Effect of metformin and insulin vs. placebo and insulin on whole body composition in overweight patients with type 2 diabetes: a randomized placebo-controlled trial.

Some studies indicate potential beneficial effects of metformin on body composition and bone. This trial compared metformin + insulin vs placebo + insulin. Metformin treatment had a small but positive effect on bone quality in the peripheral skeleton, reduced weight gain, and resulted in a more beneficial body composition compared with placebo in insulin-treated patients with type 2 diabetes. INTRODUCTION: Glucose-lowering medications affect body composition. We assessed the long-term effects of metformin compared with placebo on whole body bone and body composition measures in patients with type 2 diabetes mellitus. METHODS: This was a sub-study of the Copenhagen Insulin and Metformin Therapy trial, which was a double-blinded randomized placebo-controlled trial assessing 18-month treatment with metformin compared with placebo, in combination with different insulin regimens in patients with type 2 diabetes mellitus (T2DM). The sub-study evaluates the effects on bone mineral content (BMC), density (BMD), and body composition from whole body dual-energy X-ray absorptiometry (DXA) scans which were assessed at baseline and after 18 months. RESULTS: Metformin had a small, but positive, (p < 0.05) effect on subtotal, appendicular, and legs BMC and BMD compared with placebo. After adjustment for sex, age, vitamin D, smoking, BMI, T2DM duration, HbA1c, and insulin dose, the effects on appendicular BMC and BMD persisted (p < 0.05 for both). The changes in appendicular BMC and BMD corresponded approximately to a 0.7% and 0.5% increase in the metformin group and 0.4% and 0.4% decrease in the placebo group, respectively. These effects were mostly driven by an increase in BMC and BMD in the legs and a loss of BMC and BMD in the arms. During 18 months, all participants increased in weight, fat mass (FM), FM%, and lean mass (LM), but decreased in LM%. The metformin group increased less in weight (subtotal weight (weight-head) - 2.4 [- 3.5, - 1.4] kg, p value < 0.001) and FM (- 1.5 [- 2.3, - 0.8] kg, p value < 0.001) and decreased less in LM% (0.6 [0.2, 1.1] %, p value < 0.001) compared with the placebo group. CONCLUSION: Metformin treatment had a small positive effect on BMC and BMD in the peripheral skeleton and reduced weight gain compared with placebo in insulin-treated patients with T2DM.

Data on the use of dietary supplements in Danish patients with type 1 and type 2 diabetes.

The data in this article describe the use of dietary supplements in Danish patients with type 1 diabetes (T1D) and type 2 diabetes (T2D). The data were collected from a web-based dietary survey on dietary habits in 774 patients with T1D (n = 426) and T2D (n = 348). The data demonstrate that 99% of the patients with diabetes use dietary supplements with no gender differences. In comparison, only 64% in the general population use dietary supplements [2]. A higher proportion of people in the general population use multivitamin/mineral supplementation as compared to patients with diabetes (48% vs. 34-37%) and a higher proportion of women than men with diabetes use multivitamin/mineral supplementation (T1D: 43% women vs. 26% men and T2D: 45% women vs. 34% men). More patients with diabetes than the general population use supplements such as calcium together with vitamin D, vitamin D, vitamin B, vitamin C, vitamin E, magnesium, calcium, Q10, ginger, garlic, and other herbal supplements.

The effect of metformin versus placebo in combination with insulin analogues on bone mineral density and trabecular bone score in patients with type 2 diabetes mellitus: a randomized placebo-controlled trial.

