Dr Sujata Misra MD FICOG
Pregnancy induces progressive changes in maternal carbohydrate metabolism. As pregnancy advances insulin resistance and diabetogenic stress due to placental hormones necessitate compensatory increase in insulin secretion. When this compensation is inadequate gestational diabetes develops. ‘Gestational Diabetes Mellitus’ [GDM] is defined as carbohydrate intolerance with onset or recognition during pregnancy. Women diagnosed to have GDM are at increased risk of future diabetes predominantly type 2 DM as are their children . Thus GDM offers an important opportunity for the development, testing and implementation of clinical strategies for diabetes prevention [ . Timely action taken now in screening all pregnant women for glucose intolerance, achieving euglycemia in them and ensuring adequate nutrition may prevent in all probability, the vicious cycle of transmitting glucose intolerance from one generation to another.
Screening & Diagnosis
A number of screening procedures and diagnostic criteria (ADA, WHO, CDA, NDDG and Australasian criteria) are being followed in the same as well as in different countries. American Diabetes Association (ADA) recommends screening for selective (high risk) population. But compared to selective screening, universal screening for GDM detects more cases and improves maternal and neonatal prognosis [4,5]. Hence universal screening for GDM is essential, as it is generally accepted that women of Asian origin and especially ethnic Indians, are at a higher risk of developing GDM and subsequent type 2 diabetes.
ADA procedure
ADA recommends two step procedures. Step 1: A 50 g glucose challenge test (GCT) is used for screening without regard to the time of last meal or time of the day. Step 2: If 1 hour GCT value is more than 140 mg/dl, 100g Oral Glucose Tolerance Test (OGTT) is recommended and plasma glucose is estimated at 0, 1, 2 and 3 hours. Gestational Diabetes Mellitus is diagnosed (Carpenter and Coustan criteria) if any 2 values meet or exceed FPG > 95 mg/dl, 1 hr PG > 180 mg/dl, 2 hr PG > 155 mg/dl and 3 hr PG > 140 mg/dl. The drawback of this criteria is that, the glycemic cut off was originally validated against the future risk of these women developing diabetes and not on the fetal outcome . Further, in the community health centers, pregnant women are reluctant to undergo ADA procedures for two reasons
- The number of blood samples drawn are many (a) for screening and (b) for subsequent 3- hour OGTT to confirm the diagnosis (4 blood samples).
- They have to visit the ante-natal clinic on two occasions – (a) for screening and (b) again for diagnostic procedure.
WHO Procedure
When a glucose tolerance test is administered to a non-pregnant individual, it is standard to use the 75-g, 2-hour OGTT. Using a different glucose challenge in pregnant versus non-pregnant persons leads to confusion in the laboratory and may result in errors in applying the proper diagnostic criteria . To standardize the diagnosis of GDM, the World Health Organization (WHO) recommends using a 2 hour 75 gm OGTT with a threshold plasma glucose concentration of greater than 140 mg/dl at 2 hours, similar to that of IGT ( > 140 & < 199 mg/dl), outside pregnancy . WHO procedure also has a shortcoming in that, the criteria suggested for diagnosis of GDM was also not based on the maternal and fetal outcome but probably the criteria was recommended for its easy adaptability in clinical practice.
Reconciliation factors between ADA and WHO
GDM based on two hour 75gm OGTT defined by either WHO or ADA Criteria predicts adverse pregnancy outcome . There was no significant difference between prevalence of GDM using Carpenter & Coustan (ADA) and WHO criteria . WHO criteria of two hour PG ≥ 140mg/dl identifying a large number of cases may have a greater potential for prevention of diabetes. The glycemic criteria for diagnosis of different categories of glucose intolerance by 75 g, 2 hr OGTT is listed in table 1.
Table 1.
