HYPOGLYCEMIA : Pathophysiology and Treatment - 05/09/11
Résumé |
In the adult patient with type 1 or type 2 diabetes, optimal control of glucose concentrations to near the upper end of the normal range will prevent long-term complications.1, 42, 83, 89, 101Clearly, insulin replacement schemes are unlike normal endogenous insulin secretion, leaving the clinician with the dilemma of how to obtain normoglycemia. Although normoglycemia has a critical role in the prevention of chronic complications, patients with diabetes must constantly walk a tight rope, balancing high and low glucose concentrations. Beyond the question of how to pulse insulin physiologically to cover carbohydrate intake acutely, clinicians are challenged by the lack of accurate background insulin replacement. Declining insulin concentrations that normally occur during postprandial periods are difficult to generate outside of insulin pump therapy and, even then, ramping the insulin infusion rate up and down occurs in the absence of feedback on changes in glucose concentration. In addition to problems with insulin replacement, lack of education in regards to counting the grams of carbohydrate accurately sets the stage for excess insulin administration. Factors under the patient's control and beyond the patient's control are responsible for the frequency of hypoglycemia that is the focus of this article.
Early in the development of intensive diabetes treatment strategies, health care providers and investigators noted a diminution in the symptoms of hypoglycemia as patients approached near normoglycemia.4, 5, 12 Symptoms were reduced, and the glucose concentration required to trigger them fell also. Amiel and colleagues4 demonstrated an associated failure in epinephrine secretion that made patients vulnerable to what is now known as hypoglycemia unawareness.56 Even a single episode of hypoglycemia is sufficient to partially attenuate epinephrine secretion and the symptoms associated with hypoglycemia63; however, generally, and certainly in clinical practice, more than one episode leads to autonomic failure.35
In the fasted subject, portal vein insulin concentrations determine the endogenous rate of hepatic glucose production.28 One of the fundamental roles of insulin is to reduce the rate of gluconeogenesis and glycogenolysis.74 Of the glucose produced from the liver, 55% is consumed by the brain, and the remainder by skeletal muscle and the renal medulla.85 Of these three tissues, the brain has an absolute dependence on glucose and is incapable of storing more than a few minutes of glucose as glycogen.85 When the glucose supply is interrupted, the classic symptoms of hypoglycemia stem from neuroglycopenia, which, in turn, triggers many of the hormonal responses (counterregulation).92 Unfortunately, the counterregulatory responses are often insufficient to stimulate endogenous glucose production to offset the brain's fuel shortage, and a critical threshold is passed beyond which normal brain function is interrupted. For this reason, in more than 1 million patients with type 1 diabetes, hypoglycemia is a common limiting factor preventing them from achieving the tight metabolic control that is necessary to prevent complications. The patient with type 2 diabetes is also at some risk, but the mechanisms leading to low glucose concentrations diverge somewhat in the two forms of the disease. In either case, the net result is that, during critical deficits of glucose provision to the brain, the patient loses consciousness or experiences a seizure. Understanding brain glucose handling is a cardinal requirement to understanding the intricacies of the pathophysiology and treatment of hypoglycemia.
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| Address reprint requests to Patrick J. Boyle, MD, Department of Internal Medicine-5ACC, Division of Endocrinology, University of New Mexico Health Sciences Center, 2211 Lomas Boulevard, NE, Albuquerque, NM 87122–5217, e-mail: pboyle@salud.unm.edu This work was supported by grant K24 NS02097-02 and by a grant from General Clinical Research Program, DRR, National Institutes of Health 5 M01 RR00997-25, Bethesda, Maryland. |
Vol 29 - N° 4
P. 725-743 - décembre 2000 Retour au numéro
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- SICK-DAY MANAGEMENT IN TYPE 1 DIABETES
- Lori Laffel
- HOSPITAL MANAGEMENT OF DIABETES
- Claresa S. Levetan, Michelle Fischmann Magee
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