Catheter obstruction with continuous subcutaneous insulin infusion. Effect of insulin concentration.
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Adult↗
Biomedical subjects
I B Hirsch
Publications and source records attributed to I B Hirsch.
Intensive insulin therapy: Part I. Basic principles.
Intensive insulin therapy is a complete program of diabetes management. A multicomponent insulin regimen is just one element of this approach. Intensive insulin therapy does not necessarily strive for euglycemia, since patients require individualized glycemic goals. When prescribing insulin, the family physician should be familiar with several important pharmacokinetic issues. Insulin species, insulin absorption, injection site and timing of premeal insulin all affect glycemia. The relationship between diabetic complications and blood glucose control is also important. Although many previous studies have been flawed, evidence suggests that meticulous diabetes control decreases the risk of microvascular complications and neuropathy. Unfortunately, studies have shown no improvement in advanced retinopathy or advanced nephropathy with improved glycemic control. The major cost of improved glycemic control is an increased risk of hypoglycemia.
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Intensive insulin therapy: Part II. Multicomponent insulin regimens.
In patients with insulin-dependent diabetes mellitus, insulin is an absolute requirement for life. Once-daily insulin administration is not sufficient to maintain physiologic insulin delivery. Twice-daily delivery of a combination of intermediate-acting and regular insulin may be effective but may limit lifestyle flexibility. Other popular regimens include three daily injections (with a bedtime dose of intermediate-acting insulin) and use of a combination of ultralente and regular insulin. Continuous subcutaneous insulin infusion is another option for patients with insulin-dependent diabetes. In patients with noninsulin-dependent diabetes who require insulin, control can often be achieved with a single daily injection. Recently, the use of bedtime NPH or ultralente insulin has been emphasized for control of moderate hyperglycemia in these patients. For patients with severe hyperglycemia, insulin administration is similar to that for patients with insulin-dependent diabetes. The use of combination therapy with insulin and sulfonylurea for noninsulin-dependent diabetes is controversial.
Blood Glucose↗
Increased symptoms of hypoglycaemia in the standing position in insulin-dependent diabetes mellitus.
1. To test the hypothesis that patients with insulin-dependent diabetes mellitus perceive the symptoms of hypoglycaemia to a greater extent when they are in the standing position than when they are in the lying position, we assessed symptoms of hypoglycaemia, as well as heart rate and plasma noradrenaline and adrenaline concentrations, in both positions during hyperinsulinaemic glucose clamps on three occasions in seven patients. 2. Plasma glucose concentrations were clamped at 5.0 mmol/l (90 mg/dl) and 5.0 mmol/l on one occasion, at 5.0 mmol/l and 3.9 mmol/l (70 mg/dl) on another occasion, and at 5.0 mmol/l and 2.8 mmol/l (50 mg/dl) on yet another occasion. 3. During euglycaemia there was no effect of position on the symptom panels used to assess the symptomatic response to hypoglycaemia. However, at the plasma glucose concentration of 2.8 mmol/l, total (P less than 0.003) and neurogenic (P less than 0.005), but not neuroglycopenic, hypoglycaemic symptom scores were higher with the patients in the standing than in the lying position. Increments in total hypoglycaemic symptom scores, over those during the corresponding euglycaemic phase, were 5 +/- 2 in the lying position and 11 +/- 2 in the standing position (means +/- SEM, P less than 0.01). 4. Thus patients with insulin-dependent diabetes mellitus perceive symptoms of hypoglycaemia to a greater extent when they are in the standing position than when they are in the lying position because of enhanced neurogenic symptoms.
Adult↗
Perioperative management of surgical patients with diabetes mellitus.
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Ambulatory Surgical Procedures↗
Insulin and glucagon in prevention of hypoglycemia during exercise in humans.
To assess the roles of decrements in insulin and increments in glucagon in the prevention of hypoglycemia during moderate exercise (approximately 60% peak O2 consumption for 60 min), normal young men were studied during somatostatin infusions with insulin and glucagon infused to 1) hold insulin and glucagon levels constant, 2) decrease insulin, 3) increase glucagon, and 4) decrease insulin and increase glucagon during exercise. In contrast to a comparison study (saline infusion), when insulin and glucagon were held constant, glucose production did not increase and plasma glucose decreased from 5.5 +/- 0.2 to 3.4 +/- 0.2 mmol/l (P less than 0.001) initially during exercise. Notably, plasma glucose then plateaued and was 3.3 +/- 0.2 mmol/l at the end of exercise. This decrease was at most only delayed when either insulin was decreased or glucagon was increased independently. However, when insulin was decreased and glucagon was increased simultaneously, there was an initial increase in glucose production, and the glucose level was 4.5 +/- 0.2 mmol/l at 60 min, a value not different from that in the comparison study. Thus we conclude that both decrements in insulin and increments in glucagon play important roles in the prevention of hypoglycemia during exercise and do so by signaling increments in glucose production. However, since hypoglycemia did not develop during exercise when changes in insulin and glucagon were prevented, an additional counterregulatory factor, such as epinephrine, must be involved in the prevention of hypoglycemia during exercise, at least when the primary factors, insulin and glucagon, are inoperative.
