Hypoglycemia compensation mechanisms in dry fasting

Abstract

Background: Dry fasting (DF) presents three primary risks: hypovolemia, hypertonicity, and hypoglycemia. The first two have been shown to be effectively compensated, and the respective mechanisms have been studied. The behavior of glucose has only been roughly described, while the hypoglycemia compensation mechanisms remain unexplored.

Objectives: Studying the glucose behavior, the hypoglycemia compensation mechanisms, and the insulin resistance during DF.

Methods: Following parameters were daily monitored in ten participants undergoing a 5-day DF: Weight, body circumferences, glucose, creatinine clearance (GFR), insulin, HOMA-IR, acetoacetate in 24-h urine, glucagon, growth hormone (GH), IGF-1, TSH, T₄, T₃, leptin, cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides, and the enzymes LDH, CPK, SGPT, SGOT, and γGT.

Results: Weight, body circumferences, TSH, T₃, and T₄ decreased to minima on Day 5; insulin and HOMA-IR decreased, reaching minima on Day 4; GH, cholesterol, LDL-C, and acetoacetate increased to maxima on Day 5; Glucagon, IGF-1, and GFR increased, presenting maxima on Day 4; Glucose, leptin, and triglycerides exhibited biphasic profiles with minima on Days 3, 3, and 2, respectively; HDL-C, LDH, CPK, SGPT, SGOT, and γGT showed minimal or non-significant changes.

Conclusion: A comprehensive description of glucose behavior and the hypoglycemia compensation mechanisms in DF were presented. DF decreased insulin resistance, likely by improving the blood - cell interphase, and enhanced GFR. The increase in LDL-C, tissue-protecting IGF-1, and late increase in leptin and triglycerides were unexpected. The results may inform the development of novel therapeutic approaches for obesity, metabolic syndrome, type-2-diabetes, non-alcoholic fatty liver disease, adiposity, and atheromatous diseases.

Keywords: Blood - Cell interphase; GFR increase; IGF-1 increase in dry fasting; Insulin resistance decrease; Late leptin increase in dry fasting; Selective LDL increase in dry fasting; Tissue protection.

Fig. 1

Hypoglycemia compensation and GFR (creatinine clearance) during dry fasting (DF). A glucose in mg/dl (1 mg/dl = 0.056 mmol/L); B creatinine clearance in ml/min. The graphs present minimum, maximum, and mean values (with standard error bars) in absolute scales, before and during DF.

Fig. 2

Hypoglycemia defense and insulin resistance during dry fasting (DF). A serum insulin in μU/ml; and B HOMA-IR (homeostasis model assessment of insulin resistance) in μU∗mol/L². The graphs present mean values (with standard error bars) in absolute scales, before and during DF.

Fig. 3

Hypoglycemia defense and tissue protection during dry fasting (DF). A acetoacetate in 24-h urine (mg/24-h) and plasma glucagon [pg/ml (pg/ml = 0.287 pmol/L)]; and B serum GH [ng/ml (ng/ml = 1.18 nmol/L)], and IGF-1 [ng/ml (ng/ml = 0.13 nmol/L)]; 24-h U., 24-h urine; GH, growth hormone; IGF-1, insulin-like growth factor-1.The graphs present mean values (with standard error bars) in absolute scales, before and during DF.

Fig. 4

Hypoglycemia defense during dry fasting (DF). A serum TSH (mIU/l) and T₄ [μg/dl, (μg/dl = 12.87 nmol/l)]; B T₃ [μg/l, (μg/l = 1.54 nmol/l)], and leptin [ng/ml, (ng/ml = 62.5 pmol/l)]. The graphs present mean values (with standard error bars) in absolute scales, before and during DF.

Fig. 5

Hypoglycemia defense during dry fasting (DF). A Serum concentration of total cholesterol and LDL-C [both in mg/dl (mg/dl = 0.0259 mmol/L)] and LDL; and B HDL-C [mg/dl (mg/dl = 0.0259 mmol/L)] and triglycerides (mg/dl). LDL-C, low-density lipoprotein–cholesterol; HDL-C, high-density lipoprotein–cholesterol. The graphs present mean values (with standard error bars) in absolute scales, before and during DF.

Fig. 6

Tissue protection during dry fasting (DF). A Serum LDH, CPK, and SGPT (all in U/l); B Serum γGT and SGOT (both in U/l). LDH, lactate dehydrogenase; CPK, creatine phosphokinase; SGPT, glutamate pyruvate transaminase; γGT, gamma-glutamyl transferase; SGOT, glutamate oxaloacetate transaminase; The graphs present mean values (with standard error bars) in absolute scales, before and during DF. For SGPT, standard error bars were too small to be visible.