Severe Hyperglycemia: Effects of Rehydration on Endocrine Derangements and Blood Glucose Concentration

Abstract

Diabetic ketoacidosis is associated with an excess secretion of counterregulatory hormones. The effect of rehydration on these endocrine derangements before insulin administration is unknown. Therefore, we measured the effect of rehydration with hypoosmolal fluid (220 mosmol/kg) on blood glucose (BG), immunoreactive insulin (IRI), immunoreactive C-peptide (IRCP), immunoreactive glucagon (IRG), human pancreatic polypeptide (hPP), growth hormone (GH), prolactin (PRL), cortisol, aldosterone, renin (PRC), epinephrine, norepinepnrine, and parathyroid hormone (PTH) in ketoacidotic diabetic patients [pH 7.03 ± 0.05 (SEM); n = 8] and in patients (n = 2) with nonketotic hyperglycemia (BG, 29.8 mmol/L and 46.8 mmol/L). The cumulative net fluid balance after rehydration was 4364 ± 690 ml. Basal insulin was inappropriately low, and IRCP was below the normal range (1.5 ± 0.5 ng/ml). Serum osmolality fell during hypoosmolal rehydration (n = 9) from 335 ± 11 to 315 ± 9 mosmol/kg. Rehydration with hypoosmolal fluid with bicarbonate added at a pH of less than 7.2 induced a fall in BG ranging from 6.1 mmol/L to 22.6 mmol/L, or of 16.7% to 79.8% of the initial BG level, as well as a decrease in plasma lactate and urinary glucose. These effects were paralleled by a decrease in IRG, cortisol, epinephrine, norepinephrine, aldosterone, and PRC. No fall in BG was seen in one patient whose dehydrated state was maintained by infusion of isotonic saline. Low dose insulin treatment was initiated in all patients immediately when no further fall in blood glucose levels was achieved. We conclude that rehydration improves the metabolic situation in severe diabetic hyperglycemia and ketoacidosis by reducing (a) the availability of counterregulatory hormones and (b) peripheral insulin resistance on a cellular level. Thus, proper rehydration will support the beneficial action of simultaneous low dose insulin treatment in patients with severe hyperglycemia.

The role of ?diabetogenic? hormones on carbohydrate and lipid metabolism following oral glucose loading in insulin dependent diabetics: Effects of acute hormone administration

“…This study demonstrates that in insulin-dependent diabetics plasma concentrations of glucagon, cortisol, and growth hormone elevated acutely to the range usually observed in severe derangements of diabetic control [8] do not materially affect glucose tolerance as judged by the amount of insulin required to utilize an oral glucose load. In contrast, increased amounts of insulin were required in the presence of elevated adrenaline concentrations, which thus seem to play a most important role in the decrease of insulin action on carbohydrate metabolism.…”

“…Methods and standards used for the estimation of immunoreactive glucagon (IRG), C-peptide, growth hormone, cortisol and of insulin binding capacity have been described previously [8,23,24]. Adrenaline and noradrenaline were estimated radio-enzymatically [25].…”

“…The observations in severe derangements of diabetic control include elevated plasma levels of glucagon [3], cortisol [4], growth hormone [5,6], and catecholamines [7,8]. The hierachy of their pathogenetic significance, however, remains to be established.…”

Management of Hyperglycemic Crises in Patients With Diabetes

“…Indeed, in the setting of fixed levels of insulin, infusing mixtures of stress hormones to reach high physiological/severe stress levels, can precipitate marked increases in lipolysis and ketogenesis (44,67). Spontaneous DKA is characterized by simultaneous elevations of multiple insulin-antagonizing (counterregulatory) hormones (6,(88)(89)(90) in the face of reduced insulin, which brings about the altered metabolic profiles seen in DKA. Thus, DKA is analogous to a fasting state, where ketosis is accompanied by elevations of counterregulatory hormones and reduction of insulin but to a lesser degree than in DKA.…”

Effect of Hexagonal Water on Serum Glucose Level and Lipid Profile in Streptozotocin-Induced Diabetic Rats

“…Dehydration in ketoacidotic and nonketoacidotic hyperglycemia is accompanied by elevation in counter regulatory hormones such as catecholamines, cortisol, and growth hormone, which increase serum glucose level (11)(12)(13). Rehydration of hyperglycemic patient can reduce insulin resistance and decrease releasing of counter regulatory hormones, thus, it can facilitate glucose transmission to the cells (14).…”