Prediction of Cardiometabolic Health Through Changes in Plasma Proteins With Intentional Weight Loss in the DiRECT and DIADEM-I Randomized Clinical Trials of Type 2 Diabetes Remission.

OBJECTIVE: To determine the extent to which changes in plasma proteins, previously predictive of cardiometabolic outcomes, predict changes in two diabetes remission trials. RESEARCH DESIGN AND METHODS: We applied SomaSignal predictive tests (each derived from ∼5,000 plasma protein measurements using aptamer-based proteomics assay) to baseline and 1-year samples of trial intervention (Diabetes Remission Clinical Trial [DiRECT], n = 118, and Diabetes Intervention Accentuating Diet and Enhancing Metabolism [DIADEM-I], n = 66) and control (DiRECT, n = 144, DIADEM-I, n = 76) group participants. RESULTS: Mean (SD) weight loss in DiRECT (U.K.) and DIADEM-I (Qatar) was 10.2 (7.4) kg and 12.1 (9.5) kg, respectively, vs. 1.0 (3.7) kg and 4.0 (5.4) kg in control groups. Cardiometabolic SomaSignal test results showed significant improvement (Bonferroni-adjusted P < 0.05) in DiRECT and DIADEM-I (expressed as relative difference, intervention minus control) as follows, respectively: liver fat (-26.4%, -37.3%), glucose tolerance (-36.6%, -37.4%), body fat percentage (-8.6%, -8.7%), resting energy rate (-8.0%, -5.1%), visceral fat (-34.3%, -26.1%), and cardiorespiratory fitness (9.5%, 10.3%). Cardiovascular risk (measured with SomaSignal tests) also improved in intervention groups relative to control, but this was significant only in DiRECT (DiRECT, -44.2%, and DIADEM-I, -9.2%). However, weight loss >10 kg predicted significant reductions in cardiovascular risk, -19.1% (95% CI -33.4 to -4.91) in DiRECT and -33.4% (95% CI -57.3, -9.6) in DIADEM-I. DIADEM-I also demonstrated rapid emergence of metabolic improvements at 3 months. CONCLUSIONS: Intentional weight loss in recent-onset type 2 diabetes rapidly induces changes in protein-based risk models consistent with widespread cardiometabolic improvements, including cardiorespiratory fitness. Protein changes with greater (>10 kg) weight loss also predicted lower cardiovascular risk, providing a positive outlook for relevant ongoing trials.

COVID-19 and the hidden threat of diabetic microvascular complications.

The coronavirus disease 2019 (COVID-19) pandemic affected at least 200 million individuals worldwide and resulted in nearly 5 million deaths as of October 2021. According to the latest data from the International Diabetes Federation (IDF) in 2021, the diabetes pandemic has affected 537 million people and is associated with 6.7 million deaths. Given the high prevalence of both diabetes and COVID-19 and common pathological outcomes, a bidirectional relationship could have a catastrophic outcome. The increased risk of COVID-19 in those with obesity and diabetes and higher morbidity and mortality has received considerable attention. However, little attention has been given to the relationship between COVID-19 and microvascular complications. Indeed, microvascular complications are associated with an increased risk of cardiovascular disease (CVD) and mortality in diabetes. This review assesses the evidence for an association between diabetic microvascular complications (neuropathy, nephropathy, and retinopathy) and COVID-19. It draws parallels between the pathological changes occurring in the microvasculature in both diseases and assesses whether microvascular disease is a prognostic factor for COVID-19 outcomes in diabetes.

A systematic review of randomized controlled trials of dietary interventions for weight loss in adults in the Middle East and north Africa region.

The prevalence and incidence of obesity, and associated complications, such as type 2 diabetes, in the Middle East and north Africa (MENA) region rank among the highest in the world. Little is known about the effectiveness of dietary weight loss interventions conducted in the MENA region. We conducted a systematic review of randomized clinical trials aiming to assess the effectiveness of dietary interventions for weight loss in the adult population originating from and residing in the MENA region. In accordance with PRISMA guidelines, PubMed, CINAHL, Cochrane, and EMBASE were systematically searched for randomized controlled trials (RCT) using dietary interventions for weight loss conducted in the MENA region. RCTs examining weight loss as an outcome in adults (≥ 18 years old) were included. The Cochrane Collaboration tool for assessing risk of bias was used to ascertain the quality of the eligible RCTs and the Template for Intervention Description and Replication for population health and policy interventions (TIDieR-PHP) checklist was used to evaluate the reporting of the interventions. Twenty-nine RCTs including 2792 adults from five countries in the MENA region met the search criteria. Study participants were predominantly middle-aged females. Duration of follow up was mostly 3 months or less. Weight loss ranged from -0.7 to 16 kg across all intervention groups and the average weight loss was 4.8 kg. There was paucity of description of the weight loss interventions and variations amongst studies did not allow a meta-analysis of findings. It was not possible to draw firm conclusions on the effectiveness of dietary weight loss interventions in the region. High quality studies using more structured interventions of longer duration with standardized outcome measures are needed in the MENA region to support clinical practice with evidence-based interventions for obesity.

