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Lithium-Induced Transient Diabetes. Abstract. قد يحدث داء السكري العابر عند تناول األدوية النفسية وخصوصا ً دواء اإلضطراب ذو وقد اختلفت الدراسات حول تأثير عقار الليثيوم على استقالب.االتجاهين المسمى بالليثيوم الكربوهيدرات ففي الوقت الذي بينت فيه بعض الدراسات أن عقار الليثيوم قد يساعد في خفض نصف. معدل سكر الدم بينت دراسات أخرى أن ذلك العقار قد يتسبب في رفع معدل سكر الدم في هذا المقال حالة شاب يبلغ من العمر واحد وعشرون عاما ً أتي إلى العيادة يشكو من أعراض وقد اتضح أن المريض يعاني من داء الهوس،كالسيكية إلرتفاع سكر الدم ولمدة سبع أسابيع وقد بينت التحاليل ارتفاع،ويتناول عالج الليثيوم وعالج أوالنزابين ولمدة ناهزت الشهرين مستوى سكر الدم مع عدم وجود حموضة في الدم وبعد ايقاف عالج أوالنزابين وتخفيض جرعة ً عالج الليثيوم وبدء عالج اإلنسولين بدأ مستوى الدم بالتحسن التدريجي وبعد ايقاف اللثيوم تماما وعلى مدى ستة أسابيع بدأ مستوى سكر الدم باإلنخفاض التدريجي إلى مستويات أقل من المعدل الطبيعي مما استدعى إيقاف جميع األدوية المخفضة للسكر وحث المريض على البدء في .برنامج صحي لتغيير نمط الحياة Transient diabetes can occur as drug-induced diabetes secondary to antipsychiatric medications of which, drugs used for bipolar disorder namely lithium. Studies discussed the effect of lithium on carbohydrate metabolism were different, improvement and worsening of glucose tolerance have both been observed in patients receiving lithium. Interestingly, we report a case of 21-year-old male patient presented with a classical symptoms of hyperglycemia for seven weeks duration, patient had a history of mania for which he was receiving lithium and olanzapine for 2 month duration, Investigation revealed that blood glucose was high in the absence of ketones, after omitting olanzapine, tapering lithium's dose and giving insulin therapy blood glucose started to improve gradually, and when lithium was omitted, six weeks afterwards patient had hypoglycemic spells for which hypoglycemic medications were omitted and patient was advised to commence life style modifications. Transient diabetes can occur as drug-induced diabetes secondary to antipsychiatric medications of which, drugs used for bipolar disorder namely lithium. Studies discussed the effect of lithium on carbohydrate metabolism were different, improvement and worsening of glucose tolerance have both been observed in patients receiving lithium. Case Report. 21-year-old male patient presented with a seven-week history of polyuria, polydipsia, polyphagia and weight loss of more than six kg. No symptoms of nausea, vomiting, epigastric pain and fever were presented. He suffered from mania and has been on lithium 400mg po od and olanzapine 15 mg po od for two months. No past history of acute viral illness , neither history of acute stress that necessitated hospital admission nor diabetic ketoacidosis were occured, No history was suggestive of autoimmune disorders such as autoimmune thyroid disease, adrenal insufficiency, pernicious anemia, vitiligo, …..ect . Past medical history showed that he had mental retardation since childhood and had past history of epileptic seizure long time ago which was controlled on tegretol 200 mg po bid. Family history showed that his father was diabetic and he had been taking oral hypoglycemic medications for more than 35 years . Insulin therapy was commenced. 450 HbA1c 7.4% 400 350 300 250 200 150 Capillary Blood Glucose mg/dl Olanzapine was omitted and Lithium was reduced to 200mg. Lithium was omitted. HbA1c 5.6% , Insulin was omitted and oral hypoglycemic medications was commenced. 100 50 0 On Figure physical 1. Follow-up examination, chart showing he waseffect alert,oforiented, olanzapine his and pulse lithium wason blood glucose levels, HbA over 3 months . 1c 96/min, his blood pressure was 92/60 mm Hg, his respiratory rate was 15/min, his temperature was 37.5 C, his weight was 77kg and his body mass index was 26 kg/m2. No signs of dehydration or autoimmune skin disease were found. Rest of physical examination was normal . On arrival, his random blood glucose was 402 mg/dl, with no ketones in urine, patient was sent to the emergency department for arterial blood gases his PH =7.33, HbA1c was 7.4%, liver function tests, renal functions, ECG, chest xrays were normal (see figures 1, 2, 3). We diagnosed the case as hyperglycemia due to type 1 diabetes, patient was encouraged to increase oral fluid intake and was given twice-daily biphasic insulin therapy, at the same time patient was given referral to the psychiatrist for case assessment, lithium drug level in the blood and for medication review. Lithium drug level in the blood was 0.83 mmol/L which is above the therapeutic range (0.50-0.80 mmol/l 24hr after night administration or before a new one) with normal renal function and creatinine clearance. Consequently lithium was reduced to 200mg po od and olanzapine was omitted. The follow-up visits over five weeks later, showed successive improvement in blood glucose levels (see figure 1) without a change in the insulin dosage, at the end lithium was omitted. Four weeks later, patient experienced hypoglycemic spells, which led to cessation of insulin after 2 months. At this stage HbA1c was 5.6%, with a low insulin level to a glucose load, one-hour postprandial insulin was 14.90 µU/ml below the therapeutic range (29-88 µU/ml) and normal C-peptide level responses to a glucose load, Cpeptide level was 3.7ng/ml within range (2.37-5.74 ng/ml), because of the cost effect and normal C-peptide level , GAD and islet cell antibodies were not requested, so our primary