Insulin resistance and insulin secretion are determinants of oral glucose tolerance in normal individuals.

Plasma glucose values after oral glucose challenge vary widely in nondiabetic subjects. We have now evaluated the role of insulin resistance in determining the plasma glucose response to oral glucose in 74 volunteer subjects with normal glucose tolerance. In these subjects, we determined the plasma glucose and insulin responses over a 3-h period to a 75-g oral glucose challenge, and the steady-state plasma glucose concentration during a continuous infusion of somatostatin, glucose, and insulin (a quantitative measure of insulin resistance). The plasma glucose response was defined as the incremental increase in plasma glucose concentration above the fasting value for 3 h after the oral glucose challenge. Multiple regression analysis was used to define the relationship between the dependent variable (plasma glucose response) and various predictors of this response. These analyses indicated that both the steady-state plasma glucose and the incremental insulin response during the first 30 min after the glucose load were significant predictors of the plasma glucose response. In those individuals in whom insulin action was impaired and the 30-min plasma insulin response was decreased, plasma glucose values reached higher levels. When standardized regression coefficients were determined, the incremental glucose response was directly correlated with steady-state plasma glucose (r = 0.700, P < 0.001) and inversely with the insulin response during the first 30 min (r = 0.268, P = 0.023). Furthermore, the correlation between steady-state plasma glucose and glucose response was significantly greater (P < 0.005) than that between the glucose response and 30-min insulin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced postprandial cholecystokinin (CCK) secretion in patients with noninsulin-dependent diabetes mellitus: evidence for a role for CCK in regulating postprandial hyperglycemia.

The plasma cholecystokinin (CCK) response to a test meal was studied in 16 control subjects and 15 patients with noninsulin-dependent diabetes mellitus (NIDDM). Basal CCK levels were approximately 1 pmol in both groups. However, after the test meal, plasma CCK levels were 2-fold greater in the controls when compared to the diabetics. In controls, CCK levels maximally increased by 5.6 +/- 0.8 pmol (mean +/- SEM) 10 min after feeding, whereas in the NIDDM patients this value was 1.9 +/- 0.6 pmol (P < 0.001). After the test meal, the normal subjects showed no postprandial rise in blood glucose, whereas the diabetic patient showed a rise of 2.6 +/- 0.7 mmol. To determine whether the decreased CCK levels may have been related to the postprandial hyperglycemia, 7 diabetic subjects were infused with CCK. With this CCK infusion, postprandial glucose levels did not rise. These data suggest, therefore: 1) a role for cholecystokinin in regulating postprandial hyperglycemia in man, 2) abnormalities in CCK secretion occur in NIDDM and may contribute to the hyperglycemia seen in this disease.

Differentiating environmental from disease-related fevers in the term newborn.

It is often difficult to differentiate environmental overheating from disease-related fever in the newborn. The purpose of this study was to establish the normal relationship between peripheral skin temperature and rectal temperature in normal newborn infants whose rectal temperatures were in the upper range of normal (99.0 to 99.6 F) and to compare it with that relationship in infants with fevers known to be disease related. Seventy-eight paired rectal and anterior mid-lower leg skin temperatures were obtained from 41 normal 2-day-old infants. Thirteen similar paired temperatures were measured in 13 full-term infants admitted from home with fever (greater than 100.0 F). The rectal temperature-leg temperature (RT-LT) difference in the normal infants ranged between -1 and +4 F, with a mean of +1.14 F, whereas in the febrile infants it ranged between +5.7 and 12.9 F with a mean of 7.90 F. In febrile infants there was no trend in RT-LT difference as rectal temperatures rose whereas normal infants showed a tendency toward a decreasing RT-LT difference with increasing temperatures. When an RT-LT difference of +3 F is chosen as an arbitrary boundary between environmentally overheated infants and infants with disease-related fevers, it is estimated that 0.5% of infants with disease-related fevers would be incorrectly classified. The RT-LT difference adds an objective guideline for evaluation of temperature elevation in the full-term, appropriate for gestational age neonate.

Hypoxic effects on corneal morphology and function.

Normal corneal metabolism depends on a critical level of oxygen, below which a series of acute corneal responses occur, including an increase in stromal lactate, a reduction in intercellular pH, and an increase in corneal hydration. These acute responses are reversible when normal oxygen is restored; however, it has been shown that chronic exposure to low oxygen levels can result in permanent morphologic changes in the corneal endothelium. Clinicians have expressed concern that these observed structural changes may also be accompanied by alterations in corneal physiology. Whether such effects occur is not known, since it has been difficult to assess human corneal function accurately. Recently, we have developed an in vivo test, able to measure overall corneal hydration control, that can be used to study the effects of hypoxia on corneal function. This test provides information on several characteristics of hydration control, one of which is the percent corneal thickness recovery per hour (PRPH) after inducing corneal swelling. In this study, we assumed that corneal hypoxia accompanies both extended and polymethylmethacrylate (PMMA) contact lens wear and that the dose received is related to the years of past lens wear. Using this paradigm, we explored the relationship of hypoxic dose to an endothelial polymegethism index (EPI), endothelial cell density (ECD), and PRPH in 36 subjects with varying contact lens wearing histories. Based on multiple regression analysis, the relative change (expressed as percent per year) associated with hypoxic dose (adjusted for age and gender) was found to be dose-dependent and corresponded to estimated changes of 1.70%/yr, -0.25%/yr, and -1.26%/yr, with 95% confidence limits of (-0.3, 3.7), (-1.4, 0.9), and (-2.6, 0.06) for EPI, ECD, and PRPH, respectively. These preliminary data suggest that hypoxic exposure alters endothelial morphology and reduces corneal function; however, it is important to indicate that this was a exploratory investigation with several limitations, and that therefore these results should be viewed as preliminary until more definitive studies are completed.

Stromal acidosis affects corneal hydration control.

An estimate of overall corneal hydration control can be obtained by measuring the rate of thickness recovery following induced corneal swelling; it is expressed as the percent recovery per hour (PRPH). This recovery is nearly, but not exactly, exponential, because there appears to be an initial slower recovery phase lasting about 30-40 minutes. This 30-40 minute period of slower recovery corresponds to the time when corneal pH is reduced secondary to the contact lens-induced swelling, suggesting the possibility that stromal acidosis may retard the corneal deswelling process. In this study, we explored the effects of corneal acidosis on hydration control by monitoring corneal recovery under normal and reduced pH conditions. Corneal pH was controlled by having subjects were goggles and exposing their eyes to air (normal pH) or a gas mixture providing 21% O2 and 7% CO2 (low pH). Relative corneal pH levels were monitored by measuring fluorescence intensity (FI) ratios, which showed that the average (+/- standard deviation) FI ratio was significantly lower under 7% CO2 (0.838 +/- .024) vs air (0.985 +/- .025; P = 0.0001), corresponding to approximate pH values of 7.25 vs 7.50. Under these reduced pH conditions, open-eye steady-state (OESS) corneal thickness was not substantially affected. For 10 subjects, mean (+/- SD) corneal thickness decreased 0.93 +/- 3.7 microns vs 1.10 +/- 4.50 microns after exposures to 60 minutes of 7% CO2 and 40 minutes of air (P greater than or equal to 0.45), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Humidity effects on corneal hydration.

Overall corneal hydration control expressed as the percent recovery per hour (PRPH) can be assessed with an exponential model that uses data derived from two kinds of corneal thickness measurements; one from monitoring recovery after inducing corneal swelling, and the other from measurements made after the eye has been open long enough to reach its open-eye steady-state (OESS) corneal thickness. Up to now these thickness measurements have been made without controlling the ambient humidity. It is possible that changes in relative humidity may effect tear film osmolarity sufficiently to change the state of corneal hydration. To evaluate the effects of humidity on hydration control, the OESS and PRPH were determined under several humidity levels. For both the OESS and the PRPH, two substudies were conducted. For the OESS, substudy 1 consisted of measuring corneal thickness when humidity was changed from 30% (ambient) to 52 or 97% controlled humidity. This resulted in mean +/- standard deviation (SD) changes in OESS thickness amounting to -0.33 +/- 3.5 microns and 2.6 +/- 3.4 microns, respectively, with a differential change of 2.94 +/- 3.04 microns (95% confidence interval [CI] from 0.77 to 5.11 microns). Corresponding results for substudy 2 connected with changes from 43% (ambient) to 12 or 97% controlled humidity were -2.4 +/- 2.7 microns and -0.3 +/- 1.9 microns, respectively, with a differential change of 2.1 +/- 1.8 microns (95% CI from 0.9 to 3.4 microns).(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of corneal epithelial permeability to fluorescein. A repeatability study.

PURPOSE: Permeability (Pdc) to sodium fluorescein (F) is a characteristic of the barrier function of the corneal epithelium. The repeatability of several in vivo fluorophotometric methods used to measure permeability in humans remains largely undocumented. This study examines the repeatability of a method based on topical instillation of a single drop of F for the quantitative assessment of Pdc. METHODS: Nine healthy subjects with no history of ocular disease provided 1 (n = 1), 2 (n = 1), or 3 (n = 7) repeated measurements of each eye at successive visits. After making 3 baseline fluorescence scans centrally through the tear film and cornea, 2 microliters of 0.35% F were instilled and 10 fluorescence scans were obtained at approximately 2-minute intervals immediately after instillation. Subsequently, the eyes were rinsed three times with nonpreserved saline and four additional scans were performed. RESULTS: Pdc was calculated by dividing the baseline-corrected postrinse stromal fluorescence by the time integral of the tear film fluorescence calculated over the 20-minute exposure period. After applying a logarithmic transformation to the Pdc estimates, a mixed-model analysis was used to assess measurement repeatability. On the Pdc scale, there is an estimated 95% chance that a second measurement could be as much as 2.88 times higher or 0.35 times lower than a first measurement. CONCLUSIONS: This substantial variability between repeated measurements indicates that the single-drop procedure is unreliable for monitoring individual patient changes. However, with careful sample size planning, this technique can be used in population-based research to compare differences in treatment effects between groups of subjects.

Corneal function during normal and high serum glucose levels in diabetes.

PURPOSE: To assess corneal structure and the effects of acute hyperglycemia on corneal function in subjects with type 1 diabetes. METHODS: Twenty-one diabetic and 21 nondiabetic volunteers of similar age were recruited. Baseline measurements of intraocular pressure (IOP), corneal thickness (CT), corneal autofluorescence (CAF), corneal sensitivity (CST), central and temporal endothelial cell density (DenC and DenT), and coefficient of variation in cell area (CVC and CVT) were taken. Corneal edema was induced, and the percent recovery per hour (PRPH) from hypoxic edema and endothelial permeability to fluorescein were determined. These procedures were done twice in the diabetic subjects under controlled euglycemic (EG) and hyperglycemic (HG) conditions, and once in control subjects while they were fasting. RESULTS: Substantial differences in baseline measurements were found for IOP, CT, CAF, CST, DenC, and CVT. The mean +/- SE corneal swelling in the HG diabetic subjects (51.6 +/- 2.3 microm) was less when compared to the swelling in the EG diabetic subjects (56.2 +/- 1.87 microm, P = 0.05) and the control subjects (58.9 +/- 1.56 microm, P = 0.011). During euglycemia, the mean +/- SE PRPH was less in diabetic subjects than in control subjects (65.0 +/- 3.20 versus 73.8 +/- 1.81%/hour, P = 0.02) but did not differ in diabetic subjects under EG and HG conditions (65.0 +/- 3.20 versus 67.7 +/- 3.1%/hour, P = 0.56). No significant differences were noted between groups in endothelial permeability. CONCLUSIONS: In addition to differences in baseline corneal structure, diabetic subjects showed less corneal swelling and reduced corneal recovery from hypoxia than did control subjects. During acute hyperglycemia, corneal swelling was less than during euglycemia in diabetic subjects, which suggests that hyperglycemia affected corneal hydration control.

