Influence of dietary fat and carbohydrates proportions on plasma lipids, glucose control and low-grade inflammation in patients with type 2 diabetes-The TOSCA.IT Study.

PURPOSE: The optimal macronutrient composition of the diet for the management of type 2 diabetes is debated, particularly with regard to the ideal proportion of fat and carbohydrates. The aim of the study was to explore the association of different proportions of fat and carbohydrates of the diet-within the ranges recommended by different guidelines-with metabolic risk factors. METHODS: We studied 1785 people with type 2 diabetes, aged 50-75, enrolled in the TOSCA.IT Study. Dietary habits were assessed using a validated food-frequency questionnaire (EPIC). Anthropometry, fasting lipids, HbA1c and C-reactive protein (CRP) were measured. RESULTS: Increasing fat intake from <25 to ≥35 % is associated with a significant increase in LDL-cholesterol, triglycerides, HbA1c and CRP (p < 0.05). Increasing carbohydrates intake from <45 to ≥60 % is associated with significantly lower triglycerides, HbA1c and CRP (p < 0.05). A fiber intake ≥15 g/1000 kcal is associated with a better plasma lipids profile and lower HbA1c and CRP than lower fiber consumption. A consumption of added sugars of ≥10 % of the energy intake is associated with a more adverse plasma lipids profile and higher CRP than lower intake. CONCLUSIONS: In people with type 2 diabetes, variations in the proportion of fat and carbohydrates of the diet, within the relatively narrow ranges recommended by different nutritional guidelines, significantly impact on the metabolic profile and markers of low-grade inflammation. The data support the potential for reducing the intake of fat and added sugars, preferring complex, slowly absorbable, carbohydrates.

Randomized, double-blind, placebo-controlled trial to evaluate the effect of Helicobacter pylori eradication on glucose homeostasis in type 2 diabetic patients.

BACKGROUND AND AIMS: Literature data suggest an association between Helicobacter pylori infection and glucose homeostasis. However, a causative link between them has not been demonstrated yet. The aim of this study is to investigate the effect of H. pylori eradication on glucose homeostasis in patients with type 2 diabetes. METHODS AND RESULTS: A randomized, double-blind, placebo-controlled trial was conducted to investigate the effect of H. pylori eradication on glucose homeostasis in 154 patients with type 2 diabetes and who tested positive for H. pylori infection (mean age (SD), 63.1 (8.1) years). Subjects were assigned to H. pylori eradication treatment or placebo. Metabolic and inflammatory parameters were measured in all subjects at baseline and 4 weeks after the treatment. H. pylori eradication led to an improvement in glucose homeostasis, measured by HOMA-IR (p < 0.001) and KITT (0 = 0.041), due to the decrease in fasting insulin levels (p = 0.004). The results also showed that lower levels of inflammatory parameters were present after eradication. CONCLUSION: To our knowledge this is the first randomized, double blind, controlled study where the effect of H. pylori eradication on glucose homeostasis in subjects with type 2 diabetes has been investigated. Our findings demonstrate that H. pylori eradication improves glucose homeostasis in patients with type 2 diabetes through a decrease in pro-inflammatory factors. TRIAL REGISTRATION NUMBER: ACTRN12609000255280 (https://www.anzctr.org.au/).

Sex differences in food choices, adherence to dietary recommendations and plasma lipid profile in type 2 diabetes - The TOSCA.IT study.

