Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Diabetes Reports
Published in: Current Diabetes Reports 6/2010

01-12-2010

Biological Basis of Depression in Adults with Diabetes

Authors: Shivam Champaneri, Gary S. Wand, Saurabh S. Malhotra, Sarah S. Casagrande, Sherita Hill Golden

Published in: Current Diabetes Reports | Issue 6/2010

Login to get access

Abstract

Diabetes and depression are common comorbid conditions. Although certain health behaviors and risk factors partially explain the association of depression and diabetes, other potential mechanisms have yet to be elucidated. Certain neuroendocrine alterations such as activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) may contribute to the association. Additionally, presence of a proinflammatory state shown in recent literature in both diabetes and depression may contribute to this as well. The objectives of this review are to summarize and review the recent evidence showing alterations of these three biological systems—HPA axis, SNS, and inflammatory cascade—in depression, diabetes, and diabetes-related risk factors.
Literature
1.
Mezuk B, Eaton WW, Albrecht S, Golden SH, et al.: Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care 2008, 31:2383–2390.CrossRefPubMed
2.
Golden SH: A review of the evidence for a neuroendocrine link between stress, depression and diabetes mellitus. Curr Diabetes Rev 2007, 3:252–259.CrossRefPubMed
3.
Adam EK, Kumari M: Assessing salivary cortisol in large-scale, epidemiological research. Psychoneuroendocrinology 2009, 34:1423–1436.CrossRefPubMed
4.
Rao U, Poland RE: Electroencephalographic sleep and hypothalamic-pituitary-adrenal changes from episode to recovery in depressed adolescents. J Child Adolesc Psychopharmacol 2008, 18:607–613.CrossRefPubMed
5.
Rao U, Hammen CL, Poland RE: Risk markers for depression in adolescents: sleep and HPA measures. Neuropsychopharmacology 2009, 34:1936–1945.CrossRefPubMed
6.
Ludescher B, Najib A, Baar S, et al.: Increase of visceral fat and adrenal gland volume in women with depression: preliminary results of a morphometric MRI study. Int J Psychiatry Med 2008, 38:229–240.CrossRefPubMed
7.
Carpenter LL, Ross NS, Tyrka AR, et al.: Dex/CRH test cortisol response in outpatients with major depression and matched healthy controls. Psychoneuroendocrinology 2009, 34:1208–1213.CrossRefPubMed
8.
Hennings JM, Owashi T, Binder EB, et al.: Clinical characteristics and treatment outcome in a representative sample of depressed inpatients—findings from the Munich Antidepressant Response Signature (MARS) project. J Psychiatr Res 2009, 43:215–229.CrossRefPubMed
9.
Pruessner JC, Wolf OT, Hellhammer DH, et al.: Free cortisol levels after awakening: a reliable biological marker for the assessment of adrenocortical activity. Life Sci 1997, 61:2539–2549.CrossRefPubMed
10.
Chida Y, Steptoe A: Cortisol awakening response and psychosocial factors: a systematic review and meta-analysis. Biol Psychol 2009, 80:265–278.CrossRefPubMed
11.
Kuehner C, Holzhauer S, Huffziger S: Decreased cortisol response to awakening is associated with cognitive vulnerability to depression in a nonclinical sample of young adults. Psychoneuroendocrinology 2007, 32:199–209CrossRefPubMed
12.
Huber TJ, Issa K, Schik G, et al.: The cortisol awakening response is blunted in psychotherapy inpatients suffering from depression. Psychoneuroendocrinology 2006, 31:900–904.CrossRefPubMed
13.
Kudielka BM, Wust S: Human models in acute and chronic stress: assessing determinants of individuals hypothalamus-pituitary-axis activity and reactivity. Stress 2010, 13:1–14.CrossRefPubMed
14.
Van den Bergh BR, Van Calster B, Pinna Puissant S, et al.: Self-reported symptoms of depressed mood, trait anxiety and aggressive behavior post-pubertal adolescents: associations with diurnal cortisol profiles. Horm Behav 2008, 54:253–257.CrossRefPubMed
15.
Van den Bergh BR, Van Calster B: Diurnal cortisol profiles and evening cortisol in post-pubertal adolescents scoring high on the children’s depression inventory. Psychoneuroendocrinology 2009, 34:791–794.CrossRefPubMed
16.
Bhattacharyya MR, Molloy GJ, Steptoe A: Depression is associated with flatter cortisol rhythms in patients with coronary artery disease. J Psychosom Res 2008, 65:107–113.CrossRefPubMed
17.
Conrad A, Wilhelm FH, Roth WT, et al.: Circadian affective, cardiopulmonary, and cortisol variability in depressed and nondepressed individuals at risk for cardiovascular disease. J Psychiatr Res 2008, 42:769–777.CrossRefPubMed
18.
Taylor CB, Conrad A, Wilhelm FH, et al.: Psycho-physiological and cortisol responses to psychological stress in depressed and nondepressed older men and women with elevated cardiovascular disease risk. Psychosom Med 2006, 68:538–546.CrossRefPubMed
19.
Beluche I, Chaudieu I, Norton J, et al.: Persistence of abnormal cortisol levels in elderly persons after recovery from major depression. J Psychiatr Res 2008, 43:777–783.CrossRefPubMed
20.
Bruehl H, Wolf OT, Convit A: A blunted cortisol awakening response and hippocampal atrophy in type 2 diabetes mellitus. Psychoneuroendocrinology 2009, 34:815–821.CrossRefPubMed
21.
• Boyle SH, Surwit RS, Georgiades A, et al.: Depressive symptoms, race, and glucose concentrations: the role of cortisol as mediator. Diabetes Care 2007, 30:2484–2488. This is the largest study to date within the past 3 years that has confirmed the presence of depression having adverse effect on blood glucose control. It is also one of the first studies citing a racial disparity in this association.CrossRefPubMed
22.
Weigensberg MJ, Toledo-Corral CM, Goran MI: Association between the metabolic syndrome and serum cortisol in overweight Latino youth. J Clin Endocrinol Metab 2008, 93:1372–1378.CrossRefPubMed
23.
• Therrien F, Drapeau V, Lalonde J, et al.: Awakening cortisol response in lean, obese, and reduced obese individuals: effect of gender and fat distribution. Obesity 2007, 15:377–385. This interesting study is important in recent publishings in hypothesizing the possibility that presence of obesity and visceral fat could reflect HPA axis dysregulation. CrossRefPubMed
24.
•• Travison TG, O’ Donnell AB, Araujo AB, et al.: Cortisol levels and measures of body composition in middle-aged and older men. Clin Endocrinol (Oxf) 2007, 67:71–77. This very large study of men documented diminished awakening cortisol among obese subjects. Longitudinal analysis revealed age-related weight loss was associated with increases in serum cortisol. CrossRef
25.
• Purnell JQ, Kahn SE, Samuels MH, et al.: Enhanced cortisol productions rates, free cortisol, and 11 beta HSD 1 expression correlate with visceral fat and insulin resistance in men: effect of weight loss. Am J Physiol Endocrinol Metab 2009, 296:E351–E357. This interesting study found higher cortisol production rate correlated with higher intra-abdominal fat, suggesting that perhaps higher HPA activity in men may promote visceral fat and insulin resistance. CrossRefPubMed
26.
Bruehl H, Rueger M, Dziobek I, et al.: Hypothalamic-pituitary-adrenal axis dysregulation and memory impairments in type 2 diabetes. J Clin Endocrinol Metab 2007, 92:2439–2445.CrossRefPubMed
27.
Misra M, Bredella MA, Tsai P, et al.: Lower growth hormone and higher cortisol are associated with greater visceral adiposity, intramyocellular lipids, and insulin resistance in overweight girls. Am J Physiol Endocrinol Metab 2008, 295:E385–E392.CrossRefPubMed
28.
•• Chiodini I, Adda G, Scillitani A, et al.: Cortisol secretion in patients with type 2 diabetes: relationship with chronic complications. Diabetes Care 2007, 30:83–88. This study of 170 type 2 diabetic patients noted higher urine free cortisol levels, dexamethasone suppression, and noon cortisol values compared with nondiabetic controls. They also noted enhanced HPA activity correlated with the number of diabetes complications. It is also one of the few studies to suggest a central alteration in HPA axis activity with documentation of nonsuppressed adrenocorticotropic hormone levels. CrossRefPubMed
29.
Godoy-Matos AF, Vieira AR, Moreira RO, et al.: The potential role of increased adrenal volume in the pathophysiology of obesity-related type 2 diabetes. J Endocrinol Invest 2006, 29:159–163.PubMed
30.
Golden SH, Malhotra S, Wand GS, et al: Adrenal gland volume and dexamethasone-suppressed cortisol with total daily salivary cortisol in African-American women. J Clin Endocrinol Metab 2007, 92:1358–1363.CrossRefPubMed
31.
