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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
43
Eight weeks of supervised training with four sessions per week: two whole-body resistance training sessions and two high-intensity interval cycling sessions, totalling approximately five hours of vigorous exercise per week. Resistance sessions comprised three lower-body and six upper-body exercises, 1-4 sets per exercise, progressing from 19 sets in the first sessions to 28 sets in the last sessions. Each set consisted of 12 repetitions during weeks 1-3 and 10 repetitions during weeks 4-8, with 1-4 repetitions in reserve. Interval sessions were performed on a cycle ergometer. One weekly session used 7-minute bouts at 82-87% of maximal heart rate with 3 minutes of rest between bouts, progressing from 3 to 5 bouts. The other weekly session used 2-minute bouts at an intensity reaching at least 90% of maximal heart rate during the final 30 seconds, with 2 minutes of rest between bouts, progressing from 6 to 9 bouts.
Aker sykehus
Oslo, Norway
Change in postprandial whole-body insulin sensitivity measured as glucose metabolic clearance rate per unit insulin (MCR/I)
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.
Time frame: Baseline and 8 weeks (at 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)
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.
Time frame: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Change in suppression of endogenous glucose production (EGP) during oral glucose tolerance test
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.
Time frame: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Change in duration of suppression of endogenous glucose production (EGP) during oral glucose tolerance test
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.
Time frame: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Change in suppression of glycerol rate of appearance (Ra) during oral glucose tolerance test
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.
Time frame: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Change in duration of suppression of glycerol rate of appearance (Ra) during oral glucose tolerance test
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.
Time frame: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Change in hepatic insulin resistance index (Hepatic IR)
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.
Time frame: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Change in adipose tissue insulin resistance index (Lipo-IR)
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.
Time frame: 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
Maximal oxygen uptake (VO2max) measured during a graded cardiopulmonary exercise test to volitional exhaustion on an electronically braked cycle ergometer (Lode Excalibur Sport). The protocol starts at 30 W and increases by 20 W every minute. Gas exchange is measured continuously with a mixing-chamber ergospirometry system (Vyntus CPX). VO2max is defined as the highest oxygen uptake sampled over a 60-second interval and is expressed in mL/kg/min. The outcome is the change from baseline to the end of the 8-week exercise intervention.
Time frame: 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
Maximal upper body muscle strength assessed as one-repetition maximum (1RM) in the chest press exercise on a weight-stack machine (Technogym Selection Line), expressed in kilograms. Participants are familiarised with the equipment and lifting technique on a separate day before testing. After a standardised warm-up, load is increased stepwise until the heaviest load that can be lifted once through the full range of motion with correct technique is reached, normally within 2-5 attempts with 2-3 minutes of rest between attempts. Grip width is standardised. The outcome is the change from baseline to the end of the 8-week exercise intervention.
Time frame: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Change in maximal lower body strength measured as one-repetition maximum (1RM) in leg press
Maximal lower body muscle strength assessed as one-repetition maximum (1RM) in the leg press exercise on a weight-stack machine (Technogym Selection Line), expressed in kilograms. Participants are familiarised with the equipment and lifting technique on a separate day before testing. After a standardised warm-up, load is increased stepwise until the heaviest load that can be lifted once through the full range of motion with correct technique is reached, normally within 2-5 attempts with 2-3 minutes of rest between attempts. Knee flexion is standardised at 90 degrees. The outcome is the change from baseline to the end of the 8-week exercise intervention.
Time frame: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
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Sustained change in 2-hour plasma glucose during 75 g oral glucose tolerance test at 12-month follow-up
At a single follow-up visit approximately 12 months after completion of the 8-week exercise intervention, glucose tolerance was reassessed with a shortened 75 g oral glucose tolerance test lasting 2 hours and performed without stable-isotope tracers. The outcome is the plasma glucose concentration measured 120 minutes after glucose ingestion, expressed in mmol/L. Lower values indicate better glucose tolerance. The outcome describes whether the change observed immediately after the intervention was sustained at 12 months.
Time frame: 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
Fat mass assessed by bioelectrical impedance analysis at a single follow-up visit approximately 12 months after completion of the 8-week exercise intervention, expressed in kilograms. The outcome describes whether the change observed immediately after the intervention was sustained at 12 months.
Time frame: 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
Interstitial glucose recorded continuously for 14 days during free-living conditions using a continuous glucose monitor, at a single follow-up visit approximately 12 months after completion of the 8-week exercise intervention. The outcome is the mean interstitial glucose concentration across the recording period, expressed in mmol/L. Lower values indicate better free-living glycaemic control. The outcome describes whether the change observed immediately after the intervention was sustained at 12 months.
Time frame: 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
Insulin sensitivity estimated from the shortened 2-hour 75 g oral glucose tolerance test performed at a single follow-up visit approximately 12 months after completion of the 8-week exercise intervention, without stable-isotope tracers. The oral glucose insulin sensitivity index (OGIS, Mari et al.) is calculated from plasma glucose at 0, 90 and 120 minutes and plasma insulin at 0 and 90 minutes, together with body surface area, and is expressed in mL/min/m2. Higher values indicate greater insulin sensitivity. The outcome describes whether the change observed immediately after the intervention was sustained at 12 months.
Time frame: 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
Fat-free mass assessed by bioelectrical impedance analysis at a single follow-up visit approximately 12 months after completion of the 8-week exercise intervention, expressed in kilograms. The outcome describes whether the change observed immediately after the intervention was sustained at 12 months.
Time frame: Baseline, 8 weeks, and 12 months after completion of the 8-week exercise intervention
Sustained change in body weight at 12-month follow-up
Body weight measured on a calibrated scale at a single follow-up visit approximately 12 months after completion of the 8-week exercise intervention, expressed in kilograms. The outcome describes whether the change observed immediately after the intervention was sustained at 12 months.
Time frame: Baseline, 8 weeks, and 12 months after completion of the 8-week exercise intervention
Sustained change in waist circumference at 12-month follow-up
Waist circumference measured with a tape measure at a single follow-up visit approximately 12 months after completion of the 8-week exercise intervention, expressed in centimetres. The outcome describes whether the change observed immediately after the intervention was sustained at 12 months.
Time frame: Baseline, 8 weeks, and 12 months after completion of the 8-week exercise intervention
Sustained change in hip circumference at 12-month follow-up
Hip circumference measured with a tape measure at a single follow-up visit approximately 12 months after completion of the 8-week exercise intervention, expressed in centimetres. The outcome describes whether the change observed immediately after the intervention was sustained at 12 months.
Time frame: 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
Whole-body insulin sensitivity estimated from plasma glucose and insulin concentrations measured during the 75 g oral glucose tolerance test, without the use of stable-isotope tracers. The Matsuda index is calculated from the fasting and mean postprandial plasma glucose and insulin concentrations and is reported as a dimensionless index. Higher values indicate greater insulin sensitivity. The outcome is the change from baseline to the end of the 8-week exercise intervention.
Time frame: Baseline and 8 weeks (at the end of the 8-week exercise intervention)
Change in fasting insulin resistance measured as HOMA-IR
Fasting insulin resistance estimated from fasting plasma glucose and fasting plasma insulin concentrations, without the use of stable-isotope tracers. HOMA-IR is calculated with the standard homeostasis model assessment formula as the product of fasting glucose and fasting insulin divided by a fixed constant, and is reported as a dimensionless index. Higher values indicate greater insulin resistance. The outcome is the change from baseline to the end of the 8-week exercise intervention.
Time frame: Baseline and 8 weeks (at the end of the 8-week exercise intervention)