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Objective: We examined longitudinal associations between emotional distress (specifically, depressive symptoms and diabetes distress) and medication adherence in Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), a large randomized controlled trial comparing four glucose-lowering medications added to metformin in adults with relatively recent-onset type 2 diabetes mellitus (T2DM)., Research Design and Methods: The Emotional Distress Substudy assessed medication adherence, depressive symptoms, and diabetes distress in 1,739 GRADE participants via self-completed questionnaires administered biannually up to 3 years. We examined baseline depressive symptoms and diabetes distress as predictors of medication adherence over 36 months. Bidirectional visit-to-visit relationships were also examined. Treatment satisfaction, beliefs about medication, diabetes care self-efficacy, and perceived control over diabetes were evaluated as mediators of longitudinal associations., Results: At baseline, mean ± SD age of participants (56% of whom were White, 17% Hispanic/Latino, 18% Black, and 66% male) was 58.0 ± 10.2 years, diabetes duration 4.2 ± 2.8 years, HbA1c 7.5% ± 0.5%, and medication adherence 89.9% ± 11.1%. Higher baseline depressive symptoms and diabetes distress were independently associated with lower adherence over 36 months (P < 0.001). Higher depressive symptoms and diabetes distress at one visit predicted lower adherence at the subsequent 6-month visit (P < 0.0001) but not vice versa. Treatment assignment did not moderate relationships. Patient-reported concerns about diabetes medications mediated the largest percentage (11.9%-15.5%) of the longitudinal link between emotional distress and adherence., Conclusions: Depressive symptoms and diabetes distress both predict lower adherence to glucose-lowering medications over time among adults with T2DM. Addressing emotional distress and concerns about anticipated negative effects of taking these treatments may be important to support diabetes treatment adherence., (© 2024 by the American Diabetes Association.)

Endocrine care of pediatric and adult patients continues to be plagued by health and health care disparities that are perpetuated by the basic structures of our health systems and research modalities, as well as policies that impact access to care and social determinants of health. This scientific statement expands the Society's 2012 statement by focusing on endocrine disease disparities in the pediatric population and sexual and gender minority populations. These include pediatric and adult lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA) persons. The writing group focused on highly prevalent conditions-growth disorders, puberty, metabolic bone disease, type 1 (T1D) and type 2 (T2D) diabetes mellitus, prediabetes, and obesity. Several important findings emerged. Compared with females and non-White children, non-Hispanic White males are more likely to come to medical attention for short stature. Racially and ethnically diverse populations and males are underrepresented in studies of pubertal development and attainment of peak bone mass, with current norms based on European populations. Like adults, racial and ethnic minority youth suffer a higher burden of disease from obesity, T1D and T2D, and have less access to diabetes treatment technologies and bariatric surgery. LGBTQIA youth and adults also face discrimination and multiple barriers to endocrine care due to pathologizing sexual orientation and gender identity, lack of culturally competent care providers, and policies. Multilevel interventions to address these disparities are required. Inclusion of racial, ethnic, and LGBTQIA populations in longitudinal life course studies is needed to assess growth, puberty, and attainment of peak bone mass. Growth and development charts may need to be adapted to non-European populations. In addition, extension of these studies will be required to understand the clinical and physiologic consequences of interventions to address abnormal development in these populations. Health policies should be recrafted to remove barriers in care for children with obesity and/or diabetes and for LGBTQIA children and adults to facilitate comprehensive access to care, therapeutics, and technological advances. Public health interventions encompassing collection of accurate demographic and social needs data, including the intersection of social determinants of health with health outcomes, and enactment of population health level interventions will be essential tools., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Social determinants of health play a role in diabetes management and outcomes, including potentially life-threatening complications of severe hypoglycemia and diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar state (HHS). Although several person-level socioeconomic factors have been associated with these complications, the implications of area-level socioeconomic deprivation are unknown., Objective: To examine the association between area-level deprivation and the risks of experiencing emergency department visits or hospitalizations for hypoglycemic and hyperglycemic crises (ie, DKA or HHS)., Design, Setting, and Participants: This cohort study used deidentified administrative claims data for privately insured individuals and Medicare Advantage beneficiaries across the US. The analysis included adults with diabetes who met the claims criteria for diabetes between January 1, 2016, and December 31, 2017. Data analyses were performed from November 17, 2020, to November 11, 2021., Exposures: Area deprivation index (ADI) was derived for each county for 2016 and 2017 using 17 county-level indicators from the American Community Survey. ADI values were applied to patients who were living in each county based on their index dates and were categorized according to county-level ADI quintile (with quintile 1 having the least deprivation and quintile 5 having the most deprivation)., Main Outcomes and Measures: The numbers of emergency department visits or hospitalizations related to the primary diagnoses of hypoglycemia and DKA or HHS (ascertained using validated diagnosis codes in the first or primary position of emergency department or hospital claims) between 2016 and 2019 were calculated for each ADI quintile using negative binomial regression models and adjusted for patient age, sex, health plan type, comorbidities, glucose-lowering medication type, and percentage of White residents in the county., Results: The study population included 1 116 361 individuals (563 943 women [50.5%]), with a mean (SD) age of 64.9 (13.2) years. Of these patients, 343 726 (30.8%) resided in counties with the least deprivation (quintile 1) and 121 810 (10.9%) lived in counties with the most deprivation (quintile 5). Adjusted rates of severe hypoglycemia increased from 13.54 (95% CI, 12.91-14.17) per 1000 person-years in quintile 1 counties to 19.13 (95% CI, 17.62-20.63) per 1000 person-years in quintile 5 counties, corresponding to an incidence rate ratio of 1.41 (95% CI, 1.29-1.54; P < .001). Adjusted rates of DKA or HHS increased from 7.49 (95% CI, 6.96-8.02) per 1000 person-years in quintile 1 counties to 8.37 (95% CI, 7.50-9.23) per 1000 person-years in quintile 5 counties, corresponding to an incidence rate ratio of 1.12 (95% CI, 1.00-1.25; P = .049)., Conclusions and Relevance: This study found that living in counties with a high area-level deprivation was associated with an increased risk of severe hypoglycemia and DKA or HHS. The concentration of these preventable events in areas of high deprivation signals the need for interventions that target the structural barriers to optimal diabetes management and health.

