1.Prevalence of Polypharmacy and Potentially Inappropriate Prescribing (PIP) among Older Adults Aged 65 Years and above in Brunei Darussalam
Sebastian Eng Chong KOH ; Maggie SIM ; Lina Maziyyah PG METUSSIN ; Pey Siaw LIM ; Su Ying YEO ; Yung Shin YEO ; Wai See WONG ; Shyh Poh TEO ; Li Ling CHAW
Brunei International Medical Journal 2026;22():97-104
Introduction: Polypharmacy and potentially inappropriate prescribing (PIP) are increasingly recognised as important contributors to medication -related harm among older adults. However, published national data on the prevalence of polypharmacy and PIP in Brunei Darussalam are unavailable. The objectives of this study was to determine the prevalence of polypharmacy and PIP among adults aged 65 years and above in Brunei Darussalam using Screening Tool of Older Persons ’ potentially inappropriate Prescriptions (STOPP) version 2 criteria. Materials and Methods: A retrospective cross -sectional study was conducted using data from the Brunei Healthcare Information Management System (Bru -HIMS). A stratified proportional random sample of 2,000 older adults with documented medical encounters in 2016 was selected. Polypharmacy was defined as the concurrent use of five or more medications. PIP was assessed using STOPP version 2 criteria. Descriptive statistics were used to summarise prescribing patterns. Results: Of the 2000 older adults included (mean age 73.0 ± 6.6 years), 1,181 (59.1%) had polypharmacy. Among those with polypharmacy, 1,057 (89.5%) could be assessed using STOPP criteria, and 206 (19.5%) had at least one PIP. The most frequently identified PIPs involved prolonged use of proton pump inhibitors for uncomplicated peptic ulcer disease at full therapeutic dosage for more than eight weeks, where dose reduction, discontinuation, or transition to maintenance therapy (e.g. H2 receptor antagonists) is indicated, prescribing without evidence -based indication, duplication of drug classes, use of ACE inhibitors or angiotensin receptor blockers in patients with hyperkalaemia, and use of first -generation antihistamines. Conclusion: Polypharmacy and PIP are common among older adults in Brunei Darussalam. The findings highlight the need for systematic medication review and deprescribing strategies to optimise pharmacotherapy and improve medication safety in older populations
2.Prevalence of Polypharmacy and Potentially Inappropriate Prescribing (PIP) among Older Adults Aged 65 Years and above in Brunei Darussalam
Sebastian Eng Chong KOH ; Maggie SIM ; Lina Maziyyah PG METUSSIN ; Pey Siaw LIM ; Su Ying YEO ; Yung Shin YEO ; Wai See WONG ; Shyh Poh TEO ; Li Ling CHAW
Brunei International Medical Journal 2026;22():97-104
Introduction: Polypharmacy and potentially inappropriate prescribing (PIP) are increasingly recognised as important contributors to medication -related harm among older adults. However, published national data on the prevalence of polypharmacy and PIP in Brunei Darussalam are unavailable. The objectives of this study was to determine the prevalence of polypharmacy and PIP among adults aged 65 years and above in Brunei Darussalam using Screening Tool of Older Persons ’ potentially inappropriate Prescriptions (STOPP) version 2 criteria. Materials and Methods: A retrospective cross -sectional study was conducted using data from the Brunei Healthcare Information Management System (Bru -HIMS). A stratified proportional random sample of 2,000 older adults with documented medical encounters in 2016 was selected. Polypharmacy was defined as the concurrent use of five or more medications. PIP was assessed using STOPP version 2 criteria. Descriptive statistics were used to summarise prescribing patterns. Results: Of the 2000 older adults included (mean age 73.0 ± 6.6 years), 1,181 (59.1%) had polypharmacy. Among those with polypharmacy, 1,057 (89.5%) could be assessed using STOPP criteria, and 206 (19.5%) had at least one PIP. The most frequently identified PIPs involved prolonged use of proton pump inhibitors for uncomplicated peptic ulcer disease at full therapeutic dosage for more than eight weeks, where dose reduction, discontinuation, or transition to maintenance therapy (e.g. H2 receptor antagonists) is indicated, prescribing without evidence -based indication, duplication of drug classes, use of ACE inhibitors or angiotensin receptor blockers in patients with hyperkalaemia, and use of first -generation antihistamines. Conclusion: Polypharmacy and PIP are common among older adults in Brunei Darussalam. The findings highlight the need for systematic medication review and deprescribing strategies to optimise pharmacotherapy and improve medication safety in older populations
