[Obesity and Eating Disorders. Indications for the different levels of care. An Italian Expert Consensus Document]. / Documento di Consensus. Obesità e Disturbi dell'Alimentazione Indicazioni per i diversi livelli di trattamento.

This paper is an Italian Expert Consensus Document on multidimensional treatment of obesity and eating disorders. The Document is based on a wide survey of expert opinion. It presents, in particular, considerations regarding how clinicians go about choosing the most appropriate site of treatment for a given patient suffering from obesity and/or eating disorders: outpatient, partial hospitalization, residential rehabilitation centre, inpatient hospitalization. In a majority of instances obesity and eating disorders are long-term diseases and require a multiprofessional team-approach. In determining an initial level of care or a change to a different level of care, it is essential to consider together the overall physical condition, medical complications, disabilities, psychiatric comorbidity, psychology, behaviour, family, social resources, environment, and available services. We first created a review manuscript, a skeleton algorithm and two rating scales, based on the published guidelines and the existing research literature. As the second point we highlighted a number of clinical questions that had to be addressed in the specific context of our National Health Service and available specialized care units. Then we submitted eleven progressive revisions of the Document to the experts up to the final synthesis that was approved by the group. Of course, from point to point, some of the individual experts would differ with the consensus view. The document can be viewed as an expert consultation and the clinical judgement must always be tailored to the particular needs of each clinical situation. We will continue to revise the Document periodically based on new research information and on reassessment of expert opinion to keep it up-to-date. The Document was not financially sponsored.

Low ghrelin concentrations in nonalcoholic fatty liver disease are related to insulin resistance.

Several physiological and pathophysiological conditions, including changes in body fat, food intake, and insulin resistance, are known to be associated with variations in plasma ghrelin concentrations. We tested the hypothesis that insulin resistance exerts a primary role by measuring ghrelin in 86 patients with nonalcoholic fatty liver disease (NAFLD), a condition in which insulin resistance is relatively independent of obesity. Compared with 40 matched healthy subjects, patients with NAFLD had similar glucose levels and higher plasma insulin and insulin resistance [homeostasis model assessment (HOMA)-R index] by over 60%. Ghrelin was reduced (mean +/- SD, 226 +/- 72 pmol/liter in NAFLD vs. 303 +/- 123 in controls; P < 0.0001). In relation to quartiles of body mass index, ghrelin progressively decreased in controls (P = 0.003), but not in patients (P = 0.926). In relation to quartiles of HOMA-R, ghrelin decreased in both groups, and significantly correlated with HOMA-R. After adjustment for age and sex, HOMA-R was the sole factor significantly associated with low ghrelin in the whole group (odds ratio, 5.79; 95% confidence interval, 2.62-12.81; P < 0.0001) and specifically in NAFLD (2.96; 1.12-7.79; P = 0.028). The study suggests that insulin resistance is a major factor controlling ghrelin levels in subjects with and without NAFLD.

The QUOVADIS Study: features of obese Italian patients seeking treatment at specialist centers.

Obesity is a major risk factor for several chronic diseases, but the burden associated with it also extends to psychosocial areas and to perceived health status. In 1999 an observational study on health-related quality of life in obesity was planned. The study was entirely web-based. Case Report Forms and the individual items of 7 self-administered questionnaires were directly implemented on a general database via an extranet system from 25 Italian centers. By December 2001, after enrolment had stopped, the database included anthropometric, socioeconomic and clinical data of 1944 patients (78% females). Weight-cycling was reported in over 80% of cases, overeating in 60-65%, structured physical activity in only 13-15%. Several chronic illnesses were associated. Whereas the prevalence of diabetes and hypertension was related to the degree of obesity, hyperlipidemia and coronary heart disease did not increase further with increasing obesity. A disturbed psychological mood was twice more common in females. Concern for present health was the main reason for seeking treatment in both genders; concern for body appearance was more common in females. Male subjects were more frequently assigned to dietary counseling and physical exercise, whereas in females psychotherapy was more frequently considered. Various forms of behavioral approach were planned in approximately 50% of patients. Finally, very few patients were initially considered for pharmacological intervention or bariatric surgery. The study provides a comprehensive picture of Italian patients seeking treatment for obesity. Data on perceived health status, psychological well being, body image awareness, eating behavior disorders and psychopathological distress will provide clues to a comprehensive assessment of obesity, the effects of treatments and reasons for failure.

