[Show abstract][Hide abstract] ABSTRACT: Objective: Patients treated for nonfunctioning pituitary macroadenoma (NFMA) frequently have fatigue and alterations in sleep characteristics and sleep-wake rhythmicity. Since NFMA often compress the optic chiasm, these complaints might be related to dysfunction of the adjacent suprachiasmatic nucleus (SCN). We aimed to explore whether indirect indices of SCN functioning are altered in the long-term after surgery for NFMA. Methods: We studied 17 NFMA patients in long-term remission after transsphenoidal surgery, receiving adequate and stable hormone replacement for hypopituitarism, and 17 controls matched for age, gender, and BMI. Indirect indices of SCN function were assessed from ambulatory 24-hour recordings of skin and core body temperature, blood pressure, and salivary melatonin levels. Altered melatonin secretion was defined as absent evening rise, considerable irregularity, or daytime values >3 pg/ml. We additionally studied 8 patients treated for craniopharyngioma. Results: Distal-proximal skin temperature gradient did not differ between NFMA and controls, but proximal skin temperature was decreased during daytime (P=0.006). Core body temperature and non-dipping of blood pressure did not differ, whereas melatonin secretion was often altered in NFMA (OR 5.3, 95%CI 0.9-30.6). One or more abnormal parameters (≥2.0 SD score of controls) were observed during nighttime in twelve and during daytime in seven NFMA patients. Similar patterns were observed in craniopharyngioma patients. Conclusion: Heterogeneous patterns of altered diurnal rhythmicity in skin temperature and melatonin secretion parameters were observed in the majority of patients treated for NFMA. On a group level, both NFMA and craniopharyngioma patients showed lower daytime proximal skin temperature than controls, but other group average were not significantly different. The observations suggest altered function of central (or peripheral) clock machinery, possibly by disturbed entrainment or damage of the hypothalamic SCN by the suprasellar macroadenoma or its treatment.
European Journal of Endocrinology 05/2014; · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with type 1 diabetes have altered sleep characteristics and are thought to have deficits in sustained attention. We compared the Sustained Attention to Response Task (SART) of patients with type 1 diabetes to that of healthy controls, and related results with sleep characteristics and disease- related factors.
The SART was applied in 122 patients and 109 controls. Glucoregulation was assessed by HbA1c -values and a questionnaire assessing glycaemic history. Clinical parameters were obtained from medical charts. Polyneuropathy was assessed by neurological examination and quantitative sensory testing. Sleep characteristics were assessed with sleep questionnaires. Anxiety and depression scores were assessed by the Hospital Anxiety and Depression Scale (HADS).
The SART reaction time (RT) was significant longer than in controls (327 ± 5 ms vs. 285 ± 3 ms, p < 0.001), although there were no significant differences in error scores. Repeated measurement analyses showed that diabetes per se was associated with prolonged RT (P < 0.001). None of the sleep-related and diabetes-related factors were associated with SART parameters.
Patients with type 1 diabetes had prolonged RT as evidence of impaired sustained attention, which was associated with diabetes per se, but not with disturbed sleep characteristics. This article is protected by copyright. All rights reserved.
Diabetes/Metabolism Research and Reviews 09/2013; · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: GH treatment of short children born small for gestational age (SGA) results in a decline in fat mass (FM) and an increase in lean body mass (LBM). It is, however, unknown whether these changes persist into adulthood.
Our objective was to assess the long-term impact of GH treatment during childhood on body composition and fat distribution.
A total of 377 young adults participated in this cross-sectional study: 59 previously GH-treated young SGA adults compared to 52 untreated SGA adults with short stature (SGA-S), 161 SGA adults with spontaneous catch-up growth (SGA-CU), and 105 healthy normal-statured controls born appropriate for gestational age (AGA).
Body composition and fat distribution were determined by dual-energy x-ray absorptiometry.
Mean (SD) duration of GH treatment was 7.7 (2.4) yr and period after discontinuation 6.8 (1.8) yr. FM, fat distribution, and LBM of GH-treated SGA adults were not significantly different from that of untreated SGA-S adults. GH-treated SGA adults also had a similar FM and fat distribution as SGA-CU adults but a lower LBM. All SGA subgroups had a lower LBM and tended to have a higher FM than healthy AGA controls.
