Later chronotype is associated with higher hemoglobin A1c in prediabetes patients

The circadian system is known to play a role in glucose metabolism. Chronotype reflects the interindividual variability in the phase of entrainment. Those with later chronotype typically prefer later times in the day for different activities such as sleep or meals. Later chronotype has been shown to be associated with metabolic syndrome, increased diabetes risk and poorer glycemic control in type 2 diabetes patients. In addition, “social jetlag”, a form of circadian misalignment due to a mismatch between social rhythms and the circadian clock, has been shown to be associated with insulin resistance. Other sleep disturbances (insufficient sleep, poor sleep quality and sleep apnea) have also been shown to affect glucose metabolism. In this study, we explored whether there was a relationship between chronotype, social jetlag and hemoglobin A1c (HbA1c) levels in prediabetes patients, independent of other sleep disturbances. A cross-sectional study was conducted at the Department of Family Medicine, Ramathibodi Hospital, Bangkok, from October 2014 to March 2016 in 1014 non-shift working adults with prediabetes. Mid-sleep time on free day adjusted for sleep debt (MSFsc) was used as an indicator of chronotype. Social jetlag was calculated based on the absolute difference between mid-sleep time on weekdays and weekends. The most recent HbA1c values and lipid levels were retrieved from clinical laboratory databases. Univariate analyses revealed that later MSFsc (p = 0.028) but not social jetlag (p = 0.48) was significantly associated with higher HbA1c levels. Multivariate linear regression analysis was applied to determine whether an independent association between MSFsc and HbA1c level existed. After adjusting for age, sex, alcohol use, body mass index (BMI), social jetlag, sleep duration, sleep quality and sleep apnea risk, later MSFsc was significantly associated with higher HbA1c level (B = 0.019, 95% CI: 0.00001, 0.038, p = 0.049). The effect size of one hour later MSFsc on HbA1c (standardized coefficient = 0.065) was approximately 74% of that of the effect of one unit (kg/m²) increase in BMI (standardized coefficient = 0.087). In summary, later chronotype is associated with higher HbA1c levels in patients with prediabetes, independent of social jetlag and other sleep disturbances. Further research regarding the potential role of chronotype in diabetes prevention should be explored.     

Relationships among sleep timing,sleep duration and glycemic control in Type 2 diabetes in Thailand

There is evidence that the sleep and circadian systems play a role in glucose metabolism. In addition to physiological factors, sleep is also affected by behavioral, environmental, cultural and social factors. In this study, we examined whether morning or evening preference, sleep timing and sleep duration are associated with glycemic control in patients with type 2 diabetes residing in Thailand. Two hundred and ten type 2 diabetes patients who were not shift workers completed an interview and questionnaires to collect information on diabetes history, habitual sleep duration and sleep timing. Chronotype, an individual’s tendency for being a “morning” or “evening” person, was assessed using the Composite Score of Morningness (CSM), which reflects an individual’s subjective preference for activities in the morning or evening, as well as mid-sleep time on weekend nights (MSF), which reflects their actual sleep behavior. Most recent hemoglobin A1c (HbA1c) values were retrieved from medical records. Evening preference (as indicated by lower CSM), later bedtime on weekends, and shorter sleep duration correlated with higher HbA1c (r?=??0.18, p?=?0.01; r?=?0.17, p?=?0.01 and r?=??0.17, p?=?0.01, respectively), while there was no association between MSF or wake up time and glycemic control. In addition, later bedtime on weekends significantly correlated with shorter sleep duration (r?=??0.34, p?<?0.001). Hierarchical regression analyses adjusting for age, sex, body mass index, insulin use and diabetes duration revealed that later bedtime on weekends was significantly associated with poorer glycemic control (B?=?0.018, p?=?0.02), while CSM was not. Mediation analysis revealed that this association was fully mediated by sleep duration. In summary, later bedtime on weekends was associated with shorter sleep duration and poorer glycemic control in patients with type 2 diabetes. It is likely that patients with later weekend bedtimes curtail their sleep by waking up earlier. Exploring the potential reasons for this phenomenon (e.g. cultural influences, metropolitan lifestyle, environmental factors, family and social obligations) specific to a Thai population may help identify behavioral modifications (i.e. earlier bedtime and/or sleep duration extension) that could possibly lead to improved glycemic control in this population.     

