The perception of safe driving ability during hypoglycemia in patients with type 1 diabetes mellitus.

PURPOSE: Insulin-induced hypoglycemia and its sequelae of cognitive impairment may place patients with type 1 diabetes at risk when driving and when making decisions about driving. Little is known about the factors that influence judgments of safe driving ability during hypoglycemia in these patients. PATIENTS AND METHODS: Thirty men and 30 women with uncomplicated type 1 diabetes (age [mean +/- SD] 33 +/- 9 years, duration 9 +/- 3 years, hemoglobin A1c level 8.7% +/- 1.0%) underwent a stepped hypoglycemic insulin clamp. Serum glucose levels were reduced from 120 mg/dL to 80, 70, 60, 50, and then 40 mg/dL during 190 minutes. At each glucose plateau, patients completed a symptom questionnaire and neuropsychological test, estimated their glucose level, and reported whether they could drive safely. RESULTS: The proportion of patients judging that they could drive safely decreased as serum glucose levels decreased from 70% at 120 mg/dL to 22% at 40 mg/dL. Men and middle-aged patients were more likely to consider it safe to drive during hypoglycemia than women and those under 25 years of age. Those who were symptomatic and those who recognized hypoglycemia were less likely to report safe driving ability during hypoglycemia. Most patients who were cognitively impaired appeared to recognize this and reported that they could not drive safely at a serum glucose level of 40 mg/dL. CONCLUSIONS: Adults with type 1 diabetes need educational reinforcement of safe driving habits, particularly to check glucose levels before driving. Glucose levels less than 70 mg/dL should be treated before driving. This information is as important for middle-aged, experienced drivers as it is for younger, inexperienced drivers.

Blood glucose awareness training and epinephrine responses to hypoglycemia during intensive treatment in type 1 diabetes.

OBJECTIVE: To determine the effect of blood glucose awareness training (BGAT) on epinephrine and symptom responses to hypoglycemia in patients with type 1 diabetes enrolled in an intensive diabetes treatment (IDT) program. RESEARCH DESIGN AND METHODS: A total of 47 subjects with uncomplicated diabetes (duration 9 +/- 3 years: HbA1c 9.0 +/- 1.2%; reference range 4-6%) enrolled in a 4-month outpatient IDT program were randomized to classes in BGAT (n = 25) (BGAT group) or cholesterol awareness (n = 22) (control group). Subjects underwent stepped hypoglycemic clamp studies before and at completion of IDT. Plasma glucose was lowered from 6.7 mmol/l (baseline) to 4.4, 3.9, 3.3, 2.8, and 2.2 mmol/l over 190 min. Symptoms, counterregulatory hormones, and ability of the subject to estimate their glucose level were assessed at each plateau. At home, subjects used a handheld computer to first estimate and then measure and record blood glucose levels for 70 trials over a 4-week period immediately before IDT and again immediately following the educational intervention. RESULTS: HbA1c decreased in both BGAT group (9.1 +/- 1.4 to 7.9 +/- 1.1%; P < 0.001) and control group (9.0 +/- 1.1 to 7.8 +/- 0.8%; P < 0.001) (NS between groups). Frequency of hypoglycemia (< 3.9 mmol/l) increased in both groups, from 0.45 +/- 0.06 to 0.69 +/- 0.07 episodes per day (P < 0.001) in the BGAT group and from 0.50 +/- 0.08 to 0.68 +/- 0.06 episodes per day (P < 0.05) in the control group NS between groups). Epinephrine responses after IDT were greater in the BGAT group (repeated measure analysis of variance [ANOVA], F = 3.5, P < 0.05). A separate analysis of subjects n = 26) most at risk for hypoglycemia (HbA1c after IDT < 7.8% or an HbA1c improvement of > 2 percentage points) showed that frequency of hypoglycemia increased in both the groups: from 0.50 +/- 0.09 to 0.80 +/- 0.11 episodes per day (P < 0.01) in the BGAT group (n = 14) and from 0.43 +/- 0.11 to 0.75 +/- 0.07 episodes per day (P < 0.05) in the control group (n = 12) (NS between groups). However, the epinephrine response in control subjects decreased with IDT while the response in the BGAT subjects was preserved (repeated measure ANOVA, F = 4.4, P < 0.02). CONCLUSIONS: BGAT is a useful intervention to decrease blunting of counterregulatory responses associated with improved glycemic control and may modify the severity of hypoglycemia associated with improved glycemic control in type 1 diabetes.

Effect of glycemic control on glucose counterregulation during hypoglycemia in NIDDM.

OBJECTIVE: We examined the effect of glycemic control of NIDDM on counterregulatory hormone responses to hypoglycemia and compared the effect with that seen in patients with IDDM. RESEARCH DESIGN AND METHODS: Eleven subjects with NIDDM and eight age- and weight-matched control subjects and ten subjects with IDDM and ten age- and weight-matched control subjects were studied. All subjects underwent a stepped hypoglycemic-hyper-insulinemic clamp study during which plasma glucose levels were lowered in a stepwise manner from 5.0 to 2.2 mmol/l in steps of 0.6 mmol/l every 30 min. Counterregulatory hormones (epinephrine, norepinephrine, glucagon, ACTH, cortisol, and growth hormone [GH]) were measured, and a symptom survey was administered during the last 10 min of each 30-min interval. RESULTS: The threshold for release of epinephrine, norepinephrine, ACTH, and cortisol occurred at higher plasma glucose levels in NIDDM than in IDDM patients (P < 0.05-0.01). The glucose threshold for release of epinephrine and norepinephrine correlated with glycemic control as measured by glycosylated hemoglobin (P < 0.05-0.01). However, for a given level of glycemic control, the threshold for release of epinephrine and norepinephrine occurred at a higher glucose level in NIDDM versus IDDM patients (P < 0.05-0.01). At the nadir level of hypoglycemia, glucagon, ACTH, and cortisol levels were all higher in NIDDM compared with IDDM subjects, whereas GH levels were lower. CONCLUSIONS: Glycemic control alters counterregulatory responses to hypoglycemia in NIDDM as has been previously reported in IDDM. However, at similar levels of glycemic control, NIDDM patients release counterregulatory hormones at a higher plasma glucose level than patients with IDDM. In addition, subjects with NIDDM maintain their glucagon response to hypoglycemia. These data suggest that patients with NIDDM may be at reduced risk of severe hypoglycemia when compared with a group of IDDM patients in similar glycemic control, thus providing a more favorable risk-benefit ratio for intensive diabetes therapy in NIDDM.

Prolactin and beta-endorphin responses to hypoglycemia are reduced in well-controlled insulin-dependent diabetes mellitus.

Several pituitary hormones, including corticotropin (ACTH), growth hormone (GH), prolactin, and beta-endorphin (but not thyrotropin, follicle-stimulating hormone, or luteinizing hormone), are released in response to hypoglycemia in normal subjects. In patients with insulin-dependent diabetes mellitus (IDDM), the degree of glycemic control is known to alter ACTH and GH responses to hypoglycemia. The current study was performed to examine the effect of glycemic control on prolactin and beta-endorphin responses to hypoglycemia in subjects with IDDM. We performed 3-hour stopped hypoglycemic-hyperinsulinemic clamp studies (12 pmol/kg/min) during which plasma glucose was decreased from 5.0 mmol/L to 2.2 mmol/L in steps of 0.6 mmol/L every 30 minutes in 20 subjects with uncomplicated IDDM (12 males and eight females; age, 26 +/- 2 years; IDDM duration, 10 +/- 1 years; body mass index, 23.6 +/- 0.6 kg/m2) and 10 healthy subjects (five males and five females aged 30 +/- 1 years). The 10 diabetic subjects in good glycemic control (mean hemoglobin A1 [HbA1], 7.5% +/- 0.3%; normal range, 5.4% to 7.4%) were compared with the 10 poorly controlled patients (mean HbA1, 12.6% +/- 0.5%; P < .001 v well-controlled diabetic group). During hypoglycemia, prolactin levels in the well-controlled diabetic group did not change (7 +/- 1 microgram/L at plasma glucose 5.0 mmol/L to 9 +/- 2 micrograms/L at plasma glucose 2.2 mmol/L), whereas prolactin levels increased markedly in the poorly controlled diabetic group (7 +/- 2 micrograms/L to 44 +/- 17 micrograms/L) and healthy volunteers (12 +/- 2 micrograms/L to 60 +/- 19 micrograms/L, P < .05 between IDDM groups). The plasma glucose threshold required for stimulation of prolactin secretion was 2.2 +/- 0.1 mmol/L in well-controlled IDDM, 3.0 +/- 0.4 mmol/L in poorly controlled IDDM, and 2.4 +/- 0.1 mmol/L in healthy subjects (P < .05 between IDDM groups). Responses in males and females were similar. The increase in beta-endorphin levels was also attenuated in well-controlled IDDM patients (4 +/- 1 pmol/L at plasma glucose 5.0 mmol/L to 11 +/- 4 pmol/L at plasma glucose 2.2 mmol/L) versus poorly controlled IDDM patients (5 +/- 1 pmol/L to 26 +/- 7 pmol/L) and healthy subjects (8 +/- 1 pmol/L to 56 +/- 13 pmol/L). The plasma glucose threshold required for stimulation of beta-endorphin release was again lower in well-controlled IDDM versus poorly controlled IDDM patients (2.2 +/- 0.1 v 3.0 +/- 0.3 mmol/L) and healthy subjects (2.5 +/- 0.4 mmol/L, P < .05 between IDDM groups). In conclusion, prolactin and beta-endorphin responses to a standardized hypoglycemic stimulus (plasma glucose, 2.2 mmol/L) are reduced and plasma glucose levels required to stimulate release of prolactin and beta-endorphin are lower in well-controlled IDDM compared with poorly controlled IDDM and healthy subjects. Thus, stress hormones not previously considered to have a primary role in plasma glucose recovery from hypoglycemia are affected by glycemic control, suggesting a more generalized alteration of hypothalamic-pituitary responses to hypoglycemia in IDDM patients with strict glycemic control.

