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The purpose of the present study was to compare the degrees of nonenzymatically glycosylated proteins in the skin (stratum corneum), the nail, the hair, and hemoglobin obtained simultaneously from the same subject and to evaluate the most useful sample for management of diabetic complications. Fifty-one diabetic patients and 20 control patients were examined, utilizing furosine determination. Furosine value of the skin in diabetics was 2.14 +/- 1.70%, whereas that in controls was 1.65 +/- 0.47%. Furosine value of the nail in diabetics was 6.67 +/- 3.30%, whereas that in controls was 4.16 +/- 1.62%. Furosine value of the hair in diabetics was 1.30 +/- 1.11%, whereas that in controls was 1.29 +/- 1.71%. Close correlations were detected between HbA1 (glycosylated hemoglobin) and furosine of the nail (r = 0.58, p less than 0.001), HbA1 and furosine of the skin (r = 0.48, p less than 0.001), and HbA1 and furosine of the hair (r = 0.43, p less than 0.01); however, poor correlations were found between furosine of the hair and the skin (r = 0.35, p less than 0.05) and furosine of the nail and the hair (r = 0.33, p less than 0.05). Furosine of the nail was significantly correlated with the FBS (fasting blood sugar) of the same time, previous 6, and previous 12 months. Furosine value of the nail, we believe, is the most useful indicator for evaluating long term control of diabetics and may provide useful information for management of diabetic complications.

The purpose of the present study was to examine the effect of non-enzymatic glycosylation and subsequent heating on the browning of the plantar stratum corneum and the finger-nail, and to elucidate the pathogenesis of the yellow skin and the yellow nail seen in diabetic subjects. We incubated stratum corneum and nail from non-diabetics in 0 (control) 10 (only nail) 20 (only nail) 100 and 250 mM glucose buffer at 37°C for 5 days. These glycosylated samples were dialysed against distilled water for 96 h. Distilled water was changed every 24 h. Then samples were dried for 24 h. The extent of non-enzymatic glycosylation was measured by furosine content. Each 5 mg of sample was hydrolysed by 6 N HCl and processed for measurement of furosine by high-performance liquid chromatography. The rest of each sample was stored at 37, 42 (only nail), 47 and 52 °C for 14 days. Browning of the stratum corneum was assessed macroscopically and that of the nail by spectrophotometry. Based on their spectrophotometric reflectances, Munsell’s scores (H = hue score V = lightness score C = saturation score) and (H + C)/V were calculated for objective evaluation of browning. Incubation of the stratum corneum and nail with glucose buffer increased their non-enzymatic glycosylation (furosine) dose dependently. Macroscopically, the browning of the stratum corneum was enhanced in proportion to the glucose concentration and storage temperature. However, samples incubated in 10 and 20 mM glucose and stored at 42 °C did not show visible browning. Munsell’s score of the nail samples treated by glycosylation and heating showed increased hue and saturation but reduced lightness. (H + Q/V values of these nail samples were significantly higher than those of the control. We could not detect any fluorescence with Wood light in the browned samples. The present in vitro study demonstrated that the browning of the stratum corneum and the nail depended on the extent of both non-enzymatic glycosylation and storage temperature. We suggested a hypothesis that the non-enzymatic glycosylation and the storage temperature of the stratum corneum and the nail might be a contributory factor in the development of yellow skin and yellow nail in diabetic patients.

Nonenzymatic glycosylation of protein may play some role in the development of diabetic complications. To study the association of nonenzymatically glycosylated protein in keratinized tissues with the prevalence of cutaneous manifestations frequently observed in diabetics, we measured furosine values of stratum corneum, nail and hair from 61 diabetics and assessed their cutaneous manifestations. The manifestation most frequently found in this study was 10 cases of pigmented pretibial patches. We did not detect significant correlations between the prevalence of any cutaneous manifestations and furosine values of any keratinized tissues. However, 11 of the 17 patients with yellow nail showed high nail furosine values. Our data suggest that nonenzymatically glycosylated protein levels in the keratinized tissues do not correlate with the prevalence of cutaneous manifestations in diabetics, but do not exclude a role in the formation of yellow nail.

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