Subclinical Reactive Hypoglycemia Is Associated with Higher Eating and Snacking Frequencies in Obese or Overweight Men without Diabetes

Abstract

Impacts of subclinical reactive hypoglycemia on food ingestion are not well studied. In the present study, in obese/overweight males without diabetes (n = 34), continuous glucose monitoring and eating behavior were recorded for 6 days after the 75 g glucose challenge. In 50% of subjects, the minimal sensor glucose levels within 24 h post-challenge (CGMmin) were <70 mg/dL, while symptoms, if any, were subtle. Median eating and snacking frequencies were 3.45 and 0.45 times/day, respectively. In subjects with eating frequency > 3 times/day, CGMmin was significantly lower than CGMmin in those without. The receiver operating characteristic curve of CGMmin for detecting eating frequency > 3 times/day showed the area under the curve of 0.74 with the cutoff point of 65 mg/dL (p = 0.027). Eating frequency of subjects with CGMmin < 65 mg/dL was significantly higher than that of subjects with CGMmin ≥ 65 mg/dL (3.68 vs. 3.3 times/day, p = 0.047). When it was defined as reactive hypoglycemia that either the 2 h post-load blood glucose level, the minimal self-monitored blood glucose level within the 1st day, or CGMmin, was below their respective cutoff for detecting eating frequency > 3 times/day, eating frequency of subjects with the reactive hypoglycemia was significantly higher than that of the subjects without the reactive hypoglycemia (3.75 times/day vs. 3.15 times/day, p = 0.001). In addition, the median snacking frequency was 6 times higher in subjects with reactive hypoglycemia compared to those without it (0.9 times/day vs. 0.15 times/day, p < 0.001). In conclusion, in obese/overweight males without diabetes, subclinical reactive hypoglycemia is significantly associated with higher eating/snacking frequencies.

Lower Glucose Effectiveness Is Associated with Subclinical Reactive Hypoglycemia, Snacking Habits, and Obesity

“…Evaluation and management of hypoglycemia are recommended only in patients in whom Whipple’s triad—symptoms consistent with hypoglycemia, a low plasma glucose concentration, and resolution of the symptom(s) after the plasma glucose level is elevated—is documented [ 14 ]. In our recent study, half of the non-diabetic obese/overweight subjects exhibited minimal glucose levels of less than 70 mg/dL (3.9 mmol/L) within 24 h after OGTT, without notable hypoglycemic symptoms except hunger [ 5 ]. However, without Whipple’s triad (thus, subclinical), the glucose dip after a glycemic load was significantly associated with a higher eating/snacking frequency, suggesting that glucose levels that are in the hypoglycemic range, but above the threshold of neurogenic symptoms, induce appetite mostly without the patient’s awareness.…”

“…This indicates that an increase in glucose effectiveness could play a crucial role in the establishment of symptomatic hypoglycemia, especially when gastric retention is reduced. Since SRH is significantly correlated with higher eating/snacking frequencies [ 5 ], a higher eating frequency in subjects with higher SgIo can be regarded as an innate protective mechanism to maintain normal glucose levels and to prevent symptomatic hypoglycemia.…”

“…(3) Since the present study only showed associations, it is not possible to determine causality or the direction of causality from the results themselves. In the literature, it is reported that mild hypoglycemia, the glucose levels of which are higher than the threshold of symptomatic autonomic activation [ 4 ] but sufficiently lower than that of appetite activation [ 17 ], could lead to an increased frequency of snacking, either consciously with hunger or subconsciously [ 5 ]. Ingesting sugary snacks could lead to postprandial hyperglycemia followed by hypoglycemia with an excess of insulin action, especially in people with lower glucose effectiveness [ 12 ].…”

“…Using the hyperinsulinemic glucose clamp, activation of autonomic symptoms such as palpitations, tremors, and sweating develops at a plasma glucose concentration of approximately 58 mg/dL (3.2 mmol/L) [ 4 ]. Recently, we have examined diurnal glycemic patterns using continuous glucose monitoring (CGM) in obese or overweight subjects without diabetes mellitus, and we reported that more than half of the participants exhibited low glucose levels (<70 mg/dL (3.9 mmol/L)) after a 75 g glucose load, which did not provoke typical adrenergic symptoms of hypoglycemia [ 5 ]. Nonetheless, the snacking frequency of the participants with subclinical (asymptomatic except hunger) reactive hypoglycemia (SRH) was significantly higher than that of the participants without SRH [ 5 ], indicating that glucose levels that are lower than the lower limit of the normal range (70 mg/dL (3.9 mmol/L)), but higher than the hypoglycemic threshold for activation of autonomic symptoms (approximately 58 mg/dL (3.2 mmol/L)), still induce appetite and lead to an increased frequency of snacking in daily life.…”

“…Although the specific causes have not been fully determined, too much insulin in the bloodstream at the incorrect time is thought to be involved in symptomatic reactive hypoglycemia. However, in our previous study, the associations between SRH and insulin-related indices, such as homeostatic model assessment (HOMA)-β, HOMA-R, Matsuda index, disposition index, or insulinogenic index, were minor [ 5 ], suggesting that a mechanism other than delayed hyperinsulinemia might be involved in SRH.…”