A study in the December 2022 issue of Diabetes explored the mechanisms behind the increased risk of developing type 2 diabetes following gestational diabetes mellitus (GDM) in South Asian women. The study from Archana Sama and colleagues compared incidence of type 2 diabetes following GDM in South Asian women compared to Nordic women.
Investigating Postpartum Diabetes Risk in South Asian Women
Previous studies identified that South Asian women who experienced GDM are at a greater risk for developing type 2 diabetes at one year postpartum, as well as an increased presence of other risk factors for cardiovascular disease. According to the authors of the study in Diabetes, “the mechanisms behind this higher risk for impaired glucose tolerance are still highly debated.”
To investigate this issue, the research team looked at insulin sensitivity, β-cell function, and hepatic insulin clearance (HIC) in a population of South Asian and Nordic women, at a mean of 17 months following GDM. The cohort included 179 South Asian and 108 Nordic women. The mean age was 35.3 years, and the mean body mass index was 29.1 kg/m2.
South Asian participants had both parents born in either Pakistan, India, Bangladesh, or Sri Lanka, while Nordic participants had parents born in Norway, Sweden, Denmark, Finland, or Iceland. Exclusions included new pregnancies after the index pregnancy, exclusive breastfeeding at the time of examination, known diabetes prior to index pregnancy, ongoing inflammatory disease or other serious comorbidity, or a surgical procedure fewer than 3 months before the study.
Participants underwent a physical examination, blood collection, and oral glucose tolerance test using deconvolution of C-peptide kinetics. The use of C-peptide kinetics was selected to estimate participants’ HIC. “Emerging evidence suggests that lower HIC could contribute to increased peripheral insulin levels and acts as an early adaption to insulin resistance and hyperglycemia,” the authors wrote. “On the other hand, higher insulin levels are also associated with higher insulin resistance and an increased risk of type 2 diabetes. Although HIC is difficult to measure directly in humans, it can be estimated indirectly by prehepatic insulin levels based on C-peptide deconvolution kinetics.”
Insulin Sensitivity and HIC Following Pregnancy
At the time of measurement, 31% of South Asian women were normoglycemic, compared with 53% of Nordic women. Notably, South Asian participants had higher parity and more first-degree relatives with a history of diabetes than Nordic participants.
In the subgroup of patients with normal glucose tolerance (NGT), there were no statistical differences between ethnicities with regards to fasting or 2-hour glucose tolerance findings. However, South Asian participants had a 7% higher area under the curve (AUC) for glucose (P<.001). In addition, the AUCs for prehepatic and peripheral insulin were both significantly higher for South Asian women compared to Nordic women (23% higher and 67% higher, respectively; both P<.001). South Asian women in the NGT group demonstrated lower insulin sensitivity, disposition index, and fasting hepatic insulin clearance compared to Nordic women.
Sixty-nine percent of South Asian participants and 47% of Nordic participants were considered prediabetic or diabetic. In this subgroup, there were no ethnic differences found in AUCs for glucose and prehepatic insulin. However, South Asian participants in this cohort had a higher AUC for peripheral insulin than Nordic participants (34% higher; P<.01). Similar to the NGT subgroup, South Asian women in the prediabetic or diabetic group had lower insulin sensitivity, disposition index, and fasting hepatic insulin clearance.
Importance of Waist-to-Height Ratio
The authors found that “the waist-to-height ratio mediated ∼25–40% of the ethnic differences in insulin sensitivity in participants with normoglycemia.”
“Our data in women with NGT indicate that waist-to-height ratio, potentially capturing important ethnic differences in body composition and central fat accumulation, mediated significant ethnic differences in insulin sensitivity,” the authors summarized. They suggested that “central adiposity is instrumental for the lower insulin sensitivity in South Asian individuals. This is important, as the Diabetes Prevention Program reported a 50% decline in type 2 diabetes incidence after GDM if weight loss was obtained, while no effect on glucose deterioration was observed in a similar study in South Asian individuals without weight loss.”
Regarding limitations, the author acknowledged that the findings are not applicable to women without a history of GDM, as well as differences in age between Nordic and South Asian participants. “The older age among participating Nordic women could have led to an overestimation of the proportion of women with prediabetes or diabetes in this group and, thereby, might have led to an underestimation of the ethnic differences in prevalence,” the authors wrote.
In summary, the authors stated that “South Asian women with NGT investigated a few years after GDM showed lower β-cell function, lower HIC, and higher insulin resistance compared with Nordic women,” the authors wrote. “Our novel observations accordingly add to our understanding of diabetes pathophysiology in South Asian and White people in general and in the context of previous GDM.”
References
- Sharma A, Lee-Ødegård S, Qvigstad E, et al. β-Cell Function, Hepatic Insulin Clearance, and Insulin Sensitivity in South Asian and Nordic Women After Gestational Diabetes Mellitus. Diabetes. 2022 Dec 1;71(12):2530-2538.
- Goyal A, Gupta Y, Kalaivani M, et al. Long term (>1 year) postpartum glucose tolerance status among Indian women with history of Gestational Diabetes Mellitus (GDM) diagnosed by IADPSG criteria. Diabetes Res Clin Pract. 2018 Aug;142:154-161.
