Effects of Physical Exercise on Glucose Metabolism and Related Metabolic Signatures in South Asian and Nordic Women With Previous Gestational Diabetes (DIASA-Ex)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Change in postprandial whole-body insulin sensitivity measured as glucose metabolic clearance rate per unit insulin (MCR/I)
研究概览
简要总结
South Asian women have a high risk of developing type 2 diabetes, and the risk is particularly high after gestational diabetes. This study examined whether eight weeks of supervised vigorous exercise improves insulin sensitivity in South Asian women with previous gestational diabetes, and whether the response differs from that of Nordic women with the same history.
Participants trained four times per week, with two whole-body resistance sessions and two high-intensity interval cycling sessions. Before and after the intervention, insulin sensitivity was measured with an oral glucose tolerance test combined with stable-isotope tracers, and cardiorespiratory fitness, muscle strength and body composition were assessed. Blood, urine and tissue samples were collected for multi-omics analyses.
详细描述
Background: South Asians develop type 2 diabetes approximately ten years earlier than people of Nordic origin and at a lower body mass index. Women with previous gestational diabetes are at particularly high risk and represent an informative model of early diabetes pathophysiology, characterised by insulin resistance and inadequate beta-cell compensation. The effect of vigorous exercise on tissue-specific insulin resistance in this population has not been established.
Objective
To assess the effect of an eight-week supervised exercise intervention on insulin sensitivity in South Asian women with previous gestational diabetes, to compare the response with that of Nordic women with previous gestational diabetes, and to characterise the underlying molecular changes across tissues.
Design: Single-centre, single-group interventional study with identical assessments before and after the intervention in two ethnic groups (South Asian and Nordic).
Intervention: Eight weeks of supervised training comprising two whole-body resistance sessions and two high-intensity interval cycling sessions per week, corresponding to approximately five hours of vigorous exercise per week. Resistance sessions included three lower-body and six upper-body exercises with 1-4 sets per exercise. Interval sessions were performed on a cycle ergometer and used 2-minute and 7-minute work bouts, with one session of each type per week. Participants were instructed not to change their habitual diet, which was monitored by 24-hour dietary recall before and after the intervention.
Assessments before and after the intervention: a 75 g oral glucose tolerance test combined with stable-isotope tracer infusion to quantify whole-body, hepatic, skeletal muscle and adipose tissue insulin sensitivity; C-peptide deconvolution to estimate insulin secretion and hepatic insulin clearance; indirect calorimetry; maximal oxygen uptake by cardiopulmonary exercise testing; one-repetition maximum tests of upper and lower body strength; body composition and fat distribution by imaging; and collection of blood, urine, subcutaneous adipose tissue and skeletal muscle for DNA methylation, transcriptomic, proteomic, metabolomic and lipidomic analyses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Woman aged 18 years or older
- •Previous gestational diabetes
- •South Asian or Nordic origin, with both parents of the same ethnic background
排除标准
- •Habitual physical activity above national recommendations (more than 75 minutes of vigorous exercise per week) at inclusion
- •Known type 1 or type 2 diabetes
- •Use of glucose-lowering medication, or other drugs known to interfere with glucose or lipid metabolism or with the response to exercise
- •Pregnancy
- •Liver, renal, cardiopulmonary, oncological or other debilitating disease that could jeopardise participant safety or compliance with the protocol
研究组 & 干预措施
Exercise
All participants received the same supervised exercise programme: eight weeks of combined resistance and high-intensity aerobic training, four sessions per week. Both ethnic groups (South Asian and Nordic) followed the identical regime.
干预措施: Exercise (Behavioral)
结局指标
主要结局
Change in postprandial whole-body insulin sensitivity measured as glucose metabolic clearance rate per unit insulin (MCR/I)
时间窗: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Whole-body (predominantly skeletal muscle) insulin sensitivity assessed during a 75 g oral glucose tolerance test combined with a 6-hour triple stable-isotope tracer study: a primed continuous intravenous infusion of \[6,6-2H2\]glucose and \[1,1,2,3,3-2H5\]glycerol, plus 2.5 g oral \[U-13C\]glucose. Insulin sensitivity is expressed as the postprandial glucose metabolic clearance rate relative to the corresponding plasma insulin concentration (MCR/I, mL/min/kg per nmol/L). Higher values indicate greater insulin sensitivity. The outcome is the change from baseline to the end of the 8-week exercise intervention.
Change in fasting whole-body insulin sensitivity measured as glucose metabolic clearance rate per unit insulin (MCR/I)
时间窗: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Fasting whole-body insulin sensitivity assessed during a 6-hour triple stable-isotope tracer study with a primed continuous intravenous infusion of \[6,6-2H2\]glucose and \[1,1,2,3,3-2H5\]glycerol. Insulin sensitivity is expressed as the fasting glucose metabolic clearance rate relative to the corresponding plasma insulin concentration (MCR/I, mL/min/kg per nmol/L). Higher values indicate greater insulin sensitivity. The outcome is the change from baseline to the end of the 8-week exercise intervention.
Change in suppression of endogenous glucose production (EGP) during oral glucose tolerance test
时间窗: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Hepatic insulin sensitivity assessed as the suppression of endogenous glucose production (EGP) during a 75 g oral glucose tolerance test combined with a 6-hour triple stable-isotope tracer study. EGP is calculated with the Steele non-steady-state one-compartment model from \[6,6-2H2\]glucose and oral \[U-13C\]glucose enrichments. The outcome is the absolute suppression of EGP from the fasting value during the test, expressed in mmol/min/kg. Greater suppression indicates greater hepatic insulin sensitivity. The outcome is the change from baseline to the end of the 8-week exercise intervention.
