Psychological stress mobilizes biological responses implicated in type 2 diabetes mellitus (T2DM), including the release of glucose and lipids into the circulation, inflammatory cytokine expression and increased blood pressure
Repeated or sustained stress exposure leads to chronic allostatic load, with dysregulation of glucose metabolism and neuroendocrine function and chronic low grade inflammation. Dysregulation of the diurnal profile of cortisol release predicts incident T2DM in population studies
Epidemiological studies implicate depression, chronic work stress and early life adversity as risk factors for T2DM
The adverse effect of psychological stress on health behaviours such as food choice, physical activity and adherence to medication also contributes to T2DM risk
Among individuals with established diabetes mellitus, depression and diabetes mellitus-related distress are associated with poor glycaemic control and cardiovascular complications
Stress management interventions seem to alleviate stress symptoms in T2DM, but effects on disease progression have not been established
Psychological stress is common in many physical illnesses and is increasingly recognized as a risk factor for disease onset and progression. An emerging body of literature suggests that stress has a role in the aetiology of type 2 diabetes mellitus (T2DM) both as a predictor of new onset T2DM and as a prognostic factor in people with existing T2DM. Here, we review the evidence linking T2DM and psychological stress. We highlight the physiological responses to stress that are probably related to T2DM, drawing on evidence from animal work, large epidemiological studies and human laboratory trials. We discuss population and clinical studies linking psychological and social stress factors with T2DM, and give an overview of intervention studies that have attempted to modify psychological or social factors to improve outcomes in people with T2DM.
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Brotman, D. J., Golden, S. H. & Wittstein, I. S. The cardiovascular toll of stress. Lancet 370, 1089–1100 (2007).
Ulrich-Lai, Y. M. & Herman, J. P. Neural regulation of endocrine and autonomic stress responses. Nat. Rev. Neurosci. 10, 397–409 (2009).
Dallman, M. F. et al. Feast and famine: critical role of glucocorticoids with insulin in daily energy flow. Front. Neuroendocrinol. 14, 303–347 (1993).
Kahn, S. E. et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 42, 1663–1672 (1993).
Picard, M., Juster, R.-P. & McEwen, B. S. Mitochondrial allostatic load puts the 'gluc' back in glucocorticoids. Nat. Rev. Endocrinol. 10, 303–310 (2014).
Picard, M. & Turnbull, D. M. Linking the metabolic state and mitochondrial dna in chronic disease, health, and aging. Diabetes 62, 672–678 (2013).
McEwen, B. S. & Wingfield, J. C. The concept of allostasis in biology and biomedicine. Horm. Behav. 43, 2–15 (2003).
Korczak, D. J., Pereira, S., Koulajian, K., Matejcek, A. & Giacca, A. Type 1 diabetes mellitus and major depressive disorder: evidence for a biological link. Diabetologia 54, 2483–2493 (2011).
Gong, S. et al. Dynamics and correlation of serum cortisol and corticosterone under different physiological or stressful conditions in mice. PLoS ONE 10, e0117503 (2015).
Karatsoreos, I. N. et al. Endocrine and physiological changes in response to chronic corticosterone: a potential model of the metabolic syndrome in mouse. Endocrinology 151, 2117–2127 (2010).
Fransson, L. et al. β-Cell adaptation in a mouse model of glucocorticoid-induced metabolic syndrome. J. Endocrinol. 219, 231–241 (2013).
Shpilberg, Y. et al. A rodent model of rapid-onset diabetes induced by glucocorticoids and high-fat feeding. Dis. Model. Mech. 5, 671–680 (2012).
McEwen, B. S. & Stellar, E. Stress and the individual. Mechanisms leading to disease. Arch. Intern. Med. 153, 2093–2101 (1993).
Chavez, M. et al. Adrenalectomy increases sensitivity to central insulin. Physiol. Behav. 62, 631–634 (1997).