Nonalcoholic fatty liver disease: a feature of the metabolic syndrome.

Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU. m(-2). min(-1)) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m(2). Of those 30 subjects, 9 had pure fatty liver and 21 had evidence of steatohepatitis. In addition, 10 patients with type 2 diabetes under good metabolic control and 10 healthy subjects were studied. Most NAFLD patients had central fat accumulation, increased triglycerides and uric acid, and low HDL cholesterol, irrespective of BMI. Glucose disposal during the clamp was reduced by nearly 50% in NAFLD patients, as well as in patients with normal body weight, to an extent similar to that of the type 2 diabetic patients. Basal free fatty acids were increased, whereas insulin-mediated suppression of lipolysis was less effective (-69% in NAFLD vs. -84% in control subjects; P = 0.003). Postabsorptive hepatic glucose production (HGP), measured by [6,6-(2)H(2)]glucose, was normal. In response to insulin infusion, HGP decreased by only 63% of basal in NAFLD vs. 84% in control subjects (P = 0.002). Compared with type 2 diabetic patients, NAFLD patients were characterized by lower basal HGP, but with similarly reduced insulin-mediated suppression of HGP. There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status. Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis. We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity. NAFLD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistance.

Oxidative stress and anti-oxidant metabolites in patients with hyperthyroidism: effect of treatment.

OBJECTIVE: Oxygen free radicals (OFR) play a role in the pathogenesis of tissue damage in many pathological conditions via the peroxidation of membrane phospholipids. Experimental studies showed an elevated oxidative stress during hyperthyroidism, which is reduced by treatment. Therapy per se might decrease oxidative stress. DESIGN: Fasting plasma levels of thiobarbituric acid reacting substances (TBARS), vitamin E and coenzyme Q10 were measured in 22 hyperthyroid patients, before treatment for their thyroid disease, after 13.9 [SD 9.2] weeks, when they achieved an euthyroid state on thyrostatic drugs, and again after 47.7 [21.0] weeks, off therapy. No patient presented additional risk factors for increased lipoperoxidation and/or increased OFR levels. Smokers were asked to abstain from smoking overnight. METHODS: All analytes were measured by HPLC. RESULTS: In hyperthyroidism, plasma levels of TBARS were increased, whereas vitamin E and coenzyme Q10 were reduced. Average levels of TBARS and antioxidant agents returned to normal in euthyroid patients, without differences in relation to stop of thyrostatic therapy. CONCLUSIONS: Our data confirm the presence of oxidative stress and decreased anti-oxidant metabolites in hyperthyroid patients, which are corrected in euthyroidism, without any influence of thyrostatic drugs per se. Nutritional support with antioxidant agents, which are defective during hyperthyroidism, is warranted.

Cardiovascular disease in cirrhosis--a point-prevalence study in relation to glucose tolerance.

OBJECTIVE: Impaired glucose tolerance or diabetes are frequently observed in cirrhosis. Overt diabetes was reported to affect long term survival of cirrhotic patients by increasing the risk of hepatocellular failure, without increasing the risk of diabetes-associated cardiovascular events. METHODS: We evaluated the prevalence of cardiovascular disease in 122 patients with cirrhosis, subdivided according to their glucose tolerance. The following parameters were considered: arterial pressure, peripheral vascular disease (ankle to brachial pressure ratio), ischemic heart disease, microalbuminuria, retinopathy. The prevalence of abnormal findings was compared with that observed in 60 randomly selected patients with noninsulin-dependent diabetes and in 40 controls. RESULTS: Noninsulin-dependent diabetic patients and patients with cirrhosis and diabetes were comparable for age, metabolic control, and smoking habits; the duration of diabetes was 5 yr longer for noninsulin-dependent diabetes. In cirrhosis, the prevalence of micro- and peripheral macroangiopathy, as well as coronary heart disease, was not different in relation to glucose tolerance, it was comparable to that of controls, and significantly lower than that observed in non-insulin-dependent diabetes. CONCLUSIONS: Cirrhotic patients, even in the presence of overt diabetes, are at low risk of cardiovascular disease. The low prevalence may be related to shorter duration of diabetic disease, also in relation to reduced life expectancy, as well as to liver disease-induced abnormalities protecting the cardiovascular system from atherosclerosis.

The relative contribution of androgens and insulin in determining abdominal body fat distribution in premenopausal women.

To investigate the relative contribution of insulin and sex hormones in determining the abdominal pattern of fat distribution in premenopausal women, five groups of age-matched subjects were examined: Group 1 consisted of 14 normal weight eumenorrheic women (NO); Group 2 of 9 obese eumenorrheic women (OB); Group 3 of 14 normal weight hyperandrogenic women with polycystic ovary syndrome (NO-HA); Group 4 of 10 obese hyperandrogenic women with polycystic ovary syndrome (OB-HA) and, finally, Group 5 of 10 obese hyperandrogenic women with polycystic ovary syndrome and acanthosis nigricans (OB-HA-AN). Both the two normal weight groups and the three obese groups were matched for body mass index values. Sex hormone pattern showed significantly higher LH and testosterone levels in hyperandrogenic women with respect to NO and OB women but obese hyperandrogenic groups (OB-HA and OB-HA-AN) presented significantly lower LH concentrations than NO-HA. Fasting and glucose-stimulated insulin levels were significantly higher in OB than NO, in OB-HA and OB-HA-AN than in OB and NO-HA, and in OB-HA-AN than in OB-HA, without any significant difference between OB and NO-HA. Body fat distribution, expressed by the waist to hip ratio (WHR), showed progressively higher values (p less than 0.01) from NO to OB, NO-HA, OB-HA and, particularly, OB-HA-AN women. Determination coefficients r2 obtained from simple regression analysis showed that the sum of insulin values during the glucose tolerance test and testosterone levels had a more significant power in determining WHR variability.(ABSTRACT TRUNCATED AT 250 WORDS)

[Obesity and adipose tissue distribution in men: relation to sex steroids and insulin]. / Obesità e distribuzione del tessuto adiposo nell'uomo: relazione con gli steroidi sessuali e l'insulina.

The aim of this study was to assess the correlation between the distribution of adipose tissue, sexual hormones and hyperinsulinemia in male obesity. Fifty-two obese males, aged 40.0 +/- 10.9 years old and with a body mass index (BMI) of 35.0 +/- 6.1 (m +/- SD), not suffering from diabetes or any other endocrine disease, were included in the study. A group of 20 subjects aged 30.5 +/- 7.9 (p less than 0.005 vs obese subjects) and with a BMI of 23.0 +/- 2.0 were used as controls. Body fat distribution was assessed using the waist/hip ratio (w/h ratio): 0.985 +/- 0.052 in obese subjects and 0.913 +/- 0.061 in controls (p less than 0.005). In comparison to control subjects, significantly lower levels of total (T) (357 +/- 132 vs 498 +/- 142 ng/dl; p less than 0.005) and free testosterone (FT) (14.2 +/- 2.9 vs 17.1 +/- 2.6 pg/ml; p less than 0.05) were found in the obese group, as well sex hormone binding globulin (SHBG) (41.7 +/- 31.9 vs 66.2 +/- 18.6 nmol/l; p less than 0.001). None of the other steroids (androstenedione, dehydroepiandrosterone-sulphate, estrone, 17 beta-estradiol, dihydrotestosterone) or FSH and LH gonadotropins assayed differed between the two groups. Significantly higher levels of insulin and C-peptide, both fasting and after a oral glucose tolerance test, were also found in obese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss.