Body composition and fat distribution of previously GH-treated SGA adults was similar to that of untreated SGA-S adults. GH-induced catch-up growth has no unfavorable effect on FM and fat distribution compared with spontaneous catch-up growth. However, our study shows that SGA adults in general may have a different body composition than healthy AGA controls.
The Journal of Clinical Endocrinology and Metabolism 09/2011; 96(12):3710-6. · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Decreased sleep duration and/or impaired sleep quality negatively influence glucoregulation. The aim of this study was to assess subjective sleep characteristics in patients with type 1 diabetes, to relate sleep characteristics to long-term glycaemic control and to assess possible risk factors for impaired sleep.
We studied 99 adult patients with type 1 diabetes (55 men, 44 women, duration of diabetes 26.9 ± 1.2 years) and 99 age-, sex- and BMI-matched non-diabetic controls. Subjective sleep characteristics were assessed by validated questionnaires, i.e. Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and the Berlin Questionnaire. Glucoregulation was assessed by HbA(1c) values. Clinical variables were obtained from medical charts. Depression was assessed by the Hospital Anxiety and Depression Scale (HADS). Peripheral polyneuropathy was assessed by neurological examination and quantitative sensory testing.
Of the patients with type 1 diabetes, 35% had subjective poor sleep quality compared with 20% of the control participants (p = 0.021). A higher proportion of the patients with type 1 diabetes were at increased risk for obstructive sleep apnoea (OSA) (17.2% vs 5.1%, p = 0.012). There was no significant association between individual sleep characteristics and HbA(1c) values. On logistic regression analysis, the HADS depression score, presence of peripheral polyneuropathy, habitual snoring and other sleep disturbances (e.g. hypoglycaemia) were independently associated with poor sleep quality.
Adult patients with long-standing type 1 diabetes mellitus have disturbed subjective sleep quality and a higher risk for OSA compared with control participants. Subjective sleep disturbances are part of the complex syndrome of long-standing type 1 diabetes.
[Show abstract][Hide abstract] ABSTRACT: Fatigue and excessive sleepiness have been reported after treatment of nonfunctioning pituitary macroadenomas (NFMA). Because these complaints may be caused by disturbed nocturnal sleep, we evaluated objective sleep characteristics in patients treated for NFMA.
We conducted a controlled cross-sectional study.
We studied 17 patients (8 women; mean age, 54 yr) in remission of NFMA during long-term follow-up (8 yr; range, 1-18 yr) after surgery (n = 17) and additional radiotherapy (n = 5) without comorbidity except for hypopituitarism and 17 controls matched for age, gender, and body mass index. Sleep was assessed by nocturnal polysomnography, sleep and diurnal movement patterns by actigraphy, and quality of life and subjective sleep characteristics by questionnaires.
Compared to controls, patients had reduced sleep efficiency, less rapid eye movement sleep, more N1 sleep, and more awakenings in the absence of excessive apnea or periodic limb movements. Actigraphy revealed a longer sleep duration and profound disturbances in diurnal movement patterns, with more awakenings at night and less activity during the day. Patients scored higher on fatigue and reported impaired quality of life.
Patients previously treated for NFMA suffer from decreased subjective sleep quality, disturbed distribution of sleep stages, and disturbed circadian movement rhythm. These observations indicate that altered sleep characteristics may be a factor contributing to impaired quality of life and increased fatigue in patients treated for NFMA.
The Journal of Clinical Endocrinology and Metabolism 03/2011; 96(5):1524-32. · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Subsequent nights with partial sleep restriction result in impaired glucose tolerance, but the effects on insulin sensitivity have not been characterized.
The aim of this study was to evaluate the effect of a single night of partial sleep restriction on parameters of insulin sensitivity.
Nine healthy subjects (five men, four women) were studied once after a night of normal sleep duration (sleep allowed from 2300 to 0730 h), and once after a night of 4 h of sleep (sleep allowed from 0100 to 0500 h). Sleep characteristics were assessed by polysomnography. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp studies (from 1130 to 1430 h) with infusion of [6,6-(2)H(2)]glucose.