Relevance of chronotype for eating patterns in adolescents

During adolescence, a shift from morningness to eveningness occurs, yet school continues to start early in the morning. Hence, adolescents are at risk for social jetlag, i.e. a discrepancy between biological and social timing. It remains to be determined whether chronotype associates with daily and daytime-specific eating patterns during this potentially critical period. Therefore, the aim of the present study was to investigate whether chronotype is decisive for daily eating patterns [total energy intake (TEI, kcal), total macronutrient intake (% of TEI), eating occasion frequency (n/day), meal frequency (n/day), snack frequency (n/day), duration of nightly fasting], or daytime-specific eating patterns [morning (before 11 am) energy intake (% of TEI), morning macronutrient intake (% of morning energy intake), regular breakfast skipping (no morning energy intake at least on 2 of 3?days, yes/no), evening (after 6 pm) energy intake (% of TEI), evening macronutrient intake (% of evening energy intake), regular dinner skipping (no evening energy intake at least on 2 of 3?days, yes/no)] in German adolescents. Chronotype was assessed by use of the Munich Chronotype Questionnaire and is defined as the midpoint of sleep corrected for sleep-debt accumulated over the workweek (the later the midpoint of sleep, the later the chronotype). A total of 223 participants (10–18?years) provided 346 questionnaires and concurrent 3-day weighed dietary records. Associations between chronotype and eating patterns were analyzed cross-sectionally using multivariable linear and logistic mixed-effects regression models. Adolescents with earlier and later chronotypes did not differ in their daily eating patterns. With respect to daytime-specific eating patterns, 1?h delay in chronotype was associated with 4.0 (95% CI 2.5–6.6) greater odds of regular breakfast skipping (p < 0.0001). In addition, later chronotype was associated with higher evening energy intake (p = 0.0009). In conclusion, our data show that a later chronotype among adolescents is associated with a shift of food consumption toward later times of the day. Hence, adolescents’ eating patterns appear to follow their internal clock rather than socially determined schedules.     

Trace elements,oxidative stress and glycemic control in young people with type 1 diabetes mellitus

Trace elements and oxidative stress are associated with glycemic control and diabetic complications in type 1 diabetes mellitus. In this study, we analyzed the levels of serum copper, zinc, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and urinary MDA and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in 33 type 1 diabetic patients with optimal and suboptimal glycemic control (HbA_1C < 9.0%) and 40 patients with poor glycemic control (HbA_1C ≥ 9%) and 27 age- and sex-matched non-diabetic controls to evaluate the differences between these markers in different glycemic control states. Diabetic patients, especially poor-glycemic-control subjects (HbA_1C ≥ 9%), exhibited significantly lower levels of serum zinc and increased levels of serum copper (and, therefore, increased serum copper-to-zinc ratios), serum SOD, blood MDA, and urinary MDA and 8-OHdG, relative to non-diabetic subjects. Furthermore, significant correlations existed in these patients between the serum copper, serum copper-to-zinc ratio, and urinary MDA (all p < 0.001) and the levels of urinary 8-OHdG (p = 0.007) and HbA_1C. Our results suggest that high serum copper levels and oxidative stress correlate with glycemic control. Therefore, strict glycemic control, decreased oxidative stress, and a lower copper concentration might prevent diabetic complications in patients with type 1 diabetes mellitus.     

High-energy breakfast based on whey protein reduces body weight,postprandial glycemia and HbA1C in Type 2 diabetes

Acute studies show that addition of whey protein at breakfast has a glucose-lowering effect through increased incretin and insulin secretion. However, whether this is a long-term effect in Type 2 diabetes is unknown. Fifty-six Type 2 diabetes participants aged 58.9±4.5 years, BMI 32.1±0.9 kg/m² and HbA_1C 7.8±0.1% (61.6±0.79 mmol/mol) were randomized to one of 3 isocaloric diets with similar lunch and dinner, but different breakfast: 1) 42 g total protein, 28 g whey (WBdiet, n=19); 2) 42 g various protein sources (PBdiet, n=19); or 3) high-carbohydrate breakfast, 17 g protein from various sources (CBdiet, n=18). Body weight and HbA_1C were examined after 12 weeks. All participants underwent three all-day meal challenges for postprandial glycemia, insulin, C-peptide, intact glucagon-like peptide 1 (iGLP-1), ghrelin and hunger and satiety scores. Overall postprandial AUC_glucose was reduced by 12% in PBdiet and by 19% in WBdiet, compared with CBdiet (P<.0001). Compared with PBdiet and CBdiet, WBdiet led to a greater postprandial overall AUC for insulin, C-peptide, iGLP-1 and satiety scores, while postprandial overall AUC for ghrelin and hunger scores were reduced (P<.0001). After 12 weeks, HbA_1C was reduced after WBdiet by 0.89±0.05% (11.5±0.6 mmol/mol), after PBdiet by 0.6±0.04% (7.1±0.31 mmol/mol) and after CBdiet by 0.36±0.04% (2.9±0.31 mmol/mol) (P<.0001). Furthermore, the participants on WBdiet lost 7.6±0.3 kg, PBdiet 6.1±0.3 kg and CBdiet 3.5±0.3 kg (P<.0001). Whey protein-based breakfast is an important adjuvant in the management of Type 2 diabetes.     

