Diabetes Treatment And Depression Biology Essay

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Background: Depression has been reported to be positively associated with diabetes, but fewer studies have investigated the relationship between fasting glucose Level, glycohemoglobin, diabetes treatment and depression. This study investigates their association with well-established data from the National Health and Nutrition Examination Survey (NHANES).

Methods: In the cross-sectional NHANES survey from 2005-2008, 9,756 US men and women aged 18-85 years were surveyed for depression symptoms and diabetes mellitus. Depression was measured by the Patient Health Questionnaire (PHQ-9). Plasma fasting glucose level was categorized into these ranges: normal (<100mg/dl), impaired fasting glucose (100-125mg/dl) and diabetes (>125mg/dl). Glycohemoglobin (HbA1C) was categorized into the ranges: normal (<6%), subdiabetic A1C (6-6.4%) and diabetes (≥6.5%). Diabetes treatment was further dichotomized into: untreated, taking insulin and those taking oral hypoglycemic agents. A logistic regression model was used to evaluate the odds ratio after adjusting all covariants.

Results: Diabetes was associated with a 70% increased risk of depression (odds ratio (OR), 1.73; 95% confidence interval, 1.47-1.61), which was attenuated but still significant after adjustment for all DM-related covariants (OR, 1.49; CI, 1.25-1.77). After adjusted for all covariants, impaired fasting glucose and sub-diabetic A1C might increase the risk of depression as well but not significant. Among participants with diabetes, participants taking oral hypoglycemic agents (OHA) tended to have an increased risk of depression (OR, 1.2, 95% confidence interval, 0.76-1.91).

Conclusion: Our results suggested that diabetes mellitus is independently and positively associated with a heightened risk of depression. Our data conflict with the previous findings that suggested that individuals with impaired fasting glucose and individuals with untreated diabetes have a lower risk of depression.

Fasting Glucose Level, Glycohemoglobin, Diabetes Treatment and Depression: Findings from the National Health and Nutrition Examination, 2005-2008

Introduction

The positive association among depression and diabetes was reported in many studies.1-4 However, the mechanism linking these disorders and the causal direction of the association remains unclear. These associations may be related to an increased risk of depressive symptoms in individuals with diabetes, an increased risk of type 2 diabetes in individuals with depressive symptoms, or both. Several longitudinal studies5-9 but not all10 have reported that elevated depressive symptoms are increased in incidence in Type 2 diabetes. In contradistinction, there are also some prospective studies that have suggested that diabetes is associated with increased risk of depression.11-13 The hypotheses for depression increasing incident diabetes include less physical activities and increasing obesity-promoting health behaviors,5-7, 9, 14, 15 and increasing inflammatory responses which might induce insulin resistance and cause Type 2 diabetes.16, 17 Alternatively, the most commonly explanations for diabetes elevating the risk of depression are that depression and the sense of hopelessness that may arise from having a chronic disease such as diabetes.18-20

A recent prospective longitudinal study reported a bidirectional association between depressive symptoms and diabetes.13 In this study, investigators surprisingly found that participants impaired fasting glucose and untreated diabetes was associated with a lower risk of elevated depressive symptoms,13 and treating diabetes might increase depressive symptoms13 as well.

In this study, we used the data from National Health and Nutrition Examination Survey (NHANES) 2005-2008 to exam the association between fasting glucose level, glycohemoglobin, diabetes treatment and depression.

Materials and Methods

Study design and population

Participants are from part of the continuous National Health and Nutrition Examination Survey (NHANES) 2005-2008. The NHANES program began in the early 1960s and has been conducted as a series of surveys focusing on different population groups or health topics. In 1999, the survey became a continuous program that has a changing focus on a variety of health and nutrition measurements to meet emerging needs. The survey examines a nationally representative sample of about 5,000 persons each year. These persons are located in counties across the country, 15 of which are visited each year.21 Continuous NHANES, conducted from 1999 to current, was a cross-sectional survey of health conditions and health-related behaviors in a probability sample of the non-institutionalized civilian population of the United States aged 1-85 years and older. Participants in continuous NHANES abstracted in every two-year cycle, 1999-2000, 2001-2003, 2003-2004, 2005-2006, 2007-2008, 2009-2010, etc. A detailed description of the study design and sampling methods is available elsewhere.22

This study includes the subset of NHENES, 2005-2008 participants who received depression screen, diabetes questionnaire, plasma fasting glucose and glycohemoglobin laboratory examination (HbA1C) (n = 9,756). This paper includes information on participants: 4,774 men and 4,982 women; age from 18 year-old to 85 year-old.

