The Somogyi phenomenon revisited using continuous glucose monitoring in daily life

Abstract

In 1959, Michael Somogyi reported that hypoglycaemia during the night was often followed by heavy glycosuria next morning [1]. Moreover, a high morning fasting blood glucose value was later attributed to nocturnal hypoglycaemia and the need to reduce the evening or bedtime dose of insulin. The Somogyi phenomenon-hypoglycaemia begetting hyperglycaemia-is believed to be due to the release of counterregulatory hormones in response to (nocturnal) insulin-induced hypoglycaemia. Despite the fact that experimental studies have rejected the existence of the Somogyi phenomenon [2][3][4], it is, in our experience, still widely believed to exist by health care professionals. Previous experimental research has been based on hospitalised patients using nocturnal blood glucose profiles or real life data with a single nocturnal blood glucose measurement. The sensitivity of the latter method for the detection of nocturnal hypoglycaemia is low [3,5], which may explain some of the reluctance to accept that the phenomenon does not exist. The recent development of continuous glucose monitoring systems has made it possible to monitor patients with type 1 diabetes in daily life.Using this technology, we tested the existence of the Somogyi phenomenon in daily life in a large cohort of type 1 diabetic subjects.All 262 patients with type 1 diabetes from a cohort included in a study of hypoglycaemia in 1999 [6] were invited to participate in a prospective observational study in 2002. The protocol was approved by the regional ethics committee. Of the patients invited, 126 (48%) gave written informed consent to participate, while four (2%) were dead, 23 (9%) had moved or did not participate for other specific reasons, 37 (14%) did not respond to the invitation, and 72 (27%) declined to participate. The participants (35% women ) had a mean (SD) age of 46 (12) years and a diabetes duration of 21 (12) years. Most (86%) of the patients were on basal bolus treatment with NPH and human insulin. The remaining patients were receiving one-or two-dose therapy, and the mean HbA 1 c was 8.5±1.0%. Patients underwent 6 days of continuous subcutaneous glucose monitoring using a continuous glucose monitoring system (CGMS) (Medtronic MiniMed; Medtronic Diabetes, Northridge, CA, USA). At day 1, the sensor was inserted into the abdominal wall. Following careful instruction about the device and protocol, initial calibration was performed and patients went home with instructions to live as normally as possible. At day 4, the sensors were replaced, and at day 7 the sensors were dismantled and data were analysed. Calibration measurements were performed four times daily with a glucose analyser (HemoCue B; HemoCue, Vedbaek, Denmark) in order to obtain optimal accuracy of the calibration curve. The glucose analysers used in the present study were calibrated identically by the manufacturer. Participants kept a diary during the entire study period, documenting insulin doses, meals and snacks, episodes of symptomatic hypoglycaemia, and the blood glucose level during t...

Insulin Resistance and Hyperinsulinemia

“…He attributed this phenomenon to episodes of hypoglycemia (often undetected) that provoked release of counterregulatory hormones. Recent studies, including studies of such patients with sensitive methods that have excluded antecedent hypoglycemia as the cause, have shed doubt on his original explanation (15). We suggest that insulininduced insulin resistance is the most likely mechanism.…”

Reply to comment on: Høi-Hansen T, Pedersen-Bjergaard U, Thorsteinsson B (2005) The Somogyi phenomenon revisited using continuous glucose monitoring in daily life. Diabetologia 48:2437–2438

“…In our research letter, we reported a significant difference in mean fasting morning blood glucose between nights without hypoglycaemia and the other two categories of glycaemia [5]. Similarly, we found that 1 h after measurement of fasting morning blood glucose, the mean glucose value for nights without hypoglycaemia (mean ± SEM: 11.9±0.3 mmol/l) was significantly different from that for possible hypoglycaemic nights (9.8±0.6 mmol/l, p<0.003, Bonferroni corrected) and that for hypoglycaemic nights (10.3±0.4 mmol/l, p<0.006, Bonferroni corrected).…”

“…With the years, this phrase has been interpreted as nocturnal hypoglycaemia inducing high morning blood glucose values [4]. In our letter we rejected this clinical statement by showing that if patients have a nocturnal hypoglycaemic episode during the night there was a high probability that blood glucose the following morning was low [5]. This finding suggests that hormonal counter-regulation alone is not capable of inducing hyperglycaemic excursions in type 1 diabetic patients.…”

In search of the Somogyi effect

“…Все ночи были разделены на 3 группы: с ночной гипогликемией (уровень глюкозы по дан-ным НМГ ниже 2,2 ммоль/л в течение как минимум 10 минут), с возможной гипогликемией (уровень глю-козы от 2,3 до 3,5 ммоль/л) и без гипогликемии (уровень глюкозы >3,5 ммоль/л) (табл. 4) [22]. Уровень глюкозы крови натощак был значительно ниже после ночи с гипогликемией или с возможной гипогликемией по сравнению с ночами без гипоглике-мий.…”

“…Таким образом, Т. Hoi-Hansen и соавт. заключают, что полученные данные не подтверждают существование феномена Сомоджи, и риск ночной гипогликемии посте-пенно возрастает при снижении уровня глюкозы крови натощак [22].…”