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Mounting evidence supports the hypothesis that functional foods containing physiologically-active components may be healthful. Longitudinal cohort studies have shown that some food classes and dietary patterns are beneficial in primary prevention, and this has led to the identification of putative functional foods. This field, however, is at its very beginning, and additional research is necessary to substantiate the potential health benefit of foods for which the diet-health relationships are not yet scientifically validated. It appears essential, however, that before health claims are made for particular foods, in vivo randomized, double-blind, placebo-controlled trials of clinical end-points are necessary to establish clinical efficacy. Since there is need for research work aimed at devising personalized diet based on genetic make-up, it seems more than reasonable the latter be modeled, at present, on the Mediterranean diet, given the large body of evidence of its healthful effects. The Mediterranean diet is a nutritional model whose origins go back to the traditional diet adopted in European countries bordering the Mediterranean sea, namely central and southern Italy, Greece and Spain; these populations have a lower incidence of cardiovascular diseases than the North American ones, whose diet is characterized by high intake of animal fat. The meeting in Naples and this document both aim to focus on the changes in time in these two different models of dietary habits and their fall out on public health.

The present study was aimed at evaluating in patients with type 2 diabetes: (1) the glycaemic response to four starchy foods based on wheat, typical of the Italian diet; (2) the importance of some food characteristics in relation to their effects on postprandial glucose response. Seventeen patients with type 2 diabetes (eleven men and six women) participated in the study. All patients consumed, in random order and on alternate days, 50 g available carbohydrate provided by 90 g white bread and, according to a randomised procedure, an equivalent amount of carbohydrate provided by one (n 8) or two (n 9) of three other different test foods (g): pizza 85, potato dumplings 165, hard toasted bread 60. Foods had a similar nutrient composition. Plasma glucose response, measured for 180 min, was significantly lower after the potato dumplings than after white bread at 90 (Pin vitro hydrolysis with α-amylase was about 30 % lower for potato dumplings than for the other foods. However, no differences in the resistant starch content, the rate of diffusion of simple sugars added to a dialysis tube containing the food, and the viscosity of digesta were observed among the test foods. Scanning electron microscopy of potato dumplings showed a compact structure compatible with impaired accessibility of starch to digestive enzymes. In conclusion, carbohydrate-rich foods typical of the Italian diet which are often consumed as an alternative to pasta dishes are not equivalent in terms of metabolic impact in diabetic patients. Due to their low blood glucose response, potato dumplings represent a valid alternative to other starchy foods in the diabetic diet. Food structure plays an important role in determining starch accessibility to digestion, thus influencing the postprandial blood glucose response.

Objective To evaluate insulin sensitivity of essential hypertensive patients with different salt sensitivities of blood pressure in the absence of confounding factors such as obesity, glucose intolerance and the inclusion both of normotensive and of hypertensive subjects that have affected most previous studies. Patients Ninety-nine patients with untreated mild or moderate essential hypertension, World Health Organization class I-II, participated in the study. Methods Salt sensitivity was estimated using the Weinberger protocol with minor modifications and the patients were classified into tertiles of salt sensitivity. Results Patients with high NaCI sensitivities were slightly older and had somewhat higher blood pressures than did subjects with low salt sensitivities. Plasma renin activity significantly decreased with increasing salt sensitivity. There were no differences among the three groups in terms of body mass index, fasting blood glucose and insulin plasma levels. There were no differences among the groups in the integrated glucose and insulin response to a standard oral-glucose tolerance test However, there was a significant difference in insulin sensitivity between two subgroups of the upper and lower tertile of salt sensitivity, the salt-sensitive hypertensives having a markedly lower utilization of glucose than did the salt-resistant ones, with a minor overlap (5.4 ± 0.6 versus 7.4 ± 0.3 mg/kg per min, P< 0.01). Conclusions This study showed that essential hypertensive patients with high NaCI sensitivities were relatively insulin resistant compared with those with low NaCI sensitivities, independently of confounding factors such as age, obesity and glucose intolerance. Insulin resistance was not associated with overt hyperinsulinaemia among these patients.

Bariatric surgery (BS) is able to positively influence fasting lipid profile in obese type 2 diabetic patients (T2DM), but no data is available on the impact of BS on postprandial lipid metabolism neither on its relation with incretin hormones. We evaluated the short-term (2 weeks) effects of BS on fasting and postprandial lipid metabolism in obese T2DM patients and the contribution of changes in active GLP-1. We studied 25 obese T2DM patients (age = 46 ± 8 years, BMI = 44 ± 7 kg/m2), of which 15 underwent sleeve gastrectomy and 10 underwent gastric bypass. Lipid and incretin hormone concentrations were evaluated for 3 h after ingestion of a liquid meal before and 2 weeks after BS. After BS, there was a significant reduction in body weight (p

The aim of the study was to evaluate the effects of a supervised physical training added to a healthy diet-rich in either carbohydrate and fibre (CHO/fibre) or monounsaturated fatty acids (MUFA)-on postprandial dyslipidaemia, an independent cardiovascular risk factor particularly relevant in type 2 diabetes (T2D). Participants were forty-five overweight/obese subjects with T2D, of both genders, in good blood glucose control with diet or diet+metformin, with normal fasting plasma lipids. According to a parallel groups 2 × 2 factorial design, participants were randomized to an 8-week isoenergetic intervention with a CHO/fibre or a MUFA diet, with or without a supervised low-volume aerobic training programme. The main outcome of the study was the incremental area under the curve (iAUC) of lipid concentrations in the plasma chylomicron+VLDL lipoprotein fraction, isolated by preparative ultracentrifugation (NCT01025856). Body weight remained stable during the trial in all groups. Physical fitness slightly improved with training (VO2 peak, 16 ± 4 vs. 15 ± 3 ml/kg/min, M ± SD, p

Purpose: Cigarette smoking and diabetes mellitus predisposes to vascular disease. Our study aimed to evaluate the chronic effects of cigarette smoking on peripheral microcirculation assessed with contrast-enhanced ultrasound (CEUS) in diabetic patients. Materials and methods: The study population comprised ten smoker (7/3 M/W, age 42-76 years) and 16 nonsmoker (8/8 men/women, age 47-80 years) diabetic patients. The ankle-brachial index (ABI) was determined, and colour Doppler ultrasound (CDUS) of the lower legs was performed to determine the presence of peripheral arteriopathy disease (PAD). Microvascular blood flow in the gastrocnemius muscle was evaluated with CEUS. Results: No differences were observed in ABI and CDUS examination between smokers and nonsmokers. Smoking had a significant effect on microcirculatory function. Timeto-peak (TTP), arrival time in tissue (ATt) and artery/ tissue transit time (A/Ttt) were significantly prolonged in smokers (TTP 43.76±9.38 s vs. 34.12±6.8 s, p=0.011, ATt 28.9±7.5s vs. 22.4±6.4 s, p=0.017 and A/Ttt 6.81±4.52 s vs. 3.25±3.27 s, p=0.02), with no significant differences between patients with and without PAD. Conclusions: The long-term exposure to cigarette smoke affects microcirculatory function. Contrast imaging is a noninvasive technique that can document these effects