Some antihyperglycemic medications have been found to affect bone metabolism. We assessed the long-term effects of metformin compared with placebo on bone mineral density (BMD) and trabecular bone score (TBS) in patients with type 2 diabetes. Metformin had no significant effect on BMD in the spine and hip or TBS compared with a placebo. INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures despite a high bone mass. Some antihyperglycemic medications have been found to affect bone metabolism. We assessed the long-term effects of metformin compared with placebo on bone mineral density (BMD) and trabecular bone score (TBS). METHODS: This was a sub-study of a multicenter, randomized, 18-month placebo-controlled, double-blinded trial with metformin vs. placebo in combination with different insulin regimens (the Copenhagen Insulin and Metformin Therapy trial) in patients with T2DM. BMD in the spine and hip and TBS in the spine were assessed by dual-energy X-ray absorptiometry at baseline and after 18 months follow-up. RESULTS: Four hundred seven patients were included in this sub-study. There were no between-group differences in BMD or TBS. From baseline to 18 months, TBS decreased significantly in both groups (metformin group, - 0.041 [- 0.055, - 0.027]; placebo group - 0.046 [- 0.058, - 0.034]; both p < 0.001). BMD in the spine and total hip did not change significantly from baseline to 18 months. After adjustments for gender, age, vitamin D, smoking, BMI, duration of T2DM, HbA1c, and insulin dose, the TBS between-group differences increased but remained non-significant. HbA1c was negatively associated with TBS (p = 0.009) as was longer duration of diabetes, with the femoral neck BMD (p = 0.003). Body mass index had a positive effect on the hip and femoral neck BMD (p < 0.001, p = 0.045, respectively). CONCLUSIONS: Eighteen months of treatment with metformin had no significant effect on BMD in the spine and hip or TBS in patients with T2DM compared with a placebo. TBS decreased significantly in both groups. TRIAL REGISTRATION: ClinicalTrials.gov (NCT00657943).

Glycaemic threshold for diabetes-specific retinopathy among individuals from Saudi Arabia, Algeria and Portugal.

We studied the glycaemic threshold and prevalence of diabetic retinopathy in screen-detected diabetes in Saudi Arabia, Algeria and Portugal. The prevalence of diabetes-specific retinopathy started to increase at an HbA1c level of 6-6.4% (42-47 mmol/mol) and in individuals with HbA(1c) >7.0% the prevalence was 6.0%.

Reduced incidence of lower-extremity amputations in a Danish diabetes population from 2000 to 2011.

AIMS: Diabetic foot disease and amputations severely reduce quality of life and have major economic consequences. The aim of this study was to estimate time trends in the incidence of lower-extremity amputations in Danish people with diabetes. METHODS: We studied major and minor lower-extremity amputations from 2000 to 2011 among 11,332 people with diabetes from the Steno Diabetes Center. Amputations were identified by linkage of the electronic medical system with the National Patient Registry. Sex-specific incidence rates of amputations by age, diabetes duration, calendar time and diabetes type were modelled by Poisson regression. RESULTS: From 2000 to 2011, 384 incident lower-extremity amputations (205 major, 179 minor) occurred during 100,495 years of patient follow-up. From 2000 to 2011, the incidence of all lower-extremity amputations decreased by 87.5% among men and 47.4% among women with type 1 diabetes and by 83.3% among men and 79.1% among women with type 2 diabetes (P < 0.001). In particular, there was a decline in major lower-extremity amputations. In 2011, the incidence rates of major lower-extremity amputations were 0.25 (95% CI 0.07-0.82) among men and 0.21 (95% CI 0.06-0.71) among women per 1000 patient-years at age 50 years and 0.56 (95% CI 0.18-1.89) among men and 0.41 (95% CI 0.16-1.09) among women per 1000 patient-years at age 70 years. No significant change in incidence of minor amputations was observed. CONCLUSION: The incidence of major lower-extremity amputations reduced significantly from 2000 to 2011 in Danish people with diabetes followed at a diabetes specialist centre.

Reproducibility of ultrasonography for assessing abdominal fat distribution in a population at high risk of diabetes.

BACKGROUND: Visceral fat plays an important role in the development of metabolic disease independently of the effect of overall abdominal fat. Ultrasonography is an accessible method of accurately assessing abdominal fat distribution in epidemiological studies, but few details about the reproducibility of this method have been published. OBJECTIVE: The aim of this study was to investigate the reproducibility of ultrasonography in the assessment of abdominal fat distribution in a population at high risk of type 2 diabetes. DESIGN AND METHODS: Ultrasonography was used to estimate visceral and subcutaneous abdominal fat. Intra- and interobserver variation, short-term variation and variation between estimates in the fasting and non-fasting state were examined in three samples of 30, 33 and 23 participants from the ADDITION-PRO study. A variance components model was used to calculate intra- and interobserver variation, and Bland-Altman plots were drawn for all three substudies. RESULTS: Coefficients of variation for intra- and interobserver variation were in the range 3.4-6.1%, except for interobserver variation for subcutaneous fat (9.5%). Short-term variation over a median of 35 days had a coefficient of variation of 15%. The effect of a meal was primarily on the visceral estimates and did not extend beyond the first postprandial hour. Non-fasting visceral estimates were larger than fasting estimates. CONCLUSION: Both visceral and subcutaneous fat can be estimated with ultrasonography with adequate intra- and interobserver reproducibility by clinical researchers with limited training, making it a feasible method of assessing abdominal fat distribution in epidemiological studies.

