Intro The burden involved with chronic medical illness constitutes a significant lifetime risk factor for psychiatric

illness. Diabetes is one of the most psychologically and behaviourally demanding chronic illness; on one hand removing a patients sense of God-given autonomy and control over their daily lives and lifestyle choices, and on the other, demands a high level of vigilance in that an estimated 95% of diabetes management is carried out by the patient. Therefore, the perception of subjective burden of living with the condition is particularly relevant when considering the relationship between mental health and diabetes. By far, the most common psychiatric diagnosis in patients with diabetes is depression. Several studies have reported a significant 27.3% lifetime prevalence of comorbid Depression in diabetic patients in contrast to 59% for women and 2-3% for men in the general population, with an estimated 33% of diabetics experiencing depressive symptoms of sufficient severity to warrant psychiatric treatment during the course of their disease (http://www.tbmseminars.com/pdf/Riley%20%20Depression%20as%20a%20Comorbidity%20to%20Diabetes.pdf)

Comorbidity between diabetes and anxiety or specifically, Generalised Anxiety Disorder has also been demonstrated in that 1 in 7 people with DMII experience GAD during the course of their illness. Elevated symptoms of GAD are present in 40% of individuals with diabetes (Grigsby et al., 2002).(Beyond blue) Alternatively, according to a large cohort study by E.Atlantis et al, patients with diagnosis of Major Depressive Disorder or GAD have a 10fold risk of developing DMII compared to patients who are psychologically well. Patients with negative cognitions and low expressed emotion tend to internalise their difficulties and have a harder time adjusting to their diagnosis. Alternatively, diabetes with its stressors and comorbidities may incite and reinforce psychological and physiological complications in patients with previously intact mental states. This complex relationship between mood states and diabetic control leads to the consideration of a bidirectional model of negative feedback between diabetes and mental illness. Bidirectional relationship Diabetes causes mental issues Studies have proposed that depression and other psychopathologies may stem from the psychosocial burden and physiological changes related to diabetes and its treatment (refer to diagram which high lights the relationship between emotional distress and perceived threat of illness, self esteem, and autonomy). Additionally, diabetes is unique from other chronic illnesses in that despite its myriad of severe medical complications, the patient with DM is encouraged to

lead a normal life without many of the concessions usually made to a person with chronic illness. (http://alert.psychiatricnews.org/2012/05/diabetes-depression-combo-raisesrisk.html)

Other theories include biochemical disturbances induced by diabetic complications such as neuronal and structural damage secondary to hypoglycaemia, or as a result of classic conditioning through the pairing of symptoms of hypoglycaemia with environmental cues and feelings of anxiety, fear and helplessness (PSYCHIATRIC MORBIDITY IN ENDOCRINE DISORDERS Gary R.
Geffken, PhD, Herbert E. Ward, MD, Jeffrey P. Staab, MD, MS, Stacy L. K. Carmichael, BS, and Dwight L. Evans, MD)

The diagnosis of Diabetes often happens in the context of sudden onset diabetic ketoacidosis and hospital admission. Psychological upheaval and abrupt shifts in the patients esteem and identity take place as they are forced to quickly adjust to their illness and its accompanying strict management plans and lifestyle changes. This event is likely to initiate and perpetuate feelings of fear, upheaval and mortality in the patient. Anxiety about the future, the possibility of serious complications, and doubts as to the patients ability to fulfil prior life commitments and goals appear to be among the most common diabetes specific emotional problems in study samples (PSYCHIATRIC MORBIDITY IN ENDOCRINE DISORDERS Gary R. Geffken, PhD, Herbert E. Ward, MD, Jeffrey P. Staab, MD, MS, Stacy L. K. Carmichael, BS, and Dwight L. Evans, MD) Not only that, but the continual threat of hypoglycaemic episodes and its associated unpleasant and embarrassing symptoms (tremors, profuse sweating, cognitive dysfunction, seizures and LOC) may also function as signification perpertuators of anxiety for some people. Additionally, the presence of diabetes is prone to negatively influence a patients perception of their physical and psychological well being, and subsequently their Quality of Life, especially in the context of the severe medical complications of diabetes including but not restricted to heart attack, stroke, amputation and blindness. (The association between quality of life, depressive symptoms and glycemic control in a a,b,* a a,b group of type 2 diabetes patients. M. Papelbaum , H.M. Lemos , M. Duchesne , R. a a a Kupfer , R.O. Moreira , W.F. Coutinho diabetes research and clinical practice 89 (2010) 227230) Papelbaum et al have gone as far as to identify a positive correlation between the severely of psychopathology and increased HbA1c levels in diabetics.