Clinical and metabolic characteristics of the Diabetes Intervention Accentuating Diet and Enhancing Metabolism (DIADEM-I) randomised clinical trial cohort.

OBJECTIVES: Diabetes Intervention Accentuating Diet and Enhancing Metabolism-I (DIADEM-I) is the first randomised controlled trial (RCT) in the Middle East and North Africa (MENA) region testing the effectiveness of an intensive lifestyle intervention (ILI) for weight loss and diabetes remission. We report on the recruitment process and baseline characteristics of the DIADEM-I cohort based on origin (Middle East vs North Africa), and waist circumference. DESIGN: DIADEM-I is an open-label randomised, controlled, parallel group RCT recruiting young individuals (18-50 years) with early type 2 diabetes (≤3 years since diagnosis) originating from MENA. Individuals from primary care were randomised to usual medical care or ILI (total dietary replacement phase using meal replacement products, followed by staged food reintroduction and physical activity support). The primary outcome is weight loss at 12 months. Other outcomes are glycaemic control and diabetes remission. SETTING: Primary care, Qatar. PARTICIPANTS: 147 (73% men) randomised within DIADEM-I who were included in the final trial data analysis. OUTCOME MEASURES: Recruitment metrics, and baseline clinical and metabolic characteristics. RESULTS: Of 1498 people prescreened, 267 (18%) were invited for screening and 209 (78%) consented. 173 (83%) were eligible. 15 (7%) withdrew before randomisation and the remaining 158 were randomised. Mean age was 42.1 (SD 5.6) years and mean body mass index was: 36.3 (5.5) kg/m2 (women) and 34.4 (5.4) kg/m2 (men). Mean diabetes duration was 1.8 (1.0) years and mean glycosylated haemoglobin (HbA1c) was 7.0% (1.30) (52.5 mmol/mol (SD 14.3)). Participants originated from 13 countries. Those from North Africa reported greater physical activity and had lower family history of diabetes. 90% of subjects were taking diabetes medications and 31% antihypertensives. Those with greater waist circumference had significantly higher insulin resistance and lower quality of life. CONCLUSION: Recruitment of participants originating from the MENA region into the RCT was successful, and study participation was readily accepted. While DIADEM-I participants originated from 13 countries, there were few baseline differences amongst participants from Middle East versus North Africa, supporting generalisability of RCT results. TRIAL REGISTRATION NUMBER: ISRCTN20754766; NCT03225339.

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

BACKGROUND: Type 2 diabetes is affecting people at an increasingly younger age, particularly in the Middle East and in north Africa. We aimed to assess whether an intensive lifestyle intervention would lead to significant weight loss and improved glycaemia in young individuals with early diabetes. METHODS: This open-label, parallel-group, randomised controlled trial (DIADEM-I), done in primary care and community settings in Qatar, compared the effects of an intensive lifestyle intervention with usual medical care on weight loss and glycaemic outcomes in individuals with type 2 diabetes, aged 18-50 years, with a short diabetes duration (≤3 years), had a BMI of 27·0 kg/m2 or more, and who were from the Middle East and north Africa region. Participants were randomly allocated (1:1) either to the intensive lifestyle intervention group or the usual medical care control group by a computer-generated sequence and an online randomisation service. The intensive lifestyle intervention comprised a total diet replacement phase, in which participants were given formula low-energy diet meal replacement products followed by gradual food reintroduction combined with physical activity support, and a weight-loss maintenance phase, involving structured lifestyle support. Participants in the control group received usual diabetes care, which was based on clinical guidelines. The primary outcome was weight loss at 12 months after receiving the assigned intervention. Our analysis was based on the intention-to-treat principle. Key secondary outcomes included diabetes control and remission. The trial was registered with the ISRCTN registry, ISRCTN20754766, and ClinicalTrials.gov, NCT03225339. FINDINGS: Between July 16, 2017, and Sept 30, 2018, we enrolled and randomly assigned 158 participants (n=79 in each group) to the study. 147 participants (70 in the intervention group and 77 in the control group) were included in the final intention-to-treat analysis population. Between baseline and 12 months, the mean bodyweight of participants in the intervention group reduced by 11·98 kg (95% CI 9·72 to 14·23) compared with 3·98 kg (2·78 to 5·18) in the control group (adjusted mean difference -6·08 kg [95% CI -8·37 to -3·79], p<0·0001). In the intervention group, 21% of participants achieved more than 15% weight loss between baseline and 12 months compared with 1% of participants in the control group (p<0·0001). Diabetes remission occurred in 61% of participants in the intervention group compared with 12% of those in the control group (odds ratio [OR] 12·03 [95% CI 5·17 to 28·03], p<0·0001). 33% of participants in the intervention group had normoglycaemia compared with 4% of participants in the control group (OR 12·07 [3·43 to 42·45], p<0·0001). Five serious adverse events were reported in four participants in the control group; four admissions to hospital because of unanticipated events (supraventricular tachycardia, abdominal pain, pneumonia, and epididymo-orchitis), and one admission to hospital for an anticipanted event (hyperglycaemia). INTERPRETATION: Our findings show that the intensive lifestyle intervention led to significant weight loss at 12 months, and was associated with diabetes remission in over 60% of participants and normoglycaemia in over 30% of participants. The provision of this lifestyle intervention could allow a large proportion of young individuals with early diabetes to achieve improvements in key cardiometabolic outcomes, with potential long-term benefits for health and wellbeing. FUNDING: Qatar National Research Fund.

Factors Associated With Presenteeism at Work in Type 2 Diabetes Mellitus.

OBJECTIVE: Our study aimed to identify factors associated with decreased presenteeism in type 2 diabetes mellitus (T2DM). METHODS: Data were collected from 147 T2DM participants. Questionnaires were completed: Stanford Presenteeism Scale (SPS-6) assessing health status and employee productivity, Hospital Anxiety and Depression Scale (HADS) for mental health, SF-36 for quality of life, Problem Areas in Diabetes (PAID) to measure diabetes-related emotional distress, and Michigan Neuropathy Screening Instrument for diabetic neuropathy. RESULTS: PAID score was negatively related to the SPS-6 score (r = -0.527, P < 0.001). Both anxiety and depression were negatively correlated with SPS-6 (r = -0.377, P < 0.001 and r = -0.603, P < 0.001, respectively). Seven out of eight different categories of SF-36 were significantly associated with SPS-6 score. Neuropathy was negatively related to presenteeism (r = -0.228, P = 0.07). CONCLUSION: Factors related to decreased presenteeism in T2DM include diabetes-associated stress, poor mental health, poor quality of life, and a history of neuropathy.

Diabetes Intervention Accentuating Diet and Enhancing Metabolism (DIADEM-I): a randomised controlled trial to examine the impact of an intensive lifestyle intervention consisting of a low-energy diet and physical activity on body weight and metabolism in early type 2 diabetes mellitus: study protocol for a randomized controlled trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and obesity are syndemic and will have a significant impact on affected individuals and healthcare services worldwide. Evidence shows that T2DM remission can be achieved with significant weight loss in those who are younger with early diabetes and requiring fewer medications for glycaemic control. DIADEM-I aims to examine the impact of an intensive lifestyle intervention (ILI) using a low-energy diet (LED) meal replacement approach combined with physical activity in younger individuals with early T2DM. METHODS: The planned study is an ongoing, non-blinded, pragmatic, randomised controlled, parallel-group trial examining the impact of an LED-based ILI on body weight and diabetes remission in younger (18-50 years) T2DM individuals with early diabetes (≤ 3-year duration). The ILI will be compared to usual medical care (UMC). The primary outcome will be weight loss at 12 months. Other key outcomes of interest include diabetes remission, glycaemic control, diabetes complications, cardiovascular health, physical activity, mental health, and quality of life. It is planned for the study to include 138 subjects for assessment of the primary outcome. Safety will be assessed throughout. DISCUSSION: If DIADEM-I demonstrates a clinically significant effect for younger individuals with early T2DM, it will inform clinical guidelines and services of the future for management of T2DM. TRIAL REGISTRATION: ISRCTN: ISRCTN20754766 (date assigned: 7 June 2017); ClinicalTrials.gov, ID: NCT03225339 Registered on 26 June 2017.

Investigating physiological glucose excursions before, during, and after Ramadan in adults without diabetes mellitus.

AIM: The study aimed to investigate physiological effects of Ramadan fasting on continuously monitored glucose levels in relation to Ramadan in young non-diabetic adults. METHODS: Continuous glucose monitoring was employed to measure interstitial glucose for several days 1-2weeks before Ramadan, in the middle of Ramadan, and 4-6weeks after Ramadan to assess glucose exposure and glucose variability. RESULTS: A total of 34,182 accurate glucose sensor readings and 438 capillary blood glucose values [mean absolute difference median (interquartile range) 8.5 (6.9-11.1)%] were obtained from 18 non-diabetic adults [13 females; aged 24 (21-27) years; baseline body mass index 23.9 (20.6-28.9) kg/m2]. The continuous glucose monitoring profiles showed an increase in the hyperglycemic (above 140mg/dL) area under the curve after Ramadan compared to both before (P=0.004) and during Ramadan (P=0.003), along with an increased glucose variability after Ramadan (P=0.014). Both the area under the interstitial glucose concentration curve for the entire day and the average glucose were positively associated with body mass index during (P=0.004 and P=0.005, respectively) and after Ramadan (P=0.013 and P=0.01, respectively). Atypical continuous glucose patterns were recognized in 11% of subjects, distinguished by a prolonged increased glucose exposure, particularly in response to a meal. CONCLUSION: The time-point 4-6weeks after Ramadan was distinguished by greater glucose exposure and wider glucose variability that may reflect ongoing changes in insulin sensitivity in response to altering lifestyle patterns in non-diabetic young adults across the spectrum of body weight.