Change in duration of suppression of endogenous glucose production (EGP) during oral glucose tolerance test
时间窗: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Duration of hepatic insulin action assessed during a 75 g oral glucose tolerance test combined with a 6-hour triple stable-isotope tracer study. Endogenous glucose production (EGP) is calculated with the Steele non-steady-state one-compartment model from \[6,6-2H2\]glucose and oral \[U-13C\]glucose enrichments. The outcome is the time for which EGP remains suppressed below the fasting rate, expressed in minutes. Longer duration indicates more sustained hepatic insulin action. The outcome is the change from baseline to the end of the 8-week exercise intervention.
Change in suppression of glycerol rate of appearance (Ra) during oral glucose tolerance test
时间窗: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Adipose tissue insulin sensitivity assessed as the suppression of lipolysis during a 75 g oral glucose tolerance test combined with a 6-hour triple stable-isotope tracer study. Whole-body glycerol rate of appearance (Ra) is calculated with the Steele non-steady-state one-compartment model from a primed continuous infusion of \[1,1,2,3,3-2H5\]glycerol. The outcome is the absolute suppression of glycerol Ra from the fasting value over the first 60 minutes of the test, expressed in mmol/min/kg. Greater suppression indicates greater adipose tissue insulin sensitivity. The outcome is the change from baseline to the end of the 8-week exercise intervention.
Change in duration of suppression of glycerol rate of appearance (Ra) during oral glucose tolerance test
时间窗: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Duration of adipose tissue insulin action assessed during a 75 g oral glucose tolerance test combined with a 6-hour triple stable-isotope tracer study. Whole-body glycerol rate of appearance (Ra) is calculated with the Steele non-steady-state one-compartment model from a primed continuous infusion of \[1,1,2,3,3-2H5\]glycerol. The outcome is the time for which glycerol Ra remains suppressed below the fasting rate, expressed in minutes. Longer duration indicates more sustained suppression of lipolysis. The outcome is the change from baseline to the end of the 8-week exercise intervention.
Change in hepatic insulin resistance index (Hepatic IR)
时间窗: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Hepatic insulin resistance assessed in the fasting state during a 6-hour triple stable-isotope tracer study. The hepatic insulin resistance index (Hepatic IR) is calculated as fasting endogenous glucose production multiplied by the fasting plasma insulin concentration, following Gastaldelli 2022, and is expressed in mmol/min/kg x pmol/L. Endogenous glucose production is derived with the Steele non-steady-state one-compartment model from a primed continuous infusion of \[6,6-2H2\]glucose. Higher values indicate greater hepatic insulin resistance. The outcome is the change from baseline to the end of the 8-week exercise intervention.
Change in adipose tissue insulin resistance index (Lipo-IR)
时间窗: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Adipose tissue insulin resistance assessed in the fasting state during a 6-hour triple stable-isotope tracer study. The adipose tissue insulin resistance index (Lipo-IR) is calculated as the product of fasting glycerol rate of appearance and the fasting plasma insulin concentration, following Gastaldelli 2022, and is expressed in mmol/min/kg x pmol/L. Glycerol rate of appearance is derived with the Steele non-steady-state one-compartment model from a primed continuous infusion of \[1,1,2,3,3-2H5\]glycerol. Higher values indicate greater adipose tissue insulin resistance. The outcome is the change from baseline to the end of the 8-week exercise intervention.
次要结局
- Change in maximal lower body strength measured as one-repetition maximum (1RM) in leg press(Baseline and 8 weeks (at the end of the 8-week exercise intervention))
- Change in maximal oxygen uptake (VO2max) measured by graded cardiopulmonary exercise test on a cycle ergometer(Baseline and 8 weeks (at the end of the 8-week exercise intervention))
- Change in maximal upper body strength measured as one-repetition maximum (1RM) in chest press(Baseline and 8 weeks (at the end of the 8-week exercise intervention))
- Sustained change in 2-hour plasma glucose during 75 g oral glucose tolerance test at 12-month follow-up(Baseline, 8 weeks, and 12 months after completion of the 8-week exercise intervention)
- Sustained change in fat mass measured by bioelectrical impedance analysis at 12-month follow-up(Baseline, 8 weeks, and 12 months after completion of the 8-week exercise intervention)
- Sustained change in mean interstitial glucose measured by 14-day continuous glucose monitoring at 12-month follow-up(Baseline, 8 weeks, and 12 months after completion of the 8-week exercise intervention)
- Sustained change in insulin sensitivity measured by the oral glucose insulin sensitivity index (OGIS) at 12-month follow-up(Baseline, 8 weeks, and 12 months after completion of the 8-week exercise intervention)
- Sustained change in fat-free mass measured by bioelectrical impedance analysis at 12-month follow-up(Baseline, 8 weeks, and 12 months after completion of the 8-week exercise intervention)
- Sustained change in body weight at 12-month follow-up(Baseline, 8 weeks, and 12 months after completion of the 8-week exercise intervention)
- Sustained change in waist circumference at 12-month follow-up(Baseline, 8 weeks, and 12 months after completion of the 8-week exercise intervention)
- Sustained change in hip circumference at 12-month follow-up(Baseline, 8 weeks, and 12 months after completion of the 8-week exercise intervention)
- Change in whole-body insulin sensitivity measured as the Matsuda index(Baseline and 8 weeks (at the end of the 8-week exercise intervention))
- Change in fasting insulin resistance measured as HOMA-IR(Baseline and 8 weeks (at the end of the 8-week exercise intervention))
研究者
Sindre Lee-Ødegård
Principal Investigator
Oslo University Hospital