We studied a group of obese hyperandrogenic amenorrheic women to determine the effects of weight loss on anthropometry, hormonal status, menstrual cycles, ovulation, and fertility. Fourteen women had polycystic ovaries, two the hyperandrogenism-insulin resistance-acanthosis nigricans syndrome, one hirsutism of adrenal origin, and three idiopathic chronic anovulation. The duration of amenorrhea before the study ranged from 3-17 months [mean, 8.6 +/- 4.5 (+/- SD)]. All women ate a hypocaloric diet for a period of 8.0 +/- 2.4 months. Weight loss ranged from 4.8 to 15.2 kg (mean, 9.7 +/- 3.1 kg; 1.35 +/- 0.56 kg/month) and the waist to hip ratio, which was used as a measurement of body fat distribution, decreased from 0.86 +/- 0.1 to 0.81 +/- 0.06 (P less than 0.0001). The women's mean plasma testosterone and LH concentrations decreased significantly (P less than 0.001 and P less than 0.005, respectively). A significant positive correlation was found between the decreases in plasma testosterone levels and the decreases in glucose-stimulated insulin levels. Moreover, the decreases in the waist to hip ratio correlated positively with the decreases in glucose-stimulated insulin levels and inversely with the decreases in plasma 17 beta-estradiol. No relationships were found between weight loss and the changes in plasma insulin, steroid, and gonadotropin concentrations. The responsiveness to the weight reduction program was evaluated by comparing the number of menstrual cycles during the study period with the number reported before it. Eight women had significantly improved menstrual cyclicity (responders), while 12 did not (nonresponders). The clinical characteristics and hormone values were similar in responder and nonresponder women. In the group as a whole, 33% of the menstrual cycles during the study were ovulatory, and 4 pregnancies occurred. Hirsutism improved significantly in more than half of the women, as did acanthosis nigricans when present. We conclude that weight loss is beneficial in all obese hyperandrogenic women regardless of the presence of polycystic ovaries, the degree of hyperandrogenism, and the degree and distribution of obesity.

Erythrocyte Na-K-ATPase membrane activity in obese patients fed over a long-term period with a very-low-calorie diet.

In a search for the role of long-term hypocaloric feeding on the expression of the erythrocyte Na pump in obesity, we examined three groups of subjects. Group 1 consisted of 10 obese subjects who had been under treatment for a long period of time with a very-low-calorie diet (500 kcal/d) while group 2 consisted of 10 age-, sex-, and body mass index-matched obese subjects on their usual diet; in the third group, 12 normal-weight subjects on a free diet served as controls. There was no difference between the groups in the number of erythrocyte binding sites per cell. On the contrary, the Na-K-ATPase activity was significantly lower in the obese group 1 (0.35 +/- 0.09 mumol Pi x mg protein-1 x h-1) compared to that observed in the obese group 2 (0.42 +/- 0.07, P less than .05) and in control subjects (0.45 +/- 0.06, P less than .05). Sex, duration of hypocaloric feeding, and the amount of weight loss before the study in the obese group 1 seemed not to be related to the Na pump parameters. We conclude that long-term severe hypocaloric feeding may be a factor in altered erythrocyte Na-K-ATPase in obese individuals.

Insulin as a factor of increased androgen production in women with obesity and polycystic ovaries.

To evaluate the possible role of moderate hyperinsulinemia on abnormal androgen secretion, we examined 4 age and weight-matched groups of obese subjects: 2 groups of women with normal menses whose fasting insulin (IRI) levels were less than or equal to 20 microU/ml (OB-I) or greater than or equal to 40 microU/ml (OB-I) and 2 groups of women with polycystic ovaries who were similarly grouped. All subjects underwent an oral glucose tolerance test, blood sex hormone determination and multiple LH determinations. Compared to OB, OB-PCO women showed significantly higher values of LH, androgen and estrogen concentrations. OB-I and OB-II showed similar hormonal patterns. On the contrary, OB-PCO-II presented significantly (p less than 0.05) higher androstenedione concentrations (348.7 +/- 129.9 ng/dl) (m +/- SD) than OB-PCO-I women (237.0 +/- 73.7 ng/dl). These differences were evident despite similar plasma LH concentrations. In conclusion, these results suggest that insulin may be a factor amplifying LH-dependent androgen secretion in hyperandrogenized women with obesity and PCO.

Sex hormones in obese premenopausal women and their relationships to body fat mass and distribution, B cell function and diet composition.

We examined sex hormone blood concentrations in a group of 33 obese non-hirsute premenopausal women with normal menses and in 14 age-matched normal-weight controls, and evaluated their relationship with anthropometric parameters, dietary habits and insulin levels. Obese women showed lower than control sex hormone-binding globulin (24.9 +/- 14.6 vs 38.6 +/- 12.5 nmol/l; p less than 0.005) and 5 alpha-dihydrotestosterone (13.7 +/- 5.4 vs 18.2 +/- 4.8 ng/dl; p less than 0.005) values. Despite their consensual behavior, the correlation coefficient between 5 alpha-dihydrotestosterone and sex hormone-binding globulin was not significant in the obese while in controls it was 0.68 (p less than 0.01). This suggests that mechanisms operating to lower the plasma levels of these compounds may be regulated differently in obesity. Body Mass Index, per cent body fat and its distribution showed a highly significant negative correlation with sex-hormone binding-globulin and 5 alpha-dihydrotestosterone values. Insulin levels did not appear to be correlated with sex hormone values. On the contrary, in the obese women we found a highly significant correlation between dietary lipids and sex-hormone-binding-globulin levels (r = -0.54; p less than 0.005) and between dietary carbohydrates and estrone values (r = 0.47; p less than 0.005); all these relationships were independent of body weight. These results confirm that in premenopausal women obesity may be characterized by detectable changes in sex steroid metabolism and suggest a possible causal role not only of the excessive quantity of metabolically active adipose tissue but also of specific dietary factors.

