Jennifer M. Kilkus

Insufficient Sleep Undermines Dietary Efforts to Reduce Adiposity

BACKGROUND Sleep loss can modify energy intake and expenditure. OBJECTIVE To determine whether sleep restriction attenuates the effect of a reduced-calorie diet on excess adiposity. DESIGN Randomized, 2-period, 2-condition crossover study. SETTING University clinical research center and sleep laboratory. PATIENTS 10 overweight nonsmoking adults (3 women and 7 men) with a mean age of 41 years (SD, 5) and a mean body mass index of 27.4 kg/m² (SD, 2.0). INTERVENTION 14 days of moderate caloric restriction with 8.5 or 5.5 hours of nighttime sleep opportunity. MEASUREMENTS The primary measure was loss of fat and fat-free body mass. Secondary measures were changes in substrate utilization, energy expenditure, hunger, and 24-hour metabolic hormone concentrations. RESULTS Sleep curtailment decreased the proportion of weight lost as fat by 55% (1.4 vs. 0.6 kg with 8.5 vs. 5.5 hours of sleep opportunity, respectively; P = 0.043) and increased the loss of fat-free body mass by 60% (1.5 vs. 2.4 kg; P = 0.002). This was accompanied by markers of enhanced neuroendocrine adaptation to caloric restriction, increased hunger, and a shift in relative substrate utilization toward oxidation of less fat. LIMITATION The nature of the study limited its duration and sample size. CONCLUSION The amount of human sleep contributes to the maintenance of fat-free body mass at times of decreased energy intake. Lack of sufficient sleep may compromise the efficacy of typical dietary interventions for weight loss and related metabolic risk reduction. PRIMARY FUNDING SOURCE National Institutes of Health.

Eight Hours of Nightly Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea Improves Glucose Metabolism in Patients with Prediabetes. A Randomized Controlled Trial

RATIONALE Although obstructive sleep apnea (OSA) is associated with impaired glucose tolerance and diabetes, it remains unclear whether OSA treatment with continuous positive airway pressure (CPAP) has metabolic benefits. OBJECTIVES To determine the effect of 8-hour nightly CPAP treatment on glucose metabolism in individuals with prediabetes and OSA. METHODS In a randomized controlled parallel group study, 39 participants were randomly assigned to receive either 8-hour nightly CPAP (n = 26) or oral placebo (n = 13). Sleep was polysomnographically recorded in the laboratory on each night. CPAP adherence was ensured by continuous supervision. Participants continued their daily routine activities outside the laboratory. Glucose metabolism was assessed at baseline and after 2 weeks of assigned treatment using both the oral and intravenous glucose tolerance tests. The primary outcome was the overall glucose response as quantified by the area under the curve for glucose during 2-hour oral glucose tolerance testing. Secondary outcomes included fasting and 2-hour glucose and insulin, the area under the curves for insulin and insulin secretion, norepinephrine, insulin sensitivity, acute insulin response to glucose, and 24-hour blood pressure. MEASUREMENTS AND MAIN RESULTS The overall glucose response was reduced (treatment difference: -1,276.9 [mg/dl] · min [95% confidence interval, -2,392.4 to -161.5]; P = 0.03) and insulin sensitivity was improved (treatment difference: 0.77 [mU/L](-1) · min(-1) [95% confidence interval, 0.03-1.52]; P = 0.04) with CPAP as compared with placebo. Additionally, norepinephrine levels and 24-hour blood pressure were reduced with CPAP as compared with placebo. CONCLUSIONS In patients with prediabetes, 8-hour nightly CPAP treatment for 2 weeks improves glucose metabolism compared with placebo. Thus, CPAP treatment may be beneficial for metabolic risk reduction. Clinical trial registered with www.clinicaltrials.gov (NCT 01156116).

Elevated ghrelin predicts food intake during experimental sleep restriction

Sleep curtailment has been linked to obesity, but underlying mechanisms remain to be elucidated. This study assessed whether sleep restriction alters 24‐h profiles of appetite‐regulating hormones ghrelin, leptin, and pancreatic polypeptide during a standardized diet and whether these hormonal alterations predict food intake during ad libitum feeding.

Effects of sleep restriction on the human plasma metabolome.

This study examined the effects of recurrent sleep restriction on the plasma metabolome of adults with familial risk of type 2 diabetes. Eleven healthy adults (6M/5F; mean [SD] age: 26 [3]years; BMI 23.5 [2.3]kg/m(2)) with parental history of type 2 diabetes participated in a two-condition, two-period randomized crossover study at the Clinical Resource Center at an academic hospital. Each participant completed two 8-night inpatient sessions with restricted (5.5-h time-in-bed) vs. adequate (8.5-h time-in-bed) sleep opportunity while daily food intake and physical activity were carefully controlled. A combination of two UHPLC/MS/MS platforms and one GC/MS platform was used to measure 362 biochemicals in fasting plasma samples collected from study participants the morning after each 8-night sleep treatment. Relative concentrations of 12 amino acids and related metabolites were increased when sleep was curtailed. Sleep restriction also induced elevations in several fatty acid, bile acid, steroid hormone, and tricarboxylic acid cycle intermediates. In contrast, circulating levels of glucose, some monosaccharides, gluconate, and five-carbon sugar alcohols tended to decline when sleep was reduced. Recurrent sleep curtailment affected multiple pathways of intermediary metabolism in adults at risk for type 2 diabetes. An elevation in plasma amino acids and related biochemicals was the most pronounced metabolic signature seen in response to 8 nights of sleep restriction.

Sleep and Eating Behavior in Adults at Risk for Type 2 Diabetes

Insufficient quantity and quality of sleep may modulate eating behavior, everyday physical activity, overall energy balance, and individual risk of obesity and type 2 diabetes. We examined the association of habitual sleep quantity and quality with the self‐reported pattern of eating behavior in 53 healthy urban adults with parental history of type 2 diabetes (30 F/23 M; mean (s.d.) age: 27 (4) years; BMI: 23.9 (2.3) kg/m2) while taking into consideration the amount of their everyday physical activity. Participants completed 13 (3) days of sleep and physical activity monitoring by wrist actigraphy and waist accelerometry while following their usual lifestyle at home. Overnight laboratory polysomnography was used to screen for sleep disorders. Subjective sleep quality was measured with the Pittsburgh Sleep Quality Index. Eating behavior was assessed using the original 51‐item and the revised 18‐item version of the Three‐Factor Eating Questionnaire including measures of cognitive restraint, disinhibition, hunger, and uncontrolled and emotional eating. In multivariable regression analyses adjusted for age, BMI, gender, race/ethnicity, level of education, habitual sleep time measured by wrist actigraphy and physical activity measured by waist accelerometry, lower subjective sleep quality was associated with increased hunger, more disinhibited, uncontrolled and emotional eating, and higher cognitive restraint. There was no significant association between the amount of sleep measured by wrist actigraphy and any of these eating behavior factors. Our findings indicate that small decrements in self‐reported sleep quality can be a sensitive indicator for the presence of potentially problematic eating patterns in healthy urban adults with familial risk for type 2 diabetes.

Two Nights of Recovery Sleep Reverses the Effects of Short-term Sleep Restriction on Diabetes Risk

Sleep restriction is associated with insulin resistance and an increased risk for type 2 diabetes (1–3). Here, we investigated whether only 2 nights of recovery sleep, as may occur on weekends, reverses the negative effects of short-term sleep restriction on glucose homeostasis. Nineteen healthy young lean men were studied under controlled laboratory conditions during normal sleep and sleep restriction in a randomized order, as previously reported (1,2,4). The institutional review board of The University of Chicago approved the protocol, and all participants gave written informed consent. During normal sleep, participants were allowed 8.5 h in bed (2300–0700) for 4 consecutive nights. During sleep restriction, participants were allowed 4.5 h in bed (0100–0530) for 4 consecutive nights, immediately followed by recovery sleep for 2 consecutive nights with 12 h in bed on the first night (2200–1000) and 10 h in bed on the second night (2200–0800). A frequently sampled intravenous glucose tolerance test (ivGTT) was performed at 1000 after 4 nights of normal sleep, 4 nights of sleep restriction, and 2 nights …

