Abstract
There is scarcity of available information on the possible significant risk factors related to diabetes mellitus (DM) prediction among expectant Saudi mothers with gestational diabetes mellitus (GDM). The present study is the first to identify such risk factors in the Arab cohort. A total of 300 pregnant subjects (mean age 33.45 ± 6.5 years) were randomly selected from all the deliveries registered at the Obstetrics Department of King Fahad Medical City, Riyadh Saudi Arabia from April 2011 to March 2013. Demographic and baseline glycemic information were collected. A total of 7 highly significant and independent risk factors were identified: age, obesity, and family history of DM, GDM < 20 weeks, macrosomia, insulin therapy and recurrent GDM. Among these factors, subjects who had insulin therapy use are 5 times more likely to develop DMT2 (p-value 3.94 × 10-14) followed by recurrent GDM [odds-ratio 4.69 (Confidence Interval 2.34-4.84); P = 1.24 × 10-13). The identification of the risk factors mentioned with their respective predictive powers in the detection of DMT2 needs to be taken seriously in the post-partum assessment of Saudi pregnant patients at highest risk.
Keywords: GDM, Saudi, pregnancy, diabetes mellitus
Introduction
Gestational diabetes mellitus (GDM) is a common pregnancy-associated complication defined as “any degree of glucose intolerance with onset or first recognition during pregnancy” [1,2]. It has been reported recently that an increase in the prevalence of GDM has been reported in several ethnic groups in the past 20 years, and this increase grossly reflects the incidence of diabetes mellitus type 2 (DMT2) in the concerned population [3]. The role of ethnicity as an independent predictor on the progression of GDM to DMT2 aside from conventional risk factors such as advanced maternal age, obesity and family history of DM is consistently confirmed in several studies, with non-European women, Asian women in particular, having a higher predisposition than other groups [4,5]. Granted that there has been a considerable amount of literature on GDM done in the Arab world, Saudi Arabia in particular, remains understudied as compared to other developed nations with respect to maternal hyperglycemia progressing to full blown DMT2. Previous studies done in Saudi Arabia were able to identify unique risk factors for GDM such as multi-parity and presence of periodontal disease [6,7]. In this single center cross-sectional study, we aimed to determine the risk factors for DMT2 among randomly selected pregnant subjects with GDM.
Methodology
Subjects were taken from a database of all deliveries that took place from April 2011 to March 2013 at the Obstetrics Department of King Fahad Medical City, Riyadh, Saudi Arabia. Out of the total 1700 deliveries, 400 were randomly selected using the RAND function of MS Excel 2010. Information gathered include demographics such as nationality, family history of GDM, date of GDM diagnosis (if any), history of macrosomia, insulin therapy and recurrent GDM. Clinical data include age, pre-pregnancy weight (kg), oral glucose tolerance test results, HBA1c and post-partum weight (kg). Exclusion criteria include subjects with other co-morbidities aside from DMT2 such as thyroid, heart, kidney, liver and infectious diseases. Those with incomplete information were also taken out, bringing the final total sample size to N = 300. The study has been approved by the Institutional Review Board of King Fahad Medical City Research Center, Riyadh, Saudi Arabia.
Data analysis
Data was analyzed using the Statistical Package for the Social Sciences (SPSS) version 16.5 (Chicago IL, USA). Frequencies were presented as percentages and continuous variables were presented as mean ± standard deviation. Analysis of variance (ANOVA) was used to compare groups. Multiple logistic regression analysis was used to determine risk using DMT2 as dependent variable and age, obesity, family history of DMT2, GDM less than 20 weeks, macrosomia, insulin therapy and recurrent GDM as independent variables. Significance set at P < 0.05.
Results
Table 1 shows the clinical characteristics of all subjects. Almost all of the expectant mothers who participated in the present study were Saudis (94.7%). More than 70% of the subjects had a family history of DM, 37.3% had a previous history of GDM, 28.4% were on insulin therapy and more than 20% had a history of macrosomia. The rest of the characteristics are shown in Table 1.
Table 1.
Demographics and Characteristics of Subjects
| Parameter | |
|---|---|
| N | 300 |
| Saudi Nationality | 283 (94.7) |
| Family History of DM | 215 (71.9) |
| GDM Duration (more than 20 weeks) | 216 (72.0) |
| History of Macrosomia | 62 (20.7) |
| Insulin Therapy | 85 (28.4) |
| Recurrent GDM | 112 (37.3) |
| Age (years) | 33.45 ± 6.5 |
| Pre-pregnancy weight (kg) | 73.8 ± 18.4 |
| OGTT (0-hour) (mmol/l) | 5.5 ± 1.3 |
| OGTT (2-hour) (mmol/l) | 7.7 ± 3.1 |
| HbA1c | 5.9 ± 0.9 |
| Post-partum weight (kg) | 76.2 ± 18.7 |
Note: Data presented as percentage (%) for frequencies; mean ± standard deviation for continuous variables.
Next we compared the subjects based on the presence of IFG and DMT2 (Table 2). Subjects with DMT2 had the highest prevalence of family history of DM (93.2%) and the lowest prevalence of GDM beyond 20 weeks (20.5%) than both normal and IFG groups. In addition, half of the DMT2 group had a history of macrosomia with an overwhelming majority (84.1%) on insulin therapy, and these were statistically significant as compared to normal and IFG groups. In the normal group and as expected, the mean age was significantly younger than both the DMT2 and IFG group. The normal group also had the lowest pre-pregnancy weight, BMI, HBA1c and post-partum weight as compared to both group. The rest of the comparisons are shown in Table 2.
Table 2.