Diabetic autonomic neuropathy and impaired human pancreatic polypeptide secretion in response to food.

In normal subjects, the early human pancreatic polypeptide (hPP) increase induced by food is mainly dependent on vagal activity. Parasympathetic function and plasma hPP response to a standard mixed meal were evaluated in 10 long term insulin-dependent (type I) diabetic patients (group A), 6 age-matched newly diagnosed type I diabetic patients (group B), and 8 normal subjects. The indices of vagal function (beat to beat heart rate variation during deep breathing and the Valsalva maneuver) were uniformly altered in group A, while they were in the normal range in group B, thus excluding in these latter patients the presence of vagal damage. Plasma hPP in response to standard mixed meal was measured at 5, 15, 30, 60, and 120 min. Fasting plasma hPP concentrations (determined by RIA) in groups A and B (mean +/- SEM, 113 +/- 21 and 83 +/- 21 pg/ml, respectively) did not significantly differ from normal (59 +/- 12 pg/ml). In group A, the initial meal-induced hPP increase was significantly lower than normal (5 min, 139 +/- 12; 15 min, 173 +/- 24; 30 min, 137 +/- 17 pg/ml; P less than 0.01 vs. 5 min, 412 +/- 76; 15 min, 446 +/- 57; 30 min, 325 +/- 56 pg/ml). All group B patients had a marked early increase in the peptide, similar to that in the normal subjects. These results suggest that diabetic autonomic neuropathy is associated with dysfunction of hPP secretion, and the evaluation of hPP in response to SMM may be considered a sensitive and nonstressful method for the assessment of parasympathetic impairment in diabetes.

Effect of weight loss and antiandrogenic therapy on sex hormone blood levels and insulin resistance in obese patients with polycystic ovaries.

This study was performed in two randomly defined groups of obese patients with polycystic ovaries to investigate the overall effects of hypocaloric diet combined (group 2) or not combined (group 1) with an antiandrogenic therapy (cyproterone acetate, 50 mg/day, plus ethinyl estradiol, 0.05 mg/day) on sex hormone plasma levels, insulin secretion and resistance, and body weight loss and on their reciprocal interrelationships. All obese patients with polycystic ovaries showed elevated luteinizing hormone and androgen levels, hyperinsulinemia, and marked insulin resistance. After an average period of 3 months both groups showed a similar weight loss and a similar reduction in the insulin-resistant state. During treatment in group 1 three patients had a greater frequency of menstrual bleeding, and in one of them an ovulatory cycle was documented. Whereas, no changes in gonadotropin and sex steroid levels were found in group 1, a significant fall was observed in group 2. No relationships were observed between these changes and those which occurred on insulin levels. We conclude that hyperandrogenism in obese patients with polycystic ovaries does not appear to be a primary factor leading to the insulin-resistant state.

Heterogeneity of the erythrocyte Na-K pump status in human obesity.

The number of Na-K pump units, the Na-K-ATPase activity, the K transport turnover rate per pump unit and the intracellular Na and K concentrations were measured in the erythrocytes of 56 obese patients and 20 normal subjects. No differences were found between the two groups. In obese patients, we failed to observe any influence of dietary habits, age of onset, or family history of obesity on the Na pump status. On the other hand, we found that the number of pump units was not a close reflection of the membrane cation transport and in some patients with an abnormally high number of pump units, an inappropriately low Na-K-ATPase activity was observed. We also identified two small groups of obese patients with, respectively, abnormally high or low K transport turnover rate per pump unit. Our study seems to support the hypothesis that abnormalities in the erythrocyte Na-K pump system are not usual in the obese population but are probably present only in a limited number of selected patients.

