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Genetic Predictors of Depressive Symptoms in the Look AHEAD Trial.

ABSTRACT: OBJECTIVES:Numerous studies have found elevated depressive symptoms among individuals with Type 2 diabetes, yet the mechanisms remain unclear. We examined whether genetic loci previously associated with depressive symptoms predict depressive symptoms among overweight/obese individuals with Type 2 diabetes or change in depressive symptoms during behavioral weight loss. METHODS:The Illumina CARe iSelect (IBC) chip and Cardiometabochip were characterized in 2118 overweight or obese participants with Type 2 diabetes from Look AHEAD (Action for Health in Diabetes), a randomized trial to determine the effects of intensive life-style intervention and diabetes support and education on cardiovascular morbidity and mortality. Primary analyses focused on baseline Beck Depression Inventory (BDI) scores and depressive symptom change at 1 year. RESULTS:Of eight single nucleotide polymorphisms (SNPs) in six loci, three a priori SNPs in two loci (chromosome 5: rs60271; LBR: rs2230419, rs1011319) were associated with baseline BDI scores, but in the opposite direction of prior research. In joint analysis of 90,003 IBC and Cardiometabochip SNPs, rs1543654 in the region of KCNE1 predicted change in BDI scores at Year 1 in diabetes support and education (? = -1.05, standard error [SE] = 0.21, p = 6.9 × 10(-7)) at the level of chip-wide significance, while also showing a nominal association with baseline BDI (? = 0.35, SE = 0.16, p = .026). Adjustment for antidepressant medication and/or limiting analyses to non-Hispanic white individuals did not meaningfully alter results. CONCLUSIONS:Previously reported genetic associations with depressive symptoms did not replicate in this cohort of overweight/obese individuals with Type 2 diabetes. We identified KCNE1 as a potential novel locus associated with depressive symptoms.

SUBMITTER: McCaffery JM

PROVIDER: S-EPMC4643359 | biostudies-literature | 2015 Nov-Dec

REPOSITORIES: biostudies-literature

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Genetic Predictors of Depressive Symptoms in the Look AHEAD Trial.

McCaffery Jeanne M JM Papandonatos George D GD Faulconbridge Lucy F LF Erar Bahar B Peter Inga I Wagenknecht Lynne E LE Pajewski Nicholas M NM Anderson Andrea A Wadden Thomas A TA Wing Rena R RR

Psychosomatic medicine 20151101 9

<h4>Objectives</h4>Numerous studies have found elevated depressive symptoms among individuals with Type 2 diabetes, yet the mechanisms remain unclear. We examined whether genetic loci previously associated with depressive symptoms predict depressive symptoms among overweight/obese individuals with Type 2 diabetes or change in depressive symptoms during behavioral weight loss.<h4>Methods</h4>The Illumina CARe iSelect (IBC) chip and Cardiometabochip were characterized in 2118 overweight or obese p ...[more]

PMID: 26489030

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Project description:BACKGROUND:The decision to initiate insulin in patients with type 2 diabetes is a challenging escalation of care that requires an individualized approach. However, the sociodemographic and clinical factors affecting insulin initiation are not well understood. OBJECTIVE:We sought to identify patient factors that were independent predictors of insulin initiation among participants in the Look AHEAD (Action for Health in Diabetes) clinical trial. DESIGN:Retrospective analysis of a randomized clinical trial. PARTICIPANTS:Beginning in 2001, Look AHEAD enrolled ambulatory U.S. adults with type 2 diabetes who were overweight or obese and had a primary healthcare provider. Participants were randomized (1:1) to an intensive lifestyle intervention, or diabetes support and education. This study examined 3913 participants across the two trial arms who were not using insulin at baseline. MAIN MEASURES:We used Cox proportional hazards models to estimate the association between participant characteristics and time to insulin initiation. We performed time-varying adjustment for HbA1c measured eight times over the 10-year study period, as well as for multiple clinical and socioeconomic factors. KEY RESULTS:A total of 1087 participants (27.8%) initiated insulin during a median follow-up of 8.0 years. Age was inversely associated with insulin initiation (adjusted hazard ratio [aHR] 0.88 per 10 years, P?=?0.025). The risk of insulin initiation was greater with a higher number of diabetes complications (P?<?0.001 for trend); chronic kidney disease and cardiovascular disease were independently associated with insulin initiation. There was a lower risk of insulin initiation in black (aHR 0.77, P?=?0.008) and Hispanic participants (aHR 0.66, P?<?0.001) relative to white participants. Socioeconomic factors were not associated with insulin initiation. CONCLUSIONS:Patient age, race/ethnicity, and diabetes complications may influence insulin initiation in type 2 diabetes, independent of glycemic control. Future work is needed to understand the drivers of racial differences in antihyperglycemic treatment, and to identify patients who benefit most from insulin.

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Genetic Predictors of Depressive Symptoms in the Look AHEAD Trial.

Publications

Genetic Predictors of Depressive Symptoms in the Look AHEAD Trial.

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