BACKGROUND AND AIMS: Diabetic women have a more adverse plasma lipid profile than men. Sex differences in dietary habits may play a role, but are little investigated. The study evaluates the quality of diet, adherence to the nutritional recommendations of the Diabetes and Nutrition Study Group and their relation with plasma lipid in men and women with diabetes. METHODS AND RESULTS: We studied 2573 people, aged 50-75, enrolled in the TOSCA.IT study (clinicaltrials.gov; NCT00700856). Plasma lipids were measured centrally. Diet was assessed with a semi-quantitative food frequency questionnaire. Women had a more adverse plasma lipid profile than men. Women consumed significantly more legumes, vegetables, fruits, eggs, milk, vegetable oils, and added sugar, whereas men consumed more starchy foods, soft drinks and alcoholic beverages. This stands for a higher proportion (%) of energy intake from saturated fat and added sugar (12.0 ± 2.4 vs 11.5 ± 2.5 and 3.4 ± 3.2 vs 2.3 ± 3.2, P < 0.04), and a higher intake of fiber (11.2 ± 2.8 vs 10.4 ± 2.6 g/1000 Kcal/day) in women. Adherence to the recommendations for saturated fat and fiber consumption was associated with significantly lower LDL-cholesterol regardless of sex. Adherence to the recommendations for added sugars was associated with significantly lower triglycerides and higher HDL-cholesterol in men and women. CONCLUSIONS: Men and women with diabetes show significant differences in adherence to nutritional recommendations, but sex differences in plasma lipid profile are unlikely to be explained by nutritional factors. Adherence to the nutritional recommendations is associated with a better plasma lipid profile regardless of sex, thus reinforcing the importance of substituting saturated for unsaturated fat sources, increasing fiber and reducing added sugar intake.

Dietary habits in type II diabetes mellitus: how is adherence to dietary recommendations?

OBJECTIVE: To clarify adherence of type II diabetic patients to dietary recommendations. SUBJECTS AND METHODS: The dietary habits of a group of 540 patients, with type II diabetes (male 322/female 218, mean age 61+/-5 years, body mass index (BMI) 29.7+/-5.2 kg/m(2); mean+/-s.d.) referring to six Italian diabetes centres were evaluated by means of a 3-day diet record (2 workdays, 1 holiday). Diet records were analysed according to Italian food composition tables and compared with the dietary recommendations of the Diabetes and Nutrition Study Group of the European Association for the study of Diabetes. RESULTS: Calorie intake was 1725+/-497 kcal (1800 for men, 1610 for women). Mean intake for each nutrient was close to the recommended amount, except for fibre (12/1000 vs 20 g/1000 kcal). Calculating the percentage of patients who complied with each recommendation, the intakes of saturated fat and fibre least reflected the dietary target: in 43% of patients saturated fat was >10% of total calories, in only 6% was fibre intake > or =20 g/1000 kcal (considered ideal), and in 25% it was > or =15 g/1000 kcal (acceptable). CONCLUSIONS: These results indicate that compliance to dietary recommendations is not completely satisfactory, even in Italy. Calorie intake is a bit elevated, given the high BMI of our diabetic population. As to dietary composition, there are two crucial issues: the high intake of saturated fat and--most importantly--the low intake of fibre. All strategies aiming to a proper implementation of guidelines should take these results into due account.

C-reactive protein is directly related to plasminogen activator inhibitor type 1 (PAI-1) levels in diabetic subjects with the 4G allele at position -675 of the PAI-1 gene.

BACKGROUND AND AIMS: C-reactive protein (CRP) has been identified as a possible factor able to promote atherosclerosis. "In vitro" studies have demonstrated that CRP induces plasminogen activator inhibitor type 1 (PAI-1) expression, suggesting a hypofibrinolytic role for CRP. As CRP and PAI-1 levels increase in type 2 diabetic subjects, we decided to study the relationship between CRP and PAI-1, and the role of the 4G/5G polymorphism of the PAI-1 gene on this relationship in a diabetic population without complications. METHODS AND RESULTS: Two hundred and ninety-five type 2 diabetic patients (age 60.9+/-10.5 years) and 290 healthy controls (age 59.2+/-11.5 years) were enrolled. A significant correlation between PAI-1 and CRP in diabetic subjects was found (r=0.45, p<0.001), whereas no relationship was evident in the control subjects between these inflammatory markers. Multiple regression analysis highlighted that CRP is the only one significant variable of PAI-1 antigen in diabetic subjects (partial r=0.31, p<0.01). Stratifying by genotype, a positive correlation between PAI-1 and CRP in 4G/4G (partial r=0.64 p<0.001) and 4G/5G (partial r=0.47, p<0.001) subjects was found, whereas no correlation in 5G/5G was present. Multiple regression analysis confirmed the presence of this correlation in 4G/4G (partial r=0.45, p<0.001) and in 4G/5G (partial r=0.34, p=0.007) diabetic patients. CONCLUSIONS: These findings demonstrate that CRP plays an important role in the complex mechanism regulating PAI-1 antigen in 4G diabetic carriers.

