Latent autoimmune diabetes in adults (LADA) is a progressive form of autoimmune diabetes, characterized with clinical symptoms of both type 1 and 2 diabetes mellitus, and thus it can be considered as type 1.5 diabetes mellitus. The major hallmarks of LADA are the expression of diabetes below 50 years old: body mass index (BMI) <25 kg/m2, acute symptoms, positive family history, and positive personal history of autoimmune disease. To date, the etiology of LADA remains completely unclear and whether its onset is similar to/or different from that in type 1 diabetes needs to be further investigated. Recent researches have indicated that common genetic characteristics of LADA existed in type 1 and type 2 diabetes mellitus.[4,5] In addition, some studies have illuminated that metabolic diseases such as obesity, family history of diabetes, and hypertension are linked to a rising incidence of LADA.[6,7]
Here, we report an emotional exhaustion induced by LADA in a young woman. In general, patients diagnosed with LADA are over 35-year old and often have high body-mass index (BMI, ≥ 25 kg/m2).[3,8] However, this study reports a 27-year old Chinese young woman with a BMI of 17.58 kg/m2 and diagnosed as LADA in connection of emotional exhaustion. In physiology, emotions are a state of feeling that can lead to physical and psychological changes influenced the behavior.
2 Narrative of the episode of care
This study was approved by the Ethics Committee of Guilin Medical University. A 27-year old female accountant diagnosed with LADA in 2012 was used insulin for treatment, accompanied with polydipsia, polyuria, and weight loss (5 kg). Psychiatrists had evaluated the patient's psychopathic condition to exclude mental illness and diabetic family history.
According to the results of a specific validated questionnaire, a figure was made to show the emotional fluctuation, clinical symptom, laboratory indexes, drug treatment, and diet change of the patient during 2009–2016 (Fig. 1). During the observation and follow-up, laboratory tests such as fasting blood glucose (FBG), glutamic acid decarboxylase autoantibodies (GADA), hemoglobin A1c (HbA1c), and urine glucose (UGLU) were determined in 2 different teaching hospitals. The patient's psychological diagnosis about emotional exhaustion was accessed with a subscale of the Maslach Burnout Inventory-General Survey and the subscale consisted 5 items with response options on a 7-point scale from “never” to “always, every day.” The score is from 1 to 6 and emotional exhaustion is considered as ≥3.80. In this study, the score of the young patient is 5.5 in the year 2012 and significantly displayed emotional exhaustion.
Generally, the criterion about the diagnosis of LADA is according to the presence of 4 major circulating islet autoantibodies, GADA, insulinoma-associated antigen-2 (IA-2A), insulin autoantibodies (IAA), and islet cell autoantibodies (ICA), which also exist in classic type 1 diabetes mellitus (T1DM). And GADA is considered to be the most sensitive and specific biomarker of LADA. The positivity of ICA and GADA in 10% to 30% of people with type 2 diabetes reflects the fact that type 1 diabetes in older patients show type 2 diabetes-like phenotype that is known as LADA. The specific identifications of potential diagnosis among T1DM, T2DM, and LADA in this case showed in Table 1.
As shown in Fig. 1, in the year 2009, the FBG was 5.8 mmol/L. Exercise and diet-control were major methods to keep healthy for the patient. A 14-year romantic relationship was ended in 2012, which led to her emotional flooding such as anxiety, irritability, depression, and unhappiness. Then, the physical examination (PE) displayed that the FBG was 14 mmol/L. Furthermore, the level of GADA was 63.83 U/mL and HbA1c was 10.9%, which significantly exceeded normal levels. According to a strongly positive GADA titer, the patient was diagnosed as LADA rather than other disease. Then, the patient, treated with insulin, moved back to her homeland and started a new relationship, which led to a new GADA level of 27.007 IU/mL and the FBG level of 5.46 mmol/L in July 7, 2015.
In this case report, type of intervention were pharmacologic and self-care. Insulin aspart 30 and insulin detemir were used for treatment. Initially, the dosage of insulin detemir was 12U per day (Pd). After pregnancy, the dosage of insulin detemir was changed as 8U Pd and insulin aspart 30 was changed as 3U three times a day (Tid). Especially, running, diet-control, and emotion treatment were combined. The medicine treatment could keep level of glucose stable and running and diet may make emotion recovery.
The clinician assessed the outcomes of PE that the patient with LADA was gradually improved especially based on glutamic acid decarboxylase (GAD) indicator. A 4-year follow-up observation was used to comprehensively evaluate the effect of emotion. The patient's parents and husband supervised the intervention adherence and tolerability. The execution of the patient was assessed according to their feedback. The 4-year duration was associated with insulin treatment, without any adverse effects.
Here, we report a novel LADA case involved emotional exhaustion, with a BMI of 17.58 kg/m2, ending a 14-year romantic relationship. It is interesting to note, however, that an emotional recovery based on a new romantic relationship and a baby leading to the GAD65 and FBG level within normal range.
Modern psychology has revealed that emotions have a significant effect on the onset of disease.[15–17] Any systemic stress, psychological trauma, or emotional conflicts, induces a similar syndrome from most individuals, such as diabetes. Mirsky, who made important contributions for us to understand meaning of stress, suggested that a failure of psychological and physiological adaptation to stress indicated the development of diabetes. Furthermore, experience with stressful events usually produces depression and anxiety, which often co-exist with insufficient sleep and many chronic diseases.[20,21] A highly significant relationship is demonstrated between insufficient sleep and frequent mental distress (FMD), also between FMD and chronic disease.[22,23] In addition, considerable data proposed that chronic mental distress can lead to changes in appetite-regulating hormones and insulin resistance. The former conditions can further develop into chronic metabolic impairments like diabetes. It is worth noting, however, that the research has demonstrated that emotional stresses were majorly related to the occurrence of LADA. Relative mechanisms potentially underlying the influences that we have found are further elucidated subsequently.
Several suggestions of mechanisms may account for this influence. First, the stress alone can evoke the acute phase response (APR),[25,26] which may take the form of the sickness response, and the abduction in the liver of amyloid precursor proteins (APPs) such as C-reactive protein. Cytokines, interleukin-6, are the primary inductors of the APR. To a variable extent, catecholamines and corticosteroids, the main stress inducers, reinforce this induction. Corticoids may directly stimulate the presentation of most APPs. Furthermore, together with cytokines, glucocorticoids induce an enhancement of most APPs. Therefore, chronic stress could elicit chronic APR, which may mediate the metabolism events such as diabetes. Second, the increasing evidence indicated that the stress emerged it functions was via parasympathetic stimulation or by the hypothalamic-pituitary-adrenal axis, which could significantly affect the immune systems of the body.[27,28] A third explanation was that the chronic stressful situations could evoke an increase in the sensitivity of α-adrenergic stimulation which would reduce insulin secretion and disturb glucose metabolism.[29,30] LADA may be considered therefore as a problem of a regulated homeostasis in which the autonomic nervous system and emotional stress interact.
We conducted this case report through personally interview and a continuous 4-year follow-up observation to express adjusting emotion is of crucial significance for the development of disease prevention. However, this study also had some limitations. First, a 2-year window period, due to she left homeland. Second, the patient had taken Chinese medicine to decrease glucose before diagnosing as LADA.
Taken together, we present this case to highlight emotional fluctuations as a psychological factor that might play a significant role in the induction of LADA. Therefore, individuals at risk for LADA are advised to maintain optimism, cheer, and a positive attitude. This suggestion is also significant for clinical practice. Learning to develop strong relationships with significant others can really do wonders for his or her health.
The authors gratefully acknowledge all the participants for their support in this research work. They would like to thank Mr. Rong Li and Mr. Nelson for their English proofing.
. Rodrigues AV, Puri CP, Bhanushali PB, et al. Development of an indirect immunofluorescence based assay for diagnosis of ulcerative colitis in Indian population. Immunol Lett 2016;181:20–5.
. Zouidi F, Bouzid D, Fourati H, et al. CREM variant rs17583959 conferred susceptibility to T1D risk in the Tunisian families. Immunol Lett 2016;181:1–5.
. Mosaad NA, Lotfy HM, Farag YM, et al. Study of serum syndecan-1 levels in a group of Egyptian juvenile systemic lupus erythematosus patients. Immunol Lett 2016;181:16–9.
. D’Auria E, Barberi S, Cerri A, et al. Vitamin D status and body mass index in children with atopic dermatitis: A pilot study in Italian children. Immunol Lett 2016;181:31–5.
. Mormile R. Acute myocardial infarction or stroke in occult colorectal cancer: Epiphenomena of the degree of epigenetic deregulation of SEPT9 gene? Immunol Lett 2017;181:116–7.
. Nagaya T, Kawata K, Kamekura R, et al. Lipid mediators foster the differentiation of T follicular helper cells. Immunol Lett 2016;181:51–7.
. Ribeiro A, Ritter T, Griffin M, et al. Corrigendum to: “Development of a flow cytometry-based potency assay for measuring the in vitro immunomodulatory properties of mesenchymal stromal cells” [J. Immunol. Lett. 177 (2016) 38-46]. Immunol Lett 2016;180:81.