Measurements

The Depression Screener (DPQ) questions are from the Patient Health Questionnaire (PHQ-9), a version of the Prime-MD diagnostic instrument. They are a self-reported assessment of the past 2 weeks, based on nine DSM-IV signs and symptoms from depression. The nine symptom questions are scored from "0" (not at all) to "3" (nearly every day). Depression severity can be defined by several cut points from the total score that ranges from 0-27.23 A final follow-up question assesses the overall impairment of the depressive symptoms.23, 24

Participants were asked the following 9 questions 23: "Over the last 2 weeks, how often have you been bothered by the following problems: little interest or pleasure in doing things? Would you say..."; "Over the last 2 weeks, how often have you been bothered by the following problems: feeling down, depressed, or hopeless?"; "Over the last 2 weeks, how often have you been bothered by the following problems: trouble falling or staying asleep, or sleeping too much?"; "Over the last 2 weeks, how often have you been bothered by the following problems: feeling tired or having little energy?"; "Over the last 2 weeks, how often have you been bothered by the following problems: poor appetite or overeating?"; "Over the last 2 weeks, how often have you been bothered by the following problems: feeling bad about yourself - or that you are a failure or have let yourself or your family down?"; "Over the last 2 weeks, how often have you been bothered by the following problems: trouble concentrating on things, such as reading the newspaper or watching TV?"; "Over the last 2 weeks, how often have you been bothered by the following problems: moving or speaking so slowly that other people could have noticed? Or the opposite - being so fidgety or restless that you have been moving around a lot more than usual?", and "Over the last 2 weeks, how often have you been bothered by the following problems: Thoughts that you would be better off dead or of hurting yourself in some way?" Responses are provided on a Likert scale, with higher values indicating a more depressed mood. 23

In this study, depression was defined by PHQ-9 score > or =10.23 Analysis were based on previous research indicating that scores of 5-9 correspond with mild depression, scores of 10-14 indicate moderate depression, scores of 15-19 indicate moderately severe, and scores of 20-27 indicate severe depression. Using the mental health professional reinterview as the criterion standard, a PHQ-9 score > or =10 had a sensitivity of 88% and a specificity of 88% for major depression (MDD).23

Diabetes was defined by self-report as whether a doctor told you have diabetes. Participants were asked "Other than during pregnancy, have you ever been told by a doctor or health professional that you have diabetes or sugar diabetes? We could not identify whether incident diabetes was type 1 or type 2, but type 2 diabetes represents over 90 percent of diabetes diagnoses and is much more likely to develop after age 30 years.25

For fasting glucose level, participants aged 12 years and older who were examined in the morning session were tested. Fasting glucose level was categorized into following ranges for analysis: Normal (<100mg/dl), impaired fasting glucose (100-125mg/dl) and diabetes (>125mg/dl).26-29 Blood specimens were processed, stored and shipped to Fairview Medical Center Laboratory at the University of Minnesota, Minneapolis Minnesota for analysis. Detailed specimen collection and processing instructions are discussed in the NHANES Laboratory/Medical Technologists Procedures Manual (LPM).30

Glycohemoglobin (HbA1C) was categorized into three ranges: normal (<6.0%), sub-diabetic A1C levels (6.0-6.4%) and diabetes (≥6.5)28, 29 in Analysis 1- Diabetes and Depression. The association between depression and glycohemoblobin among participants with diabetes were examined continuously (2-15.6%) in Analysis 2- Diabetes treatment and Depression. Blood specimens were processed, stored and shipped to Fairview Medical Center Laboratory at the University of Minnesota, Minneapolis Minnesota for analysis. Detailed specimen collection and processing instructions are discussed in the NHANES LPM. In this assay, the stable (SA1c) and labile (LA1c) A1c forms can be individually resolved on the chromatogram without manual pretreatment, allowing accurate measurement of the stable form of HbA1c. The analyzer dilutes the whole blood specimen with a hemolysis solution, and then injects a small volume of the treated specimen onto the HPLC analytical column. Separation is achieved by utilizing differences in ionic interactions between the cation exchange group on the column resin surface and the hemoglobin components. The hemoglobin fractions (A1c, A1b, F, LA1c, SA1c, A0 and H-Var) are subsequently removed from the column material by step-wise elution using elution buffers each with a different salt concentration. The separated hemoglobin components pass through the photometer flow cell where the analyzer measures changes in absorbance at 415 nm. The analyzer integrates and reduces the raw data, and then calculates the relative percentages of each hemoglobin fraction. Analysis requires three minutes. There were changes to the equipment from NHANES 2005-2006 to NHANES 2007-2008. For NHANES 2005-2006, glycohemoglobin measurements were performed on the A1c 2.2 Plus Glycohemoglobin Analyzer (Tosoh Medics, Inc., 347 Oyster Pt. Blvd., Suite 201, So. San Francisco, Ca 94080.). For NHANES 2007-2008 glycohemoglobin measurements were performed on the A1c G7 HPLC Glycohemoglobin Analyzer (Tosoh Medics, Inc., 347 Oyster Pt. Blvd., Suite 201, So. San Francisco, Ca 94080.).31

Diabetes treatment was analyzed "taking insulin now", "take diabetic pill to lower blood sugar" and both. Participants were asked the following questions: "Are you now taking insulin?" and "Are you now taking diabetic pills to lower blood sugar? These are sometimes called oral agents or oral hypoglycemic agents."32

We controlled for universal covariants including age, gender, race, marital status associated with diabetes and depression. In addition, we also controlled for cigarette smoking status, alcohol drinking, blood pressure and body mass index, which associated with diabetes and caused depression.8, 13, 33 Briefly, age at interview, gender, ethnic race and marital status were obtained via self-report. On the basis of information collected from health interview surveys, we categorized cigarette smoking status (every day, some days, or not at all)34, and number of drinks of alcohol per day (0, 1-2, or ≥3)35. At the baseline medical examination, blood pressure was measured while participants were seated36. We identified a participant as hypertensive if he or she met one of the following conditions: antihypertensive medication use, or a previous physician diagnosis of hypertension.36 We calculated baseline body mass index as the ratio of measured weight (in kilograms) to squared standing height (in meters).37

Statistical methods

We compared the distribution of baseline characteristics by self-report diabetes status, fasting glucose categories, glycohemoglobin categories and diabetes treatment. We evaluated statistical significance by using t tests for means and χ2 tests for proportions. In Analysis 1-Diabetes and Depression, we used logistic regression model to estimate the odds ratio of depression (PHQ9 > or =10) by diabetes status, fasting glucose categories and glycohemoglobin categories. In Analysis 2-Diabetes treatment and Depression, we further estimated the odds ratio of depression (PHQ9 > or =10) among diabetes participants by diabetes treatment (untreated, taking insulin and taking oral hypoglycemic agents (OHA)).

All covariates were evaluated as potential effect modifiers (heterogeneity) by using first- order interaction terms between each covariate and self-report diabetes status. A significant (p < 0.05) change in the maximum likelihood χ2 value following removal of the interaction term from the model indicated statistical interaction. When there was evidence of effect modification, we retained the interaction term in the model.

All analyses were conducted by using Sata software, version 11.0 for Mac (StataCorp, 4905 Lakeway Dr., College Station, TX 77845, USA). Statistical significance is denoted at p < 0.05.

Results

Analysis 1- Diabetes status and Depression

Baseline Characteristics

Table 1 summarized the characteristics of the participants by diabetes and non-diabetes. Compared with non-diabetes participants, participants with diabetes were more likely to be older, less never married and have hypertension (p <0.001). In addition, participants with diabetes tend to have higher BMI (p <0.001).

Table 2 listed the distribution of the participants by fasting glucose categories. In comparison to normal fasting glucose, the participants with impaired fasting glucose and diabetes were older and had higher BMI. In addition, Participants with diabetes were more likely to be hypertension.

The distribution of participants' characteristics by plasma glycohemoglobin categories were tabulated in Table 3. Compared to participants with normal glycohemoglobin level, participants with sub-diabetic A1C and diabetes tended to be older, have hypertension and higher BMI.

