Depressive symptom profiles and glucose tolerance status

Depression is known to be two to three times more prevalent among individuals who have diabetes than among those without it1. The conventional hypothesis suggests that the higher prevalence of depression among individuals with diabetes is a consequence of the psychological distress created by the diagnosis, namely its stigmatizing effects and the long‐term complications. However, there is contradictory evidence that an association can also be observed between insulin resistance and depression among individuals without diabetes2. To address this inconsistency, three recent reviews3, 4, 5, including one published in this journal5, have called for greater precision in studies, proposing that specific depression profiles (e.g., atypical depression) should be further investigated.

We conducted a population‐level investigation on the importance of atypical and non‐atypical depressive symptoms in specific pre‐diabetic states as well as in previously undiagnosed and diagnosed diabetes mellitus. The 75 g oral glucose tolerance test was used to define each person's glucose tolerance status. Depressive symptom profiles were defined by using the 21‐item Beck Depression Inventory (BDI‐II). Participants who scored at least 14 points and responded positively (at least one point) to both reversed vegetative symptoms (oversleeping and overeating) were defined as having atypical depressive symptoms6. The rest of the participants with at least 14 BDI‐II points were defined as having non‐atypical depressive symptoms.

In the study sample (N=4838; Northern Finland Birth Cohort 1966 members with written consent who volunteered to participate in clinical examination at the age of 46 years), we found 379 (7.8%) and 74 (1.5%) participants with non‐atypical and atypical depressive symptoms, respectively. The prevalence of normal glucose tolerance, defined as having a fasting plasma glucose (FPG) concentration <6.1 mmol/l and a two‐hour glucose <7.8 mmol/l, was only 61% among those with atypical depressive symptoms, whereas it was 73% and 79% among those with non‐atypical and no depressive symptoms, respectively.

The proportions of all abnormal glucose tolerance states were highest among participants with atypical depressive symptoms. The prevalence of impaired fasting glucose (FPG 6.1‐6.9 mmol/l and a two‐hour glucose <7.8 mmol/l) among those with atypical, non‐atypical and no depressive symptoms was 8%, 7% and 7%, respectively. The corresponding prevalence of impaired glucose tolerance (FPG <7.0 mmol/l and a two‐hour glucose of 7.8‐11.0 mmol/l) was 15%, 11% and 8%, respectively. The prevalence of previously undiagnosed type 2 diabetes (FPG ≥7.0 mmol/l or a two‐hour glucose ≥11.1 mmol/l) was 5%, 3% and 2%, respectively.

Previously diagnosed diabetes was designated if any of the following was observed: self‐reported diagnosis of diabetes made by a physician; self‐reported medication for diabetes; inpatient or outpatient visit at a hospital due to diabetes (all hospital visits were obtained from the Finnish Care Register for Health Care); or the right to purchase diabetes medication at a subsidized cost (data obtained through national medication registers from the Social Insurance Institution of Finland). The prevalence of previously diagnosed type 2 diabetes was 11%, 6% and 3% among those with atypical, non‐atypical and no depressive symptoms, respectively.

Differences in the distribution of glucose tolerance status between depressive symptoms profile groups were statistically significant (Pearson's chi‐square test: F/χ²=40.26, df=10, p=0.00002). Mean body mass index was 30.8 ± 7.5 kg/m², 28.0 ± 5.7 kg/m² and 26.7 ± 4.7 kg/m² among those with atypical depressive symptoms, non‐atypical depressive symptoms and no depressive symptoms, respectively (p=0.002, Kruskal‐Wallis test, pairwise; atypical vs. non‐atypical). The participants self‐reported their physical activity, education level, smoking status, alcohol and antidepressant medication use; of these, when tested pairwise, only use of selective serotonin reuptake inhibitors was different among the subtypes (30% for atypical vs. 11% for non‐atypical, p=0.0001, Fisher's exact test).

Taken together with previous findings5, 7, our results support the importance of subtyping depression in people with type 2 diabetes, as recently postulated in this journal5. The current results also highlight the phenomenon already in pre‐diabetic states. We speculate that the results of previous studies on the association between depression and type 2 diabetes might have been different if depression subtypes had been analyzed.

Pasi J. Eskola1,2, Juha P. Auvinen1,3, Jari Jokelainen1,3, Timo Liukkonen1,4, Sylvain Sebert1,5,6, Aimo Ruokonen7,8, Katri Puukka7,8, Markku Timonen1, Sirkka Keinänen‐Kiukaanniemi1‐3
1Center for Life Course Health Research, University of Oulu, Oulu, Finland; 2Kontinkangas Wellness Centre, Oulu, Finland; 3Unit of Primary Care, Oulu University Hospital, Oulu, Finland; 4Mikkeli Central Hospital, Mikkeli, Finland; 5Biocenter Oulu, University of Oulu, Finland; 6Department of Genomics of Complex Diseases, Imperial College London, London, UK; 7NordLab Oulu, Oulu University Hospital, Oulu, Finland; 8Department of Clinical Chemistry, University of Oulu, Oulu, Finland

The two first and the last two authors contributed equally to this piece.