Purpose: HbA1c levels are higher in blacks than non-Hispanic whites (NHWs). We investigated whether genetics could explain this difference in Diabetes Prevention Program (DPP) participants., Methods: We tested (i) genetic variants causing hemoglobinopathies, (ii) a genetic risk score (GRS) based on 60 variants associated with HbA1c from genome-wide association meta-analysis, and (iii) principal component (PC) factors that capture continental ancestry derived from genetic markers distributed across the genome., Results: Of 2658 eligible DPP participants, 537 (20%) self-identified as black and 1476 (56%) as NHW. Despite comparable fasting and 2-hour glucose levels, blacks had higher HbA1c (mean ± SD = 6.2 ± 0.6%) compared with NHWs (5.8 ± 0.4%; P < 0.001). In blacks, the genetic variant causing sickle cell trait was associated with higher HbA1c [β (SE) = +0.44 (0.08)%; P = 2.1 × 10-4]. The GRS was associated with HbA1c in both blacks and NHWs. Self-identified blacks were distributed along the first PC axis, as expected in mixed ancestry populations. The first PC explained 60% of the 0.4% difference in HbA1c between blacks and NHWs, whereas the sickle cell variant explained 16% and GRS explained 14%., Conclusions: A large proportion of HbA1c difference between blacks and NHWs was associated with the first PC factor, suggesting that unidentified genetic markers influence HbA1c in blacks in addition to nongenetic factors.

Background: Subclinical hypercortisolism and hypothalamic-pituitary-adrenal (HPA) axis dysfunction are associated with type 2 diabetes (T2DM), cardiovascular disease, and metabolic dysfunction. Intronic methylation of FKBP5 has been implicated as a potential indicator of chronic cortisol exposure. Our overall objective in this study was to determine the association of chronic cortisol exposure, measured via percent methylation of FKBP5 at intron 2, with percent glycosylated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-cholesterol), waist circumference (WC), and body mass index (BMI), in a clinic-based sample of 43 individuals with T2DM., Results: Greater percent methylation of the FKBP5 intron 2 at one CpG-dinucleotide region was significantly associated with higher HbA1c ( β  = 0.535, p  = 0.003) and LDL cholesterol ( β  = 0.344, p  = 0.037) and a second CpG-dinucleotide region was significantly associated with higher BMI and WC ( β  = 0.516, p  = 0.001; β  = 0.403, p  = 0.006, respectively)., Conclusions: FKBP5 methylation may be a marker of higher metabolic risk in T2DM, possibly secondary to higher exposure to cortisol. Further work should aim to assess the longitudinal association of FKBP5 with cardiovascular disease and glycemic outcomes in T2DM as a first step in understanding potential preventive and treatment-related interventions targeting the HPA axis., Competing Interests: Patients who were willing to participate provided written informed consent. This study was approved by the Johns Hopkins University School of Medicine Institutional Review Board.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Purpose of Review: This review focuses on evaluating and identifying gaps in the current literature regarding culturally specific dietary influences for patients with type 2 diabetes. As this topic has previously been examined in African American populations, we chose to focus on four other distinct populations (Hispanic, Middle Eastern, Western Pacific, South Asian). Given the rapid increase in global rates of type 2 diabetes and high rates of diabetes among certain ethnic groups, it is important to understand how culturally adapted strategies in diabetes management have been described in different regions and populations., Recent Findings: The specific role of nutrition in controlling diabetes is tied to cultural habits and customs. Variation in cultural practices, including diet, create unique environments in which patients with diabetes must navigate. The role of family, particularly among Hispanics, is crucial to cultural adaptations of diabetes management. Incorporating alternative medicine, namely observed in Chinese and Indian populations, also guided diabetes care strategies. Language barriers, health literacy, and acculturation were all unique factors affecting cultural approaches to diabetes management in these four populations. Understanding such cultural determinants is crucial to addressing diabetes disparities and improving outcomes.