Predictors of treatment response to liraglutide in type 2 diabetes in a real-world setting.

AIMS: There is an unmet need among healthcare providers to identify subgroups of patients with type 2 diabetes who are most likely to respond to treatment. METHODS: Data were taken from electronic medical records of participants of an observational, retrospective study in Italy. We used logistic regression models to assess the odds of achieving glycated haemoglobin (HbA1c) reduction ≥ 1.0% point after 12-month treatment with liraglutide (primary endpoint), according to various patient-related factors. RECursive Partitioning and AMalgamation (RECPAM) analysis was used to identify distinct homogeneous patient subgroups with different odds of achieving the primary endpoint. RESULTS: Data from 1325 patients were included, of which 577 (43.5%) achieved HbA1c reduction ≥ 1.0% point (10.9 mmol/mol) after 12 months. Logistic regression showed that for each additional 1% HbA1c at baseline, the odds of reaching this endpoint were increased 3.5 times (95% CI: 2.90-4.32). By use of RECPAM analysis, five distinct responder subgroups were identified, with baseline HbA1c and diabetes duration as the two splitting variables. Patients in the most poorly controlled subgroup (RECPAM Class 1, mean baseline HbA1c > 9.1% [76 mmol/mol]) had a 28-fold higher odds of reaching the endpoint versus patients in the best-controlled group (mean baseline HbA1c ≤ 7.5% [58 mmol/mol]). Mean HbA1c reduction from baseline was as large as - 2.2% (24 mol/mol) in the former versus - 0.1% (1.1 mmol/mol) in the latter. Mean weight reduction ranged from 2.5 to 4.3 kg across RECPAM subgroups. CONCLUSIONS: Glycaemic response to liraglutide is largely driven by baseline HbA1c levels and, to a lesser extent, by diabetes duration.

Interleukin-6-174 G > C polymorphism affects the association between IL-6 plasma levels and insulin resistance in type 2 diabetic patients.

Interleukin-6 (IL-6), a powerful inflammatory mediator, plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. Recently, the IL-6 promoter polymorphism, at position -174 (G > C), has been associated to insulin sensitivity although contrasting data have been reported. The aim of this study was to evaluate the effect of the IL-6-174 G > C polymorphism on insulin resistance. In 238 type 2 diabetic patients without diabetic complications and in 255 control subjects, age and gender-matched, we evaluated the IL-6 -174 G > C genotype, the IL-6 plasma levels and the insulin resistance by the homeostasis model assessment (HOMA). The levels of IL-6 and HOMA were not genotype-dependent and were higher in diabetic patients (p < 0.01). Control subjects, both C+ (CG + CC genotypes) and C- (GG genotype) carriers, showed IL-6 plasma levels significantly related to BMI, fasting insulin and HOMA. The same relationships were found in C+ diabetic carriers. Differently, diabetic C- carriers did not show any relationship between IL-6 levels and all the evaluated variables. Interestingly, all the correlations were dependent on BMI. These findings highlight that IL-6-174 G > C polymorphism affects insulin resistance in type 2 diabetes, where C+ carriers have an insulin resistance "IL-6-sensitive", while C- carriers do not. The identification of two categories of diabetic patients may, therefore, lead to different therapeutic strategies in the management of insulin resistance.

Zinc-dependent low thymic hormone level in type I diabetes.

