Download Lithium-Induced Transient Diabetes. Abstract.

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