Aims: We examined whether problem-solving and diabetes self-management behaviors differ by depression diagnosis - major depressive disorder (MDD) and minor depressive disorder (MinDD) - in adults with Type 2 diabetes (T2DM)., Methods: We screened a clinical sample of 702 adults with T2DM for depression, identified 52 positive and a sample of 51 negative individuals, and performed a structured diagnostic psychiatric interview. MDD (n=24), MinDD (n=17), and no depression (n=62) were diagnosed using Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) Text Revised criteria. Health Problem-Solving Scale (HPSS) and Summary of Diabetes Self-Care Activities (SDSCA) questionnaires determined problem-solving and T2DM self-management skills, respectively. We compared HPSS and SDSCA scores by depression diagnosis, adjusting for age, sex, race, and diabetes duration, using linear regression., Results: Total HPSS scores for MDD (β=-4.38; p<0.001) and MinDD (β=-2.77; p<0.01) were lower than no depression. Total SDSCA score for MDD (β=-10.1; p<0.01) was lower than for no depression, and was partially explained by total HPSS., Conclusion: MinDD and MDD individuals with T2DM have impaired problem-solving ability. MDD individuals had impaired diabetes self-management, partially explained by impaired problem-solving. Future studies should assess problem-solving therapy to treat T2DM and MinDD and integrated problem-solving with diabetes self-management for those with T2DM and MDD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To estimate the crude prevalence of minor depressive disorder (MinD) in a clinic-based population of adults with type 2 diabetes., Methods: We screened a clinical sample of 702 adults with type 2 diabetes for depressive symptoms using the Patient Health Questionnaire-2 and performed a structured diagnostic psychiatric interview on 52 screen-positive and a convenience sample of 51 screen-negative individuals. Depressive disorder diagnoses were made using Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) Text Revised criteria and categorized as MinD, major depressive disorder (MDD), or no depressive disorder. We estimated prevalence of MinD and MDD and derived 95% CIs., Results: The crude prevalence of current, past, and current or past MinD was 4.3% (95% CI: 0.9-9.2%), 9.6% (95% CI: 3.9-15.9%), and 13.9% (95% CI: 7.7-21.2%), respectively. The crude prevalence of current, past, and current or past MDD was slightly higher-5.0% (95% CI: 1.9-9.4%), 12.0% (95% CI: 6.1-19.5%), and 17.0% (95% CI: 10.1-24.8%), respectively. There was a high prevalence of coexisting anxiety disorders in individuals with MinD (42.2%) and MDD (8.1%). Hemoglobin A1c levels were not significantly different in individuals with MinD or MDD compared to those without a depressive disorder., Conclusions: MinD is comparably prevalent to MDD in patients with type 2 diabetes; both disorders are associated with concomitant anxiety disorders. MinD is not included in the DSM-5; however, our data support continuing to examine patients with chronic medical conditions for MinD., (Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the effectiveness of three delivery modalities of Decision-making Education for Choices In Diabetes Everyday (DECIDE), a nine-module, literacy-adapted diabetes and cardiovascular disease (CVD) education and problem-solving training, compared with an enhanced usual care (UC), on clinical and behavioral outcomes among urban African Americans with type 2 diabetes., Research Design and Methods: Eligible participants (n = 182) had a suboptimal CVD risk factor profile (A1C, blood pressure, and/or lipids). Participants were randomized to DECIDE Self-Study (n = 46), DECIDE Individual (n = 45), DECIDE Group (n = 46), or Enhanced UC (n = 45). Intervention duration was 18-20 weeks. Outcomes were A1C, blood pressure, lipids, problem-solving, disease knowledge, and self-care activities, all measured at baseline, 1 week, and 6 months after completion of the intervention., Results: DECIDE modalities and Enhanced UC did not significantly differ in clinical outcomes at 6 months postintervention. In participants with A1C ≥7.5% (58 mmol/mol) at baseline, A1C declined in each DECIDE modality at 1 week postintervention (P < 0.05) and only in Self-Study at 6 months postintervention (b = -0.24, P < 0.05). There was significant reduction in systolic blood pressure in Self-Study (b = -4.04) and Group (b = -3.59) at 6 months postintervention. Self-Study, Individual, and Enhanced UC had significant declines in LDL and Self-Study had an increase in HDL (b = 1.76, P < 0.05) at 6 months postintervention. Self-Study and Individual had a higher increase in knowledge than Enhanced UC (P < 0.05), and all arms improved in problem-solving (P < 0.01) at 6 months postintervention., Conclusions: DECIDE modalities showed benefits after intervention. Self-Study demonstrated robust improvements across clinical and behavioral outcomes, suggesting program suitability for broader dissemination to populations with similar educational and literacy levels., (© 2016 by the American Diabetes Association.)

Type 1 (T1D) and Type 2 diabetes (T2D) represent a demanding set of biopsychosocial challenges for patients and their families, whether the age of disease onset occurs in childhood, adolescence, or adulthood. Psychological conditions, defined as syndromes, disorders, and diabetes-specific psychological issues affect a larger proportion of individuals with T1D and T2D compared to the general population. In this review, we summarize the prevalence, impact and psychological treatments associated with the primary categories of psychological conditions that affect adults with T1D and T2D: depressive symptoms and syndromes, anxiety disorders, eating behaviors and disorders and serious mental illness. The implications of the literature for psychologists are discussed, and priorities for future research to advance the science of psychological conditions for adults with T1D and T2D are identified. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Cross-sectional association has been shown between type 2 diabetes and hypothalamic-pituitary-adrenal (HPA) axis dysregulation; however, the temporality of this association is unknown. Our aim was to determine if type 2 diabetes is associated with longitudinal change in daily cortisol curve features. We hypothesized that the presence of type 2 diabetes may lead to a more blunted and abnormal HPA axis profile over time, suggestive of increased HPA axis dysregulation. This was a longitudinal cohort study, including 580 community-dwelling individuals (mean age 63.7 ± 9.1 years; 52.8 % women) with (n = 90) and without (n = 490) type 2 diabetes who attended two MultiEthnic Study of Atherosclerosis Stress ancillary study exams separated by 6 years. Outcome measures that were collected were wake-up and bedtime cortisol, cortisol awakening response (CAR), total area under the curve (AUC), and early, late, and overall decline slopes. In univariate analyses, wake-up and AUC increased over 6 years more in persons with as compared to those without type 2 diabetes (11 vs. 7 % increase for wake-up and 17 vs. 11 % for AUC). The early decline slope became flatter over time with a greater flattening observed in diabetic compared to non-diabetic individuals (23 vs. 9 % flatter); however, the change was only statistically significant for wake-up cortisol (p-value: 0.03). Over time, while CAR was reduced more, late decline and overall decline became flatter, and bedtime cortisol increased less in those with as compared to those without type 2 diabetes, none of these changes were statistically significant in adjusted models. We did not identify any statistically significant change in cortisol curve features over 6 years by type 2 diabetes status.

