The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with an increased risk of diabetes-related complications. Hence, it is plausible that continuous positive airway pressure (CPAP) could have a favorable impact on these complications. We assessed the feasibility of conducting a randomized control trial in patients with type 2 diabetes and OSA over 2 years. METHODS: We conducted an open-label multicenter feasibility randomized control trial of CPAP vs no CPAP in patients with type 2 diabetes and OSA. Patients with resting oxygen saturation < 90%, central apnea index > 15 events/h, or Epworth Sleepiness Scale ≥ 11 were excluded. OSA was diagnosed using a multichannel portable device (ApneaLink Air, ResMed). The primary outcome measures were related to feasibility and the secondary outcomes were changes in various clinical and biochemical parameters related to diabetes outcomes. RESULTS: Eighty-three (40 CPAP vs 43 no CPAP) patients were randomly assigned, with a median (interquartile range) follow-up of 645 (545, 861) days. CPAP compliance was inadequate, with a median usage of approximately 3.5 hours/night. Early CPAP use predicted longer-term compliance. The adjusted analysis showed a possible favorable association between being randomly assigned to CPAP and several diabetes-related end points (chronic kidney disease, neuropathy, and quality of life). CONCLUSIONS: It was feasible to recruit, randomly assign, and achieve a high follow-up rate over 2 years in patients with OSA and type 2 diabetes. CPAP compliance might improve by a run-in period before randomization. A full randomized control trial is necessary to assess the observed favorable association between CPAP and chronic kidney disease , neuropathy, and quality of life in patients with type 2 diabetes. CLINICAL TRIAL REGISTRATION: Registry: ISRCTN; Name: The impact of sleep disorders in patients with type 2 diabetes; URL: https://www.isrctn.com/ISRCTN12361838; Identifier: ISRCTN12361838. CITATION: Makhdom EA, Maher A, Ottridge R, et al. The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial. J Clin Sleep Med. 2024;20(6):947-957.

The Impact of Sleep Debt on Excess Adiposity and Insulin Sensitivity in Patients with Early Type 2 Diabetes Mellitus.

STUDY OBJECTIVES: We examined cross-sectional and prospective associations between sleep debt and adiposity measures, as well as homeostatic model assessment-insulin resistance (HOMA-IR) in early type 2 diabetes. METHODS: Prospective data analysis from participants of a randomized controlled trial based on an intensive lifestyle intervention (usual care, diet, or diet and physical activity). Data were collected at baseline, 6 months, and 12 months post-intervention. The study was performed across five secondary care centers in the United Kingdom. Patients (n = 593) with a recent diagnosis of type 2 diabetes were recruited. Objective height and weight were ascertained for obesity status (body mass index [BMI]; ≥ 30 kg/m(2)), waist circumference (cm) for central adiposity, and fasting blood samples drawn to examine insulin resistance (IR). Seven-day sleep diaries were used to calculate weekday sleep debt at baseline, calculated as average weekend sleep duration minus average weekday sleep duration. RESULTS: At baseline, compared to those without weekday sleep debt, those with weekday sleep debt were 72% more likely to be obese (OR = 1.72 [95% CI:1.03-2.88]). At six months, weekday sleep debt was significantly associated with obesity and IR after adjustment, OR = 1.90 (95% CI:1.10-3.30), OR = 2.07 (95% CI:1.02-4.22), respectively. A further increase at 12 months was observed for sleep debt with obesity and IR: OR = 2.10 (95% CI:1.14-3.87), OR = 3.16 (95% CI:1.38-7.24), respectively. For every 30 minutes of weekday sleep debt, the risk of obesity and IR at 12 months increased by 18% and 41%, respectively. CONCLUSIONS: Sleep debt resulted in long-term metabolic disruption, which may promote the progression of type 2 diabetes in newly diagnosed patients. Sleep hygiene/education could be an important factor for future interventions to target early diabetes.

An investigation of the associations among sleep duration and quality, body mass index and insulin resistance in newly diagnosed type 2 diabetes mellitus patients.

OBJECTIVES: To examine direct and indirect associations of sleep duration and quality with insulin resistance, considering body mass index (BMI) as a potential mediator in newly diagnosed type 2 diabetes mellitus patients. METHODS: Cross-sectional data from patients enrolled in the Early Activity in Diabetes study. We studied 522 newly diagnosed type 2 diabetes mellitus patients, 65.9% male, mean age 63.5 ± 10.1 years. Of the total sample 53% had a BMI of ⩾30 kg/m(2). Participants completed a 7-day sleep diary and sleep questionnaire. Average sleep duration (minutes), average nap duration (minutes) and average number of night awakenings were derived. Objective measures of height and body weight were obtained for the BMI calculation (kg/m(2)). Insulin resistance was obtained using the homeostatic model assessment - insulin resistance (HOMA2-IR) standardized technique. RESULTS: Average number of night awakenings was positively correlated with BMI (r= 0.22, p < 0.001) and negatively associated with logged HOMA2-IR (r= -0.16, p = 0.04). Path analysis demonstrated night awakenings were directly associated with BMI and indirectly associated with insulin resistance, whilst considering BMI as a potential mediator (p < 0.05). Sleep duration was not associated with BMI or insulin resistance (p > 0.05). CONCLUSIONS: Sleep quality, not sleep duration, plays an important role in insulin resistance in newly diagnosed type 2 diabetes mellitus patients. BMI may mediate the relationship between indicators of sleep quality and insulin resistance. There is a need to examine the impact of improving sleep quality on obesity and insulin resistance in patients with type 2 diabetes mellitus.

Bariatric surgery in morbidly obese insulin resistant humans normalises insulin signalling but not insulin-stimulated glucose disposal.

AIMS: Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB), and compared this to lean volunteers. MATERIALS AND METHODS: The hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR) in eight morbidly obese (body mass index, BMI=47.3 ± 2.2 kg/m(2)) patients, before and after RYGB, and in eight lean volunteers (BMI=20.7 ± 0.7 kg/m2). Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50) and maximal (GDR100) GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity. RESULTS: Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001). Weight-loss of 29.9 ± 4 kg after surgery significantly improved GDR50 (P=0.004) but not GDR100 (P=0.3). These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001). Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA), and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA), and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively). CONCLUSIONS: Our data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss.