Incidence, prevalence, costs and quality of care of type 1 diabetes in Italy, age 0-29 years: The population-based CINECA-SID ARNO Observatory, 2002-2012.

BACKGROUND AND AIMS: To assess temporal trend in incidence (2003-12) and prevalence (2002-12) of type 1 diabetes in children and young adults, direct costs and selected indicators of quality of care under the coverage of the universalistic Italian National Health System (NHS). METHODS AND RESULTS: The ARNO Observatory, a healthcare monitoring system based on administrative data, identified a population-based multiregional cohort of subjects aged 0-29 years. Type 1 diabetes was defined by at least two prescriptions of insulin over 12 months and continuous insulin-treatment in the following year. Indicators of quality of care and directs costs were assessed in persons with diabetes and in people without diabetes, individually matched for age, gender and health unit (1:4 ratio). We identified 2357 incident cases of type 1 diabetes aged 0-29 years (completeness of ascertainment, 99%). Incidence rates were similar in ages 0-14 (15.8, 95% CI 14.9-16.8) and 15-29 years (16.3, 15.4-17.2), with no significant trend. Prevalence increased from 137 to 166.9/100,000, particularly in the age 15-29 years. Direct costs accounted for € 2117 in persons with diabetes and € 292 in control individuals. A statistically significant decreasing trend in hospitalization for acute complications was evident (p < 0.001), which was almost completely due to ketoacidosis. People with at least one HbA1c measurement over the year were 48.5%. CONCLUSION: We showed high incidence and increasing prevalence of type 1 diabetes in young adults in Italy, which impact on direct costs under the universalistic coverage of the NHS.

The relative burden of diabetes complications on healthcare costs: The population-based CINECA-SID ARNO Diabetes Observatory.

BACKGROUND AND AIMS: In the present population-based study, we aimed to describe the per patient annual healthcare cost of people with diabetes in 2007-2012, to assess the relative burden of diabetes complications and other potential determinants on healthcare costs in the 2012 cohort, and to describe and analyse the determinants of the cost of incident cases diagnosed in 2012. METHODS AND RESULTS: We analysed data from a retrospective cohort of residents in four Italian areas that were served by Local Health Units participating in the ARNO Observatory. Per patient annual healthcare costs (Euros) were estimated as the sum of all the resources supplied during that year (drugs, outpatient care, and hospitalisations). The mean per patient annual healthcare cost increased from €2752 in 2007 to €3191 in 2010, before decreasing to €2791 in 2012. The largest component of these costs was represented by hospitalisations (around €1550, on average; 51.7% of total cost), followed by outpatient care (€422; 14.6%) and drugs (€973; 33.7%). In 2012, the most relevant cost determinants were chronic diabetes complications, with an additional cost due to nephropathy/end stage renal disease (€4683), amputations (€5042), lower extremity revascularization (€4808), and cerebrovascular diseases (€3861). Costs associated with incidence cases were higher than those associated with prevalent. CONCLUSION: The present study provides evidence on the excess of healthcare costs due to diabetes complications in both prevalent and incident cases.

Under-treatment of migrants with diabetes in a universalistic health care system: the ARNO Observatory.

AIMS: To assess whereas prevalence, treatment and direct costs of drug-treated diabetes were similar in migrants and in people of Italian citizenship under the universalistic Italian health care system. METHODS AND RESULTS: Drug-treated diabetic individuals were identified in the population-based multiregional ARNO Observatory on the basis of 2010 prescriptions. Migrants were identified by the country-of-birth code on the fiscal identification code. Diabetes prevalence was calculated for Italians (n = 7,328,383) and migrants (n = 527,965). To assess the odds of migrants of having diabetes compared to Italians, we individually matched all migrants to Italians for major confounders (age, sex and place of residence). Finally, all migrants with diabetes were individually matched for confounders to Italians with diabetes to compare prescriptions, hospitalization rates, services use and direct costs for the National Health System. We identified 368,797 subjects with diabetes among Italians and 10,336 among migrants, giving prevalence of 5.03% and 1.96%, respectively. Migrants with diabetes were younger than Italians (52 ± 13 years vs. 68 ± 14 years, P < 0.001); after matching, their risk of disease was higher (odds ratio, 1.55, 95% confidence interval, 1.50-1.60). The total cost was 27% lower in migrants, due to lower cost of drugs (-29%), hospital admission (-27%) and health services (-22%). The number of packages/treated person-year of all glucose-lowering drugs was also lower in migrants (-15%) (P < 0.001). CONCLUSIONS: Compared to subjects of Italian ancestry, migrants to Italy show a higher risk of diabetes but less intense treatment. Inequalities in health care use are likely and are maintained also in a universalistic system.

PPARG2 Pro12Ala and ADAMTS9 rs4607103 as "insulin resistance loci" and "insulin secretion loci" in Italian individuals. The GENFIEV study and the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 4.

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 (ßF) 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 ßF 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 ßF (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 ßF (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 ßF. Thus, at least in Italians, they may be considered bona fide "insulin resistance genes".

Women show worse control of type 2 diabetes and cardiovascular disease risk factors than men: results from the MIND.IT Study Group of the Italian Society of Diabetology.

BACKGROUND AND AIMS: 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. METHODS AND RESULTS: 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) (p < 0.001), and prevalence of abdominal obesity was 86% vs 44% (p < 0.001). 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%; p < 0.05 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. CONCLUSIONS: 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.

Metabolic syndrome in subjects at high risk for type 2 diabetes: the genetic, physiopathology and evolution of type 2 diabetes (GENFIEV) study.

BACKGROUND AND AIM: We evaluated the relationship between insulin resistance (IR) and insulin secretion with the metabolic syndrome (MS) in 885 subjects (377 men/508 women, age 49±11 years, BMI 29±5.2kgm(-2)) at risk of diabetes enrolled in the genetics, pathophysiology and evolution of type 2 diabetes (GENFIEV) study. METHODS AND RESULTS: All subjects underwent a 75-g oral glucose tolerance test (OGTT) for the estimation of plasma levels of glucose and C-peptide, as well as fasting insulin and lipid profile. IR was arbitrarily defined as HOMA-IR value above the 75th centile of normal glucose tolerance (NGT) subjects. Overall MS prevalence (National Cholesterol Treatment Panel-Adult Treatment Panel (NCEP-ATPIII) criteria) was 33%, 19% in subjects with NGT, 42% in impaired fasting glucose (IFG), 34% in impaired glucose tolerance (IGT), 74% in IFG+IGT subjects, and 56% in newly diagnosed diabetic patients. Prevalence was slightly higher with IDF criteria. MS prevalence was >50% in subjects with 2h glucose >7.8mmoll(-1), independently of fasting plasma glucose. IR prevalence was higher in subjects with MS than in those without (63% vs. 23%; p<0.0001) and increased from 54% to 73% and 88% in the presence of three, four or five traits, respectively. IR occurred in 42% of subjects with non-diabetic alterations of glucose homeostasis, being the highest in those with IFG+IGT (IFG+IGT 53%, IFG 45%, IGT 38%; p<0.0001). Individuals with MS were more IR irrespective of glucose tolerance (p<0.0001) with no difference in insulinogenic index. Hypertriglyceridaemia (OR: 3.38; Confidence Interval, CI: 2.294.99), abdominal obesity (3.26; CI: 2.18-4.89), hyperglycaemia (3.02; CI: 1.80-5.07) and hypertension (1.69; CI: 1.12-2.55) were all associated with IR. CONCLUSIONS: These results show that in subjects with altered glucose tolerance (in particular IFG+IGT) MS prevalence is high and is generally associated to IR. Some combinations of traits of MS may significantly contribute to identify subjects with IR.

Postprandial hyperglycemia is a determinant of platelet activation in early type 2 diabetes mellitus.