Agent Orange exposure and posttraumatic stress disorder.

Evidence of organic psychological deficits in Vietnam veterans exposed to the herbicide Agent Orange was established through a neuropsychological battery. Also, the exposed Vietnam veterans, in contrast to a matched control group of Vietnam veterans, showed a significantly higher rate of posttraumatic stress disorder and its associated features: depression, anxiety, and increased aggression. The latter was subdivided into uncontrollable pressures, verbal violence, violence against objects, assaults, and suicidal thoughts. Active cases of chloracne, a medical indicator, were used to determine Agent Orange exposure.

Skin testing in the investigation of reactions to intravenous anaesthetic drugs. A prospective trial of atracurium and tubocurarine.

Intradermal skin testing is widely used to determine the causative drugs of presumed anaphylactic anaesthetic reactions. This paper sets out to evaluate the usefulness of skin tests, both intradermal and prick testing, in the prediction of anaesthetic reactions. The muscle relaxant drugs tubocurarine and atracurium were chosen for study since they are known to produce a high incidence of minor histaminoid reactions. A trial was conducted in 22 female patients about to undergo elective gynaecological surgery for non-malignant conditions. In intradermal tests, positive wheal and flare reactions to one or other relaxant (diluted 1 in 1,000) occurred in 17 patients and reactions to both drugs in 11 patients. Despite this high incidence of positive reactions, none of the patients had received either drug previously, a view confirmed by the negative results of prick testing. Likewise, when anaesthetized for surgery using atracurium or tubocurarine allocated randomly, the minor histaminoid manifestations observed showed no correlation whatsoever with the intradermal tests results. The results of the trial, combined with external reports to this centre, indicate that intradermal testing of anaesthetic drugs, particularly muscle relaxants, produces a high incidence of false positive results. This probably reflects their pharmacological activity rather than antigenicity. It is recommended, therefore, that skin testing should be reserved for situations in which there are strong indications from laboratory tests, backed by case history, of immune sensitization.

Taste aversions conditioned by the aversiveness of insulin and formalin: role of CS specificity.

Experimenters in the past have reported that when insulin is used as the unconditioned stimulus (US), rats will learn an aversion to a sodium chloride but not a sucrose solution, whereas with formalin as the US, they will learn an aversion to a sucrose but not a saline solution. The present experiments failed to confirm these findings. Aversions to sucrose were conditioned with insulin and aversions to sodium chloride were conditioned with formalin. The use of a more concentrated sucrose solution in the present study may have been responsible for the successful sucrose-aversion conditioning with insulin. Although the source of the discrepancy in findings concerning aversion conditioning with formalin remains unclear, experiments ruled out numerous possibilities. These experiments also showed that sodium chloride aversion conditioning with formalin is a highly robust phenomenon that occurs with a variety of conditioned stimulus durations and formalin doses, with distributed and massed training, in male and female rats, and even if saline is not the only novel solution presented during conditioning. Furthermore, the aversion can be detected with both single-stimulus and choice test procedures.

Demonstrations of neophobia and enhanced neophobia in the albino rat.

The conditions under which neophobia and enhanced neophobia occur in the albino rat were studied. Neophobia to a .1% saccharin solution was demonstrated in a 10-min single-bottle test. This neophobia was enhanced by pairing water ingestion with a radiation exposure of 100 r. or an injection of lithium chloride 24 hr prior to the saccharin test. In addition, it was found that the differences in consumption of saccharin in a 10-min single-bottle test due to neophobia and enhanced neophobia were produced by consistent differences in drinking rates which appeared early in the 10-min period. The disappearance of neophobia and enhanced neophobia in a 1-hr single-bottle test suggested that the effects of neophobia and enhanced neophobia are short-lived and are best measured in a brief single-bottle test. Finally, enhanced neophobia was not found when 2 days of water drinking were interposed between LiCl poisoning and saccharin testing.

Antihistamines block radiation-induced taste aversions.

When rats are treated with an antihistamine prior to being given sublethal doses of ionizing radiation, the formation of a conditioned saccharin aversion is completely inhibited. A profound aversion could be conditioned with histamine diphosphate as the aversive stimulus. The increase in histamine production after radiation exposure represents the physiological basis of radiation-induced taste aversions.