Reproducibility of the oral glucose tolerance test in overweight children.

OBJECTIVE: We examined the reproducibility of the oral glucose tolerance test (OGTT) in overweight children and evaluated distinguishing characteristics between those with concordant vs. discordant results. DESIGN: Sixty overweight youth (8-17 yr old) completed two OGTTs (interval between tests 1-25 d). Insulin sensitivity was assessed by the surrogate measures of fasting glucose to insulin ratio, whole-body insulin sensitivity index, and homeostasis model assessment of insulin resistance, and insulin secretion by the insulinogenic index with calculation of the glucose disposition index (GDI). RESULTS: Of the 10 subjects with impaired glucose tolerance (IGT) during the first OGTT only three (30%) had IGT during the second OGTT. The percent positive agreement between the first and second OGTT was low for both impaired fasting glucose and IGT (22.2 and 27.3%, respectively). Fasting blood glucose had higher reproducibility, compared with the 2-h glucose. Youth with discordant OGTTs, compared with those with concordant results, were more insulin resistant (glucose/insulin 2.7+/-1.4 vs. 4.1+/-1.8, P=0.006, whole-body insulin sensitivity index of 1.3+/-0.6 vs. 2.2+/-1.1, P=0.003, and homeostasis model assessment of insulin resistance 10.6+/-8.1 vs. 5.7+/-2.8, P=0.001), had a lower GDI (0.45+/-0.58 vs. 1.02+/-1.0, P=0.03), and had higher low-density lipoprotein cholesterol (117.7+/-36.6 vs. 89.9+/-20.1, P=0.0005) without differences in physical characteristics. CONCLUSIONS: Our results show poor reproducibility of the OGTT in obese youth, in particular for the 2-h plasma glucose. Obese youth who have discordant OGTT results are more insulin resistant with higher risk of developing type 2 diabetes mellitus, as evidenced by a lower GDI. The implications of this remain to be determined in clinical and research settings.

Structure characterization of human serum proteins in solution and dry state.

The present report describes application of advanced analytical methods to establish correlation between changes in human serum proteins of patients with coronary atherosclerosis (protein metabolism) before and after moderate beer consumption. Intrinsic fluorescence, circular dichroism (CD), differential scanning calorimetry and hydrophobicity (So) were used to study human serum proteins. Globulin and albumin from human serum (HSG and HSA, respectively) were denatured with 8 m urea as the maximal concentration. The results obtained provided evidence of differences in their secondary and tertiary structures. The thermal denaturation of HSA and HSG expressed in temperature of denaturation (Td, degrees C), enthalpy (DeltaH, kcal/mol) and entropy (DeltaS kcal/mol K) showed qualitative changes in these protein fractions, which were characterized and compared with fluorescence and CD. Number of hydrogen bonds (n) ruptured during this process was calculated from these thermodynamic parameters and then used for determination of the degree of denaturation (%D). Unfolding of HSA and HSG fractions is a result of promoted interactions between exposed functional groups, which involve conformational changes of alpha-helix, beta-sheet and aperiodic structure. Here evidence is provided that the loosening of the human serum protein structure takes place primarily in various concentrations of urea before and after beer consumption (BC). Differences in the fluorescence behavior of the proteins are attributed to disruption of the structure of proteins by denaturants as well as by the change in their compactability as a result of ethanol consumption. In summary, thermal denaturation parameters, fluorescence, So and the content of secondary structure have shown that HSG is more stable fraction than HSA.

Beer consumption and changes in stability of human serum proteins.

