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Objective: To ascertain to which extent the use of HbA(1c) and oral glucose tolerance test (OGTT) for diagnosis of glucose tolerance could identify individuals with different pathogenetic mechanisms and cardiovascular risk profile.Research Design and Methods: A total of 844 subjects (44% men; age 49.5 ± 11 years; BMI 29 ± 5 kg/m(2)) participated in this study. Parameters of β-cell function were derived from deconvolution of the plasma C-peptide concentration after a 75-g OGTT and insulin sensitivity assessed by homeostasis model assessment of insulin resistance (IR). Cardiovascular risk profile was based on determination of plasma lipids and measurements of body weight, waist circumference, and blood pressure. Glucose regulation categories by OGTT and HbA(1c) were compared with respect to insulin action, insulin secretion, and cardiovascular risk profile.Results: OGTT results showed 42% of the subjects had prediabetes and 15% had type 2 diabetes mellitus (T2DM), whereas the corresponding figures based on HbA(1c) were 38 and 11%, with a respective concordance rate of 54 and 44%. Subjects meeting both diagnostic criteria for prediabetes presented greater IR and impairment of insulin secretion and had a worse cardiovascular risk profile than those with normal glucose tolerance at both diagnostic methods. In a logistic regression analyses adjusted for age, sex, and BMI, prediabetic subjects, and even more T2DM subjects by OGTT, had greater chance to have IR and impaired insulin secretion.Conclusions: HbA(1c) identifies a smaller proportion of prediabetic individuals and even a smaller proportion of T2DM individuals than OGTT, with no difference in IR, insulin secretion, and cardiovascular risk profile. Subjects fulfilling both diagnostic methods for prediabetes or T2DM are characterized by a worse metabolic profile. [ABSTRACT FROM AUTHOR]

To determine the predictive value of serum triglyceride levels (TG) for neonatal weight in pregnant women with positive diabetic screening but normal glucose tolerance.We enrolled 180 pregnant Caucasian women with positive diabetic screening. All women underwent a 3-h 100-g oral glucose tolerance test (OGTT) at 27th ± 4 week of gestation. At the time of OGTT, we measured: fasting plasma glucose, fasting lipids profile and determined ApoE polymorphisms to evaluate the effects on lipid levels. In 83 women with normal glucose tolerance and at term delivery we evaluated the association between maternal serum TG, specific maternal parameters known to affect fetal growth and newborn weight.Based on OGTT, gestational diabetes mellitus (GDM) was diagnosed in 36 women (20%), impaired glucose tolerance (IGT) in 23 (13%), and normal glucose tolerance (NGT) in 121 (67%). Serum TG concentration was significantly higher in women with GDM (2.47 ± 0.77 mmol/l) as compared with NGT (1.99 ± 0.64 mmol/l) or IGT (1.98 ± 0.81 mmol/l) (P < 0.01). ApoE3 allelic frequency was 86%, ApoE2 and ApoE4 were 5 and 9%, respectively. We found no clear-cut association between apoE genotype and serum TG concentration. Macrosomia and LGA newborns were more frequent in IGT than in GDM or NGT (P < 0.01). In the 83 women with positive diabetic screening but normal glucose tolerance who delivered at term, the incidence of LGA infants was significantly higher in those with TG levels higher than the 75th percentile (> 2.30 mmol/l) (21%) than in mothers who had normal TG levels (4.5%) (P < 0.05). Pre-pregnancy BMI (r2 = 0.067), weight gain during pregnancy (r2 = 0.062), fasting serum TG (r2 = 0.09), and 2-h post-OGTT glucose levels (r2 = 0.044) were all associated with neonatal body weight (allP < 0.05 or less). However, on a multiple regression analysis, only pre-pregnancy BMI (F-test = 7.26,P < 0.01), and fasting serum TG (F-test = 4.07,P < 0.01) were independently associated with birth weight.Pre-pregnancy BMI and fasting maternal serum TG determined in the last trimester of gestation were independently associated with neonatal birth weight in women with normal glucose tolerance, but positive screening test. TG levels measured in the third trimester of pregnancy are independent of the genetic polymorphism of ApoE.Diabet. Med. (2004) [ABSTRACT FROM AUTHOR]

