Preliminary evidence for genetic anticipation in Crohn's disease.

BACKGROUND: The term genetic anticipation is used to describe earlier onset of disease, increased severity, or both, in succeeding generations of families affected by a particular disease. This process has been linked with expanded genomic trinucleotide repeat regions in some neurological disorders. Crohn's disease, an inflammatory bowel disorder, has genetic influences, which remain undefined. We studied pairs of two-generation first-degree relatives with Crohn's disease to seek evidence for genetic anticipation in this disorder. METHODS: Through retrospective review of the records of 552 patients treated for Crohn's disease at Johns Hopkins Hospital, we identified 27 pairs of two-generation first-degree relatives. We also studied 32 such pairs identified through a multicentre survey. After exploratory analyses by t tests, a generalised estimating equations approach was used to fit a marginal regression model. FINDINGS: The age at diagnosis was earlier in the younger member of the pair both in the Johns Hopkins Hospital dataset (18.9 [SE 6.9] vs 31.4 [12.0] years) and in the multicentre survey dataset (16.9 [7.4] vs 33.1 [11.9] years). The regression model confirmed the findings: the best-fitting model for the Johns Hopkins Hospital data showed an average 10.8 (SE 4.2) year difference in age at diagnosis between parent and child; that for the multicentre data showed an average difference of 15.1 (1.5) years. There was evidence of a further difference between the second and third generations. Disease was more extensive in the offspring than in the parent for 15 of the 27 pairs at Johns Hopkins Hospital; in 13 of these pairs the affected parent was the father. INTERPRETATION: The evidence of a lower age at diagnosis and a greater extent of disease in the younger member of two-generation pairs affected by Crohn's disease, as well as the association with paternal transmission, suggest that genetic anticipation does occur in Crohn's disease. A search for triplet repeat regions is warranted.

Effect of guar gum on mineral balances in NIDDM adults.

The self-selected diet of 16 subjects with non-insulin-dependent diabetes mellitus (NIDDM) was supplemented for 6 mo with either a granolalike bar containing 35.5 g carbohydrate and 6.6 g guar gum/bar or a placebo bar containing carbohydrate but no guar gum. Subjects consumed a mean of 4.8 bars/day. Average guar gum consumption at the end of the study was 31.7 g/day. One week before and at the end of the study, subjects were admitted to a metabolic ward and fed a controlled diet similar to their self-selected diet. Food, feces, and urine were composited for analysis of iron, zinc, copper, calcium, magnesium, and manganese. Eight subjects consuming the guar gum supplement and 6 subjects consuming the placebo bar completed collections for mineral balance. Neither consumption of guar gum nor placebo bar significantly changed apparent mineral balance for iron, copper, zinc, calcium, manganese, or magnesium from prestudy levels to 6-mo levels, and no significant differences were observed between the two groups. With the exception of copper, men consumed significantly more minerals than women. We conclude that consumption of guar gum by patients with NIDDM does not adversely affect apparent mineral balance.

Diet and colorectal cancer.

Data on the relationship of dietary intakes to the risk of colorectal cancer is controversial. The identification of any single causal feature in human diet for colorectal cancer is an improbable outcome because of the complexity of neoplasia, interaction of dietary factors and carcinogens, and the varied forms of colorectal cancer. The same general dietary program advocated for reduced cardiovascular risk is probably suitable for cancer reduction as well.

Nutritional risk of high-carbohydrate, guar gum dietary supplementation in non-insulin-dependent diabetes mellitus.