BACKGROUND: Chronic hyperglycemia is a major contributor to in vivo platelet activation in diabetes mellitus. OBJECTIVES: To evaluate the effects of acarbose, an alpha-glucosidase inhibitor, on platelet activation and its determinants in newly diagnosed type 2 diabetic patients. METHODS: Forty-eight subjects (26 males, aged 61 +/- 8 years) with early type 2 diabetes (baseline hemoglobin A(1c) < or = 7% and no previous hypoglycemic treatment) were randomly assigned to acarbose up to 100 mg three times a day or placebo, and evaluated every 4 weeks for 20 weeks. The main outcome measures were urinary 11-dehydro-thromboxane (TX)B(2) (marker of in vivo platelet activation) and 8-iso-prostaglandin (PG)F(2alpha) (marker of in vivo lipid peroxidation) excretion rate, 2-h postprandial plasma glucose (PPG) after a test meal, and assessment of glucose fluctuations by mean amplitude of glycemic excursions (MAGE). RESULTS: Baseline measurements revealed biochemical evidence of enhanced lipid peroxidation and platelet activation. As compared with the placebo group, patients treated with acarbose had statistically significant reductions in urinary 11-dehydro-TXB(2) and 8-iso-PGF(2alpha) excretion rate as early as after 8 weeks and at each subsequent time point (between-group P < 0.0001 at 12, 16 and 20 weeks), following earlier decreases in PPG and MAGE. Multiple regression analyses in the acarbose group revealed that PPG was the only significant predictor of 11-dehydro-TXB(2) urinary excretion rate (beta = 0.39, P = 0.002) and MAGE the only predictor of 8-iso-PGF(2alpha) urinary excretion rate (beta = 0.42, P = 0.001). CONCLUSIONS: Postprandial hyperglycemia is associated with enhanced lipid peroxidation and platelet activation in early type 2 diabetes. A moderate decrease in PPG achieved with acarbose causes time-dependent downregulation of these phenomena, suggesting a causal link between early metabolic abnormalities and platelet activation in this setting.

The metabolic syndrome is related to albuminuria in Type 2 diabetes.

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.

The clinical reality of guidelines for primary prevention of cardiovascular disease in type 2 diabetes in Italy.

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.

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

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

Pharmacological intervention in prediabetes: considering the risks and benefits.

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.

Glucose tolerance is negatively associated with circulating progenitor cell levels.

AIMS/HYPOTHESIS: Circulating progenitor cells participate in cardiovascular homeostasis. Depletion of the pool of endothelial progenitor cells (EPCs) is associated with increased cardiovascular risk. Furthermore, EPCs are reduced in the presence of classical risk factors for atherosclerotic disease, including diabetes mellitus. This study was designed to evaluate progenitor cell levels in volunteers with different degrees of glucose tolerance. METHODS: Cardiovascular parameters and the levels of circulating CD34(+) and CD34(+) kinase insert domain receptor (KDR)(+) cells were determined in 219 middle-aged individuals with no pre-diagnosed alterations in carbohydrate metabolism. Glucose tolerance was determined by fasting and 2 h post-challenge glucose levels, with IFG and IGT considered as pre-diabetic states. RESULTS: CD34(+) and CD34(+)KDR(+) cells were significantly reduced in individuals who were found to have diabetes mellitus, and were negatively correlated with both fasting and post-challenge glucose in the whole population. While only CD34(+) cells, but not CD34(+)KDR(+) cells, were significantly reduced in pre-diabetic individuals, post-challenge glucose was an independent determinant of the levels of both CD34(+) and CD34(+)KDR(+) cells. CONCLUSIONS/INTERPRETATION: Glucose tolerance was negatively associated with progenitor cell levels in middle-aged healthy individuals. Depletion of endothelial progenitors with increasing fasting and post-meal glucose may be one cause of the high incidence of cardiovascular damage in individuals with pre-diabetes.

Evaluation of metalloproteinase 2 and 9 levels and their inhibitors in diabetic and healthy subjects.