Mental issues predispose to diabetes Papelbaum et al have gone as far as to identify a positive correlation between the severely of psychopathology and increased HbA1c levels in diabetics. Alternatively, some studies have suggested that psychopathology; depression in particular, precedes, predisposes and is one of the best predictors of micro and macrovascular complications in diabetes. A meta-analysis of 9 longitudinal studies
showed that adults who were depressed were 37% more likely to develop type 2

diabetes than their non- depressed counterparts

This theory proposes that there is a common pathway between the physiological manifestations of depression and diabetes, including obesity, hypercaloric diet, somnolence, physical inactivity, and smoking. Biological complications of depression such as activation of the HPA axis, high cortisol levels, dysregulation of the sympathetic nervous system and stimulation of inflammatory cytokines also factor into the development of insulin resistance in patients with MDD. Perpetuating factors such as depression mediated adverse health behaviours, decreased adherence to medication, diet and exercise regimes have also been identified as stressors that negotiate the worsening course of diabetes.
Even subclinical depression, such as decreased motivation, lack of energy, and hopelessness, interferes with the ability to perform demanding diabetes selfmanagement tasks [39].

(Common mental disorders associated with 2-year diabetes incidence: The Netherlands
Study of Depression and Anxiety (NESDA) Evan Atlantisa,b,*, Nicole Vogelzangsc, Kara Cashmand, Brenda J.W.H. Penninxc Journal of Affective Disorders 142S1 (2012) S30 S35)

Additionally, studies have suggested that decreased ability to sufficiently manage the illness may be related to poor coping strategies and inadequate levels of learned resourcefulness an intraindividual coping resource that is deficient in depression. Indeed, effective glucose management depends largely on self care with heavy emphasis on self monitoring and medication administration. Patients must engage in rigorous self monitoring and adhere to mandatory annual podiatrist, opthamologist and dental exams. Therefore psychopathologies such as depression and anxiety do not simply factor into the provocation of Diabetes but also play a significant role in negotiating the worsening course of this chronic illness. This is manifested in the association between depression and increased rates of diabetic complications e.g. retinopathy, neuropathy, nephropathy, sexual dysfunction and macrovascular complications. (MAIN ARTICLE)
Bidirection Studies has demonstrated a complex relationship between depression and diabetes. But (http://www.grouphealthresearch.org/news-and-events/newsrel/2008/081203.html) perhaps the most important issue is not accurate identification of the perpetuator but rather the acceptance of the two as a manifestation of the intimate relationship between body and mind first suggested by Benjamin Rush. According to Von Korff, "Although the relationship probably goes both ways, we think chronic physical and mental health problems are intertwined. They seem to influence each other continually." The most appropriate conclusion at this stage is the proposal of a bidirectional model to mediate the mechanisms of causation between psychopathology and diabetes. A study that apetly demonstrates this bidirectional relationship within the same study cohort is Golden et als (Golden SH, Lazo M, Carnethon M, et al. Examining a bidirectional association between depressive symptoms and diabetes. JAMA. 2008;299(23):2751 2759.) 2008 study produced results showing that DMII patients were 52% likely to

experience depressive symptoms than non-diabetics while otherwise medically healthy adults with elevated depression scores were 21% more likely to develop DMII. However, evidence shows that approximately only 1/3 to half of cases of comorbid depression and diabetes have their depression accurately diagnosed in primary care, and a further half of those diagnosed patients receive the appropriate guideline level of medical and psychological healthcare. However, what is most shocking is that although most patients prefer for their mental health care and physical health care to be integrated into one clinical modality, this is very rarely carried out in general practice. The bi-directional model highlights the urgent need for a successful integrated form of quality mental health and general health care for patients with comorbid depressive and diabetic illnesses. It is not sufficient to simply address depression as an isolated phenomenon steps must be taken to implement cohesive behavioural and pharmacological interventions aimed at promoting self care and minimising emotional distress in the context of comorbid diagnosis of Diabetes, MDD and/or GAD. Other psychiatric illness e.g. schizo Disordered eating Young women with diabetes are two times more likely to have an eating disorder than the general population. Diabetics with an eating disorder have inadequate glycemic control and elevated HbA1c levels which predisposes to increased risk of microvascular complications. They are also at higher risk of comorbid anxiety, panic attacks and alcohol abuse disorder. Type 1 diabetics are at particular risk of Bulimia Nervosa. A common manifestation of this disorder is insulin purging a form of insulin omission where patients take inadequate amounts of insulin to lose weight, resulting in damaging hyperglycaemia and glycosuria. These patients have poor glycemic control, higher levels of anxiety and higher rates of retinopathy and neuropathy. Schizophrenia The association between Schizophrenia and Diabetes is controversial. Although there appears to be an increased risk of DMII in schizophrenic patients, it is highly that this due to weight gain caused by antipsychotic medication such as Clozapine or Olanzapine. Negative symptoms such as social withdrawal may also contribute somewhat to diabetic risk in Schizophrenics.

Overdose One of the most alarming aspects of managing comorbid depression in a diabetic patient is the high potential of risk associated with suicide by prescription insulin overdose.

