Physical activity and NIDDM in African-Americans. The Pitt County Study.

OBJECTIVE: Studies directly examining the association between physical activity and NIDDM in African-Americans are rare. Consequently, the strength of this association in this ethnic minority group remains unclear. The current study broadly characterizes the types of physical activity engaged in by a community sample of working-class African-Americans and then quantifies the association between physical activity and NIDDM risk in this population. RESEARCH DESIGN AND METHODS: During the 1993 reexamination of participants in the Pitt County Study in North Carolina, data on NIDDM history, current use of insulin or oral hypoglycemic drugs, and approximately 12-h overnight fasting blood glucose (FBG) were obtained from 598 women and 318 men, ages 30-55 years. The presence of NIDDM was determined by current insulin or medication use and FBG > or = 140 mg/dl. Study participants were assigned to one of four categories of physical activity: strenuous, moderate, low, or inactive. RESULTS: The weighted prevalence of NIDDM in the sample was 7.1%. After adjustment was made for age, sex, education, BMI, and waist-to-hip ratio, NIDDM risk for moderately active subjects was one-third that for the physically inactive subjects (odds ratio [OR], 0.35; 95% CI, 0.12-0.98). The ORs for low (OR, 0.51; 95% CI, 0.20-1.29) and strenuous (OR, 0.65; 95% CI, 0.26-1.63) activity also tended to be lower. A summary OR that contrasted any activity versus no activity was 0.51 (95% CI, 0.23-1.13). CONCLUSIONS: Moderate physical activity was strongly associated with reduced risk for NIDDM in this sample. While replication of these findings is needed, public health interventions designed to increase moderate (leisure-time) physical activity in black adults should be strongly encouraged.

Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12)

OBJECTIVE: To evaluate protein-bound cyanocobalamin (vitamin B12) absorption before and after omeprazole (Prilosec) therapy in healthy male volunteers. DESIGN: Clinical trial in which each volunteer served as his own control. SETTING: Outpatient department of a university medical center. PARTICIPANTS: Ten healthy, male volunteers 22 to 50 years old. INTERVENTION: Each participant had a modified Schilling test (protein-bound cyanocobalamin) and a gastric analysis, as well as measurements of serum vitamin B12, gastrin, and folate levels. Five patients were then randomly assigned to take either 20 mg or 40 mg of omeprazole daily. After 2 weeks of omeprazole therapy, these tests were repeated. MEASUREMENTS: The modified Schilling test, gastric analysis, serum gastrin level, folate level, and cyanocobalamin level. RESULTS: At the end of the 2-week treatment period, cyanocobalamin absorption decreased from 3.2% to 0.9% (P = 0.031) in participants receiving 20 mg of omeprazole daily. In patients taking 40 mg of omeprazole daily, cyanocobalamin absorption decreased from 3.4% to 0.4% (P < 0.05). CONCLUSIONS: Omeprazole therapy acutely decreased cyanocobalamin absorption in a dose-dependent manner.

Surgical treatment of obesity and its effect on diabetes: 10-y follow-up.

Since 1980 we have performed the identical Greenville gastric bypass (GGB) procedure on 479 morbidly obese patients with an acceptable morbidity and a mortality rate of 1.2%. The weight loss in the series was well maintained over the follow-up period of 10 y. The GGB can control non-insulin-dependent diabetes mellitus (NIDDM) in most patients. The group of 479 patients included 101 (21%) with NIDDM and another 62 (13%) who were glucose impaired. Of these 163 individuals, 141 reverted to normal and only 22 (5%) remained with inadequate control of their carbohydrate metabolism. Those patients who were older or whose diabetes was of longer duration were less likely to revert to normal values. The gastric bypass operation is an effective approach for the treatment of morbid obesity. Along with its control of weight, the operation also controls the hyperglycemia, hyperinsulinemia, and insulin resistance of the majority of patients with either glucose impairment or frank NIDDM.

The solubility of calcium and phosphorus in neonatal total parenteral nutrition solutions.

Precipitation of calcium phosphate in neonatal total parenteral nutrition (TPN) solutions remains a significant problem. Whereas numerous studies have attempted to establish guidelines for maximum concentrations of various combinations that can be mixed, differences in study design and reliance upon subjective visual assessment severely limit their applicability. The purpose of this study was to quantitatively determine calcium and phosphate compatibility in commonly used neonatal TPN solutions containing a final concentration of either 1 or 2% amino acids. The final dextrose concentration was 10%. Electrolytes, heparin, and pediatric vitamins and trace minerals were also added. Calcium gluconate (10%) and potassium phosphate (mono and dibasic) were added by calibrated micropipetors. Calcium concentrations ranged from 5 to 60 mEq/L and phosphate from 5 to 40 mM/L with a minimum of 84 combinations tested for each amino acid concentration. Calcium concentrations were measured in duplicate for each tested combination. Control solutions containing calcium but no phosphate were included to validate the assay methodology. All samples were stored at room temperature for 23.5 hours and then placed in a water bath at 37 degrees C for 30 minutes to simulate incubator conditions encountered during TPN infusion. Calcium determinations were then repeated and precipitation was judged to have occurred whenever calcium concentrations fell below 90% of the initial measured values. These data allowed plotting a calcium and phosphorus reference curve for TPN solutions containing 1 and 2% amino acids based on quantitative assessment. These reference curves should allow pharmacists to avoid compounding TPN solutions that will precipitate, thus saving considerable cost to the pharmacy and preventing complications.

Liver pathology in morbidly obese patients with and without diabetes.

The contribution of obesity and/or diabetes to liver pathology in the morbidly obese patient is controversial. We studied the liver biopsies of 100 consecutive patients undergoing gastric bypass surgery for morbid obesity. Multiple morphologic parameters were analyzed and graded independently, without knowledge of the clinical history, liver function tests, and oral glucose tolerance results of the patients. Six percent of the entire group demonstrated no fat, 42% mild fat, 20% moderate fat, and 24% severe fatty metamorphosis of the liver. Twenty-three percent of the patients had central vein fibrosis, 23% sinusoidal fibrosis, 19% bridging fibrosis, and 4% cirrhosis. Thirty-six percent of the patients had some degree of steatohepatitis, 66% possessed so-called glycogen nuclei of hepatocytes, 6% had PAS-positive thickening of blood vessels in the portal tracts, and 1% had lipogranulomas. The degree of fatty metamorphosis and fibrosis was analyzed in three separate groups, categorized by the glycemic status of the patient: 46 patients with normal glucose tolerance (NGT), 23 patients with impaired glucose tolerance (IGT), and 31 patients with non-insulin-dependent diabetes mellitus (NIDDM). Increasing severity of fatty metamorphosis from the normoglycemic obese to the diabetic obese patients was found, which was statistically significant by chi 2 analysis. Four of the six patients showing no fatty metamorphosis were normoglycemic. Glycogen nuclei and PAS-positive blood vessels were significantly more prevalent in the diabetic obese than in the normal obese. In conclusion, the distribution of significant liver histopathology in the morbidly obese patient correlates in severity with the degree of impaired glycemic status.

Mechanism of IGF-I-stimulated glucose transport in human adipocytes. Demonstration of specific IGF-I receptors not involved in stimulation of glucose transport.

We demonstrate the presence of specific insulinlike growth factor I (IGF-I) receptors in human adipocytes. Competition studies with 125I-labeled IGF-I and unlabeled IGF-I, IGF-II, and insulin showed the specificity of 125I-IGF-I binding to the IGF-I receptors in adipocytes, membranes, and partially purified detergent-solubilized extracts. The monoclonal antibody to the IGF-I receptor (alpha-IR3) inhibits 125I-IGF-I binding and immunoprecipitates the IGF-I receptor. In addition, the alpha-subunit of IGF-I receptor is approximately 10,000 Mr larger than the alpha-subunit of insulin receptor, and IGF-I stimulates phosphorylation of the beta-subunit of the IGF-I receptor. IGF-I stimulates basal glucose transport in human adipocytes, but the concentrations of IGF-I required for half-maximal and maximal stimulation of glucose transport are 800- and 1000-fold greater than that of insulin. The possibility of IGF-I stimulating glucose transport by interacting predominantly with insulin receptors is suggested by data showing that 1) IGF-I competes with insulin-binding sites, 2) there is a lack of an additive effect with IGF-I and insulin in stimulating glucose transport, 3) alpha-IR3, which specifically inhibits IGF-I binding, does not inhibit IGF-I or insulin-stimulated glucose transport, 4) insulin-receptor antibody MA-10 inhibits IGF-I and insulin-stimulated glucose transport, and 5) IGF-I stimulates insulin-receptor autophosphorylation, although its effect is markedly decreased compared with insulin. In summary, human adipocytes possess specific IGF-I receptors. However, IGF-I stimulates glucose transport predominantly by interacting with the insulin receptor.