Objective: Prior studies have shown a bidirectional association between depression and type 2 diabetes mellitus (T2DM); however, the prospective associations of anger and anxiety with T2DM have not been established. We hypothesized that trait anger and anxiety would predict incident T2DM, independently of depressive symptoms., Research Design and Methods: In the Multi-ethnic Study of Atherosclerosis (MESA), we prospectively examined the association of trait anger and trait anxiety (assessed via the Spielberger Trait Anger and Anxiety Scales, respectively) with incident T2DM over 11.4 years in 5598 White, Black, Hispanic, and Chinese participants (53.2% women, mean age 61.6 years) at baseline without prevalent T2DM or cardiovascular disease. We used Cox proportional hazards models to calculate the hazard ratios (HR) of incident T2DM by previously defined anger category (low, moderate, high), and anxiety quartile, as there were no previously defined categories., Results: High total trait anger was associated with incident T2DM (HR 1.50; 95% CI 1.08-2.07) relative to low total trait anger. The association was attenuated following adjustment for waist circumference (HR 1.32; 95% CI 0.94-1.86). Higher anger reaction was also associated with incident T2DM (HR=1.07; 95% CI 1.03-1.11) that remained significant after adjusting for potential confounders/explanatory factors. In contrast, trait anxiety did not predict incident T2DM., Conclusions: High total trait anger and anger reaction are potential modifiable risk factors for T2DM. Further research is needed to explore the mechanisms of the anger-diabetes relationship and to develop preventive interventions., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Cardiovascular disease risk factor control as primary prevention in patients with type 2 diabetes mellitus has changed substantially in the past few years. The purpose of this scientific statement is to review the current literature and key clinical trials pertaining to blood pressure and blood glucose control, cholesterol management, aspirin therapy, and lifestyle modification. We present a synthesis of the recent literature, new guidelines, and clinical targets, including screening for kidney and subclinical cardiovascular disease for the contemporary management of patients with type 2 diabetes mellitus., (© 2015 by the American Diabetes Association and the American Heart Association, Inc.)

We systematically reviewed the effectiveness and safety of continuous subcutaneous insulin infusion (CSII) with insulin analogs compared with multiple daily injections (MDI) in pregnant women with diabetes mellitus. We searched Medline®, Embase®, and the Cochrane Central Register of Controlled Trials through May 2013. Studies comparing CSII with MDI in pregnant women with diabetes mellitus were included. Studies using regular insulin CSII were excluded. We conducted meta-analyses where there were two or more comparable studies based on the type of insulin used in the MDI arm. Seven cohort studies of pregnant women with type 1 diabetes reported improvement in hemoglobin A1c (HbA1c) in both groups. Meta-analysis showed no difference in maternal and fetal outcomes for CSII versus MDI. Results were similar when CSII was compared with MDI with insulin analogs or regular insulin. Studies had moderate to high risk bias with incomplete descriptions of study methodology, populations, treatments, follow up, and outcomes. We conclude that observational studies reported similar improvements in HbA1c with CSII and MDI during pregnancy, but evidence was insufficient to rule out possible important differences between CSII and MDI for maternal and fetal outcomes. This highlights the need for future studies to examine the effectiveness and safety of CSII with insulin analogs and MDI in pregnant women with diabetes mellitus.

Aims: We investigated the longitudinal association of depression, with and without cognitive dysfunction, with hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein (LDL) in a predominantly minority cohort., Methods: There were 613 participants. Presence of depression was defined by a score ≥7 on the Short-CARE depression scale. We tested participants for executive dysfunction using the Color Trails Test (CTT), part 2, and for memory dysfunction using the total recall task of the Selective Reminding Test (TR-SRT). We classified performance in these tests as abnormal based on standardized score cutoffs (<16th percentile and one standard deviation below the sample mean). Random effects models were used to compare repeated measures of the diabetes control measures between those with depression versus those without depression and ever versus never cognitively impaired., Results: Baseline depression was present in 36% of participants. Over a median follow-up of 2 years, depression was not related to worse HbA1c, SBP, or LDL. The presence of (1) abnormal performance on a test of executive function and depression (n=57) or (2) abnormal performance on a test of verbal recall and depression (n=43) was also not associated with clinically significant worse change in diabetes control., Conclusions: Depression, with or without low performance in tests of executive function and memory, may not affect clinically significant measures of diabetes control in the elderly., (Copyright © 2014. Published by Elsevier Inc.)

Diabetes and depression occur together approximately twice as frequently as would be predicted by chance alone. Comorbid diabetes and depression are a major clinical challenge as the outcomes of both conditions are worsened by the other. Although the psychological burden of diabetes may contribute to depression, this explanation does not fully explain the relationship between these 2 conditions. Both conditions may be driven by shared underlying biological and behavioral mechanisms, such as hypothalamic-pituitary-adrenal axis activation, inflammation, sleep disturbance, inactive lifestyle, poor dietary habits, and environmental and cultural risk factors. Depression is frequently missed in people with diabetes despite effective screening tools being available. Both psychological interventions and antidepressants are effective in treating depressive symptoms in people with diabetes but have mixed effects on glycemic control. Clear care pathways involving a multidisciplinary team are needed to obtain optimal medical and psychiatric outcomes for people with comorbid diabetes and depression.

Purpose of Review: Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM), and modifying cardiovascular risk through lifestyle intervention and pharmacologic therapy is paramount. This review focuses on recent advances in treatment of classical (traditional) cardiovascular risk factors and highlights the impact of novel risk factors, including sleep disorders, socioeconomic status and chronic psychological stress on CVD in T2DM., Recent Findings: Obesity is a substantial cardiovascular risk factor, and recently, large trials of lifestyle and surgical (e.g. gastric bypass) interventions impact on CVD in overweight and obese patients have been reported. Lifestyle intervention including low calorie diet and exercise reduced individual cardiovascular risk factors but did not decrease the rate of long-term cardiovascular events. Bariatric surgery was beneficial in reducing cardiovascular risk factors and long-term cardiovascular events. Sleep insufficiency, poor sleep quality and obstructive sleep apnoea lead to higher CVD and further research is needed to characterize the benefit of treating sleep disorders on long-term cardiovascular events in T2DM. Lastly, socioeconomic status and chronic psychological stress independently have a major impact on increasing CVD in T2DM, and public health policies to reduce this burden will be important to address over the coming decade., Summary: CVD in T2DM is multifactorial and requires a multifaceted approach in reducing known cardiovascular risks at the individual patient level through lifestyle, pharmacotherapy and surgical interventions and at the societal level through public health policies that support reduction in classical and novel cardiovascular risk factors.