Motherhood,Apple Pie,Hemoglobin A1c,and the DCCT

ObjectiveTo review recent literature on the limitations of hemoglobin A_1c (HbA_1c) as a marker of glycemic control.MethodsEnglish-language literature published between 1985 and 2011 was reviewed specific to analyses of major trials relating glycemic control to complications of diabetes mellitus, as expressed through HbA_1c as a marker of glycemic control.ResultsHbA_1c has been accepted as the most fundamental biomarker in diabetes, if not all of medicine, as it clearly predicts risk for diabetes-related complications. What is not generally appreciated is that HbA_1c is a crude marker of glycemia with many limitations. It is now accepted that HbA_1c does not reflect mean glucose for many people, and even for those it does, any level could represent a wide range of glycemia. While we have learned HbA_1c is not a perfect biomarker, we also know that in the Diabetes Control and Complications Trial, HbA_1c could only explain 11% of the variation in retinopathy risk between the conventional and intensive therapy groups. This important finding suggests that other glycemic and nonglycemic factors may be responsible for the pathogenesis of diabetes-related complications. One candidate is glycemic variability, which must be differentiated from postprandial hyperglycemia since hypoglycemia can also result in inflammatory activation. Importantly, although it is clear that in insulin-requiring patients glycemic variability is associated with hypoglycemia, we require a definitive prospective trial to confirm glycemic variability’s association with one or more vascular complications.ConclusionsWhat is abundantly clear is that the HbA_1c message, as we know it, is too simplistic. While certain wholesome concepts such as motherhood and apple pie are accepted by all, the HbA_1c message may be more complex than originally appreciated, and it may be time to reevaluate our most basic premise in diabetes. (Endocr Pract. 2012;18:78-84)     

Dietary Intake of Whole and Refined Grain Breakfast Cereals and Weight Gain in Men

Objective: Prospective studies have suggested that substituting whole grain for refined grain products may lower the risk of overweight and obesity. Breakfast cereal intake is a major source of whole and refined grains and has also been associated with having a lower BMI. The aim of this study was to prospectively assess the association between whole and refined grain breakfast cereal intakes and risk of overweight (BMI ≥ 25 kg/m²) and weight gain. Research Methods and Procedures: We examined 17, 881 U.S. male physicians 40 to 84 years of age in 1982 who were free of cardiovascular disease, diabetes mellitus, and cancer at baseline and reported measures of breakfast cereal intake, weight, and height. Results: Over 8 and 13 years of follow‐up, respectively, men who consumed breakfast cereal, regardless of type, consistently weighed less than those who consumed breakfast cereals less often (p value for trend = 0.01). Whole and refined grain breakfast cereal intake was inversely associated with body weight gain over 8 years, after adjustment for age, smoking, baseline BMI, alcohol intake, physical activity, hypertension, high cholesterol, and use of multivitamins. Compared with men who rarely or never consumed breakfast cereals, those who consumed ≥1 serving/d of breakfast cereals were 22% and 12% less likely to become overweight during follow‐up periods of 8 and 13 years (relative risk, 0.78 and 0.88; 95% confidence interval, 0.67 to 0.91 and 0.76 to 1.00, respectively). Discussion: BMI and weight gain were inversely associated with intake of breakfast cereals, independently of other risk factors.     

Associations between chronotype,morbidity and mortality in the UK Biobank cohort

Later chronotype (i.e. evening preference) and later timing of sleep have been associated with greater morbidity, including higher rates of metabolic dysfunction and cardiovascular disease (CVD). However, no one has examined whether chronotype is associated with mortality risk to date. Our objective was to test the hypothesis that being an evening type is associated with increased mortality in a large cohort study, the UK Biobank. Our analysis included 433 268 adults aged 38–73 at the time of enrolment and an average 6.5-year follow-up. The primary exposure was chronotype, as assessed through a single self-reported question-defining participants as definite morning types, moderate morning types, moderate evening types or definite evening types. The primary outcomes were all-cause mortality and mortality due to CVD. Prevalent disease was also compared among the chronotype groups. Analyses were adjusted for age, sex, ethnicity, smoking, body mass index, sleep duration, socioeconomic status and comorbidities. Greater eveningness, particularly being a definite evening type, was significantly associated with a higher prevalence of all comorbidities. Comparing definite evening type to definite morning type, the associations were strongest for psychological disorders (OR 1.94, 95% CI 1.86–2.02, p = < 0.001), followed by diabetes (OR 1.30, 95% CI 1.24–1.36, p = < 0.001), neurological disorders (OR 1.25, 95% CI 1.20–1.30, p = < 0.001), gastrointestinal/abdominal disorders (OR 1.23, 95% CI 1.19–1.27, p = < 0.001) and respiratory disorders (OR 1.22, 95% CI 1.18–1.26, p = < 0.001). The total number of deaths was 10 534, out of which 2127 were due to CVD. Greater eveningness, based on chronotype as an ordinal variable, was associated with a small increased risk of all-cause mortality (HR 1.02, 95% CI 1.004–1.05, p = 0.017) and CVD mortality (HR 1.04, 95% CI 1.00–1.09, p = 0.06). Compared to definite morning types, definite evening types had significantly increased risk of all-cause mortality (HR 1.10, 95% CI 1.02–1.18, p = 0.012). This first report of increased mortality in evening types is consistent with previous reports of increased levels of cardiometabolic risk factors in this group. Mortality risk in evening types may be due to behavioural, psychological and physiological risk factors, many of which may be attributable to chronic misalignment between internal physiological timing and externally imposed timing of work and social activities. These findings suggest the need for researching possible interventions aimed at either modifying circadian rhythms in individuals or at allowing evening types greater working hour flexibility.     