Corneal hydration control in Fuchs' dystrophy.

Corneal hydration control was tested in 22 patients with Fuchs' dystrophy, and eight subjects of similar age without the disease, by measuring the corneal thickness recovery from swelling induced by hypoxia or following overnight sleep. Measurement precision was enhanced by using a modified optical pachometer and conducting two test procedures which were analyzed by a coupled exponential model. We have identified three parameters of the recovery from corneal swelling which may be used to describe hydration control: percent recovery per hour (PRPH) (mean 25.4% for Fuchs' and 34.2% for normals), time for 95% of corneal thickness recovery (mean 10.2 hr for Fuchs' and 7.1 hr for normals), and the open-eye steady-state thickness (mean 562 microns for Fuchs' and 537 microns for normals.) A PRPH of 17.1%/hr was identified as the minimum below which the cornea could not regain its open-eye steady state during the entire day and approaches decompensation. Our test procedure quantifies the corneal hydration control mechanism and may provide a test of endothelial function which can be used to monitor the progression of Fuchs' disease and guide decisions related to corneal surgery.

Multivariate prediction of coronary heart disease during 8.5 year follow-up in the Western Collaborative Group Study.

The Western Collaborative Group Study is a prospective study of 3,154 employed men aged 39 to 59 years. Ischemic heart disease occurred in 257 subjects during 8.5 years of follow-up. Risk of coronary heart disease was studied with use of the multiple logistic risk model. The incidence of coronary heart disease had a highly significant association with serum cholesterol level, behavior pattern, cigarette smoking and systolic blood pressure in younger (39 to 49 years) and older (50 to 59 years) men and also with age and corneal arcus in the younger group. Type A behavior pattern was strongly related to the incidence of coronary disease in both age groups, independent of interrelations of behavior patterns with any other risk factor.

Corneal change accompanying orthokeratology. Plastic or elastic? Results of a randomized controlled clinical trial.

Effects of orthokeratology on refractive error, visual acuity, and corneal curvature were monitored on two randomized comparison groups for 364 days of lens wear and 95 days of follow-up after lens wear was discontinued. Approximately 36% of the treatment group compared with 13% of the control group had 1 diopter or more change in refractive error; however, after lens wear was discontinued, there was substantial remission and differences between the groups were small. Although there was a positive correlation between the amount of change during lens wear and the persistence of change after discontinuation, neither the magnitude of persistence nor differences between groups were clinically important. The lack of persistence indicates that the cornea is either highly elastic or has some other memory mechanism. We conclude that orthokeratology produces modest reductions in myopia; however, the effect will not persist without continued lens wear and therefore is of limited clinical value in permanently reducing myopia.

Type A behavior and cancer mortality. Theoretical considerations and preliminary data.

If stress and cancer are related by coping failure, that connection presumably involves the immune system. This involvement has already been shown in animals. It can be hypothesized that Type A personalities (driving, impatient, sometimes hostile) go through states of repeated frustration because of unachieved goals. From that point of view, Type A individuals are alternately able to cope and unable to cope. Such a pattern would theoretically tend toward repeated episodes of suppression and recovery of the immune system, with increased probability of growth of transformed cells. An opposing hypothesis, derived from human survival studies, suggests that a subgroup of Type B individuals (termed "Type C"--accepting, giving-up) are more likely to suffer a poor prognosis. A preliminary study relating Type A/B behavior pattern to cancer mortality was done in a cohort of 3154 men from the Western Collaborative Group Study (WCGS). The cancer mortality rate for the period 1960-1977 was 0.037 for Type A subjects (58 cancer deaths/1589 Type A subjects), and 0.025 for Type B subjects, yielding an odds ratio of 1.55. The odds ratio dropped to 1.29 (95% confidence interval = 0.84-1.96) when controlled for age, cigarette smoking, serum cholesterol, systolic blood pressure, and education. Preliminary analysis from a follow-up to mid-1983 shows a similar association. The findings suggest that, if anything, Type A subjects are more likely to die of cancer than Type B subjects. Although the finding is not strongly suggestive of a clinically or theoretically significant association between Type A/B behavior pattern and cancer mortality, it is sufficiently interesting to warrant further investigation.

Tear mixing under a soft contact lens: effects of lens diameter.

PURPOSE: Tear exchange under a soft contact lens is modest, and higher exchange rates may be necessary to reduce extended-wear complications; what is not known is the optimal soft lens design to increase tear mixing. We explored the effect of lens diameter on tear mixing. METHODS: Twenty-three subjects wore four different soft contact lenses with diameters of 12.0, 12.5, 13.0, and 13.5 mm. Tear mixing was quantified by placing fluorescein isothiocyanate-dextran on the posterior lens surface, inserting the lens, and monitoring the changes in fluorescence intensity in the postlens tear film. Tear mixing, expressed as the percentage decrease in fluorescence intensity per blink, was estimated using an exponential model. Lens movement was videotaped and lens comfort was graded on a 50-point scale (50 = excellent comfort). Subjects reporting a comfort level of less than 35 were excluded. RESULTS: The mean +/- SE tear mixing rates were 1.82% +/- 0.17%, 1.61% +/- 0.16%, 1.34% +/- 0.17%, and 1.24% +/- 0.17% per blink for the 12.0-, 12.5-, 13.0-, and 13.5-mm diameter lenses, respectively. By regression analysis we found that, on average, mixing under the 12.0-mm lens was 0.59% per blink greater than with the 13.5-mm lens (P = .0024). Lens diameter was a significant predictor of lens comfort, and adjusting for the effects of comfort weakened the relationship between diameter and tear replenishment rate, although the mean rate under the 12.0-mm lens was still 0.43% per blink greater than with the 13.5-mm lens (P = .0468). CONCLUSIONS: These data suggest that smaller-diameter soft lenses provide substantially better tear mixing than larger lenses; however, even small lenses provide modest tear mixing compared with rigid contact lenses.

Epithelial permeability reflects subclinical effects of contact lens wear.

AIMS: Recently, it was reported by the authors that a single drop fluorophotometric technique for estimating corneal epithelial permeability (Pde) to fluorescein is not sufficiently precise for monitoring permeability changes in individual patients., but may be useful for evaluating mean differences in Pdc in population based research. To determine whether this technique provides a more sensitive index of epithelial integrity compared with conventional clinical assessments, the effects of mild corneal trauma on Pdc, the slit lamp appearance of the cornea, and corneal thickness (CT) were assessed. METHODS: After baseline slit lamp examinations (SLE) and CT measurements, one randomly chosen eye of each of 32 normal subjects underwent 1 hour of closed eye soft contact lens (CL) wear while the fellow eye served as a control (no CL). After removing the CL, the SLE and CT measurements were repeated. Then, Pdc to fluorescein was assessed using a single drop fluorophotometric method refined to enhance feasibility, precision, and accuracy. RESULTS: The mean (95% confidence interval) difference in natural log (Pdc) between 32 pairs of eyes (CL minus no CL) was 0.341 (0.069, 0.613), p = 0.016. By contrast, none of the 32 subjects exhibited corneal epithelial disruption upon SLE with white light following the closed eye period. Also, no substantial differences were apparent in the corneal swelling response between paired eyes, mean delta CT (95% CI) = -2.31(-7.53, 2.91) microns, p = 0.37. CONCLUSIONS: Pdc measurements, used in studies of modest sample size, appear capable of detecting average differences in corneal barrier function that remain undetectable by SLE or pachymetry.

Food choices of obese and non-obese persons.

An observational study of food choices of patrons of a campus cafeteria was conducted to ascertain whether obese and non-obese individuals had the same eating patterns. Subjects were unaware of the monitoring of their food choices. Patrons were categorized by visual appraisal into forty-eight cross-classified groups according to sex (male, female), body build (slender, sturdy, stocky, obese), height (tall, average, short), and age (less than and more than thirty years of age). Servings of food were estimated visually as it was not possible to determine exact amounts. Foods were classified as either protective foods with good contributions of nutrients in proportion to calories (Group B) or as high-calorie, low-nutrient foods (Group A). Significant findings were the tendency for those in the obese category to select more servings of food and more foods from the high-calorie, low-nutrient Group A foods, when compared with selections of persons in the other body-build groups. A more controlled study is suggested for more definitive results. Also pointed out was the importance of recognizing that excessive food intake may be one possibility among many in cases of refractory obesity.

Physical workplace factors and return to work after compensated low back injury: a disability phase-specific analysis.

Little is known about predictors of duration of work disability (DOD). This cohort study of 433 workers' compensation claimants estimated DOD for job, injury, and demographic factors during consecutive disability phases using Cox regression analysis. DOD was calculated from administrative records. Results show that DOD increases with the time spent bending and lifting or pushing or pulling heavy objects at work, but it is unrelated to sitting, standing, or vibration. Younger age, longer pre-injury employment, less severe injuries, and a previous back injury predicted shorter disability, the latter factor only during the subacute/chronic disability phases. The effect of injury severity decayed over time. This study demonstrates the usefulness of a phase-specific analysis and shows that physical job and injury factors have a significant and time-varying impact on DOD.

Doctor proactive communication, return-to-work recommendation, and duration of disability after a workers' compensation low back injury.

Although doctors are increasingly evaluated on the basis of return-to-work (RTW) outcomes, the effect of doctor-patient communication about the workplace and RTW after an occupational injury has received little research attention. The effect of patient-reported doctor communication on duration of disability was examined retrospectively in a 3-year cohort of 325 claimants with a lost-time low back injury. Although doctor proactive communication was associated with a greater likelihood of RTW during the acute phase (< 30 days of disability), this effect disappeared when injury and workload characteristics were taken into account. A positive RTW recommendation was associated with about a 60% higher RTW rate during the subacute/chronic phase (> 30 days of disability) only. Prospective studies are needed to confirm this effect. The impact of physician communication on RTW is largely confounded by injury and workplace factors.

The association between pH level and corneal recovery from induced edema.

Corneal acidosis has been shown to reduce corneal hydration control (CHC) as measured by the rate, expressed as the percent recovery per hour (PRPH), at which the thickness of the cornea decreases exponentially after an increased hydration load. Since the effect of pH on corneal function is of scientific interest and may have clinical implications, we explored the relationship between pH and PRPH in greater detail by examining the effect of different stromal pH levels on corneal hydration control. Corneal edema was induced using a 90-min exposure to wearing a hypoxic contact lens (CL). Following removal of the CL, random assignment over four eye-test combinations of either 0, 3, 5, and 7% CO2 were made while pH and corneal thickness were monitored using slit lamp fluorophometry and optical pachometry to measure corneal pH and corneal thickness, respectively. From these measurements we determined the pH-dose/PRPH relationship. The average stromal pH +/- 1SD resulting from exposure to either the 0, 3, 5, and 7% CO2, was 7.65 +/- 0.11, 7.30 +/- 0.09, 7.15 +/- 0.08 and 7.04 +/- 0.07 (p < 0.001), respectively. Analysis based on a quadratic model of the dose-response relationship between PRPH and corneal pH indicates that PRPH is relatively unchanged for pH in the physiological range (pH = 7.40-7.65) and then decreases notably below the physiological range.

A two-state recurrent stochastic model with time-dependent transition rates.

The two-state recurrent stochastic model with time-independent transition rates is generalized to a model with time-dependent transition rates. The rates can be any general function of external time, that is, any general function of the calendar time in which the process unfolds. Formulas for the state transition probabilities, the proportion of individuals in a particular state at time t, the distribution function, and the expectation of the number of individuals in a particular state at time t are derived.