RIASSUNTO Nonostante gli sforzi per diffondere e implementare le raccomandazioni nutrizionali per il trattamento del diabete, la loro applicazione nella pratica clinica è ancora largamente insufficiente. Tra le possibili ragioni va considerato il fatto che le abitudini alimentari risentono molto delle tradizioni gastronomiche locali. Lo studio si propone di valutare le abitudini alimentari delle persone con diabete in tre macroaree geografiche italiane, nord, centro e sud, per studiare in che misura le tradizioni gastronomiche locali possano influenzare l'adesione alle raccomandazioni nutrizionali. Sono stati studiati 1786 pazienti diabetici di tipo 2; le abitudini alimentari sono state indagate con un questionario alimentare semiquantitativo di frequenza validato (EPIC, European Prospective Investigation on Cancer and Nutrition). L'introito energetico è sovrapponibile nelle 3 macroaree geografiche, ma gli alimenti che contribuiscono alla composizione della dieta sono diversi a seconda della locazione geografica: al nord si osserva un maggiore consumo di carne, salumi e grassi animali; al sud, un maggiore consumo di pane integrale e legumi. Questo si traduce in una differente composizione in nutrienti della dieta: il consumo di grassi totali, grassi saturi e polinsaturi risulta significativamente più basso al sud e al centro rispetto al nord (p < 0,05); il contrario si osserva, invece, per i carboidrati totali e la fibra alimentare (p < 0,05). Infine, la proporzione di pazienti che aderiscono alle raccomandazioni nutrizionali è generalmente scarsa sia per il consumo di fibra, mediamente inferiore rispetto a quanto raccomandato, sia per il consumo di grassi saturi, mediamente superiore ai livelli consigliati. In conclusione, le raccomandazioni nutrizionali sono scarsamente seguite su tutto il territorio nazionale; si osservano, tuttavia, significative differenze geografiche verosimilmente dovute all'influenza delle tradizioni gastronomiche locali che vanno tenute in conto per migliorare l'adesione dei pazienti alle raccomandazioni dietetiche.

Summary Background & aims Intervention studies investigating the effects of wholegrain intake on glucose and insulin metabolism have provided conflicting results. Aim of this study was the evaluation of glucose and insulin metabolism in response to long-term consumption of rye and whole wheat compared with a diet containing the same amount of refined cereal foods, in individuals with metabolic syndrome from two European locations (Kuopio-Finland/Naples-Italy). Methods 146 individuals of both genders, age range 40–65 years with metabolic syndrome, were recruited to this study with parallel groups. After a 2–4 week run-in period, participants were assigned to a diet based on wholegrain (wholegrain group) or on refined cereal products (control group), each one for a duration of 12 weeks. Peripheral insulin sensitivity, assessed by FSIGT, lipids and inflammatory markers were measured before and at the end of intervention. Results 61 participants in the control group and 62 in the wholegrain group completed the dietary intervention. Compliance to the two diets was good. At the end of the intervention, insulin sensitivity indices and secretion (SI, QUICKI, DI, dAIRG) and lipids and inflammatory markers did not change significantly in the wholegrain and control groups as compared with baseline and no differences between the two groups were observed. Conclusions Wholegrain cereal foods consumption compared with refined cereals for 12 weeks did not affect peripheral insulin sensitivity. The study was registered with ClinicalTrials.gov identifier NCT00945854 .

Oxidative stress (OS) – defined as the imbalance between free radical production and antioxidant defences – is a condition associated with chronic-degenerative disease, such as cancer, metabolic and disease cardiovascular diseases (CVDs). Several studies have shown that diet and some of its components could influence the intensity of OS damage. The aim of this review was to critically examine some pieces of evidence from observational and intervention study in human beings to assess whether diet and its components can really modify OS in vivo. Furthermore, we tried to find out the possible mechanism behind this association. We considered all studies in MEDLINE which fitted with the following criteria: (1) adult subjects who were healthy or affected by metabolic disease and CVDs; (2) no food supplements, pillows, powder but only common foods and beverages and (3) OS assessment with well-known and validated in vivo biomarkers.

Background and aims Metformin is the first-line therapy in type 2 diabetes. In patients inadequately controlled with metformin, the addition of a sulfonylurea or pioglitazone are equally plausible options to improve glycemic control. However, these drugs have profound differences in their mechanism of action, side effects, and impact on cardiovascular risk factors. A formal comparison of these two therapies in terms of cardiovascular morbidity and mortality is lacking. The TOSCA.IT study was designed to explore the effects of adding pioglitazone or a sulfonylurea on cardiovascular events in type 2 diabetic patients inadequately controlled with metformin. Methods Multicentre, randomized, open label, parallel group trial of 48 month duration. Type 2 diabetic subjects, 50–75 years, BMI 20–45 Kg/m 2 , on secondary failure to metformin monotherapy will be randomized to add-on a sulfonylurea or pioglitazone. The primary efficacy outcome is a composite endpoint of all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned coronary revascularization. Principal secondary outcome is a composite ischemic endpoint of sudden death, fatal and non-fatal myocardial infarction and stroke, endovascular or surgical intervention on the coronary, leg or carotid arteries, major amputations. Side effects, quality of life and economic costs will also be evaluated. Efficacy, safety, tolerability, and study conduct will be monitored by an independent Data Safety Monitoring Board. End points will be adjudicated by an independent external committee. Conclusions TOSCA.IT is the first on-going study investigating the head-to-head comparison of adding a sulfonylurea or pioglitazone to existing metformin treatment in terms of hard cardiovascular outcomes. Registration: Clinicaltrials.gov ID NCT00700856.

In view of the high incidence of macrovascular diseases in patients with type 2 diabetes mellitus and microalbuminuria, the study evaluates the association of microalbuminuria with fasting plasma Apo B48 levels, a marker of the residual presence of intestinally derived TRLs lipoproteins, thought to be highly atherogenic. We studied 50 patients with type 2 diabetes aged 35–75 years. Exclusion criteria were overt macrovascular disease, overt nephropathy (Glomerular filtration rate (GFR)

OBJECTIVE To evaluate the effects of qualitative dietary changes and the interaction with aerobic exercise training on liver fat content independent of weight loss in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS With use of a factorial 2 × 2 randomized parallel-group design, 37 men and 8 women, aged 35–70 years, with type 2 diabetes in satisfactory blood glucose control on diet or diet plus metformin treatment were assigned to one of the following groups for an 8-week period: 1) high-carbohydrate/high-fiber/low–glycemic index diet (CHO/fiber group), 2) high-MUFA diet (MUFA group), 3) high-carbohydrate/high-fiber/low–glycemic index diet plus physical activity program (CHO/fiber+Ex group), and 4) high-MUFA diet plus physical activity program (MUFA+Ex group). Before and after intervention, hepatic fat content was measured by 1H NMR. RESULTS Dietary compliance was optimal and body weight remained stable in all groups. Liver fat content decreased more in MUFA (−29%) and MUFA+Ex (−25%) groups than in CHO/fiber (−4%) and CHO/fiber+Ex groups (−6%). Two-way repeated-measures ANOVA, including baseline values as covariate, showed a significant effect on liver fat content for diet (P = 0.006), with no effects for exercise training (P = 0.789) or diet-exercise interaction (P = 0.712). CONCLUSIONS An isocaloric diet enriched in MUFA compared with a diet higher in carbohydrate and fiber was associated with a clinically relevant reduction of hepatic fat content in type 2 diabetic patients independent of an aerobic training program and should be considered for the nutritional management of hepatic steatosis in people with type 2 diabetes.

Objective: To assess whether a diet containing foods enriched with beta-glucans (3.6 g/d), folic acid (1600 mu g/d), long-chain (800 mg/d) and short-Chain (400 mg/d) n-3 fatty acids, and tocopherols (120 mg/d) is able to modulate positively the cardiovascular risk profile in people at slightly increased cardiovascular risk. Methods: Sixteen subjects with mild plasma lipid abnormalities were studied according to a randomized crossover design. After a 2-week run-in period, they followed a diet containing baked products enriched with active nutrients (active diet) or a diet containing the same products but without active nutrients (control diet) for 1 month and then crossed over to the other diet. At the end of each period, a test meal of the same composition as the corresponding diet was administered, and plasma samples were obtained before and for 6 hours after the meal. Hunger and satiety were evaluated by the visual analog scale at fasting and after the meal. Results: Fasting plasma triglycerides were significantly lower after the active versus the control diet (1.56 +/- 0.18 vs 1.74 +/- 0.16 mmol/l, p < 0.05), as was the postprandial level of chylomicron triglycerides and the insulin peak (p < 0.05). The active diet also reduced fasting homocysteine (8 +/- 0.6 vs 10 +/- 0.8 mu mol/l, p < 0.05) and the feeling of hunger at the fifth and sixth hour (p < 0.05). Conclusions: Baked functional products enriched with n-3 fatty acids, folates, beta-glucans, and tocopherols within the context of a balanced diet lower fasting and postprandial plasma triglycerides, fasting homocysteinemia, and the postprandial insulin peak. They induce a greater feeling of satiety with possible beneficial implications on energy intake.

OBJECTIVES--To compare the long term metabolic effects of two diets for treating hyperlipidaemia. DESIGN--Randomised controlled study: after three weeks of normal (control) diet, subjects were randomly allocated to one of two test diets and followed up for six months. SETTING--Lipid clinic of tertiary referral centre in Naples. SUBJECTS--63 subjects with primary type IIa and IIb hyperlipoproteinaemia entered the study, and 44 completed it. Exclusion criteria were taking drugs known to influence lipid metabolism, evidence of cardiovascular disease, homozygous familial hypercholesterolaemia, and body mass index over 30. INTERVENTIONS--Two test diets with reduced saturated fat (8%) and cholesterol (approximately 200 mg/day): one was also low in total fat and rich in carbohydrate and fibre, and the other was low in carbohydrate and fibre and rich in polyunsaturated and monounsaturated fats. MAIN OUTCOME MEASURES--Fasting plasma lipid and lipoprotein concentrations; blood glucose, insulin, and triglyceride concentrations before and after a test meal. RESULTS--In comparison with the control diet, both test diets induced significant and similar decreases in low density lipoprotein cholesterol concentrations (by a mean of 0.72 (SE 0.15) mmol/l, P < 0.001, for low total fat diet; by 0.49 (0.18) mmol/l, P < 0.05, for high unsaturated fat diet) and plasma triglyceride concentrations (by 0.21 (0.09) mmol/l, P < 0.05, for low total fat diet; by 0.39 (0.15) mmol/l, P < 0.05, for high unsaturated fat diet), while high density lipoprotein cholesterol concentrations after fasting and plasma glucose and insulin concentrations during test meals were not modified by either diet. CONCLUSIONS--Both test diets are suitable (alone or in combination) for treatment of hypercholesterolaemia.

The Italian Standards for the Treatment of Diabetes Mellitus represent a consensus document of the two Italian scientific diabetes societies (AMD and SID), providing specific recommendations for the diagnosis and treatment of diabetes and its complications. The level of scientific evidence behind every recommendation has been classified in accordance with the National Guidelines Plan. An original processing system was employed: the document prepared by the Editorial Team was published online for 20 days, and the suggestions and criticisms of about 30 persons were evaluated and integrated to those provided by a panel of diabetologists and members of other healthcare professions dedicated to diabetes care, as well as lay members. Lastly, the document was approved by AMD and SID National Steering Committees. In this version, some highlights of the full document (www.siditalia.it; www.aemmedi.it) concerning the main and most representative recommendations on diagnosis and treatment of diabetes and its complications as well as on diabetes care in some specific contexts, are reported.

Women with diabetes have a high risk of cardiovascular disease that, almost completely eliminates the gender difference in cardiovascular morbidity and mortality between non-diabetic men and women. In this chapter we have reviewed data showing that cardiovascular risk factors are more common, more likely to cluster, or more severe in diabetic women than men; this may be due to biological or behavioural factors. Disparities in accessibility, quality and, possibly, effectiveness of care further disadvantage diabetic women. Based on available data it can be concluded that a large number of CVD deaths are preventable in diabetic women; therefore special attention should be paid to risk factors detection and correction, as well as timely CHD diagnosis and treatment in diabetic women. To meet these needs gender specific guidelines and implementation measures may be in order.

BACKGROUND AND AIM: The intake of wholemeal foods is consistently associated with reduced risk of type 2 diabetes and cardiovascular diseases in epidemiological studies, although the mechanisms of this association are unclear. Here we aim to compare in healthy subjects the metabolic effects of a diet rich in wholemeal wheat foods versus one based on the same products in refined form. METHODS AND RESULTS: Fifteen healthy individuals (12 M/3 F), mean age 54.5+/-7.6 years, BMI 27.4+/-3.0 kg/m(2) (mean+/-SD), participated in a randomized sequential crossover study. After 2 weeks run-in, participants were randomly assigned to two isoenergetic diets with similar macronutrient composition, one rich in wholemeal wheat foods and the other with the same foods but in refined form (cereal fibre 23.1 vs. 9.8 g/day). After the two treatment periods (each lasting 3 weeks) plasma glucose and lipid metabolism, antioxidant activity, acetic acid, magnesium, adipokines, incretins and high-sensitivity C-reactive protein (hs-CRP) were measured at fasting and for 4h after a standard test meal (kcal 1103, protein 12%, CHO 53%, fat 35%) based on wholemeal or refined wheat foods, respectively. After the two diets there were no differences in fasting nor in postprandial plasma parameter responses; only glucose was slightly but significantly lower at 240 min after the refined wheat food meal compared to the wholemeal wheat food meal. Conversely, after the wholemeal diet both total (-4.3%; p

Background Fatty liver is commonly associated with insulin-resistant conditions, often related to increased abdominal visceral fat. Our objective was to elucidate the specific roles of obesity, type 2 diabetes mellitus, insulin-resistance and abdominal fat distribution. Materials and methods The study population comprised 13 diabetic obese (DO), 10 nondiabetic obese (NDO), and nine normal-weight control (C) men aged 28-65 years, with normal plasma triglyceride levels. DO were in good glycaemic control (HbA1c = 6Æ8 ± 0Æ8%) (M ± SD) with diet (n = 8) or diet + metformin (n = 5). Liver fat content was measured by 1H-magnetic resonance spectroscopy, abdominal fat distribution by magnetic resonance imaging and insulin sensitivity by hyperinsulinaemic euglycaemic clamp. Results DO and NDO subjects had similar whole-body insulin resistance, BMI and waist circumference, higher than those of C subjects (P < 0Æ001). DO had more liver fat (11Æ9 ± 7Æ0%) than NDO (5Æ2 ± 2Æ8%, P < 0Æ05) and C (1Æ6 ± 1Æ0%, P < 0Æ001). Abdominal fat was greater in DO and NDO than in C (visceral: DO 3184 ± 843, NDO 2843 ± 1378 vs. C 1212 ± 587 cm3, P < 0Æ001; subcutaneous: DO 4029 ± 362, NDO 5197 ± 1398 vs. C 2312 ± 626 cm3, P < 0Æ001), visceral fat being not significantly different between the two obese groups, and subcutaneous fat significantly less in DO than in NDO (P < 0Æ05). Conclusions Type 2 diabetes is associated with increased fat accumulation in the liver, independent of obesity and whole-body insulin resistance. The increased liver fat in DO patients may be part of an altered regional fat distribution that includes an inadequate subcutaneous fat storing capacity, rather than simply being a consequence of increased abdominal visceral content.

We investigated postprandial plasma and adipose tissue (AT) adiponectin changes in relation to obesity and type 2 diabetes mellitus. Fasting and 6 hours after a standard fat-rich meal blood samples (adiponectin, glucose, insulin, lipids) and needle biopsies of abdominal subcutaneous AT (adiponectin messenger RNA, lipoprotein lipase activity) were taken in 10 obese diabetic (OD), 11 obese nondiabetic (OND), and 11 normal-weight control (C) men. The OD and OND subjects had similar adiposity (body mass index, waist circumference) and insulin resistance (hyperinsulinemic euglycemic clamp). Fasting plasma adiponectin and AT gene expression were not significantly different between groups. After meal, plasma adiponectin decreased in OD but significantly increased in OND and C, the changes being significantly different between groups (analysis of variance, P = .01); adiponectin messenger RNA decreased in OD (-0.27 +/- 0.25 AU, P = .01) but was unchanged in OND (P = .59) and C (P = .45). After meal, plasma adiponectin correlated inversely with triglyceride and cholesterol concentrations in chylomicrons and large very low-density lipoprotein, and directly with AT lipoprotein lipase activity (P < .05 for all). Type 2 diabetes mellitus is associated with lower postprandial plasma levels and AT gene expression of adiponectin independently of degree of adiposity and whole-body insulin sensitivity. In patients with diabetes, this may exacerbate postprandial abnormalities of lipoprotein metabolism.

Diabetes mellitus is commonly associated with both microvascular and macrovascular complications (coronary artery disease, cerebrovascular events, severe peripheral vascular disease, nephropathy and retinopathy). There is wide evidence demonstrating that platelet degranulation and synthesis of TxA2 are increased in diabetic patients. For this reason, many studies on anti-platelet therapy have been made to reduce thrombotic complication of diabetes mellitus. Some diabetic patients, although treated with ASA, have a high prevalence of recurrent thrombotic events, which may presumably be due to an "ASA resistance". Nevertheless, this drug remains the one with the greatest benefit. To optimize its function, we should try to understand the causes of "aspirin resistance", try to find the most suitable dosage, recommending patients to comply constantly with the prescription given and to avoid interactions with other drugs. "Clopidogrel resistance" is a term not clearly defined. The clinical implications of "clopidogrel resistance" are unknown. An important consideration affecting the use of aspirin in diabetic patients is its interaction with ACE-inhibitors. Another question is antiplatelet therapy in nephropathic diabetic patients. Although these patients are at high thrombotic and haemorrhagic risk, they should nevertheless be considered eligible to undergo antithrombotic therapy, taking into account the individual's haemorrhagic risk.

Peroxisome proliferator-activated receptor (PPAR)-gamma is a major regulator of adipogenesis and insulin sensitivity. The PPAR-gamma gene generates two isoforms through alternative splicing, PPAR-gamma1 and -gamma2, the latter having an additional stretch of 28 amino acids at its NH2-terminus in the ligand-independent activation domain. This extension renders PPAR-gamma2 more sensitive to insulin action. Since there is a Pro12Ala substitution in this domain, we tested whether it is related to type 2 diabetes or insulin resistance. Therefore, 131 type 2 diabetic patients and 312 normoglycemic control subjects were screened for the presence of the mutation and for major clinical and metabolic features. The frequency of the mutation did not differ significantly between diabetic patients and control subjects. BMI, insulin, and other metabolic and anthropometric variables were also not associated with the mutation. Although the study was carried out on a sufficiently large sample, the conclusions do not support a major role for the Pro12Ala substitution of the PPAR-gamma gene in the etiology of type 2 diabetes.

Background and aims: Hepatic lipase (HL) catalyzes the hydrolysis of triglycerides and phospholipids from lipoproteins, and promotes the hepatic uptake of tipoproteins. A common G-250A polymorphism in the promoter of the hepatic lipase gene (LIPC) has been described. The aim was to study the effects of the G-250A polymorphism on HL activity, serum lipid profile and insulin sensitivity. Methods and results: Altogether 151 healthy subjects (age 49 +/- 8 years, BMI 26.5 +/- 3.0 kg/m(2)) were randomly assigned for 3 months to an isoenergetic diet containing either a high proportion of saturated fatty acids (SFA diet) or monounsaturated fatty acids (MUFA diet). Within groups there was a second random assignment to supplements with fish oil (3.6 g n-3 FA/day) or placebo. At baseline, the A-250A genotype was associated with high serum LDL cholesterol concentration (P = 0.030 among three genotypes). On the MUFA diet carriers of the A-250A genotype presented a greater decrease in LDL cholesterol concentration than subjects with other genotypes (P = 0.007 among three genotypes). The rare -250A allele was related to Low HL activity (P < 0.001 among three genotypes). The diet did not affect the levels of HL activity among the genotypes. Conclusion: The A-250A genotype of the LIPC gene was associated with high LDL cholesterol concentration, but the MUFA-enriched diet reduced serum LDL cholesterol concentration especially in subjects with the A-250A genotype. (c) 2006 Elsevier B.V. All rights reserved.

BACKGROUND Post-prandial lipid abnormalities might contribute to the excess of cardiovascular risk typical of type 2 diabetic patients. The study evaluated the effects of atorvastatin (20 mg d(-1)) vs. fenofibrate (200 mg d(-1)) on post-prandial lipids in type 2 diabetic patients with mixed hyperlipidaemia. MATERIALS AND METHOD Eight type 2 diabetic patients, male/female (M/F) 6/2, age 58 +/- 5 years, body mass index (BMI) 28 +/- 3 kg m(-2) with cholesterol of low-density lipoprotein (LDL) between 100-160 mg dL(-1) and triglycerides between 150-400 mg dL(-1), participated in a randomized, cross-over study (3 months on atorvastatin and 3 months on fenofibrate). At baseline and at the end of the two treatments, the patients were given a standard fat meal; blood samples were taken before the meal and every 2 h after for the assay of cholesterol, triglycerides, apoB-48 and apoB-100 (determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis) in plasma lipoproteins and very low-density lipoprotein (VLDL) subfractions (large and small VLDL), separated by density gradient ultracentrifugation. RESULTS Data on fasting lipids confirmed that atorvastatin was more effective on the reduction of LDL-cholesterol, whereas fenofibrate was a better triglyceride-lowering agent. Concerning the post-prandial phase, the incremental areas under the curve (IAUC) for chylomicrons and large VLDL were reduced after both treatments, reaching statistical significance for cholesterol, triglyceride and apoB-100 content of chylomicrons only after fenofibrate administration [IAUC, (5.2 +/- 4.6 vs. 10.7 +/- 9.3) mg dL(-1) h(-1), P = 0.03; (131.3 +/- 95.1 vs. 259.1 +/- 201.5) mg dL(-1) h(-1), P = 0.02; (0.46 +/- 1 vs. 3 +/- 3.7) mg dL(-1) h(-1), P = 0.025, all respectively]. CONCLUSIONS During the post-prandial state fenofibrate appeared to be more effective than atorvastatin in reducing the chylomicron response.

Nutrient determinants of postprandial triglyceride (TG) are matter of debate, especially for type II diabetes.This study was performed to evaluate the impact of dietary habits on postprandial TG response in a population-based sample of type II diabetic patients.One-hundred and forty type II diabetic patients (63 men/77 women, age 45-70 years) referring to the same health district, not on hypolipidemic drugs and without any other chronic disease, performed four TG profiles (at fasting, before, 2 and 3 h after lunch) with a specific device (Accutrend GCT, Roche Diagnostics Mannheim, Germany) validated previously. Dietary habits were recorded by a dietitian utilizing a previously validated semiquantitative questionnaire.Triglyceride values (mmol/l, mean +/- s.d.) were 2.22 +/- 0.93 at fasting, decreased before lunch (2.03 +/- 0.81), reached peak values 3 h after lunch (2.73 +/- 1.11). Postprandial TG increments (3 h after lunch minus pre-lunch concentration) significantly correlated with the intake (g/day) of animal protein (r = 0.20, P0.02), total fat (r = 0.21, P0.01), animal fat (r = 0.19, P0.03) and vegetable fat (r = 0.19, P0.03), also after adjusting for fasting TG and high-density lipoprotein cholesterol levels. Expressing nutrient intake as percentage of total calorie intake, total and animal fat remained significantly and directly related to postprandial TG increment (r = 0.21, P0.01 for total fat; r = 0.19, P0.03 for animal fat) whereas the percentage of carbohydrates was inversely related (r = -0.23, P0.007).Fat intake seems the major nutritional determinant of postprandial TG response in type II diabetic patients.