OBJECTIVES: We hypothesized that molecules active in vascular remodeling (i.e. MMPs and their TIMPs) could be modified in diabetic patients, as indirect markers of the diabetes related generalized abnormality of vascular activity. To test this hypothesis, we measured the plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 in type 2 diabetic patients and in healthy subjects. METHODS: We enrolled 181 diabetic patients and 165 controls. We measured body mass index (BMI), glycosylated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment index (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hct) fibrinogen (Fg), high sensitivity C-reactive protein (hs-CRP), and plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. RESULTS: A significant increase (P<0.0001) of BMI, HbA(1c), FPG, FPI, HOMA index, SBP, DBP, TC, LDL-C, Tg, Lp(a), PAI-1, Hct, Fg, and hs-CRP was present in the diabetic group, with a significant decrease (P<0.0001) of HDL-C levels compared to healthy subjects. MMP-2 and MMP-9 levels were significantly higher (P<0.0001) in diabetic patients. Significant TIMP-1, and TIMP-2 increase was also observed (P<0.0001) in the diabetic group. CONCLUSION: Plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 are increased in diabetic patients which may reflect abnormal extracellular matrix (ECM) metabolism.

C-reactive protein and metabolic syndrome in women with previous gestational diabetes.

BACKGROUND: This study evaluates the presence of metabolic syndrome (MS) and its association with C-reactive protein (CRP) and other cardiovascular (CV) risk factors, in a sample of women with and without previous Gestational Diabetes (pGDM). METHODS: One hundred and sixty-six women with pGDM and 98 women (controls) with uncomplicated pregnancy were studied 16 months after delivery. In all women, plasma glucose, insulin, lipid profile, serum uric acid, C-reactive protein, fibrinogen and homocysteine were measured. MS was defined according to NCEP ATPIII criteria. RESULTS: MS was identified in 15 pGDM women (9%) versus 1 control (1%) (p < 0.001). The more frequent metabolic traits were abdominal obesity (36% vs 17%) and low HDL-cholesterol (34% vs 17% in pGDM women and controls, respectively; all p < 0.01). HOMA-R, LDL-cholesterol, fibrinogen, serum uric acid and CRP resulted significantly higher in pGDM women with MS as compared to those without MS after adjustment for BMI. In women with no criteria for MS, only CRP levels were found to be higher in pGDM women compared to controls (p < 0.05). Seventeen percent of pGDM women with no criteria for MS had CRP levels >or=1 mg/L (all controls showed CRP levels <1 mg/L). After a stepwise regression analysis, CRP levels were independently correlated to HOMA-R (r2 = 0.27, p < 0.001) and fibrinogen (r2 = 0.30, p < 0.001). CONCLUSIONS: In our population, MS occurs in a sizable proportion of pGDM women and is associated with increased levels of CRP, fibrinogen, uric acid and LDL-cholesterol. Moreover, higher levels of CRP, a marker of chronic low-grade inflammation, are present in a subset of women with pGDM, independently of MS.

Maternal triglyceride levels and newborn weight in pregnant women with normal glucose tolerance.

OBJECTIVE: To determine the predictive value of serum triglyceride levels (TG) for neonatal weight in pregnant women with positive diabetic screening but normal glucose tolerance. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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 (r(2) = 0.067), weight gain during pregnancy (r(2) = 0.062), fasting serum TG (r(2) = 0.09), and 2-h post-OGTT glucose levels (r(2) = 0.044) were all associated with neonatal body weight (all P < 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. CONCLUSIONS: 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.

[Integrin Beta 3 PlA1/PlA2 polimorphism does not contribute to complications in both type 1 and type 2 diabetes]. / Il polimorfismo PlA1/PlA2 dell'integrina Beta 3 non contribuisce al rischio di complicanze micro- e macrovascolari nel diabete tipo 1 e tipo 2.

