Effect of intensive lifestyle intervention on bodyweight and glycaemia in early type 2 diabetes (DIADEM-I): an open-label, parallel-group, randomised controlled trial

Taheri, Shahrad; Zaghloul, Hadeel; Chagoury, Odette; Elhadad, Sara; Ahmed, Syed Thouheed; Khatib, Neda El; Amona, Rasha Abou; Nahas, Katie El; Suleiman, Noor; Alnaama, Abdulla; Al-Hamaq, Abdulla O.A.A.; Charlson, Mary E.; Wells, Martin T.; Abdulla, Samya Al; Abou‐Samra, Abdul Badi

doi:10.1016/s2213-8587(20)30117-0

Cited by 241 publications

(302 citation statements)

References 30 publications

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“…We previously reported that intensive lifestyle intervention leads to diabetes remission in over 60% of participants and normoglycaemia in over 30% of participants, as well as a decrease in total TG and an increase in HDL levels 3 . Thus, it could be reasoned that sensitivity to insulin might potentially be restored by healthy lifestyle and diet choices, which have a positive impact on body metabolism by normalizing lipid levels.…”

Section: Discussionmentioning

confidence: 98%

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The metabolic footprint of compromised insulin sensitivity under fasting and hyperinsulinemic-euglycemic clamp conditions in an Arab population

Halama

Suleiman

Kuliński

et al. 2020

Sci Rep

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Metabolic pathways that are corrupted at early stages of insulin resistance (IR) remain elusive. This study investigates changes in body metabolism in clinically healthy and otherwise asymptomatic subjects that may become apparent already under compromised insulin sensitivity (IS) and prior to IR. 47 clinically healthy Arab male subjects with a broad range of IS, determined by hyperinsulinemic-euglycemic clamp (HIEC), were investigated. Untargeted metabolomics and complex lipidomics were conducted on serum samples collected under fasting and HIEC conditions. Linear models were used to identify associations between metabolites concentrations and IS levels. Among 1896 identified metabolites, 551 showed significant differences between fasting and HIEC, reflecting the metabolic switch in energy utilization. At fasting, 336 metabolites, predominantly di- and tri-acylglycerols, showed significant differences between subjects with low and high levels of IS. Changes in amino acid, carbohydrate and fatty acid metabolism in response to insulin were impaired in subjects with low IS. Association of altered mannose and amino acids with IS was also replicated in an independent cohort of T2D patients. We identified metabolic phenotypes that characterize clinically healthy Arab subjects with low levels of IS at their fasting state. Our study is providing further insights into the metabolic pathways that precede IR.

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Section: Discussionmentioning

confidence: 98%

“…The onset of IR, quantified by impaired insulin sensitivity (IS), provides an early identification of subjects that are at increased risk of developing T2D. At this point, reversal of IR may still be possible through life style intervention 3 , 4 . However, impaired IS is asymptomatic and cannot be easily detected.…”

Section: Introductionmentioning

confidence: 99%

The metabolic footprint of compromised insulin sensitivity under fasting and hyperinsulinemic-euglycemic clamp conditions in an Arab population

Halama

Suleiman

Kuliński

et al. 2020

Sci Rep

Self Cite

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“…Plasma concentrations of BCAA have been found as a suitable metabolic predictor of insulin sensitivity improvement in overweight individuals after a lifestyle intervention [ 49 ]. Considering that lifestyle interventions have important health benefits, including T2D postponement [ 50 ], DRI could be a potential tool to assess the effect of lifestyle intervention in order to improve its efficacy. Future research is needed to evaluate the utility of DRI on that regard.…”

Section: Discussionmentioning

confidence: 99%

A Newly Developed Diabetes Risk Index, Based on Lipoprotein Subfractions and Branched Chain Amino Acids, is Associated with Incident Type 2 Diabetes Mellitus in the PREVEND Cohort

Flores‐Guerrero

Gruppen

Connelly

et al. 2020

JCM

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Objective: Evaluate the ability of a newly developed diabetes risk score, the Diabetes Risk Index (DRI), to predict incident type 2 diabetes mellitus (T2D) in a large adult population. Methods: The DRI was developed by combining the Lipoprotein Insulin Resistance Index (LP-IR), calculated from 6 lipoprotein subspecies and size parameters, and the branched chain amino acids, valine and leucine, all of which have been shown previously to be associated with future T2D. DRI scores were calculated in a total of 6134 nondiabetic men and women in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study. Cox proportional hazards regression was used to evaluate the association of DRI scores with incident T2D. Results: During a median follow-up of 8.5 years, 306 new T2D cases were ascertained. In analyses adjusted for age and sex, there was a significant association between DRI scores and incident T2D with the hazard ratio (HR) for the highest versus lowest quartile being 12.07 (95% confidence interval: 6.97–20.89, p < 0.001). After additional adjustment for body mass index (BMI), family history of T2D, alcohol consumption, diastolic blood pressure, total cholesterol, triglycerides, HDL cholesterol and HOMA-IR, the HR was attenuated but remained significant (HR 3.20 (1.73–5.95), p = 0.001). Similar results were obtained when DRI was analyzed as HR per 1 SD increase (HR 1.37 (1.14–1.65), p < 0.001). The Kaplan–Meier plot demonstrated that patients in the highest quartile of DRI scores presented at higher risk (p-value for log-rank test <0.001). Conclusions: Higher DRI scores are associated with an increased risk of T2D. The association is independent of clinical risk factors for T2D including HOMA-IR, BMI and conventional lipids.

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“…Patients randomised to the TDR were about 12-fold more likely than controls to attain diabetes remission (HbA1c <6.5% [<48mmol/mol], 61% and 12% respectively; OR 12.03) and normoglycaemia (HbA1c <5.7% [<39mmol/mol] and no diabetes medication for ≥3 months; 33% and 4% respectively; OR 12.07). 4 Despite a marked reduction in weight, some cases of T2D may be too advanced for TDR to induce remission. Ms Barnes notes that some patients may have relatively advanced T2D on enrolment.…”

Section: Increasing Evidencementioning

confidence: 99%

“…Meanwhile, increasing evidence suggests that losing sufficient weight to put type 2 diabetes (T2D) into remission can reduce the need for glucose-lowering medicines and drugs for comorbidities. [2][3][4] 'Deprescribing of medicines tends to be the most important factor when patients decide to follow a low calorie diet,' [LCD] comments Huda Latif, Diabetes Specialist Pharmacist at Luton Clinical Commissioning Group.…”

mentioning

confidence: 99%

The billion pound challenge: deprescribing, diabetes and diets

Greener¹

2020

Practical Diabetes

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Effect of intensive lifestyle intervention on bodyweight and glycaemia in early type 2 diabetes (DIADEM-I): an open-label, parallel-group, randomised controlled trial

Cited by 241 publications

References 30 publications

The metabolic footprint of compromised insulin sensitivity under fasting and hyperinsulinemic-euglycemic clamp conditions in an Arab population

The metabolic footprint of compromised insulin sensitivity under fasting and hyperinsulinemic-euglycemic clamp conditions in an Arab population

A Newly Developed Diabetes Risk Index, Based on Lipoprotein Subfractions and Branched Chain Amino Acids, is Associated with Incident Type 2 Diabetes Mellitus in the PREVEND Cohort

The billion pound challenge: deprescribing, diabetes and diets

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