Objective: There is some evidence that acute hyperglycemia (H) may cause vascular dysfunction in normal subjects. This study investigates whether acute, short-term H affects coronary vasodilatory function in healthy subjects. Design: Diastolic peak flow velocity in the left anterior descending coronary artery was measured at rest and after dipyridamole (0.56 mg/kg over 4 min) using transthoracic color Doppler echocardiography in 13 healthy men. Coronary flow reserve (CFR) was defined as the ratio of dipyridamole-induced coronary peak diastolic to resting peak diastolic flow velocity. CFR was measured both in euglycemia (E) and after 3 h H (∼14 mmol/liter) by a variable infusion of glucose and octreotide (0.4 mg/h) to prevent increase in insulin concentration. Results: Fasting plasma glucose increased to 14.3 ± 0.33 mmol/liter during the study and maintained variability within less than 10%. Plasma insulin remained nearly stable during H. Resting diastolic flow velocity was 18.5 ± 0.6 cm/sec in E and increased to 20.0 ± 0.7 cm/sec during H (P < 0.005). Dipyridamole infusion produced a marked increase in coronary flow velocity, which reached values of 50.8 ± 2.9 cm/sec in E and 51.8 ± 2.1 cm/sec in H (P = not significant). CFR was 2.78 ± 0.16 in E and 2.59 ± 0.12 in H (P = not significant). Conclusion: Our study indicates that short-term hyperglycemia does not affect the vasodilatory response of coronary microcirculation in healthy subjects.

Insulin resistance is the pathogenetic link underlying the different metabolic abnormalities clustering in the metabolic syndrome. It can be induced by different environmental factors, including dietary habits. Consumption of energy-dense/high fat diets is strongly and positively associated with overweight that, in turn, deteriorates insulin sensitivity, particularly when the excess of body fat is located in abdominal region. Nevertheless the link between fat intake and overweight is not limited to the high-energy content of fatty foods; the ability to oxidize dietary fat is impaired in some individuals genetically predisposed to obesity. Insulin sensitivity is also affected by the quality of dietary fat, independently of its effects on body weight. Epidemiological evidence and intervention studies clearly show that in humans saturated fat significantly worsen insulin-resistance, while monounsaturated and polyunsaturated fatty acids improve it through modifications in the composition of cell membranes which reflect at least in part dietary fat composition. A recent multicenter study (KANWU) has shown that shifting from a diet rich in saturated fatty acids to one rich in monounsaturated fat improves insulin sensitivity in healthy people while a moderate alpha-3 fatty acids supplementation does not affect insulin sensitivity. There are also other features of the metabolic syndrome that are influenced by different types of fat, particularly blood pressure and plasma lipid levels. Most studies show that alpha-3 fatty acids reduce blood pressure in hypertensive but not in normotensive subjects while shifting from saturated to monounsaturated fat intake reduces diastolic blood pressure. In relation to lipid abnormalities alpha-3 fatty acids reduce plasma triglyceride levels but in parallel, increase LDL cholesterol. Substitution of unsaturated fat for saturated fat not only reduces LDL cholesterol but contributes also to reduce plasma triglycerides in insulin resistant individuals. In conclusion, there is evidence available in humans indicating that dietary fat quality influences insulin sensitivity and associated metabolic abnormalities. Therefore, prevention of the metabolic syndrome has to be targeted: (1) to correct overweight by reducing the energy density of the habitual diet (i.e., fat intake) and (2) to improve insulin sensitivity and associated metabolic abnormalities through a reduction of dietary saturated fat, partially replaced, when appropriate, by monounsaturated and polyunsaturated fats. Copyright 2004 Elsevier Ltd.

Self-monitoring of plasma triglycerides (TG) may be a very useful tool to monitor, on a daily basis, the TG responses to different nutrients, particularly carbohydrates (CHO) and fat, whose influence on postprandial TG levels is not very well known. Therefore, the aim of the present study was to evaluate the TG response of hypertriglyceridemic patients to a similar amount of calories deriving from different sources of CHO and fat. Thirty-nine hypertriglyceridemic patients were randomly assigned to 1 of 2 experimental groups. In 1 group (the fat group), patients were given a standard meal plus a fat supplement of 300 kcal derived from different types of fat (butter, sunflower margarine, olive oil) for dinner, once a week for 3 weeks. In the other group (the CHO group), patients consumed the same standard meal plus a supplement of 300 kcal derived from different types of CHO (bread, coke, fruit). In both groups, patients measured their plasma TG before and 3 hours after each meal by Accutrend GCT (ROCHE, Mannheim, Germany). A subgroup of patients (n = 18) also performed TG determinations 2 hours after the test meals. The 3-hour TG increments were not significantly different between the different test meals (f = 0.671; P = .52); instead, the TG increments induced by fat supplements were significantly higher than those induced by the CHO supplements (f = 14.31; P = .0001). Similar results were also obtained 2 hours after the test meals. In conclusion, this study shows that the 2- and 3-hour TG responses to fat are higher compared with that induced by carbohydrate. This point, especially if confirmed by experiments with more frequent after meal measurements and of longer duration, should be taken into account in defining the best dietary approach to lower plasma TG levels throughout the whole day.

Background: The intake of 10 g/day of short-chain-fructo-oligosaccharides (sc-FOS) has been shown to increase significantly bifidus counts and to produce high amounts of short-chain fatty acids (SCFA), presumed to influence glucose and lipid metabolism. Aim: To evaluate the effects of moderate intake of sc-FOS on glucose and lipid metabolism in individuals with mild hypercholesterolaemia. Design: A randomized double-blind sequential cross-over study. Subjects and methods: Thirty subjects of both genders (20 M/10 F), mean age 45.5±9.9 years (M±SD), BMI 26.6±2.2 kg/m2, with plasma cholesterol >5.17 and

Objective— To evaluate the role of insulin resistance in development of postprandial dyslipidemia in type 2 diabetic patients in an experimental setting in which these patients were compared with nondiabetic subjects at similar glucose and insulin blood levels. Methods and Results— Eight type 2 diabetic patients in optimal blood glucose control and 7 control subjects (aged 50.0±2.6 and 48.1±1.3 years; body mass index 28.3±1.2 and 25.6±1.1 kg/m 2 ; fasting plasma triglycerides 1.12±0.13 and 0.87±0.08 mmol/L, respectively; mean±SEM; NS) consumed a mixed meal during an 8-hour hyperinsulinemic glycemic clamp. Mean blood glucose during clamp was ≈7.8 mmol/L, and plasma insulin during the preprandial steady state was ≈480 pmol/L in both groups, that differed for insulin sensitivity (M/I value lower in diabetic subjects [1.65±0.30 and 3.42±0.60; P P P P Conclusions— Insulin resistance is also associated with postprandial lipoprotein abnormalities in type 2 diabetes after acute correction for hyperglycemia and hyperinsulinemia.

The influence of the quality of dietary fat on some aspects of lipid metabolism-i.e. lipoprotein concentrations, post-prandial lipids and LDL size-is not completely understood, especially in healthy individuals.Aim of this study was to evaluate the effects of different types of dietary fat (monounsaturated vs. saturated fatty acids, and n-3 or placebo supplementation) on fasting lipoproteins, LDL size and post-prandial lipids in healthy people.One hundred and sixty-two individuals were randomly assigned to follow two isoenergetic diets, one rich in saturated fatty acids (SFA diet) and the other in monounsaturated fatty acids (MUFA diet). Each group was further randomised to receive supplementation with fish oil (3.6 g/day) or placebo.The type of diet significantly affected LDL cholesterol and triacylglycerol content, which was higher with the SFA diet and lower with the MUFA diet. The changes between the two diets were statistically significant for cholesterol (P0.01) and triacylglycerol (P0.03). VLDL cholesterol and triacylglycerol were significantly reduced and LDL cholesterol significantly increased by fish oil supplementation. Plasma triacylglycerol was significantly lower in those taking n-3 fatty acids, also 1 and 3 h after a test-meal. Neither type of diet nor n-3 supplementation affected LDL size.A moderate substitution of saturated fatty acids with monounsaturated fatty acids has beneficial effects on lipid metabolism also in healthy individuals. A moderate supplementation of long-chain n-3 fatty acids in healthy individuals reduces both fasting and post-prandial triacylglycerol concentrations but increases LDL cholesterol, irrespective of the type of diet.

Background. Homocysteine is involved in a complex and dynamic system of vascular injury and repair and may thus contribute to the development of diabetic microangiopathy. This still debated issue has important scientific and clinical implications, since hyperhomocysteinemia can be corrected nutritionally.Aims. 1) To evaluate the association between fasting plasma homocysteine, type I diabetes and its microvascular complications; 2) to elucidate the basis of this association by investigating the major determinants of plasma homocysteine in relation to diabetic microangiopathy.Methods. We studied sixty-six consecutive patients with type 1 diabetes mellitus of >10 years duration and normal serum creatinine (mol/L, 1.3 mg/dL), and free from clinically detectable cardiovascular diseases. Forty;four non-diabetic controls were also studied. Plasma concentrations of homocysteine, folate and vitamin B12 were investigated together with the C677T mutation in the gene coding for methylenetetrahydrofolate reductase (MTHFR), a key enzyme in homocysteine metabolism. Renal and retinal diabetic complications were evaluated as albumin/creatinine ratio on early-morning urine spot collection and fundus photographs.Findings. Fasting plasma homocysteine levels were very similar in patients and controls. Patients with microalbuminuria or proliferative retinopathy had significantly higher values than those without: 9.4 +/-3.1 vs 7.4 +/-2.8 mu mol/L, p2.6 vs 7.3 +/-3.0 mu mol/L, p

We report the case of a 20-yr-old girl with thiamine-responsive megaloblastic anemia (TRMA) associated with diabetes mellitus and bilateral sensorineural deafness (1, 2). Megaloblastic anemia was diagnosed at 7 months and was successfully treated with multiple vitamin preparations. Diabetes was diagnosed at age 2 yr and was treated with insulin for 6 months at a dose of 0.5 IU/kg BW. The diagnosis of TRMA syndrome was clinically confirmed when bilateral sensorineural deafness was detected. Thereafter, thiamine treatment was started (50 mg/day), and insulin was discontinued because of frequent episodes of hypoglycemia. At age 9 yr, due to reoccurrence of hyperglycemia, the patient underwent glibenclamide treatment (2.5 mg/day), which was replaced by insulin at menarche. Glycemic control was satisfactory, as evidenced by hemoglobin A1c (HbA1c) values between 7.5–8%. Laboratory parameters, including coagulation factors, were in the normal range. At age 17 yr, because of secondary amenorrhea and echographic findings of small ovarian cysts, the patient was diagnosed as having polycystic ovary syndrome and was treated with estro-progestins (12 cycles/yr of ciproterone, ethinyl estradiol). One year later, at age 18 yr, the patient developed motor seizures initially involving the left leg, then rapidly extending to the whole body, followed by unconsciousness. On admission, left hemiplegia was observed. Arterial blood pressure and plasma lipid concentrations were normal (100/60 mm Hg; total cholesterol, 147 mg/dL; total triglycerides, 84 mg/dL). The patient was receiving insulin therapy (30–35 IU/24 h), and the average HbA1c levels had been between 7.1–7.3% during the previous year. A computed tomography scanning revealed a small area of edema at the right cerebral hemisphere; 24 h later an ischemic area involving the territory of the right middle cerebral artery became manifest. One month later, during antiepileptic and ticlopidine therapy, the patient developed clonic movements of the left leg followed by generalized coreic movements and unconsciousness. Brain magnetic resonance (MR) imaging and angiography showed severely reduced blood flow in the right middle cerebral artery, with a large ischemic area in the corresponding territory, absence of flow in the distal internal carotid arteries, and slight compensatory hypertrophy of the basilar artery (Fig. 1). X-Ray digital arteriography confirmed MR findings and showed narrowing of the left superficial femoral and popliteas arteries. Hemostasis tests revealed high fibrinogen levels (612 mg/dL), whereas prothrombin, APTT, antithrombin III, and protein S were normal. Anticardiolipin (IgG and IgM) and lupus anticoagulant antibodies were also normal. In contrast, a low activity of protein C (60% vs. 98 6 15%) was found, which reverted to normal after a year. Further investigation for a hypercoagulable state showed negative factor V Leiden and a homocysteine concentration in the normal range. In addition, screening for prothrombin gene G20210A mutation and mutations of two enzymes involved in homocysteine metabolism, i.e. C677T in the coding region for N,N-methylenetetrahydrofolate reductase and cystathionine b-synthase 844INS68, gave negative results. On hospital discharge, the patient had left-sided hemiparesis. Oral anticoagulant and antiepileptic drugs were prescribed together with insulin and thiamine, which induced satisfactory glycemic control and resumption of menses. During the 1-yr follow-up the patient progressively recovered upper limb motility and is now independent with regard to everyday life needs.

OBJECTIVE: To prospectively evaluate progression to diabetes in individuals with impaired glucose regulation as defined according to fasting glucose alone or an oral glucose tolerance test (OGTT) (i.e., both fasting and postload glucose) to compare the ability of these two screening methods to identify people at high risk of developing diabetes. RESEARCH DESIGN AND METHODS: A working population of 1,245 nondiabetic telephone company employees aged 40-59 years was studied by OGTT in 1980. Participants were classified according to baseline fasting glucose only (as encouraged by the American Diabetes Association [ADA]) or OGTT (as recommended by the 1998 World Health Organization [WHO] consultation). Progression to diabetes was evaluated 11.5 years later according to the 1997 ADA criteria of a fasting plasma glucose level > or =7.0 mmol/l. RESULTS: With the use of the OGTT, baseline prevalence of impaired glucose regulation was substantially higher than that with fasting glucose alone (7.2 vs. 3.2%); the two groups only overlap for 40.9% of the cases because a fairly large number of people with postload hyperglycemia (59.1%) have normal fasting glucose. Progression to diabetes in participants with normal fasting glucose and postload hyperglycemia is significantly more frequent than that of people with normoglycemia (32.5 vs. 7.2%; P < 0.001) and not significantly different from that of people with both fasting and postload hyperglycemia (i.e., 44.0%). However, the former are not identified as being at unusually high risk of diabetes unless an OGTT is performed. When the use of fasting glucose alone or OGTT was validated as a marker of progression to diabetes, sensitivity was substantially higher for the OGTT (33.3 vs. 9.0%) without major differences in specificity (92.6 vs. 97.0%). CONCLUSIONS: These data (the only data so far available in Caucasians) support the viewpoint that for the identification of people at high risk of diabetes, the use of the OGTT should be maintained.

OBJECTIVE To evaluate whether hyperfibrinogenemia represents a component of the metabolic syndrome. RESEARCH DESIGN AND METHODS A cross-sectional study was conducted on the relation between fibrinogen and the metabolic syndrome in a working population of 1,252 nondiabetic men, aged 35–64 years, randomly selected among all men participating in a health screening. We measured anthropometric characteristics, blood pressure, fasting plasma fibrinogen, cholesterol (total, LDL, and HDL), triglycerides, glucose, and insulin. Individuals with two or more metabolic abnormalities (defined as being in the highest quartile of the distribution of diastolic blood pressure, plasma glucose, or triglycerides or being in the lowest quartile of HDL cholesterol) were considered to have the metabolic syndrome. RESULTS Age-adjusted fibrinogen levels correlated significantly with BMI, waist-to-hip ratio, systolic and diastolic blood pressure, plasma total cholesterol, LDL cholesterol, triglycerides, insulin, and HDL cholesterol (inversely). Subjects with the metabolic syndrome had significantly higher plasma fibrinogen levels than those without (285.1 ± 1.9 vs. 300.2 ± 3.0 mg/dl, mean ± SE, P = 0.0001). Plasma fibrinogen concentrations and the prevalence of hyperfibrinogenemia (defined as ≥350 mg/dl) increased progressively from 279 to 307 mg/dl (P = 0.0001) and from 9 to 22% (P = 0.0024), respectively, across categories with an increasing number of metabolic disorders characterizing the syndrome (only one, any two, three or more). In multivariate analyses, both plasma insulin and the metabolic syndrome were significantly and independently associated with plasma fibrinogen. CONCLUSIONS The finding suggests that hyperfibrinogenemia may be considered a component of the metabolic syndrome. This may also explain the increased cardiovascular risk associated with hyperinsulinemia/insulin resistance.