The impact of the diabetes epidemic will be staggering in terms of costs to individuals and society. Social educational initiatives are imperative to altering the lifestyle trends that drive the growth of the epidemic. Targeted lifestyle or drug interventions aimed at preventing progression from prediabetes to type 2 diabetes mellitus carry costs and risks that need to be considered in the context of expected benefits, which also need to be carefully defined. In terms of pharmacological intervention as part of a primary prevention programme, the risk/benefit assessment must include the potential for adverse effects in a large population of asymptomatic individuals, a significant proportion of whom would not progress to diabetes in the absence of treatment and in whom impaired glucose regulation may reflect different underlying pathogenetic mechanisms. Improving the balance of risks and benefits in drug interventions will require a greater ability to determine which treatments are likely to safely improve glucose regulation and prevent diabetes and its adverse cardiovascular outcomes in individual patients. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases represent, today, the principal cause of mortality in the general population, especially in subjects with type 2 diabetes mellitus. In these patients the risk of death from cardiovascular diseases is equal to that of non-diabetic subjects with a previous episode of myocardial infarction. Many factors concur to determine such high risk. Hyperglycaemia contributes to the increase in morbidity and cardiovascular mortality associated with diabetes mellitus. Hyperglycaemia acts as a multipler of cardiovascular risk due to frequent association of multiple risk factors in diabetic patients. Therefore, effective treatment requires a more complete assessment of quantitative and qualitative aspects of glycemic control as well as all components of the diabetic syndrome or, more commonly, metabolic syndrome. [ABSTRACT FROM AUTHOR]

We investigated cross-sectionally whether the type 2 diabetes (T2DM) risk alleles of rs1801282 ( PPARG2) and rs4607103 ( ADAMTS9) were associated with T2DM and/or insulin sensitivity (IS) and beta cell function (βF) in Italians without and with newly diagnosed T2DM. In 676 nondiabetic subjects (336 NGR and 340 IGR) from the GENFIEV study and in 597 patients from the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS), we (1) genotyped rs1801282 and rs4607103, (2) assessed βF by C-peptide/glucose modeling after OGTT, and (3) assessed IS by HOMA-IR in both studies and by euglycemic insulin clamp in VNDS only. Logistic, linear, and two-stage least squares regression analyses were used to test (a) genetic associations with T2DM and with pathophysiological phenotypes, (b) causal relationships of the latter ones with T2DM by a Mendelian randomization design. Both SNPs were associated with T2DM. The rs4607103 risk allele was associated to impaired βF ( p < 0.01) in the GENFIEV study and in both cohorts combined. The rs1801282 genotype was associated with IS both in the GENFIEV study ( p < 0.03) and in the VNDS ( p < 0.03), whereas rs4607103 did so in the VNDS only ( p = 0.01). In a Mendelian randomization design, both HOMA-IR (instrumental variables: rs1801282, rs4607103) and βF (instrumental variable: rs4607103) were related to T2DM ( p < 0.03-0.01 and p < 0.03, respectively). PPARG2 and ADAMTS9 variants are both associated with T2DM and with insulin resistance, whereas only ADAMTS9 may be related to βF. Thus, at least in Italians, they may be considered bona fide 'insulin resistance genes'. [ABSTRACT FROM AUTHOR]

Aims To determine the relationships between metabolic syndrome (MetS), diabetic nephropathy (DN) and renal function in Type 2 diabetes. Methods In a clinic-based cohort of 1314 Type 2 diabetic patients (58% male; age 62 ± 10 years), we analysed MetS, detected DN and estimated glomerular filtration rate (eGFR). Results Prevalence of both microalbuminuria and macroalbuminuria were higher in subjects with MetS than in those without. Prevalence of DN (microalbuminuria and macroalbuminuria) increased with the number of MetS components. eGFR was lower in subjects with MetS than in those without (87 ± 23 vs. 92 ± 20 ml/min per 1.73 m2; P < 0.001). The lowest eGFR values were found in those with four or more components of the MetS. Prevalence of low eGFR increased with the stage of DN and was affected by MetS only in normoalbuminuric patients. MetS was independently associated with DN, also after adjustment for confounders [odds ratio (OR) 2.82, confidence interval (CI) 1.93, 4.11] and the presence of low eGFR in the model (OR 2.74, CI 1.87, 4.01). Similarly, MetS was a predictor of low eGFR (OR 1.93, CI 1.11, 3.36), but after adjustment for DN, the association was lost. Finally, MetS per se was independently associated with DN, but not with low eGFR after adjustment for all of the individual components of the MetS. Conclusions This study suggests a close and independent association between MetS and renal impairment. However, it is unclear whether and to what extent treating MetS by an intensive multifactorial therapeutic approach will prevent or delay progression to renal failure. [ABSTRACT FROM AUTHOR]