Background: Patients with diabetes mellitus need information about the effectiveness of innovations in insulin delivery and glucose monitoring., Purpose: To review how intensive insulin therapy (multiple daily injections [MDI] vs. rapid-acting analogue-based continuous subcutaneous insulin infusion [CSII]) or method of monitoring (self-monitoring of blood glucose [SMBG] vs. real-time continuous glucose monitoring [rt-CGM]) affects outcomes in types 1 and 2 diabetes mellitus., Data Sources: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through February 2012 without language restrictions., Study Selection: 33 randomized, controlled trials in children or adults that compared CSII with MDI (n=19), rt-CGM with SMBG (n=10), or sensor-augmented insulin pump use with MDI and SMBG (n=4)., Data Extraction: 2 reviewers independently evaluated studies for eligibility and quality and serially abstracted data., Data Synthesis: In randomized, controlled trials, MDI and CSII showed similar effects on hemoglobin A1c (HbA1c) levels and severe hypoglycemia in children or adults with type 1 diabetes mellitus and adults with type 2 diabetes mellitus. In adults with type 1 diabetes mellitus, HbA1c levels decreased more with CSII than with MDI, but 1 study heavily influenced these results. Compared with SMBG, rt-CGM achieved a lower HbA1c level (between-group difference of change, 0.26% [95% CI, 0.33% to 0.19%]) without any difference in severe hypoglycemia. Sensor-augmented insulin pump use decreased HbA1c levels more than MDI and SMBG did in persons with type 1 diabetes mellitus (between-group difference of change, 0.68% [CI, 0.81% to 0.54%]). Little evidence was available on other outcomes., Limitation: Many studies were small, of short duration, and limited to white persons with type 1 diabetes mellitus., Conclusion: Continuous subcutaneous insulin infusion and MDI have similar effects on glycemic control and hypoglycemia, except CSII has a favorable effect on glycemic control in adults with type 1 diabetes mellitus. For glycemic control, rt-CGM is superior to SMBG and sensor-augmented insulin pumps are superior to MDI and SMBG without increasing the risk for hypoglycemia., Primary Funding Source: Agency for Healthcare Research and Quality.

Background: Diabetes mellitus is defined as a group of metabolic diseases characterized by hyperglycemia, which when untreated can lead to long-term complications, including micro- and macrovascular complications. Tight glycemic control with intensive insulin therapy has been suggested to reduce the risk of such complications in several diabetes populations; however, such an approach can also be associated with risks and challenges. There are currently several modalities available to deliver insulin and monitor glucose levels to achieve glycemic goals in diabetic patients. In July 2012, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review on the comparative effectiveness of insulin delivery systems and glucose-monitoring modalities in diabetic patients receiving intensive insulin therapy. Studies from 44 publications included in the review compared the effects of continuous subcutaneous insulin infusion (CSII) with multiple daily injections (MDI) and/or real time-continuous glucose monitoring (rt-CGM) with self-monitoring of blood glucose (SMBG) among children, adolescents, or adults with either type 1 (T1DM) or type 2 diabetes (T2DM), or pregnant women with pre-existing diabetes (either T1DM or T2DM). This comparative effectiveness review evaluated which modality results in improved glycemic control, less hypoglycemia, better quality of life, and/or improved clinical outcomes. The numerous technologies and the challenges that clinicians face when determining which patient population may benefit from different insulin delivery systems and glucose-monitoring approaches motivated AHRQ to synthesize the available information to assist health professionals in making evidence-based practice decisions for their patients. The review also delineates advances in insulin delivery and glucose-monitoring systems, practical methods to achieve tight glycemic control and strategies to minimize associated risks, as well as highlights gaps in research and areas that need to be addressed in the future. , Objectives: To (a) educate health care professionals on the findings from AHRQ's 2012 comparative effectiveness review on insulin delivery and glucose-monitoring modalities in patients with diabetes; (b) apply review findings to make treatment decisions in clinical practice; and (c) identify shortcomings in the current research and future directions relating to the comparative effectiveness of insulin delivery and glucose-monitoring modalities for patients with diabetes., Summary: The AHRQ systematic review of randomized clinical trials reveals that both insulin delivery modalities (CSII and MDI) demonstrate similar effectiveness on glycemic control and severe hypoglycemia in children and adolescents with T1DM and in adults with T2DM. In adults with T1DM, hemoglobin A1c decreased more with CSII than with MDI with low strength of evidence, but one study heavily influenced these results. In children and adults with T1DM, the use of CSII was associated with improved quality of life compared with MDI, with low strength of evidence, while there was insufficient strength of evidence to make conclusions regarding the quality of life for adults with T2DM. The study investigators suggest that the modality to deliver intensive insulin therapy can be individualized to patient preference in order to maximize quality of life. On all measured outcomes, there was insufficient or low strength of evidence regarding pregnant women with pre-existing diabetes.The AHRQ investigators found studies comparing the effectiveness of glucose-monitoring modalities in individuals with T1DM only. The systematic review demonstrates that rt-CGM is associated with greater lowering of A1c compared with SMBG (high strength of evidence) without affecting the risk of severe hypoglycemia (low strength of evidence) or quality of life (low strength of evidence) in nonpregnant individuals with T1DM, particularly when compliance with device use is high. Additional findings suggest that the use of sensor-augmented insulin pumps (rt-CGM + CSII) is superior to the use of MDI/SMBG use in lowering A1c in nonpregnant individuals with T1DM (moderate strength of evidence). Comparison of other outcome measures did not yield firm conclusions due to low or insufficient evidence.