Parathyroid hormone (PTH) assay of parathyroid cysts examined by fine-needle aspiration biopsy.

The authors report three cases of parathyroid cysts examined by the fine-needle aspiration biopsy technic. A presumptive diagnosis of parathyroid cyst was made when characteristic water-clear fluid was aspirated. The diagnosis was then confirmed by parathyroid hormone (PTH) assay. The authors believe that the C-terminal/midmolecule determination should be the assay of choice, because the N-terminal-specific assay gave normal or slightly elevated results in all the cases studied. If only an N-terminal-specific PTH assay is obtained, potential for a false negative diagnosis exists. With a correct PTH assay, a specific diagnosis of parathyroid cyst can be rendered, which enables appropriate treatment of total fluid aspiration, which thereby eliminates the need for thyroid hormone treatment or surgery in most cases. A discussion of PTH assays is presented along with speculations concerning the secretion of PTH by the parathyroid gland. The previous literature detailing cytologic findings and the PTH assays of parathyroid cysts diagnosed by the fine-needle aspiration biopsy are reviewed.

Studies on the mechanism of insulin resistance in the liver from humans with noninsulin-dependent diabetes. Insulin action and binding in isolated hepatocytes, insulin receptor structure, and kinase activity.

We have developed a method to isolate insulin-responsive human hepatocytes from an intraoperative liver biopsy to study insulin action and resistance in man. Hepatocytes from obese patients with noninsulin-dependent diabetes were resistant to maximal insulin concentration, and those from obese controls to submaximal insulin concentration in comparison to nonobese controls. Insulin binding per cell number was similar in all groups. However, insulin binding per surface area was decreased in the two obese groups because their hepatocytes were larger. In addition, the pool of detergent-extractable receptor was further decreased in diabetics. Insulin receptors in all groups were unaltered as determined by affinity-labeling methods. However, insulin-stimulated insulin receptor kinase activity was decreased in diabetics. Thus, in obesity, decreased surface binding could explain resistance to submaximal insulin concentrations. In diabetes, diminished insulin-stimulated protein kinase activity and decreased intracellular pool of receptors could provide an explanation for postinsulin-binding defect(s) of insulin action in human liver.

Reliability of amitriptyline dose prediction based on single-dose plasma levels.

To assess prospectively the predictability of therapeutic dosage based on tricyclic antidepressant (TCA) concentrations after a single dose, 30 subjects were given amitriptyline. In the first 11 subjects maintained on a fixed amitriptyline dose regimen, predictive capacities of 18- and 24-hr single-dose levels were assessed and confirmed in relation to steady-state levels. For the other 19 subjects, the dose that would achieve a therapeutic steady-state concentration of 200 ng/ml was predicted from the 18-hr single-dose level and was rapidly instituted. Subjects achieved a mean steady-state TCA level of 204 ng/ml, with approximately 90% of the levels falling within the therapeutic range. There was clinical improvement within 2 wk in 84% of the subjects. Our results suggest that dose prediction based on TCA levels after a single dose is reliable and useful.

Single-dose single-point method in amitriptyline therapy.

Twenty-one depressed patients participated in a study that assessed the predictability of amitriptyline (AT) dosage based on plasma drug concentrations after a single dose. In 11 patients maintained on a fixed dose regimen, the 18-h single-dose level was confirmed to be predictive of steady-state levels. The dose for the next 10 patients was derived from their 18-h level aiming to attain steady-state levels of 200 ng/ml. The patients achieved a mean steady-state level of 213 ng/ml with 80% attaining therapeutic levels. All the patients improved within 2 weeks. These preliminary results suggest that dose prediction based on a single-dose TCA level is reliable and beneficial.