Table 1 - Characteristics by Diabetes status

Characteristic

Non-Diabetesa

Diabetesa

p-value

Age, mean (SD), y

43.4 (19.1)

61.16 (13.6)

<.001

Gender, No. (%)

Male

Female

48.7

51.8

49.51

50.49

<.001

Race/Ethnicity, No. (%)

Mexican American

Other Hispanic

Non-Hispanic White

Non-Hispanic Black

Other Race

19.6

7.4

49.1

20.2

3.8

19.3

8.3

39.9

30.1

2.3

<.001

Marital status, No. (%)

Married

Widowed

Divorced

Separated

Never married

Living with partner

51.2

7.1

9.6

3.1

20.8

8.3

56.6

15.5

13.5

4.0

7.4

3.0

<.001

Hypertension*, No. (%)

No

Yes*

72.8

27.2

33.1

66.9

<.001

BMI, mean (SD) (kg/m2)

28.2 (6.5)

32.3 (7.4)

<.001

Cigarettes Smoking, No. (%)

Never

Some days

Every day

22.4

3.4

17.8

34.9

1.8

13.9

<.001

Alcohol (drinks/day), No. (%)

0

1-2

>=3

38.0

20.7

16.6

57.2

19.4

10.5

<.001

aSelf-report diabetes

Table 2 - Characteristics by Plasma Fasting Glucose Categories

Characteristic

Normal

(<100mg/dl)

Impaired fasting glucose

(100-125mg/dl)

Diabetes

(>125mg/dl)

p-value

Age, mean (SD), y

40.6 (18.4)

52.3 (18.2)

60.1 (14.7)

<.001

Gender, No. (%)

Male

Female

42.0

58.0

59.1

40.9

54.6

45.4

<.001

Race/Ethnicity, No. (%)

Mexican American

Other Hispanic

Non-Hispanic White

Non-Hispanic Black

Other Race

17.8

7.0

47.4

23.9

3.9

20.0

8.3

50.3

17.2

4.2

21.9

7.4

43.6

25.9

1.3

<.001

Marital status, No. (%)

Married

Widowed

Divorced

Separated

Never married

Living with partner

48.8

5.0

8.7

2.8

25.0

9.8

54.2

9.5

11.2

3.9

14.3

6.9

56.3

15.6

11.9

3.3

8.2

4.8

<.001

Hypertension*, No. (%)

No

Yes*

79.1

20.9

60.4

39.6

36.6

63.4

<.001

BMI, mean (SD) (kg/m2)

27.1 (6.0)

29.7 (7.0)

32.1 (7.3)

<.001

Cigarettes Smoking,

No. (%)

Never

Some days

Every day

19.0

2.7

18.0

28.7

3.1

18.4

36.0

2.4

14.5

<.001

Alcohol,(drinks/day)

No. (%)

0

1-2

>=3

40.2

19.8

16.0

35.8

23.3

16.2

54.8

18.8

12.0

<.001

Table 3 - Characteristics by Glycohemoglobin Categories

Characteristic

Normal

(<6.0%)

Sub-diabetic

(6.0-6.4%)

Diabetes

(≥6.5%)

p-value

Age, mean (SD), y

44.2 (18.9)

61.7 (14.6)

60.7 (13.4)

<.001

Gender, No. (%)

Male

Female

48.5

51.5

50.8

49.3

50.8

49.2

<.001

Race/Ethnicity, No. (%)

Mexican American

Other Hispanic

Non-Hispanic White

Non-Hispanic Black

Other Race

19.7

7.3

50.0

19.2

3.8

15.3

8.1

43.3

29.9

3.4

21.6

8.5

36.1

31.6

2.2

<.001

Marital status, No. (%)

Married

Widowed

Divorced

Separated

Never married

Living with partner

51.2

6.4

9.4

3.0

21.5

8.5

52.4

16.8

13.0

4.1

9.1

4.6

57.0

15.0

13.3

3.6

7.7

3.4

<.001

Hypertension*, No. (%)

No

Yes*

74.1

26.0

43.3

56.7

38.5

61.5

<.001

BMI, mean (SD) (kg/m2)

28.0 (6.4)

31.4 (6.7)

32.7 (7.6)

<.001

Cigarettes Smoking, No. (%)

Never

Some days

Every day

22.0

3.3

17.7

34.0

3.6

16.6

32.1

2.0

15.4

<.001

Alcohol (drinks/day), No. (%)

0

1-2

>=3

37.4

20.4

17.0

49.8

23.1

11.9

55.8

19.8

10.8

<.001

Univariate and Multivariate Analyses

There was a significant association between depression and diabetes (OR, 1.73, 95% confidence interval, 1.47-2.04, p <.001) after adjusting for age, gender, race and marital status (Table 4, model A). After further adjusted for BMI, the association attenuated but was still significant (OR, 1.59, 95% confidence interval, 1.35-1.89, p <.001) (Table 4, model B). We further adjusted for alcohol drinking and hypertension status, the association was remain statistically significant (Table 4, model B and C). After adjusted all covariants, the association was persistent and significant (OR, 1.49, 95% confidence interval, 1.25-1.77, p <.001).

