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We investigated the variability of quantitative duplex Doppler measurements of portal flow. Measurements were validated in vitro using a flow phantom. The measured flow Q (ml/min), is related to the actual phantom output P (ml/min) according to the following formula: Q = 1.08 (P + 44) (r = 0.998). To estimate inter- and intra-observer variance, 38 subjects without portal hypertension were examined in two groups. Two observers examined the first group of subjects (n = 19), from a routine daily ultrasound schedule. Significant differences were found in mean +/- S.D. portal flow (692 +/- 182 ml/min vs. 613 +/- 185 ml/min, p = 0.04) and mean +/- S.D. velocity (15.3 +/- 3.9 cm/s vs. 13.2 +/- 2.6 cm/s, p = 0.01). The combined inter- and intra-observer coefficient of variation (S.D.) was 24% (158 ml/min), 9% (0.92 mm) and 24% (3.4 cm/s) for portal flow, diameter and velocity respectively. Non-systematic components of variance were the largest. Patient characteristics, age, sex, height, weight and body surface area did not influence measurement variations. In the second group of healthy volunteers (n = 19), where variance in measurements over 3 consecutive days was comparable to the combined variance in the first group, the non-systematic variance component was also the largest. We conclude that quantitative duplex Doppler measurements of portal venous flow are mainly subject to non-systematic variability. A coefficient of variation of 24% can be expected in diagnostic measurements in a single patient. Examination by a single observer is advisable. The value of this technique lies in the analysis of pathophysiological mechanisms in portal flow changes in large groups of subjects.

The influence of epidemic influenza on hospitalizations because of influenza, pneumonia and diabetic acidosis in patients with diabetes mellitus was investigated. Data on the weekly incidence of influenza-like illness were obtained from the Continuous Morbidity Registration and the cumulative data on hospitalizations in short-stay hospitals were obtained from the National Medical Registration. Patients with duodenal ulcer were used as a control population. Epidemic elevations of influenza infections were observed in 1976 and 1978. The estimated relative risk for hospitalization because of influenza infection was 1.1 and 1.0 for the two non-epidemic years 1977 and 1979, respectively. For the epidemic years 1976 and 1978 this risk was calculated to be 5.7 and 6.2, respectively. An increased relative risk was also noted for pneumonia; being 25.6 for both epidemic years. The estimated relative risk of dying during hospitalization rose from 30.9 in 1977 to 91.8 in 1978. The number of hospitalizations for ketoacidosis was 50% higher in 1978 than in the other three years. During the epidemic years, 25.7% of patients hospitalized for pneumonia died, while this percentage was 14.6% in the non-epidemic years (P less than 0.05). Differences in mortality due to diabetic acidosis were similar: 25.4% in epidemic and 14.7% in non-epidemic years (P less than 0.01). During the 1978 epidemic, one out of every 1300 patients with diabetes mellitus was hospitalized because of pneumonia. It is estimated that 1 of every 260 patients with IDDM was hospitalized for diabetic acidosis. It is concluded that patients with diabetes mellitus have indeed a very high influenza-associated morbidity.

The production of insulin autoantibodies (IAA) was studied after common viral infections in 12 children with type 1 diabetes mellitus and in their 18 healthy siblings. In addition, the production of IAA was measured after influenza vaccination with booster in 39 patients with type 1 diabetes mellitus and in 39 healthy controls. In 7 of the 12 diabetic children 13 viral infections were serologically confirmed. Among the siblings 14 periods of infection were noted in 9 individuals. A significant rise in IAA antibody titre was demonstrated in patients twice (IgG both times) and in siblings 11 times (IgM 5x, IgG 6x, difference significant P less than 0.05). In only three cases the rise in antibody titres occurred 6-12 wk after documented infection. There was a significant inverse correlation with age in both patients (r = 0.89, P less than 0.0001) and siblings (r = 0.67, P less than 0.001) for IgM IAA. After influenza vaccination a significant increase in IAA was noted twice: IgM IAA in a patient with diabetes and IgG IAA in a healthy volunteer. A four-fold decrease in IgG IAA was demonstrated in one diabetic patient. From these results it is concluded that IAA formation is not a direct sequela of viral infection or vaccination.

