Preprandial combination of lispro and NPH insulin improves overall blood glucose control in type 1 diabetic patients: a multicenter randomized crossover trial.

BACKGROUND AND AIM: While lispro insulin has been reported to lower postprandial blood glucose concentrations, less consistent effects have been shown for glycosylated hemoglobin (HbA1c) levels. Aim of this study was to determine whether pre-meal association of NPH, an intermediate-acting insulin, with lispro improves overall glycemic control in type 1 diabetic patients. METHODS AND RESULTS: Eighty-five type 1 diabetic patients were studied in a multicenter randomized comparative (human regular vs lispro insulin) crossover (3-month) study in which NPH insulin was given as a dinner or bedtime injection and at breakfast and lunch if necessary. The number of injections was kept constant: 42% and 58% of patients injected insulin 3 and 4 times per day, respectively. Fasting and preprandial blood glucose levels were similar, while postprandial levels improved after lispro compared to human regular insulin (breakfast: 8.28 +/- 2.39 vs 9.28 +/- 2.72 mmol/l; lunch: 8.33 +/- 2.67 vs 9.06 +/- 2.67 mmol/l, dinner: 8.06 +/- 2.72 vs 9.28 +/- 2.44 mmol/l, ANOVA: p = 0.003). HbA1c also improved after lispro: 8.1 +/- 0.9 vs 8.3 +/- 0.8%, p < 0.05. The rate of hypoglycemia was similar. Patients showed better acceptance of lispro treatment (p < 0.001). CONCLUSIONS: Lispro improves overall blood glucose control in type 1 diabetic patients without increasing the incidence of hypoglycemia. This can be achieved by an optimal combination of lispro insulin with NPH whenever the time intervals between meals are too long.

Low adherence of General Practitioners to National Cholesterol Education Program guidelines for the management of hyperlipidaemia.

Aim of our study was to assess adherence to the National Cholesterol Education Program Adult-Treatment Panel II (NCEP-ATP II) in patients cared for by General Practitioners (GPs) in an Italian community. The design of the work was cross-sectional cohort study; the base was an unselected cohort of 1,168 patients cared for by GPs and screened at our lipid clinic in 1994-1995 in the Province of Turin (Italy). Blood samples were collected after 12-hr fast to measure plasma levels of total cholesterol, triglycerides, HDL-cholesterol, glucose and thyroid-stimulating hormone (TSH). LDL-cholesterol was calculated using Friedewald's formula. In patients with body mass index (BMI) >30 kg/m2, an oral glucose tolerance test was performed. Blood pressure was measured in all patients, and a baseline ECG or a stress test was performed in those with unknown cardiovascular disease (CVD), then they were classified following the NCEP-ATP II criteria. Primary hyperlipidaemia accounted for 86.9% of the cohort with most patients requiring pharmacological treatment; in 34.4% of the patients, LDL-cholesterol values were > or = 6.46 mmol/l (250 mg/dl) and in 23.7% with established CVD, LDL-cholesterol levels were > or = 5.68 mmol/l (220 mg/dl). In only 7.3% of patients the NCEP treatment goals were achieved, with 1.3% among those in secondary prevention. We observed great discrepancies between clinical practice and international recommendations for the management of hyperlipidaemia.

Clinical, immunological, and genetic heterogeneity of diabetes in an Italian population-based cohort of lean newly diagnosed patients aged 30-54 years. Piedmont Study Group for Diabetes Epidemiology.

OBJECTIVE: In lean diabetic patients, the presentation of the disease does not allow one to easily distinguish between type 1 and type 2. Aims of this study were to describe clinical, immunological, and genetic features of lean newly diagnosed diabetic patients. RESEARCH DESIGN AND METHODS: A population-based cohort of 130 lean (BMI < 25 kg/m2) newly diagnosed patients, aged 30-54 years, was identified among residents of the province of Turin. Islet cell antibodies (ICAs), anti-GAD, fasting and glucagon-stimulated C-peptide values, and HLA DQA1-DQB1 susceptibility genotypes were assessed within 2 months of the diagnosis. RESULTS: A total of 45 (34.6%) and 29 (22.3%) patients were, respectively, ICA+ and anti-GAD+, with 15 (11.5%) having both antibodies. In 59 patients, ICAs and/or anti-GAD antibodies were detected, giving a high prevalence of autoimmunity (45.4%, 95% Cl 36.8-54.0); relative to patients without markers (n = 71), they were younger (40.8 +/- 7.5 vs. 45.0 +/- 6.5 years, P < 0.001) and showed lower values of fasting C-peptide (0.56 +/- 0.33 vs. 0.79 +/- 0.41 nmol/l, P < 0.001) and stimulated C-peptide (1.03 +/- 0.56 vs. 1.42 +/- 0.69 nmol/l, P < 0.001). The lowest stimulated C-peptide values were found in patients with both ICA and anti-GAD antibodies. Frequencies of adult-onset type 1 and type 2 diabetes were, respectively, 49.2 and 50.8%. Clinical and genetic features were not useful in the classification of patients. CONCLUSIONS: Almost 50% of lean young and middle-aged patients were ICA+ and/or anti-GAD+, suggesting a high prevalence of a slowly evolving form of type 1 diabetes. The evaluation at diagnosis of both beta-cell secretory capacity and markers of autoimmunity is recommended to provide a pathogenetic classification of the disease.

Comparison of incidence of insulin-dependent diabetes mellitus in children and young adults in the Province of Turin, Italy, 1984-91. Piedmont Study Group for Diabetes Epidemiology.

To document the incidence of IDDM in the Province of Turin (Italy) in the 8-year period 1984-91 in children (0-14 years) and young adults (15-29 years), in relation to age, sex, monthly-seasonal variability, calendar year and urban/rural area, (all newly diagnosed cases (502) were ascertained through primary and secondary data sources and completeness of ascertainment estimated with the two sample capture-recapture method (99% in childhood and 95% in young adults). The independent effect of age, sex, calendar year, and urban/rural area was estimated with a Poisson regression model. Age-specific incidence rates were 8.42/100,000 (95% CI 7.37-9.62) and 6.72/100,000 (95% CI 5.96-7.58), respectively, in the age groups 0-14 and 15-29 years. