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To explore intraindividual (between-meals) and interindividual (between-subjects) variability of postprandial glucose response (PGR) in type 1 diabetes (T1DM).Data were taken from five cross-over trials in 61 subjects with T1DM on insulin pump wherein the effects of different dietary components or the intraindividual-variability of PGR to the same meal were evaluated by CGM. Predictors (type of meal or nutrient composition) of early (iAUCHigh-glycemic-index (HGI) and low-glycemic-index meals were the best positive and negative predictors of glucose iAUCBeyond the meal characteristics (including glycemic index, fat and fiber content), individual traits significantly influence PGR. Specific interindividual factors should be further identified to properly predict glucose response to meals with different composition in individuals with T1DM.

Background and aims: Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown. Methods and results: As many as 66 obese (BMI 26-40 kg/m(2)) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a mixed meal test before and after fructose intervention. Fructose intervention did not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses during OGTT and fat-rich meal were unchanged. Postprandial TG response increased significantly, p = 0.004, and we observed small but significant increases in weight and liver fat content, but not in visceral or subcutaneous fat depots. However, even the subgroups who gained weight or liver fat during fructose intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049). Conclusion: In obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal. Therefore, fructose intake, even accompanied with mild weight gain, increases in liver fat and worsening of postprandial TG profile, does not impair glucose tolerance or gut incretin response to oral glucose or mixed meal challenge. (C) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

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

To evaluate feasibility and effectiveness on short-term blood glucose control of using glycaemic load counting (GLC) versus carbohydrate counting (CC) for prandial insulin dosing in patients with type 1 diabetes (T1D).Nine T1D patients on insulin pump, aged 26-58 years, HbA1c 7.7 ± 0.8 % (61 ± 8.7 mmol/mol), participated in this real-life setting study. By a crossover design, patients were randomised to calculate their pre-meal insulin dose based on the insulin/glycaemic load ratio (GLC period) or the insulin/carbohydrate ratio (CC period) for 1 week, shifting to the alternate method for the next week, when participants duplicated their first week food plan. Over either week, a blind subcutaneous continuous glucose monitoring was performed, and a 7-day food record was filled in.Total daily insulin doses (45 ± 10 vs. 44 ± 9 I.U.; M ± SD, p = 0.386) and basal infusion (26 ± 7 vs. 26 ± 8 I.U., p = 0.516) were not different during GLC and CC periods, respectively. However, the range of insulin doses (difference between highest and lowest insulin dose) was wider during GLC, with statistical significance at dinner (8.4 ± 6.2 vs. 6.0 ± 3.9 I.U., p = 0.041). Blood glucose iAUC after lunch was lower, albeit not significantly, during GLC than CC period (0.6 ± 8.6 vs. 3.4 ± 8.2 mmol/l∙3 h, p = 0.059). Postprandial glucose variability, evaluated as the maximal amplitude after meal (highest minus lowest glucose value), was significantly lower during GLC than CC period at lunch (4.22 ± 0.28 vs. 5.47 ± 0.39 mmol/l, p = 0.002) and dinner (3.89 ± 0.33 vs. 4.89 ± 0.33, p = 0.026).Calculating prandial insulin bolus based on glycaemic load counting is feasible in a real-life setting and may improve postprandial glucose control in people with T1D.

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 dietadopted 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 Look AHEAD trial, evaluating the effects of weight loss on cardiovascular (CV) morbidity and mortality in overweight/obese people with type 2 diabetes (T2D), was interrupted after a median 9.5-year follow-up because the incidence of CV events was not different between the Intensive Lifestyle Intervention (ILI) and the control groups, and unlikely to statistically change thereafter. This made health providers and patients wondering about clinical value of diet and physical exercise in diabetic patients. Many factors may have made difficult to ascertain benefits of lifestyle intervention, besides the lower than predicted CV event rates. Among others, LDL-cholesterol was lowered more, with a higher use of statins, in the control group. Anyhow, ILI significantly improved numerous health conditions, including quality of life, CV risk factors and blood glucose control, with more diabetes remissions and less use of insulin. The intervention aimed at weight loss by reducing fat calories, and using meal replacements and, eventually, orlistat, likely underemphasizing dietary composition. There is suggestive evidence, in fact, that qualitative changes in dietary composition aiming at higher consumption of foods rich in fiber and with a high vegetable/animal fat ratio favorably influence CV risk in T2D patients. In conclusion, the Look AHEAD showed substantial health benefits of lifestyle modifications. Prevention of CV events may need higher attention to dietary composition, contributing to stricter control of CV risk factors. As a better health-related quality of life in people with diabetes is an important driver of our clinical decisions, efforts on early implementation of behavioral changes through a multifactorial approach are strongly justified.

