Binge eating disorder and night eating syndrome in adults with type 2 diabetes

Objective: To determine the prevalence of binge eating disorder (BED) and night eating syndrome (NES) among applicants to the Look AHEAD (Action for Health in Diabetes) study. Research Methods and Procedures: The Eating Disorders Examination–Questionnaire (EDE‐Q) and the Night Eating Questionnaire (NEQ) were used to screen patients. Phone interviews were conducted using the EDE for those who reported at least eight episodes of objective binge eating in the past month and using the Night Eating Syndrome History and Interview for those who scored ≥25 on the NEQ. Recruitment at four sites (Birmingham, n = 200; Houston, n = 259; Minneapolis, n = 182; and Philadelphia, n = 204) yielded 845 participants (58% women; mean age = 60.1 ± 6.7 years; mean BMI = 36.2 ± 6.3 kg/m²). Results: Screening scores were met by 47 (5.6%) applicants on the EDE‐Q and 71 (8.4%) on the NEQ. Of the 85% (40/47) who completed the EDE interview, 12 were diagnosed with BED, representing 1.4% of the total sample. Of the 72% (51/71) who completed the Night Eating Syndrome History and Interview, 32 were diagnosed with NES, equal to 3.8% of the total sample. Three participants had both BED and NES. Participants with eating disorders were younger, heavier, and reported more eating pathology than those without eating disorders. Discussion: Among obese adults with type 2 diabetes, NES was reported more frequently than BED, which, in turn, was less common than expected.     

Reduced physical activity in adults at risk for type 2 diabetes who curtail their sleep

Adults with parental history of type 2 diabetes have high metabolic morbidity, which is exacerbated by physical inactivity. Self‐reported sleep <6 h/day is associated with increased incidence of obesity and diabetes, which may be mediated in part by sleep‐loss‐related reduction in physical activity. We examined the relationship between habitual sleep curtailment and physical activity in adults with parental history of type 2 diabetes. Forty‐eight young urban adults with parental history of type 2 diabetes (27 F/21 M; mean (s.d.) age 26 (4) years; BMI 23.8 (2.5) kg/m²) each completed 13 (2) days of sleep and physical activity monitoring by wrist actigraphy and waist accelerometry while following their usual lifestyle at home. Laboratory polysomnography was used to screen for sleep disorders. The primary outcome of the study was the comparison of total daily activity counts between participants with habitual sleep <6 vs. ≥6 h/night. Secondary measures included daily time spent sedentary and in light, moderate, and vigorous physical activity. Short sleepers had no sleep abnormalities and showed signs of increased sleep pressure consistent with a behavioral pattern of habitual sleep curtailment. Compared to participants who slept ≥6 h/night, short sleepers had 27% fewer daily activity counts (P = 0.042), spent less time in moderate‐plus‐vigorous physical activity (?43 min/day; P = 0.010), and remained more sedentary (+69 min/day; P = 0.026). Our results indicate that young urban adults with parental history of type 2 diabetes who habitually curtail their sleep have less daily physical activity and more sedentary living, which may enhance their metabolic risk.     

Resistance training improves depressive symptoms in individuals at high risk for type 2 diabetes

Depression is more prevalent in obese individuals and those with diabetes, compared to the general population. This study examined the effect of resistance training on depressed mood in individuals with high (HiMF, n ≥ 2) and low (LoMF, n ≤ 1) numbers of risk factors for metabolic syndrome and type 2 diabetes. The primary hypothesis was that resistance training would significantly reduce depressed mood, as measured by the Cardiac Depression Scale (CDS), in individuals with HiMF. Fifty-five middle-aged volunteers (50.8 ± 0.9 years, mean ± SEM) from the general community participated in the study. After initial allocation to HiMF or LoMF, participants were randomly allocated to 4 groups, HiMF training (HiMFT), HiMF control (HiMFC), LoMF training (LoMFT), and LoMF control (LoMFC). Participants underwent resistance training involving major muscle groups on 3 d·wk(-1) for 10 weeks. Before and after interventions (training or control), participants completed the CDS to assess change in the level of depressed mood. Following resistance training, the CDS score of the HiMFT group was reduced by -14.8 ± 4.9 points on the CDS, a significant improvement in comparison to both baseline (p = 0.01) and HiMFC (p = 0.049) values. No significant change was observed for LoMFT. In the HiMF group only, the percent change in relative muscle strength was correlated with the Δ change in CDS; r = -0.46, p = 0.008. Resistance exercise training programs that consist 7 exercises for the major muscle groups at both low-moderate and moderate-high intensities appear to alleviate depressed mood in individuals with clusters of metabolic risk factors.     

