Rheumatology Advance Access originally published online on January 25, 2008
Rheumatology 2008 47(3):378-379; doi:10.1093/rheumatology/kem378
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hypoglycaemia induced by hydroxychloroquine in a non-diabetic patient treated for RA
Division of Rheumatology, Department of Internal Medicine, Eski
ehir Osmangazi University, Eskiehir, 26480, Turkey
Correspondence to: C. KORKMAZ, Vinelik M. Alifuat Güven C. Akasya S. 11/11, 26020, Eskiehir, Turkey. E-mail: ckorkmaz{at}ogu.edu.tr
SIR, Anti-malarial drugs have become one of the most commonly prescribed drugs in the treatment of many rheumatic diseases such as RA and SLE. Anti-malarials may improve glucose tolerance. Hypoglycaemia is a rare but well-recognized adverse effect of anti-malarial therapy [1–3].
Here we described a non-diabetic patient with RA who developed hypoglycaemia under hydroxychloroquine (HCQ) treatment. We also discussed the possible mechanisms of hypoglycaemia due to HCQ.
A 62-yr-old man was admitted to our hospital with symmetric polyarthritis and morning stiffness for more than 2 h in 2005. He had a history of pain and swelling in his fingers, wrists, elbows and shoulders for 3 yrs. He had been diagnosed as having RA in another hospital and treated with sulphasalazine (SSZ) 2 g/day, methotrexate (MTX) 7.5 mg/week, prednisolone 7.5 mg/day and NSAIDs.
On examination, swelling and pain in the wrists, metacarpophalangeal joints and proximal interphalangeal joints was found. He had also subcutaneous nodules around the elbow joints. The blood count, liver function and urinalysis tests were normal. RF was 632 IU/ml and ESR was 102 mm/h. The dose of MTX was increased to 12.5 mg/week and prednisolone 15 mg daily was started. SSZ was continued and leflunomide 10 mg daily was added to treatment.
He was lost to follow-up 2 yrs after his last control. In April 2007, he was admitted with symmetric polyarthritis. Leflunomide was increased to 20 mg/day. SSZ, MTX were continued and HCQ 200 mg daily was started.
In June 2007, he was brought to the emergency department because of unconsciousness. Blood analysis showed hypoglycaemia (10 mg/dl; reference range 70–110 mg/dl). He rapidly responded to i.v. dextrose. Serum insulin and C peptide levels were determined during 72 h of the fasting test. Fasting test was stopped at 40th h due to hypoglycaemic symptoms. Glucose, insulin and C peptide levels were found to be 39 mg/dl, <2 µU/ml and 0.7 mg/dl, respectively at the end of the test. These results were not consistent with insulinoma. Cortisol and growth hormone levels were in normal ranges. Oral glucose tolerance test (oGTT) was normal. HbA1c and BMI were 5.09% and 22.9, respectively. Abdominal ultrasonography for the evaluation of the pancreas was normal. HCQ was stopped. MTX, leflunomide and prednisolone were continued. Ten days after his discharge from the hospital, hypoglycaemic attack recurred and his hypoglycaemic symptoms including perspiration and unconsciousness were treated with i.v. dextrose. Carbohydrate-rich diet as well as frequent meal was advised to patient for avoiding a possible hypoglycaemia.
In the literature, our patient is the first non-diabetic case with RA who developed hypoglycaemia secondary to HCQ. Anti-malarials are well-tolerated and safely used drugs. Hypoglycaemia is a rare adverse effect of anti-malarials. Although, some cases in the literature about hypoglycaemia related to chloroquine (CQ) is reported [1, 2], there is only one RA patient with diabetes mellitus who developed hypoglycaemia due to HCQ [3]. Our patient had no predisposing disorder that will lead to hypoglycaemia such as insulinoma, ethanol intake, oral anti-diabetic and exogenous insulin usage. There were also no clinical and laboratory manifestations of starvation, liver failure or sepsis that can lead to hypoglycaemia.
The mechanisms of hypoglycaemia due to HCQ are inferred from studies of CQ, structurally similar anti-malarials. In vitro evidence has shown that CQ reduces intracellular insulin degradation, increases intracellular insulin accumulation, slows receptor recycling and stimulates insulin-mediated glucose transport [4]. Chronic CQ treatment enhances insulin release in rats [5]. Animal data have shown that adding HCQ to streptozotocin-treated diabetic rats led to a higher insulin level and lower glucose concentrations. HCQ may reduce cytosolic insulin metabolism [6, 7].
HCQ is an anti-malarial drug that may have anti-hyperglycaemic properties in patients with type 2 diabetes mellitus and the benefical effects on glucose metabolism and insulin sensitivity was reported among patients with SLE [8, 9]. HCQ improves glycaemic control in sulphonylureas refractory patients with poorly controlled type 2 diabetes [8]. The addition HCQ to insulin therapy caused a significant decrease in the insulin requirements [8]. This effect appeared at 2 weeks and persisted for 6 months. In a prospective, multicentre, observational study, Wasko et al. [10] showed that 4905 RA patients using HCQ is associated with a reduced risk of diabetes.
HCQ may be indicated for the prevention of hyperlipidaemia and diabetes mellitus [10, 11]. Although HCQ use reduces the need for oral anti-diabetic and insulin in patients with type 2 diabetes mellitus, hypoglycaemia may develop in non-diabetic patients with RA. Therefore, fasting blood glucose and HbA1c levels should be monitored during the first 6 months of treatment for symptomatic and asymptomatic patients, respectively. We came to notice that our patient was suffering mild symptoms of hypoglycaemia, only after he had started receiving HCQ for RA treatment. This being the case, we suggest that patients who are to receive HCQ should be well informed about such ill-effects of HCQ as hypoglycaemia.
 |
Acknowledgments |
|---|
Disclosure statement: The authors have declared no conflicts of interest.
|
References |
|---|
 Top References |
|---|
- Bamber MG, Redpath A. Chloroquine and hypoglycemia. Lancet (1987) 1:1211.[Medline]
- Abu-Shakra M, Lee P. Hypoglycaemia: an unusual adverse reaction to chloroquine. Clin Exp Rheumatol (1994) 12:95.[Web of Science][Medline]
- Shojania K, Koehler BE, Elliott T. Hypoglycemia induced by hydroxychloroquine in a type II diabetic treated for polyarthritis. J Rheumatol (1999) 26:195–6.[Web of Science][Medline]
- Cynober L, Aussel C, Vaubourdolle M, Agneray J, Ekindjian OG. Modulation of insulin action on 2-deoxyglucose uptake by chloroquine in chick embryo fibroblasts. Diabetes (1987) 36:27–32.[Medline]
- Asamoah KA, Robb DA, Furman BL. Chronic chloroquine treatment enhances insulin release in rats. Diabetes Res Clin Pract (1990) 9:273–8.[CrossRef][Web of Science][Medline]
- Emami J, Pasutto FM, Mercer JR, Jamali F. Inhibition of insulin metabolism by hydroxychloroquine and its enantiomers in cytosolic fraction of liver homogenates from healthy and diabetic rats. Life Sci (1999) 64:325–35.[CrossRef][Web of Science][Medline]
- Emami J, Gerstein HC, Pasutto FM, Jamali F. Insulin sparing effect of hydroxychloroquine in diabetic rats is concentration dependent. Can J Physiol Pharmacol (1999) 77:118–23.[CrossRef][Web of Science][Medline]
- Quatraro A, Consoli G, Magno M, et al. Hydroxychloroquine in decompensated, treatment-refractory noninsulin-dependent diabetes mellitus: a new job for an old drug? Ann Intern Med (1990) 112:678–81.
[Abstract/Free Full Text] - Petri M. Hydroxychloroquine use in the Baltimore Lupus Cohort: effects on lipids, glucose and thrombosis. Lupus (1996) 5:16–22.
- Wasko MC, Hubert HB, Lingala VB, et al. Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. JAMA (2007) 298:187–93.
[Abstract/Free Full Text] - Tam LS, Gladman DD, Hallett DC, Rahman P, Urowitz MB. Effect of antimalarial agents on the fasting lipid profile in systemic lupus erythematosus. J Rheumatol (2000) 27:2142–5.[Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||