3-Hydroxybutyric Acid↗
Catecholamines in prevention of hypoglycemia during exercise in humans.
To assess the role of catecholamines in the prevention of hypoglycemia during moderate exercise (approximately 60% peak O2 consumption for 60 min), normal humans were studied with combined alpha- and beta-adrenergic blockade and with adrenergic blockade while changes in insulin and glucagon were prevented with the islet clamp technique (somatostatin infusion with insulin and glucagon infused at fixed rates). The results were compared with those from an islet clamp alone study. In contrast to a comparison study (saline infusion), adrenergic blockade resulted in a small initial decrease in plasma glucose during exercise, from 5.0 +/- 0.2 to 4.4 +/- 0.2 mmol/l (P less than 0.01), but the level then plateaued. There was a substantial exercise-associated decrement in plasma glucose when insulin and glucagon were held constant, i.e., from 5.5 +/- 0.2 to 3.4 +/- 0.2 mmol/l (P less than 0.0001), but the level again plateaued. However, when insulin and glucagon were held constant and catecholamine actions were blocked simultaneously, progressive hypoglycemia, to 2.6 +/- 0.6 mmol/l (P less than 0.001), developed during exercise. Hypoglycemia was the result of an absent increase in glucose production and an exaggerated initial increase in glucose utilization. Thus we conclude that sympathochromaffin activation plays a minor role when insulin and glucagon are operative, but a catecholamine, probably epinephrine, becomes critical to the prevention of hypoglycemia during exercise when changes in insulin and glucagon do not occur.
3-Hydroxybutyric Acid↗
Higher glycemic thresholds for symptoms during beta-adrenergic blockade in IDDM.
We tested the hypotheses that nonselective beta-adrenergic blockade does not cause absolute hypoglycemia unawareness but shifts the glycemic thresholds for symptoms to lower plasma glucose concentrations and that neither neuroglycopenic symptoms nor cognitive impairments during hypoglycemia are altered by beta-adrenergic blockade. To do so, we applied the euglycemic and stepped hypoglycemic clamp techniques to patients with moderately controlled insulin-dependent diabetes mellitus (IDDM) in the absence (n = 8) and presence (n = 9) of the nonselective beta-adrenergic antagonist propranolol. Compared with the corresponding euglycemic clamps, total symptom scores first increased at the 4.4-mM plasma glucose step (a higher level than that of 2.8 mM in nondiabetic subjects studied previously) in the absence of propranolol. Beta-adrenergic blockade did not produce absolute hypoglycemia unawareness. Indeed, at the frankly hypoglycemic step of 2.8 mM, total symptom scores tended to be higher in the presence than in the absence of propranolol. This was largely the result of greater (P less than 0.01) perception of diaphoresis. However, symptom scores did not increase until the 3.3-mM plasma glucose step during beta-adrenergic blockade. The perception of hunger, and perhaps that of tremulousness, was reduced by propranolol at the higher glucose steps. Neuroglycopenic symptoms were not reduced by propranolol. The cognitive function of memory, but not that of attention, was impaired, also starting at the 4.4-mM glucose step. This was not impaired further by propranolol. Thus, we formed the following conclusions. 1) Nonselective beta-adrenergic blockade does not cause absolute hypoglycemia unawareness but shifts the glycemic thresholds for symptoms to lower plasma glucose concentrations in patients with IDDM. 2) Beta-adrenergic blockade does not reduce neuroglycopenic symptoms, and it does not further impair cognitive function during hypoglycemia in IDDM patients.
Adult↗
Intensive insulin therapy for treatment of type I diabetes.