3.Recurrent Diabetic Ketoacidosis: Predictors and Clinical Outcomes in a 24-Year Retrospective Cohort
Liang Wei Wong ; Lisa Mohamed Nor ; Raja Nurazni binti Raja Azwan ; Adilah Zulaikha binti Abd Latib ; Hidayatil Alimi bin Keya Nordin ; Qin Zhi Lee ; Kean Heng Lim ; Jia Ling Low ; Mohd Fyzal bin Bahrudin ; Syaza binti Izhar Hisham ; Jia Whey Jacelyn Ong ; Chin Voon Tong
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):33-34
Introduction:
Diabetic ketoacidosis (DKA) is a life-threatening complication associated with significant morbidity and healthcare
burden. Despite advances in diabetes care, recurrent
DKA remains common, often reflecting gaps in treatment
adherence and patient education. Identifying predictors
of recurrence is crucial for risk stratification and targeted
intervention.
Methodology:
We conducted a retrospective observational study of all
adult DKA admissions to a tertiary centre between 2001
and 2025. Electronic medical records were reviewed for
demographic data, biochemical parameters, precipitating
factors, and clinical outcomes. DKA was defined using standard biochemical criteria. Recurrent DKA was defined as ≥2 admissions during the study period. Factors associated
with recurrent DKA admissions were analyzed. Patients
under the age of 18 years and those with missing vital
information were excluded.
Results:
A total of 667 DKA admissions, comprising 566 patients,
were identified, of which 101 admissions (15.1%) were
recurrent, involving 65 patients. Among recurrent DKA
episodes, the most common precipitating factors were
infection (64.4%) and insulin omission (62.4%). After
multivariate analyses, patients with type 1 diabetes
mellitus (T1DM) were more likely to develop recurrent
DKA compared to those with type 2 diabetes mellitus
(aOR 4.16; 95% confidence interval [CI] 2.58–6.70; p <0.001).
Insulin omission was strongly associated with recurrent
DKA (aOR 2.29; 95% CI 1.46–3.60; p <0.001). In contrast,
baseline glycated hemoglobin and chronic kidney disease
were not significantly associated with recurrence. Diabetic
counseling during the first DKA admission did not reduce
recurrent DKA. There were no significant differences in
mortality (3.9% vs 6.2%, p = 0.524) or critical care admission
rates (40.6% vs 38.7%, p = 0.718) between recurrent and first
DKA episodes.
Conclusion
Recurrent DKA accounts for a substantial proportion of
DKA admissions and is strongly associated with insulin
omission and T1DM. Our findings suggest that recurrent
DKA is driven predominantly by behavioral and adherencerelated factors, indicating the need for multidisciplinary
interventions beyond standard inpatient counseling.
Diabetic Ketoacidosis
;
Retrospective Studies
4.Clinical and Biochemical Characteristics of Adult Diabetic Ketoacidosis: T1DM vs. T2DM
Mohd Fyzal Bahrudin ; Chin Voon Tong ; Raja Nurazni Raja Azwan ; Adilah Zulaikha Abd Latib ; idayatil Alimi Keya Nordin ; Qin Zhi Lee ; Kean Heng Lim ; Jia Ling Low ; Syaza Izhar Hisham ; Liang Wei Wong ; Jia Whey Jacelyn Ong ; Lisa Mohamed Nor ; Zanariah Hussein
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):39-40
Introduction:
The rising incidence of diabetic ketoacidosis (DKA) in type 2
diabetes mellitus (T2DM) represents a paradigm shift from
its traditional recognition as a hallmark complication of
type 1 diabetes mellitus (T1DM). However, contemporary
data comparing clinical presentation, precipitating factors,
and outcomes between these two populations remain
limited.
Methodology:
In this retrospective observational study, all adult DKA
admissions with T1DM or T2DM at a tertiary centre between
2001 and 2025 were studied. DKA was defined according
to standard biochemical criteria. Electronic medical records were reviewed to extract demographic data, biochemical
parameters, precipitating factors, management details, and
clinical outcomes of all adult DKA admission in T1DM and
T2DM. Patients aged <18 years or those with incomplete
data were excluded.
Results:
A total of 601 DKA episodes were analyzed, comprising
130 (21.6%) in patients with T1DM and 471 (78.4%) in those
with T2DM. Mean age was 26.9 ± 0.71 years for T1DM and
52.1 ± 0.7 years for T2DM. Gender distribution was balanced
(male 48.3%, female 51.7%). Mean hemoglobin A1c (HbA1c)
was 11.3 ± 0.3% in T1DM and 12.1 ± 0.2% in T2DM. Infection
was the most common precipitating factor overall (69.0%),
occurring more frequently in T2DM than in T1DM (74.7%
vs. 56.2%), followed by medication non-adherence (62.4%
vs. 43.8%). Significant differences were observed between
groups in admission pH, bicarbonate (both p <0.001), blood
ketones (p = 0.028), and HbA1c (p = 0.010), whereas anion
gap (p = 0.056) and blood glucose levels (p = 0.755) did not
differ significantly. Clinical outcomes were comparable
with respect to intensive care unit (ICU) admission rates
(40.0% in T1DM vs. 39.0% in T2DM, p = 0.779) and median
resolution time (p = 0.462). However, the median length of
hospital stay was significantly longer in T2DM (8.2 ± 0.32
vs. 5.4 ± 0.4 days; p <0.001). Overall mortality was 6.0%,
with substantially higher mortality in T2DM compared to
T1DM (7.4% vs. 0.8%, p = 0.013).
Conclusion
In this large regional series of adult DKA, most episodes
occurred in T2DM. Despite similar ICU admission rates
and time to resolution, T2DM was associated with more
frequent infection-related precipitants, longer hospital
stays, and higher mortality, underscoring the need for
targeted preventive strategies in this population.
Adult
;
Diabetes Mellitus, Type 1
;
Diabetic Ketoacidosis
;
Diabetes Mellitus, Type 2
5.Diabetic Ketoacidosis in Pregnancy: Clinical Triggers, Outcomes, and Missed Opportunities—A Case Series
Jia Whey Jacelyn Ong ; Chin Voon Tong ; Raja Nurazni binti Raja Azwan ; Adilah Zulaikha binti Abd Latib ; Hidayatil Alimi bin Keya Nordin ; Qin Zhi Lee ; Kean Heng Lim ; Jia Ling Low ; Mohd Fyzal bin Bahrudin ; Syaza binti Izhar Hisham ; Liang Wei Wong ; Lisa Mohamed Nor ; Nurain Mohd Noorr
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):48-49
Introduction:
Diabetic ketoacidosis (DKA) in pregnancy is an uncommon
yet life-threatening emergency, with disproportionate risks
to both mother and fetus. Pregnancy-specific physiological changes predispose patients to rapid metabolic decompensation, often with atypical presentations. Despite
this, local data remain limited. We describe the clinical
profile, precipitating factors, and outcomes of DKA in
pregnancy in a tertiary centre, with emphasis on potentially
preventable triggers.