Abstract: Introduction and aim: Guidelines for cardiovascular prevention in diabetes have been issued by the national and international scientific societies. No audit as ever been performed to evaluate the implementation of these documents in clinical practice in Italy. The study evaluates the prevalence, treatment, and control of major cardiovascular risk factors in type 2 diabetic patients, to assess the clinical practice of primary cardiovascular prevention in type 2 diabetes. Patients and methods: Two thousand four hundred and sixty-five men and women with type 2 diabetes, aged 50–75 and free of cardiovascular events were recruited on a consecutive basis at 10 hospital based outpatients diabetes clinics. Clinical variables were measured by standard protocol. Biochemical parameters were evaluated at each centre. The laboratories were monitored by an external quality control assessment in order to reach and maintain a standard of quality and traceability among the participating centres. Results: A minority of patients (5%) met the recommended targets for LDL cholesterol, blood pressure, glycated haemoglobin and smoking habits, whereas the vast majority (66%) had unsatisfactory control of three or more of the above. Achievement of desirable control of risk factors differed according to gender and known diabetes duration. Lipid lowering and, to a lesser extent, antihypertensive medications were under-used and their titration insufficiently target-driven. Prophylactic use of antiplatelet agents was scarce, only one out of five patients was treated independent of absolute cardiovascular risk. Conclusion: In clinical practice there is poor adherence to national and international guidelines for primary cardiovascular prevention in type 2 diabetes in Italy. The study underlines the great potential for prevention, particularly in women and in high-risk patients. [Copyright &y& Elsevier]

Objective:To clarify adherence of type II diabetic patients to dietary recommendations.Subjects and methods:The dietary habits of a group of 540 patients, with type II diabetes (male 322/female 218, mean age 61±5 years, body mass index (BMI) 29.7±5.2 kg/m2; mean±s.d.) referring to six Italian diabetes centres were evaluated by means of a 3-day diet record (2 workdays, 1 holiday). Diet records were analysed according to Italian food composition tables and compared with the dietary recommendations of the Diabetes and Nutrition Study Group of the European Association for the study of Diabetes.Results:Calorie intake was 1725±497 kcal (1800 for men, 1610 for women). Mean intake for each nutrient was close to the recommended amount, except for fibre (12/1000 vs 20 g/1000 kcal). Calculating the percentage of patients who complied with each recommendation, the intakes of saturated fat and fibre least reflected the dietary target: in 43% of patients saturated fat was >10% of total calories, in only 6% was fibre intake 20 g/1000 kcal (considered ideal), and in 25% it was 15 g/1000 kcal (acceptable).Conclusions:These results indicate that compliance to dietary recommendations is not completely satisfactory, even in Italy. Calorie intake is a bit elevated, given the high BMI of our diabetic population. As to dietary composition, there are two crucial issues: the high intake of saturated fat and – most importantly – the low intake of fibre. All strategies aiming to a proper implementation of guidelines should take these results into due account.European Journal of Clinical Nutrition (2008) 62, 660–664; doi:10.1038/sj.ejcn.1602755; published online 11 April 2007 [ABSTRACT FROM AUTHOR]

In order to evaluate the prevalence of gestational diabetes mellitus (GDM) and the presence of risk factors for GDM, we conducted a retrospective study of a cohort of Italian women. In addition, we compared universal versus selective screening to validate the ADA''s recommendations in our population. From June 1st, 1995 to December 31st, 2001, universal screening for GDM was performed in 3950 women. The glucose challenge test (GCT) was positive (GCT+) in 1389 cases (35.2%). The 1-h glucose level after GCT enabled us to diagnose GDM directly in 24 pregnant women. Oral glucose tolerance test (OGTT) was performed in 1221 GCT+ women (144 cases with GGT+ dropped out) and GDM was diagnosed in 284 (23.2%) of them. OGTT was also performed in 391 randomly chosen, women from the GCT negative (GCT−) group. In this last group 25 (6.3%) women had GDM. Thus, the total number of subjects with GDM was 333 out of 3806 with a prevalence of 8.74% in the entire cohort. Assuming that the rate of GDM observed in the random sample of GCT− women is applicable to the whole group of 2561 GCT− women, then 161 GCT− patients could also have GDM. This will further increase the estimated prevalence for the whole cohort up to 12.3% (i.e. 469 out of 3806 pregnant women). There were 236 (5.6%) women with a low risk for GDM (normal weight, age less than 25 years and without a family history of diabetes). In this group we found 34 cases and five cases with positive screening test and GDM, respectively. Thus, if we excluded low risk women from the screening test, as suggested by ADA recommendations, only five women with GDM would have been missed. However, about 95% of our population were at medium or high risk for GDM and, therefore, would have been screened. The rate of GDM was significantly higher in women with a positive history of diabetes, increasing age, previous pregnancies, pre-pregnancy overweight and short stature. After logistic regression analysis, GDM diagnosis was significantly correlated with age (P<0.0001), pre-pregnancy BMI (P<0.0001), weight gain (P<0.0001) and family history of diabetes (P<0.01). [Copyright &y& Elsevier]