Herein, epidemiological data on influenza pneumonia and mortality, results of clinical studies, and the outcome of influenza vaccination trials are reviewed. All excess mortality studies that specify for underlying disease list diabetes as one of the major risk factors. During influenza epidemics, death rates among patients with diabetes mellitus may increase by 5-15%. Diabetes mellitus is also mentioned as a risk factor in most clinical studies, making up 3-14% of the patients studied. Even in recent studies, diabetes mellitus is only preceded as a risk factor by cardiovascular disease and chronic pulmonary disorders. To what extent cardiovascular disease and old age contribute to the increased influenza mortality and morbidity in diabetic patients remains unclear. The influence of epidemic influenza on the incidence of diabetic acidosis in combination with an impaired immune response to both Staphylococcus aureus and the influenza virus suggests that diabetes mellitus itself is the main risk factor. It is concluded that all patients with diabetes mellitus should receive annual vaccinations and that, in official recommendations, patients with diabetes mellitus should be mentioned as a separate risk group. Whole-virus vaccines are preferred over subunit vaccines.

The antibody response and delayed type hypersensitivity reaction to commercially available trivalent influenza vaccine in 159 patients with diabetes mellitus was compared with response and reaction in 28 healthy volunteers. A correction for prevaccination titres was made. No differences were found between diabetic patients and control subjects with respect to antibody response to the three vaccine strains as measured by the difference between geometric mean titres of post- and prevaccination sera. In Type 1 (insulin-dependent) diabetic patients the incidence of non-responders to two vaccine components was significantly increased (p less than 0.05). The delayed type hypersensitivity reaction to influenza antigen was significantly decreased in patients with high concentrations of glycosylated haemoglobin (p less than 0.01). These findings suggest a role for impaired immune response in the increased influenza morbidity and mortality in patients with diabetes mellitus. Implications for therapy and vaccination strategy are discussed.

The C-peptide increase after an oral glucose tolerance test (OGTT) and intravenous glucagon test (GT) was assessed to establish actual insulin dependency in 16 obese diabetic patients treated with insulin for years. The results, compared to five reference groups, showed two types of reaction: first, a negative response in 3 patients with a minimal C-peptide increase after either stimulation (range 0-0.1 ng/ml during GT, 0-0.5 during OGTT), not different from that in the insulin-dependent reference group (GT: 0.1 +/- 0.2, OGTT: 0.1 +/- 0.3. means +/- SD). Second, a positive response in 13 patients with a C-peptide increase, different from that in the insulin-dependent group after glucagon (range 0.7-5.6), and in 6 patients after OGTT (range 0.8-1.8). When insulin treatment was discontinued in two nonresponders, the B-hydroxybutyrate levels and ketobutyrate levels increased to over 2.1 and 0.60 mmol/L within 10 days, proving insulin dependency, and thus type I diabetes. B-hydroxybutyrate and ketobutyrate levels increased to maximal 0.4 and 0.17 after stopping insulin therapy in nine positive responders. No ketoacidosis developed during a 4-wk follow-up, indicating non-insulin dependency (type II diabetes). Measuring C-peptide after glucagon is a simple test that may be a discriminative method to establish insulin dependency in obese diabetic patients treated with insulin.

C-peptide is a polypeptide originating from proinsulin after its cleavage in the B-cell. It is secreted equimolarly with the other cleavage product, insulin, into the portal circulation. Only a minimal fraction of C-peptide is extracted by the liver; it is supposed to be mainly removed by the kidney. A small, constant proportion is excreted in the urine. C-peptide is measured in serum and urine by radioimmunoassay. The major sources of error of the assay are related to standard, tracer, antiserum specificity and reactivity with proinsulin, and to degradation of C-peptide. Many secretagogues are used to evaluate the B-cell function, of which glucagon is the most simple. Clinical applications of C-peptide include differentiating between endogenous and exogenous hyperinsulinism and establishing the need of insulin therapy in diabetic patients already treated with insulin. The primary value of C-peptide, however, is in clinical research, where it offers a unique opportunity to follow the B-cell secretion in diabetic subjects and to evaluate the difference that various factors may exert on its activity.

A focus of increased uptake on a 201Tl minus 99mTc subtraction scintigram of the parathyroid glands was found in a patient with persistent hypercalcemia. This area was not caused by an abnormal parathyroid gland but by an enlarged lymph node containing metastatic tissue from an adenocarcinoma of the ovary.

Three commercially available methods for the determination of C-peptide in human serum were evaluated. All kits were found to be acceptable with respect to precision and analytical recovery, while differences were observed with respect to sensitivity and cross-reactivity to human proinsulin. Furthermore an intermethod comparison was performed. It is pointed out that, before C-peptide determination on serum from insulin-treated diabetic subjects, a PEG precipitation, to remove antibody-bound proinsulin, should be done.