By using fasting glucose level instead of self-reported diabetes, the association between impaired fasting glucose and depression was positive, but not statistically significant (OR, 1.15, 95% confidence interval, 0.89-1.48, p = 0.28) (Table 5). However, the association between diabetes and depression was highly positive, and significant (OR, 1.69, 95% confidence interval, 1.21-2.35, p < 0.05) (Table 5).

Model

Non-diabetes

Diabetes

Base, model Aa

1 (Reference)

1.73 (1.47-2.04)

Alcohol drinking, model Bb

1 (Reference)

1.61 (1.36-1.91)

Hypertension status, model Cc

1 (Reference)

1.49 (1.26-1.77)

All covariants, model Dd

1 (Reference)

1.49 (1.25-1.77)

Table 4 - Diabetes status and Depression

aAdjusted for age, gender, ethnicity race, marital status, BMI

bAdjusted using model A criteria and alcohol drinking

cAdjusted using model B criteria and hypertension status

dFully-adjusted for all covariants

Table 5 - Plasma Fasting Glucose and Depression

Model

Normalb

Impaired fasting glucosec

Diabetesd

All covarinatsa

1 (Reference)

1.51 (0.89-1.78)

1.69 (1.21-2.35)

aFully-adjusted for all covariants: age, gender, race, marital status, hypertension, BMI, cigarettes smoking and alcohol drinking

bNormal fasting glucose (<100mg/dl)

cImpaired fasting glucose (100-125mg/dl)

dDiabetes (>125mg/dl)

Table 6 - Glycohemoglobin and Depression

Model

Normalb

Subdiabetesc

Diabetesd

All covarinatsa

1 (Reference)

1.12 (0.85-1.49)

1.37 (1.07-1.76)

aFully-adjusted for all covariants: age, gender, race, marital status, hypertension, BMI, cigarettes smoking and alcohol drinking

bNormal Glycohemoglobin <6.0%

cSubdiabetic Glycohemoglobin=6.0-6.4%

dDiabetes ≥6.5%

Analysis 2- Diabetes treatment and depression among participants with diabetes

Baseline Characteristics

Table 7 summarized the characteristics of the participants by diabetes treatment among participants with diabetes (n = 1,030). Compared with participants with untreated diabetes, participants who treated their diabetes were more likely to be older and have higher BMI (p <.001).

Table 7 - Characteristics by Diabetes Treatment

Characteristic

Untreated Diabetes

Treated Diabetes

p-value

Taking Insulin

No Yes

Taking OHA

No Yes

Age, mean (SD), y

58.4 (15.4)

61.6 (13.1)

59.9 (14.9)

57.9 (15.9)

62.4 (12.5)

<.001

Gender, No. (%)

Male

Female

45.6

51.4

48.6

51.4

52.0

48.0

52.0

48.0

48.6

51.4

<.001

Race/Ethnicity, No. (%)

Mexican American

Other Hispanic

Non-Hispanic White

Non-Hispanic Black

Other Race

22.5

7.8

42.3

24.7

2.8

21.5

8.9

39.2

27.9

2.5

13.4

6.9

41.9

36.1

1.8

19.0

7.2

41.2

30.5

2.2

19.4

8.8

39.4

30.0

2.4

<.001

Marital status, No. (%)

Married

Widowed

Divorced

Separated

Never married

Living with partner

57.5

15.8

13.6

3.7

6.8

2.6

58.3

14.2

12.8

3.9

8.0

2.9

52.0

19.0

15.4

4.4

5.9

3.3

53.8

14.2

14.9

4.4

8.0

4.7

57.7

16.0

12.9

3.9

7.2

2.4

<.001

Hypertension*, No. (%)

No

Yes*

38.7

61.3

32.7

67.3

34.3

65.7

37.6

62.4

31.4

68.6

<.001

BMI, mean (SD) (kg/m2)