A Study Assessing the Association of Glycated Hemoglobin A1C (HbA1C) Associated Variants with HbA1C,Chronic Kidney Disease and Diabetic Retinopathy in Populations of Asian Ancestry

Glycated hemoglobin A_1C (HbA_1C) level is used as a diagnostic marker for diabetes mellitus and a predictor of diabetes associated complications. Genome-wide association studies have identified genetic variants associated with HbA_1C level. Most of these studies have been conducted in populations of European ancestry. Here we report the findings from a meta-analysis of genome-wide association studies of HbA_1C levels in 6,682 non-diabetic subjects of Chinese, Malay and South Asian ancestries. We also sought to examine the associations between HbA_1C associated SNPs and microvascular complications associated with diabetes mellitus, namely chronic kidney disease and retinopathy. A cluster of 6 SNPs on chromosome 17 showed an association with HbA_1C which achieved genome-wide significance in the Malays but not in Chinese and Asian Indians. No other variants achieved genome-wide significance in the individual studies or in the meta-analysis. When we investigated the reproducibility of the findings that emerged from the European studies, six loci out of fifteen were found to be associated with HbA_1C with effect sizes similar to those reported in the populations of European ancestry and P-value ≤ 0.05. No convincing associations with chronic kidney disease and retinopathy were identified in this study.     

A prospective study of breakfast consumption and weight gain among U.S. men

Objective: The aim was to investigate the association between breakfast consumption and long‐term weight gain in an adult male population. Research Methods and Procedures: We evaluated prospective data on 20,064 U.S men, 46 to 81 years of age, who participated in the Health Professionals Follow‐up Study. Data on body weight, dietary factors, and lifestyle variables were obtained by validated questionnaires. We examined weight gain during 10 years of follow‐up. Results: Overall, 5857 men had a weight gain of 5 kg or greater during 10 years of follow‐up. Breakfast consumption was inversely associated with the risk of 5‐kg weight gain after adjustment for age [hazard ratio (HR) = 0.77 (95% confidence interval [CI], 0.72 to 0.82)], and this association was independent of lifestyle and BMI at baseline [HR = 0.87 (95% CI, 0.82 to 0.93)]. Fiber and nutrient intakes partially explained the association between breakfast consumption and weight gain. The inverse association between breakfast consumption and weight gain was more pronounced in men with a baseline BMI of 25 kg/m² or lower [multivariate HR = 0.78 (95% CI, 0.70 to 0.87)] than in men who were overweight at baseline [HR = 0.92 (95% CI, 0.85 to 1.00)]. Furthermore, we observed that an increasing number of eating occasions in addition to three standard meals was associated with a higher risk of 5‐kg weight gain [HR = 1.15 (95% CI, 1.06 to 1.25, for ≥2 vs. 0 additional eating occasions)]. Discussion: These findings suggest that the consumption of breakfast may modestly contribute to the prevention of weight gain as compared with skipping breakfast in middle‐aged and older men.     

