Does abnormal insulin action or insulin secretion explain the increase in prevalence of impaired glucose metabolism with age in populations of different ethnicities?

Feng, Na; Qiao, Qing; Tuomilehto, Jaakko; Hammar, Niklas; Ho, Sai Yin; Söderberg, Stefan; Zimmet, Paul; Shaw, Jonathan E.; Nakagami, Tomoko; Mohan, Viswanathan; Ramachandran, Ambady; Lam, Tai Hing; Andersson, Shalini; Janus, Edward; Pang, Zengchang

doi:10.1002/dmrr.1078

Cited by 16 publications

(11 citation statements)

References 33 publications

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“…It remains controversial that whether insulin resistance increases with age [22][23][24]. Szoke et al discovered that aging had no effect on insulin sensitivity, which keep consistent in our finding that age was excluded from the factors affecting log HOMA2-S. An inverse relationship between age and insulin sensitivity was found by Karakelides et al [25].…”

Section: Discussionsupporting

confidence: 87%

Comparison of Insulin Resistance and β-Cell Dysfunction Between the Young and the Elderly in Normal Glucose Tolerance and Prediabetes Population: A Prospective Study

et al. 2016

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Insulin resistance and β-cell function are different between the young and elderly diabetes individuals, which are not well elaborated in the nondiabetic persons. The aims of this study were to compare insulin resistance and β-cell function between young and old adults from normal glucose tolerance (NGT) to prediabetes [which was subdivided into isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), and a combination of both (IFG/IGT)], and compare the prevalence of diabetes mellitus (DM) in the above prediabetes subgroups between different age groups after 3 years. A total of 1 374 subjects aged below 40 or above 60 years old with NGT or prediabetes were finally included in this study. Insulin resistance and β-cell function from homeostasis model assessment (HOMA) and interactive, 24-variable homeostatic model of assessment (iHOMA2) were compared between different age groups. The rate of transition to diabetes between different age groups in all pre-diabetes subgroups was also compared. Compared with the old groups, young i-IFG and IFG/IGT groups exhibit higher log HOMA-IR and log HOMA2-S, whereas the young i-IGT groups experienced comparable log HOMA-IR and log HOMA2-S when compared with old i-IFG and IFG/IGT groups. Three prediabetes subgroups all had similar log HOMA-B and log HOMA2-B between different age groups. In addition, the prevalence of diabetes in young i-IFG was statistically higher than that in old i-IFG after 3 years. Age is negatively related to log HOMA2-B in both age groups. Considering an age-related deterioration of β-cell function, young i-IFG, young i-IGT, and young IFG/IGT all suffered a greater impairment in insulin secretion than the old groups. Young i-IFG and IFG/IGT have more severe insulin resistance than the old groups. In addition, young i-IFG characterized with a higher incidence of DM than the old i-IFG. These disparities highlight that the prevention to slow progression from prediabetes to type 2 diabetes should be additionally focused in young prediabetes individuals, especially young i-IFG.

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Section: Discussionsupporting

confidence: 87%

Comparison of Insulin Resistance and β-Cell Dysfunction Between the Young and the Elderly in Normal Glucose Tolerance and Prediabetes Population: A Prospective Study

et al. 2016

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“…In the UK, individuals of South Asian descent, for example, have a substantially higher risk of developing type 2 diabetes compared with individuals of European descent [4]. There is robust evidence that reduced insulin sensitivity contributes to this elevated risk [5–7]. Beta cell dysfunction is also a plausible aetiological factor explaining elevated risk among South Asian individuals [8, 9].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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Aims/hypothesisSouth 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.MethodsIn 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.ResultsCompared 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/interpretationWe 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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“…The case for reduced insulin sensitivity is well established in South Asians from childhood to adulthood, based on measures such as fasting insulin (FINS) or HOMA insulin sensitivity (HOMA2-%S), which are directly comparable across populations [ 9 – 16 ]. The role of insulin secretion remains equivocal [ 12 , 14 ]. Reduced insulin secretion (or pancreatic functional reserve) is a plausible aetiological factor in South Asians because fetal undernutrition is common in Asian populations and may lead to reduced growth of the pancreas [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Age trajectories of glycaemic traits in non-diabetic South Asian and white individuals: the Whitehall II cohort study

et al. 2014

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Aims/hypothesisSouth Asian individuals have an increased prevalence of type 2 diabetes, but little is known about the development of glycaemic traits in this ethnic group. We compared age-related changes in glycaemic traits between non-diabetic South Asian and white participants.MethodsIn a prospective British occupational cohort with 5-yearly clinical examinations (n = 230/5,749 South Asian/white participants, age 39–79 years at baseline), age-related trajectories of fasting glucose (FG) and 2 h post-load glucose (PLG), log-transformed fasting insulin (FINS) and 2 h post-load insulin (PLINS), HOMA insulin sensitivity (HOMA2-%S) and HOMA insulin secretion (HOMA2-%B) were fitted for South Asian and white individuals who remained free of diabetes between 1991 and 2009.ResultsIn sex-adjusted multilevel models, FG was stable in white participants but increased with age in South Asians (0.12 [SE = 0.04] mmol/l per decade). PLG, FINS and PLINS levels were lower among white participants (by 0.271 [SE = 0.092] mmol/l, 0.306 [SE = 0.046] log pmol/l, 0.707 [SE = 0.059] log pmol/l at age 50, respectively) compared with South Asians, although their age-related trajectories were parallel. HOMA2-%S was higher (0.226 [SE = 0.038] at age 50) and HOMA2-%B lower (by 0.189 [SE = 0.026] at age 50) among white than South Asian participants. The age-related decline in HOMA2-%S was similar in these groups, but the age-related increase in HOMA2-%B was greater in white participants (0.04 [SE = 0.02] per decade). This difference was explained by obesity, lifestyle and social status.Conclusions/interpretationFindings from a diabetes-free population suggest an inadequate pancreatic beta cell reserve in South Asians, as a significantly steeper age-related increase in FG was observed in this ethnic group compared with white individuals.

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Does abnormal insulin action or insulin secretion explain the increase in prevalence of impaired glucose metabolism with age in populations of different ethnicities?

Cited by 16 publications

References 33 publications

Comparison of Insulin Resistance and β-Cell Dysfunction Between the Young and the Elderly in Normal Glucose Tolerance and Prediabetes Population: A Prospective Study

Comparison of Insulin Resistance and β-Cell Dysfunction Between the Young and the Elderly in Normal Glucose Tolerance and Prediabetes Population: A Prospective Study

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

Age trajectories of glycaemic traits in non-diabetic South Asian and white individuals: the Whitehall II cohort study

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