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insulin and C-peptide rather than glucose is a more subtle form of this fallacy. It seems unwise to conclude that associations between diabetes and ethnicity are "accounted for" when the adjusted 95% confidence intervals include an odds ratio of 16 for diabetes in Afro-Caribbeans versus Europeans and an odds ratio of 31 for diabetes in Gujaratis versus Europeans. With only 23 new cases the

study is too small to answer such questions usefully. Department of Epidemiology and Population Sciences, London School of Hygiene and Tropical Medicine, London WC1E 7HT

P. M. MCKEIGUE

Sip,—Dr Cruickshank and co-workers, comparing ethnic differences in fasting plasma C-peptide and insulin in relation to glucose tolerance and blood pressure, speculate that fat intake modulates hepatic handling of insulin. The hypothesis is interesting, because both the amount and quality of fat ingested may have an impact on insulin and glucose metabolism independent of obesity or fat distribution in the body. We have studied the effects of intensified diet therapy on metabolic control and cardiovascular risk factors in patients with newly diagnosed non-insulin-dependent diabetes.’ The main determinants for improved metabolic control in a multiple regression anslysis were loss of body weight, enhanced insulin secretion in an oral glucose-tolerance test, reduction in the proportion of saturated fatty acids in serum phospholipids, and fasting blood glucose at baseline. We found that reduction in dietary intake of saturated fats may contribute to improved glucose tolerance, possibly via diminished insulin resistance. We cannot rule out an influence of diminished fat intake on hepatic handling of insulin because post-glucose insulin levels were increased in our patients after diet intervention lasting for a year. Other evidence for an impact of dietary fatty acids on insulin sensitivity comes from a study done in healthy young studentsIn this randomised, crossover study, where each diet period lasted for 3 weeks, a diet high in saturated fatty acids was compared with one high in polyunsaturated fatty acids (PUFA). Both diets provided 40% of energy from fats (20% from saturated in the first, with 15 % monounsaturated, and only 5% PUFA versus 10%, 15%, and 15%, respectively in the other). When the students changed from their usual diet to a high saturate diet there was a non-significant deterioration in glucose tolerance as measured by an intravenous glucose tolerance test (300 mg/kg). When they were on the high PUFA diet glucose tolerance improved significantly (glucose area under the curve 543 [SD 63] vs 497 [74] mmol.l-I.min before vs after diet, p = 0037, n=9). Insulin areas did not change

significantly. These preliminary results suggest that dietary fatty modify insulin sensitivity, perhaps by enhancing peripheral glucose uptake. acids

Department of Clinical Nutrition, University of Kuopio, 70211 Kuopio, Finland

MATTI UUSITUPA JAANA LAITINEN ESSI MÄKINEN URSULA SCHWAB

Last year we began a research/education pilot programme on a very isolated reservation in a canyon in northern Arizona. The

Havasupai are a tribe numbering 550, in which 55 % of women and 38% of men over the age of 35 seen in the Indian Health Service clinic have been diagnosed as having NIDDM. Apart from supporting our basic research on genetic susceptibility, the university has waived tuition fees so that the Havasupai can take college credit courses, taught on the reservation, dealing with the biology and dietary control of diabetes. Each class has been offered twice by graduate students who lived in Supai, the only village on the reservation. Free diabetes screening has been offered to those requesting it. Because compliance with pretest intake requirements for the fasting oral glucose test is often unpredictable in this community, glycosylated haemoglobin was selected as the most reliable screening device. 34 Havasupais were tested before the project began and again a year later. Many of the participants were also students in the classes, and the rest had heard about the programme through friends, relatives, or staff at the clinic at Supai. The physician member of our team (K. Z.) was at the clinic and in the community to discuss diabetes and the blood tests with community members. Of the 34 people retested after the classes and community involvement, 22 showed a decreased glycohaemoglobin level, 1 showed no change, and 11 showed an increase (sign test, p < 0-05). We believe that the screening and the accompanying educational programme have had an immediate measurable impact on the community’s health. We attribute this success to the extended presence of project personnel in the community (rather than rushed visits to the reservation from time to time) and to our emphasis on educating people on the aetiology and management of diabetes. Many research institutions have the potential to add an inexpensive educational component to clinically oriented research projects through the participation of graduate students, medical students, or residents. Our efforts in this direction have not only improved the health of the community, but also have facilitated our basic research since community members exhibit increased interest in the research and in providing the blood samples required. Our progress has been limited largely by a shortage of funds for the analysis rather than by a shortage of volunteers. In our preliminary analysis of Havasupai over the age of 35, the frequency of the HLA-A2 allele was 50% in 22 diabetics and 52% in 30 non-diabetics, suggesting that the significant association of this allele with diabetes postulated for the Pimal does not exist for the

Havasupai. Maricopa Medical Center, Phoenix, Arizona, and Department of Zoology, Arizona State University, Tempe, Arizona 85287, USA

KEVIN ZUERLEIN

Department of Anthropology, Arizona State University

JOHN F. MARTIN

Family Resources and Human Arizona State University Department of Zoology, Arizona State University 1. Williams RC,

J, Uusitupa M. Determinants for improved metabolic control in patients with recently diagnosed type 2 diabetes. Diabetologia 1991; 34 (suppl 2): A196. 2. Schwab U, Uusitupa M, Karhapaa P, Rasanen M, Mäkinen E, Laakso M. Improved glucose tolerance in healthy subjects during high polyunsaturated diet. Acta Endocrinol 1991; 124 (suppl 3): 33. 1. Laitinen

NIDDM: basic research

plus education

SIR,-Non-insulin-dependent diabetes mellitus (NIDDM) has reached epidemic

proportions in native American communities. Changes in lifestyle conspire with a genetic vulnerability, and to

turn the tide we need

changes in behaviours (diet and exercise) that disease onset, and to identify the genetic loci controlling the relevant metabolic pathways. Despite extensive efforts on both fronts, the incidence of NIDDM continues to rise and the responsible genetic factors have yet to be found. contribute

to

Development,

LINDA VAUGHAN THERESE ANN MARKOW

Knowler WC, Butler WJ, et al. HLA-A2 and type II diabetes mellitus in an association of allele frequency with age. Diabetologia 1981; 21:

Pima Indians: 460-63.

Screening for prostatic cancer S!R,—We regret that Dr Johnson and Dr Pickle (Sept 28, p 819) view our paper1 as misleading. We assessed the preventive efficacy for advanced prostatic cancer of digital rectal examinations as done by competent physicians in a real-life setting, in which the examinations were frequent for some patients and infrequent or absent for others. If appreciable prevention had occurred there should have been a clear deficit of examinations in the cases as compared with the controls. We showed a strong benefit of sigmoidoscopy in preventing death from colorectal cancer with a similar case-control study in the same setting.2 Here, too, since the vast majority of patients received no sigmoidoscopic examinations,

1272

Johnson and Pickle would presumably have "little expectation" of our finding a decrement in examinations in the case group because of the absence of "regular screening examinations at a reasonable interval in the population under study". Nevertheless, we have done additional analyses in response to their comments. The three months before diagnosis were included. There proved to be no deficit among the cases of men with frequent screening rectal examinations, defmed as at least one per two years of follow-back time (45/139 or 32 4% of cases and 42/139 or 30-2% of controls). In respect of the timing of the last screening rectal examination, which our critics say would be more informative, the median interval to diagnosis was 25 months for the 117 cases and 31 months for the 109 controls with examinations. The corresponding medians were 34 and 55 months if persons with no examinations were included and taken to have the highest values. These data corroborate the lack of preventive efficacy reported for screening during the year or two before diagnosis. Why do Johnson and Pickle criticise our comments about the findings 16-20 years before diagnosis when in the article we also concluded that "these trends are likely to be chance fluctuations". Permanente Medical Group, Inc, Division of Research, 3451 Piedmont Avenue, Oakland, California 94611, USA

1. Friedman

GARY D. FRIEDMAN ROBERT A. HIATT CHARLES P. QUESENBERRY, JR JOSEPH V. SELBY

GD, Hiatt RA, Quesenberry CP Jr, Selby JV. Case-control study of cancer by digital rectal examinations. Lancet 1991; 337:

among the L monocytogenes isolates but it was the single most common resistance in L innocua (11 strains, 10 isolated from frankfurters). This resistance in L innocua, a harmless inhabitant of the animal and human gastrointestinal tract, might be due to the

wide use of tetracycline in poultry feeding.6 In another survey of 54 L monocytogenes strains isolated from clinical specimens over the past four years, we found all but 2 to be susceptible to the antibiotics tested. These 2 were resistant to streptomycin only (MIC 64 mg/1) and contained plasmid DNA. Thus, the frequency of antibiotic-resistant L rrwnocytogenes was similar in clinical and foodbome strains but the multiple resistance found in food isolates was not encountered in clinical specimens. Infection due to ingestion of foodborne, multiresistant strains of L monocytogenes has been regarded as unlikely, because of the general susceptibility of food isolates to antibiotics,s and it has been suggested that multiple resistance might be acquired in vivo1,2,5.7 in the bowel or vagina/cervix. However, our findings show that multiresistant strains may already be present in food; human infection due to antibiotic-resistant L monocytogenes may stem from that source. Institute of Microbiology, Medical School, University of Ancona, 60131 Ancona, Italy

B. FACINELLI E. GIOVANETTI P. E. VARALDO

Institute of Microbiology, Medical School, University of Modena

P. CASOLARI U. FABIO

screening for prostatic 1526-29. 2.

Selby JV, Friedman GD, Quesenberry CP Jr, Weiss NS. Efficacy of sigmoidoscopy in asymptomatic persons. Am J Epidemiol 1991; 134: 745 (abstr).