Validity of the Japanese version of the Munich ChronoType Questionnaire

To assess circadian preference with a score, the Morningness-Eveningness Questionnaire (MEQ) has been used for more than 3 decades now. More recently, the Munich ChronoType Questionnaire (MCTQ) was developed: it asks for sleep-wake behavior on work and free days and uses the midpoint of sleep on free days (MSF), corrected for sleep debt accumulated during the work week as an indicator of chronotype (MSF_sc). In this study, we developed a Japanese version of the MCTQ by using a translation/back-translation approach including an examination of its semantic validity. In a subsequent questionnaire survey, 450 adult men and women completed the Japanese versions of the MCTQ and MEQ. Results showed that MEQ scores were significantly negatively correlated with mid-sleep parameters assessed by the MCTQ, on both, work and free days, as well as with the chronotype measure MSF_sc (r?=??0.580 to ?0.652, all p?<?0.001). As in the original German version, the strongest correlation was observed between MEQ score and MSF. A physiological validation study using dim light melatonin onset as a circadian phase marker (N?=?37) showed a high correlation between chronotype as assessed with the MSF_sc (r?=?0.542, p?<?0.001), and less so for MEQ score (r?=??0.402, p?=?0.055). These results demonstrate the validity of the Japanese MCTQ and provide further support of the adequacy of the MCTQ as a chronotype measure.     

Tumor Necrosis Factor-α, Matrix-Metalloproteinases 8 and 9 Levels in the Saliva Are Associated with Increased Hemoglobin A1c in Type 1 Diabetes Subjects

Background

Type 1 diabetes (T1D) is an autoimmune disease resulting in the targeted destruction of pancreatic β-cells and permanent loss of insulin production. Proper glucose management results in better clinical outcomes for T1D and provides a strong rationale to identify non-invasive biomarkers indicative or predictive of glycemic control. Therefore, we investigated the association of salivary inflammation with HbA_1c in a T1D cohort.

Methods

Unstimulated saliva was collected from 144 subjects with T1D at the USF Diabetes Center. BMI, duration of diabetes, and HbA_1c were recorded during clinical visit. Levels of interleukin (IL)-1β, -6, -8, -10, IFN-γ, TNF-α, MMP-3, -8, and -9 were measured using multiplexing immunoassay analysis. To account for smoking status, salivary cotinine levels were also determined.

Results

Multiple linear (HbA_1c) and logistic (self-reported gingival condition) regression analyses were performed to examine the relationships between the Principal Component Analysis (PCA) components and HbA_1c and gingival condition (adjusted for age, duration of diabetes, BMI, and sex; model for HbA_1c also adjusted for gingival condition and model for gingival condition also adjusted for HbA_1c). PCA components 1 (MMP-8 and MMP-9) and 3 (TNF-α) were significantly associated with HbA_1c (β = 0.28 ±0.14, p = 0.045; β = 0.31 ±0.14, p = 0.029), while PCA component 2 (IL-6, IL-1β, and IL-8) was significantly associated with gingival condition (OR 1.60 95% CI 1.09–2.34, p = 0.016). In general, increased salivary inflammatory burden is associated with decreased glycemic control and self-reported gingival condition.

Conclusions

The saliva may represent a useful reservoir of novel noninvasive inflammatory biomarkers predictive of the progression and control of T1D.     

Sputum Glucose and Glycemic Control in Cystic Fibrosis-Related Diabetes: A Cross-Sectional Study

Cystic fibrosis-related diabetes affects up to half of cystic fibrosis patients and is associated with increased mortality and more frequent pulmonary exacerbations. However, it is unclear to what degree good glycemic control might mitigate these risks and clinical outcomes have not previously been studied in relation to glucose from the lower airways, the site of infection and CF disease progression. We initially hypothesized that diabetic cystic fibrosis patients with glycosylated hemoglobin (HbA_1c) > 6.5% have worse pulmonary function, longer and more frequent exacerbations and also higher sputum glucose levels than patients with HbA_1c ≤ 6.5% or cystic fibrosis patients without diabetes. To test this, we analyzed spontaneously expectorated sputum samples from 88 cystic fibrosis patients. The median sputum glucose concentration was 0.70 mM (mean, 4.75 mM; range, 0-64.6 mM). Sputum glucose was not correlated with age, sex, body mass index, diabetes diagnosis, glycemic control, exacerbation frequency or length, or pulmonary function. Surprisingly, sputum glucose was highest in subjects with normal glucose tolerance, suggesting the dynamics of glycemic control, sputum glucose and pulmonary infections are more complex than previously thought. Two-year mean HbA_1c was positively correlated with the length of exacerbation admission (p < 0.01), and negatively correlated with measures of pulmonary function (p < 0.01). While total number of hospitalizations for exacerbations were not significantly different, subjects with an HbA_1c > 6.5% were hospitalized on average 6 days longer than those with HbA_1c ≤ 6.5% (p < 0.01). Current clinical care guidelines for cystic fibrosis-related diabetes target HbA_1c ≤ 7% to limit long-term microvascular damage, but more stringent glycemic control (HbA_1c ≤ 6.5%) may further reduce the short-term pulmonary complications.     