Hypoglycemia Detection and Carbohydrate Suggestion in an Artificial Pancreas

Fear of hypoglycemia is a major concern for many patients with type 1 diabetes and affects patient decisions for use of an artificial pancreas system. We propose an alternative way for prevention of hypoglycemia by issuing predictive hypoglycemia alarms and encouraging patients to consume carbohydrates in a timely manner. The algorithm has been tested on 6 subjects (3 males and 3 females, age 24.2 ± 4.5 years, weight 79.2 ± 16.2 kg, height 172.7 ± 9.4 cm, HbA1C 7.3 ± 0.48%, duration of diabetes 209.2 ± 87.9 months) over 3-day closed-loop clinical experiments as part of a multivariable artificial pancreas control system. Over 6 three-day clinical experiments, there were only 5 real hypoglycemia episodes, of which only 1 hypoglycemia episode occurred due to being missed by the proposed algorithm. The average hypoglycemia alarms per day and per subject was 3. Average glucose value when the first alarms were triggered was recorded to be 117 ± 30.6 mg/dl. Average carbohydrate consumption per alarm was 14 ± 7.8 grams. Our results have shown that most low glucose concentrations can be predicted in advance and the glucose levels can be raised back to the desired levels by consuming an appropriate amount of carbohydrate. The proposed algorithm is able to prevent most hypoglycemic events by suggesting appropriate levels of carbohydrate consumption before the actual occurrence of hypoglycemia.

Incident hyperglycemia, parenteral nutrition administration and adverse outcomes in patients with myeloma admitted for initial auto-SCT

Parenteral nutrition (PN) exacerbates hyperglycemia, which is associated with increased morbidity and mortality in various cancer populations. By using a retrospective design, we examined incident hyperglycemia in PN and non-PN recipients and the associations with clinical events and 5-year survival in a cohort treated for myeloma with melphalan and auto-SCT (n=112). Clinical comparisons were made at admission, and ‘before’ and ‘after’ initiating PN to discern differences and temporality. Actual infusion times were used for PN patients; time frames based on mean PN infusion days were created for the non-PN recipients. Oral intake was lower ‘before’ in PN vs non-PN patients (P<0.001); however, no differences in mucositis, emesis, infections or transfusions were detected ‘before.’ Incident hyperglycemia (⩾7.0 mmol/L) was significant ‘after’ PN initiation, and PN recipients experienced delays in WBC (P<0.05) and platelet engraftment (P=0.009), and required significantly greater RBC (P=0.0014) and platelet (P=0.001) support ‘after’ than non-PN patients. Neutropenic fever and longer hospital stay were more frequent among PN vs non-PN recipients (P<0.001). Differences in 5-year mortality were not apparent. The findings fail to support clinical benefits of PN administration during auto-SCT for myeloma. Further study is needed to discern if hyperglycemia or feeding per se was deleterious in this patient population.

Automated Insulin Delivery—The Light at the End of the Tunnel

T ype 1 diabetes mellitus (T1DM) results from autoimmune destruction of pancreatic b cells, resulting in an absolute loss of insulin production, and typically affects youth. Automated insulin delivery (AID) system is a term that has been used over the past 30 years to represent an alternative and incremental improvement in treatment for patients with T1DM. An ideal AID system would use trends from past blood glucose concentrations (BGCs) to normalize them to target, through automatic insulin and glucagon release or by the ingestion of carbohydrate in response to the BGC. We will briefly review AID technologies that have been developed by different research groups globally, with the objective to familiarize the general pediatric and pediatric endocrinology community about this rapidly developing area of technology that will likely revolutionize therapeutic options for their patients with T1DM. With this goal in mind, this review describes the AID components, reviewing different component brands and algorithms; then presents the human clinical trials that have been conducted under AID control to date; then summarizes the challenges of current AID systems. In conclusion, the future of AID control systems is described.