. Yan B, Zhang J, Zhang W, et al. GoTLR7 but not GoTLR21 mediated antiviral immune responses against low pathogenic H9N2 AIV and Newcastle disease virus infection. Immunol Lett 2016;181:6–15.
. Zhang M, Zhou Z, Wang J, et al. ZnT8107-115/HLA-A2 dimers attenuate the severity of diabetes by inducing CD8+ T cell tolerance. Immunol Lett 2016;180:66–72.
. Capittini C, Emmi G, De Amici M, et al. Longitudinal analysis of serum cytokines in a Behcet's patient during 9 months of IVIG infusions: how does CXCL8 bridge the immune and neuroendocrine systems? Immunol Lett 2016;180:79–80.
. Cifaldi L, Pinto RM, Rana I, et al. NK cell effector functions in a Chediak–Higashi patient undergoing cord blood transplantation: Effects of in vitro treatment with IL-2. Immunol Lett 2016;180:46–53.
. Guo T, Zhao L, Zhang Y, et al. A monoclonal antibody targeting the dimer interface of epidermal growth factor receptor (EGFR). Immunol Lett 2016;180:39–45.
. Liebl A. Management of postprandial glucose: Recommended targets and treatment with biphasic insulin. Prim Care Diabetes 2016;10:391–7.
. Giles GE, Eddy MD, Brunye TT, et al. Running augments felt positive emotion and dampens prefrontal cortical responses to negative emotions: 1531 Board #184 June 2,9: 00 AM–10: 30 AM. Med Sci Sports Exerc 2016;48(5 suppl 1):417–8.
. Rigante D, Manna R. A position for tumor necrosis factor inhibitors in the management of colchicine-resistant familial Mediterranean fever? Immunol Lett 2016;180:77–8.
. Rahbarnia L, Farajnia S, Babaei H, et al. Isolation and characterization of a novel human scFv inhibiting EGFR vIII expressing cancers. Immunol Lett 2016;180:31–8.
. Gholijani N, Ataollahi MR, Samiei A, et al. An elevated pro-inflammatory cytokines profile in Behcet's disease: A multiplex analysis. Immunol Lett 2016;186:46–51.
. Fan H, Zhao G, Ren D, et al. Gender differences of B cell signature related to estrogen-induced IFI44L/BAFF in systemic lupus erythematosus. Immunol Lett 2016;181:71–8.
. Mirsky IA. The biology of metabolic disease in man. Can Med Assoc J 1948;59:257–65.
. Levenhagen MA, Conte H, Costa-Cruz JM. Current progress toward vaccine and passive immunization approaches for Strongyloides spp. Immunol Lett 2016;180:17–23.
. Zhang M, Zhou Z, Wang J, et al. MiR-130b promotes obesity associated adipose tissue inflammation and insulin resistance in diabetes mice through alleviating M2 macrophage polarization via repression of PPAR-gamma. Immunol Lett 2016;180:1–8.
. Kresinsky A, Schneble N, Schmidt C, et al. Phagocytosis of bone marrow derived macrophages is controlled by phosphoinositide 3-kinase gamma. Immunol Lett 2016;180:9–16.
. Ysmail-Dahlouk L, Nouari W, Aribi M. 1,25-dihydroxyvitamin D3 down-modulates the production of proinflammatory cytokines and nitric oxide and enhances the phosphorylation of monocyte-expressed STAT6 at the recent-onset type 1 diabetes. Immunol Lett 2016;179:122–30.
. Yuan B, Huang S, Gong S, et al. Programmed death (PD)-1 attenuates macrophage activation and brain inflammation via regulation of fibrinogen-like protein 2 (Fgl-2) after intracerebral hemorrhage in mice. Immunol Lett 2016;179:114–21.
. Black PH, Garbutt LD. Stress, inflammation and cardiovascular disease. J Psychosom Res 2002;52:1–23.
. Black PH. The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. Brain Behav Immun 2003;17:350–64.
. Bateman A, Singh A, Kral T, et al. The immune-hypothalamic-pituitary-adrenal axis. Endocr Rev 1989;10:92–112.
. Wales JK. Does psychological stress cause diabetes? Diabet Med 1995;12:109–12.
. Surwit RS, Feinglos MN. Stress and autonomic nervous system in type II diabetes. A hypothesis. Diabetes Care 1988;11:83–5.
. Robertson RP, Halter JB, Porte D Jr. A role for alpha-adrenergic receptors in abnormal insulin secretion in diabetes mellitus. J Clin Invest 1976;57:791–5.
. Canivell S, Gomis R. Diagnosis and classification of autoimmune diabetes mellitus. Autoimmun Rev 2014;13:403–7.