It is difficult to ascertain the exact number of intentional hypoglycemic episodes versus accidental insulin overdose due to the narrow therapeutic index of insulin. However, it is known that patients with DM type 1 have 11 times the suicide rate of the general population. The most common diabetic medication used in overdoses is Sulfonylureas mostly as they are the most commonly prescribed medication for DMII. However, Insulin overdoses result in the highest number of severe medical consequences with 42.8% of overdoses involve long acting insulin, often accompanied by concurrent use of ETOH and Drugs (Benzos) (Intentional overdose with insulin: prognostic factors and
toxicokinetic/toxicodynamic profiles. Mgarbane B, Deye N, Bloch V, Sonneville R, Collet C, Launay JM, Baud FJ.)

M. A. von Mach, S. Meyer, B. Omogbehin, P. H. Kann, and L. S. Weilemann, Epidemiological assessment of 160 cases of insulin overdose recorded in a regional poisons unit, International Journal of Clinical Pharmacology and Therapeutics, vol. 42, no. 5, pp. 277280, 2004. View at Scopus The most severe neurological sequelae from Insulin overdose is hypoglycaemic encephalopathy. Areas of the brain that are particularly vulnerable to hypoglycaemia include the cortex, caudate, putamen, and the hippocampus. Consequences of hypoglycaemic encephalopathy are varied and include memory loss and cognitive dysfunction due to neuronal damage, and increased risk of Alzheimers in the future. Other consequences of insulin overdose include electrolyte abnormalities (hypokalemia, hypomagnesaemia, hypophosphatemia), convulsions, rhabdmyolysis, haemolytic anaemia, respiratory failure, Liver enzyme derangement (acute hepatic steatosis due to triglyceride accumulation in hepatocytes) and rare causes of acute pulmonary oedema. How to recognize and treat insulin overdose Symptoms of an insulin overdose include anxiety, confusion, tachycardia, anxiety, hunger, fatigue, irritability, diaphoresis, tremor and at a higher level, seizure, delirium, irreversible neurological damage, coma and death. A delay between insulin overdose and initial medical treatment of greater than 6 hours and mechanical ventilation lasting greater than 48 hours are the most accurate predictors of negative outcome post insulin overdose. Therefore it is vital for health professionals to quickly and accurately recognize a patient with insulin overdose and treat accordingly. The insulin overdose, investigations should reveal high insulin levels and low Cpeptide levels, and electrolyte abnormalities such as hypokalaemia. However in an emergency situation, time is of the essence and all patients presenting to the ED with hypoglycaemic episode should immediately be treated with dextrose

infusion upon admission. Their BGL should also be checked every 15-30min to monitor for long-acting insulin overdose. Further treatment with oral glucose, 50% dextrose boluses, IM Glucagon, excision and drainage of the injection site may also be necessary.

Dementia and CNS damage Treatment and Management The treatment of Depression in Diabetes can be complex as the side effects of many antidepressant medication be especially intolerable to diabetic patients. Tricyclic antidepressants cause significant weight gain, carbohydrate craving (86-200%) and are lethal in high doses which is inappropriate for diabetic patients who are already at a higher risk of suicide due to comorbid depression. Monoamine oxidase inhibitors exacerbate and cause episodes of hypoglycaemia due to their hydrazine structure. They also cause weight gain and impose further restrictions on an already limited diabetic diet. Fortunately, SSRIs (particularly: Fluoxetine, Sertraline and Paroxetine) are consistently well tolerated in diabetics. They are especially preferred for their anorectic effects. Fluoxetine (Prozac) is especially beneficial due to its activating properties. Patterns observed in diabetic patients on SSRIs include lowered insulin requirements, weight loss, increased dietary adherence and lowered HbA1c values. SSRIs are associated with fewer anticholinergic and cardiovascular side effects, however additional side effects such as sexual dysfunction will be of particular concern to Diabetic patients and should be clearly explained. Although SSRIs are still considered first line treatment for diabetics with comorbid depression, Buproprion is a newer generation antidepressant that has become increasingly popular in this population. Unlike SSRIs, Buproprion does not induce sexual dysfunction or affect the metabolism of oral hypoglycaemic medications in any way. It is associated with increased adherence to smoking cessation plans and medication compliance, however Buproprion has no effect on symptoms of anxiety, which is a common co-morbidity in the Diabetic population.

PSYCHIATRIC MORBIDITY IN ENDOCRINE DISORDERS Gary R. Geffken, PhD, Herbert E. Ward, MD, Jeffrey P. Staab, MD, MS, Stacy L. K. Carmichael, BS, and Dwight L. Evans, MD

J Clin Psychiatry. 1995 Apr;56(4):128-36. Treatment of depression in patients with diabetes mellitus. Goodnick PJ, Henry JH, Buki VM. Diabetic patients are at increased risk of both psychological and physical challenges that require support, counseling and pharmacotherapy. However studies have indicated that only about 33%-52% of these patients were treated with antidepressant medications while < 20% report completing 4 or more psychologist appointments. It is vital for health care professionals to pay close attention to the development of mental health disturbances in diabetic patients and vice versa. Symptoms of depression in particular, are easy to screen for. Asking simple questions, such as Have you felt down in the dumps, depressed or hopeless during the past month? and Have you found that you no longer enjoy doing some things you used to take pleasure in? is a validated, practical approach to screening for depression that can easily be used in clinical settings.