Antibiotic resistance in foodborne listeria SIR,-Listeriosis is often fatal even with antibiotic therapy, so there is every reason to be concerned at reports of Listeria monocytogenes with plasmid-mediated resistance to several antibiotics.1.2 It seems that not only epidemic listeriosis but also sporadic cases may be caused by foodborne organisms,3so both clinical specimens and food samples may need to be monitored for the emergence of resistant strains. Beginning in January, 1991, from a survey of dairy products and chicken and turkey frankfurters involved in a legal case concerning meat production, we isolated 98 strains of L monocytogenes and 85 of L innocua. By disc and agar dilution assays, all isolates were tested for susceptibility to eleven antimicrobial agents. No strains were resistant to ampicillin, vancomycin, chloramphenicol, or cotrimoxazole but 4 L monocytogenes and 15 L innocua strains were resistant to one or more antibiotics:

1. Poyart-Salmeron C, Carlier C, Tneu-Cuot P, Courtieu AL, Courvalin P. Transferable plasmid-mediated antibiotic resistance in Listeria monocytogenes. Lancet 1990; 335: 1422-26. 2. Quentin C, Thibaut MC, Horovitz J, Bebear C. Multi-resistant strain of Listeria monocytogenes in septic abortion. Lancet 1990; 336: 375. 3. Schuchat A, Swaminathan B, Broome CV. Epidemiology of human listeriosis. Clin Microbiol Rev 1991; 4: 169-83. 4. MacGowan AP, Reeves DS, McLauchlin J. Antibiotic resistance of Listeria monocytogenes. Lancet 1990; 336: 513-14. 5. Slade PJ, Collin-Thompson DL Listeria, plasmids, antibiotic resistance and food. Lancet 1990; 336: 1004. 6. Jukes TH Some historical notes on chlortetracycline. Rev Infect Dis 1985; 7: 702-07 7 Fistrovici E, Collins-Thompson DL Use of plasmid profiles and restriction endonuclease digest in environmental studies of Listeria spp from raw milk. Int J Food Microbiol 1990; 10: 43-50.

Congestive heart failure worsening with octreotide in acromegalic patient SIR,-Hyperkinetic heart syndrome develops in most patients acromegaly, and is characterised by concentric cardiac hypertrophy, high cardiac output, and lowered vascular systemic resistance. More unusually, acromegaly may induce congestive heart failure with dilated hypokinetic cardiomyopathy. Chanson et aP described a striking clinical improvement in 3 acromegalic patients with heart failure treated with the somatostatin analogue with active

octreotide. We report a man whose cardiac state worsened with such treatment.

A 44-year-old man with dyspnoea for three months was referred the cardiology intensive care unit with severe acute pulmonary oedema. Acromegaly was suspected on the basis of acral enlargement and facial changes, and was confirmed by increased plasma growth hormone (GH) values (111ng/ml; normal 1-5) and insulin-like growth factor (IGF) 1 (64-9 nmol/1; normal 1540). Computed tomography revealed a pituitary macroadenoma with suprasellar extension. Other pituitary functions were preserved. Electrocardiography showed sinus tachycardia with left bundle branch block and no abnormality suggesting coronary disorders. He had no valvular disease on echocardiography, but did have dilated ventricular cavities (left ventricular end diastolic diameter 90 mm), decreased left ventricular fractional shortening to 20%, and grade II functional mitral regurgitation. He improved with sodium and water restriction, together with treatment with frusemide, nitrates, and captopril. Haemodynamic data were obtained by left and right heart catheterisation after he was stabilised clinically: left ventricular ejection fraction and cardiac index were low (20% and 2-34 11m2 body surface area, respectively); systemic vascular resistance was to

Em = erythromycin, Km=kanamycin, Cn=gentamicin, R!fr!famp!C!n, Sm = streptomycin, Su = sulphamethoxazole, Tc = tetracycline MIC ranges (mgjl) m L monocytogenes Em 8, Km 64-> 256, Cn 8, Rlf, 32-64, MIC ranges in L Sm 32-64, Su > 1024 64, Sm 128, Su > 1024, Tc 128-> 256 Mmozzare!)a; F = frankfurter.

mnocua were.

Em 64->

256, Km

3 of the 4 antibiotic-resistant strains of L monocytogenes were isolated from soft cheese (mozzarella), whereas resistant strains of L innocua were mostly isolated from frankfurters. Screening for plasmid DNA in resistant isolates showed plasmids in 3/4 L monocytogenes and in 6/15 L innocua. Resistance patterns including streptomycin, sulphamethoxazole, and kanamycin were recorded in all 4 L monocytogenes and in 1 L innocua; 2 L innocua were resistant to streptomycin and sulphamethoxazole but not to kanamycin. Tetracycline resistance’-’"’’’ was not encountered

Screening for prostatic cancer.

1271 insulin and C-peptide rather than glucose is a more subtle form of this fallacy. It seems unwise to conclude that associations between diabetes...
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