Cases:
Nine pregnant patients with DKA were identified from a
retrospective review of all cases admitted for DKA from
2002 to 2025. Mean age was 31.67 ± 5.20 years; all were
Malay. The majority had type 2 diabetes mellitus (55.6%),
followed by type 1 diabetes (33.3%) and latent autoimmune
diabetes in adults (11.1%). The mean period of amenorrhea
was 19.67 ± 12.62 weeks.
Infection was the leading precipitant (44.4%), with
additional triggers including insulin omission (22.2%),
hyperemesis gravidarum, preterm labor, steroid exposure,
and perioperative fasting. Most diagnoses were made in
the emergency department (55.6%).
Biochemical parameters reflected significant severity (mean
bicarbonate 7.89 ± 2.98 mmol/L; anion gap 25.00 ± 5.81),
with 88.9% classified as severe DKA. Intensive Care Unit
(ICU) care was required in 77.8% of cases. The majority
(77.8%) were admitted to the ICU unit, with a median time
to resolution of 13.00 ± 12.00 hours (interquartile range
[IQR]), and the median hospital length of stay was 7.00 ±
5.00 days (IQR).
Complications during treatment included hypokalemia
(33.3%), acute kidney injury (22.2%), and hypoglycemia
(11.1%). Rebound DKA occurred in one-third of patients.
All patients were discharged clinically stable. Outcome
data demonstrated pregnancy loss in three cases and one
preterm birth.
Conclusion
DKA in pregnancy remains a severe and resource-intensive
condition. This series highlights missed opportunities in
prevention, with modifiable precipitants such as infection
and insulin omission commonly identified. The high
severity at presentation suggests delays in recognition.
Early detection, optimized metabolic care, and targeted
preventive strategies are crucial to improving maternal
and fetal outcomes.
Female
;
Pregnancy
;
Diabetic Ketoacidosis
6.Too Low From a Self-Blow: Diagnostic and Therapeutic Challenges in a Case of Hirata’s Syndrome
Tharsini Sarvanandan ; Ying Guat Ooi ; Jun Kit Khoo ; Tricia Lopez ; Nicholas Ken Yoong Hee ; Shireene Vethakkan ; Lee-Ling Lim ; Jeyakantha Ratnasingam ; Carolyn Chee ; Pavai Sthaneshwar ; Quan Hziung Lim
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):50-
Introduction:
Non-diabetic hypoglycemia in older adults warrants
careful evaluation across insulin-mediated and noninsulin-mediated causes. We present a challenging case of
insulin autoimmune syndrome (IAS; Hirata’s syndrome).
Case:
An 85-year-old female presented with severe hypoglycemia (capillary blood glucose [CBG] 1.8 mmol/L) with
reduced consciousness, preceded by 2 months of recurrent
dizziness relieved by food intake. Appetite and weight were
stable. Past medical history included stage 3 chronic kidney
disease and osteoporosis, but no diabetes. Medication
review revealed a recent 2-week course of traditional
supplement, long-term Neurobion®, but no agents with
recognized hypoglycemic potential. Physical examination
showed a moderately built elderly female with a body
mass index of 24.3 kg/m² and no Cushingoid features.
Recurrent hypoglycemia (CBG nadir 1.5 mmol/L) occurred
in both fasting and postprandial states, fulfilling Whipple’s
triad. Baseline investigations showed an estimated
glomerular filtration rate of 42 mL/min/1.73 m², AM
cortisol of 700 mmol/L, and unremarkable liver and thyroid
function tests. During a hypoglycemic episode (CBG 2.3
mmol/L), plasma insulin and C-peptide were inappropriately raised at 203.6 mU/L (reference interval [RI]: 3.0–
25.0) and 33 ng/mL (RI: 0.9–7.1), respectively, confirming
endogenous hyperinsulinemic hypoglycemia. Polyethylene
glycol precipitation showed 21% insulin recovery, raising
suspicion for an autoimmune cause. Elevated insulin
autoantibodies (175 AU/mL; RI <20) confirmed IAS.
Computed tomography of the abdomen and endoscopic
ultrasound excluded a pancreatic neuro-endocrine tumor.
