The BIGTT test: a novel test for simultaneous measurement of pancreatic beta-cell function, insulin sensitivity, and glucose tolerance

OBJECTIVE: Insulin resistance and impaired beta-cell function are key elements in the pathogenesis of type 2 diabetes. We aimed to develop valid algorithms for estimation of the insulin sensitivity index (S(I)) and acute insulin response (AIR) derived from simple and cheap physiological measurements that could be used in large-scale metabolic, genetic, and epidemiological studies. RESEARCH DESIGN AND METHODS: For our purpose, data from an oral glucose tolerance test (OGTT) (18 samples during 240 min) and a tolbutamide-modified intravenous glucose tolerance test (IVGTT) (33 samples during 180 min) from 258 individuals with fasting plasma glucose <7 mmol/l and 2-h plasma glucose <7.8 mmol/l were used for model development and internal validation. Data from an additional 28 individuals were used for external validation. Bergman's minimal model was used to calculate S(I), and the trapezoidal method was used to calculate AIR(0-8 min). Multiple linear regression was applied to derive predictive equations of log(S(I)) and log(AIR(0-8 min)) using data on sex, BMI, plasma glucose, and serum insulin levels obtained during the OGTT. RESULTS: We demonstrate that it is possible to obtain estimates of S(I) (BIGTT-S(I)) and AIR (BIGTT-AIR) that are highly correlated to IVGTT-derived values of S(I) (R(2) = 0.77) and AIR (R(2) = 0.54). In the two validation datasets we obtained similar results. CONCLUSIONS: Data from OGTTs can provide accurate measures of insulin sensitivity and beta-cell function, which can be used in large scale metabolic, genetic, and epidemiological studies.     

Normal secretion and action of the gut incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in young men with low birth weight

CONTEXT: Low birth weight (LBW) is associated with increased risk of type 2 diabetes mellitus. An impaired incretin effect was reported previously in type 2 diabetic patients. OBJECTIVE: We studied the secretion and action of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in young LBW men (n = 24) and matched normal birth weight controls (NBW) (n = 25). RESULTS: LBW subjects were 5 cm shorter but had a body mass index similar to NBW. LBW subjects had significantly elevated fasting and postprandial plasma glucose, as well as postprandial (standard meal test) plasma insulin and C-peptide concentrations, suggestive of insulin resistance. Insulin secretion in response to changes in glucose concentration ("beta-cell responsiveness") during the meal test was similar in LBW and NBW but inappropriate in LBW relative to insulin sensitivity. Fasting and postprandial plasma GLP-1 and GIP levels were similar in the groups. First- and second-phase insulin responses were similar in LBW and NBW during a hyperglycemic clamp (7 mm) with infusion of GLP-1 or GIP, respectively, demonstrating normal action of these hormones on insulin secretion. CONCLUSION: Reduced secretion or action of GLP-1 or GIP does not explain a relative reduced beta-cell responsiveness to glucose or the slightly elevated plasma glucose concentrations observed in young LBW men.     

The risk of cancer at all sites following gastric operation for benign disease. A cohort study of 4,224 patients

This report represents the results of a historical cohort analysis of 3,360 males and 864 females who had a gastric resection or gastroenterostomy for benign disease between 1990 and 1969. Within the period 1970 to 1988 the cohort was cross-checked with the data files at the Cancer Registry of Norway to identify the patients in whom cancer had been diagnosed. When analyzed according to cancer sites, increased risk was recorded for the oropharynx, stomach, colon, pancreas, liver, biliary tract, larynx, lungs, urinary bladder and non--melanomatous cancers of the skin in males. In females, increased risk was only observed for the oropharynx, but was close to a statistically significant level also for cancer of the stomach. A lower number of tumors of the central nervous system than expected was observed in both males and females. The increased risk of cancer of the lungs, larynx and urinary bladder in males can be regarded as evidence of the high prevalence of smokers in the cohort. We suggest that the increased risk of cancer of digestive organs is mainly related to life-style factors, particularly tobacco-specific nitrosamines whose effect is enhanced by surgical sequelae.     

Einige Bemerkungen über das Verhältnis des Lupus erythematodes zur Tuberkulose

Zusammenfassung Besonders Blochs, Fuchs' und Bruusgaards' Untersuchungen machten für einzelne Fälle von Lupus erythematodes eine tuberkulöse Ätiologie in recht hohem Grade wahrscheinlich. Auch in dem hier vorliegenden Material finden sich 2 Fälle (Krankengeschichte, 1 und 3), welche die Anschauung von der Abhängigkeit des Lupus erythematodes von der Tuberkulose in einzelnen Fällen stützen.Für die große Mehrzahl der L. e.-Fälle ist dagegen ein derartiges Kausalitätsverhältnis zur Tuberkulose völlig unbewiesen, und wichtige Tatsachen—in dieser Arbeit ist besonders das Verhältnis des L. e. zum Tuberkulin recht ausführlich erörtert—machen außerdem ein derartiges Kausalitätsverhältnis unwahrscheinlich.     

Evidence of carcinogenicity in humans of water-soluble nickel salts

Background  

Increased risks of nasal cancer and lung cancer in nickel refiners have been investigated scientifically and discussed since they were detected in the 1930s. Nickel compounds are considered to be the main cause of the cancer excess. Parts of the nickel producing industry and their consultants oppose the classification of water-soluble nickel salts as human carcinogens, and argue that the risk in exposed workers should be ascribed to other occupational exposures and smoking.     

The Influence of Prazosin and Propranolol on Serum Lipids and Atherosclerosis in Standard Fed Pigs

Abstract: The influence of prazosin and propranolol on serum lipids and atherosclerosis was evaluated in standard fed pigs during a nine months experimental period. The incidence and severity of atherosclerotic lesions was very low, and no difference could be observed neither between the two drugs nor between the drug groups and the placebo group. Prazosin and propranolol induced no marked change in the serum lipid profile. The results could be explained by the very low fat content, 3.6 per cent, in the present standard diet.     

Dynamic Properties of Primary Auditory Fibers Compared with Cells in the Cochlear Nucleus

The dynamic properties of the responses of single primary auditory fibers were compared with those of single cells in the cochlear nucleus. The stimuli were tones (at the unit's characteristic frequency, CF) that were amplitude-modulated with pseudorandom noise. The dynamic properties were described by the cross-covariance and integrated cross-covariance functions between the recorded discharge rate and the modulation. These two measures have earlier been shown to be valid approximations of the system's impulse and step response function, i.e. the change in discharge rate in response to a short impulsive increase (or decrease) in the stimulus intensity and a step increment (or decrement) in the stimulus intensity. The cross-covariance function computed from the responses of fibers had a narrower peak than that of cells indicating that a brief change in stimulus intensity gives rise to a faster change in the discharge rate of fibers than that of cells. The modulation of the discharge rate of cells for a certain degree of amplitude modulation of the sound is usually greater than that of fibers. The range of stimulus intensities where a change in stimulus intensity gives rise to a change in discharge rate is smaller for fibers (about 30 dB) than what was shown earlier for cells (70–80 dB). The cross-covariance function computed from the slow wave responses recorded from the surface of the cochlear nucleus in response to an amplitude-modulated tone has individual peaks that reflect distinct classes of units with regard to latency of unit discharges.     

Asbestos exposure, smoking habits, and cancer incidence among production and maintenance workers in an electrochemical plant

The incidence of cancer was studied in a cohort of 287 men who were exposed to asbestos at a nitric acid production plant from 1928 onwards. During the observation period from 1953 through 1980 all cancer cases among the cohort members were identified in The Cancer Registry. For the whole cohort 42 cases of cancer were observed versus 30.6 expected. The figures for cancer of the lungs and pleura combined were 17 observed versus 3.7 expected. The corresponding figures for a heavily exposed subcohort were 11 observed and 1.2 expected. In that group there was also an increased incidence of colon cancer with 3 cases observed against 0.8 cases expected. Within the whole cohort four cases of pleural and one case of peritoneal malignant mesothelioma were found. There was also an increased incidence of malignant melanoma of the skin with 3 cases observed against 0.6 expected. For cancer cases that were registered as of unknown origin there were 7 cases observed and 1.4 expected. There was no increased rate ratio for cancer at any site before 20 years after the first asbestos exposure. The smoking habits of all cohort members were recorded and the relative rates for lung cancer were calculated in relation to smoking habits. In common with previous studies the results indicate a multiplicative model for the interaction between asbestos exposure and smoking in regard to lung cancer risk.