Associations between nocturnal urinary 6-sulfatoxymelatonin,obstructive sleep apnea severity and glycemic control in type 2 diabetes

Reduced nocturnal secretion of melatonin, a pineal hormone under circadian control, and obstructive sleep apnea have been both identified as risk factors for the development of type 2 diabetes mellitus. Whether they interact to impact glycemic control in patients with existing type 2 diabetes is not known. Therefore, this study explores the relationships between obstructive sleep apnea, melatonin and glycemic control in type 2 diabetes. As diabetic retinopathy may affect melatonin secretion, we also explore the relationship between retinopathy, melatonin and glycemic control. Fifty-six non-shift workers with type 2 diabetes, who were not using beta-blockers, participated. Most recent hemoglobin A1c (HbA1c) levels and the results of ophthalmologic examinations were obtained from medical records. Obstructive sleep apnea was diagnosed using an ambulatory device. Sleep duration and fragmentation were recorded by 7-day wrist actigraphy. The urinary 6-sulfatoxymelatonin/creatinine ratio, an indicator of nocturnal melatonin secretion, was measured in an overnight urine sample. Mediation analyses were applied to explore whether low nocturnal urinary 6-sulfatoxymelatonin/creatinine ratio could be a causal link between increasing obstructive sleep apnea severity [as measured by an Apnea Hypopnea Index (AHI)] and poorer glycemic control, and between the presence of retinopathy and glycemic control. AHI and HbA1c were log-scale (ln) transformed. Obstructive sleep apnea was found in 76.8%, and 25.5% had diabetic retinopathy. The median (interquartile range) of urinary 6-sulfatoxymelatonin/creatinine ratio was 12.3 (6.0, 20.1) ng/mg. Higher lnHbA1c significantly correlated with lower 6-sulfatoxymelatonin/creatinine ratio (p = 0.04) but was not directly associated with OSA severity. More severe obstructive sleep apnea (lnAHI, p = 0.01), longer diabetes duration (p = 0.02), retinopathy (p = 0.01) and insulin use (p = 0.03) correlated with lower urinary 6-sulfatoxymelatonin/creatinine ratio, while habitual sleep duration and fragmentation did not. A mediation analysis revealed that lnAHI negatively correlated with urinary 6-sulfatoxymelatonin/creatinine ratio (coefficient = ?2.413, p = 0.03), and urinary 6-sulfatoxymelatonin/creatinine negatively associated with lnHbA1c (coefficient = ?0.005, p = 0.02), after adjusting for covariates. Mediation analysis indicated that the effect of lnAHI on lnHbA1c was indirectly mediated by urinary 6-sulfatoxymelatonin/creatinine ratio (B = 0.013, 95% CI: 0.0006, 0.0505). In addition, having retinopathy was significantly associated with reduced nocturnal urinary 6-sulfatoxymelatonin/creatinine ratio, and an increase in HbA1c by 1.013% of its original value (B = ?0.013, 95% CI: ?0.038, ?0.005). In conclusion, the presence and severity of obstructive sleep apnea as well as the presence of diabetic retinopathy were associated with lower nocturnal melatonin secretion, with an indirect adverse effect on glycemic control. Intervention studies are needed to determine whether melatonin supplementation may be beneficial in type 2 diabetes patients with obstructive sleep apnea.     

Late chronotype and high social jetlag are associated with burnout in evening-shift workers: Assessment using the Chinese-version MCTQshift

Chronotypes are associated with shift work tolerance and sleep in shift workers, and sleep mediates the impact of shift work on mental health. However, the role of chronotype in the association between shift work and mental health has not been clarified. In this study, we aimed to examine the association between chronotype and burnout in shift workers, using the validated Munich ChronoType Questionnaire for shift workers (MCTQ^shift). A total of 288 shift workers with irregular shift frequencies were recruited and completed the Chinese-version MCTQ^shift and the Morningness–Eveningness Questionnaire (MEQ). Chronotypes were assessed by the calculation of corrected mid-sleep time (MSF_SC) from mid-sleep time on free days (MSF) based on their exact shift schedules. Another 26 evening-shift nurses were monitored with actigraphy for at least two consecutive evening shifts and the following two free days. Burnout was evaluated using the Copenhagen Burnout Inventory. We found that MSF^E_SC, MSF^E and mid-sleep time on workdays (MSW^E) had normal distributions and correlated significantly with MEQ scores (r = ? 0.47, ?0.45 and ?0.47, respectively; all p < 0.001). MSW was more closely correlated with actigraphy-derived mid-sleep time on the free day before workdays than that on workdays (r = 0.61 and 0.48, respectively, p < 0.05). Sleep duration was significantly longer on workdays among evening-shift workers who slept late on workdays than those who slept early (β = 0.59, p < 0.001). After demographic and work characteristics were adjusted for in linear regression models, late chronotype and high social jetlag were associated with burnout scores in evening-shift workers. In conclusion, the Chinese-version MCTQ^shift is a valid tool for chronotype assessment. Interventions to improve sleep in shift workers should be tailored to chronotype due to variations in sleep behavior. Late chronotype may be an inherent feature of mental health problems, because the association with burnout was significant in both day workers in previous studies and shift workers.     