The study explores the degree of control of hyperglycaemia and cardiovascular (CV) disease risk factors in men and women with type 2 diabetes and the impact thereon of obesity, central adiposity, age and use of medications.A cross-sectional survey was conducted at 10 hospital-based outpatients diabetes clinics. 1297 men and 1168 women with no previous CV events were studied. Women were slightly (only one year) older and more obese than men: average BMI was respectively 30.7 ± 5.7 vs 28.6 ± 4.1 kg/m(2) (p0.001), and prevalence of abdominal obesity was 86% vs 44% (p0.001). Women smoked less, but had higher HbA1c, LDL cholesterol, non-HDL cholesterol, systolic blood pressure and serum fibrinogen than men. Accordingly optimal targets for HbA1c (7%), LDL cholesterol (100 mg/dL), HDL cholesterol (40 for men,50 for women, mg/dL), and systolic blood pressure (130 mmHg) were less frequently achieved by women than men (respectively 33.8% vs 40.2%; 14.6% vs 19.2%; 34.1% vs 44.5%; 68.8% vs 72%; p0.05 for all). Findings were confirmed after stratification for waist circumference (or ≥ 88 cm for women;or ≥ 102 cm for men), BMI (or ≥ 25 kg/m(2)) or age (or ≥ 65 years). As for treatment, women were more likely than men to take insulin, alone or in combination with oral hypoglycaemic drugs, to be under anti-hypertensive treatment, whereas the use of lipid lowering drugs was similar in men and women.Control of hyperglycaemia and major CVD risk factors is less satisfactory in women than men. The gender disparities are not fully explained by the higher prevalence of total and central obesity in women; or by a less intensive medical management in women.

Aim Evidence showed that LDL-cholesterol lowering is associated with a significant cardiovascular risk reduction. The initial therapeutic approach to hypercholesterolemia includes dietary modifications but the compliance to recommendations is often inadequate. Some dietary components with potential cholesterol-lowering activity are present in small amounts in food. Therefore, in recent years the use of “nutraceuticals” (i.e., nutrients and/or bioactive compounds with potential beneficial effects on human health) has become widespread. Such substances may be added to foods and beverages, or taken as dietary supplements (liquid preparations, tablets, capsules). In the present manuscript, the cholesterol-lowering activity of some nutraceuticals (i.e. fiber, phytosterols, soy, policosanol, red yeast rice and berberine) will be discussed along with: 1) the level of evidence on the cholesterol-lowering efficacy emerging from clinical trial; 2) the possible side effects associated with their use; 3) the categories of patients who could benefit from their use. Data synthesis Based on the current literature, the cholesterol-lowering effect of fiber, phytosterols and red yeast rice is consistent and supported by a good level of evidence. Over berberine, there is sufficient evidence showing significant cholesterol-lowering effects, although the results come from studies carried out almost exclusively in Asian populations. Data on the effects of soy are conflicting and, therefore, the strength of recommendation is quite low. The evidence on policosanol is inconclusive. Conclusion Although health benefits may arise from the use of nutraceuticals with cholesterol-lowering activity, their use might be also associated with possible risks and pitfalls, some of which are common to all nutraceuticals whereas others are related to specific nutraceuticals.

BACKGROUND AND AIMS: The role of the different factors associated with fatty liver is still poorly defined. We evaluated the relationships between liver fat content (LF) and metabolic, inflammatory and nutritional factors in a homogeneous cohort of individuals at high cardio-metabolic risk. METHODS AND RESULTS: In 70 individuals with high waist circumference and at least one more criterion for metabolic syndrome enrolled in a nutritional intervention study, LF was evaluated at baseline by hepatic/renal echo intensity ratio (H/R), together with dietary habits (7-day dietary record), insulin sensitivity and β-cell function (fasting and OGTT-derived indices), fasting and postprandial plasma GLP-1 and lipoproteins, and plasma inflammatory markers. H/R correlated positively with fasting and OGTT plasma glucose and insulin concentrations, HOMA-IR and β-cell function, and IL-4, IL-17, IFN-γ, TNF-α, FGF and GCSF plasma concentrations (p < 0.05 for all), and negatively with insulin sensitivity (OGIS), dietary, polyphenols and fiber (p < 0.05 for all). By multiple stepwise regression analysis, the best predictors of H/R were OGIS (β = -0.352 p = 0.001), postprandial GLP-1 (β = -0.344; p = 0.001), HDL-cholesterol (β = -0.323; p = 0.002) and IFN-γ (β = 0.205; p = 0.036). CONCLUSION: A comprehensive evaluation of factors associated with liver fat, in a homogeneous population at high cardio-metabolic risk, indicated a pathogenic combination of the same pathways underlying the atherosclerotic process, namely whole body insulin sensitivity and inflammation. The higher predictive value of postprandial variables suggests that liver fat is essentially a postprandial phenomenon, with a relevant role possibly played by GLP-1.

The aim of the study was to evaluate whether two dietary approaches recommended for diabetes mellitus and cardiovascular prevention-high-MUFA or complex carbohydrates/fiber-differently influence inflammation. A 4-week crossover study in 12 individuals with type 2 diabetes was performed. Fasting and postprandial hs-CRP plasma levels were not significantly different after a high-carbohydrate/high-fiber/low-glycemic index (CHO/fiber) and a high-MUFA diet. Compared with fasting, hs-CRP levels decreased significantly after the MUFA but not after the CHO/fiber meal. Triglyceride-rich lipoproteins were significantly lower after the CHO/fiber than the MUFA diet. At fasting and postprandially, hs-CRP correlated with triglyceride in whole plasma, chylomicrons, small and large VLDL after the CHO/fiber but not after the MUFA diet. In conclusion, a MUFA-rich diet and a carbohydrate/fiber-rich diet induced similar effects on plasma hs-CRP concentrations. However, these dietary approaches seem to influence hs-CRP levels through different mechanisms. i.e., direct acute postprandial effects by MUFA and triglyceride-rich lipoproteins mediated effects by CHO/fiber.

BACKGROUND: Fasting and post-prandial abnormalities of adipose tissue (AT) lipoprotein lipase (LPL) and hormone- sensitive lipase (HSL) activities may have pathophysiological relevance in insulin-resistant conditions. AIM: The aim of this study was to evaluate activity and gene expression of AT LPL and HSL at fasting and 6 h after meal in two insulin-resistant groups - obese with Type 2 diabetes and obese without diabetes - and in non-diabetic normal-weight controls. MATERIAL/SUBJECTS AND METHODS: Nine obese subjects with diabetes, 10 with obesity alone, and 9 controls underwent measurements of plasma levels of glucose, insulin, and triglycerides before and after a standard fat-rich meal. Fasting and post-prandial (6 h) LPL and HSL activities and gene expressions were determined in abdominal subcutaneous AT needle biopsies. RESULTS: The diabetic obese subjects had significantly lower fasting and post-prandial AT heparin-releasable LPL activity than only obese and control subjects (p

Summary Patients with diabetes often present with abnormal lipid profiles because insulin regulates several of the steps of lipid metabolism. Patients with type 1 diabetes that exhibit effective glycaemic control do not have quantitative lipoprotein abnormalities, but may exhibit qualitative abnormalities, mainly an increase in smaller, more atherogenic very low-density lipoprotein (VLDL) particles. Furthermore, in the Diabetes Control and Complications Trials (DCCT) study, the group of patients with type 1 diabetes that were characterised by consistent weight gain, exhibited lipid profiles more typical of type 2 diabetes (T2D). Dyslipidaemia in T2D is characterised by several strictly linked abnormalities: elevated fasting and postprandial triglycerides (TG), a significant decrease in high-density lipoprotein (HDL) cholesterol and an increase in smaller low-density lipoprotein (LDL) and HDL particles. The increase in plasma TG is largely explained by the increased production of TG-rich; large-sized VLDL in particular. The insulin resistant liver fails to inhibit lipid attachment to pre-VLDL molecules and synthesises larger-sized VLDL at a greater rate. Large TG-rich; VLDL enhances the transfer of core lipids between VLDL, LDL, and HDL with increased formation of smaller LDL and HDL. Also, the elevated postprandial TG that are often present in patients with T2D may be linked to insulin resistance. Therefore, the abatement of hyperglycaemia and insulin resistance should be one of the main treatment objectives to address dyslipidaemia in patients with diabetes.

