Hypoglycemia

The blood sugar level is in dynamic equilibrium, ever changing because it is dependent upon the varying balance of supply and demand. The supply of glucose comes from three main sources: absorption of digested polysaccharides and monosaccharides from the intestinal tract, liver glycogen and, lastly, other carbon fragments derived from the glucogenic amino acids, body fat and fractions remaining from partially metabolized glucose. The first and last sources probably contribute the greater share.The crucial step in glucose metabolism appears to be the phosphorylation of glucose, a reaction catabolized by the enzyme hexokinase: Glucose + adenosine triphosphate

glucose-6-phosphate + adenosine diphosphate The Coris have recently shown that this reaction is specifically inhibited by a substance obtained from the anterior lobe of the pituitary gland. This inhibiting effect is blocked by insulin and prolonged by certain adrenocortical steroids.Certain mechanisms may be suggested as operating to produce the hypoglycemia observed in various clinical disorders. Decreased absorption of glucose from the intestinal tract due to starvation or to disease of the small intestine may result in hypoglycemia, obviously because of a lowered supply. In myxedema, low blood sugar levels develop apparently because of marked slowing of the rate of passage of glucose through the intestinal mucosa. Liver glycogen is reduced not only by inadequate exogenous supply (starvation) but also from endogenous failure, as in Addison's disease; and finally by excessive utilization, as with long continued, strenuous physical effort. When the liver has been largely destroyed there may be insufficient formation and storage of glycogen. Von Gierke's disease appears to occupy a somewhat special position wherein the glycogen content of the liver is above normal but cannot be made available as glucose, hence the blood sugar values fall.In hyperinsulinism (whether due to insulin overdosage, or to endogenous overproduction by islet tumors or to other causes), the blood sugar level falls apparently because the inhibiting pituitary effect on the hexokinase reaction is blocked, at least in part, by excess insulin and the reaction is therefore accelerated. Hypoglycemia occurring in adrenal cortical insufficiency appears to be due in part to a disturbance in gluconeogenesis from certain of the amino acids.The symptomatology of hypoglycemia is diverse. In its mildest form the complaints are vague: weakness and a disinclination for physical and mental exertion. More severe episodes are characterized by congestion or pallor of the face, sweating, palpitations, hunger, thirst, tremors and anxiety. These may be followed by difficulties in speech and uncoordinated movements and finally by convulsions, paralysis and coma. The pattern of symptoms may be very different in different individuals but the characteristic train of symptoms in any one individual is apt to be recurrent.Chronic hypoglycemia of severe degree may result in damage to the central nervous system, the changes observed resembling those seen in anoxia. Edema, chromatolysis and perivascular hemorrhage, at first reversible, occur. Later there is death of nerve cells, replacement by astrocytes and loss of myelin, constituting permanent damage.Acute hypoglycemic shock is treated by intravenous administration of glucose. The response is usually prompt and dramatic. In chronic cases with irreversible damage to the central nervous system, however, the effects may be slow and disappointing.The aim of treatment in chronic, functional hypoglycemia is to supply a steady, slowly available dietary source of glucose. This is usually accomplished by small but frequent feedings of carbohydrate-rich foods. High protein diets, which cause a less marked post-prandial rise and fall in blood sugar, may be advantageous in some cases.Hypoglycemia due to islet cell adenoma or hypertrophy is amenable to surgical treatment. To avoid futile explorations, however, it is necessary to rule out “functional” hypoglycemia occurring in individuals who, for obscure reasons, have an unusually pronounced post-prandial fall in blood sugar, not due to islet tumors. To make this important differential diagnosis, too much reliance should not be placed on the glucose tolerance test; if employed, it should be borne in mind that organic hypoglycemia appears on fasting whereas the functional types show low blood sugar levels most frequently three to five hours after ingestion of glucose.The following triad is suggested as indicating exploration: (1) a repeated individual symptom pattern coming on in the fasting state; (2) a blood sugar concentration below 50 mg. per cent during an attack, or after a prolonged fast; (3) in earlier stages, relief of an acute episode by administration of glucose. When these criteria are fulfilled, careful search by the surgeon, after mobilizing the pancreas, will almost always be successful.     

