No Delay in Glucose Change at Antecubital Skin in Hypoglycemia of Normal Subjects

In the July 2001 issue of Diabetes Care, Jungheim and Koschinsky (1) reported that capillary blood glucose values at forearm lagged behind those at fingertip by maximum 30 min in their particular type 1 diabetic patient rendered to hypoglycemia. They warned that this might result in delay of hypoglycemia detection in diabetic patients and endangered their lives. They hypothesized that this was a physiological phenomenon rather than a pathological delay.

We investigated if their observation was physiological. We had 10 nondiabetic healthy volunteers (8 males and 2 females aged 35.0 ± 11.2 years with a BMI of 22.2 ± 3.0 kg/m²) who were hypoglycemic with intravenous bolus injection of human insulin 0.1 unit/kg body wt. Blood glucose levels were monitored at three different unilateral forearm sites: antecubital vein, capillary blood from antecubital skin, and fingertip. Three blood samples were taken strictly simultaneously with 5–10 min intervals for 90 min at three sites with venipuncture or pricking by three laboratory technicians. All blood samples from antecubital skin were taken after rubbing the skin. These samples were analyzed instantly for glucose by Free Style glucometers (Nipro, Osaka, Japan), which requires only 0.3 μl of whole blood for determination.

As described in Fig. 1, we found two major differences with Jungheim and Koschinsky’s findings: 1) we observed no significant difference in blood glucose levels between those from antecubital capillary blood and fingertip; and 2) we noticed no delay in blood glucose nadirs among the three monitored sites. Changes at all sites were entirely concomitant. We see no advantage of measuring fingertip glucose over antecubital capillary blood glucose for these two reasons. Different from other two sites, antecubital venous blood glucose values were always significantly lower (P < 0.01–0.05) than those levels of either antecubital or fingertip from −20 to 45 min throughout. Therefore, if we want to detect hypoglycemia as early as possible, then we have to monitor venous blood glucose rather than either antecubital or fingertip. We do not think this is feasible and practical for the patients.

Blood glucose changes in hypoglycemia at antecubital and fingertip proceed synchronously without any delay in normal subjects (Fig. 1). We observed no delay in blood glucose changes in capillary blood at forearm as described by Jungheim and Koschinsky on their type 1 diabetic patient. They hypothesized that this could be a physiological delay, which is not consistent with our findings. Since diabetes is a disease of vascular complications and of autonomic neuropathy, one cannot rule out possible vascular reorganization or vascular nerve dysfunction after decades of hyperglycemia, leading to a possible delay in some cases of forearm glucose level detection than in fingertip. Their observation in type 1 diabetes, however, cannot be generalized as physiological; rather, it may represent an inconsistent and pathological finding observed in a limited range of patients. We need further investigation of diabetic patients with a variety of vascular or neural complications caused by various length or severity of diabetes to obtain a definite conclusion.