Zinc is required for optimal functioning of the immune system. It was recently reported that one of the best-known thymic hormones responsible for the maturation and differentiation of the thymus-derived T-lymphocyte line, i.e., serum thymic factor (STF), is biologically active only when bound to zinc ions; in this form it has been called thymulin (Zn-STF). Because low serum and tissue zinc values have been reported to occur in diabetic conditions, and because defects of T-lymphocyte-dependent functions are also present in diabetic patients, even metabolically well-controlled diabetic patients, we investigated the serum level of zinc and the plasma level of both active Zn-STF and inactive STF thymic hormones in 15 young patients suffering from type I (insulin-dependent) diabetes. Serum zinc levels were significantly reduced in diabetic conditions and did not correlate with the degree of metabolic compensation measured by glycosylated hemoglobin. In diabetes, the active form of thymulin is strongly reduced, whereas the inactive form is abnormally elevated. In vitro zinc addition to diabetic plasma samples also induces zinc saturation of inactive thymic hormone molecules: the total thymic hormone measured in these experimental conditions shows values in diabetic patients comparable with those observed in healthy age-matched individuals, suggesting that low thymulin levels recorded in diabetic conditions are due not to a thymic failure in synthesizing and secreting thymic hormone but to a peripheral defect in zinc saturation of the hormone molecules. The zinc-dependent failure of thymic hormone, present even in fairly compensated diabetic conditions, might account for the apparent insulin-independent immunological abnormalities associated with type I diabetes.

Renal disease as a determinant of increased lipoprotein(a) concentrations in diabetic patients.

OBJECTIVE: This study examined the hypothesis that kidney function is an independent determinant of lipoprotein(a) [Lp(a)] concentrations in people with diabetes. RESEARCH DESIGN AND METHODS: Lp(a) concentrations were measured in plasma samples from 273 type 2 and 223 type 1 diabetic patients recruited from a diabetes clinic. Kidney function was categorized as normal or pathological according to plasma creatinine levels and creatinine clearance rates. RESULTS: Macroalbuminuria was uniformly associated with significantly raised plasma concentrations of Lp(a) regardless of the marker used to identify kidney dysfunction. In contrast, in patients with microalbuminuria, significantly raised plasma Lp(a) levels were observed only when creatinine clearance rates or plasma creatinine levels indicated pathological kidney function. These conclusions were independent of diabetes type. CONCLUSIONS: In microalbuminuria and apparently in normoalbuminuria, altered kidney function determined by creatinine clearance rates or creatinine levels appears to be a major determinant of raised Lp(a) levels in both type 1 and type 2 diabetic patients. In contrast, Lp(a) concentrations were uniformly raised in patients with macroalbuminuria.

Apolipoprotein E polymorphism as a risk factor for vascular disease in diabetic patients.

OBJECTIVE: To examine the prevalence of cardiovascular disease in diabetic patients as a function of apolipoprotein (apo) E polymorphism. RESEARCH DESIGN AND METHODS: The apo E phenotypes and plasma lipid, lipoprotein, and apo levels were determined for 517 Italian diabetic patients. The prevalence of cardiovascular disease (defined as ischemic heart disease [HD] and/or peripheral vascular disease and/or cerebrovascular disease) was assessed as a function of apo E polymorphism at entry and after 4 years. RESULTS: The occurrence of vascular disease did not differ significantly between diabetic patients in the various categories of apo E phenotype either at entry into the study or after 4 years. When expressed as a percentage of patients with disease, we observed--for E2, E3, and E4 carriers, respectively--at entry: IHD, 20.0% (n = 14), 21.0% (n = 79), and 21.5% (n = 14); and macroangiopathy, 24.3% (n = 17), 29.3% (n = 110), and 24.6% (n = 16). Apo E polymorphism did not make a significant contribution to multiple logistic regression models designed to identify the factors associated with the occurrence of vascular disease in diabetic patients. CONCLUSION: Apo E polymorphism and, notably, the apo E4 allele cannot be universally considered as a particular risk factor for cardiovascular disease in diabetic patients.

Serum paraoxonase is reduced in type 1 diabetic patients compared to non-diabetic, first degree relatives; influence on the ability of HDL to protect LDL from oxidation.

Paraoxonase is a serum enzyme with an anti-oxidant function, protecting low density lipoproteins (LDL) from oxidative modifications. Diabetic patients are suggested to be at greater risk of oxidative stress, which may contribute to the significantly higher incidence of vascular disease in this population. Less efficient protection mechanisms may be one feature of the greater susceptibility to oxidation in diabetes. In this context, the present study examined the hypothesis that serum paraoxonase is reduced in type 1 (insulin-dependent) diabetic patients and that the reduction can affect the anti-oxidant capacity of HDL. Serum paraoxonase concentrations and activities were compared in type 1 patients and first degree, non-diabetic relatives with particular attention paid to the confounding effects of paraoxonase gene polymorphisms. In addition, the ability of HDL-paraoxonase to protect low density lipoproteins from oxidation was analysed in an in vitro system. Serum concentrations and enzyme activities of paraoxonase were significantly lower in type 1 patients compared to non-diabetic, first degree relatives. The differences were independent of promoter and coding region polymorphisms, which influence serum concentrations and activities of the enzyme. Overall, paraoxonase concentrations were a mean 13.3+/-4.5% lower (P<0.02) in type 1 patients. Specific activities did not differ between diabetic and non-diabetic groups. The concentration ratios of LDL cholesterol:paraoxonase (1.37+/-0.51 vs. 1.18+/-0.37, P=0.003) and apolipoprotein B:paraoxonase (0.84+/-0.33 vs. 0.71+/-0.40; P=0.012) were significantly higher in diabetic patients, consistent with a reduced capacity to protect LDL from oxidation. In vitro oxidation studies showed that a significantly higher level of lipid hydroperoxides was generated in LDL in the presence of HDL, containing paraoxonase levels equivalent to those of type 1 patients, compared to HDL containing paraoxonase levels equivalent to those of control subjects (mean difference 8.1%, P<0.05). The study demonstrates that serum concentrations of the antioxidant enzyme paraoxonase are significantly lower in type 1 (insulin-dependent) diabetic patients compared to non-diabetic, first-degree relatives, independently of known gene polymorphisms. Concentrations are reduced to an extent that can affect its anti-oxidant capacity. The results are consistent with the contention that modifications to serum paraoxonase in type 1 patients can increase risk of lipoprotein oxidation and, consequently, risk of vascular disease.

One- and two-compartment minimal models detect similar alterations of glucose metabolism indexes in hypertension.

A standard intravenous glucose tolerance test (IVGTT) was performed in 10 nondiabetic patients with essential hypertension (H group) and 9 normotensive control subjects (N group). A 2-compartment minimal model (2CMM) of glucose kinetics was applied to estimate indexes of glucose effectiveness, S2G and insulin sensitivity, S2I, by means of a maximum a posteriori (MAP) bayesian estimation technique. These estimates were contrasted to the S1G and S1I indexes provided by the classic minimal model (1CMM). In both the N group and the H group, the 2CMM underestimated the glucose effectiveness and overestimated the insulin sensitivity. In the H group, S2G was, on average, 63% of S1G (P > .05) and S2I was 137% of S1I (P > .05). In the N group S2G was 67% of S1G (P > .05) and S2I was 134% of S1I (P > .05). The 2CMM detected a reduction of approximately 40% (P > .05) and approximately 48% (P > .05) in S2G and S2I estimates, respectively, from the N group to the H group. Despite its reduced complexity, the 1CMM also detected a reduction of approximately 35% (P < .05) and approximately 49% (P < .05) in the S1G and in S1I indexes, respectively. Thus, the 1CMM and 2CMM showed a substantial equivalence in detecting a severe reduction in insulin sensitivity and impaired glucose effectiveness in hypertensive patients compared with normal.

Random fasting hyperglycemia as cardiovascular risk factor in the elderly: a 6-year longitudinal study.

A large body of evidence suggests that diabetes increases the risk of coronary heart disease (CHD), but whether fasting hyperglycemia is associated with a major risk for CHD is still under debate. The aim of the present study was to investigate the role played by fasting hyperglycemia in the development of cardiovascular disease (CVD) in an elderly population when associated with common risk factors for CVD (i.e., hypertension, hypercholesterolemia, smoking, etc). We analyzed a sample of 455 subjects aged > or = 60 years. The risk factors taken into account were systolic and diastolic blood pressure levels, use of antihypertensive drugs, total serum cholesterol, serum triglycerides, and smoking habit. Glycemia was measured at entry on a fasting sample. During the follow-up period (mean 6 years), the occurrence of CVD was monitored (criteria for the occurrence of CVD included total cardiovascular mortality, fatal or nonfatal myocardial infarction, symptomatic coronary heart disease [stable and unstable angina], the need for percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal or nonfatal stroke, and transient ischemic attack). A total of 427 subjects completed the follow-up. During this period, 73 subjects (17.10%) developed CVD according to the above criteria. A Cox proportional hazard model was designed to evaluate the contribution of variables in predicting CVD. Relative risks and 95% confidence intervals for CVD were calculated from the regression coefficients to study the association between the risk of developing CVD and predicting variables. We found a relation between occurrence of CVD and fasting hyperglycemia: subjects with fasting glycemia, > 126 mg/dl at enrollment, but without previous clinical diagnosis of diabetes, showed a 2.01 times higher risk than those with fasting glycemia < 126 mg/dl. Hence, random fasting hyperglycemia can predict the occurrence of CVD in elderly subjects.

Age-related macular disease in diabetes mellitus.

Age-related macular degeneration (ARMD) is one of the leading causes of vision impairment in the elderly and its frequency in general population increases with aging. The etiology of this disease has remained so far unknown. The relationship between ARMD and diabetes mellitus was studied in the present work. Fundus oculi was investigated in 292 diabetic patients older than 50 years and with more than 14 years of duration of diabetes (time since diagnosis). A group of 375 non diabetic, non hypertensive subjects matched for age was studied as control. ARMD frequency was significantly higher in diabetics compared to controls (p < 0.005); and also in type II diabetics (non-insulin dependent diabetes mellitus = NIDDM) compared to type I (insulin dependent diabetes mellitus = IDDM) (p < 0.001). Older diabetic patients showed an increased frequency of ARMD while no correlation with the duration of the disease emerged. Macular damage was not linked to microangiopathy (retinopathy), hypertension or gender; on the contrary, it appeared to be associated with dyslipidemia. On the basis of these data one can conclude that diabetes mellitus can exert an unfavorable effect on macular age-related phenomena even if the pathogenetic mechanism is at present obscure.

Diabetes mellitus and chronic heart failure.

Cardiovascular disease has a high prevalence in diabetic patients. Diabetes mellitus is an important risk factor for atherosclerosis and coronary disease mainly through obesity, hyperlipidemia, insulin-resistance, hyperinsulinemia, hyperglycemia and altered homeostasis. The correlation between diabetes and chronic heart failure is not widely documented in the literature. According to the Framingham study, the incidence of cardiovascular morbidity per year is 39.1% in diabetic males and 17.2% in diabetic females; chronic heart failure afflicts 7.6% of diabetic males and 11.4% of diabetic females. Actual knowledge about pathophysiology suggests that cardiac involvement in diabetes is not only related to macrovascular injury but also to other factors, such as alterations of autonomic nervous system, that can contribute to diabetic cardiopathy. The present study evaluated the prevalence of chronic heart failure in an Italian diabetic population in order to discuss the rationale of the therapeutic strategies.

Coronary heart disease, type 2 diabetes mellitus and cardiovascular disease risk factors: a study on a middle-aged and elderly population.

