14th September 2020, Dr Chee L Khoo
We have many patients who have borderline high fasting glucose in their routine check-up. In non-pregnant adults, we have been able to use HbA1c as a generic screening test for type 2 diabetes (T2D) for some time. Unfortunately, neither non-diabetic fasting glucose readings nor HbA1c totally exclude the presence of diabetes. I am sure you have come across patients with non-diabetic fasting glucose and HbA1c but yet fail their oral glucose tolerance test (OGTT). During the Covid-19 pandemic, there are many women who hesitate to wait 2 hours at the pathology collection centres for their OGTT. Can we use the HbA1c to screen pregnant women for GDM?
We know that diabetes mellitus occurs when the body cannot produce enough insulin to meet demand. Insulin resistance (IR) plays a large part in type 2 diabetes but so does the tenacity of the beta-cells. As long as the beta-cells can keep up with the increased demands of IR, diabetes does not occur. There are other abnormalities in the pathophysiology of T2D but at the end of the day, it’s a supply and demand equation. Some patients have more of an insulin resistance problem while others just have pretty lousy beta-cells. Hence, the different phenotypes we see in our patients with T2D. How does that apply to how we screen for gestational diabetes mellitus (GDM)?
Insulin resistance is not uniformly the same in all tissues. Some patients have more IR in the muscles while others have more IR in the hepatic tissue. Their glucose profile over the 24-hour period must also differ. It is thought that patients with more hepatitic IR tend to have higher fasting hyperglycaemia while those with more muscle IR tend to have more post prandial hyperglycaemia.
If you observed some of your patients with T2D, you probably have noticed that patients with T2D from the Asian (especially South Asian) community in generally, tend to be smaller built with less muscles. Many of them do have excessive adiposity but probably not as excessive as one would see in Caucasians with T2D. These are the patients who has T2D more because of poor beta-cells capacity than insulin resistance. Because they have less of an IR issue including hepatic IR, their fasting glucose tends to be lower. If we depend on fasting glucose readings for the diagnosis of T2D, we are likely to miss a substantial proportion of patients with T2D in these subgroups of patients.
OGTT is a test of the body’s insulin response to peak demand (after 75g of glucose challenge). The fasting glucose may be within range but when pushed to maximum, does the body have enough insulin to do the job? This is the basis of the 75g glucose challenge test.
One aspect of GDM of immediate concern is the use of the 75 g two‐hour oral glucose tolerance test to diagnose GDM during a time of social isolation and risk of SARS‐CoV‐2 contagion. The need to diagnose GDM using an OGTT, which assesses both fasting and post‐prandial glycaemia, is now considered best practice by all relevant international organisations, with the International Association of Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria for GDM (fasting glucose ≥ 5.1 mmol/L, 1 hour ≥ 10.0 mmol/L, two hours ≥ 8.5 mmol/L) most used in Australia.
Alternatives to 2 hr 75g OGTT?
Using fasting BGL alone:
Fasting blood glucose level (BGL) physiologically drops in the first trimester making fasting glucose unreliable as a diagnostic tool for early GDM (1). In late pregnancy, if we set the cut off reading at 4.7 mmol/L, we will miss about 25% of patients with GDM based on 75g OGTT. If we were to set the cut off at 5.1 mmol/L, which is what we have in SWS, we will still miss 55% of patients with GDM (2).
Using 1-hour 75g OGTT alone
If we were to use only a 1-hour 75g OGTT, 12% of GDM will be missed (3).
Using HbA1c alone
While this appears to be easier and more convenient to perform, the accuracy of the results is substantially influenced by red cell life, haemodilution in early pregnancy, increased erythropoiesis and ethnic differences (4). In South Asians, in early pregnancy if we use 5.9% as the cut off for diagnosis, HbA1c only has a sensitivity of 1.2% (5). In the same group of women, in late pregnancy, the sensitivity improves but it is still only 24.7% (6).
Other markers?
Fructosamine, capillary testing and self monitored blood glucose have all been suggested but suffer from the lack of validated data.
Recommendations
The OGTT remains the gold standard for diagnosis throughout pregnancy and, as ADIPS suggests, should still be offered to all women. If social distancing requirements cannot be observed, there are alternative diagnostic approaches, which should identify the majority of women with GDM while limiting the potential within‐laboratory exposure to the virus. Both physician and patients should be aware of that a significant proportion of GDM will be missed. The full OGTT with attendance of 2 hours has 100% sensitivity. Women could perhaps be allowed to wait outside the collection centre, such as in their own car, which may reduce the sensitivity (inaccurate timing and physical activity) but may be more acceptable to some women.
References:
- Immanuel J, Simmons D. Screening and treatment for early‐onset gestational diabetes mellitus: a systematic review and meta‐analysis. Curr DiabRep 2017; 17(11): 115.
- Greater Western Sydney‐unpublished data: #1 Bankstown‐Lidcombe Hospital, #2 Liverpool Hospital, #3 Westmead Hospital.
- Sacks DA, Hadden DR, Maresh M et al. Frequency of gestational diabetes mellitus at collaborating centers based on IADPSG consensus panel–recommended criteria: the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Diabetes Care 2012; 35(3): 526–528.
- Church DS, Simmons D. More evidence of the problems of using HbA1c for diagnosing diabetes?: the known knowns, the known unknowns and the unknown unknowns. J Intern Med 2014; 276(2): 171–173.
- Punnose J, Malhotra RK, Sukhija K et al. Glycated haemoglobin in the first trimester: a predictor of gestational diabetes mellitus in pregnant Asian Indian women. Diabetes Res Clin Pract 2020; 159: 107953.
- Renz PB, Chume FC, Timm JR et al. Diagnostic accuracy of glycated hemoglobin for gestational diabetes mellitus: a systematic review and meta‐analysis. Clin Chem Lab Med 2019; 57(10): 1435–1449.
- Simmons D, Rudland VL, Wong V, et al. Options for screening for gestational diabetes mellitus during the SARS-CoV-2 pandemic [published online ahead of print, 2020 Aug 10] . Aust N Z J Obstet Gynaecol. 2020;10.1111/ajo.13224. doi:10.1111/ajo.13224