Rapid intravenous sodium acetoacetate infusion in man. Metabolic and kinetic responses.

The metabolic and kinetic responses to rapidly intravenously administered sodium acetoacetate (1.0 mmol/kg body wt) was studied after an overnight fast in 12 male and female adults weighing between 88 and 215% of average body weight. Blood was obtained before, during, and after the infusion for determination of circulating concentrations of immunoreactive insulin, glucose, acetoacetate, beta-hydroxybutyrate and free fatty acids. In three obese subjects the studies were repeated after 3 and 24 days of total starvation. After the overnight fast acetoacetate rose rapidly reaching a peak concentration at the end of the infusion; beta-hydroxybutyrate concentrations also increased rapidly and exceeded those of acetoacetate 10 min postinfusion. Total ketone body concentration at the end of the infusion period was comparable to that found after prolonged starvation. After the initial mixing period, acetoacetate, beta-hydroxybutyrate and total ketone bodies rapidly declined in a parallel manner. There were no obvious differences between the subjects with regard to their blood concentrations of ketone bodies. The mean plasma free fatty acid concentration decreased significantly during the 20th to 90th min postinfusion period; for example the control concentration of 0.61 mmol/liter fell to 0.43 mmol/liter at 60 min. In the three obese subjects studied repeatedly, fasting plasma free fatty acids decreased with acetoacetate infusion from 0.92 to 0.46 mmol/liter after the 3 day fast and from 1.49 to 0.71 mmol/liter after the 24 day fast. Acetoacetate infusion caused no changes in blood glucose concentration after an overnight fast. However, in the three obese subjects restudied after 3- and 24-day fasts blood glucose decreased, respectively, from 3.49 to 3.22 mmol/liter and from 4.07 to 3.49 mmol/liter. The mean serum insulin concentration in all subjects significantly increased from 21 to 46 muU/ml at the completion of the infusion and rapidly declined. In the three obese subjects restudied after 3- and 24-day fasts an approximate two-fold increase of serum insulin was observed after each acetoacetate infusion. The mean fractional utilization rate of exogenously derived ketone bodies for all 12 subjects after an overnight fast was 2.9% min(-1). In the three obese subjects studied after an overnight, 3 and 24 day fast the mean fractional utilization rates were 2.1%, 1.5%, and 0.6% min(-1), respectively. Ketone body volumes of distribution in the overnight fasted subjected varied from about 18% to 31% of body wt, suggesting that ketone bodies are not homogenously distributed in the body water. In the three obese subjects restudied after 3- and 24-day fasts volumes of distribution remained approximately constant. When total ketone body concentrations in the blood were below 2.0 mmol/liter, there was a linear relationship between ketone body utilization rates and ketone body concentrations; no correlation was found when blood concentrations were higher.

Salvage of extremities with ischemic necrosis in diabetic patients by infrapopliteal arterial bypass.

Initial and long-term limb salvage can be achieved by infrapopliteal bypass in diabetic patients with ischemic necrosis of the distal extremity. Mortality is low in all groups, and mortality of subsequent amputation apparently is not affected by the previous bypass. An adequate arteriogram and consideration of distal bypass are frequently indicated in the diabetic patients in whom ischemic necrosis is present. Limb salvage may be feasible even in those diabetic patients in whom popliteal artery is not patent on preoperative arteriogram by bypasses to anterior tibial, posterior tibial, or peroneal artery.

Glipizide: an overview.

This is a brief summary of the extensive clinical experience with glipizide in the treatment of noninsulin-dependent diabetes mellitus. The data demonstrate that this agent, one of the newest oral hypoglycemics, is an effective and safe compound with unique properties. Among its other qualities, it has been shown (1) to stimulate insulin action through extrapancreatic effects that affect insulin-receptor binding and enhance tissue responsiveness to insulin; (2) to favorably influence the principal pathophysiologic abnormalities, defective secretory dynamics, and target-cell resistance to insulin observed in noninsulin-dependent diabetes; (3) to improve control of blood glucose, and when used in conjunction with insulin, to achieve glycemic control with reductions in insulin dosage; (4) to lower the level of plasma glucose and to maintain this effect despite a short half-life; (5) to stimulate insulin secretion following its oral administration; (6) to be more effective than tolbutamide in elderly patients with long-standing diabetes; and (7) to be well tolerated with few side effects. The occurrence of hypoglycemia with its use is uncommon and can be avoided by appropriate precautions and correct usage. These factors seem to recommend its use for the management of noninsulin-dependent diabetes mellitus.