Risk scores for diabetes and impaired glycaemia in the Middle East and North Africa.

AIMS: To develop risk scores for diabetes and diabetes or impaired glycaemia for individuals living in the Middle East and North Africa region. In addition, to derive national risk scores for Algeria, Saudi Arabia and the United Arab Emirates and to compare the performance of the regional risk scores with the national risk scores. METHODS: An opportunistic sample of 6588 individuals aged 30-75 years was screened. Screening consisted of a questionnaire and a clinical examination including measurement of HbA(1c). Two regional risk scores and national risk scores for each of the three countries were derived separately by stepwise backwards multiple logistic regression with diabetes [HbA(1c) ≥ 48 mmol/mol (≥ 6.5%)] and diabetes or impaired glycaemia [HbA(1c) ≥ 42 mmol/mol (≥ 6.0%)] as outcome. The performance of the regional and national risk scores was compared in data from each country by receiver operating characteristic analysis. RESULTS: The eight risk scores all included age and BMI, while additional variables differed between the scores. The areas under the receiver operating characteristic curves were between 0.67 and 0.70, and for sensitivities approximately 75%; specificities varied between 50% and 57%. The regional and the national risk scores performed equally well in the three national samples. CONCLUSIONS: Two regional risk scores for diabetes and diabetes or impaired glycaemia applicable to the Middle East and North Africa region were identified. The regional risk scores performed as well as the national risk scores derived in the same manner.

Patient factors and glycaemic control--associations and explanatory power.

AIMS: To investigate the association between glycaemic control and patient socio-demographics, activation level, diabetes-related distress, assessment of care, knowledge of target HbA(1c), and self-management behaviours, and to determine to what extent these factors explain the variance in HbA(1c) in a large Danish population of patients with Type 2 diabetes. METHODS: Cross-sectional survey and record review of 2045 patients from a specialist diabetes clinic. Validated scales measured patient activation, self-management behaviours, diabetes-related emotional distress, and perceived care. The electronic patient record provided information about HbA(1c), medication, body mass index, and duration of diabetes. Data were analysed using multiple linear regression models with stepwise addition of covariates. RESULTS: The response rate was 54% (n = 1081). Good glycaemic control was significantly associated with older age, higher education, higher patient activation, lower diabetes-related emotional distress, better diet and exercise behaviours, lower body mass index, shorter duration of disease and knowledge of HbA(1c) targets (P < 0.05 for all). Patient socio-demographics, behaviour; perceptions of care and diabetes distress accounted for 14% of the total variance in HbA(1c) levels (P = 0.0134), but the variance explained was higher for respondents treated with medications other than insulin. CONCLUSIONS: Our study emphasizes the complex relationships between patient activation, distress and behaviour, specific treatment modalities and glycaemic control. Knowledge of treatment goals, achieving patient activation in coping with diabetes, and lowering disease-related emotional stress are important patient education goals. However, the large unexplained component of HbA(1c) variance highlights the need for more research to understand the mechanisms of glycaemic control.

Impaired fasting glucose in combination with silent myocardial ischaemia is associated with poor prognosis in healthy individuals.

AIM: As both impaired fasting glucose and silent myocardial ischaemia are risk factors for cardiovascular disease and death, we hypothesized that these risk factors in combination would identify those subjects at the highest risk of adverse events. METHODS: Healthy individuals without diabetes (n=596, 55-75 years) were examined for silent myocardial infarction (≥ 1 mm ST-interval during ≥ 1 min) by ambulant 48-h continuous electrocardiogram monitoring and impaired fasting glucose (fasting plasma glucose 5.6-6.9 mmol/l). RESULTS: After 6.3 years, 77 subjects met the endpoint of myocardial infarction and/or death. The prevalence of silent myocardial ischaemia at inclusion was 12.3% in subjects with impaired fasting glucose and 11.7% in subjects with normal fasting glucose, P=0.69. Subjects with impaired fasting glucose/silent myocardial ischaemia more often met the endpoint (36%) than subjects with impaired fasting glucose/no silent myocardial ischaemia (15%), subjects with normal fasting glucose/silent myocardial ischaemia (12%), and subjects with normal fasting glucose/no silent myocardial ischaemia (10%), respectively, (P<0.001). In a Cox model including these four study groups of interest, gender, age, smoking habits, blood pressure and total cholesterol, only subjects with impaired fasting glucose/silent myocardial ischaemia exhibited an increased risk of death or myocardial infarction (hazard ratio 2.5, P=0.016). CONCLUSION: The combination of impaired fasting glucose and silent myocardial ischaemia was associated with the poorest prognosis in middle-aged and older subjects without previously known glucose metabolic aberration and heart disease.

