Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes: a longitudinal analysis from the Whitehall II cohort study

Adam Hulman, Rebecca K. Simmons, Eric J. Brunner, Daniel R. Witte, Kristine Færch, Dorte Vistisen, Satoyo Ikehara, Mika Kivimaki, A. Tabák

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Aims/hypothesis: South Asian individuals have reduced insulin sensitivity and increased risk of type 2 diabetes compared with white individuals. Temporal changes in glycaemic traits during middle age suggest that impaired insulin secretion is a particular feature of diabetes development among South Asians. We therefore aimed to examine ethnic differences in early changes in glucose metabolism prior to incident type 2 diabetes. Methods: In a prospective British occupational cohort, subject to 5 yearly clinical examinations, we examined ethnic differences in trajectories of fasting plasma glucose (FPG), 2 h post-load plasma glucose (2hPG), fasting serum insulin (FSI), 2 h post-load serum insulin (2hSI), HOMA of insulin sensitivity (HOMA2-S) and secretion (HOMA2-B), and the Gutt insulin sensitivity index (ISI0,120) among 120 South Asian and 867 white participants who developed diabetes during follow-up (1991–2013). We fitted cubic mixed-effects models to longitudinal data with adjustment for a wide range of covariates. Results: Compared with white individuals, South Asians had a faster increase in FPG before diagnosis (slope difference 0.22 mmol/l per decade; 95% CI 0.02, 0.42; p = 0.03) and a higher FPG level at diagnosis (0.27 mmol/l; 95% CI 0.06, 0.48; p = 0.01). They also had higher FSI and 2hSI levels before and at diabetes diagnosis. South Asians had a faster decline and lower HOMA2-S (loge-transformed) at diagnosis compared with white individuals (0.33; 95% CI 0.21, 0.46; p < 0.001). HOMA2-B increased in both ethnic groups until 7 years before diagnosis and then declined; the initial increase was faster in white individuals. ISI0,120 declined steeply in both groups before diagnosis; levels were lower among South Asians before and at diagnosis. There were no ethnic differences in 2hPG trajectories. Conclusions/interpretation: We observed different trajectories of plasma glucose, insulin sensitivity and secretion prior to diabetes diagnosis in South Asian and white individuals. This might be due to ethnic differences in the natural history of diabetes. South Asian individuals experienced a more rapid decrease in insulin sensitivity and faster increases in FPG compared with white individuals. These findings suggest more marked disturbance in beta cell compensation prior to diabetes diagnosis in South Asian individuals.

Original languageEnglish
Pages (from-to)1252-1260
Number of pages9
JournalDiabetologia
Volume60
Issue number7
DOIs
Publication statusPublished - Jul 1 2017

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Type 2 Diabetes Mellitus
Insulin Resistance
Cohort Studies
Insulin
Glucose
Fasting
Serum
Natural History
Ethnic Groups
Research Design

Keywords

  • Cohort study
  • Ethnicity
  • Glucose
  • Glycaemic trajectory
  • Insulin
  • South Asia

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes : a longitudinal analysis from the Whitehall II cohort study. / Hulman, Adam; Simmons, Rebecca K.; Brunner, Eric J.; Witte, Daniel R.; Færch, Kristine; Vistisen, Dorte; Ikehara, Satoyo; Kivimaki, Mika; Tabák, A.

In: Diabetologia, Vol. 60, No. 7, 01.07.2017, p. 1252-1260.