Glycemic Criteria for Diagnosis of different categories of glucose intolerance by
75 g, 2 hr OGTT
| Criteria | FPG mg/dl | 2-hr PG mg/dl |
| Normal Glucose Tolerance [NGT] | < 100 | < 140 |
| Impaired Fasting Glucose [IFG] | 100 – 125 | – |
| Impaired Glucose Tolerance [IGT]* | – | 140 – 199 |
| >Diabetes Mellitus [DM] | ≥ 126 and / or | ≥ 200 |
*Glycemic cut-off for the diagnosis of IGT outside pregnancy is the same for the diagnosis of GDM during pregnancy.
Significance of cut-point of 2 hr plasma glucose level of 140 mg/dl
Increasing maternal carbohydrate intolerance in pregnant women is associated with a graded increase in the adverse maternal and fetal outcome . The primary outcomes of both birth weight and Serum C peptide level > 90th percentile occurs at the cut point of 2 hr PG > 140 mg/dl . In yet another follow-up study of children born to mothers who had third trimester plasma glucose, 120-139 mg/dl, the cumulative risk of type 2 diabetes was 19% at age 24 years and this risk increased to 30% with respect to those women who had 2 h plasma glucose 140 -199 mg/dl. Thus both short–term and long-term morbidity in the offspring occurs at the inflective cut-point of maternal 2 hr plasma glucose > 140 mg/dl and as such, this level assumes clinical significance. A pregnant woman, whose 2 hour plasma glucose is 120-139 mg/dl, needs follow-up.
A single test procedure to diagnose gestational diabetes mellitus in the community
Seldom, a pregnant woman visiting the ante-natal clinic for the first time comes in the fasting state. If she is asked to come on another day in the fasting state she may not return . Hence it is important to have a test that detects the glucose intolerance without the woman necessarily undergoing a test in the fasting state and it is preferable to perform the diagnostic test at the first visit itself.
In the antenatal clinic, a pregnant woman after undergoing preliminary clinical examination, has to be given a 75g oral glucose load*, without regard to the time of the last meal. A venous blood sample is collected at 2 hours for estimating plasma glucose by the GOD-POD method. GDM is diagnosed if 2 hr plasma glucose is ≥ 140 mg/dl.
* If 75g glucose packet is not available, remove 5 level teaspoons (not heaped) of glucose from a 100 g packet which is freely available. In hospitals where glucose is supplied in bulk, a cup or container of 75 g may be used.
Performing this test procedure in the non-fasting state is rational, as glucose concentrations are affected little by the time since the last meal in a normal glucose tolerant woman, whereas it will, in a woman with gestational diabetes. After a meal, a normal glucose tolerant woman would be able to maintain euglycemia despite glucose challenge due to brisk and adequate insulin response, whereas, a woman with GDM who has impaired insulin secretion, her glycemic level increases with a meal and with glucose challenge, the glycemic excursion exaggerates further. Therefore, this procedure assumes clinical relevance as WHO criteria based on glucose concentration 2 h after 75 g glucose load was able to correctly identify subjects with GDM . Yet another reason for recommending the single step procedure is that, the specificity of ADA screening with 50 gm 1-hr GCT without regard to time of the last meal is low . Hence, instead of performing screening test using 50 gm-1 hr test and then 100 gm OGTT, this single step procedure serves both as screening and diagnostic test for GDM, is simple, economical and feasible.
ADVANTAGES
- The pregnant women need not be fasting .
- Causes least disturbance in a pregnant woman’s routine activities.
- Serves as both screening and diagnostic procedure.
Clarity in Labeling the Different Magnitude of Abnormal Glucose Intolerance in Pregnancy
Increasing maternal carbohydrate intolerance in pregnant women without GDM is associated with a graded increase in adverse maternal and fetal outcomes implying that the fetal morbidity starts at a lower maternal glycemic level (<140 mg/dl). The occurrence of macrosomia was continuum as the 2 h plasma glucose increased from 120 mg/dl . Yet another study on long-term follow-up documented that, the cumulative risk of type 2 diabetes at 24 years in the offspring born to mothers who had third trimester plasma glucose, 120-139 mg/dl was 19% . In the same study, the cumulative risk was found to be 30% in offspring born to women who had 2 h plasma glucose > 140 mg/dl. Hence it may be prudent to label 2 hr plasma glucose value > 140 mg/dl as GDM and a 2 hr plasma glucose value ≥ 120 and ≤ 139 mg/dl as ‘Gestational Glucose Intolerance’ (GGI). The term IGT is used outside pregnancy and as such should not be used to denote any abnormal value during pregnancy. The nomenclature and glycemic levels suggested in table 2 are easy to remember.
Table 2:
With 75 gm OGTT (WHO criteria)
| Plasma Glucose | In Pregnancy | Outside Pregnancy |
| 2 hr ≥ 200 mg/dl | Diabetes | Diabetes |
| 2 hr ≥ 140 mg/dl & ≤ 199 mg/dl |
GDM | IGT |
| 2 hr ≥ 120 mg/dl & ≤ 139 mg/dl |
GGI | — |
| 2 hr < 120 mg/dl | Normal | Normal |
Gestational Weeks at Which Screening is Recommended
Insulin is detectable in the fetal pancreas as early as 9 weeks after conception. An increase in pancreatic beta cell mass and insulin secretion in the fetus occurs by the 16th week of gestation, in response to maternal hyperglycemia. The priming of the fetal beta cells may account for the persistence of fetal hyperinsulinemia throughout pregnancy and the risk of accelerated fetal growth. This necessitates performing the test procedures to diagnose GDM in the first trimester itself.
By following the usual recommendation for screening between 24 and 28 weeks of gestation, the chance of detecting unrecognized type 2 diabetes before pregnancy (pre- GDM) is likely to be missed . If the 2 – h PG is > 200 mg/dl in the early weeks of pregnancy, she may be a pre-GDM and A1c of > 6 is confirmatory {Normal A1c levels during pregnancy is 5.3 – 6}. A pregnant woman found to have normal glucose tolerance [NGT], in the first trimester, should be tested for GDM again around 24th – 28th week and finally around 32nd – 34th week.
Women with a history of GDM as well as offspring exposed to maternal diabetes in utero should be a major area of focus for preventive medicine . Preventive measures against Type 2 DM should start during intrauterine period and continue throughout life from early childhood [8]. In conclusion, a short term intensive care gives a long term pay off in the primary prevention of obesity, IGT and diabetes in the offspring, as preventive medicine starts before birth. The maternal health and fetal outcome depends upon the care by the committed team of diabetologists, obstetricians and neonatologists.
FURTHUR READING
- Dornhorst A, Rossi M. Risk and Prevention of Type 2 Diabetes in women with Gestational Diabetes. Diabetes Care 1998 Aug; 21(suppl 2): B43-9.
- Thomas A Buchanan, Anny Xiang, Siri L Kjos, Richard Watanabe. “What is gestational diabetes?” Diabetes Care 2007 July; 30 (2): S105-111
- Seshiah V, Balaji V, Madhuri S Balaji. Scope for Prevention of Diabetes – Focus Intrauterine milieu Interieur. JAPI 2008 Feb; 56: 109-113.
- Cosson E. Screening and insulin sensitivity in gestational diabetes. Abstract volume of the 40th Annual Meeting of the EASD, September 2004: A 350.
- Griffin ME, Coffey M, Johnson H, Scanlon P, Foley M, Stronge J et al. Universal vs risk factor-based screening for gestational diabetes mellitus: detection rates, gestation at diagnosis and outcome. Diabet Med 2000 Jan; 17(1): 26 – 32.
- Dornhorst A, Paterson CM, Nicholls JS, Wadsworth J, Chiu DC, Elkeles RS et al. High prevalence of GDM in women from ethnic minority groups. Diabet Med. 1992 Nov; 9 (9): 820-5.
- Beischer NA, Oats JN, Henry OA, Sheedy MT, Walstab JE. Incidence and severity of gestational diabetes mellitus according to country of birth in women living in Australia. Diabetes 1991 Dec; 40 Suppl 2: 35-8.
- Tuomilehto J. A paradigm shift is needed in the primary prevention of type 2 diabetes. In: Manfred Ganz, editor. Prevention of type 2 diabetes. England: John Willey & Sons Ltd; 2005. p. 153 – 165.