Thyroid-associated orbitopathy developed during hormone replacement therapy.

Thyroid-associated orbitopathy (TAO) developed in relation to estrogen combined with progesterone therapy has not been reported previously. We report a case of a 56-year-old postmenopausal woman who during estrogen/progesterone treatment developed signs and symptoms of orbitopathy. The patient had no previous history of autoimmune- or thyroid disorders. The initial eye symptoms disappeared after withdrawal of hormone replacement therapy. Five years later estrogen/progesterone treatment was re-instituted. The patient had relapse of orbitopathy. The hormones were discontinued and the eye symptoms disappeared again. This suggests that estrogen and/or progesterone could be of some pathogenetic importance in the induction of orbitopathy

Prognostic value of nutritional status in chronic obstructive pulmonary disease.

The association between low body mass index (BMI) and poor prognosis in patients with chronic obstructive pulmonary disease (COPD) is a common clinical observation. We prospectively examined whether BMI is an independent predictor of mortality in subjects with COPD from the Copenhagen City Heart Study. In total, 1,218 men and 914 women, aged 21 to 89 yr, with airway obstruction defined as an FEV(1)-to-FVC ratio of less than 0.7, were included in the analyses. Spirometric values, BMI, smoking habits, and respiratory symptoms were assessed at the time of study enrollment, and mortality from COPD and from all causes during 17 yr of follow-up was analyzed with multivariate Cox regression models. After adjustment for age, ventilatory function, and smoking habits, low BMI was predictive of a poor prognosis (i.e., higher mortality), with relative risks (RRs) in underweight subjects as compared with that in subjects of normal weight of 1.64 (95% confidence interval [CI]: 1.20 to 2.23) in men and 1.42 (95% CI: 1.07 to 1.89) in women. However, the association between BMI and survival differed significantly with stage of COPD. In mild and moderate COPD there was a nonsignificant U-shaped relationship, with the lowest risk occurring in normal-weight to overweight subjects, whereas in severe COPD, mortality continued to decrease with increasing BMI (test for trend: p < 0.001). Similar results were found for COPD-related deaths, with the strongest associations found in severe COPD (RR for low versus high BMI: 7.11 [95% CI: 2.97 to 17.05]). We conclude that low BMI is an independent risk factor for mortality in subjects with COPD, and that the association is strongest in subjects with severe COPD.

[Interaction between warfarin and coenzyme Q10]. / Interaktion mellem warfarin og coenzym Q10.

Coenzyme Q10 (Ubidecarenone) is marketed as a dietary supplement. Drug interaction between coenzyme Q10 and warfarin has previously been reported. In the present case, a 72-year-old female treated with warfarin showed less responsiveness to warfarin than previously. It appeared she had taken coenzyme Q10, and when this was stopped, her responsiveness to warfarin was the same as before. Coenzyme Q10 is chemically similar to K-vitamins, which may explain the interaction with warfarin. Patients in treatment with warfarin should be aware of the possible risk of treatment failure when taking coenzyme Q10. The need for questioning patients concerning not only medications but also use of dietary supplements and alternative medications is emphasised.

[Adverse effects of selective serotonin uptake inhibitors. Hyponatremia caused by Schwartz-Bartter syndrome]. / Bivirkninger ved behandling med selektive serotoningenoptagelseshaemmere. Hyponotrioemi på grund af Schwartz-Bartters syndrom.

This report describes three cases of hyponatraemia/syndrome of inappropriate secretion of antidiuretic hormone. The cases are most likely caused by treatment/intoxication with three different selective serotonin reuptake inhibitors: Fluoxetine, paroxetine and citalopram. All three patients were elderly women (75-83 years). Serum sodium values returned to normal or near normal after discontinuation of the drug and concomitant fluid restriction. Hyponatraemia has previously been described as an adverse effect to fluoxetine and paroxetine, but not to citalopram.