Altered erythrocyte Na-K pump in anorectic patients.

The status of the erythrocyte sodium pump was evaluated in a group of patients suffering from anorexia nervosa and a group of healthy female control subjects. Anorectic patients showed significantly higher mean values of digoxin-binding sites/cell (ie, the number of Na-K-ATPase units) with respect to control subjects while no differences were found in the specific 86Rb uptake (which reflects the Na-K-ATPase activity) between the two groups. A significant correlation was found between relative weight and the number of Na-K-ATPase pump units (r = -0.66; P less than 0.0001). Anorectic patients showed lower serum T3 concentrations (71.3 +/- 53 ng/dL) with respect to control subjects (100.8 +/- 4.7 ng/dL; P less than 0.0005) and a significant negative correlation between T3 levels and the number of pump units (r = -0.52; P less than 0.003) was found. Our study therefore shows that the erythrocyte Na-K pump may be altered in several anorectic patients. We suggest that this feature could be interrelated with the degree of underweight and/or malnutrition.

Erythrocyte Na+-ATPase in obese patients.

Na+-K+-ATPase activity, as measured by erythrocytic 86Rb uptake and number Digoxin Binding Sites were evaluated in 34 obese patients and in 39 control subjects. No differences were found in 86Rb uptake and Digoxin Binding Sites between obese and controls. Likewise no differences were found between obese patients on their spontaneous caloric intake and those studied during various hypocaloric regimens. Finally, no relationship between thyroid hormone serum concentrations and ATPase activity was found in the group of obese patients.

Insulin resistance in patients with polycystic ovaries: its relationship to body weight and androgen levels.

Using a combined infusion of somatostatin, insulin and glucose, insulin resistance was assessed in vivo in two groups of females with polycystic ovaries (PCO), obese (PB-PCO) and normal weight (NO-PCO) and in two groups of matched (for age, sex and body mass index) controls (OB and NO). A steady state plasma glucose (SSPG) and insulin (SSPI) was attained after 90 min. OB-PCO and NO-PCO showed higher SSPG with respect to matched controls. The SSPG levels were related to body mass index (r = 0.69; P less than 0.001). The SSPG values were significantly correlated with the fasting insulin levels (r = 0.47; P less than 0.003). Gonadotrophin and steroid peripheral blood concentrations were also evaluated in the PCO females. A significant correlation was found between the SSPG values and the dehydroepiandrosterone sulphate levels (r = 0.46; P less than 0.05) and between the fasting insulin levels and the androstenedione concentrations (r = 0.64; P less than 0.01). Moreover, significant correlation coefficients were found between the glucose to insulin ratio and the A (r = -0.59; P less than 0.01) and the DHEA-S (r = -0.50; P less than 0.05) plasma levels. Finally, no relationship between body mass index and A or DHEA-S levels was found in PCO females considered as a group. We conclude that insulin resistance is present in females with PCO and it is mainly due to the presence of obesity, but other factors such as androgen levels, probably of adrenal sources, must be considered as a cause.

Clinical application of the 24-H urinary C-peptide excretion rate and its relationship to metabolic control in diabetics.

In this study, we evaluated in normal subjects, insulin-dependent (IDD) and non-insulin-dependent (NIDD) diabetics, the diurnal urinary C-peptide excretion rate (CPR-U) and its relationship to serum C-peptide concentration and glucose:C-peptide molar ratio, and to the common parameters of metabolic control. The CPR-U (and CPR-U/g creatinine) were significantly lower in IDD and higher in NIDD compared to control subjects. Moreover, a good and significant correlation with serum C-peptide concentrations and the glucose:C-peptide ratio in diabetic subjects as well as in controls and diabetics considered together was found. A slight but significant correlation was present in diabetic subjects between CPR-U and body mass index (r = 0.45), 24-h glycosuria (r = 0.36), HbA1 levels (r = 0.31), post-prandial glucose concentrations (r = 0.26) and per cent glucose variation after each meal (r = 0.34). No differences were found in CPR-U and the degree of metabolic control between obese and non-obese NIDD. In conclusion, CPR-U may be a useful and simple method of defining the secretory activity of the B-cell. Metabolic control in diabetics is slightly correlated to the degree of B-cell function as evaluated by the diurnal excretion rate of C-peptide in urine.