The aim of this study was to evaluate the influence of beer consumption (BC) on the functional and structural properties of human serum proteins (HSP). Thirty-eight volunteers (after coronary bypass) were divided into two groups: experimental (EG) and control (CG). Nineteen volunteers of the EG consumed 330 mL per day of beer (about 20 g of alcohol) for 30 consecutive days. The CG volunteers consumed mineral water instead of beer. Blood samples were collected from EG and CG patients before and after the experiment. Albumin (Alb), globulin (Glo), and methanol-precipitable proteins (MPP) from human serum were denatured with 8 M urea. Fluorescence and electrophoresis were employed in order to elucidate urea-induced conformational changes and structural behavior of proteins. The measured fluorescence emission spectra were used to estimate the stability of native and denatured protein fractions before and after BC. It was found that before BC the fractions most stable to urea denaturation were Glo, Alb, and MPP fractions. After BC in most of the beer-consuming patients (EG) some changes in native and denatured protein fractions were detected: a tendency to lower stability and minor structural deviations. These qualitative changes were more profound in MPP than in Alb and Glo. Thus, Glo is more resistible to alcohol influence than Alb, which in turn is more resistible than MPP. No serum protein changes were detected in patients of CG.

Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group.

OBJECTIVE: To investigate and monitor the patterns in incidence of childhood type 1 diabetes worldwide. RESEARCH DESIGN AND METHODS: The incidence of type 1 diabetes (per 100,000 per year) from 1990 to 1994 was determined in children < or =14 years of age from 100 centers in 50 countries. A total of 19,164 cases were diagnosed in study populations totaling 75.1 million children. The annual incidence rates were calculated per 100,000 population. RESULTS: The overall age-adjusted incidence of type 1 diabetes varied from 0.1/100,000 per year in China and Venezuela to 36.8/100,000 per year in Sardinia and 36.5/100,000 per year in Finland. This represents a >350-fold variation in the incidence among the 100 populations worldwide. The global pattern of variation in incidence was evaluated by arbitrarily grouping the populations with a very low (<1/100,000 per year), a low (1-4.99/100,000 per year), an intermediate (5-9.99/100,000 per year), a high (10-19.99/100,000 per year), and a very high (> or =20/100,000 per year) incidence. Of the European populations, 18 of 39 had an intermediate incidence, and the remainder had a high or very high incidence. A very high incidence (> or =20/ 100,000 per year) was found in Sardinia, Finland, Sweden, Norway Portugal, the U.K., Canada, and New Zealand. The lowest incidence (<1/100,000 per year) was found in the populations from China and South America. In most populations, the incidence increased with age and was the highest among children 10-14 years of age. CONCLUSIONS: The range of global variation in the incidence of childhood type 1 diabetes is even larger than previously described. The earlier reported polar-equatorial gradient in the incidence does not seem to be as strong as previously assumed, but the variation seems to follow ethnic and racial distribution in the world population.

Intrinsic tryptophan fluorescence of human serum proteins and related conformational changes.

The unfolding of human serum proteins (HSP) was studied by measuring the intrinsic fluorescence intensity at a wavelength of excitation corresponding to tryptophan's or typosine's fluorescence and surface hydrophobicity. The maxima emission wavelengths (lambdamax) of human serum albumin (HSA) and human serum globulin (HSG) before beer consumption (BC) were 336.0 and 337.0 nm and after BC shifted to 335.0 and 334.0 nm, respectively. The surface hydrophobicity slightly increased after BC. In a solution of 8 M urea the lambdamax of BSA shifted to 346.4 and that of BSG to 342.5 nm. In contrast, in the same solution but after BC the lambdamax positions of HSA and HSG shifted to 355.9 and 357.7 nm, respectively. A decrease in fluorescence intensity, a shift in the maximum of emission, and an increase in surface hydrophobicity which reflected unfolding of proteins were observed. Here we provide evidence that the loosening of the HSP structure takes place primarily in various concentrations of urea before and after beer consumption. Differences in the fluorescence behavior of the proteins are attributed to disruption of the structure of proteins by denaturants as well as by the change in their compactability as a result of ethanol consumption.

Type II diabetes mellitus: no longer just adults.

Type II diabetes mellitus is no longer exclusively a disease of adults. Health care professionals and agencies must gain a better understanding of (1) the epidemiology of type II diabetes mellitus in childhood; (2) the phenotypic, biochemical, metabolic, and autoimmune characteristics at diagnosis and during the course of the disease; (3) therapeutic modalities; (4) screening of high-risk populations; and (5) prevention strategies. This will be one of the challenges in pediatric diabetes as we approach the 21st century.

Islet cell autoimmunity in white and black children and adolescents with IDDM.

OBJECTIVE: To compare the frequency of islet cell antibodies (ICA) and antibodies to GAD65 and IA-2(ICA512) between black and white children and adolescents at the diagnosis of IDDM in a large consecutive series of cases from Children's Hospital of Pittsburgh. RESEARCH DESIGN AND METHODS: ICA and antibodies to GAD65 and IA-2 were measured in 437 white and black children and adolescents who were diagnosed with IDDM at < 19 years of age at Children's Hospital of Pittsburgh from January 1983 to December 1985, from January to December 1989, and from January 1996 to December 1997. RESULTS: The prevalence of ICA(H), GAD65, and IA-2 antibodies was significantly lower in blacks than whites at onset of the disease. In contrast, the prevalence of ICA(R) alone was higher in blacks. None of the antibodies were present in 12% of the blacks compared with 4% in whites. The same pattern was seen in both sexes. The prevalence of antibodies in white patients with onset of IDDM at <11 years of age was no different than in those who developed IDDM during adolescence. In contrast, black patients showed a significantly lower prevalence of almost all antibodies in the adolescent group. CONCLUSIONS: Black adolescents were more likely to not have antibodies, suggesting either that they have a nonautoimmune type of diabetes or that antibodies are not being detected by these assays.

Was there an epidemic of diabetes in nonwhite adolescents in Allegheny County, Pennsylvania?

OBJECTIVE: To determine the incidence of IDDM in children aged < 20 years at diagnosis in Allegheny County, Pennsylvania, for the period from 1 January 1990 to 31 December 1994 and to compare the incidence between whites and nonwhites in the same area and for the same time period. RESEARCH DESIGN AND METHODS: All new patients diagnosed between January 1990 and December 1994 who were aged < 20 years, on insulin, and residents of Allegheny County at diagnosis were identified from medical records of 23 hospitals in the Allegheny County area. To verify the completeness of the hospitals using the capture-recapture method, pediatricians and diabetologists were used as a secondary source. RESULTS: A total number of 257 patients were identified. The overall age-standardized incidence rate was 16.7/100,000. Nonwhites had a slightly higher incidence (17.6/100,000) than whites (16.5/100,000). In the 15-19 years age-group, the incidence in nonwhites (30.4/100,000) was almost three times higher than that in white (11.2/100,000) and more than two times higher than that in the previous period (from 1985 to 1989) (13.8/100,000). CONCLUSIONS: For the first time in the Allegheny County registry, and in any other registry, nonwhites showed a higher incidence of IDDM than whites. The high incidence in the 15-19 years age-group was responsible for this phenomenon. This epidemic of diabetes in adolescent nonwhites may be the result of a rising incidence of classical IDDM or another type of diabetes. Further studies using population-based registries are needed to determine whether this increase is being seen in other areas and other ethnic groups and to clarify the reasons for the increase in IDDM among blacks.

Effect of beer consumption on plasma magnesium: randomized comparison with mineral water.

Moderate consumption of ethanol lowers mortality from coronary artery disease, and one of the possible mechanisms is an antiarrhythmic action. We therefore investigated the effect of a small daily dose of beer on plasma electrolytes. 52 men who seldom drank alcohol, clinically stable more than one year after coronary bypass surgery, were randomized to drink either 330 mL beer (containing about 20 g ethanol) or mineral water with similar potassium, magnesium, calcium and sodium content daily for 30 days. Plasma electrolytes and liver function indices, and also heart rate, blood pressure and weight, were measured before and after the trial period. The only significant before-and-after difference was in the group consuming beer, whose plasma magnesium rose from 0.89 (SD 0.01) to 0.98 (SD 0.02) mmol/L (P < 0.0025). This level of beer consumption did no obvious harm to liver function and its possibly beneficial effect on plasma magnesium deserves further investigation.

Moderate beer consumption and positive biochemical changes in patients with coronary atherosclerosis.