Loizzo, S. et al. Post-natal stress-induced endocrine and metabolic alterations in mice at adulthood involve different pro-opiomelanocortin-derived peptides. Peptides 31, 2123–2129 (2010).
Loizzo, A. et al. Overweight and metabolic and hormonal parameter disruption are induced in adult male mice by manipulations during lactation period. Pediatr. Res. 59, 111–115 (2006).
Maniam, J., Antoniadis, C. P. & Morris, M. J. The effect of early-life stress and chronic high-sucrose diet on metabolic outcomes in female rats. Stress 18, 524–537 (2015).
Paternain, L. et al. Postnatal maternal separation modifies the response to an obesogenic diet in adulthood in rats. Dis. Model. Mech. 5, 691–697 (2012).
Sadeghimahalli, F., Karbaschi, R., Zardooz, H., Khodagholi, F. & Rostamkhani, F. Effect of early life stress on pancreatic isolated islets' insulin secretion in young adult male rats subjected to chronic stress. Endocrine 48, 493–503 (2015).
Rosenblum, L. A. & Smiley, J. Therapeutic effects of an imposed foraging task in disturbed monkeys. J. Child Psychol. Psychiatry 25, 485–497 (1984).
Kaufman, D. et al. Early-life stress and the development of obesity and insulin resistance in juvenile bonnet macaques. Diabetes 56, 1382–1386 (2007).
McEwen, B. S. Protective and damaging effects of stress mediators: central role of the brain. Dialogues Clin. Neurosci. 8, 367–381 (2006).
Di Dalmazi, G., Pagotto, U., Pasquali, R. & Vicennati, V. Glucocorticoids and type 2 diabetes: from physiology to pathology. J. Nutr. Metab. 2012, 1–9 (2012).
Lacroix, A., Feelders, R. A., Stratakis, C. A. & Nieman, L. K. Cushing's syndrome. Lancet 386, 913–927 (2015).
Clore, J. & Thurby-Hay, L. Glucocorticoid-induced hyperglycemia. Endocr. Pract. 15, 469–474 (2009).
Asfeldt, V. H. Hypophyseo-adrenocortical function in diabetes mellitus. Acta Med. Scand. 191, 349–354 (1972).
Chiodini, I. et al. Association of subclinical hypercortisolism with type 2 diabetes mellitus: a case-control study in hospitalized patients. Eur. J. Endocrinol. 153, 837–844 (2005).
Adam, E. K. & Kumari, M. Assessing salivary cortisol in large-scale, epidemiological research. Psychoneuroendocrinology 34, 1423–1436 (2009).
Fries, E., Dettenborn, L. & Kirschbaum, C. The cortisol awakening response (CAR): facts and future directions. Int. J. Psychophysiol. 72, 67–73 (2009).
Hackett, R. A., Steptoe, A. & Kumari, M. Association of diurnal patterns in salivary cortisol with type 2 diabetes in the Whitehall II study. J. Clin. Endocrinol. Metab. 99, 4625–4631 (2014).
Lederbogen, F. et al. Flattened circadian cortisol rhythm in type 2 diabetes. Exp. Clin. Endocrinol. Diabetes 119, 573–575 (2011).
Kumari, M., Shipley, M., Stafford, M. & Kivimaki, M. Association of diurnal patterns in salivary cortisol with all-cause and cardiovascular mortality: findings from the Whitehall II study. J. Clin. Endocrinol. Metab. 96, 1478–1485 (2011).
Bruehl, H., Wolf, O. T. & Convit, A. A blunted cortisol awakening response and hippocampal atrophy in type 2 diabetes mellitus. Psychoneuroendocrinology 34, 815–821 (2009).
Champaneri, S. et al. Diurnal salivary cortisol and urinary catecholamines are associated with diabetes mellitus: the Multi-Ethnic Study of Atherosclerosis. Metabolism 61, 986–995 (2012).
Vreeburg, S. A. et al. Associations between sociodemographic, sampling and health factors and various salivary cortisol indicators in a large sample without psychopathology. Psychoneuroendocrinology 34, 1109–1120 (2009).
Hackett, R. A., Kivimäki, M., Kumari, M. & Steptoe, A. Diurnal cortisol patterns, future diabetes, and impaired glucose metabolism in the Whitehall II cohort study. J. Clin. Endocrinol. Metab. 101, 619–625 (2016).
Donath, M. Y. & Shoelson, S. E. Type 2 diabetes as an inflammatory disease. Nat. Rev. Immunol. 11, 98–107 (2011).
Galic, S., Oakhill, J. S. & Steinberg, G. R. Molecular and cellular endocrinology: adipose tissue as an endocrine organ. Mol. Cell. Endocrinol. 316, 129–139 (2010).
Ehses, J. A., Ellingsgaard, H., Böni-Schnetzler, M. & Donath, M. Y. Pancreatic islet inflammation in type 2 diabetes: from α and ß cell compensation to dysfunction. Arch. Physiol. Biochem. 115, 240–247 (2009).
Tilg, H. & Moschen, A. Inflammatory mechanisms in the regulation of insulin resistance. Mol. Med. 14, 222–231 (2008).
Grossmann, V. et al. Profile of the immune and inflammatory response in individuals with prediabetes and type 2 diabetes. Diabetes Care 38, 1356–1364 (2015).
Wang, X. et al. Inflammatory markers and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care 36, 166–175 (2012).
Davey Smith, G. & Hemani, G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum. Mol. Genet. 23, R89–R98 (2014).
Swerdlow, D. I. et al. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet 379, 1214–1224 (2012).
Swerdlow, D. I. Mendelian randomization and type 2 diabetes. Cardiovasc. Drugs Ther. 30, 51–57 (2016).
International Diabetes Federation. IDF Diabetes Atlas 7th edn. (International Diabetes Federation, 2015).
Emdin, C. A., Anderson, S. G., Woodward, M. & Rahimi, K. Usual blood pressure and risk of new-onset diabetes. J. Am. Coll. Cardiol. 66, 1552–1562 (2015).
Knowles, J. W. & Reaven, G. Usual blood pressure and new-onset diabetes risk evidence from 4.1 million adults and a meta-analysis. J. Am. Coll. Cardiol. 67, 1656–1657 (2016).
Aune, D., ó Hartaigh, B. & Vatten, L. J. Resting heart rate and the risk of type 2 diabetes: a systematic review and dose–response meta-analysis of cohort studies. Nutr. Metab. Cardiovasc. Dis. 25, 526–534 (2015).
Licht, C. M. M. et al. Increased sympathetic and decreased parasympathetic activity rather than changes in hypothalamic–pituitary–adrenal axis activity is associated with metabolic abnormalities. J. Clin. Endocrinol. Metab. 95, 2458–2466 (2010).
Mancia, G. et al. The sympathetic nervous system and the metabolic syndrome. J. Hypertens. 25, 909–920 (2007).
Thayer, J. F. & Sternberg, E. Beyond heart rate variability: vagal regulation of allostatic systems. Ann. NY Acad. Sci. 1088, 361–372 (2006).
Marvar, P. J. et al. T lymphocytes and vascular inflammation contribute to stress-dependent hypertension. Biol. Psychiatry 71, 774–782 (2012).
Sattar, N. et al. Serial metabolic measurements and conversion to type 2 diabetes in the West of Scotland Coronary Prevention Study: specific elevations in alanine aminotransferase and triglycerides suggest hepatic fat accumulation as a potential contributing factor. Diabetes 56, 984–991 (2007).
Tabák, A. G. et al. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 373, 2215–2221 (2009).
Nowotny, B. et al. Effects of acute psychological stress on glucose metabolism and subclinical inflammation in patients with post-traumatic stress disorder. Horm. Metab. Res. 42, 746–753 (2010).
Mattei, J., Demissie, S., Falcon, L. M., Ordovas, J. M. & Tucker, K. Allostatic load is associated with chronic conditions in the Boston Puerto Rican Health Study. Soc. Sci. Med. 70, 1988–1996 (2010).
Carlsson, A. C., Nixon Andreasson, A. & Wandell, P. E. Poor self-rated health is not associated with a high total allostatic load in type 2 diabetic patients — but high blood pressure is. Diabetes Metab. 37, 446–451 (2011).
Steptoe, A. et al. Disruption of multisystem responses to stress in type 2 diabetes: investigating the dynamics of allostatic load. Proc. Natl Acad. Sci. USA 111, 15693–15698 (2014).
Steptoe, A. in Handbook of Psychophysiology (eds Cacioppo, J. T., Tassinary, L. G. & Berntson, G. G.) 526–547 (Cambridge Univ. Press, 2016).
Rod, N. H., Grønbæk, M., Schnohr, P., Prescott, E. & Kristensen, T. S. Perceived stress as a risk factor for changes in health behaviour and cardiac risk profile: a longitudinal study. Clin. Pharmacol. Ther. 92, 1–2 (2012).
Gonzalez, J. S. et al. Depression and diabetes treatment nonadherence: a meta-analysis. Diabetes Care 31, 2398–2403 (2008).
Sinha, R. & Jastreboff, A. M. Stress as a common risk factor for obesity and addiction. Biol. Psychiatry 73, 827–835 (2013).
Hamer, M. et al. Objectively assessed physical activity, adiposity, and inflammatory markers in people with type 2 diabetes. BMJ Open Diabetes Res. Care 2, e000030 (2014).
Knol, M. J. et al. Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis. Diabetologia 49, 837–845 (2006).
Mezuk, B., Eaton, W. W., Albrecht, S. & Golden, S. H. Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care 31, 2383–2390 (2008).
Demakakos, P., Zaninotto, P. & Nouwen, A. Is the association between depressive symptoms and glucose metabolism bidirectional? Evidence From English Longitudinal Study of Ageing. Psychosom. Med. 76, 555–561 (2014).
Rotella, F. & Mannucci, E. Depression as a risk factor for diabetes: a meta-analysis of longitudinal studies. J. Clin. Psychiatry 74, 31–37 (2013).
Engum, A. The role of depression and anxiety in onset of diabetes in a large population-based study. J. Psychosom. Res. 62, 31–38 (2007).
Abraham, S. et al. Trait anger but not anxiety predicts incident type 2 diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA). Psychoneuroendocrinology 60, 105–113 (2015).
Farvid, M. S. et al. Phobic anxiety symptom scores and incidence of type 2 diabetes in US men and women. Brain. Behav. Immun. 36, 176–182 (2014).
Atlantis, E., Vogelzangs, N., Cashman, K. & Penninx, B. J. W. H. Common mental disorders associated with 2-year diabetes incidence: the Netherlands Study of Depression and Anxiety (NESDA). J. Affect. Disord. 142, S30–35 (2012).
Demmer, R. T. et al. Sex differences in the association between depression, anxiety, and type 2 diabetes mellitus. Psychosom. Med. 77, 467–477 (2015).
Vancampfort, D. et al. Type 2 diabetes among people with posttraumatic stress disorder: systematic review and meta-analysis. Psychosom. Med. 78, 465–473 (2016).
Mommersteeg, P. M. C., Herr, R., Zijlstra, W. P., Schneider, S. & Pouwer, F. Higher levels of psychological distress are associated with a higher risk of incident diabetes during 18 year follow-up: results from the British household panel survey. BMC Public Health 12, 1109 (2012).
Virtanen, M. et al. Psychological distress and incidence of type 2 diabetes in high-risk and low-risk populations: the Whitehall II cohort study. Diabetes Care 37, 2091–2097 (2014).
Eriksson, A. K. et al. Psychological distress and risk of pre-diabetes and type 2 diabetes in a prospective study of Swedish middle-aged men and women. Diabet. Med. 25, 834–842 (2008).
Nyberg, S. T. et al. Job strain as a risk factor for type 2 diabetes: a pooled analysis of 124,808 men and women. Diabetes Care 37, 2268–2275 (2014).
Kivimäki, M. et al. Long working hours, socioeconomic status, and the risk of incident type 2 diabetes: a meta-analysis of published and unpublished data from 222 120 individuals. Lancet Diabetes Endocrinol. 3, 27–34 (2014).
Twig, G. et al. Self-perceived emotional distress and diabetes risk among young men. Am. J. Prev. Med. 50, 737–745 (2016).
Novak, M. et al. Perceived stress and incidence of type 2 diabetes: a 35-year follow-up study of middle-aged Swedish men. Diabet. Med. 30, e8–e16 (2013).
Toshihiro, M. et al. Psychosocial factors are independent risk factors for the development of type 2 diabetes in Japanese workers with impaired fasting glucose and/or impaired glucose tolerance. Diabet. Med. 25, 1211–1217 (2008).
Williams, E. D., Magliano, D. J., Tapp, R. J., Oldenburg, B. F. & Shaw, J. E. Psychosocial stress predicts abnormal glucose metabolism: the Australian diabetes, obesity and lifestyle (AusDiab) study. Ann. Behav. Med. 46, 62–72 (2013).
Kato, M., Noda, M., Inoue, M., Kadowaki, T. & Tsugane, S. Psychological factors, coffee and risk of diabetes mellitus among middle-aged Japanese: a population-based prospective study in the JPHC study cohort. Endocr. J. 56, 459–468 (2009).
Wiernik, E. et al. Association between current perceived stress and incident diabetes is dependent on occupational status: evidence from the IPC cohort study. Diabetes Metab. 42, 328–335 (2016).
Golden, S. H. et al. Anger temperament is modestly associated with the risk of type 2 diabetes mellitus: the Atheroslcerosis Risk in Communities Study. Psychoneuroendocrinology 31, 325–332 (2006).
Huang, H. et al. Adverse childhood experiences and risk of type 2 diabetes: a systematic review and meta-analysis. Metabolism 64, 1408–1418 (2015).
Crump, C., Sundquist, J., Winkleby, M. A. & Sundquist, K. Stress resilience and subsequent risk of type 2 diabetes in 1.5 million young men. Diabetologia 59, 728–733 (2016).
Okely, J. A. & Gale, C. R. Well-being and chronic disease incidence: the English Longitudinal Study of Ageing. Psychosom. Med. 78, 335 (2016).
Feller, S., Teucher, B., Kaaks, R., Boeing, H. & Vigl, M. Life satisfaction and risk of chronic diseases in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany Study. PLoS ONE 8, e73462 (2013).
Boehm, J. K., Trudel-Fitzgerald, C., Kivimaki, M. & Kubzansky, L. D. The prospective association between positive psychological well-being and diabetes. Health Psychol. 34, 1013–1021 (2015).
Barnard, K. D., Peyrot, M. & Holt, R. I. G. Psychosocial support for people with diabetes: past, present and future. Diabet. Med. 29, 1358–1360 (2012).
Ali, S., Stone, M. A., Peters, J. L., Davies, M. J. & Khunti, K. The prevalence of co-morbid depression in adults with type 2 diabetes: a systematic review and meta-analysis. Diabet. Med. 23, 1165–1173 (2006).
Anderson, R. J., Freedland, K. E., Clouse, R. E. & Lustman, P. J. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 24, 1069–1078 (2001).
Roy, T. & Lloyd, C. E. Epidemiology of depression and diabetes: a systematic review. J. Affect. Disord. 142, S8–21 (2012).
Vancampfort, D. et al. Type 2 diabetes in patients with major depressive disorder: a meta-analysis of prevalence estimates and predictors. Depress. Anxiety 32, 763–773 (2015).
Grigsby, A. B., Anderson, R. J., Freedland, K. E., Clouse, R. E. & Lustman, P. J. Prevalence of anxiety in adults with diabetes a systematic review. J. Psychosom. Res. 53, 1053–1060 (2002).
Smith, K. J. et al. Association of diabetes with anxiety: a systematic review and meta-analysis. J. Psychosom. Res. 74, 89–99 (2013).
Fisher, L. et al. Diabetes distress but not clinical depression or depressive symptoms is associated with glycemic control in both cross-sectional and longitudinal analyses. Diabetes Care 33, 23–28 (2010).
Fisher, L., Hessler, D. M., Polonsky, W. H. & Mullan, J. When is diabetes distress clinically meaningful? Establishing cut points for the diabetes distress scale. Diabetes Care 35, 259–264 (2012).
Nicolucci, A. et al. Diabetes Attitudes, Wishes and Needs second study (DAWN2TM): Cross-national benchmarking of diabetes-related psychosocial outcomes for people with diabetes. Diabet. Med. 30, 767–777 (2013).
Rotella, F. & Mannucci, E. Diabetes mellitus as a risk factor for depression. A meta-analysis of longitudinal studies. Diabetes Res. Clin. Pract. 99, 98–104 (2013).
Nouwen, A. et al. Type 2 diabetes mellitus as a risk factor for the onset of depression: a systematic review and meta-analysis. Diabetologia 53, 2480–2486 (2010).
Moussavi, S. et al. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet 370, 851–858 (2007).
Ali, S. et al. The association between depression and health-related quality of life in people with type 2 diabetes: a systematic literature review. Diabetes. Metab. Res. Rev. 26, 75–89 (2010).
Schram, M. T., Baan, C. A. & Pouwer, F. Depression and quality of life in patients with diabetes: a systematic review from the European depression in diabetes (EDID) research consortium. Curr. Diabetes Rev. 5, 112–119 (2009).
Lustman, P. J. et al. Depression and poor glycemic control: a meta-analytic review of the literature. Diabetes Care 23, 934–942 (2000).
Katon, W. J. et al. The relationship between changes in depression symptoms and changes in health risk behaviors in patients with diabetes. Int. J. Geriatr. Psychiatry 25, 466–475 (2010).
Aikens, J. E. Prospective associations between emotional distress and poor outcomes in type 2 diabetes. Diabetes Care 35, 2472–2478 (2012).
Hajós, T. R. S., Polonsky, W. H., Pouwer, F., Gonder-Frederick, L. & Snoek, F. J. Toward defining a cutoff score for elevated fear of hypoglycemia on the hypoglycemia fear survey worry subscale in patients with type 2 diabetes. Diabetes Care 37, 102–108 (2014).
Anderson, R. J. et al. Anxiety and poor glycemic control: a meta-analytic review of the literature. Int. J. Psychiatry Med. 32, 235–247 (2002).
Miller, S. A. et al. Associations between posttraumatic stress disorder and hemoglobin A1C in low-income minority patients with diabetes. Gen. Hosp. Psychiatry 33, 116–122 (2011).
Collins, M. M., Corcoran, P. & Perry, I. J. Anxiety and depression symptoms in patients with diabetes. Diabet. Med. 26, 153–161 (2009).
Kendzor, D. E. et al. The association of depression and anxiety with glycemic control among Mexican Americans with diabetes living near the U.S.–Mexico border. BMC Public Health 14, 176 (2014).
Deschênes, S. S., Burns, R. J. & Schmitz, N. Anxiety symptoms and functioning in a community sample of individuals with type 2 diabetes: a longitudinal study. J. Diabetes 8, 854–862 (2015).
Tsenkova, V. K., Love, G. D., Singer, B. H. & Ryff, C. D. Socioeconomic status and psychological well-being predict cross-time change in glycosylated hemoglobin in older women without diabetes. Psychosom. Med. 69, 777–784 (2007).