Hypoglycemia unawareness

Iatrogenic hypoglycemia is the limiting factor in the glycemic control of diabetes. It causes recurrent symptomatic and sometimes, at least temporally, disabling episodes in most people with type 1 diabetes, as well as in many with advanced type 2 diabetes. Furthermore, iatrogenic hypoglycemia precludes maintenance of euglycemia during the lifetime of a person with diabetes and thus full realization of the well established benefits of glycemic control. In this article I discuss the clinical problem of hypoglycemia in diabetes from the perspective of pathophysiology. First, the syndromes of defective glucose counterregulation and hypoglycemia without warning symptoms (known as hypoglycemia unawareness) are described, followed by the unifying concept of Hypoglycemia-Associated Autonomie Failure (HAAF). The concept of hypoglycemia-associated autonomie failure in diabetes posits that recurrent antecedent hypoglycemia causes both defective glucose counterregulation and hypoglycemia unawareness and thus leads to a vicious cycle of recurrent hypoglycemia and further impairment of glucose counterregulation. The clinical relevance of this phenomenon is now well established, but the mechanisms and mediators remain largely unknown. The short-term avoidance of hypoglycemia reverses hypoglycemia unawareness in most affected patients. The ultimate goal of lifelong maintenance of euglycemia in patients with diabetes remains elusive because of the pharmacokinetic imperfections of all current glucose-lowering therapies and the resulting barrier of hypoglycemia. Nonetheless, it is now possible both to improve the control of glycemia and to reduce the frequency of hypoglycemia in many people with diabetes. These results can be accomplished by recognizing the problem of hypoglycemia applying the principles of aggressive glycemic therapy and reducing the risk factors of hypoglycemia in people with diabetes.     

Hypoglycemia.

Under physiologic conditions, glucose plays a critical role in providing energy to the central nervous system. A precipitous drop in the availability of this substrate results in dramatic symptoms that signal a medical emergency and warrant immediate therapy aimed at restoring plasma glucose to normal levels. A systemic approach to the differential diagnosis is useful in identifying the cause of hypoglycemia. Once established, a specific and/or definitive intervention that addresses that underlying problem can be implemented. In most cases, this systemic approach to diagnosis and therapy is rewarded with a good outcome for the patient.     

Hypoglycemia in adults

Hypoglycemia is a clinical and biological syndrome, caused by an abnormal decrease in plasma glucose levels to below 0.55 g/l (3.0 mmol/l). Hypoglycemia is responsible for non-specific signs and symptoms which should be noted in a particular pathological context, and for secretion of counterregulatory hormones (mainly glucagon and catecholamines). Difficulty in identifying the etiology is variable, based upon history and physical examination, and hormonal investigations or imaging procedures, according to the results. Drug-related hypoglycemia is the most frequent observed cause (mainly in insulin-treated diabetic patients, but many drugs may be involved), followed par toxicity (alcohol mainly). Tumor-induced hypoglycemia is secondary to inappropriate insulin secretion by a beta-cell pancreatic tumor (insulinoma), and, rarely to an extrapancreatic mesenchymal large tumor secreting IGF-II. Hypoglycemia is present in other diseases, such as hormonal deficiencies, hepatic, or renal failure, or acute cardiac insufficiency. Multifactorial hypoglycemia seems to be underdiagnosed, mainly in hospitalized, underfed older patients with severe disease or sepsis. Autoimmune hypoglycemia is rare, due to insulin or insulin-receptor autoantibodies. Reactive hypoglycemia is observed after gastrectomy, but true primitive hypoglycemia appears to be rare, with false excess diagnosis in the majority of the cases.     

Statistical Hypoglycemia Prediction

Background

Hypoglycemia presents a significant risk for patients with insulin-dependent diabetes mellitus. We propose a predictive hypoglycemia detection algorithm that uses continuous glucose monitor (CGM) data with explicit certainty measures to enable early corrective action.

Method

The algorithm uses multiple statistical linear predictions with regression windows between 5 and 75 minutes and prediction horizons of 0 to 20 minutes. The regressions provide standard deviations, which are mapped to predictive error distributions using their averaged statistical correlation. These error distributions give confidence levels that the CGM reading will drop below a hypoglycemic threshold. An alarm is generated if the resultant probability of hypoglycemia from our predictions rises above an appropriate, user-settable value. This level trades off the positive predictive value against lead time and missed events.

