We studied the effects of cigarette smoking, sham smoking and smoking during adrenergic blockade in 10 subjects to determine whether smoking released the sympathetic neurotransmitter norepinephrine, as well as the adrenomedullary hormone epinephrine, and whether smoking-associated hemodynamic and metabolic changes were mediated through adrenergic mechanisms. Smoking-associated increments in mean (+/- S.E.M.) plasma norepinephrine (227 +/- 23 to 324 +/- 39 pg per milliliter, P less than 0.01) and epinephrine (44 +/- to 113 +/- 27 pg per milliliter, P less than 0.05) were demonstrated. Smoking-associated increments in pulse rate, blood pressure, blood glycerol and blood lactate/pyruvate ratio were prevented by adrenergic blockade; increments in plasma growth hormone and cortisol were not. Since significant smoking-associated increments, in pulse rate, blood pressure and blood lactate/pyruvate ratio, preceded measurable increments in plasma catecholamine concentrations, but were adrenergically mediated, these changes should be attributed to norepinephrine released locally from adrenergic axon terminals within the tissues rather than to increments in circulating catecholamines.

This study examined sharing of diabetes responsibilities between mothers and their diabetic children and the relationship between patterns of mother-child sharing of responsibility for diabetes tasks and demographic variables, adherence, and metabolic functioning in children with insulin-dependent diabetes mellitus (IDDM). A factor analysis of the Diabetes Family Responsibility Questionnaire (DFRQ), a 17-item questionnaire developed for the present study, resulted in a meaningful three-factor solution. Factors included responsibilities related to regimen tasks, General Health Maintenance, and Social Presentation of Diabetes. Analysis indicated that the DFRQ had adequate internal consistency and concurrent validity. One hundred and twenty-one children with IDDM, 6-21 years of age, and their mothers completed the DFRQ. Glycosylated hemoglobin (HbA1c) was used to index the child's level of metabolic control. Results of multiple regression analyses indicated that the child's age, disease duration, and sex are significant predictors of mother and child patterns of sharing diabetes responsibilities. Disagreements between mothers and children in perceptions of who is assuming responsibility and adherence level were significant predictors of HbA1c. Results indicated that children assume increasing responsibility with increasing age. Clinicians should not assume that mothers and children communicate about the sharing of diabetes responsibilities in the family or about changes in expectations of who is responsible as children develop. To foster better control and adherence in diabetic children, members of the health care team can help to identify diabetes tasks for which no one in the family takes responsibility.

Evaluated and compared the support provided by family members and friends for adolescents' diabetes care. Family and friend support also were examined in relation to other measures of social support, to demographic variables (age, gender, duration of diabetes) and to adherence. Using a structured interview, 74 adolescents with diabetes described the ways that family members and friends provided support for diabetes management (insulin shots, blood glucose monitoring, eating proper meals, exercise), and for helping them to "feel good about their diabetes." Families provided more support than friends for three management tasks (insulin injections, blood glucose monitoring, meals); this support was largely instrumental. In contrast, friends provided more emotional support for diabetes than families. Greater family support was related to younger age, shorter disease duration, and better treatment adherence. Implications of the findings include encouraging parents to remain involved in adolescents' treatment management, and involving peers as supportive companions for meals and exercise.

During intravenous insulin infusions (40 mU per kilogram of body weight per hour for up to 100 minutes), 9 of 22 patients with insulin-requiring diabetes mellitus had neurologic signs or symptoms of hypoglycemia, plasma glucose concentrations that were below 35 mg per deciliter (1.9 mmol per liter) and continued to decline, or both. This inadequate glucose counterregulation resulted from the combined effect of deficient glucagon and epinephrine responses. In 8 of the 9 patients with inadequate counterregulation severe hypoglycemia developed during subsequent intensive therapy, whereas such episodes occurred in only 1 of 13 patients with adequate counterregulation. Thus, an intravenous insulin-infusion test can prospectively identify patients who are at increased risk for recurrent severe hypoglycemia during intensive therapy for diabetes.

A B S T R A C T Sequential determinations of glucose outflow and inflow, and rates of gluconeogenesis from alanine, before, during and after insulin-induced hypoglycemia were obtained in relation to alterations in circulating epinephrine, norepinephrine, glucagon, cortisol, and growth hormone in six normal subjects. Insulin decreased the mean (+SEM) plasma glucose from 89+3 to 39+2 mg/dl 25 min after injection, but this decline ceased despite serum insulin levels of 153±22 gtU/ml.Before insulin, glucose inflow and outflow were constant, averaging 125.3±7.1 mg/kg per h. 15 min after insulin, mean glucose outflow increased threefold, but then decreased at 25 min, reaching a rate 15% less than the preinsulin rate. Glucose inflow decreased 80% 15 min after insulin, but increased at 25 min, reaching a maximum of twice the basal rate. Gluconeogenesis from alanine decreased 68% 15 min after insulin, but returned to preinsulin rates at 25 min, and remained constant for the next 25 min, after which it increased linearly. A fourfold increase in mean plasma epinephrine was found 20 min after insulin, with maximal levels 50 times basal. Plasma norepinephrine concentrations first increased significantly at 25 min after insulin, whereas significantly increased levels of cortisol and glucagon occurred at 30 min, and growth hormone at 40 min after insulin.Thus, insulin-induced hypoglycemia in man results from both a decrease in glucose production and an increase in glucose utilization. Accelerated glycogenolysis