Postprandial lipaemia is considered an emerging risk factor for cardiovascular disease also in the Type 2 diabetic population. However, little information exists on the daily triglyceride profile of these patients, especially during everyday life. The aim of the study was to evaluate the daily triglyceride profile of Type 2 diabetic patients during their everyday life.145 Type 2 diabetic patients (66 men/79 women, age range 45-65 years) at a health district near Naples, Italy, participating in a screening survey for the evaluation of diabetic complications, and 30 non-diabetic subjects of the same area underwent four daily capillary triglyceride profiles by Accutrend (Roche)-a previously validated method.Triglyceride values (mmol/l; Means +/- SE) were 2.22+/-0.08 at fasting, decreased before lunch (2.03+/-0.07), reached a peak 3 h after lunch (2.73+/-0.09) and remained substantially high before dinner (2.47+/-0.09) (all p0.001 vs fasting). The triglyceride profile of non-diabetic subjects was significantly lower at each point (average difference of 0.73 mmol/l). The percentage of patients with values above 2.25 mmol/l was 61% 3 h after lunch and 49% before dinner. Moreover, in 30% of patients with optimal fasting values (1.69 mmol/l) triglyceride concentrations 3 h after lunch ranged between 1.69 and 2.25 mmol/l, and in 31% they were above 2.25 mmol/l.Most Type 2 diabetic patients have postprandial triglycerides above optimal concentrations for several hours after meals. Moreover, optimal fasting concentrations are not always a good predictor of postprandial triglycerides.

OBJECTIVE: To evaluate whether postprandial abnormalities of energy expenditure and/or lipid oxidation are present in healthy, normal-weight subjects with a strong family history of obesity and thus at high risk to become obese. DESIGN: Case-control study. SUBJECTS: A total of 16 young healthy men participated in the study. Eight subjects had both parents overweight (father's and mother's body mass index (BMI) >25 kg/m(2)) and eight had both parents with normal body weight (father's and mother's BMI

Diabet. Med. 28, 227–229 (2011) Abstract Objective To evaluate the impact of high-glycaemic index and low-glycaemic index meals on postprandial blood glucose in patients with Type 1 diabetes treated with continuous subcutaneous insulin infusion. Methods Sixteen patients with Type 1 diabetes under continuous subcutaneous insulin infusion treatment, age 36 ± 0.5 years (mean ± sem), HbA1c 7.6 ± 0.2% (56 ± 1.1 mmol/mol), consumed two test meals with an identical macronutrient composition, but with a different glycaemic index: 59 vs. 90. Blood glucose was checked before the test meal and every 30 min thereafter for 180 min. The same preprandial insulin dose was administered on the two occasions. Results Blood glucose concentrations following the low-glycaemic index meal were significantly lower than those of the high-glycaemic index meal (P

Subtle abnormalities of very-low-density lipoprotein (VLDL) composition and distribution seem to be associated with increased cardiovascular risk. The aims of this study were first, to evaluate whether hyperinsulinaemia per se is able to produce VLDL abnormalities and second, whether this occurs through a stimulation of lipolytic enzymes. Eight normal male volunteers, age 36 +/- 7 years (M +/- SD), body mass index (BMI) 26+/-3 kg m-2, underwent a 5-h euglycaemic hyperinsulinaemic clamp (1.2 mU insulin/kg b.w. min-1). Nine sex, age and BMI comparable subjects underwent control experiments (saline infusion). Three VLDL subfractions of decreasing size were isolated by density gradient ultracentrifugation; lipoprotein lipase (LPL) and hepatic lipase (HL) post-heparin plasma activities were determined by the 3H-labelled triolein method. Hyperinsulinaemia ( approximately 65 mU mL-1) produced the expected plasma free fatty acid suppression. Triglyceride levels were reduced in total VLDL (- 27 +/- 32% vs. + 38 +/- 52% after saline, P < 0.05) and in the larger VLDL (- 56 +/- 19 vs. + 34 +/- 38, P < 0.001). Moreover the relative contribution of the larger subfraction was decreased (- 39 +/- 15% vs. - 3 +/- 21%, P < 0.01), while the percentage of smaller particles was increased (+17 +/- 20 vs. - 9 +/- 22, P < 0.05). LPL and HL activities were decreased to the same degree during either insulin or saline infusion. Exogenous hyperinsulinaemia produced lipoprotein abnormalities partially similar to those previously shown in type 1 diabetic patients, indicating that these abnormalities may be secondary to insulin therapy.