Gutt M, Davis CL, Spitzer SB, et al.: Validation of the insulin sensitivity index (ISI(0,120)): comparison with other measures. Diabetes Res Clin Pract 2000, 47:177–184.CrossRefPubMed
32.
Kirschbaum C, Pirke KM, Hellhammer DH: The ‘Trier Social Stress Test’—a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 1993, 28:76–81.CrossRefPubMed
33.
Carney RM, Freedland KE, Veith RC: Depression, the autonomic nervous system, and coronary heart disease. Psychosom Med 2005, 67:S29–S33.CrossRefPubMed
34.
Udupa K, Sathyaprabha TN, Thirthalli J, et al.: Alteration of cardiac autonomic functions in patients with major depression: a study using heart rate variability measures. J Affect Disord 2007, 100:137–141.CrossRefPubMed
35.
• Carroll D, Phillips AC, Hunt K, et al.: Symptoms of depression and cardiovascular reactions to acute psychological stress: evidence from a population study. Biol Psychol 2007, 75:68–74. This is one of the largest studies to document the presence of higher depression scores associated with less heart rate response despite adjustments for gender, BMI, and antidepressant medication. CrossRefPubMed
36.
Mancia G, Bousquet P, Elghozi JL, et al.: The sympathetic nervous system and the metabolic syndrome. J Hypertens 2007, 25:909–920.CrossRefPubMed
37.
• Stein PK, Barzilay JL, Domitrovich PP, et al.: The relationship of heart rate and heart rate variability to non-diabetic fasting glucose levels and the metabolic syndrome. The Cardiovascular Health Study. Diabet Med 2007, 24:855–863. This interesting study cited that patients with two or more components of metabolic syndrome had lower heart rate variability compared to those with only one feature. CrossRefPubMed
38.
Aso Y, Wakabayashi S, Nakano T, et al.: High serum high-sensitivity C-reactive protein concentrations are associated with relative cardiac sympathetic overactivity during the early morning period in type 2 diabetic patients with metabolic syndrome. Metabolism 2006, 55:1014–1021.CrossRefPubMed
39.
Skrapari I, Tentolouris N, Perrea D, et al.: Baroreflex sensitivity in obesity: relationship with cardiac autonomic nervous system activity. Obesity 2007, 15:1685–1693.CrossRefPubMed
40.
Tentolouris N, Liatis S, Katsilambros N: Sympathetic system activity in obesity and metabolic syndrome. Ann N Y Acad Sci 2006, 1083:129–152.CrossRefPubMed
41.
Grassi G, Quarti-Trevano F, Seravalle G, et al.: Cardiovascular risk and adrenergic overdrive in the metabolic syndrome. Nutr Metab Cardiovasc Dis 2007, 17:473–481.CrossRefPubMed
42.
Wiesner TD, Bluher M, Windgassen M, et al.: Improvement of insulin sensitivity after adrenalectomy in patients with pheochromocytoma. J Clin Endocrinol Metab 2003, 88:3632–3636.CrossRefPubMed
43.
Kong AP, Chan NN, Chan JC: The role of adipocytokines and neurohormonal dysregulation in metabolic syndrome. Curr Diabetes Rev 2006, 2:397–407.PubMed
44.
Brummett BH, Boyle SH, Ortel TL, et al.: Associations of depressive symptoms, trait hostility, and gender with C-reactive protein and interleukin-6 response after emotion recall. Psychosom Med 2010, 72:333–339.CrossRefPubMed
45.
Elovainio M, Aalto AM, Kivimaki M, et al.: Depression and C-reactive protein: population-based Health 2000 study. Psychosom Med 2009, 71:423–430.CrossRefPubMed
46.
• Kobrosly R, van Wijngaarden E: Associations between immunologic, inflammatory, and oxidative stress markers with severity of depressive symptoms: an analysis of the 2005–2006 National Health and Nutrition Examination Survey. Neurotoxicity 2010, 31:126–133. This NHANES analysis is among the largest to document risk of moderate to severe depression being higher in the highest quartiles of CRP. CrossRef
47.
Frasure-Smith N, Lesperance F, Irwin MR, et al.: The relationships among heart rate variability, inflammatory markers and depression in coronary heart disease patients. Brain Behav Immun 2009, 23:1140–1147.CrossRefPubMed
48.
•• Stewart JC, Rand KL, Muldoon MF, et al.: A prospective evaluation of the directionality of the depression-inflammation relationship. Brain Behav Immun 2009, 23:936–944. This study is one of the few prospective trials, and it was suggestive of depressive symptoms possibly preceding and contributing to inflammatory processes. CrossRefPubMed
49.
• Gimeno D, Kivimaki M, Brunner EJ, et al.: Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study. Psychol Med 2009, 39:413–423. This prospective cohort of over 3000 subjects revealed baseline CRP and IL-6 were predictive of cognitive symptoms of depression. CrossRefPubMed
50.
Weinstein AA, Deuster PA, Francis JL, et al.: Neurohormonal and inflammatory hyper-responsiveness to acute mental stress in depression. Biol Psychol 2010, 84:228–234.CrossRefPubMed
51.
•• Bertoni AG, Burke GL, Owusu JA, et al.: Inflammation and the incidence of type 2 diabetes: the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care 2010, 33:804–810. This recent longitudinal analysis noted the higher CRP, IL-6, and fibrinogen levels predicted incident diabetes in a cohort of over 5000 subjects. CrossRefPubMed
52.
Anagnostis P, Athyros VG, Tziomalos K, et al.: Clinical Review: the pathogenic role of cortisol in the metabolic syndrome: a hypothesis. J Clin Endocrinol Metab 2009, 94:2692–2701.CrossRefPubMed
53.
Valle Gotlieb MG, da Cruz IB, Duarte MM, et al.: Associations among metabolic syndrome, ischemia, inflammatory, oxidatives, and lipids biomarkers. J Clin Endocrinol Metab 2010, 95:586–591.
54.
• Rytter E, Vessby B, Asgard R, et al.: Glycaemic status in relation to oxidative stress and inflammation in well-controlled type 2 diabetes subjects. Br J Nutr 2009, 101:1423–1426. This is one of the few studies to show that glycemic status is associated with oxidative stress even in well-controlled diabetic patients. CrossRefPubMed
55.
Chou HH, Hsu LA, Liu CJ, et al.: Insulin resistance is associated with C-reactive protein independent of abdominal obesity in nondiabetic Taiwanese. Metabolism 2010, 59:824–830.CrossRefPubMed
56.
Pou KM, Massaro JM, Hoffmann U, et al: Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: the Framingham Heart Study. Circulation 2007, 116:1234–1241.CrossRefPubMed
57.
Zeugmann S, Quante A, Heuser I, et al.: Inflammatory biomarkers in 70 depressed inpatients with and without the metabolic syndrome. J Clin Psychiatry 2010, 71:1007–1016.CrossRefPubMed
58.
Swellam M, Sayed Mahmoud AM, Abdel-Fatah AA: Clinical implications of adiponectin and inflammatory biomarkers in type 2 diabetes mellitus. Dis Markers 2009, 27:269–278.PubMed
59.
• Saltevo J, Kautiainen H, Vanhala M: Gender differences in adiponectin and low-grade inflammation among individuals with normal glucose tolerance, prediabetes, and type 2 diabetes. Gend Med 2009, 6:463–470. This large study noted progressively higher hs-CRP and IL-1 receptor antagonist levels from normal glucose tolerant to prediabetes to diabetes with a higher increase in women compared with men. CrossRefPubMed
60.
Bardini G, Dicembrini I, Cresci B, et al.: Inflammation markers and metabolic characteristics of subjects with 1-h plasma glucose levels. Diabetes Care 2010, 33:411–413.CrossRefPubMed
61.
Zhuang XF, Zhao MM, Weng CL, et al.: Adipocytokines: a bridge connecting obesity and insulin resistance. Med Hypotheses 2009, 73:981–985.CrossRefPubMed
62.
Rizvi AA: Cytokine biomarkers, endothelial inflammation, and atherosclerosis in the metabolic syndrome: emerging concepts. Am J Med Sci 2009, 338:310–318.CrossRefPubMed
63.
Misaki Y, Miyauchi R, Mochizuki K, et al.: Plasma interleukin-1 beta concentrations are closely associated with fasting blood glucose levels in healthy and preclinical middle-aged nonoverweight and overweight Japanese men. Metabolism 2010 Feb 18 [Epub ahead of print].
Metadata
Title
Biological Basis of Depression in Adults with Diabetes
Authors
Shivam Champaneri
Gary S. Wand
Saurabh S. Malhotra
Sarah S. Casagrande
Sherita Hill Golden
Publication date
01-12-2010
Publisher
Current Science Inc.
Published in
Current Diabetes Reports / Issue 6/2010
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-010-0148-9

Other articles of this Issue 6/2010

Current Diabetes Reports 6/2010 Go to the issue

ReviewPaper

The Genetics of Insulin Resistance: Where’s Waldo?

ReviewPaper

From Genetic Association to Molecular Mechanism

ReviewPaper

Getting (the Most) Out of the Research Business: Interventions for Youth with T1DM

ReviewPaper

Preventing Poor Psychological and Health Outcomes in Pediatric Type 1 Diabetes

ReviewPaper

Patient Web Portals to Improve Diabetes Outcomes: A Systematic Review

ReviewPaper

The Genetics of Obesity
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits