Type 1 Diabetes Mellitus in Homozygous Sickle CellAnaemia
The prevalence of diabetes mellitus is very low amongpatients with sickle cell disease. A number of studiesfailed to detect a single case of diabetes among patientswith sickle cell anaemia.1,2 However, few case reports ofcombined presentation of both the diseases without anycomplication have been reported among blackpopulation.3-5 No such case has been reported from Indiatill date. This case report describes a patient of sicklecell anaemia with Type 1 diabetes mellitus complicatedwith ketosis.
SRK, a 17 years girl admitted to the 4th unit ofDepartment of Medicine, VSS Medical College Hospital,Burla, Orissa with the complaints of loss of weight for 5months; fever, pain in abdomen, and burning sensationduring micturation for 7 days. She is a known case ofsickle cell anaemia, diagnosed at the age of 12 years. Shehad been hospitalized thrice for painful crisis. Herparents had sickle cell trait. There is no family history ofdiabetes mellitus.
On examination, the patient had average built, height5ft. 3 inches, weight-34 Kg, pulse rate-120 per minute,blood pressure (right hand and supine)-110/70 mm ofHg. She was anaemic and icteric. On abdominalexamination liver was enlarged 3cm below the costalmargin. Spleen was not palpable. Investigations showed:Hb.-8 gm/dl, differential count- N: 82%, L:10%, E:6%,M:1%, B:1%, total leukocyte count-16,000/cmm, fastingblood glucose-530.0 mg/dl, blood urea-23.0 mg/dl,serum creatinine-1.1mg/dl, serum bilirubin-2.6mg/dl,C-peptide-0.2 ng/ml, glycosylated haemoglobin(Hb.A1c)-11.5%, lipid profile: S. cholesterol-181.0mg/dl, triglycerides-174.0mg/dl, LDL-121.2mg/dl, HDL-25.0mg/dl, VLDL-34.8mg/dl. Urine examinationshowed the presence of reducing sugar, protein, ketonebodies, and clumps of pus cells. E. coli was grown inculture and was sensitive to Amikacin. Haemoglobinelectrophoresis showed SS band. High performanceliquid chromatography (Variant, ß-thalassemia ShortProgram, Biorad) showed Hb S window-76.8%, Hb F-10.5%, Hb A0 – 1.9%.
The diagnosis of sickle cell anaemia with diabetesmellitus, complicated with urinary tract infection andketoacidosis was made and treated with normal saline,Inj. Ceftriaxone 1000 mg I.V.daily, Inj. Amikacin (15mg/Kg) 250mg twice daily, human neutral insulin, and othersupportive measures. Human neutral insulin wasadministered intramuscularly at the dose of 4 IU/hour.Blood glucose was normalized with 90 units/day on 4thday. She recovered and was discharged on the 12th day.
Concurrent sickle cell anaemia with diabetes mellitusis very rare and with ketosis, still rarer. Only few casereports of this uncommon association of these twodiseases are available.3-5 A couple of homozygous sicklecell patients with pregnancy and insulin dependentdiabetes mellitus had been reported earlier.3 Combinationof these two diseases in two children had also beenreported from Nigeria.4,5 All previously reported caseswere not associated with any complication of diabetesmellitus. The present case reported here is the first caseof sickle cell anaemia with Type-1 diabetes mellituscomplicated with ketosis. This patient presented withfever and abdominal pain, hence initially a provisionaldiagnosis of sickle cell anaemia with crisis had beenmade. This is because abdominal pain is one of thepresenting features of sickle cell crisis with or withoutacute pancreatitis.6 Diabetes mellitus was diagnosed inthis patient only when fasting blood glucose was doneas a routine investigation. Because of the young age at onset, absent family history of diabetes, and thepresenation with ketosis, the diagnossis of Type-1diabetes mellitus was made.
To investigate the prevalence of diabetes mellitusamong sickle cell anaemia patients, Morrison et alconducted a study with pregnant black patients withsickle cell anaemia. The authors selected pregnantpatients because it is well known that pregnancy isdiabetogenic and latent diabetes may be unmasked after28 weeks of gestation. However, the authors could notdetect a single case of diabetes as compared to 4%prevalence in the control.1 Another study, which hadbeen conducted in Nigeria to detect the beneficial effectof glycosylated sickle Hb (HbSS) also failed to detect asingle case of HbSS-diabetic.2 Similarly from Orissa,India where the frequency of sickle cell gene is very high(15.1%), diabetes has not been reported among patientshomozygous and heterozygous for sickle cell gene.6,7
There are no satisfactory explanations for theuncommon association of these two diseases. Oneexplanation is that majority of patients with sickle cellanaemia died early, therefore, relatively small numberof patients survived for the clinical manifestation ofdiabetes.5 However, sickle cell anaemia found in Indiaand Saudi Arabia (Asian haplotype) is less severe thanAfrican haplotype and a significant proportion ofpatients survived more than 30 years of age.6 Inspite oflonger survival, concurrent diabetes with sickle cellanaemia has not been reported from India.6,7 Hence, some other unknown factor(s) may be responsible for this rareassociation. Another explanation is genetic. In supportof this hypothesis is the fact that both the b-globin andthe insulin genes are present in short arm of chromosome11.1 It is not known whether the genetic loci of insulinand b-globin have any inhibitory effect on the inheritancepattern or penetrance of the other. Therefore, the relationbetween diabetes mellitus and sickle cell anaemia needsfurther evaluation.
1.Morrison JC, Schneider JM, Kraaus AP, Kitabchi AE. Theprevalence of diabetes mellitus in sickle cellhaemoglobinopathies. J Clin Endocrinology and Metablism1979;48:192-95.
2.Reid HL, Photiades DP, Oli JM, Kaine W. Concurrent sicklecell disease and diabetes mellitus. Trop Geogr Med1988;40:201-4.
3.Miodovnik M, Hurd WW, Lobel JS, Siddiqi TA. Pregnancyassociated with both insulin dependent diabetes mellitusand sickle cell disease – a report of two cases. J Reprod Med1987;32:317-9.
4.Reid HL, Ene MD, Photiades DP, Famodu AA. Insulindependent diabetes mellitus in homozygous sickle cellanaemia. Trop Geogr Med 1990;42:172-3.
5.Adekile AD, Jegenda AO. Juvenile onset diabetes mellitus
in a sickle cell anaemia patient. East Afr Med J
6.Kar BC. Sickle cell disease in India. J Asso Phy Ind1991;39:954-60.
7.Kar BC, Clinical profile of sickle cell trait. J Asso Phy Ind2002;50:1368-71.