Contrasting associations of insulin resistance with diabetes, cardiovascular disease and all-cause mortality in the elderly: PROSPER long-term follow-up

Welsh, Paul; Preiss, David; Lloyd, Suzanne M.; Craen, Anton Jm de; Jukema, J. Wouter; Westendorp, Rudi G.J.; Buckley, Brendan M.; Kearney, Patricia M.; Briggs, Andrew; Stott, David J.; Ford, Ian; Sattar, Naveed

doi:10.1007/s00125-014-3383-9

Cited by 33 publications

(25 citation statements)

References 24 publications

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“…Information on the associations between fasting insulin and HOMA-IR with incident type 2 diabetes is scarce. In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) study, HOMA-IR was more strongly associated with incident type 2 diabetes than fasting insulin [ 25 ], which corresponds to the observations in our study. Moreover, in the PROSPER study and the San Antonio Heart Study, fasting insulin was significantly associated with the risk of developing type 2 diabetes after adjustment for confounders, while in our study the association between fasting insulin and incident type 2 diabetes was no longer statistically significant after adjusting for metabolic and lifestyle risk factors [ 25 , 26 ].…”

Section: Discussionsupporting

confidence: 88%

Size and shape of the associations of glucose, HbA1c, insulin and HOMA-IR with incident type 2 diabetes: the Hoorn Study

et al. 2017

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Aims/hypothesis Glycaemic markers and fasting insulin are frequently measured outcomes of intervention studies. To extrapolate accurately the impact of interventions on the risk of diabetes incidence, we investigated the size and shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose (2hPG), HbA 1c , fasting insulin and HOMA-IR with incident type 2 diabetes mellitus. Methods The study population included 1349 participants aged 50-75 years without diabetes at baseline (1989) from a population-based cohort in Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011 criteria or known diabetes at follow-up. Logistic regression models were used to determine the associations of the glycaemic markers, fasting insulin and HOMA-IR with incident type 2 diabetes. Restricted cubic spline logistic regressions were conducted to investigate the shape of the associations.Results After a mean follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes (11.3%); the majority were screen detected by high FPG. In multivariate adjusted models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7) for 2hPG, 3.8 (2.0, 7.2) for HbA 1c , 1.9 (0.9, 3.6) for fasting insulin and 2.8 (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA 1c with incident diabetes were non-linear, rising more steeply at higher values. Conclusions/interpretation FPG was most strongly associated with incident diabetes, followed by 2hPG, HbA 1c , HOMA-IR and fasting insulin. The strong association with FPG is probably because FPG is the most frequent marker for diabetes diagnosis. Non-linearity of associations between glycaemic markers and incident type 2 diabetes should be taken into account when estimating future risk of type 2 diabetes based on glycaemic markers.

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Section: Discussionsupporting

confidence: 88%

Size and shape of the associations of glucose, HbA1c, insulin and HOMA-IR with incident type 2 diabetes: the Hoorn Study

et al. 2017

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“…Differences in fasting glucose of 0.5 mmol/L (~5 times higher than found in the trials with higher PUFA intake in our meta-analysis) are associated with a 10% increased risk of coronary heart disease35 and a two to threefold increased risk of type 2 diabetes 36 37. Fasting insulin and HOMA-IR are related to diabetes risk, per 0.5 unit difference in HOMA-IR (~4 times the current observations), risk for diabetes increases with 20%–80% 36 38…”

Section: Discussionsupporting

confidence: 48%

Plant-derived polyunsaturated fatty acids and markers of glucose metabolism and insulin resistance: a meta-analysis of randomized controlled feeding trials

Wanders

Blom

Zock

et al. 2019

BMJ Open Diab Res Care

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The objective of this meta-analysis was to investigate the effects of plant-derived polyunsaturated fatty acids (PUFAs) on glucose metabolism and insulin resistance. Scopus and PubMed databases were searched until January 2018. Eligible studies were randomized controlled feeding trials that investigated the effects of a diet high in plant-derived PUFA as compared with saturated fatty acids (SFA) or carbohydrates and measured markers of glucose metabolism and insulin resistance as outcomes. Data from 13 relevant studies (19 comparisons of plant-derived PUFA with control) were retrieved. Plant-derived PUFA did not significantly affect fasting glucose (−0.01 mmol/L (95 % CI − 0.06 to 0.03 mmol/L)), but lowered fasting insulin by 2.6 pmol/L (−4.9 to −0.2 pmol/L) and homeostatic model assessment-insulin resistance (HOMA-IR) by 0.12 units (-0.23 to − 0.01 units). In dose–response analyses, a 5% increase in energy (En%) from PUFA significantly reduced insulin by 5.8 pmol/L (95% CI −10.2 to −1.3 pmol/L), but not glucose (change −0.07, 95% CI −0.17 to 0.04 mmol/L) and HOMA-IR (change − 0.24, 95% CI −0.56 to 0.07 units). In subgroup analyses, studies with higher PUFA dose (upper tertiles) reduced insulin (-6.7, –10.5 to −2.9 pmol/L) and HOMA-IR (-0.28, –0.45 to −0.12 units), but not glucose (−0.09, 95% CI −0.18 to 0.01 mmol/L), as compared with an isocaloric control. Subgroup analyses showed no differences in effects between SFA and carbohydrates as replacement nutrients (p interaction ≥0.05). Evidence from randomized controlled trials indicated that plant-derived PUFA as an isocaloric replacement for SFA or carbohydrates probably reduces fasting insulin and HOMA-IR in populations without diabetes.

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“…Insulin resistance, assessed by HOMA-IR, is a direct and important predictor of diabetes (Welsh et al 2014). In the present study, only HIIT improved insulin resistance and these findings were not confounded by changes in body weight or adiposity.…”

Section: Discussionmentioning

confidence: 99%

Novel all-extremity high-intensity interval training improves aerobic fitness, cardiac function and insulin resistance in healthy older adults

Hwang

Yoo

Kim

et al. 2016

Experimental Gerontology

116

100

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Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1 years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4 minutes 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4x/week for 8 weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (P<0.0001) and 4% (P=0.001) respectively in HIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; P<0.0001). Insulin resistance (homeostatic model assessment) decreased only in HIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance.

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Contrasting associations of insulin resistance with diabetes, cardiovascular disease and all-cause mortality in the elderly: PROSPER long-term follow-up

Cited by 33 publications

References 24 publications

Size and shape of the associations of glucose, HbA1c, insulin and HOMA-IR with incident type 2 diabetes: the Hoorn Study

Size and shape of the associations of glucose, HbA1c, insulin and HOMA-IR with incident type 2 diabetes: the Hoorn Study

Plant-derived polyunsaturated fatty acids and markers of glucose metabolism and insulin resistance: a meta-analysis of randomized controlled feeding trials

Novel all-extremity high-intensity interval training improves aerobic fitness, cardiac function and insulin resistance in healthy older adults

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