Yi, J. P., Vitaliano, P. P., Smith, R. E., Yi, J. C. & Weinger, K. The role of resilience on psychological adjustment and physical health in patients with diabetes. Br. J. Health Psychol. 13, 311–325 (2008).
Fowler, M. J. Microvascular and macrovascular complications of diabetes. Clin. Diabetes 26, 77–82 (2008).
Williams, L. H. et al. Depression and incident diabetic foot ulcers: a prospective cohort study. Am. J. Med. 123, 748–754 (2010).
Sieu, N. et al. Depression and incident diabetic retinopathy: a prospective cohort study. Gen. Hosp. Psychiatry 33, 429–435 (2011).
Novak, M. et al. Increased risk of incident chronic kidney disease, cardiovascular disease, and mortality in patients with diabetes with comorbid depression. Diabetes Care 39, 1940–1947 (2016).
Gonzalez, J. S. et al. Depression predicts first but not recurrent diabetic foot ulcers. Diabetologia 53, 2241–2248 (2010).
Iversen, M. M. et al. Is depression a risk factor for diabetic foot ulcers? 11-years follow-up of the Nord-Trøndelag Health Study (HUNT). J. Diabetes Compl. 29, 20–25 (2015).
Ting, R. Z. W. et al. High risk for cardiovascular disease in Chinese type 2 diabetic patients with major depression — a 7-year prospective analysis of the Hong Kong Diabetes Registry. J. Affect. Disord. 149, 129–135 (2013).
Scherrer, J. F. et al. Increased risk of myocardial infarction in depressed patients with type 2 diabetes. Diabetes Care 34, 1729–1734 (2011).
Lin, E. H. B. et al. Depression and advanced complications of diabetes: a prospective cohort study. Diabetes Care 33, 264–269 (2010).
Radholm, K., Wirehn, A.-B., Chalmers, J. & Ostgren, C. J. Use of antidiabetic and antidepressant drugs is associated with increased risk of myocardial infarction: a nationwide register study. Diabet. Med. 33, 218–223 (2015).
Park, M., Katon, W. J. & Wolf, F. M. Depression and risk of mortality in individuals with diabetes: a meta-analysis and systematic review. Gen. Hosp. Psychiatry 35, 217–225 (2013).
van Dooren, F. E. P. et al. Depression and risk of mortality in people with diabetes mellitus: a systematic review and meta-analysis. PLoS ONE 8, e57058 (2013).
Hofmann, M., Köhler, B., Leichsenring, F. & Kruse, J. Depression as a risk factor for mortality in individuals with diabetes: a meta-analysis of prospective studies. PLoS ONE 8, e79809 (2013).
Iversen, M. M. et al. Anxiety and depressive symptoms as predictors of all-cause mortality among people with insulin-naïve type 2 diabetes: 17-year follow-up of the second Nord-Trøndelag health survey (HUNT2), Norway. PLoS ONE 11, e0160861 (2016).
Edwards, L. E. & Mezuk, B. Anxiety and risk of type 2 diabetes: evidence from the Baltimore Epidemiologic Catchment Area Study. J. Psychosom. Res. 73, 418–423 (2012).
Dalsgaard, E. M. et al. Psychological distress, cardiovascular complications and mortality among people with screen-detected type 2 diabetes: follow-up of the ADDITION-Denmark trial. Diabetologia 57, 710–717 (2014).
Moskowitz, J. T., Epel, E. S. & Acree, M. Positive affect uniquely predicts lower risk of mortality in people with diabetes. Health Psychol. 27, S73–S82 (2008).
Surwit, R. S. et al. Stress management improves long-term glycemic control in type 2 diabetes. Diabetes Care 25, 30–34 (2002).
Wagner, J. A. et al. A randomized, controlled trial of a stress management intervention for Latinos with type 2 diabetes delivered by community health workers: outcomes for psychological wellbeing, glycemic control, and cortisol. Diabetes Res. Clin. Pract. 120, 162–170 (2016).
Fisher, L. et al. REDEEM: a pragmatic trial to reduce diabetes distress. Diabetes Care 36, 2551–2558 (2013).
Hermanns, N. et al. The effect of a diabetes-specific cognitive behavioral treatment program (diamos) for patients with diabetes and subclinical depression: results of a randomized controlled trial. Diabetes Care 38, 551–560 (2015).
Noordali, F., Cumming, J. & Thompson, J. L. Effectiveness of mindfulness-based interventions on physiological and psychological complications in adults with diabetes: a systematic review. J. Health Psychol. http://dx.doi.org/10.1177/1359105315620293 (2015).
Baumeister, H., Hutter, N. & Bengel, J. Psychological and pharmacological interventions for depression in patients with diabetes mellitus and depression. Cochrane Database Syst. Rev. 12, CD008381 (2012).
National Institute for Health and Care Excellence. Depression in Adults with a Chronic Physical Health Problem: recognition and management (National Institute for Health and Care Excellence, 2009).
Atlantis, E., Fahey, P. & Foster, J. Collaborative care for comorbid depression and diabetes: a systematic review and meta-analysis. BMJ Open 4, e004706 (2014).
The Emerging Risk Factors Collaboration. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375, 2215–2222 (2010).
Goff, D. C. et al. Prevention of cardiovascular disease in persons with type 2 diabetes mellitus: current knowledge and rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J. Cardiol. 99, 4i–20i (2007).
Virk, J. et al. Prenatal exposure to bereavement and type-2 diabetes: a Danish longitudinal population based study. PLoS ONE 7, e43508 (2012).
de Groot, M., Anderson, R., Freedland, K., Clouse, R. & Lustman, P. Association of depression and diabetes complications: a meta-analysis. Psychosom. Med. 63, 619–630 (2001).
Bartoli, F. et al. Association between depression and neuropathy in people with type 2 diabetes: a meta-analysis. Int. J. Geriatr. Psychiatry 31, 829–836 (2016).
Black, S. A., Markides, K. S. & Ray, L. A. Depression predicts increased incidence of adverse health outcomes in older Mexican Americans with type 2 diabetes. Diabetes Care 26, 2822–2828 (2003).
Cummings, D. M. et al. Consequences of comorbidity of elevated stress and/or depressive symptoms and incident cardiovascular outcomes in diabetes: results from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Diabetes Care 39, 101–109 (2016).
Bruce, D. G., Davis, W. A., Dragovic, M., Davis, T. M. E. & Starkstein, S. E. Comorbid anxiety and depression and their impact on cardiovascular disease in type 2 diabetes: the Fremantle Diabetes Study phase II. Depress. Anxiety 33, 960–966 (2016).
The authors' work was supported by the British Heart Foundation (grant RG/10/005/28296).
The authors declare no competing financial interests.
- Psychological stress
A broad term referring to a range of psychological phenomena including exposure to external challenges (stress conditions in adult or earlier life), psychological distress (including depression and anxiety) and personal traits, such as anger or hostility.
- Psychological distress
A measure that encompasses depressive symptoms, anxiety, general stress and sleep disturbance.
- Diurnal cortisol pattern
The distinct pattern of daily cortisol output in humans.
An umbrella term for inflammatory factors expressed in adipose tissue.
- The metabolic syndrome
A combination of factors (including central obesity, raised blood pressure and raised levels of cholesterol) that increases the risk of type 2 diabetes mellitus.
- Self-care behaviours
In type 2 diabetes mellitus, these include behaviours such as glucose monitoring, managing complications and adhering to medication and lifestyle recommendations.
- Collaborative care
A multidisciplinary form of management that can include a combination of lifestyle, pharmacological and psychological therapies, as well as patient education and regular practitioner monitoring.
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Hackett, R., Steptoe, A. Type 2 diabetes mellitus and psychological stress — a modifiable risk factor. Nat Rev Endocrinol 13, 547–560 (2017). https://doi.org/10.1038/nrendo.2017.64
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