Dietary supplementation with high-carbohydrate, guar gum fiber (HCF) is effective in acutely blunting postprandial blood glucose levels. We report the effect of such supplementation on the diet and nutritional status of a group of 16 subjects with non-insulin-dependent diabetes mellitus (NIDDM) who incorporated either HCF bars (35.7 g carbohydrate and 6.6 g guar gum/bar) or placebo bars (identical except for the absence of guar gum) into the diet for 6 mo as part of a double-blind, randomized clinical trial. The HCF subjects achieved mean daily intake of 4.8 +/- 0.4 bars, constituting 51.2 +/- 3.1% of total calories and providing 29.7 +/- 2.6 g guar gum daily. Energy intakes and body weight did not change significantly in either group. Food consumption patterns and nutrient intakes did change, although not enough to impair the nutritional integrity of the diet because the bars themselves served as a source of nutrients. The bars were rich in thiamin, B6, folacin, phosphorus, iron, zinc, and copper, adequately replacing any decrease in nutrient intake as a result of foods being dropped from the diet. In fact, daily intakes of B6, folacin, and copper actually increased due to contributions from the bars. Nutrients in which the bars were poor (vitamins A, C and B12) resulted in suboptimal intakes (less than 66% RDA). Although no significant change in nutritional status of the HCF group occurred as determined by arm muscle area, arm fat area, hemoglobin, hematocrit, or serum albumin, transferrin, iron, ferritin, calcium, phosphate, B12, and magnesium levels, these indicators of nutritional status are rather insensitive.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term effects of guar gum on blood lipids.

While guar gum has been shown to lower total cholesterol and low density lipoprotein cholesterol (LDL-C) in diabetic patients over the short-term, the long-term effects are less well studied and may be unpredictable. Granola bars with and without 6.6 g guar gum were developed and fed to 16 adult volunteers with Type II diabetes mellitus who had been randomized in a double-blind fashion into guar and placebo groups of equal size. Four to six bars were consumed daily with an ad lib diet over a 6-month period. Total cholesterol, total high density lipoprotein cholesterol (HDL-C), subfractions HDL2-C and HDL3-C, LDL-C, and beta-apoprotein were measured at 0 and 6 months. Although LDL-C was lower and triglycerides higher at 6 months than at baseline, these changes were of equal magnitude and direction in both guar and placebo groups. Using each subject as his own control, only the change in triglycerides was statistically significant (P less than 0.025). When male subjects alone were analyzed, the guar group showed a statistically significant decrease in LDL, while the placebo group did not. Other lipid parameters were not significantly changed during the study, despite a positive effect on carbohydrate metabolism from the guar bars. The data suggest either that the hypolipemic effects of guar gum in patients with Type II diabetes mellitus are not sustained for 6 months, or the effects occur only in men.

Long-term ingestion of guar gum is not toxic in patients with noninsulin-dependent diabetes mellitus.

The use of diets rich in unabsorbable carbohydrate ("fiber") has been advocated for the treatment of noninsulin-dependent diabetes mellitus (NIDDM). The soluble viscous fibers such as guar gum are most effective in normalizing carbohydrate intolerance in such patients; particulate fibers such as cellulose have little or no effect. While the latter are known to affect many aspects of nutrition when consumed in great quantity, little is known of the toxicity of guar gum. Eight adults with NIDDM are reported here who consumed at least 30 grams of guar gum for at least 16 weeks without any change in hematologic, hepatic, or renal function. Serologic screening revealed no change in lipid, protein or mineral metabolism, and no change in electrolyte balance. It is concluded that consumption of 30 grams of guar gum per day for prolonged periods is without serious consequences.

Flattening postprandial blood glucose responses with guar gum: acute effects.

It has been proposed that high-carbohydrate, high-fiber (HCF) diets might serve as useful therapeutic modality in non-insulin-dependent diabetes mellitus (NIDDM). One problem in evaluating clinical trials of this therapy is that, by their very nature, the trials cannot be double blinded. We have developed HCF and placebo granola-type bars using complex absorbable carbohydrate and guar gum fiber to circumvent this methodologic problem. The HCF bars, when consumed with an ad lib. diet, assure an HCF intake without imposing other dietary restrictions. To test the short-term efficacy of the bars, 9 normal adult volunteers, 2 women with impaired glucose tolerance, and 20 patients with NIDDM consumed the bars alone or with meals. Blood glucose responses when HCF bars were consumed alone were blunted when compared with the placebo response (P less than 0.0005 to P less than 0.002), with the most marked suppression occurring in the early postprandial period. In contrast, when the bars were consumed along with breakfast, HCF and placebo responses were virtually identical in the early postprandial period, but showed a progressively greater difference from 90 to 240 min (P less than 0.02 to P less than 0.0005). When consumed with lunch as well as breakfast, the HCF bars caused flattening of blood glucose responses during the late postprandial period after breakfast and maintained flattened responses during the early and late postprandial periods after lunch (P less than 0.05 to P less than 0.005). It is concluded that these HCF bars can be used to blunt postprandial blood glucose responses, in subjects with either normal or abnormal carbohydrate metabolism.

Trends in incidence rates of ulcerative colitis and Crohn's disease.

Between 1960 and 1979, three studies were conducted in the Baltimore Standard Metropolitan Statistical Area to ascertain the incidence rates of first hospitalizations for ulcerative colitis and Crohn's disease. The age-adjusted rates per 100,000 population for the 1977-1979 survey for ulcerative colitis in white and nonwhite males and females were 2.92, 1.79, 1.29, and 2.90, respectively; the Crohn's disease rates were 3.39, 3.54, 1.29, and 4.08, respectively. In Baltimore the age-adjusted rate for Crohn's disease has increased to exceed the ulcerative colitis rate for whites of both sexes and nonwhite females. The ulcerative colitis and Crohn's disease rates for nonwhite males are similar. The rate for white males exceeds that for nonwhite males for both ulcerative colitis and Crohn's disease, but the converse is true for females. Females have higher rates than males for Crohn's disease in both color groups and for ulcerative colitis among nonwhites. White ulcerative colitis rates are higher for males than for females. From the first to the second surveys, the white male and female rates for ulcerative colitis converge with increasing male and decreasing female rates, but then both decline from the second to the third surveys. For Crohn's disease, the age-adjusted rates increased for whites of both sexes and nonwhite females from the first to second surveys. The Crohn's disease rates appeared to stabilize for whites of both sexes between the second and present surveys, but they increased for nonwhites of both sexes. Trends in age-adjusted rates for other areas are also discussed.

Incidence rates of ulcerative colitis and Crohn's disease in fifteen areas of the United States.

A study was carried out during 1973 to determine the incidence of first hospitalizations for ulcerative colitis and Crohn's disease in 15 areas of the United States, including communities of widely varied size, climatic, ethnic, racial, and socioeconomic characteristics. The following descriptions apply to incidence rates per 100,000 population for the aggregate of the 15 areas. Ulcerative colitis had a bimodal age distribution in white males (with peaks at ages 20-29 and 70-79 yr) and females (with peaks at ages 30-39 and 70-79 yr). Crohn's disease had a bi- or trimodal age distribution in white males (with peaks at ages 20-29, 50-59, and 70-79 yr) and females (with peaks at ages 20-29, 50-59, and 70-79 yr). The age, sex, and geographic distributions that were observed in this study may have important etiologic implications.

Upper gastrointestinal bleeding. Nature and magnitude of the problem in the U.S.

This study examines the frequency of upper GI bleeding in the United States population, and the use of diagnostic endoscopy in its evaluation. Data from the National Hospital Discharge Survey and National Ambulatory Medical Care Survey are used, as well as limited data from the Veteran's Administration and State of Wisconsin. There were almost 1.1 million discharges from U.S. hospitals in 1978 with diagnoses related to UGI bleeding. Using an indirect method of estimation based on cases of peptic ulcer specified as bleeding, we estimate the rate of hospitalization with UGI bleeding as 150 per 100,000 population per year. About one-sixth of these patients underwent gastroscopy and/or esophagoscopy in 1978, approximately a three-fold increase over five years previously. National mortality from UGI bleeding decreased approximately 40 percent between 1968 and 1977, but data are inadequate to infer a relationship to increased use of endoscopy. Suggestions for further research are specified.