Endocrine Abstracts

Alstrom syndrome is an autosomal recessive disorder characterised by obesity, sensorineural deafness, cone-rod dystrophy and hypergonadotrophic hypogonadism. Diabetes in these patients is characterised by severe insulin resistance.
We describe the management of diabetes in a 28 year old male patient with Alstrom syndrome and severe insulin resistance. Obesity developed early in childhood and at 3 years weight was 22.2 kg. Genetic studies revealed that the patient is a compound heterozygote, with a frameshift mutation and translocation break point in the paternal and maternal alleles, respectively of the ALMS1 gene.
Diabetes was diagnosed at age 14. Islet cell antibodies were negative. Peripheral insulin resistance was assessed by the hyperinsulinaemic isoglycaemic clamp technique.Insulin sensitivity, expressed as the glucose infusion rate [M value] was 48mg/m²/min.Mean M values for a similar group of moderately obese subjects was 80 mg/m²/min indicating marked peripheral insulin resistance.
Initial treatment with diet alone maintained glycated haemoglobin (HbA1c) values of 5.5-8.2%. Metformin was started at age 21 but glycaemic control deteriorated(HbA1c 8.9%).Insulin(52 units/day)was started in addition to Metformin a year later following which glycaemic control improved(HbA1c 7%).A thiazolidinedione was considered in view of the theoretical impact on insulin resistance.Rosiglitazone 4 mg once daily was substituted for insulin.
Glycaemic control has since remained stable on Rosiglitazone (HbA1c 6.9%).Weight gain however has been progressive and BMI has increased from 32.1 kg/ m² to 35.2 kg/m² over 15 months of treatment. Total cholesterol and serum triglycerides have increased from 6.28mmol/l and 3.71mmol/l to 9.02 mmol/l and 6.94 mmol/l respectively over the same period.
Thiazolidinediones are highly effective in reducing insulin resistance. Rosiglitazone improved glycaemic control in our patient with Alstrom syndrome though this was associated with deterioration in lipid control and progressive weight gain.