Research output: Contribution to journalArticle

Hulman, Adam ; Simmons, Rebecca K. ; Brunner, Eric J. ; Witte, Daniel R. ; Færch, Kristine ; Vistisen, Dorte ; Ikehara, Satoyo ; Kivimaki, Mika ; Tabák, A. / Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes : a longitudinal analysis from the Whitehall II cohort study. In: Diabetologia. 2017 ; Vol. 60, No. 7. pp. 1252-1260.
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abstract = "Aims/hypothesis: South Asian individuals have reduced insulin sensitivity and increased risk of type 2 diabetes compared with white individuals. Temporal changes in glycaemic traits during middle age suggest that impaired insulin secretion is a particular feature of diabetes development among South Asians. We therefore aimed to examine ethnic differences in early changes in glucose metabolism prior to incident type 2 diabetes. Methods: In a prospective British occupational cohort, subject to 5 yearly clinical examinations, we examined ethnic differences in trajectories of fasting plasma glucose (FPG), 2 h post-load plasma glucose (2hPG), fasting serum insulin (FSI), 2 h post-load serum insulin (2hSI), HOMA of insulin sensitivity (HOMA2-S) and secretion (HOMA2-B), and the Gutt insulin sensitivity index (ISI0,120) among 120 South Asian and 867 white participants who developed diabetes during follow-up (1991–2013). We fitted cubic mixed-effects models to longitudinal data with adjustment for a wide range of covariates. Results: Compared with white individuals, South Asians had a faster increase in FPG before diagnosis (slope difference 0.22 mmol/l per decade; 95{\%} CI 0.02, 0.42; p = 0.03) and a higher FPG level at diagnosis (0.27 mmol/l; 95{\%} CI 0.06, 0.48; p = 0.01). They also had higher FSI and 2hSI levels before and at diabetes diagnosis. South Asians had a faster decline and lower HOMA2-S (loge-transformed) at diagnosis compared with white individuals (0.33; 95{\%} CI 0.21, 0.46; p < 0.001). HOMA2-B increased in both ethnic groups until 7 years before diagnosis and then declined; the initial increase was faster in white individuals. ISI0,120 declined steeply in both groups before diagnosis; levels were lower among South Asians before and at diagnosis. There were no ethnic differences in 2hPG trajectories. Conclusions/interpretation: We observed different trajectories of plasma glucose, insulin sensitivity and secretion prior to diabetes diagnosis in South Asian and white individuals. This might be due to ethnic differences in the natural history of diabetes. South Asian individuals experienced a more rapid decrease in insulin sensitivity and faster increases in FPG compared with white individuals. These findings suggest more marked disturbance in beta cell compensation prior to diabetes diagnosis in South Asian individuals.",
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T1 - Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes

T2 - a longitudinal analysis from the Whitehall II cohort study

AU - Hulman, Adam

AU - Simmons, Rebecca K.

AU - Brunner, Eric J.

AU - Witte, Daniel R.

AU - Færch, Kristine

AU - Vistisen, Dorte

AU - Ikehara, Satoyo

AU - Kivimaki, Mika

AU - Tabák, A.

PY - 2017/7/1

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N2 - Aims/hypothesis: South Asian individuals have reduced insulin sensitivity and increased risk of type 2 diabetes compared with white individuals. Temporal changes in glycaemic traits during middle age suggest that impaired insulin secretion is a particular feature of diabetes development among South Asians. We therefore aimed to examine ethnic differences in early changes in glucose metabolism prior to incident type 2 diabetes. Methods: In a prospective British occupational cohort, subject to 5 yearly clinical examinations, we examined ethnic differences in trajectories of fasting plasma glucose (FPG), 2 h post-load plasma glucose (2hPG), fasting serum insulin (FSI), 2 h post-load serum insulin (2hSI), HOMA of insulin sensitivity (HOMA2-S) and secretion (HOMA2-B), and the Gutt insulin sensitivity index (ISI0,120) among 120 South Asian and 867 white participants who developed diabetes during follow-up (1991–2013). We fitted cubic mixed-effects models to longitudinal data with adjustment for a wide range of covariates. Results: Compared with white individuals, South Asians had a faster increase in FPG before diagnosis (slope difference 0.22 mmol/l per decade; 95% CI 0.02, 0.42; p = 0.03) and a higher FPG level at diagnosis (0.27 mmol/l; 95% CI 0.06, 0.48; p = 0.01). They also had higher FSI and 2hSI levels before and at diabetes diagnosis. South Asians had a faster decline and lower HOMA2-S (loge-transformed) at diagnosis compared with white individuals (0.33; 95% CI 0.21, 0.46; p < 0.001). HOMA2-B increased in both ethnic groups until 7 years before diagnosis and then declined; the initial increase was faster in white individuals. ISI0,120 declined steeply in both groups before diagnosis; levels were lower among South Asians before and at diagnosis. There were no ethnic differences in 2hPG trajectories. Conclusions/interpretation: We observed different trajectories of plasma glucose, insulin sensitivity and secretion prior to diabetes diagnosis in South Asian and white individuals. This might be due to ethnic differences in the natural history of diabetes. South Asian individuals experienced a more rapid decrease in insulin sensitivity and faster increases in FPG compared with white individuals. These findings suggest more marked disturbance in beta cell compensation prior to diabetes diagnosis in South Asian individuals.

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KW - Cohort study

KW - Ethnicity

KW - Glucose

KW - Glycaemic trajectory

KW - Insulin

KW - South Asia

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