The risk for all the manifestations of atherosclerotic disease is increased in patients affected by type 2 diabetes mellitus. The aim of the present work was to evaluate the prevalence of coronary heart disease (CHD) in a well-characterized middle-aged and elderly Italian diabetic population. The population studied included 3862 subjects, i.e. all the patients affected by type 2 diabetes of age >or=50 years attending the outpatient diabetes care unit of INRCA in Ancona (Italy) from 1 August 1997 to 31 July 1998. We collected and analysed both clinical and laboratory data by means of a computerized data base for the outpatient clinic management. The prevalence rate of CHD was 20.25% in this population. The groups with CHD and without CHD did not differ significantly with respect to age at onset of diabetes, body mass index and HbA1c levels, while patients with CHD were significantly older than patients without CHD and had a longer duration of diabetes. The prevalence of patients with hypertension (52.9 vs 63.0%, P<0.001), hypercholesterolemia (11.6 vs 14.1%, P<0.05) and hyperlipidemia (17.8 vs 23.3%, P<0.001) was significantly higher in the group of diabetic subjects affected by CHD than in patients not affected by heart ischemic disease. It might be hypothesized that the improvement of metabolic profile and the currently feasible control of non-diabetic risk factors could reduce cardiovascular disease rates in type 2 diabetic patients.

Influence of body mass on glycemic control in a type 2 diabetic population: a 3-year follow-up.

Obesity is often associated with type 2 (non insulin-dependent) diabetes. A growing body of evidence support the hypothesis that these two diseases share a common pathogenesis. Nevertheless, experience derived from clinical observation on type 2 diabetic patients indicates that reduction of body weight is not always accompanied by an improvement in metabolic control and that a good metabolic control is often obtained without influencing body composition. Aim of the present study was to evaluate the relationship between body mass and glycemic control in a type 2 diabetic population by a 3 years observational study. A cohort of 562 subjects was studied. At entry more than 80% of patients were overweight or obese according to the body mass index (BMI) scale and this proportion was not significantly reduced at the end of the follow-up. At entry all patients had a glycosylated hemoglobin (HbA1c) value above 8.1% whereas at the end of follow-up more than 2/3 of patients were in good metabolic control. No relationship was observed between modification of body mass and metabolic control. These data confirm the high frequency of obesity among type 2 diabetic individuals but they suggest that impaired glucose metabolism and alteration of body weight have different pathogenesis.

[Hemo-rheologic changes following treatment with human recombinant erythropoietin in chronic hemodialysis patients]. / Alterazioni emoreologiche in seguito a trattamento con eritropoietina umana ricombinante in pazienti emodializzati cronici.

Human recombinant erythropoietin constitutes a remarkable improvement in the treatment of uraemic anemia. Nevertheless, it causes haemorheological changes, which in turn may affect smaller blood vessel circulation. Our study was conducted on a pool of chronic uraemic patients under hemodialytic treatment who were given erythropoietin therapy. Substantial increases in overall blood viscosity and red cell aggregation were recorded, with no change in erythrocyte deformation. An increase in cardiovascular morbidity might occur in these patients who are already liable to this condition. Several years will have to elapse and thorough studies will have to be conducted on a large number of patients, to have conclusive evidence on this point.

The prevalence of cardiovascular autonomic neuropathy and of retinopathy in relation to the duration of diabetes.

In a study on the prevalence of cardiovascular autonomic neuropathy and retinopathy in a group of 57 diabetic subjects, an increased prevalence of these complications related to the duration of diabetes has been found.

Relationships between obesity and ischaemic heart disease in type II diabetic subjects homozygous for the apoprotein E3 allele.

The purpose of the present study was to evaluate the influence of obesity on ischaemic heart disease frequency in a well-documented type II diabetic population. To eliminate one of the possible sources of variability for plasma lipid concentrations, only subjects showing the apoprotein E phenotype, indicative of homozygosity for the epsilon 3 allele (i.e. an E3/E3 genotype), have been recruited. A larger prevalence of ischaemic heart disease was noticed among obese patients as compared to non-obese or merely overweight subjects according to a higher frequency of hypertension and to higher triglyceride concentrations. These results corroborate the hypothesis of a common pathogenesis of the major cardiovascular risk factors.