In patients with diabetes, maintenance therapy with sertraline prolongs the depression-free interval following recovery from major depression. Depression recovery with sertraline as well as sustained remission with or without treatment are associated with improvements in glycosylated hemoglobin levels for at least 1 year.

OBJECTIVE -Depression management in both short-and longer-term treatment studies has been associated with improvement in glycemic control. We used bupropion hydrochloride (Wellbutrin XL) to determine whether this improvement could be attributed to changes in anthropometrics or diabetes self-care.RESEARCH DESIGN AND METHODS -Ninety-three patients with type 2 diabetes and major depressive disorder (MDD) received bupropion hydrochloride in a two-phase, openlabel treatment trial. Those who completed the acute phase (10 weeks; n ϭ 75) and whose depression remitted (n ϭ 63) continued bupropion at the remission dose and were followed in the maintenance phase (24 weeks) until attrition (n ϭ 8) or relapse of MDD (n ϭ 0). Self-report scales were used to measure depression symptom severity and diabetes self-care behaviors. Body composition and glycemic control were determined using dual-energy X-ray absorptiometry and serial determinations of A1C.RESULTS -BMI, total fat mass, and A1C decreased and composite diabetes self-care improved over the acute phase (Ϫ0.5 kg/m 2 , Ϫ0.7 kg, Ϫ0.5%, and ϩ0.4, respectively, P Ͻ 0.01 for each), effects that persisted through the maintenance phase for BMI, A1C, and self-care (P Յ 0.01 for each). Reductions in BMI (B ϭ 0.30, P ϭ 0.01) and depression severity (B ϭ 0.04, P ϭ 0.046) independently predicted lower A1C after acute-phase treatment, whereas only reduction in depression severity (B ϭ 0.08, P ϭ 0.001) predicted A1C over the maintenance interval.CONCLUSIONS -In the short term, improvement in glycemic control during bupropion treatment is predicted independently by improvements in mood and body composition. Longerterm improvements in glycemic control are predicted primarily by sustained improvement in mood via mechanisms independent of anthropometric and self-care modifications. Diabetes Care 30:459 -466, 2007

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SUMMARY Background The beta-2 adrenergic receptor (ADRB2) is an important target for epinephrine, a neurotransmitter in pain signalling. ADRB2 haplotypes affect receptor expression and ligand response, and have been linked to painful non-GI disorders. Aims To assess whether ADRB2 polymorphisms (rs1042713, rs1042714) are risk alleles for functional GI (FGID) and extraintestinal functional (EIFD) diagnoses, and whether ADRB2 predicts GI symptoms and health-related quality of life (HRQOL). Methods Of 398 subjects (49.6 ± 2.9 years, 68.0% female), 170 (42.5%) met Rome III criteria for ≥1 FGID [IBS (n = 139, 34.9%); functional dyspepsia (FD, n = 136, 34.1%), functional chest pain (FCP, n = 25, 6.2%)], while 228 were healthy controls. FGID subjects reported on bowel symptom severity and burden (10-cm VAS), frequency (days/last 2 weeks), EIFD, psychiatric diagnoses and HRQOL (SF 36). Multivariable models determined the contribution of ADRB2 polymorphisms to HRQOL, and mediational analyses assessed functional diagnoses as potential intermediates. Results rs1042714 minor G alleles were associated with FGID diagnoses (OR 1.8; 95% CI 1.2–2.7; P = 0.009), particularly FD (OR 2.1, 95% CI 1.3–3.3), with trends towards IBS (P = 0.19) and FCP (P = 0.06) diagnoses. Within IBS, G allele carriers had more severe bowel symptoms (P = 0.025), and symptomatic days (P = 0.009). G allele carriers had greater numbers of EIFD (1.0 ± 0.1 vs. 0.4 ± 0.07, P < 0.001) and poorer HRQOL. The effect of ADRB2 on HRQOL was partially mediated by FGID, EIFD and psychiatric diagnoses. Conclusions ADRB2 minor alleles at rs1042714 predict FGID and EIFD, and may influence bowel symptom severity and HRQOL. These findings provide indirect evidence of sympathetic nervous system role in FGID pathophysiology.