Nutritional management comprising frequent low glycemic
index feeds and uncooked cornstarch was commenced.
Diazoxide 100 mg TDS caused fluid overload and severe
hyponatremia, while hypoglycemia persisted at lower doses, necessitating discontinuation. Subcutaneous octreotide 100 mg QID was required to control hypoglycemia.
Prednisolone 30 mg BD improved glycemic stability. Insulin
autoantibodies titer remained 175 AU/mL at 2 weeks;
reassessment was conducted at 4 weeks with consideration for biologics if persistent.
:
doses, necessitating discontinuation. Subcutaneous octreotide 100 mg QID was required to control hypoglycemia.
Prednisolone 30 mg BD improved glycemic stability. Insulin
autoantibodies titer remained 175 AU/mL at 2 weeks;
reassessment was conducted at 4 weeks with consideration for biologics if persistent.
Conclusion
Endogenous hyperinsulinemic hypoglycemia, after
excluding insulinoma, should raise suspicion for IAS.
Management includes removing triggers, supportive care,
and immunomodulatory therapy in severe cases.
7.Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women
Claudia Ha-ting TAM ; Ying WANG ; Chi Chiu WANG ; Lai Yuk YUEN ; Cadmon King-poo LIM ; Junhong LENG ; Ling WU ; Alex Chi-wai NG ; Yong HOU ; Kit Ying TSOI ; Hui WANG ; Risa OZAKI ; Albert Martin LI ; Qingqing WANG ; Juliana Chung-ngor CHAN ; Yan Chou YE ; Wing Hung TAM ; Xilin YANG ; Ronald Ching-wan MA
Diabetes & Metabolism Journal 2025;49(1):128-143
Background:
The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications.
Methods:
We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants.
Results:
Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals.
Conclusion
Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.
8.Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women
Claudia Ha-ting TAM ; Ying WANG ; Chi Chiu WANG ; Lai Yuk YUEN ; Cadmon King-poo LIM ; Junhong LENG ; Ling WU ; Alex Chi-wai NG ; Yong HOU ; Kit Ying TSOI ; Hui WANG ; Risa OZAKI ; Albert Martin LI ; Qingqing WANG ; Juliana Chung-ngor CHAN ; Yan Chou YE ; Wing Hung TAM ; Xilin YANG ; Ronald Ching-wan MA
Diabetes & Metabolism Journal 2025;49(1):128-143
Background:
The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications.
Methods:
We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants.
Results:
Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals.
Conclusion
Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.
9.Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women
Claudia Ha-ting TAM ; Ying WANG ; Chi Chiu WANG ; Lai Yuk YUEN ; Cadmon King-poo LIM ; Junhong LENG ; Ling WU ; Alex Chi-wai NG ; Yong HOU ; Kit Ying TSOI ; Hui WANG ; Risa OZAKI ; Albert Martin LI ; Qingqing WANG ; Juliana Chung-ngor CHAN ; Yan Chou YE ; Wing Hung TAM ; Xilin YANG ; Ronald Ching-wan MA
Diabetes & Metabolism Journal 2025;49(1):128-143
Background:
The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications.
Methods:
We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants.
Results:
Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals.
Conclusion
Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.
10.Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women
Claudia Ha-ting TAM ; Ying WANG ; Chi Chiu WANG ; Lai Yuk YUEN ; Cadmon King-poo LIM ; Junhong LENG ; Ling WU ; Alex Chi-wai NG ; Yong HOU ; Kit Ying TSOI ; Hui WANG ; Risa OZAKI ; Albert Martin LI ; Qingqing WANG ; Juliana Chung-ngor CHAN ; Yan Chou YE ; Wing Hung TAM ; Xilin YANG ; Ronald Ching-wan MA
Diabetes & Metabolism Journal 2025;49(1):128-143
Background:
The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications.
Methods:
We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants.
Results:
Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals.
Conclusion
Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.


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