Results

The algorithm was evaluated using data from 26 inpatient admissions of Navigator® 1-minute readings obtained as part of a DirecNet study. CGM readings were postprocessed to remove dropouts and calibrate against finger stick measurements. With a confidence threshold set to provide alarms that correspond to hypoglycemic events 60% of the time, our results were (1) a 23-minute mean lead time, (2) false positives averaging a lowest blood glucose value of 97 mg/dl, and (3) no missed hypoglycemic events, as defined by CGM readings. Using linearly interpolated FreeStyle capillary glucose readings to define hypoglycemic events provided (1) the lead time was 17 minutes, (2) the lowest mean glucose with false alarms was 100 mg/dl, and (3) no hypoglycemic events were missed.

Conclusion

Statistical linear prediction gives significant lead time before hypoglycemic events with an explicit, tunable trade-off between longer lead times and fewer missed events versus fewer false alarms.     

Hypoglycemia in infants

Because the infant's brain is to a large extent dependent on glucose utilization, hypoglycemia of infants can have grave effects on brain function, and it is important to diagnose it and, when possible, treat it promptly. Causes of hypoglycemia in infants are (a) excess insulin secretion, (b) factitious hyperinsulinemia, (c) GH or ACTH deficiency, (d) primary glucocorticoid deficiency, (e) defects of the enzymes involved in hepatic glucose production, or (f) defects in hepatic fatty acid oxidation.     

Severe Hypoglycemia in Adults

Reviews in Endocrine and Metabolic Disorders -     

Technology to Reduce Hypoglycemia

Hypoglycemia is a major barrier toward achieving glycemic targets and is associated with significant morbidity (both psychological and physical) and mortality. This article reviews technological strategies, from simple to more advanced technologies, which may help prevent or mitigate exposure to hypoglycemia. More efficient insulin delivery systems, bolus advisor calculators, data downloads providing information on glucose trends, continuous glucose monitoring with alarms warning of hypoglycemia, predictive algorithms, and finally closed loop insulin delivery systems are reviewed. The building blocks to correct use and interpretation of this range of available technology require patient education and appropriate patient selection.     

老年糖尿病患者的低血糖症

老年糖尿病(DM)是老年人内分泌代谢疾病中最常见的病种,它包括60岁以后发生的DM或者60岁以前发病而延续到60岁以后的老年患者。老年DM绝大多数是2型,占90％～95％;1型DM也见于少部分老年人,这主要包括两部分人:一部分是年轻时患1型DM,治疗护理成功而存活到老年期;另一部分是老年期发     

Hypoglycemia following partial gastrectomy

Summary 1. One hundred and twenty-two patients were seen who had had a gastric resection for peptic ulcer.2. Fifty of these had an oral or intravenous glucose tolerance test, and the results were compared with those in controls and in patients with a peptic ulcer or gastroenterostomy. Hypoglycemia was not an immediate effect of the operation but was due to secondary changes in carbohydrate metabolism.3. The results of these investigations have been discussed in relation to previous findings in the literature. A possible relationship to a disorder of the adrenal cortex was considered. More direct evidence is required before such a relationship between post-gastrectomy hypoglycemia and the adrenal cortex can be justified.     

Hypoglycemia following pancreas transplantation

Mild symptoms of hypoglycemia in individuals with type 1 diabetes who have undergone pancreas transplantation are common, but biochemical evidence of hypoglycemia in these individuals often remains scant. Rarely, more overt cases with profound neuroglycopenic symptoms and documented hypoglycemia after transplantation have been described. Although the diagnosis of hypoglycemia in most cases of adrenergic symptoms alone, without documented hypoglycemia, remains questionable and likely not clinically significant, several potential etiologies have been identified in the more severe cases. This article reports a case with severe hypoglycemia after pancreas transplantation for type 1 diabetes, reviews several potential mechanisms underlying pancreas allograft-associated hypoglycemia, and discusses current treatment strategies for minimizing symptomatic hypoglycemia after transplant.