Gestational Diabetes Mellitus Prevalence and Progression to Type 2 Diabetes Mellitus: A Matter of Global Concern

Gestational diabetes mellitus (GDM) is, by definition, glucose intolerance that is recognised first at the time of pregnancy. This may also include cases of pre-existing type 2 diabetes mellitus (T2DM) that were undiagnosed.[1] The prevalence of this common pregnancy complication has risen by over 30% in many countries in the last two decades and is becoming a global epidemic.[2–4] GDM may result in various short-term adverse outcomes in expecting mothers and offspring. In addition to such short-term harmful effects, there is a higher risk of developing cardiometabolic adversities such as hypertension, ischaemic heart disease and T2DM [Figure 1].[5–7]Figure 1: The various complications of Gestational Diabetes Mellitus. This figure has been drawn with the premium version of BioRender (https://biorender.com/) with license number QT25HLNJE6. Image Credit: Rahnuma Ahmad.GDM is an established risk factor for the development of T2DM in later life. A ten times higher risk of developing T2DM has been observed in women with a history of GDM than the control group in a meta-analysis.[8,9] Other studies have noted a twenty-fold higher risk of T2DM development in women with a history of suffering GDM.[6,9] Nouhjah et al. reported that pre-diabetes prevalence in post-GDM women ranged from 3.8% to 50.9%.[10] T2DM incidence in women with a history of GDM 6 weeks to 28 years after parturition was between 2.6% and 70%. It was also reported that the highest risk of type 2 diabetes development was 3–6 years after delivery.[11,12] The rising GDM prevalence may reflect the global epidemic of underlying T2DM.[1] Furthermore, various studies on the progression of GDM to T2DM note that women with GDM have a much higher risk of developing T2DM in later life,[7,9–12] suggesting that GDM is a fueling factor for the T2DM global epidemic.[1] ASSESSMENT OF GESTATIONAL DIABETES MELLITUS GLOBALLY Screening for GDM worldwide includes three approaches: routine screening in case of all pregnant women, screening those women selectively with high risk depending on some risk factors or combining of these approaches. It is ideal for performing routine screening for all pregnant women and not restricted to only women under high risk to identify all likely cases of GDM. Even though selective screening for GDM may be less burdening in terms of economic costs, since the benefit of performing the test is less for women with low risk, screening selectively may result in the missing diagnosis of more than 40% of cases of GDM.[1,13,14] The approaches for screening differ between years, countries and regions. For example, in the USA, the screening rate, depending on the adopted practices of healthcare providers, ranges from 87.5% to 96.5%.[15,16] Whereas in Sweden, the risk factor-dependent screening is done, and only about 30.7% of women who met the risk factor criteria underwent screening for GDM.[17,18] The timing of screening may also differ between healthcare providers, like in Nigeria, irrespective of the standards of GDM diagnosis and screening may be conducted at different times in various adapted approaches such as between 24 and 28 weeks,[19] 4 and 40 weeks,[20] 24 weeks and above[21] and third trimester.[22] DIAGNOSTIC CRITERIA FOR GESTATIONAL DIABETES MELLITUS Several diagnostic criteria have been suggested over time which, includes that recommended by O’Sullivan and Mahan in 1964 with an oral glucose tolerance test (OGTT) using 100 g glucose with the Somogyi–Nelson technique;[1,23] the National Diabetes Data Group (NDDG) in 1979, which was recommended by the American Diabetes Association (ADA) until 1999;[1,24] Carpenter and Coustan (C and C) criteria in 1982 which was the recommendation by ADA since 2000 up to 2010.[1,25,26] The new one-step approach International Association of Diabetes and Pregnancy Study Group (IADPSG) to GDM diagnosis has emerged, in 2011.[27] In 2014 ADA recommendation was modified and endorsed either the one-step approach of IADPSG or the C and C or NDDG criteria [Figure 2].[28]Figure 2: The different diagnostic criteria for Gestational Diabetes Mellitus recommended by the American Diabetes Association over the years. This figure has been drawn with the premium version of BioRender (https://biorender.com/) with license number UO25HLN3NV. Image Credit: Rahnuma Ahmad. GDM: Gestational Diabetes Mellitus, IADPSG: International Association of Diabetes and Pregnancy Study Group.The one-step strategy with a 75-g OGTT that was suggested by the IADPSG is to be done during the gestation period between 24 and 28 weeks and one or more values of the plasma glucose equal to or more than 5.1 mmol/L (fasting), 10 mmol/L (1 h after 75 g OGTT) and 8.5 mmol/L (2 h after 75 g OGTT) were set as threshold levels for GDM diagnosis.[29] The IADPSG criteria for diagnosis of GDM is considered a milestone in the GDM diagnostic criteria history and has been supported by international organisations such as the World Health Organization (WHO), ADA and the International Federation of Gynaecology and Obstetrics.[30–32] These organisations acknowledged the use of OGTT with 75 g glucose during the gestation period of 24–28 weeks as the test for diagnosis of GDM with the diagnostic criteria to be the cut-off value per the recommendation by the IADPSG.[8] The basis for the new criteria is the Hyperglycaemia and Adverse Pregnancy Outcome Study (HAPO) study that revealed unfavourable outcomes of pregnancy such as hypoglycaemia in neonate, >90th percentile in C peptide of cord, >90th percentile in case of weight at birth and primary caesarean section was 1.75 times more in comparison to mean values of glucose.[33] The ADA criteria for diagnosing GDM are only for women who are pregnant. On the other hand, the WHO proposed that the criteria for diagnosing GDM should be the same as that for impaired tolerance to glucose or diabetes mellitus without pregnancy with 75 g glucose 2 h OGTT with one or more abnormal values.[1,34] The WHO, in 2013, suggested that for hyperglycaemia first detected during pregnancy (HFDP), the new definition and criteria need to include both GDM and diabetes not diagnosed before.[1,30,35] The intent of WHO is to distinguish between the various HFDP severities and differentiate HFDP due to diabetes in pregnancy from GDM. The International Diabetes Federation has used extrapolated data to find the estimates of HFDP in place of GDM, keeping in line with the new definition of HFDP given by WHO.[4] Due to the adoption of these new criteria, there has been a rise in GDM prevalence. Among women attending the Northern California Kaiser Permanente Medical Care Program, it was noted that the use of C and C criteria resulted in a 33%–70% higher GDM prevalence in comparison to the outcome of the use of criteria recommended by NDDG.[36] The IADPSG threshold is even lower, increasing the GDM prevalence by 2–7 times compared with the other criteria.[37–41] The prevalence of GDM was noted to differ when different criteria were applied in Brazil, that is, 2.3% (with ADA criteria), 7.1% (with WHO 1999 criteria) and 18% (with IADPSG criteria).[37] Another study observed a marked difference in the prevalence of GDM when different criteria were used. They noted the majority to 13.3% (with ADA 2004 criteria), 24.5% (with WHO 1999 criteria) and 45.3% (with IADPSG criteria).[40] A study in Spain also noted a higher prevalence of GDM for IADPSG criteria (35.5%) compared to C and C criteria (10.6%).[41] The various risk factors of GDM, such as ethnicity/race, parity, GDM history within the family, high body mass index (BMI) and age, impact the prevalence of GDM globally, even if a single criterion is used.[1] It was observed in the HAPO study in which 9 countries with 15 centres were included that GDM estimates varied within and between countries owing to the different risk factors of GDM.[42] PREVALENCE OF GESTATIONAL DIABETES MELLITUS ACROSS THE GLOBE The lowest prevalence for GDM was noted in Europe at 1.8%–22.3%; that in Southeast Asia, Africa, South and Central America, North America and the Caribbean and Western Pacific was found to be 11.7%, 8.9%, 11.2%, 7.0% and 11.7%, respectively and the highest prevalence was observed in the Middle East and North Africa, ranging between 8.4% and 24.5% [Figure 3]. The prevalence of GDM varied depending on the diagnostic criteria used. In the Western Pacific, Japan had a majority of 4.5% using the criteria recommended by Gynaecology and Obstetrics Society of Japan in 1984 and IADPSG,[1,33,43] while Singapore had a GDM prevalence of 25.1% with the IADPSG criteria. In Europe, Norway uses the WHO 1999 and IADPSG criteria and had a prevalence of GDM of 22.3%, while Ireland had a 1.8% prevalence when the criteria recommended by the National Institute for Health and Care Excellence was used.[34,44] In the regions of North America and the Caribbeans, Canada had the least GDM prevalence using Canadian Diabetes Association criteria, and the highest prevalence was noted in Barbados using IADPSG criteria of 11.9%.[1,45,46] In Southeast Asia, the highest prevalence of GDM was registered in Malaysia (18.3%), next was 13.6% in India, 9.70% in Bangladesh and 8.10% in Sri Lanka. In the Middle East and North Africa, Iran reported a prevalence of 8.4%, which was the lowest and the highest in the United Arab Emirates, 24.5%. In Cuba and Brazil, the prevalence of GDM was 16.6% and 5.7%, respectively. In Nigeria, the majority was 8.2%, and in Tanzania was 9.5%. The Nigeria and Tanzania of African continent utilized WHO and IADPSG criteria for necessary assessment.[1]Figure 3: The prevalence of Gestational Diabetes Mellitus globally. This figure has been drawn with the premium version of BioRender (https://biorender.com/) with license number JB25HLSWNJ. Image Credit: Rahnuma Ahmad. GDM: Gestational Diabetes Mellitus.UNDERLYING GESTATIONAL DIABETES MELLITUS FACTORS OF RISK The underlying factors of risk in a study population also influence GDM prevalence.[1] A study performed in Turkey reported that GDM acts as a significant risk factor with advances of mother’s age. They noted that when comparison was made with women of ≤24 years of age, there was a fourfold higher prevalence of GDM in women >30 years of age.[47] Race/ethnicity is another decisive risk factor for GDM. In Australia, South Asian women had a 4.22 times higher risk of GDM development than those from Australia or New Zealand.[3] In the USA, a study observed that the highest GDM prevalence was in the Filipino population (10.9%) and Asian population (10.2%). Among Hispanics, the prevalence was 6.8%, and the least values of prevalence were noted among Caucasians (4.5%) and African-Americans (4.4%).[48] Possible mechanisms for the racial differences may be related to variations in the body’s composition, physical activity, diet, genetic predisposition, reporting and system of healthcare.[49] Asians are more susceptible to visceral and abdominal fat accumulation.[50] They are more likely to suffer from impairment of the β cell function and insulin resistance.[51,52] High prevalence of GDM may be attributed to genetic predisposition.[53,54] Nativity, even within the same race, may exhibit differences in GDM prevalence. For example, a study done in Florida found a two times higher risk of GDM among Asians born outside of the USA compared to those born in the USA, irrespective of age, BMI, height and BMI.[55] Family history of diabetes, sedentary lifestyle, socioeconomic factors, unhealthy diet and high BMI before pregnancy may affect the GDM prevalence in a population.[56] It was noted in a study that Caucasian Hungarians with pre-pregnancy higher than normal BMI had twice the risk of GDM development, irrespective of the criteria of diagnosis (WHO 1999 and IADPSG).[57] Urbanisation is another risk factor, particularly in developing countries. In Tanzania, it was reported that those residing in the urban areas showed about five-fold higher prevalence of GDM compared to the rural population when IADPSG criteria were used. When WHO 1999 criteria were used, the risk was even higher, about eight folds.[58] Therefore it is imperative to consider the underlying risk factors while determining GDM prevalence within a population. PROGRESSION OF GESTATIONAL DIABETES MELLITUS TO TYPE 2 DIABETES MELLITUS Progress of GDM to T2DM exhibited heterogeneity for studies and countries, which may be partly attributed to the diagnosing GDM and/or T2DM criteria, population characteristics, follow-up years and retention rate. Among the countries of Europe, the risk estimate in Finland was 47,[59] while in German’s was 2.7.[60,61] The incidence of T2DM following GDM was noted to be 35.7% in the case of Sweden[62] and 2.1% in Germany.[61] The follow-up length mean value ranged between 5.5 months and 15 years.[62] The follow-up length following GDM had shown that when follow-up was performed after a short duration, like in one study after the 1-year insignificant rise in T2DM development risk that is 9.2% was found.[63] In contrast, long-term follow-up in a study in Sweden found a cumulative risk of 35.7% when follow-up was done after 15 years.[61] In studies done in the USA, the cumulative risk varied from 25.9% to 36.4%, with follow-up lengths ranging between 4.8 and 28 years.[1,64] Another study reported a cumulative risk of 66.7% in the USA when the follow-up length was 7 years.[1,65] In Southeast Asia, South Indian women had a 23 times higher risk of developing T2DM, with a cumulative risk of 37.1% when follow-up was after 5 years.[66] A meta-analysis noted that among Southeast Asian women, the cumulative incidence of T2DM at follow-up after 5 years was 17.34% and that after 10 years was 33%.[67] In South and Central America, studies in Brazil found cumulative risk of incidence to be 8.6%[68] and 30.4%,[69] with the length of follow-up after 6.2 years and 16–24 weeks, respectively. Diabetes mellitus is an enormous global challenge for public health. GDM may harm the pregnancy outcome and eventually contribute to chronic diseases like T2DM development later in life. The prevalence of GDM varies globally, possibly due to variations in applied diagnostic criteria, screening processes and population risk factors. Middle East and North Africa, Western Pacific and Southeast Asia suffer the highest prevalence of GDM, while Europe has the lowest GDM prevalence. The new IADPSG diagnostic criteria have led to a more significant prevalence estimation. Those who have suffered from GDM are at a high risk of T2DM development after pregnancy. However, data on this progression risk are limited. Global efforts and collaboration need to continue informing makers of health policy and health-care providers to develop more effective management and prevention of diabetes mellitus. Consent for publication The author reviewed and approved the final version and has agreed to be accountable for all aspects of the work, including any accuracy or integrity issues. Data availability Information is taken from freely available sources for this editorial. Authorship contribution All authors contributed significantly to the work, whether it be in the conception, design, utilization, collection, analysis and interpretation of data or in all these areas. They also participated in the article’s drafting, revision or critical review, gave their final approval for the version that would be published, decided on the journal to which the article would be submitted and made the responsible decision to be held accountable for all aspects of the work.

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