Urinary F2-isoprostanes in young healthy children at risk for type 1 diabetes mellitus

Oxidative stress has been linked to many diseases, but little information exists on biomarkers of oxidative stress in healthy children. The purpose of this study was to describe factors that correlate with urinary F2-isoprostanes, an indicator of oxidative stress, and to establish normal concentrations of F2-isoprostanes in children at risk to develop type 1 diabetes mellitus. Creatinine-adjusted urinary F2-isoprostanes were assessed in 342 Denver children under the age of 7 years, from whom we had collected data during 769 clinic visits from August 1997 through January 2001 (mean 2.3 visits per child). Children were identified by newborn screening for HLA-markers, of varying degrees of prediction, for the development of type 1 diabetes. Plasma antioxidants and carotenoids, age at clinic visit, vitamin supplement use, exposure to environmental tobacco smoke, gender, and race were evaluated as correlates to the degree of oxidative stress, using mixed models for longitudinal data. F2-isoprostane levels were highest in infancy and decreased nonlinearly until 7 years. Female gender, HLA-DR3/4 genotype, higher plasma gamma-tocopherol:total lipids ratio, and lower alpha-carotene:total lipids ratio correlated with higher F2-isoprostane levels. Normal values in this healthy population can be used as the basis for future studies of disease mechanisms involving oxidative stress.     

Effects of pioglitazone and metformin on beta-cell function in nondiabetic subjects at high risk for type 2 diabetes

Thiazolidinediones (TZDs) and metformin decreased the incidence of diabetes in subjects at risk for developing diabetes and improved peripheral or hepatic insulin sensitivity, respectively. Whether they also directly improved beta-cell function is not clear. In vitro studies showed improved beta-cell function in response to TZDs and metformin; however, the effects of TZDs or metformin on beta-cell function in humans are still uncertain. We hypothesized that both TZDs and metformin directly affect beta-cell function. We evaluated beta-cell function and insulin sensitivity (S(I)) in subjects with impaired glucose tolerance or a history of gestational diabetes using oral and intravenous glucose tolerance tests in addition to the glucose-potentiated arginine stimulation test. In contrast to metformin, pioglitazone improved S(I), glucose tolerance, and insulin-independent glucose disposal [glucose effectiveness (S(G))]. Neither pioglitazone nor metformin significantly improved beta-cell compensation for insulin resistance [disposition index (DI)], but the change in DI significantly correlated with baseline S(I). Insulin secretion in response to arginine at maximally potentiating glucose levels (AIR(max)) tended to increase after metformin and to decrease after pioglitazone; however, when adjusted for S(I), the changes were not significant. Our results demonstrate that, in nondiabetic subjects at risk for diabetes, pioglitazone, but not metformin, significantly improved glucose tolerance by improving S(I) and S(G). We did not find any evidence that either pioglitazone or metformin improved beta-cell function. Improved beta-cell compensation was observed primarily in the subgroup of subjects that had the lowest S(I) at baseline.     

Extending precision medicine tools to populations at high risk of type 2 diabetes

In this Perspective, Shivani Misra and Jose C Florez discuss the application of precision medicine tools in under-represented populations.