diagnosis which was type 1 diabetes was changed to drug induced type 2 diabetes namely olanzapine and lithium, at that moment we commenced oral hypoglycemic agents; gliclazide 80 mg po od, and metformin 500 mg po bid , two weeks later patient complained from hypoglycemic spells for that reason we omitted oral hypoglycemic agents, at that stage 2-hour oral glucose tolerance test was normal, patient was advised to maintain lifestyle modification. Shirt Buttons Figure 2. PA Chest x-ray shows normal lung's field, no evidence of chest infection. Figure3. ECG was normal, no ST segment changes , or T wave inversion. Discussion . In this case, We considered several explanations for the unusual profile of diabetes in this patient. The initial presentation was suggestive of type 1 diabetes, but the remitting course makes this diagnosis unlikely. Although remission may occur in early type 1 diabetes, as what we call it "honeymoon period", but this suggestion was unlikely because of normal postprandial C-peptide level. Atypical type 2 diabetes, characterized by ketosis at onset and subsequent remission, has been described in African patients(1) also unlikely because of normal blood PH and negative urine ketones. Nonetheless, normal C-peptide and subsequent insulin independence in this case favor type 2 diabetes as the more likely diagnosis. In this case the onset of diabetes followed the initiation of lithium and olanzapine by one week, thus; olanzapine was omitted based on the rising issue about the role of the newer antipsychotic drugs in causing hyperglycemia(2,3) , at the same time lithium was tapered to 200mg after documenting lithium overdose, this was followed by 5 weeks period of subsequent improvement in blood glucose levels but the patient was still insulin dependent. When lithium was omitted, blood glucose levels returned to normal values over 8 weeks and patient became insulin independent. Literature review revealed that the effects of lithium on carbohydrate metabolism are complex, and improvement and worsening of glucose tolerance have both been observed in patients receiving lithium(4,5). Studies in rats show that lithium exerts antidiabetic effects by increasing glycogenesis, either through an insulin-sensitizing action or through direct activation of enzymes involved in hepatic glycogenesis(5). Another study was conducted among domestic pigeons (Columba livia) to assess the effects of lithium chloride on the histological and biochemical parameters of the endocrine pancreas namely, islets of Langerhans(6) . No cytomorphological alteration was not noted in alpha cells after giving doses of 3 m.eq and 6 m.eq lithium chloride but, more prominent changes in alpha cells were noted after giving a dose of 9 m.eq lithium chloride, granules among these cells became large and densely packed when compared to the cells of control pancreas . Alterations in beta cells were not so profound. Another study found that Lithium chloride has an inhibitory effect on the expression and secretion of insulinlike growth factor-binding protein-1 (IGFBP1)(7), which has an important role in insulin regulatory effects for blood sugars, and subsequent decrease in the concentration of insulin-like growth factor (IGF) and insulin-like growth factor binding protein-1 (IGFBP1) are associated with insulin resistance, diabetes and cardiovascular disease. according to eHealth's study which is a website for healthcare practice supported by electronic processes and communication; revealed that the time intervals between the initiation of lithium carbonate and the development of type 1 diabetes in people reported in that study were 1-6 months in 33.3% of cases, 2-5 years in 33.3% of cases, 5-10 years in 33.3% (8). In conclusion, the effects of lithium on carbohydrate metabolism are complex especially if there was concurrent administration with newer antipsychotic drugs, and Each psychiatric case should be assessed before the initiation of psychiatric medication, baseline HbA1c level, lipid profile, LFTs, renal function test and weight measurement. Follow-up all patients who are taking newer antipsychotic medications or lithium, careful observation, reporting for possible adverse effects, HbA 1c should be done every 3 month for two successive visits, then if levels are still within range, repeat HbA1c every 6 month for two successive visits, then if levels are still within range, repeat HbA1c annually. References : 1. Sobngwi E, Mauvais-Jarvis F, Vexiau P, Mbanya JC, Gautier JF: Diabetes in Africans. Part 2: ketosis-prone atypical diabetes mellitus. Diabetes Metab 28 : 5 –12,2002. 2. “Important Safety Information about ZYPREXA® (olanzapine),” Eli Lilly and Company, 5 Oct. 2007; “Lilly Announces Updates to the Zyprexa and Symbyax U.S. Labels,” PRNewswire, Bio-Medicine, 5 Oct. 2007. 3. ZYPREXA Safety Information, www.zyprexa.com. 4. Saran AS: Antidiabetic effects of lithium. J Clin Psychiatry 43 : 383 – 384,1982. 5. Rodriguez-Gil JE, Fernandez-Novell JM, Barbera A, Guinovart JJ: Lithium’s effects on rat liver glucose metabolism in vivo. Arch Biochem Biophys 375 : 377 –384,2000. 6. Ghosh S. (2007) : Effect of Lithium chloride on the Endocrine Pancreas of Domestic Pigeon . Asian J. Exp. Sci., Vol. 21, No. 2, 2007, 323-326. 7. " Lithium chloride inhibits the expression and secretion of insulin-like growth factor-binding protein-1", www.endocrinology.org 8. "Could Lithium carbonate cause Type 1 diabetes mellitus ? ", www.ehealthme.com/ds/lithium+carbonate/type+1+diabetes+mellitus