Characteristics of Subjects According to Glucose Tolerance
| Parameters | Normal | IFG | T2DM |
|---|---|---|---|
| N | 158 | 98 | 44 |
| Saudi Nationality | 94.9 | 93.9 | 93.2 |
| Family History of DM | 63.9 | 75.3 | 93.2* |
| GDM Duration (more than 20 weeks) | 87.3 | 70.4 | 20.5*,! |
| History of Macrosomia | 11.4 | 22.4 | 50.0*,! |
| Insulin Therapy | 13.3 | 27.8 | 84.1*,! |
| Recurrent GDM (≥ 2 times) | 7.0 | 18.4 | 18.2 |
| Age (years) | 32.17 ± 6.91 | 34.50 ± 6.03* | 35.70 ± 5.33* |
| Pre-pregnancy weight (kg) | 68.67 ± 16.7 | 76.90 ± 18.56* | 85.18 ± 17.33! |
| Body Mass Index (kg/m2) | 28.17 ± 6.37 | 30.95 ± 7.14* | 33.62 ± 5.97*,! |
| OGTT (0-hour) (mmol/l) | 4.86 ± 0.37 | 5.51 ± 0.64* | 7.88 ± 1.61*,! |
| OGTT (2-hour) (mmol/l) | 5.84 ± 1.08 | 7.96 ± 1.69* | 13.61 ± 3.06*,! |
| HbA1c | 5.51 ± 0.44 | 5.88 ± 0.64* | 7.04 ± 1.42*,! |
| Post-partum weight (kg) | 70.78 ± 16.26 | 80.12 ± 18.64* | 87.21 ± 20.34* |
Note: Data presented as percentage (%) for frequencies; mean ± standard deviation for continuous variables;
denotes significance as compared to normal;
denotes significance as compared to IFG;
significant at P < 0.01.
Table 3 shows the odds-ratios for DMT2 using the different risk factors identified. Subjects on insulin therapy and those who had GDM less than 20 weeks had the highest risk for DMT2, with the presence of either factor translating to 5 times more likely to harbor DMT2 independent of other factors [OR 4.94 (3.27-7.75), P = 3.94 × 10-14; OR 4.69 (3.12-7.06), P = 1.24 × 10-13, respectively]. Furthermore, patients who had recurrent GDM are 3.37 times more likely to have DMT2 (P = 6.56 × 10-11). Other independent significant risk factors identified include age, obesity, family history of DMT2 and macrosomia (Table 3).
Table 3.
Odds Ratio for DMT2 using several variables of interest as dependent variables
| Risk Factor | Odds-Ratio | 95% Confidence Interval | P-Value |
|---|---|---|---|
| Age > 35 years | 1.87 | 1.31-2.49 | 3.36 × 10-4 |
| Obesity (> 30 kg/m2) | 2.40 | 1.70-3.38 | 6.29 × 10-7 |
| Family History of DMT2 | 2.21 | 1.46-3.34 | 0.00017 |
| GDM less than 20 weeks | 4.69 | 3.12-7.06 | 1.24 × 10-13 |
| Macrosomia | 2.75 | 1.87-4.05 | 3.04 × 10-7 |
| Insulin Therapy | 4.94 | 3.27-7.75 | 3.94 × 10-14 |
| Recurrent GDM | 3.37 | 2.34-4.84 | 6.56 × 10-11 |
Note: P-value significant at P < 0.01.
Discussion
The present cross-sectional study provides first-hand additional information on the capacity of several risk factors to detect who among pregnant Saudi women are at highest risk for DMT2 progression. In the results, expectant mothers with DMT2 had the highest pre-pregnancy weight and BMI, confirming a very recent study that having a high pre-pregnancy BMI is an independent predictor for both early and late DMT2 converters after GDM [8]. Other conventional significant risk factors for GDM such as advancing age and family history of DM were also observed to be consistent in predicting DMT2 in the present study.
Other highly significant risk factors in the progression to DMT2 among Saudi expectant mothers are the use of insulin therapy and GDM recurrence. Insulin treatment has also been one of the major risk factors for post-partum diabetes in a Turkish population [9]. The use of insulin per se in the treatment of hyperglycemia is an indication of poor β-cell function. It has been observed that patients who formerly had gestational diabetes also had a marked decrease in insulin sensitivity and a modest decline in β-cell function, and these changes are significantly associated with diabetes onset [10]. It is worthy to note that insulin therapy is commonly used among pregnant patients with diabetes mellitus type 1 (DMT1), is frequently needed to optimize glycemic control among pregnant patients with DMT2 and less common among those with GDM [11]. Recurrent GDM on the other hand, while significantly associated with DMT2 among Saudi pregnant patients, has not been associated thus far in the deterioration of glucose metabolism and cardiovascular risk, at least in European women [12].
The authors acknowledge some limitations. The cross-sectional nature of the present study cannot determine whether the outcome (DMT2) followed exposure (risk factors) in time or vice versa. This needs to be confirmed using a longitudinal design. Furthermore while the sample size was enough to elicit extremely significant p-values, the findings cannot be generalized since it is a single-center study. Nevertheless, the identification of highly significant risk factors, specifically insulin use and recurrent GDM to predict DMT2 among randomly selected Saudi pregnant women is the first documentation in this cohort, and carries both scientific merit and clinical significance in the assessment and management of this population post-partum, particularly in this part of the world. Further studies involving neonatal outcomes and other variables not included such as socio-economic factors, diet and physical activity should be done to determine these factors also affect DMT2 progression.
Acknowledgements
The authors would like to thank King Fahd Medical City Research Center for funding and approving the study. The authors are also grateful to Carla Suguitanm, Noron Sybil and Marife de Vera for their assistance.
Disclosure of conflict of interest
None.
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