People of South Asian ancestry carry a 3-fold higher risk of developing type 2 diabetes (T2D) than white European individuals [1], with the disease typically manifesting a decade earlier [2] and at a leaner body mass index (BMI) [3]. The South Asian population is often considered as a uniform group, but significant heterogeneity in the prevalence of T2D and its phenotype manifestations across south Asia exists, with a higher prevalence in those from Bangladeshi and Pakistani communities [4]. Genome-wide association studies (GWAS) have not fully explained the excess risk observed in South Asian individuals [5,6], and attention has turned to strategies through which genetic information may be leveraged for clinical benefit, such as generating an aggregate of weighted single nucleotide polymorphisms (SNPs) that capture the overall genetic burden for a trait into a polygenic score (PS) (sometimes described as a polygenic risk score) [7]. However, constructing a PS remains challenging in populations that are underrepresented in GWAS.In the accompanying article in PLOS Medicine [8], Hodgson and colleagues investigate the use of a PS to predict T2D in the Genes & Health (G&H) cohort, addressing a key knowledge gap in the applicability of such tools in underrepresented ethnicities. G&H is a pioneering community-based cohort of approximately 48,000 participants of predominantly British Bangladeshi and Pakistani heritage combining genetic and longitudinal electronic healthcare record data. They first assessed the transferability of known T2D genetic risk loci in G&H and constructed a PS using variants from a multi-ancestry GWAS, adjusting the scores for Pakistani and Bangladeshi individuals and selecting the one with the highest odds for prediction. This score was then integrated with 3 versions of a clinical model (QDiabetes) to predict T2D onset over 10 years in 13,642 individuals diabetes free at baseline. The authors show that incorporation of a PS with QDiabetes provided better discrimination of progression to T2D, especially in those developing T2D under 40 years of age and in women with a history of gestational diabetes. Finally, they incorporated the PS into cluster analyses of baseline routine clinical characteristics, replicating clusters defined in European populations and identifying a cluster resembling a subgroup of severe insulin deficiency. This study significantly advances the field on the transferability of PSs, reproducibility of T2D clusters, and clinical translation of these findings to precision medicine for diabetes.     

Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes.

Chronic sleep loss as a consequence of voluntary bedtime restriction is an endemic condition in modern society. Although sleep exerts marked modulatory effects on glucose metabolism, and molecular mechanisms for the interaction between sleeping and feeding have been documented, the potential impact of recurrent sleep curtailment on the risk for diabetes and obesity has only recently been investigated. In laboratory studies of healthy young adults submitted to recurrent partial sleep restriction, marked alterations in glucose metabolism including decreased glucose tolerance and insulin sensitivity have been demonstrated. The neuroendocrine regulation of appetite was also affected as the levels of the anorexigenic hormone leptin were decreased, whereas the levels of the orexigenic factor ghrelin were increased. Importantly, these neuroendocrine abnormalities were correlated with increased hunger and appetite, which may lead to overeating and weight gain. Consistent with these laboratory findings, a growing body of epidemiological evidence supports an association between short sleep duration and the risk for obesity and diabetes. Chronic sleep loss may also be the consequence of pathological conditions such as sleep-disordered breathing. In this increasingly prevalent syndrome, a feedforward cascade of negative events generated by sleep loss, sleep fragmentation, and hypoxia are likely to exacerbate the severity of metabolic disturbances. In conclusion, chronic sleep loss, behavioral or sleep disorder related, may represent a novel risk factor for weight gain, insulin resistance, and Type 2 diabetes.     

Breast size and risk of type 2 diabetes mellitus

Background

Elevated waist circumference and body mass index (BMI), both traditional measures of obesity, are accepted risk factors for type 2 diabetes mellitus. Girls who are obese experience earlier onset of puberty and possibly greater breast development. We sought to evaluate whether a woman''s breast size in late adolescence is associated with an increased risk of type 2 diabetes mellitus in adulthood.

Methods

In conjunction with the ongoing Nurses'' Health Study II, which began to study risk factors for breast cancer among women in 1989, we conducted a prospective cohort study involving 92 106 of the participants. We assessed the risk of type 2 diabetes mellitus in relation to self-reported bra cup sizes, categorized as ≤ A, B, C and ≥ D cups, among participants at age 20.