A multicenter, randomized, double-blind, place-bo-controlled study evaluated the possible worsening of glycemic control after a moderate daily intake of n-3 fatty acid ethyl esters in patients with hypertriglyceridemia with and without glucose intolerance or diabetes. A total of 935 patients of both sexes in 63 Italian clinical centers were selected; 55% had either impaired glucose tolerance or non-insulin-dependent diabetes mellitus (NIDDM). They received for 2 mo either 1 g n-3 ethyl esters three times a day or a corresponding placebo, followed by 4 mo of either 1 g n-3 ethyl esters twice a day or placebo. In addition to the complete lipid and lipoprotein evaluation, patients with impaired glucose tolerance also underwent an oral-glucose-tolerance test; in patients with NIDDM, serum insulin and glycated hemoglobin (Hb A1c) concentrations were determined. Plasma triacylglycerol concentrations decreased significantly, up to 21.53% at 6 mo compared with baseline (decreased 15% compared with placebo), with a tendency toward a progressive reduction with time. There was no evidence for a different response in patients with either NIDDM or impaired glucose tolerance. Among NIDDM patients, the triacylglycerol reduction was greater in those with high-density-lipoprotein cholesterol < or = 0.91 mmol/L. There was no alteration in the major glycemic indexes: fasting glucose, Hb A1c, insulinemia, and oral glucose tolerance in patients with impaired glucose tolerance or NIDDM after treatment with n-3 ethyl esters. Treatment with a moderate daily dose of n-3 ethyl esters over a prolonged period of time significantly reduced triacylglycerol concentrations without any worsening of glucose tolerance in patients with hypertriglyceridemia with and without impaired glycemic regulation.

OBJECTIVE To compare the effects of a nigh-carbohydrate diet on blood glucose and plasma lipids in NIDDM patients with either mild or severe glucose intolerance. RESEARCH DESIGN AND METHODS A crossover design with a 15-day intervention diet was used. Eighteen patients were separated into two groups on the basis of hypoglycemic treatment (diet, n = 9, or diet plus glibenclamide, n = 9) and were assigned to a 15-day treatment with a high-carbohydrate/low-fiber diet containing 60% energy from carbohydrate and 20% from fat or a low-carbohydrate/low-fiber diet with 40% energy from carbohydrate and 40% from fat and then crossed over to the other diet for 15 more days. RESULTS The high-carbohydrate diet produced a significant increase in postprandial blood glucose in patients on glibenclamide (13.6 ± 1.4 vs. 11.0 ± 1.8 mmol/l, P < 0.002, while no difference was recorded in the group on diet alone (9.7 ± vs. 8.9 ± 0.6 mmol/l). Postprandial insulin levels were significantly higher after the high-carbohydrate diet in the group on diet along (248 ± 32 vs. 192 ± 28 pmol/l, P < 0.01), while no significant differences were observed in the other group (226 ± 19 vs. 202 ± 24 pmol/l) The high-carbohydrate diet also induced a significant increase in fasting plasma triglyceride concentrations in both groups (1.36 ± 0.2 vs. 1.12 ± 0.2 mmol/l, P < 0.05 and 1.4 ± 0.3 vs. 1.1 ± 0.1 mmol/l, P < 0.05). No differences were observed in fasting plasma cholesterol and HDL. CONCLUSIONS The effects of the high-carbohydrate diet on blood glucose control in NIDDM patients differ according to severity of glucose intolerance.

Normolipidaemic insulin-dependent diabetic (IDDM) patients are characterized by an increase in the smaller VLDL particles, considered to be the most atherogenic. Since blood glucose control is one of the main regulators of lipid metabolism in diabetic patients, it could influence the shift in the distribution of VLDL subfractions towards smaller particles. To evaluate this possibility, VLDL subfractions, post-heparin lipoprotein lipase and hepatic lipase activities have been evaluated in male IDDM patients with either unsatisfactory blood glucose control (group 1, HbA1c8%, n = 18) or good blood glucose control (group 2, HbA1c8%, n = 16) and in 16 normoglycaemic individuals. The three groups were comparable for sex, age, body mass index, and plasma lipid levels. Three VLDL subfractions (large, Svedberg flotation unit (Sf) 175-400; intermediate, Sf 100-175; small, Sf 20-100) were separated by density gradient ultracentrifugation and analysed for cholesterol, triglyceride, and phospholipid levels. When compared to control subjects both groups of IDDM patients showed a clear shift in VLDL subfraction distribution with a significant increase in the proportion of small VLDL (group 1; 49 +/- 2%; p0.005; group 2: 51 +/- 3%, p0.01; control subjects 40 +/- 2%) (mean +/- SEM) in relation to total VLDL. By contrast, the absolute lipid concentration of small VLDL was higher only in group 1, compared to control subjects (35 +/- 4 vs 27 +/- 3 mg/dl, p = 0.05). Post-heparin hepatic lipase activity was significantly reduced in both IDDM groups (group 1: 254 +/- 19 mU/ml, p0.05; group 2: 202 +/- 19 mU/ml, p0.005; control subjects 317 +/- 31 mU/ml). In conclusion, normolipidaemic IDDM patients show an increase in the smallest VLDL, whatever their degree of blood glucose control. However, this abnormality may be clinically relevant only in patients with unsatisfactory blood glucose control, since absolute lipid concentration of these potentially atherogenic particles is only increased in this group.

Very low density lipoproteins (VLDL) have an abnormal lipid composition in Type 1 (insulin-dependent) diabetic patients. Since VLDL represent a heterogeneous lipoprotein class, this might be due either to a shift in the distribution or to an abnormal composition of VLDL subclasses or both. In order to investigate these possibilities and to evaluate possible pathogenetic mechanisms, lipid composition (non-esterified and esterified cholesterol, triglycerides, phospholipids) of four VLDL subfractions of decreasing size (A: Svedberg flotation unit [Sf]>400, B: Sf, 175–400, C: Sf 100–175, D: Sf 20–100), isolated by density gradient preparative ultracentrifugation, and plasma post-heparin lipolytic activity (lipoprotein lipase and hepatic lipase) were evaluated in 13 male normolipidaemic insulin-dependent diabetic patients in good glycaemic control (HbA1c 6.9±0.5%) (mean±SEM) and 9 male control subjects matched for age, body mass index and plasma lipid values. Compared to control subjects, diabetic patients showed a reduced total lipid concentration of VLDL of intermediate size (B and C) reaching statistical significance only for VLDL C (0.16±0.02 vs 0.24±0.03 mmol/l; p

Background The endocannabinoids, anandamide and 2-AG, are produced by adipocytes, where they stimulate lipogenesis via cannabinoid CB1 receptors and are under the negative control of leptin and insulin. Endocannabinoid levels are elevated in the blood of obese individuals and nonobese type 2 diabetes patients. To date, no study has evaluated endocannabinoid levels in subcutaneous adipose tissue (SAT) of subjects with both obesity and type 2 diabetes (OBT2D), characterised by similar adiposity and whole body insulin resistance and lower plasma leptin levels as compared to non-diabetic obese subjects (OB). Design and Methods The levels of anandamide and 2-AG, and of the anandamide-related PPARα ligands, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), in the SAT obtained by abdominal needle biopsy in 10 OBT2D, 11 OB, and 8 non-diabetic normal-weight (NW) subjects, were measured by liquid chromatography-mass spectrometry. All subjects underwent a hyperinsulinaemic euglycaemic clamp. Results As compared to NW, anandamide, OEA and PEA levels in the SAT were 2-4.4-fold elevated (p < 0.05), and 2-AG levels 2.3-fold reduced (p < .05), in OBT2D but not in OB subjects. Anandamide, OEA and PEA correlated positively (p < .05) with SAT leptin mRNA and free fatty acid during hyperinsulinaemic clamp, and negatively with SAT LPL activity and plasma HDL-cholesterol, which were all specifically altered in OBT2D subjects. Conclusions The observed alterations emphasize, for the first time in humans, the potential different role and regulation of adipose tissue anandamide (and its congeners) and 2-AG in obesity and type 2 diabetes.

