
B SL HS B
LisproNPH
LisproNPH
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. 1st 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
4040
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):2003-2015May 8, 2008
Monitoring HbA1c LevelsMonitoring 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
ILLNESSWELLNESS
THANK YOU