BACKGROUND: The glycoprotein IIIa (beta3 integrin) is an integral part of two glicoprotein receptors of platelets and, respectively, endothelium and vascular smooth muscle cells. The gene encoding the GPIIIa, a receptor for fibrinogen, vWF and fibronectin, shows polymorphism (PlA1/PlA2); the PlA2 allele has been associated with myocardial infarction, stroke and cardiovascular disease. METHODS: Seven hundred and thirty-two subjects with type 1 diabetes and 605 subjects with type 2 were recruited. The prevalence of complications in type 1 diabetes was: microalbuminuria (uA) 17%, overt nephropathy (MA) 10%; background retinopathy (bR) 27%, proliferative retinopathy (pR) 22%; hypertension (HYP) 13%; coronary heart disease (CHD) 9%. The respective figures for type 2 diabetes were: uA 34%, MA 21%; bR 38%, pR 18%; HYP 80%; CHD 26%. A 247 bp fragment (exon 2) was amplified by PCR. For the detection of the point mutation CDGE (Constant Denaturing Gel Electrophoresis) after optimum denaturing conditions setting by DGGE (Denaturing Gradient GE) and/or RFLP by NciI digestion were employed. RESULTS: In type 1 diabetes, PlA1PlA1/PlA1PlA2 distribution was 77/23%. No differences were found among normoalbuminuric (nA: 76/24%), microalbuminuric (uA: 79/21%) and macroalbuminuric subjects (MA: 75/25%, p=0.79) as well as among subjects with no retinopathy (Ret-) (74/26%), bR (76/24%) and pR (78/22%, p=0.81), and between HYP- (78/22%) and HYP+ (72/28%, p=0.27) as well as CHD- (76/24%) and CHD+ (75/25%, p=0.72). Systolic blood pressure, HbA1c and retinopathy were independent predictors of nephropathy. No contribution of diastolic BP, sex, BMI, duration of diabetes and PlA2 allele was found for the risk of nephropathy. In type 2 diabetes, PlA1PlA1/PlA1PlA2/PlA2PlA2 distribution was 74.4/23.3/2.3%, with no differences foud among nA (73/25/2%), uA (75/23/2%) and MA (81/17/2%, p=0.66). No significant difference was detected among subjects with Ret- (74/22/4%), bR (77/22/1%) and pR (77/22/1%, p=0.62). Also, no differences were found between HYP- (81/17/2%) and HYP+ (74/24/2%, p=0.28) as well CHD- (76/22/2%) and CHD+ (74/24/2%, p=0.93). Systolic BP, HbA1c, presence of retinopathy, gender and BMI were independent predictors of nephropathy. Diastolic BP, duration of diabetes and PlA2 allele did not contribute to the risk of nephropathy. CONCLUSIONS: The PlA1/PlA2 polymorphism of the GPIIIa gene does not contribute to the development of nephropathy or retinopathy in type 1 and type 2 diabetes. Furthermore, no association was found between the PlA1/PlA2 polymorphism, hypertension, and coronary heart disease.

Prevalence and risk factors for gestational diabetes assessed by universal screening.

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 GCT+ 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).

Intermediate metabolism in normal pregnancy and in gestational diabetes.

Complex though integrated hormonal and metabolic changes characterize pregnancy. In the face of progressive decline in insulin action, glucose homeostasis is maintained through a compensatory increase in insulin secretion. This switches energy production from carbohydrates to lipids, making glucose readily available to the fetus. This precise and entangled hormonal and metabolic condition can, however, be disrupted and diabetic hyperglycemia can develop (gestational diabetes). The increase in plasma glucose level is believed to confer significant risk of complications to both the mother and the fetus and the newborn. Moreover, exposition of fetal tissues to the diabetic maternal environment can translate into an increased risk for development of diabetes and/or the metabolic syndrome in the adult life. In women with previous gestational diabetes, the risk of developing type 2 diabetes is greatly enhanced, to the point that GDM represents an early stage in the natural history of type 2 diabetes. In these women, accurate follow-up and prevention strategies are needed to reduce the subsequent development of overt diabetes. This paper will review current knowledge on the modifications occurring in normal pregnancy, while outlining the mechanisms. In this paper, we will review the changes of intermediary metabolism occurring during pregnancy. In particular, we will outline the mechanisms responsible for gestational diabetes; the link between these alterations and associated maternal and neonatal morbidity will be examined.

Hyperglycaemia and cardiovascular risk.

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 multiplier 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.