OBJECTIVES: The aim of this study was to evaluate the influence of moderate beer consumption on lipid metabolism and antioxidant activity in patients (pts) with coronary artery disease (CAD). SUBJECTS: Forty-eight male pts with CAD not alcohol beverages consumers were randomly divided into experimental (EG) and control (CG) groups, 24 pts each. SETTING: Rehovot University Hospital, Israel. INTERVENTION: Every patient of the EG during a period of 30 consecutive days consumed 330 ml of Maccabee beer (> 20 g of alcohol). The pts of the CG did not consume alcohol during the trial period. METHODS: A wide range of tests including total cholesterol, LDL-C, HDL-C, total tocopherol and alpha-tocopherol. RESULTS: Only in the pts of the EG were found a tendency to an increase of the level of HDL-C and a statistically significant rise in the level of total tocopherol (P < 0.025) and alpha-tocopherol (P < 0.025). CONCLUSIONS: Even a short period of moderate beer consumption leads to some favourable biochemical changes in blood of pts with CAD which are widely regarded as indicators of CAD prevention.

Moderate beer consumption and the blood coagulation in patients with coronary artery disease.

OBJECTIVES: To evaluate the influence of a short period of moderate beer consumption on the status of the thrombolitic activity in patients with coronary artery disease (CAD). SUBJECTS AND DESIGN: From 28 patients with two- or three-vessel CAD 22 were randomly assigned to an experimental group (EG) and six to control group (CG). Before and after completion of the study every one of the 28 patients was examined and a wide range of laboratory tests was performed. SETTING: A University Hospital in Israel. INTERVENTION: Of the EG, 22 patients consumed 330 mL of beer day-1 (20 g of alcohol) for the 30-day period in addition to the usual antiatherosclerotic diet. Patients of the CG did not consume alcohol beverages. MAIN OUTCOME MEASURES: Fibrinogen, prothrombin time (PT), coagulant activity of Factor VII (F VIIc) and Factor VII antigen (F VIIag), and plasminogen activator inhibitor (PAI) levels were studied. RESULTS: After the investigation a statistically significant decrease was found in F VIIc (P < 0.01) and F VIIag (P < 0.001) and to a lesser extent a decrease in the value of PAI. Fibrinogen and PT remained unchanged in the EG also. CONCLUSIONS: Even a short period of moderate beer consumption results in a decrease in thrombogenic activity. The only sensitive tests were F VIIc and F VIIag. The decrease in thrombogenic activity may be the main cause of decreased mortality in patients with CAD who consume moderate quantities of alcoholic beverages.

The need for a global health disaster network.

When a disaster occurs, a major difficulty is knowing where to find accurate information, and how to help coordinate efforts to share accurate information in a quick and organized manner. The establishment of a global information network, that is in place before a disaster occurs, could link all the communication efforts for relief. We propose that a Global Health Unit for Disaster and Relief Coordination be set up as part of the Global Health Network, utilizing the Internet as its backbone. This Unit would establish the links for the disaster information mosaic.

Telepreventive medicine.

There have been dramatic improvements in health during the past 50 years, and public health measures have made a major contribution. Much of public health consists of information transfer. The application of telecommunications technology to public health and preventive medicine would enhance our ability to transmit information and improve global health. The idea of telemedicine has received considerable attention but has not thus far included preventive medicine. We have outlined a global electronic health network with seven main components: connectivity, telemonitoring of disease, "distance education" for public health workers, electronic connection of nongovernment organizations, a combined degree in public health and communications, an electronic scientific research server, and a home page on the World Wide Web. A commitment to the integration of telecommunications and public health holds great promise for improving the health status of the world's population.

Global epidemiology and public health in the 21st century. Applications of new technology.

Epidemiology and public health need to change for the upcoming problems of the 21st century and beyond. We outline a four-point approach to produce this change. The first one is to take a systems approach to disease. The second approach discussed is the use of new techniques to "count" disease using capture-recapture. The third represents the application of telecommunications, especially the Internet, to public health. The fourth and final component represents the application, at the local health department level, of a total quality approach, as espoused by Deming, for the prevention of disease.