Substrate, hormone, and temperature responses in males and females to a common breakfast.

To evaluate the response to a mixed meal we studied oral temperature, metabolite, and hormonal responses to a common American breakfast containing 11 kcal/kg body weight (carbohydrate 43%, fat 42%, and protein 15%) in 12 normal volunteers (6 males and 6 females). There was a significant rise in oral temperature during the postcibal period. This change in oral temperature did not depend upon food consumption in males but was meal-dependent in females. Food ingestion caused increases in the peripheral circulating concentrations of glucose, lactate, pyruvate, and amino acids and reciprocal decreases in the concentrations of free fatty acids, glycerol, and urea nitrogen. Acetoacetate and beta-hydroxybutyrate decreased during the postcibal period but the changes were not statistically significant. Although peripheral venous serum insulin and plasma glucagon concentrations were indistinguishable between the sexes, males had higher concentrations of plasma triglycerides, plasma amino acids, and serum urea nitrogen. Peripheral venous plasma somatostatin and secretin remained unchanged, but pancreatic polypeptide hormone showed a large biphasic response to the meal. After breakfast the blood glucose concentration tended to be greater in males than in females and this difference was significant at 60 and 120 min postcibal. Furthermore, every female had a 120 min postcibal glucose concentration that was lower than her basal fasting glucose concentration. This suggests that postcibal glucose concentrations should be related to gender in making the diagnosis of carbohydrate intolerance or reactive hypoglycemia.

Human splanchnic metabolism during diabetic ketoacidosis.

Splanchnic exchange rates of glucose, acetoacetate, beta-hydroxybutyrate, lactate, pyruvate, glycerol, alanine, glutamine, glutamate, free fatty acids, and triglycerides were measured in eight patients during moderate to severe diabetic ketoacidosis. Their arterial glucose concentration was 20.68 (9.80-52.79) mumole/liter and tic glucose release was 0.77 (0.09-2.44) mmole/min. Gluconeogenesis accounted for about one-half of net splanchnic glucose release, assuming quantitative conversion of net splanchnic extracted lactate, pyruvate, glycerol, alanine, and alpha-ketoglutarate equivalents to glucose. Net splanchnic free fatty acid extraction was 0.24 (0.09-0.52) mmole/min. There was a positive correlation between free fatty acid uptake and ketone-body release. Net splanchnic acetoacetate release was 0.50 (0.05-0.92) mmole/min and beta-hydroxybutyrate release was 0.35 (-0.16 to 0.84) mmole/min. Total ketone-body release was 0.84 (0.37-1.61) mmole/min. The wide ranges of net splanchnic glucose and ketone-body production rates show the heterogeneous characteristics of the diabetic patient in ketoacidosis. It is concluded that the hyperglycemia and hyperketonemia of diabetic ketoacidosis is due to the lack of reciprocity among rates of hepatic glycogenlysis, gluconeogenesis, and ketogenesis resulting in inappropriate net splanchnic release of glucose and ketone bodies.

Femorotibial bypass in the diabetic patient for salvage of the ischemic lower extremity.

Severe ischemia of the lower extremity in diabetic patients without runoff in the popliteal artery should not deter an aggressive diagnostic and therapeutic approach. Femorotibial or femoroperoneal bypass can effect limb salvage and avoid primary amputation if distal small vessel patency can be demonstrated by arteriography.

Long-term results of femoroinfrapopliteal bypass in diabetic patients with severe ischemia of the lower extremity.

In patients with severe lower extremity ischemia (ischemic necrosis or pain at rest associated with physical findings of peripheral arterial insufficiency), diabetes mellitus should not deter thorough arteriography and consideration of arterial reconstruction. Infrapopliteal bypass can produce prolonged limb salvage in diabetic patients in lieu of primary amputation.

Control of vascular disease in patients with diabetes mellitus.