The objective was to examine the cross-sectional association of diurnal salivary cortisol curve components and urinary catecholamines with diabetes status. Up to 18 salivary cortisol samples over 3 days and overnight urinary catecholamines were collected from 1002 participants in the Multi-Ethnic Study of Atherosclerosis. Diabetes was defined as a fasting blood glucose of at least 126 mg/dL or medication use. Cortisol curve measures included awakening cortisol, cortisol awakening response, early decline, late decline, and cortisol area under the curve (AUC). Urinary catecholamines included epinephrine, norepinephrine, and dopamine. Participants with diabetes had significantly lower cortisol awakening response (β = -0.19; 95% confidence interval [CI], -0.34 to -0.04) than those without diabetes in multivariable models. Whereas men with diabetes had a nonsignificant trend toward lower total AUC (β = -1.56; 95% CI, -3.93 to 0.80), women with diabetes had significantly higher total AUC (β = 2.62; 95% CI, 0.72 to 4.51) (P = .02 for interaction) compared with those without diabetes. Men but not women with diabetes had significantly lower urinary catecholamines compared with those without diabetes (P < .05). Diabetes is associated with neuroendocrine dysregulation, which may differ by sex. Further studies are needed to determine the role of the neuroendocrine system in the pathophysiology of diabetes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Women with a history of gestational diabetes mellitus (GDM) are at high risk for type 2 diabetes mellitus (T2DM)., Objective: We reviewed prospective studies of antepartum glucose tolerance test results as risk factors for development of T2DM among women with a history of GDM., Methods: We searched 4 electronic databases and hand-searched 13 journals for literature published through January 2007. The search strategy consisted of medical subject headings and text words for GDM, T2DM, and other relevant terms. Articles were excluded for the following reasons: (1) not written in English; (2) no human data; (3) no original data; (4) <90% of sample was diagnosed with GDM without a separate analysis for women with GDM; (5) case report or series; (6) diagnosis of GDM not based on 3-hour 100-g oral glucose tolerance test (OGTT) or 2-hour 75-g OGTT; (7) T2DM not evaluated as outcome; (8) no relative measure of association or incidence reported; or (9) design did not address antepartum OGTT as a predictor of T2DM. Two investigators independently reviewed citations, performed serial data abstraction on full articles, and assessed the quality of each article. Data were abstracted for study participants and characteristics, T2DM diagnosis, length of follow-up, regression model covariates, and measures of association and variability., Results: Of 11,400 unique citations, we identified 11 articles that evaluated antepartum glucose testing and risk of T2DM in women with a history of GDM. Five studies found that the fasting blood glucose (FBG) on the antepartum diagnostic OGTT was a significant predictor of T2DM (odds ratio [OR] range: 11.1-21.0; relative risk [RR] range: 1.37-1.5; relative hazard [RH] = 2.47). Risk of incident T2DM was predicted by the antepartum 2-hour OGTT plasma glucose in 3 studies (OR range: 1.02-1.03; RR = 1.3) and by the antepartum OGTT glucose AUC in 3 other studies (OR range: 3.64-15; RH = 2.13). Overall, study quality was limited by high losses to follow-up (>20% in 6 studies) and short duration. Few studies adjusted for adiposity, an established diabetes risk factor., Conclusion: FBG, OGTT 2-hour blood glucose, and OGTT glucose AUC appeared to be strong and consistent predictors of subsequent T2DM among women who met diagnostic criteria for GDM using the OGTT.

Objective: It has been argued that the relationship between depression and diabetes is bi-directional, but this hypothesis has not been explicitly tested. This systematic review examines the bi-directional prospective relationships between depression and type 2 diabetes., Research Design and Methods: A search was conducted using Medline for publications from 1950 through 2007. Reviewers assessed the eligibility of each report by exposure/outcome measurement and study design. Only comparative prospective studies of depression and type 2 diabetes that excluded prevalent cases of depression (for diabetes predicting depression) or diabetes (for depression predicting diabetes) were included. Two sets of pooled risk estimates were calculated using random effects: depression predicting type 2 diabetes and type 2 diabetes predicting depression., Results: Of 42 full-text publications reviewed, 13 met eligibility for depression predicting onset of diabetes, representing 6,916 incident cases. Seven met criteria for diabetes predicting onset of depression, representing 6,414 incident cases. The pooled relative risk (RR) for incident depression associated with baseline diabetes was 1.15 (95% CI 1.02-1.30). The RR for incident diabetes associated with baseline depression was 1.60 (1.37-1.88)., Conclusions: Depression is associated with a 60% increased risk of type 2 diabetes. Type 2 diabetes is associated with only modest increased risk of depression. Future research should focus on identifying mechanisms linking these conditions.

Objectives: We investigated the association between major depressive disorder and type 2 diabetes, whether that association is explained by health behaviors, and whether it is influenced by educational attainment., Methods: We used discrete-time Cox proportional hazards models to determine the risk of type 2 diabetes associated with depression in a 23-year population-based cohort study., Results: Major depressive disorder was associated with higher risk of type 2 diabetes (hazard ratio [HR]=1.62) after we controlled for age, gender, race, education, smoking status, alcohol use, social network size, and antidepressant use. This association was more pronounced after we controlled for body mass index, family history, and health behaviors (HR=2.04; 95% confidence interval=1.09, 3.81). In stratified analyses, the risk associated with major depressive disorder was elevated among those with 12 or fewer years of education compared with those with at least some education beyond high school., Conclusions: The risk of type 2 diabetes associated with major depressive disorder persists over the life course and is independent of the effects of health behaviors, body mass index, and family history. Education is an important moderator of this association.