Sleep duration was shorter in the night with sleep restriction than in the unrestricted night (226 +/- 11 vs. 454 +/- 9 min; P< 0.0001). Sleep restriction did not affect basal levels of glucose, nonesterified fatty acids, insulin, or endogenous glucose production. Sleep restriction resulted in increased endogenous glucose production during the hyperinsulinemic clamp study compared to the unrestricted night (4.4 +/- 0.3 vs. 3.6 +/- 0.2 micromol x kg lean body mass(-1) x min(-1); P = 0.017), indicating hepatic insulin resistance. In addition, sleep restriction decreased the glucose disposal rate during the clamp (32.5 +/- 3.6 vs. 40.7 +/- 5.1 micromol x kg lean body mass(-1) x min(-1); P = 0009), reflecting decreased peripheral insulin sensitivity. Accordingly, sleep restriction decreased the rate of glucose infusion by approximately 25% (P = 0.001). Sleep restriction increased plasma nonesterified fatty acid levels during the clamp study (68 +/- 5 vs. 57 +/- 4 micromol/liter; P = 0.005).
Partial sleep deprivation during only a single night induces insulin resistance in multiple metabolic pathways in healthy subjects. This physiological observation may be of relevance for variations in glucoregulation in patients with type 1 and type 2 diabetes.
The Journal of Clinical Endocrinology and Metabolism 04/2010; 95(6):2963-8. · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sleep restriction results in decreased insulin sensitivity and glucose tolerance in healthy subjects. We hypothesized that sleep duration is also a determinant of insulin sensitivity in patients with type 1 diabetes.
We studied seven patients (three men, four women) with type 1 diabetes: mean age 44 +/- 7 years, BMI 23.5 +/- 0.9 kg/m(2), and A1C 7.6 +/- 0.3%. They were studied once after a night of normal sleep duration and once after a night of only 4 h of sleep. Sleep characteristics were assessed by polysomnography. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp studies with an infusion of [6,6-(2)H(2)]glucose. RESULTS Sleep duration was shorter in the night with sleep restriction than in the unrestricted night (469 +/- 8.5 vs. 222 +/- 7.1 min, P = 0.02). Sleep restriction did not affect basal levels of glucose, nonesterified fatty acids (NEFAs), or endogenous glucose production. Endogenous glucose production during the hyperinsulinemic clamp was not altered during the night of sleep restriction compared with the night of unrestricted sleep (6.2 +/- 0.8 vs. 6.9 +/- 0.6 micromol x kg lean body mass(-1) x min(-1), NS). In contrast, sleep restriction decreased the glucose disposal rate during the clamp (25.5 +/- 2.6 vs. 22.0 +/- 2.1 micromol x kg lean body mass(-1) x min(-1), P = 0.04), reflecting decreased peripheral insulin sensitivity. Accordingly, sleep restriction decreased the rate of glucose infusion by approximately 21% (P = 0.04). Sleep restriction did not alter plasma NEFA levels during the clamp (143 +/- 29 vs. 133 +/- 29 micromol/l, NS).
Partial sleep deprivation during a single night induces peripheral insulin resistance in these seven patients with type 1 diabetes. Therefore, sleep duration is a determinant of insulin sensitivity in patients with type 1 diabetes.
Diabetes care 03/2010; 33(7):1573-7. · 7.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Disturbances in thyroid function have been described in small-for-gestational age (SGA) children but the influence of prematurity is unclear. In addition, the effect of GH treatment on thyroid function has not been studied in short SGA children.
To determine whether short SGA children have higher TSH levels compared to age-matched controls and evaluate the influence of gestational age. To investigate whether GH treatment alters thyroid function.
A total of 264 short SGA children (116 preterm), prepubertal and non-GH deficient.
Serum FT4 and TSH at baseline and after 6, 12 and 24 months of GH treatment.
Baseline mean TSH was higher in preterm short SGA children than in age-matched controls (P < 0.05). Mean FT4 was not significantly different between short SGA children and controls. Baseline FT4 or TSH did not correlate with gestational age, or SDS for birth weight, birth length, height, body mass index, IGF-I or IGFBP-3. Mean FT4 decreased significantly during the first 6 months of GH treatment, but remained within the normal range. TSH did not change during treatment. The change in FT4 did not correlate with the change in height SDS during 24 months of GH treatment.
Preterm short SGA children have higher, although within the normal range, TSH levels than controls. The level of TSH does not correlate with gestational age, birth weight SDS or birth length SDS. FT4 decreases during GH treatment, but is neither associated with an increase in TSH nor does it affect the response to GH treatment. As these mild alterations in thyroid function do not appear clinically relevant, frequent monitoring of thyroid function during GH therapy is not warranted in short SGA children.