Cockayne syndrome (CS) is autosomal recessive disorder characterized by developmental delay, pigmentary retinopathy, cutaneous photosensitivity, and cachectic dwarfism (1). Although few CS patients present with diabetes, no previous report has described a suitable treatment. Here, we report such a case where pioglitazone administration successfully improved hyperglycemia in a case of CS with diabetes.
A 24-year-old male came to our department for the treatment of diabetes. The medical history included growth failure and psychomotor retardation at the age of 1 year and pigmentary retinopathy at the age of 3 years. Thereafter, sensorineural deafness appeared at the age of 6, and a diagnosis of CS based on clinical conditions was made at the age of 8. He eventually developed diabetes at the age of 24. The patient’s height was 106 cm, weight was 17.0 kg, BMI was 15.1 kg/m2, and subcutaneous and visceral fat areas on computer tomography were 54.4 and 13.7 cm2, respectively. A feeding tube was placed. The following results were obtained on initial examination: casual blood glucose level was 253 mg/dL and A1C level was 8.6% (70 mmol/mol). The respective results at 0, 30, 60, and 120 min after a 75-g glucose tolerance test were as follows: blood glucose levels of 131, 339, 467, and 534 mg/dL and insulin levels of 16.8, 36.1, 109, and 132 IU/mL. Sitagliptin, an inhibitor of dipeptidyl peptidase-4, was then introduced at 12.5 mg/day and increased to 25 mg/day after 1 month. Sitagliptin was effective for the first 2 months, but the A1C level gradually increased thereafter. Insulin glargine was combined; however, the A1C level failed to decrease to 8.5% (69 mmol/mol) after 7 months. Because the patient showed insulin resistance (IR), 7.5 mg pioglitazone was added, resulting in an eventual decrease in the A1C level to 6.4% (46 mmol/mol) after 6 months. Changes in adipocytokine levels before and after a 6-month administration of pioglitazone were as follows: leptin, 30.5 to 119 ng/mL; adiponectin, 8.5 to 13 mg/mL; and interleukin-6, 7.6 to 5.6 pg/mL. Six months after initiation of pioglitazone, the patient’s subcutaneous and visceral fat areas were 63 cm2 and 17.8 cm2, respectively. These results indicate that pioglitazone administration effectively increased the amount of fat tissue leading to an improvement in hyperglycemia in CS with diabetes.
In a review of 140 CS patients, Nance and Berry (2) reported relatively few patients with IR and glucose intolerance. A literature review returned only five cases of CS with diabetes, from which four were reported in Japan (3–5).
The mechanisms of how CS develops into IR remain largely unknown. CS usually presents with subcutaneous fat atrophy. Therefore, IR that is seen in CS might be due to partial lipodystrophy, although serum leptin levels in our case were not as low as in patients with idiopathic lipodystrophy. Indeed, pioglitazone improved hyperglycemia conjunction, as indicated by increased levels of not only leptin but also adiponectin and by the amount of subcutaneous and visceral fat, thereby demonstrating that lipodystrophic-like conditions contribute to IR seen in CS.
Therefore, pioglitazone is considered to be the primary treatment option for cases of CS with diabetes.
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Duality of Interest. No potential conflicts of interest relevant to this article were reported.
Author Contributions. A.Hay., M.S., A.Hat., and K.S. researched data. M.T. wrote the manuscript and researched data. K.Y. contributed to the discussion and reviewed and edited the manuscript. M.T. and K.Y. are the guarantors of this work and, as such, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