Results

The mean age of participants at baseline was 38.1 years. A total of 1844 new cases of type 2 diabetes mellitus arose at a mean age of 44.9 years during 886 443 person-years of follow-up. Relative to bra cup size ≤ A, the respective age-adjusted hazard ratios (and 95% confidence intervals [CIs]) were 2.30 (1.99–2.66) for B cup, 4.32 (3.71–5.04) for C cup and 4.99 (4.12–6.05) for ≥ D cup. Upon further adjustments for age at menarche, parity, physical activity, smoking status, diet, multivitamin use, family history of diabetes mellitus, BMI at age 18 and current BMI, the corresponding hazard ratios (and 95% CIs) were 1.37 (1.18–1.59) for B cup, 1.80 (1.53- 2.11) for C cup and 1.64 (1.34–2.01) for ≥ D cup. The addition of waist circumference to this model minimally changed the hazard ratios (and 95% CIs): 1.32 (1.14–1.53) for B cup, 1.71 (1.46–2.01) for C cup and 1.58 (1.29–1.94) for ≥ D cup.

Interpretation

A large bra cup size at age 20 may be a predictor of type 2 diabetes mellitus in middle-aged women. Whether this relation is independent of traditional indicators of obesity remains to be determined.Obesity is an established risk factor for type 2 diabetes mellitus.^1,2 Affected individuals show signs of insulin resistance and hyperinsulinemia, a process that may begin in childhood.^3,4 Pre-adolescent obesity is also an important predictor of age of onset of breast development in young women, and of breast size after puberty.^5,6 Premature onset of puberty is preceded by childhood insulin resistance, hyperinsulinemia and hyperandrogenemia,⁷ which may persist after puberty⁸ and continue into early adulthood.⁹Although an elevated body mass index (BMI)^10,11 and central adiposity¹² are established risk factors for insulin resistance and the onset of type 2 diabetes mellitus, little is known about the contribution of extra-abdominal adipose tissue, including breast tissue, about 60% of which is fatty tissue, to this process.^13,14 We hypothesized that a woman''s breast size in late adolescence reflects her predisposition to insulin resistance and type 2 diabetes mellitus that is both additive to, and independent of, BMI. We explored this hypothesis in conjunction with the Nurses'' Health Study II by relating bra cup size, a proxy for breast size, to the onset of type 2 diabetes mellitus.     

Plasma bicarbonate and risk of type 2 diabetes mellitus

Background:

Several biomarkers of metabolic acidosis, including lower plasma bicarbonate and higher anion gap, have been associated with greater insulin resistance in cross-sectional studies. We sought to examine whether lower plasma bicarbonate is associated with the development of type 2 diabetes mellitus in a prospective study.

Methods:

We conducted a prospective, nested case–control study within the Nurses’ Health Study. Plasma bicarbonate was measured in 630 women who did not have type 2 diabetes mellitus at the time of blood draw in 1989–1990 but developed type 2 diabetes mellitus during 10 years of follow-up. Controls were matched according to age, ethnic background, fasting status and date of blood draw. We used logistic regression to calculate odds ratios (ORs) for diabetes by category of baseline plasma bicarbonate.

Results:

After adjustment for matching factors, body mass index, plasma creatinine level and history of hypertension, women with plasma bicarbonate above the median level had lower odds of diabetes (OR 0.76, 95% confidence interval [CI] 0.60–0.96) compared with women below the median level. Those in the second (OR 0.92, 95% CI 0.67–1.25), third (OR 0.70, 95% CI 0.51–0.97) and fourth (OR 0.75, 95% CI 0.54–1.05) quartiles of plasma bicarbonate had lower odds of diabetes compared with those in the lowest quartile (p for trend = 0.04). Further adjustment for C-reactive protein did not alter these findings.

Interpretation:

Higher plasma bicarbonate levels were associated with lower odds of incident type 2 diabetes mellitus among women in the Nurses’ Health Study. Further studies are needed to confirm this finding in different populations and to elucidate the mechanism for this relation.Resistance to insulin is central to the pathogenesis of type 2 diabetes mellitus.¹ Several mechanisms may lead to insulin resistance and thereby contribute to the development of type 2 diabetes mellitus, including altered fatty acid metabolism, mitochondrial dysfunction and systemic inflammation.² Metabolic acidosis may also contribute to insulin resistance. Human studies using the euglycemic and hyperglycemic clamp techniques have shown that mild metabolic acidosis induced by the administration of ammonium chloride results in reduced tissue insulin sensitivity.³ Subsequent studies in rat models have suggested that metabolic acidosis decreases the binding of insulin to its receptors.^4,5 Finally, metabolic acidosis may also increase cortisol production,⁶ which in turn is implicated in the development of insulin resistance.⁷Recent epidemiologic studies have shown an association between clinical markers of metabolic acidosis and greater insulin resistance or prevalence of type 2 diabetes mellitus. In the National Health and Nutrition Examination Survey, both lower serum bicarbonate and higher anion gap (even within ranges considered normal) were associated with increased insulin resistance among adults without diabetes.⁸ In addition, higher levels of serum lactate, a small component of the anion gap, were associated with higher odds of prevalent type 2 diabetes mellitus in the Atherosclerosis Risk in Communities study⁹ and with higher odds of incident type 2 diabetes mellitus in a retrospective cohort study of the risk factors for diabetes in Swedish men.¹⁰ Other biomarkers associated with metabolic acidosis, including higher levels of serum ketones,¹¹ lower urinary citrate excretion¹² and low urine pH,¹³ have been associated in cross-sectional studies with either insulin resistance or the prevalence of type 2 diabetes mellitus. However, it is unclear whether these associations are a cause or consequence. We sought to address this question by prospectively examining the association between plasma bicarbonate and subsequent development of type 2 diabetes mellitus in a nested case–control study within the Nurses’ Health Study.     

A risk score to predict type 2 diabetes mellitus in an elderly Spanish Mediterranean population at high cardiovascular risk

Introduction

To develop and test a diabetes risk score to predict incident diabetes in an elderly Spanish Mediterranean population at high cardiovascular risk.

Materials and Methods

A diabetes risk score was derived from a subset of 1381 nondiabetic individuals from three centres of the PREDIMED study (derivation sample). Multivariate Cox regression model ß-coefficients were used to weigh each risk factor. PREDIMED-personal Score included body-mass-index, smoking status, family history of type 2 diabetes, alcohol consumption and hypertension as categorical variables; PREDIMED-clinical Score included also high blood glucose. We tested the predictive capability of these scores in the DE-PLAN-CAT cohort (validation sample). The discrimination of Finnish Diabetes Risk Score (FINDRISC), German Diabetes Risk Score (GDRS) and our scores was assessed with the area under curve (AUC).

Results

The PREDIMED-clinical Score varied from 0 to 14 points. In the subset of the PREDIMED study, 155 individuals developed diabetes during the 4.75-years follow-up. The PREDIMED-clinical score at a cutoff of ≥6 had sensitivity of 72.2%, and specificity of 72.5%, whereas AUC was 0.78. The AUC of the PREDIMED-clinical Score was 0.66 in the validation sample (sensitivity = 85.4%; specificity = 26.6%), and was significantly higher than the FINDRISC and the GDRS in both the derivation and validation samples.

Discussion

We identified classical risk factors for diabetes and developed the PREDIMED-clinical Score to determine those individuals at high risk of developing diabetes in elderly individuals at high cardiovascular risk. The predictive capability of the PREDIMED-clinical Score was significantly higher than the FINDRISC and GDRS, and also used fewer items in the questionnaire.     

Serum fetuin-A associates with type 2 diabetes and insulin resistance in Chinese adults

Background

Previous studies have demonstrated that fetuin-A is related to insulin resistance among subjects with normal glucose tolerance but not patients with type 2 diabetes. There are limited data available concerning fetuin-A and insulin resistance in Chinese. We aimed to study the association of feuin-A with insulin resistance among participants with or without type 2 diabetes in a large sample size of adults aged 40 and older.