Intensive insulin therapy is best defined as a comprehensive system of diabetes management with the patient and management team as partners. The system is directed at improvement of glycemia and patient well-being. Glycemic targets should be individually defined. Frequent self-monitoring of blood glucose, probably at least four times per day, is essential for meticulous control. The benefits include improved psychosocial functioning and the potential of lessening the risks of chronic complications of diabetes. The risks relate to problems associated with hypoglycemia, which are increased if meticulous glycemic control is sought. One of the important elements of intensive therapy is a multiple-component insulin program designed to provide effective insulinemia coinciding with each major meal and continuous basal insulinemia throughout the 24-h day. This may be achieved with continuous subcutaneous insulin infusion (CSII) or multiple injections with various insulin regimens, although CSII may offer real advantages in terms of the pharmacokinetics of insulin delivery. Other pharmacokinetic issues to be considered involve selection of injection sites, timing of premeal insulin, and mixing insulins. Many studies have shown that, albeit with effort, excellent glycemic control can be achieved by various intensive insulin-therapy regimens. The implementation of a program of intensive therapy involves patient self-management in terms of altering insulin dosages, food intake, and/or activity in an attempt to achieve the target level of glycemia selected. In motivated patients willing to embark on such a course of therapy, intensive insulin therapy can be worthwhile. It should be considered for all patients with type I (insulin-dependent) diabetes mellitus.
Diabetes Mellitus, Type 1↗
Failure of nocturnal hypoglycemia to cause daytime hyperglycemia in patients with IDDM.
To test the hypothesis that nocturnal hypoglycemia causes postprandial hyperglycemia the next day (the Somogyi phenomenon) in patients with insulin-dependent diabetes mellitus (IDDM), we studied 10 moderately well controlled patients, who were on their usual therapeutic regimens, from 2000 to 2000 on three occasions. On a control day, samples were obtained without intervention. On another day, nocturnal hypoglycemia was prevented (by intravenous infusion of glucose, if necessary, from 2200 to 0400 to keep plasma glucose levels at greater than 5.6 mM). On another day, nocturnal hypoglycemia was induced (by stepped intravenous insulin infusions between 2200 and 0200 to reduce plasma glucose levels to less than 2.8 mM). After nocturnal hypoglycemia (1.9 +/- 0.2 mM), fasting (0800), morning (0800-1100), afternoon (1200-1500), evening (1600-2000), and entire-day (0800-2000) plasma glucose concentrations were no higher than those after prevention of nocturnal hypoglycemia or sampling only. On the control day, fasting and daytime plasma glucose levels were directly related to the preceding 2200 (r = 0.723, P less than 0.02, and r = 0.762, P = 0.01, respectively) and nocturnal nadir (r = 0.714, P less than 0.02, and r = 0.728, P less than 0.02) plasma glucose concentrations. Daytime plasma glucose levels were unrelated to peak nocturnal plasma glucagon, epinephrine, norepinephrine, growth hormone, or cortisol concentrations. We conclude that nocturnal hypoglycemia does not appear to cause clinically important daytime hyperglycemia in patients representative of most patients with IDDM.
3-Hydroxybutyric Acid↗
Role of insulin in management of surgical patients with diabetes mellitus.
Because surgery is a likely event during the lifetime of patients with diabetes, health-care team members need to be aware of the metabolic problems that may occur during the perioperative period. Surgery, especially in the presence of general anesthesia, will produce a diabetogenic response. This is generally due to an elevation of counterregulatory hormones, although endogenous insulin is also suppressed. The excessive lipolysis and ketogenesis that can occur during surgery can have particularly deleterious effects for patients with diabetes. Thus, sufficient insulin must be provided during this period to suppress these catabolic processes. The major controversy regarding surgery and diabetes concerns the route of insulin administration. This article reviews the various treatment options for patients with insulin-dependent and non-insulin-dependent diabetes mellitus, with particular emphasis on the role of insulin. Special situations, e.g., outpatient surgery, coronary artery bypass, and emergency surgery, are also discussed.
Diabetes Mellitus, Type 1↗
The important 3:00 am blood glucose.
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Blood Glucose↗
The effect of ejaculation on albumin excretion rate.
Microalbuminuria predicts the development of diabetic nephropathy. Large daily variations in albumin excretion rates are frequently observed. Because seminal fluid contains protein and albumin, we reasoned that sexual activity, ejaculation, or residual urethral semen could contribute to albumin content in urine and thus effect determination of albumin excretion rate. Our study was designed to determine the effect of ejaculation of albumin excretion rate and to ascertain if patients routinely should be advised to refrain from sexual activity during or before the urine collection period. Ten normotensive, nondiabetic men (age 31.0 +/- 2.3 years) collected 24-h urine specimens on three occasions: after 3 days of abstinence from sexual activity, during a 24-h period which included one ejaculatory episode, and on a day following sexual activity. Results for albumin excretion rate were: abstinence day: 4.8 +/- 0.7 micrograms/min; sex day: 6.3 +/- 1.1 microgram/min; post-sex day: 4.9 +/- 1.0 micrograms/min. There was no significant difference between these values when compared directly or after log transformation. There also were no differences in urinary creatinine excretion or clearance. We conclude that in nondiabetic individuals ejaculation does not influence albumin excretion rate.
Adult↗