Impact of the look AHEAD intervention on NT-pro brain natriuretic peptide in overweight and obese adults with diabetes

Look AHEAD (Action for Health in Diabetes) is a randomized trial determining whether intensive lifestyle intervention (ILI) aimed at long‐term weight loss and increased physical fitness reduces cardiovascular morbidity and mortality in overweight and obese individuals with type 2 diabetes compared to control (diabetes support and education, DSE). We investigated the correlates of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), a biomarker associated with heart failure (HF) risk, in a subsample from 15 of 16 participating centers and tested the hypothesis that ILI decreased NT‐proBNP levels. Baseline and 1‐year blood samples were assayed for NT‐proBNP in a random sample of 1,500 without, and all 628 with, self‐reported baseline CVD (cardiovascular disease) (N = 2,128). Linear models were used to assess relationships that log‐transformed NT‐proBNP had with CVD risk factors at baseline and that 1‐year changes in NT‐proBNP had with intervention assignment. At baseline, the mean (s.d.) age, BMI, and hemoglobin A_1c (HbA_1c) were 59.6 (6.8) years, 36.0 kg/m² (5.8), and 7.2% (1.1), respectively. Baseline geometric mean NT‐proBNP was not different by condition (ILI 53.3 vs. DSE 51.5, P = 0.45), was not associated with BMI, and was inversely associated with HbA_1c. At 1 year, ILI participants achieved an average weight loss of 8.3% compared to 0.7% in DSE. At 1 year, NT‐proBNP levels increased to a greater extent in the intervention arm (ILI +21.3% vs. DSE +14.2%, P = 0.046). The increased NT‐proBNP associated with ILI was correlated with changes in HbA_1c, BMI, and body composition. In conclusion, among overweight and obese persons with diabetes, an ILI that reduced weight was associated with an increased NT‐proBNP.     

The Effect of Comorbidity on Glycemic Control and Systolic Blood Pressure in Type 2 Diabetes: A Cohort Study with 5 Year Follow-Up in Primary Care

Aims

To explore the longitudinal effect of chronic comorbid diseases on glycemic control (HbA₁C) and systolic blood pressure (SBP) in type 2 diabetes patients.

Methods

In a representative primary care cohort of patients with newly diagnosed type 2 diabetes in The Netherlands (n = 610), we tested differences in the five year trend of HbA₁C and SBP according to comorbidity profiles. In a mixed model analysis technique we corrected for relevant covariates. Influence of comorbidity (a chronic disease already present when diabetes was diagnosed) was tested as total number of comorbid diseases, and as presence of specific disease groups, i.e. cardiovascular, mental, and musculoskeletal disease, malignancies, and COPD. In subgroup effect analyses we tested if potential differences were modified by age, sex, socioeconomic status, and BMI.

Results

The number of comorbid diseases significantly influenced the SBP trend, with highest values after five years for diabetes patients without comorbidity (p = 0.005). The number of diseases did not influence the HbA₁C trend (p = 0.075). Comorbid musculoskeletal disease resulted in lower HbA₁C at the time of diabetes diagnosis, but in higher values after five years (p = 0.044). Patients with cardiovascular diseases had sustained elevated levels of SBP (p = 0.014). Effect modification by socioeconomic status was observed in some comorbidity subgroups.

Conclusions

Presence of comorbidity in type 2 diabetes patients affected the long-term course of HbA₁C and SBP in this primary care cohort. Numbers and types of comorbidity showed differential effects: not the simple sum of diseases, but specific types of comorbid disease had a negative influence on long-term diabetes control parameters. The complex interactions between comorbidity, diabetes control and effect modifiers require further investigation and may help to personalize treatment goals.     

Dose- and Time-Dependent Association of Smoking and Its Cessation with Glycemic Control and Insulin Resistance in Male Patients with Type 2 Diabetes Mellitus: The Fukuoka Diabetes Registry

Objective

Cigarette smoking is an important modifiable risk factor for cardiovascular diseases. However, the effect of smoking and its cessation on glycemic control in diabetic patients has not been fully examined yet. The aim of the present study was to examine the association of smoking status with glycemic level and markers of insulin resistance and secretion in patients with type 2 diabetes mellitus.

Research Design and Methods

A total of 2,490 Japanese male patients with type 2 diabetes mellitus aged ≥20 years were divided according to smoking status, amount of cigarettes smoked and years since quitting. The associations with glycemic level and markers of insulin resistance and secretion were examined cross-sectionally.