This study evaluates the effects of insulin versus glibenclamide on lipoprotein metabolism at comparable levels of blood glucose control, in particular on the concentration and distribution of VLDL subfractions and lipolytic enzyme activities in nine NIDDM men (aged 56 ± 3 years, BMI 26.5 ± 0.9 kg/m2) (means ± SE) participating in a crossover study. After a 3-week washout period, patients were randomly assigned to 2-month treatment periods (insulin or glibenclamide); thereafter, each patient crossed to the other treatment. At the end of each period, mean daily blood glucose (MDBG), HbA1c, plasma lipids, lipoproteins (VLDL, LDL, HDL), lipoprotein subfractions (VLDL1, 2, 3; HDL2) HDL3), and post-heparin lipase activities (lipoprotein lipase [LPL], hepatic lipase [HL]) were evaluated. Although glucose control was similar at the end of both periods (MDBG 8.3 ± 0.3 vs. 7.9 ± 0.3 mmol/l HbA1c 7.4 ± 0.3 vs. 7.0 ± 0.2%, insulin versus glibenclamide), insulin compared with glibenclamide induced a significant reduction in plasma triglycerides (0.9 ± 0.1 vs. 1.1 ± 0.1 mmoH, P < 0.05), VLDL triglycerides (50.1 ± 12.2 vs. 63.6 ± 12.3 mg/dl, P < 0.02), VLDL1 lipid concentration (24.9 ± 7.5 vs. 39.9 ± 9.5 mg/dl, P < 0.006), and increased HDL2 cholesterol (25.2 ± 1.6 vs. 20.3 ± 1.3 mg/dl, P < 0.03). In terms of VLDL percentage subfraction distribution, with insulin, there was a decrease in the larger subfractions (VLDL1 26.5 ± 3.0 vs. 37.8 ± 3.4%, P < 0.02) and an increase in the smallest (VLDL3 47.3 ± 3.8 vs. 37.3 ± 3.3%, P < 0.05). Moreover, HL activity was significantly lower after insulin than after glibenclamide (HL 247.2 ± 22.3 vs. 263.5 ± 22.6 mU/ml, P < 0.05). In conclusion, compared with glibenclamide, insulin treatment (independent of variations in glucose control) is able to decrease significantly plasma triglycerides, to increase HDL2 cholesterol, and to reduce only the concentration of the larger VLDL subfractions, with a consequent redistribution of their profile.

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

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.

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)

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 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.

Evidence-based nutritional approaches to the treatment and prevention of diabetes mellitus.

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

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.

Summary Aims The aim of the study was to evaluate the efficacy and safety of acarbose in patients with Type 1 diabetes mellitus (DM). Methods A multicentre double-blind, randomized, placebo-controlled study was performed. After a 6-week run-in, 121 patients were randomized to acarbose or placebo and to high- or low-fibre diet for 24 weeks. Acarbose dose was 50 mg t.d.s. for the first 2 weeks and 100 mg t.d.s. for the subsequent weeks. Results At the end of 24 weeks of treatment the intention to treat analysis showed that acarbose compared with placebo decreased 2 h postprandial plasma glucose levels (12.23 ± 0.83 vs. 14.93 ± 0.87 mmol/l;F = 6.1, P

This study evaluates prospectively the relationship between impaired glucose tolerance (IGT) and blood pressure. From a population of 1376 men and women aged 40-59 years, all those with IGT (n = 54) plus 133 age- weight- and sex-matched normoglycaemic control subjects were selected after excluding treated hypertensive patients. Blood pressure, fasting and postload blood glucose and plasma insulin were measured. At 11.5 years after the first visit 76% of the IGT patients and 80% of the control subjects were re-examined. At baseline blood pressure was significantly higher in IGT patients than in control subjects (systolic 135.5 +/- 2.3 vs 127.9 +/- 1.4 mmHg, p0.001; and diastolic 88.0 +/- 1.5 vs 84.7 +/- 0.7 mm Hg, p0.05) independent of age, gender, weight, antihypertensive medication and insulinaemia. Accordingly, hypertension was more frequent in subjects with IGT (odds ratio 2.1, 95% confidence, interval (CI) 0.9-4.9). Postload insulin was significantly associated with hypertension--both at univariate and multivariate analysis--in normoglycaemic subjects, but not in those with IGT. At follow-up systolic blood pressure increased in both groups; the increase was smaller in patients with IGT (6.0 +/- 2.4 vs 12.3 +/- 1.6 mm Hg p0.05). Likewise, the 11.5 years' cumulative incidence of hypertension was not significantly different in subjects with baseline IGT or normoglycaemia; if anything it was lower in the IGT group (odds ratio 0.36, 95% CI 0.1-1.2). In multivariate analysis incidence of hypertension was associated positively with baseline blood pressure (p0.0003) and negatively with IGT status p0.03), while no significant association was found with insulin. In conclusion, the findings of this study question IGT as a risk factor for hypertension. Furthermore, these data do not indicate a major role for hyperglycaemia and hyperinsulinaemia per se in the aetiology of hypertension and suggest that IGT and hypertension share one or more pathogenetic factor(s) (i.e., insulin resistance, hyperactivity of the sympathetic nervous system, etc.), which induce deterioration of blood pressure control first, and hyperglycaemia later.

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.

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

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)