Original Article

Acta Diabetologica

, Volume 52, Issue 1, pp 11-19

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Failing beta-cell adaptation in South Asian families with a high risk of type 2 diabetes

  • Sjaam JainandunsingAffiliated withDepartment of Internal Medicine, Erasmus MC - University Medical Center Rotterdam
  • , Behiye ÖzcanAffiliated withDepartment of Internal Medicine, Erasmus MC - University Medical Center Rotterdam
  • , Trinet RietveldAffiliated withDepartment of Internal Medicine, Erasmus MC - University Medical Center Rotterdam
  • , Joram N. I. van MiertAffiliated withDepartment of Internal Medicine, Erasmus MC - University Medical Center Rotterdam
  • , Aaron J. IsaacsAffiliated withDepartment of Epidemiology, Erasmus MC - University Medical Center Rotterdam
  • , Janneke G. LangendonkAffiliated withDepartment of Internal Medicine, Erasmus MC - University Medical Center Rotterdam
  • , Felix W. M. de RooijAffiliated withDepartment of Internal Medicine, Erasmus MC - University Medical Center Rotterdam Email author 
  • , Eric J. G. SijbrandsAffiliated withDepartment of Internal Medicine, Erasmus MC - University Medical Center Rotterdam

Abstract

We performed an extended oral glucose tolerance test (OGTT) to investigate the relationship between early and late beta-cell response and type 2 diabetes (T2D) in families of South Asian origin and indigenous Dutch, burdened by T2D. Based on the OGTT, 22 individuals were normoglycemic, 12 glucose intolerant and 23 had T2D in the South Asian families; these numbers were 34, 12 and 18 in the Caucasian families, respectively. The OGTT had 11 blood samplings in 3.5 h for glucose, insulin and C-peptide measurements. Through early and late insulin secretion rate (ISR), the above basal glucose area-under-the-curve after glucose load (glucose disposal) and insulin sensitivity index (ISI), we obtained early and late disposition indices (DI). South Asians on average had lower ISI than Caucasians (3.8 ± 2.9 vs. 6.5 ± 4.7, respectively, P < 0.001), with rapid decline of their early and late DI between normal glucose tolerance versus impaired fasting glucose/impaired glucose tolerance (late DI; P < 0.0001). Adjusted for ISI, age, gender and waist-to-hip ratio, early ISR was significantly associated with glucose disposal in South Asians (β = 0.55[0.186; 0.920]), but not in Caucasians (β = 0.09[−0.257; 0.441]). Similarly, early ISR was strongly associated with late ISR (β = 0.71[0.291; 1.123]; R 2 = 45.5 %) in South Asians, but not in Caucasians (β = 0.27[−0.035; 0.576]; R 2 = 17.4 %), with significant interaction between ethnicity and early ISR (β = 0.341[0.018; 0.664]). Ordinal regression analyses confirmed that all South Asian OGTT subgroups were homogenously resistant to insulin and solely predicted by early ISR (β = −0.782[−1.922; 0.359], β = −0.020[−0.037; −0.002], respectively), while in Caucasian families both ISI and early ISR were related to glucose tolerance state (β = −0.603[−1.105; −0.101], β = −0.066[−0.105; −0.027], respectively). In South Asian individuals, rapid beta-cell deterioration might occur under insulin resistant conditions. As their early insulin response correlates strongly with both glucose disposal and late insulin response, alterations in beta-cell dynamics may give an explanation to their extreme early onset of T2D, although larger prospective studies are required.

Keywords

Type 2 diabetes OGTT: insulin Glucose South Asian