[Treatment of obesity in patient groups]. / Behandling af adipositas i patientgrupper.

The purpose of this study was to assess the results of group treatment in obesity. Patients referred to a department of endocrinology were on referral given individual diet counselling, and the patients were then seen every second week for control weighing and supplemental counselling either in groups of 10-12, or individually. One hundred and twenty-three (97 female and 26 male) patients who during a two year period, 1991-1993, were referred to the outpatient clinic of the Department of Endocrinology were identified. Ninety-five percent of the patients were markedly obese, body mass index > 30 m2/kg. Seventy percent of the patients continued the treatment and were either followed in the groups or individually. The patients followed in the groups (n = 66) lost 5.2 kg during 127 days (median), and this is not significantly different from those followed individually (n = 22) who lost 4.9 kg during 98 days. In conclusion, only a small weight reduction is seen in obese patients treated either in groups or individually. These results are comparable with previously reported results from a Danish study only using individual counselling.

Effects of xylitol on urea synthesis in normal humans: relation to glucagon.

BACKGROUND: Xylitol exerts a nitrogen-sparing effect in stress catabolic states with hyperglucagonemia, but the mechanism(s) is unknown. We examined the effects of xylitol on urea synthesis during physiologic glucagon concentrations and during hyperglucagonemia. METHODS: Urea synthesis was measured independently of blood amino acid concentration by means of functional hepatic nitrogen clearance (FHNC) (ie, the linear slope of the relation between urea synthesis rate and blood alpha-amino nitrogen concentration during infusion of alanine). FHNC was measured on four separate occasions in each of seven healthy subjects: during constant infusion of alanine alone, alanine superimposed on a constant infusion of xylitol (blood xylitol 1 mmol/L), alanine superimposed on infusion of glucagon, and alanine superimposed on infusions of xylitol and glucagon. RESULTS: During alanine infusion alone, plasma glucagon rose to -170 ng/L, and FHNC was (mean +/- sem) 27.9 +/- 1.3 L/h. Xylitol did not affect plasma glucagon and only moderately reduced FHNC to 24.3 +/- 1.0 L/h (p < .05). Glucagon infusion increased plasma glucagon to -450 ng/L and FHNC twofold to 50.9 +/- 6.2 L/h; this increase was totally prevented by the addition of xylitol that reduced FHNC to 27.4 +/- 2.6 L/h (p < .01). CONCLUSIONS: The results show that xylitol only inhibited FHNC minimally during spontaneous glucagon levels. In contrast, xylitol completely inhibits the increase in FHNC by glucagon. This suggests that the mechanism whereby xylitol reduces nitrogen loss in stress catabolic conditions with hyperglucagonemia involves an effect on liver metabolism. The mechanism is unknown but may be related to depletion of hepatocyte adenine nucleotides.

Control of non-insulin-dependent diabetes mellitus partially normalizes the increase in hepatic efficacy for urea synthesis.

The relation of urea synthesis rate to blood alanine concentration was assessed in seven healthy controls and eight patients with non-insulin-dependent diabetes mellitus (NIDDM) before (hemoglobin A1c [HbA1c] = 9.9% +/- 1.9%, mean +/- SD) and after (HbA1c = 7.9% +/- 0.8%) improvement of metabolic control. Following an overnight fast, alanine was infused at a rate of 2 mmol/(h.kg body weight [BW]). The hourly rate of urea synthesis was determined as the urinary excretion of urea corrected for accumulation of urea in total body water (TBW) and intestinal hydrolysis. The functional hepatic nitrogen clearance (FHNC) was calculated as the slope of the linear relation of urea synthesis rate to blood alanine concentration. The glucagon level was increased by twofold at the first investigation, but was not increased at the second. The insulin level was moderately increased at both investigations. In controls FHNC was 21.8 +/- 4.4 L/h, in poorly controlled patients it was increased to 36.6 +/- 4.3 L/h (P < .01), and following improvement of metabolic control it was not different from control levels at 28.6 +/- 4.3 L/h. By correlation analyses, FHNC was found only to be related to the fasting glucose value, albeit weakly (R2 = .39). In conclusion, hepatic kinetics of urea synthesis in poorly controlled NIDDM patients are changed in favor of increased conversion of alanine N to urea N at any amino acid concentration. This perturbation is partially normalized by improved metabolic control.