To achieve the optimal management program for the diabetic vasculopathic patient, a multidisciplinary approach incorporating the necessary major elements is required. The endocrinologist is essential in tight metabolic control of blood sugars and diet modifications. The podiatrist is indispensable in the early detection of foot ulcerations and preventive care. Visiting nurses function as a vital component in outpatient wound assessment and daily care. With this approach, the vascular surgeon is ensured of the most favorable outcome with conservative measures.

Optimum insulin use in older diabetics.

Insulin treatment of the elderly diabetic patient differs little from that advocated for the younger adult population, although in general the standards for blood glucose control are raised in the elderly by 10 mg/dl per decade, starting at age 60. These higher standards are recommended primarily to minimize the risk of hypoglycemia. Within these limits, control of diabetes will retain the older patient's vigor, alertness, and health. Insulin therapy can also be flexible to suit the requirements of individual patients. For those with residual endogenous insulin secretory capacity, a single dose of modified insulin may suffice. For those with greater insulin needs, split-dose schedules supplemented with regular insulin can be instituted, depending on the severity of the deficiency. Most important, the program for the aging diabetic should be simple and practical, and family members or community health personnel can be enlisted to assist in diabetic care and monitoring.

Managed psychiatric care: a suburban medical department activity model.

Munson Army Community Hospital has successfully realized substantial cost savings by instituting psychiatric managed care. The development of an external partnership with a civilian psychiatric facility is a unique aspect of the psychiatric managed care initiative and has resulted in most of the savings. We staff this partnership hospital with one-half full-time-equivalent psychiatrist. Other psychiatric managed care program elements include: (1) using CHAMPUS "recapture" funds to hire additional personnel; (2) maximizing personnel utilization by combining mental health staff from the social work and psychiatry services; (3) working closely with the community to identify local mental health needs; (4) offering additional therapeutic modalities; and (5) reducing rehospitalization rates through improved discharge planning. We reduced our financial-year first quarter costs by 76% from 1993 to 1995. We attributed much of these savings to reduced residential treatment admissions. Although the total number of outpatient visits increased, Munson's psychiatric services reduced outpatient costs by increasing clinic access. We have used the Gateway to Care program to prepare for the initiation of Tri-Care in our region.

Foot disorders in diabetics. Source of serious morbidity.

In the diabetic patient, the foot is particularly vulnerable to disorders resulting from vascular insufficiency, neuropathy, and infection. Without proper treatment, these disorders can lead to serious disability or amputation. Hyperglycemia, smoking, hypertension, and obesity contribute to the development of foot lesions. Early recognition of pedal lesions allows institution of measures (eg, special shoes, fitted inserts) that reduce risks of serious disorders. Patient education regarding foot care also plays an important role in prevention and management of disease. Aggressive treatment of infection and local care of lesions prevent extension of disease to adjacent areas. In cases of established infection or occlusive vascular disease amenable to bypass procedures, surgical intervention is frequently necessary. When amputation is required, rehabilitation professionals can assist the physician in patient education regarding personal care and readjustment.

Managing insulin-dependent diabetic patients.

About 95% of insulin-dependent diabetics can be managed satisfactorily with one or a combination of the follwoing insulin preparations: single-peak U-100 beef-pork NPH, Lente, and Regular. Complications of insulin therapy are commonly attributable to poor regulation of insulin dosage, irregular or excessive food intake, or unusual physical activity. One form of hyperglycemia is induced by insulin. Generalized allergic reactions to insulin sometimes require desensitization. Insulin-resistant patients are treated with a glucocorticoid.

Surgery in the diabetic patient.

The condition of the diabetic patient--reduced availability of insulin and an enhanced reaction to the counter-regulatory hormones elicited during major surgical stress--necessitates the administration of insulin to prevent hyperglycemia, fat mobilization and ketosis, and wastage of body protein. Crucial items in management are the maintenance of fluid and electrolyte balance and prevention of infection. The recognition of diabetes-related complications, particularly those involving the cardiovascular system, will forestall problems related to these conditions during the perioperative period. For both type I and type II diabetes the use of intravenous glucose-insulin infusion provides a safe and effective method for management during surgery. During surgery, monitoring of blood glucose concentration determines the adequacy of insulin dosage, which can be adjusted to maintain glucose concentrations within the desired range. With this system, the hazards of hyperglycemia are avoided and significant hypoglycemia is rarely encountered. For elective operations as well as for emergency surgical procedures, this method can provide a simple and effective regimen for use in most hospitals.