This research compares the family environments of diabetic adolescents in good (HbA1c less than 10), fair (10 greater than or equal to HbA1c less than or equal to 14), and poor (HbA1c greater than 14) control. Fifty-eight adolescents diagnosed with type 1 diabetes and their parents (mothers) were independently assessed with structured interviews, the Moos Family Environment Scale, and adolescents also completed the Piers-Harris Children's Self-Concept Scale. As compared with adolescents in poor control, those in good control reported fewer diabetes-related symptoms and had less anxiety and a more positive self-concept. Well-controlled youths also reported more cohesion and less conflict among family members. More parents of well-controlled youths stated that family members were encouraged to behave independently. In addition, more parents of poorly controlled adolescents believed that diabetes had negatively affected the child's personality, physical well-being, schooling, and participation in activities away from home. These findings suggest a complex interplay between the diabetic adolescent's psychological and physical functioning, metabolic control, and the family environment.

D-chiro-Inositol is a rare inositol isomer present in inositol phosphoglycans which are proposed mediators of insulin action. To study D-chiro-inositol metabolism in diabetes mellitus, a sensitive and specific assay was developed using negative-ion chemical ionization gas chromatography/mass spectrometry. Median urinary D-chiro-inositol excretion, which was 2.1 ,umol/day in nondiabetics, was substantially increased to 12 ,umol/day in non-insulin-dependent diabetes (P < 0.0001) and to 74 j,mol/day in insulin-dependent diabetes (P < 0.0001). Urinary D-chiro-inositol was strongly correlated with fasting plasma glucose (r = 0.568, P < 0.0001), glycated hemoglobin (r = 0.529, P < 0.0001), and urinary glucose (r = 0.368, P = 0.01). The renal clearance of D-chiro-inositol was selectively elevated in both non-insulin-dependent and insulindependent diabetes when compared with the clearances of L-chiro-inositol or myo-inositol and exceeded the glomerular filtration rate in 71% of the diabetics but in none of the nondiabetics. In poorly controlled diabetic patients insulin treatment reduced urinary D-chiro-inositol losses by 63% and increased plasma levels by 8.8-fold. The metabolism of D-chiroinositol is abnormal in diabetes and appears to be influenced by short-and long-term metabolic control.One of the most important problems in endocrinology is the rigorous description of the mechanism of insulin action. Previous work suggests that some (but not all) of the actions of insulin may be mediated through inositol phosphoglycan molecules released from cell membranes (1-4). When such putative mediators were hydrolyzed and analyzed chemically it was found unexpectedly that in some preparations much or all of the inositol present was not myo-inositol (which is, by far, the most common mammalian inositol) but rather the rare epimer D-chiro-inositol (5, 6). Kennington et al. (7) reported abnormally low or unmeasurable levels of D-chiro-inositol in urine and muscle from patients with non-insulin-dependent diabetes mellitus (NIDDM) and suggested that D-chiroinositol deficiency might be related to the insulin resistance observed in NIDDM.However (9) and urinary albumin (Diagnostic Products, Los Angeles) were determined by radioimmunoassay, and glycated hemoglobin was determined by affinity chromatography (Pierce; normal range 4.4-6.3%).Inositol Analysis. Twenty-four-hour urine specimens were collected with cooling but without preservatives and aliquots were stored frozen at -20°C. D-chiro-Inositol levels changed <3% after incubation of nonsterile urine from two poorly controlled diabetics and two normal subjects for 24 hr at 25°C, indicating that urinary D-chiro-inositol levels are stable during collection. To 0.25 ml of urine were added 10 nmol of deuterated DL-chiro-inositol and 20 nmol of deuterated myoinositol as internal standards. The samples were then purified by a modification of a procedure (7) in which the sample was first passed over a 0.6-ml column of water-washed Amberlite IR-120(+) (Aldrich) and then over a 0....

Recent studies suggest that leptin, the ob gene product absent in ob/ob mice, is a negative regulator of adiposity. We developed an RIA to measure human leptin in plasma or serum. The minimum detectable concentration by the assay is 0.5 microg/L leptin and the limit of linearity is 100 microg/L. Recovery of leptin added to serum was 99-104% over by the linear range of the assay. The RIA agreed reasonably well with rough quantification by Western blot (RIA = 0.90 blot + 3.7 microg/L, Sy/x = 10.9 microg/L). CVs within- and between-run ranged from 3.4% to 8.3% and from 3.6% to 6.2%, respectively. Variation in plasma leptin concentrations in specimens collected on consecutive mornings was large (CVs of 10.9% and 22.5%). After an overnight fast, leptin concentrations were similar to those 1-2 h after 1-2 meals. Plasma leptin concentrations in specimens from 83 lean and obese adults correlated directly with body mass index (BMI; kg/m2): r = 0.72, P &lt;0.001. Correlations were significantly improved by separating results by gender (men r = 0.84, women r = 0.87; p &lt;0.001). The increase in leptin concentrations with increasing BMI was greater in women than in men (slope 2.53 vs 0.97 microg/L per unit BMI, respectively). Leptin concentrations determined in lean subjects (BMI between 18 and 25) were higher in women (7.36 +/- 3.73 microg/L) than in men (3.84 +/- 1.79 microg/L) (P &lt;0.001). Plasma leptin varied little with age and no significant difference was observed between whites and blacks. We conclude that: (a) plasma leptin concentrations are accurately and precisely measured by this new RIA; (b) leptin concentrations vary little due to short-term fasting, age, or race; but (c) plasma leptin concentrations are gender specific.