Context: Depressive symptoms are associated with development of type 2 diabetes, but it is unclear whether type 2 diabetes is a risk factor for elevated depressive symptoms., Objective: To examine the bidirectional association between depressive symptoms and type 2 diabetes., Design, Setting, and Participants: Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000-2002 and followed up until 2004-2005., Main Outcome Measures: Elevated depressive symptoms defined by Center for Epidemiologic Studies Depression Scale (CES-D) score of 16 or higher, use of antidepressant medications, or both. The CES-D score was also modeled continuously. Participants were categorized as normal fasting glucose (< 100 mg/dL), impaired fasting glucose (100-125 mg/dL), or type 2 diabetes (> or = 126 mg/dL or receiving treatment). Analysis 1 included 5201 participants without type 2 diabetes at baseline and estimated the relative hazard of incident type 2 diabetes over 3.2 years for those with and without depressive symptoms. Analysis 2 included 4847 participants without depressive symptoms at baseline and calculated the relative odds of developing depressive symptoms over 3.1 years for those with and without type 2 diabetes., Results: In analysis 1, the incidence rate of type 2 diabetes was 22.0 and 16.6 per 1000 person-years for those with and without elevated depressive symptoms, respectively. The risk of incident type 2 diabetes was 1.10 times higher for each 5-unit increment in CES-D score (95% confidence interval [CI], 1.02-1.19) after adjustment for demographic factors and body mass index. This association persisted following adjustment for metabolic, inflammatory, socioeconomic, or lifestyle factors, although it was no longer statistically significant following adjustment for the latter (relative hazard, 1.08; 95% CI, 0.99-1.19). In analysis 2, the incidence rates of elevated depressive symptoms per 1000-person years were 36.8 for participants with normal fasting glucose; 27.9 for impaired fasting glucose; 31.2 for untreated type 2 diabetes, and 61.9 for treated type 2 diabetes. Compared with normal fasting glucose, the demographic-adjusted odds ratios of developing elevated depressive symptoms were 0.79 (95% CI, 0.63-0.99) for impaired fasting glucose, 0.75 (95% CI, 0.44-1.27) for untreated type 2 diabetes, and 1.54 (95% CI, 1.13-2.09) for treated type 2 diabetes. None of these associations with incident depressive symptoms were materially altered with adjustment for body mass index, socioeconomic and lifestyle factors, and comorbidities. Findings in both analyses were comparable across ethnic groups., Conclusions: A modest association of baseline depressive symptoms with incident type 2 diabetes existed that was partially explained by lifestyle factors. Impaired fasting glucose and untreated type 2 diabetes were inversely associated with incident depressive symptoms, whereas treated type 2 diabetes showed a positive association with depressive symptoms. These associations were not substantively affected by adjustment for potential confounding or mediating factors.

Objective: To assess the cross-sectional association between depression and glucose tolerance status., Methods: We conducted a study of 6754 White, Black, Hispanic, and Chinese men and women aged 45 to 84 years in the Multiethnic Study of Atherosclerosis (MESA). Depression was defined as Center for Epidemiologic Studies Depression scale score of > or =16 and/or antidepressant use. Glucose tolerance status was defined as normal, impaired fasting glucose (IFG) or Type 2 diabetes mellitus (untreated and treated)., Results: In the minimally adjusted model, although depression was not associated with a greater odds of IFG (odds ratio (OR) = 1.01; 95% confidence interval (CI): 0.87-1.18) or untreated diabetes (OR = 1.03; 95% CI: 0.74-1.45), it was associated with a greater odds of treated diabetes (OR = 1.57; 95% CI: 1.27-1.96). This persisted following adjustment for body mass index (OR = 1.52; 95% CI: 1.22-1.90), metabolic (OR = 1.54; 95% CI: 1.23-1.93), and inflammatory (OR=1.53; 95% CI: 1.21-1.92) factors, daily caloric intake and smoking (OR = 1.48; 95% CI: 1.16-1.88), and socioeconomic markers (OR = 1.47; 95% CI: 1.17-1.85). Among individuals with treated diabetes, median depression scores were higher in those with microalbuminuria compared with those without microalbuminuria (median = 7; interquartile range: 3-13 versus median = 6; interquartile range: 2-11; p = .046). Depression scores were not associated with homeostatic model assessment of insulin resistance among individuals without diabetes., Conclusions: In MESA, depression was significantly associated with treated diabetes. Further studies are needed to determine the temporality of this association.

Objective: Trait anger has been shown to predict coronary heart disease; however, there are no prior studies evaluating anger as a risk factor for type 2 diabetes. The objective of this study was to determine if anger proneness predicted type 2 diabetes using prospective analyses., Methods: We analyzed data on trait anger, assessed by questionnaire, in a longitudinal, bi-racial cohort study of 11,615 initially non-diabetic adults aged 48-67, who were subsequently followed for 6 years for the development of type 2 diabetes., Results: There was no relation between overall trait anger and the subsequent risk of diabetes; however, individuals in the highest tertile of trait anger temperament scores had a 34% increased risk of developing diabetes compared to those in the lowest tertile (Relative hazard [RH] = 1.34; 95% confidence interval: 1.10, 1.62), following adjustment for age, race, gender, and education. The relation between anger temperament and diabetes remained significant following adjustment for behavioral factors (smoking, physical activity, and caloric intake) (RH = 1.31; 95% CI: 1.08, 1.60) but was non-significant after additional adjustment for waist-to-hip ratio and body-mass index (RH = 1.18; 95% CI: 0.97, 1.44)., Conclusions: While we found no relation between overall trait anger and incident diabetes, persons who had higher anger temperament subscale scores had a slightly increased risk of type 2 diabetes, which was largely explained by adiposity. Anger temperament may deserve further attention as a potential risk factor for type 2 diabetes.

Background: In persons with diabetes, chronic hyperglycemia (assessed by glycosylated hemoglobin level) is related to the development of microvascular disease; however, the relation of glycosylated hemoglobin to macrovascular disease is less clear., Purpose: To conduct a meta-analysis of observational studies of the association between glycosylated hemoglobin and cardiovascular disease in diabetic persons., Data Sources: Search of the MEDLINE database by using Medical Subject Heading search terms and key words related to glycosylated hemoglobin, diabetes, and cardiovascular disease., Study Selection: Prospective cohort studies with data on glycosylated hemoglobin levels and incident cardiovascular disease., Data Extraction: Relative risk estimates were derived or abstracted from each cohort study that met the inclusion criteria., Data Synthesis: Adjusted relative risk estimates for glycosylated hemoglobin (total glycosylated hemoglobin, hemoglobin A1, or hemoglobin A1c levels) and cardiovascular disease events (coronary heart disease and stroke) were pooled by using random-effects models. Three studies involved persons with type 1 diabetes (n = 1688), and 10 studies involved persons with type 2 diabetes (n = 7435). The pooled relative risk for cardiovascular disease was 1.18; this represented a 1-percentage point increase in glycosylated hemoglobin level (95% CI, 1.10 to 1.26) in persons with type 2 diabetes. Results in persons with type 1 diabetes were similar but had a wider CI (pooled relative risk, 1.15 [CI, 0.92 to 1.43])., Limitations: This review largely reflects the limitations of the literature. Important concerns were residual confounding, the possibility of publication bias, the small number of studies, and the heterogeneity of study results., Conclusions: Pending confirmation from large, ongoing clinical trials, this analysis shows that observational studies are consistent with limited clinical trial data and suggests that chronic hyperglycemia is associated with an increased risk for cardiovascular disease in persons with diabetes.