Methodology and Principal Findings

A community-based cross-sectional study was performed among 5,227 Chinese adults. The average age of our study was 61.5±9.9 years. Serum fetuin-A concentrations were not significantly different between male and female (296.9 vs. 292.9 mg/l, p = 0.11). Compared with the lowest quartile, the highest quartile of serum fetuin-A revealed a significant higher proportion of type 2 diabetic patients (34.8% vs. 27.3%, p<0.0001). In the multinomial logit models, the risk of type 2 diabetes was associated with each one quartile increase of serum fetuin-A concentrations when referenced not only to normal glucose tolerance (OR 1.24, 95% CI 1.07–1.43, p = 0.004) but also to impaired glucose regulation (OR 1.25, 95% CI 1.08–1.44, p = 0.003, respectively), after adjustment for age, sex, community, current smoking, and current drinking. The logistic regression analysis showed that fetuin-A were associated with elevated HOMA-IR and fasting serum insulin both among the participants with or without type 2 diabetes in the full adjusted analysis. There was no significant association between elevated serum fetuin-A concentrations and impaired glucose regulation (all p≥0.12).

Conclusions and Significance

Higher fetuin-A concentrations were associated with type 2 diabetes and insulin resistance in middle aged and elderly Chinese.     

Different strategies for screening and prevention of type 2 diabetes in adults: cost effectiveness analysis

Objective To compare four potential screening strategies, and subsequent interventions, for the prevention and treatment of type 2 diabetes: (a) screening for type 2 diabetes to enable early detection and treatment, (b) screening for type 2 diabetes and impaired glucose tolerance, intervening with lifestyle interventions in those with a diagnosis of impaired glucose tolerance to delay or prevent diabetes, (c) as for (b) but with pharmacological interventions, and (d) no screening.Design Cost effectiveness analysis based on development and evaluation of probabilistic, comprehensive economic decision analytic model, from screening to death.Setting A hypothetical population, aged 45 at time of screening, with above average risk of diabetes.Data sources Published clinical trials and epidemiological studies retrieved from electronic bibliographic databases; supplementary data obtained from the Department of Health statistics for England and Wales, the screening those at risk (STAR) study, and the Leicester division of the ADDITION study.Methods A hybrid decision tree/Markov model was developed to simulate the long term effects of each screening strategy, in terms of both clinical and cost effectiveness outcomes. The base case model assumed a 50 year time horizon with discounting of both costs and benefits at 3.5%. Sensitivity analyses were carried out to investigate assumptions of the model and to identify which model inputs had most impact on the results.Results Estimated costs for each quality adjusted life year (QALY) gained (discounted at 3.5% a year for both costs and benefits) were £14 150 (€17 560; $27 860) for screening for type 2 diabetes, £6242 for screening for diabetes and impaired glucose tolerance followed by lifestyle interventions, and £7023 for screening for diabetes and impaired glucose tolerance followed by pharmacological interventions, all compared with no screening. At a willingness-to-pay threshold of £20 000 the probability of the intervention being cost effective was 49%, 93%, and 85% for each of the active screening strategies respectively.Conclusions Screening for type 2 diabetes and impaired glucose tolerance, with appropriate intervention for those with impaired glucose tolerance, in an above average risk population aged 45, seems to be cost effective. The cost effectiveness of a policy of screening for diabetes alone, which offered no intervention to those with impaired glucose tolerance, is still uncertain.     

Mental ability performance among adults with type 2 diabetes in primary care

Aim and method The present university-based outpatient clinic, cross-sectional study assessed cognitive performance in a sample of 137 adults, with the primary objective of determining differences in cognitive performance as a function of gender and hypertension status in a type 2 diabetes cohort.Results Approximately 64% of the sample was 65 years old and younger, and 50 subjects had > 13 years of education. Global mental ability scores were relatively similar by age grouping, and higher-ordered cognitive functioning and reading literacy were strongly correlated, r (98) = 0.62, P < 0.01. Approximately 30% of the sample posted global mental ability scores in the slow learner range on tasks measuring attention, immediate memory and verbal reasoning. Males achieved higher cognitive functioning scores compared to females on multiple mental ability tasks. The presence of hypertension was associated with significantly worse cognitive performance compared to those subjects without hypertension, t = 2.11, P = 0.03. Approximately 57% of the hypertension group was classified as mild cognitive impaired.Conclusion While approximately half of the general population can be expected to demonstrate an average range of performance on cognitive ability measures, such an expectation could be inappropriately generalised to persons diagnosed with type 2 diabetes, even among those who were high school educated.