Glucagon immunoneutralization in diabetic rats normalizes urea synthesis and decreases nitrogen wasting.

To study the effect of glucagon neutralization on urea synthesis in diabetic rats, animals with newly induced (75 mg/kg streptozocin) experimental diabetes mellitus were divided into two groups. One group was given one weekly injection of nonimmune rabbit serum (n = 6), and the other group was given one weekly injection of a specific high-titer antibody against pancreatic glucagon (n = 6). Four weeks later, serum-treated diabetic rats had fasting glucagon concentrations 2-3 times higher than nondiabetic controls given one weekly injection of saline (control). Plasma glucagon binding capacity of diabetic rats given glucagon antibodies was 10-15 times higher than the glucagon concentration. A second group of nondiabetic controls were given nonimmune serum. Blood glucose concentration and urinary glucose output were identical in both groups of diabetic animals. Food intake doubled in both groups of diabetic rats. In control rats, the accumulated nitrogen balance, determined weekly for 4 wk, was positive at 81 +/- 3.1 mmol/96 h; in serum-treated diabetic rats, the accumulated nitrogen balance was negative, -8.3 +/- 2.4 mmol/96 h throughout the 4 wk, whereas it was higher at 4.7 +/- 2.3 mmol/96 h in the glucagon antibody-treated diabetic rats (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Blockade of glucocorticoid receptors prevents the increase in urea synthesis after hysterectomy in rats.

The postoperative increase in hepatic conversion of amino nitrogen to urea nitrogen seems to be a primary cause of post-surgical catabolism. The importance of glucocorticosteroids for the spontaneous urea nitrogen synthesis rate (UNSR) and for the maximally amino acid-stimulated capacity of urea nitrogen synthesis (CUNS) was investigated 3 and 24 h postoperatively, respectively, in hysterectomized rats. Corticosteroid effects were neutralized by glucocorticoid receptor blockade by the pharmacological analogue RU486. Hysterectomy doubled UNSR from 3.16 +/- 0.20 to 6.12 +/- 0.27 mumol (per min per 100 g body weight) after 3 h (P less than 0.01) and increased CUNS by 40% from 7.47 +/- 0.30 to 10.29 +/- 0.41 mumol (per min per 100 g body weight) after 24 h (P less than 0.01). These changes were both normalized by the receptor blockade. Hysterectomy decreased total blood alpha-amino nitrogen concentration by 25% from 3.4 +/- 0.2 to 2.6 +/- 0.2 mmol l-1 (P less than 0.05) 3 h after surgery, which was normalized by glucocorticoid receptor blockade. Hysterectomized rats lost 10 +/- 1 g the first 24 h after surgery. The blockade reduced the weight loss to 6 +/- 1 g body weight (P less than 0.05) without changing food intake. The results indicate that glucocorticoid action plays a major role in the postoperative increase in hepatic amino nitrogen conversion.

Incidence of parenchymal liver diseases in Denmark, 1981 to 1985: analysis of hospitalization registry data. The Danish Association for the Study of the Liver.

The sex-specific and age-specific incidence rates of the major parenchymal liver diseases in a North European population were estimated using a computerized registry of all admissions to somatic hospitals in Denmark. The incidence was calculated by counting all incident cases of these diseases reported to the registry in the 5-yr period 1981 to 1985 and dividing the number of cases by the number of person-years at risk in this period. The incidence rates (per million person-years) were for men and women, respectively: infectious hepatitis, 109 and 71; toxic hepatitis, 19 and 22; chronic hepatitis, 27 and 29; alcoholic cirrhosis, 190 and 85; nonalcoholic nonbiliary cirrhosis, 110 and 82; primary biliary cirrhosis, 4 and 14. The pattern of the age-specific incidence rates was similar in men and women in infectious hepatitis, alcoholic cirrhosis, nonalcoholic nonbiliary cirrhosis and primary biliary cirrhosis. Toxic and chronic hepatitis had a higher incidence in women than in men only in older age groups. The incidence of idiopathic hemochromatosis, Wilson's disease, secondary biliary cirrhosis, portal vein thrombosis and Budd-Chiari's syndrome were less than four in both sexes.