It is commonly believed that high-carbohydrate (CHO) diets improve peripheral insulin sensitivity; however, this concept is based on anecdotal evidence. Furthermore, it has been demonstrated that in non-insulin-dependent diabetic patients treated with insulin, a high-monounsaturated-fat (MUFA) diet is more effective than a high-complex-CHO diet in reducing blood glucose levels. The aim of our study was to compare the effect of a high-MUFA diet and a high-CHO diet on peripheral insulin sensitivity and metabolic control in non-insulin-dependent diabetic patients. Ten non-insulin-dependent diabetic patients aged 52 +/- 8 years with a body mass index (BMI) of 26.7 +/- 3.5 kg/m2 who were being treated with diet alone (n = 5) or with diet plus glibenclamide (n = 5) were randomly assigned to a 15-day period of either a high-MUFA/low-CHO diet (CHO, 40%; fat, 40%; protein, 20%; fiber, 24g) or a low-MUFA/high-CHO diet (CHO, 60%; fat, 20%; protein, 20%; fiber, 24g) and were then crossed-over to the other diet. Diets were similar in their content of monosaccharides, disaccharides, and saturated fats, and were administered to the patients in a metabolic ward. The dosage of hypoglycemic drugs was maintained at a constant level throughout the study. With the high-MUFA/low-CHO diet, a decrease in both postprandial glucose (8.76 +/- 2.12 v 10.08 +/- 2.76 mmol/L; P < .05) and plasma insulin (195.0 +/- 86.4 v 224.4 +/- 75.6 pmol/L; P < .02) levels was observed. Furthermore, fasting plasma triglyceride levels were reduced after the high-MUFA fat/low-CHO diet (1.16 +/- 0.59 v 1.37 +/- 0.59 mmol/L; P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid and apoprotein composition of four very low density lipoprotein (VLDL) subfractions decreasing in Sf value were evaluated in the fasting state in 12 normolipidemic Pima Indians (6 M, 6 F, age 39 +/- 1.7 yrs) (mean +/- SEM) with non-insulin-dependent diabetes mellitus (NIDDM) in poor glycemic control (HbA1 9.8 +/- 2.9%) and in 14 normoglycemic Pima controls matched for age, BMI and lipid values. Total cholesterol (CHOL), triglyceride (TG), phospholipids (PL), total protein (TP), apo B, apo CII, apo CIII and apoE were assayed in total VLDL and in each of the four VLDL subfractions designed as A (Sf greater than 400), B (Sf 175-400), C (Sf 100-175), and D (Sf 20-100). Diabetics compared to nondiabetics had higher concentrations of all constituents of VLDL D, with the largest changes being in TG (38.0 +/- 3.8 vs 28.0 +/- 2.5 mg/dl, P less than 0.04), PL (14.0 +/- 1.3 vs 10.0 +/- 1.0 mg/dl, P less than 0.04), TP (9.8 +/- 0.8 vs 7.6 +/- 2.4 mg/dl, P less than 0.05), apo B (6.3 +/- 0.5 vs 4.7 +/- 0.4 mg/dl, P less than 0.03) and apoE (0.73 +/- 0.09 vs 0.52 +/- 0.04 mg/dl, P less than 0.04). Since no difference was found between the groups in percentage composition of lipids or apoproteins in total VLDL and in all VLDL subfractions, the data suggest that in diabetics, even when normolipidemic, there is an increase in the number rather than in the composition of the smallest VLDL subfraction (VLDL D), which are usually considered to be more atherogenic.

Eight type II (non-insulin-dependent) normolipidemic diabetic patients (aged 45 +/- 15 yr, body mass index 22 +/- 2 kg/m2, means +/- SD) treated with diet alone or diet plus oral hypoglycemic agents were given, in random order for periods of 15 days, two diets with different carbohydrate (CHO) (40 vs. 60% of total calories) and fat (20 vs. 40%) levels. Simple CHO, fiber, saturated fat, cholesterol, and polyunsaturated-saturated fat ratio were similar in the two diets. Total plasma cholesterol was not significantly affected by dietary changes; conversely, plasma triglyceride (1.38 +/- 0.59 vs. 1.11 +/- 0.39 mM, P less than 0.05) and apolipoprotein CII (3.8 +/- 1.4 vs. 3.3 +/- 0.8 mg/dl) increased significantly after the high-CHO low-fat diet. Among the various lipoproteins, very-low-density lipoprotein (VLDL) was the most affected by diet: VLDL cholesterol concentrations increased from 0.30 +/- 0.19 to 0.43 +/- 0.28 mM (P less than 0.05), and triglyceride concentrations increased from 0.62 +/- 0.33 to 0.88 +/- 0.53 mM (P less than 0.05). In conclusion, increasing the amount of complex CHO in the diet induces an elevation of VLDL in normolipidemic, nonobese, mildly type II diabetic patients.

Although it has been reported that bezafibrate influences carbohydrate metabolism, this possibility has never been properly evaluated in a controlled clinical trial. In this study we attempted to evaluate the effects of bezafibrate on plasma lipoproteins, glucose tolerance, insulin secretion and peripheral insulin sensitivity in a group of hypertriglyceridemic patients with and without diabetes. Sixteen hyperlipidemic patients (10 males and 6 females) participated in the study. Eight had type IIB and 8 type IV hyperlipoproteinemia; 6 of them also had non-insulin dependent diabetes mellitus. The study was performed according to a double blind, crossover design: after 1 month wash-out period in which patients were on diet alone, they underwent, in a random order, a period of placebo therapy and another period in which they received a single daily dose of a long-acting bezafibrate preparation (400 mg) administered in the evening. Each treatment lasted 2 months. Total plasma and VLDL triglyceride concentrations were consistently reduced by bezafibrate (-46%, P less than 0.001; and -50%, P less than 0.001). Total and VLDL-cholesterol were also reduced by bezafibrate. The effects of bezafibrate on lipoproteins were similar in diabetic and non-diabetic subjects. Bezafibrate treatment did not influence fasting blood glucose concentration, glucose tolerance, peripheral insulin sensitivity or insulin secretion. In conclusion, the results of this controlled trial clearly indicate that bezafibrate can be successfully employed to lower plasma lipid levels in patients with non-insulin dependent diabetes mellitus and hyperlipidemia.

The aim of this study was to evaluate whether a relationship exists between impaired glucose tolerance and both habitual physical activity and physical working capacity. Sixty-five apparently healthy subjects with impaired glucose tolerance (according to criteria of the European Association for the Study of Diabetes), age range 40-59 years, and 125 subjects with normal tolerance, sex, age and body mass index matched, were selected among the participants in a health examination survey. They filled in a questionnaire on daily physical activity during work and leisure time and performed an exercise test on a cyclergometer. No difference in physical activity at work was recorded between the groups, but the proportion of individuals who were physically active during leisure time, was significantly lower among the subjects with impaired glucose tolerance (8.1% vs 19.7%; P less than 0.05). Moreover these subjects had a higher heart rate during and 1 min after the standard exercise test (113.4 +/- 15.8 vs 105.7 +/- 17.7 beats/min, P less than 0.005; mean +/- SD). This supports the hypothesis that low physical activity is a risk factor for impaired glucose tolerance, independent of mutual effect of obesity.