Results

HbA_1c levels increased progressively with increases in both number of cigarettes per day and pack-years of cigarette smoking compared with never smokers (P for trend = 0.001 and <0.001, respectively), whereas fasting plasma glucose did not. On the other hand, HbA_1c, but not fasting plasma glucose, decreased linearly with increase in years after smoking cessation (P for trend <0.001). These graded relationships persisted significantly after controlling for the confounders, including total energy intake, current drinking, regular exercise, depressive symptoms, and BMI. In addition, a homeostasis model assessment of insulin resistance and high-sensitivity C-reactive protein also showed similar trends.

Conclusions

Smoking and its cessation showed dose- and time-dependent relationship with glycemic control and insulin resistance in patients with type 2 diabetes mellitus. These findings may highlight the importance of smoking cessation in the clinical management of diabetes mellitus.     

Abdominal Obesity and Ethnic Differences in Diabetes Awareness,Treatment, and Glycemic Control

Objective: To compare racial/ethnic differences in diabetes awareness, treatment, and glycemic control between non-Hispanic white, non-Hispanic black, and Hispanic Americans. We also determined the impact of abdominal obesity on racial/ethnic differences in diabetes awareness, treatment, and glycemic control between these population groups. Research Methods and Procedures: Third National Health and Nutrition Examination Survey (NHANES III) data were utilized for this study. Diabetes awareness was defined as acknowledging diabetic status. Diabetes treatment was defined as current use of anti-diabetic medications, good glycemic control as HbA_1c < 8%, and abdominal obesity as waist circumference larger than expected. The impacts of abdominal obesity on racial/ethnic differences in diabetes awareness, treatment, and glycemic control were assessed using logistic regression analyses. Adjustments were made for age, education, smoking, alcohol intake, and health insurance. Results: Rates of diabetes awareness in whites, blacks, and Hispanics suffering from abdominal obesity were ∼74%, 30%, and 21% in men and 77%, 32%, and 19% in women, respectively. Rates of diabetes treatment were 70%, 23%, and 14% in men and 57%, 45%, and 23% in women, respectively. In men, rates of glycemic control were 64%, 40%, and 30%, and in women, they were 62%, 51%, and 27%, respectively. Abdominal obesity was associated with decreased diabetes awareness and glycemic control in women. Discussion: Subjects with abdominal obesity were found to have poorer glycemic controls compared to those without abdominal obesity. Because diabetes prevalences were partially explained by racial/ethnic differences in diabetes awareness, treatment, and glycemic control, there is a need to craft diabetes awareness, treatment, and control programs along racial/ethnic origins.     

Efficacy of self monitoring of blood glucose in patients with newly diagnosed type 2 diabetes (ESMON study): randomised controlled trial

Objectives To assess the effect of self monitoring of blood glucose concentrations on glycaemic control and psychological indices in patients with newly diagnosed type 2 diabetes mellitus.Design Prospective randomised controlled trial of self monitoring versus no monitoring (control).Setting Hospital diabetes clinics.Participants 184 (111 men) people aged <70 with newly diagnosed type 2 diabetes referred to the participating diabetes clinics. Major exclusion criteria were secondary diabetes, insulin treatment, previous self monitoring of blood glucose.Interventions Participants were randomised to self monitoring or no monitoring (control) groups for one year with follow-up at three monthly intervals. Both groups underwent an identical structured core education programme. The self monitoring group received additional education on monitoring.Main outcome measures Between group differences in HbA_1c, psychological indices, use of oral hypoglycaemic drugs, body mass index (BMI), and reported hypoglycaemia rates.Results 96 patients (55 men) were randomised to monitoring and 88 (56 men) to control. There were no baseline differences in mean (SD) age (57.7 (11.0) in monitoring group v 60.9 (11.5) in control group) or HbA_1c (8.8 (2.1)% v 8.6 (2.3)%, respectively). Those in the monitoring group had a higher baseline BMI (34 (7) v 32 (6.2)). There were no significant differences between groups at any time point (12 months values given) in HbA_1c (6.9 (0.8)% v 6.9 (1.2)%, P=0.69; 95% confidence interval for difference −0.25% to 0.38%), BMI (33.1 (6.4) v 31.8 (6.0); adjusted for baseline BMI, P=0.32), use of oral hypoglycaemic drugs, or reported incidence of hypoglycaemia. Monitoring was associated with a 6% higher score on the depression subscale of the well-being questionnaire (P=0.01).Conclusions In patients with newly diagnosed type 2 diabetes self monitoring of blood glucose concentration has no effect on glycaemic control but is associated with higher scores on a depression subscale.Trial registration ISRCTN 49814766.