30.9 (7.0)

31.8 (7.1)

33.6 (8.3)

31.8 (7.9)

32.4 (7.3)

<.001

Cigarettes Smoking, No. (%)

Never

Some days

Every day

37.3

2.1

16.2

33.9

1.7

14.9

37.6

2.2

11.2

37.6

1.8

14.0

33.8

1.9

13.9

<.001

Alcohol (drinks/day), No. (%)

0

1-2

>=3

47.9

20.4

9.9

54.7

19.5

11.8

63.9

19.1

6.9

55.9

19.0

7.5

57.7

19.6

11.6

<.001

Univariate and Multivariate Analyses

There was a reverse association between depression and treated diabetes after adjusting univariate and all covariates, but the result was not significant (OR, 0.8, 95% confidence interval, 0.46-1.39) (Table 8). The associations between depression and taking insulin was also reversed but also insignificant (OR, 0.85, 95% confidence interval, 0.54-1.34) (Table 8). However, the association between depression and taking OHA was positive, but remained insignificant (OR, 1.2, 95% confidence interval, 0.76-1.91) (Table 8). There was a reversed association between depression and glycohemoglobin levewl among participants with diabetes, but it was not significant as well (OR, 0.95, 95% confidence interval, 0.85-1.07) (Table 8).

Table 8 - Diabetes Treatment and Depression Among Participants with Diabetes

Model

Odds ratio

Treated Diabetesa

No

Yes

1 (Reference)

0.8 (0.46-1.39)

Taking Insulina

No

Yes

Reference

0.85 (0.54-1.34)

Taking OHAa

No

Yes

1 (Reference)

1.2 (0.76-1.91)

Glycohemoglobinab

0.95 (0.85-1.07)

aFully-adjusted for all covariants: age, gender, race, marital status, hypertension, BMI, cigarettes smoking and alcohol drinking

bPlasma Glycohemoglobin was used as continuous variant

Discussion

Analysis 1- Diabetes status and depression

These findings suggest that individuals with diabetes have a significantly higher risk of depression, which is concordant with previous studies2, 3, 13, 38. After adjusting for all covariants, the association is persistent and remains significant. However, the mechanism and causal relationship are still unclear and controversial. Several 5-8, 14 but not all 10 studies have reported that depressive symptoms increase the incidence of diabetes. On the other hand, a causal relationship suggesting that diabetes elevated the risk of depression has also been reported 11, 12, 39. Further studies are needed to establish the mechanisms and causal relationship.

One previous study found that individuals with impaired glucose level might have lower risk of elevated depressive symptoms 13. However, this finding was not supported by our results. Our results suggested that participants with impaired glucose level tended to increase risk of depression instead of lower, though it was not significant. The difference might be due to the different criteria for depression (CES-D ≥ 1613 versus PHQ-9 ≥10), different study populations (Multi-Ethnic Study of Atherosclerosis13 versus NHANES), and different sample size (n = 4,87813 versus n = 9, 756) as well. Further studies to determine the association between impaired glucose level and depression were needed.

Individuals with sub-diabetic A1C level tend to have higher risk of diabetes in the future27-29. In the analysis between plasma glycohemoglobin (HbA1C) level and depression, the individuals with sub-diabetic A1C level were more likely to, though not significant, have higher risk of depression, which corresponded to the findings in individuals with impaired glucose level in this study, and supported the finding in individuals with impaired glucose level.

Analysis 2- Diabetes treatment and depression among participants with diabetes

We cannot find a significant association between diabetes treatment and depression. However, though the association was not significant, participants taking oral hypoglycemic agents (OHA) were more likely to have higher risk of depression compared to participants taking insulin. To our knowledge, whether the OHA increases the risk of depression compared to insulin has not been studied, and the biological mechanism is still unclear. In addition, the association between glycohemoglobin and depression among participants with diabetes was also not significant in our study.

Using data from universal and rigorous NHANES survey is the strength of our study. In addition, the sufficient numbers of participants also make our result convincible. However, because the limitation of cross-sectional studies, we cannot further investigate the causal relationship between depression and diabetes.

To sum up, diabetes is positively associated with depression. We did not find evidence to support the previous finding13 that individuals with impaired fasting glucose and untreated diabetes have a lower risk of depression.

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