Whether and how the co-occurrence of depression and diabetes in pregnancy may worsen infant development has not been reported. Pregnant women with diabetes and with (n = 34) or without (n = 34) major depressive disorder (MDD) were followed during pregnancy and 6-months postpartum. The MDD subset received randomly assigned treatment with cognitive behavior therapy (CBT) or supportive counseling (SC). Depression severity was measured with the Beck Depression Inventory (BDI); infant developmental outcomes were measured with the Bayley Scales of Infant Development (BSID) and its Behavior Rating Scale (BRS). Infants of women with MDD had lower BRS scores (p = .02). Reduction in depression scores was associated with better infant outcomes on the BSID and BRS (p values <.03). These preliminary findings suggest depression occurring in pregnant women with diabetes is associated with poorer infant development and improvement in prepartum depression is associated with improvement in measures of infant development.

INTRODUCTION: Ambulatory reflux monitoring performed off proton pump inhibitor (PPI) is the gold standard diagnostic test for nonerosive gastroesophageal reflux disease (GERD). However, the diagnostic metrics and optimal duration of monitoring are not well defined. This study evaluated the performance of multiple metrics across distinct durations of wireless reflux monitoring off PPI against the ability to discontinue PPI therapy in patients with suboptimal PPI response. METHODS:This single-arm clinical trial performed over 4 years at 2 centers enrolled adults with troublesome GERD symptoms and inadequate response to >8 weeks of PPI. Participants underwent 96-hour wireless pH monitoring off PPI. Primary outcome was whether the subject successfully discontinued PPI or resumed PPI within 3 weeks.

OBJECTIVE -Sertraline maintenance therapy effectively delays recurrence of major depressive disorder in adult diabetic patients when data are examined across all age-groups. A secondary analysis was performed to assess this effect in younger and older subsets of patients.RESEARCH DESIGN AND METHODS -Younger (aged Ͻ55 years, n ϭ 85) and older (aged Ն55 years, n ϭ 67) subsets were identified from a multicenter, double-blind, placebocontrolled, maintenance treatment trial of sertraline in diabetic participants who achieved depression recovery with open-label sertraline treatment. Cox proportional hazards models were used to determine differences in time to depression recurrence between treatment arms (sertraline or placebo) for each age subset and between age subsets for each treatment.RESULTS -In younger subjects, sertraline conferred significantly greater prophylaxis against depression recurrence than placebo (hazard ratio 0.37 [95% CI 0.20 -0.71]; P ϭ 0.003). Benefits of sertraline maintenance therapy were lost in older participants (0.94 [0.39 -2.29]; P ϭ 0.89). There was no difference in time to recurrence for sertraline-treated subjects between age subsets (P ϭ 0.65), but older subjects had a significantly longer time to recurrence on placebo than younger subjects (P ϭ 0.03).CONCLUSIONS -While sertraline significantly increased the time to depression recurrence in the younger diabetic participants, there was no treatment effect in those aged Ն55 years because of a high placebo response rate. Further research is necessary to determine the mechanisms responsible for this effect and whether depression maintenance strategies specific for older patients with diabetes should be developed. Diabetes Care 30:801-806, 2007

Background The intestinal microbiota play a key role in the onset, progression, and recurrence of Crohn disease (CD). Most microbiome studies assay fecal material, which does not provide region-specific information on mucosally adherent bacteria that directly interact with host systems. Changes in luminal oxygen have been proposed as a contributor to CD dybiosis. Methods The authors generated 16S rRNA data using colonic and ileal mucosal bacteria from patients with CD and without inflammatory bowel disease. We developed profiles reflecting bacterial abundance within defined aerotolerance categories. Bacterial diversity, composition, and aerotolerance profiles were compared across intestinal regions and disease phenotypes. Results Bacterial diversity decreased in CD in both the ileum and the colon. Aerotolerance profiles significantly differed between intestinal segments in patients without inflammatory bowel disease, although both were dominated by obligate anaerobes, as expected. In CD, high relative levels of obligate anaerobes were maintained in the colon and increased in the ileum. Relative abundances of similar and distinct taxa were altered in colon and ileum. Notably, several obligate anaerobes, such as Bacteroides fragilis, dramatically increased in CD in one or both intestinal segments, although specific increasing taxa varied across patients. Increased abundance of taxa from the Proteobacteria phylum was found only in the ileum. Bacterial diversity was significantly reduced in resected tissues of patients who developed postoperative disease recurrence across 2 independent cohorts, with common lower abundance of bacteria from the Bacteroides, Streptococcus, and Blautia genera. Conclusions Mucosally adherent bacteria in the colon and ileum show distinct alterations in CD that provide additional insights not revealed in fecal material.