Objective: The goal of this study was to determine whether depressive symptoms predict type 2 diabetes., Research Design and Methods: We analyzed data on depressive symptoms (including recent fatigue, sleep disturbance, feelings of hopelessness, loss of libido, and increased irritability) in a longitudinal, biracial cohort study of 11,615 initially nondiabetic adults aged 48-67 years, who were subsequently followed for 6 years for the development of type 2 diabetes., Results: At baseline, depressive symptoms were positively associated with BMI, fasting insulin, systolic blood pressure, caloric intake, physical inactivity, and current smoking (all P < 0.05). In prospective analyses, after adjusting for age, race, sex, and education, individuals in the highest quartile of depressive symptoms had a 63% increased risk of developing diabetes compared with those in the lowest quartile (relative hazard [RH] 1.63, 95% CI 1.31-2.02). This relation persisted after adjustment for stress-associated lifestyle factors (smoking, physical activity, caloric intake, and adiposity) (1.28, 1.02-1.60) and metabolic covariates (fasting insulin and glucose, lipids, blood pressure, and adiposity) (1.38, 1.10-1.73)., Conclusions: In this cohort, depressive symptoms predicted incident type 2 diabetes. This relation is only partially explained by demographic, metabolic, and lifestyle factors. Possible neuroendocrine mediators of the stress-obesity-diabetes relationship require further evaluation in prospective cohort studies that use an established tool to assess depression and incorporate neurohormonal measurements.

Cardiovascular disease is often present in patients with newly diagnosed type 2 diabetes. It is hypothesized that both type 2 diabetes and cardiovascular disease arise from an underlying insulin resistance syndrome, including impaired glucose tolerance, hypertension, dyslipidemia, and abdominal obesity. We reviewed the literature using various epidemiologic techniques to evaluate the relation between the insulin resistance syndrome components and incident cardiovascular disease. We found that although insulin resistance is likely important in the development of cardiovascular disease seen in diabetes, lipid and blood pressure abnormalities associated with the syndrome appear to be equally important. Future studies are needed to determine the most effective treatment strategies for preventing cardiovascular disease associated with the insulin resistance syndrome and type 2 diabetes.

Objective: There is some evidence to suggest that individuals with depression are at an almost twofold increased risk of developing type 2 diabetes mellitus, but results are far from conclusive. Therefore, to determine if depressive symptoms increased the risk of type 2 diabetes, we conducted longitudinal analyses using data from the NHANES I Epidemiologic Follow-up Survey (NHEFS)., Research Design and Methods: Participants included individuals who were white or African-American, did not report previous diagnosis of diabetes, and who completed the Centers for Epidemiologic Studies Depression (CES-D) questionnaire in the 1982-1984 study (n = 8870). Participants were followed up for incident-diagnosed diabetes through 1992 (mean follow-up 9.0 years)., Results: There were 1444 (15.9%) participants with high depressive symptoms in the 1982-1984 study (CES-D score > or = 16). During follow-up, there were 465 incident cases of diabetes. Incidence of diabetes was 6.9/1000 person years among those with high depressive symptoms, 6.0/1000 person years among those with moderate symptoms, and 5.0/1000 person years among those with no symptoms. After adjusting for age, sex, and race, the relative hazard (RH) of diabetes among those with high depressive symptoms was 1.27 (95% CI: 0.93 to 1.73) compared to those without symptoms. Further adjustment for education and known diabetes risk factors (body mass index and physical activity) further attenuated the relationship (RH 1.11, 95% CI: 0.79 to 1.56)., Conclusions: There was no increased incidence of diabetes for those with high or moderate depressive symptoms compared to those with no depressive symptoms. These results do not support the etiologic relationship of depression predisposing individuals to diabetes., (Copyright 2002 John Wiley & Sons, Ltd.)

Objective: Hypertension is known to accompany type 2 diabetes in middle age, but it is unknown how early in life blood pressure (BP) begins to rise among individuals who later develop diabetes. The objective of this study was to evaluate elevated BP as a long-term predictor of type 2 diabetes., Research Design and Methods: We conducted a prospective cohort study of 1,152 white male medical students in The Johns Hopkins Precursors Study to longitudinally assess systolic BP (SBP) and diastolic BP (DBP) from young adulthood through middle age in men who went on to develop diabetes. Incident diabetes was identified by self-report through mailed questionnaires verified by medical record review., Results: During a median follow-up of 38 years, 77 cases of incident diabetes occurred. The mean age of diabetes diagnosis was 58 years. As early as age 30 years, mean SBP and DBP were significantly higher in men who developed diabetes during follow-up than in those who remained nondiabetic (SBP 122 vs. 119 mmHg, P = 0.009; DBP 78 vs. 75 mmHg, P = 0.0005). The rate of increase in SBP and DBP over time in men who developed diabetes was greater than the rate of increase in men who did not develop diabetes (SBP 0.49 vs. 0.27 mmHg/year, P < 0.00003; DBP 0.24 vs. 0.17 mmHg/year; P = 0.09). After adjustment for BMI and other risk factors for diabetes, SBP and DBP at age 30 years remained significantly higher in individuals who developed diabetes than in their nondiabetic counterparts; however, the difference in the rate of increase in SBP was no longer significant following multivariate adjustment., Conclusions: BP elevations precede the development of type 2 diabetes in middle age by 20-25 years. Higher BP in the prediabetic state might contribute to the presence of vascular disease at the time of diagnosis of type 2 diabetes.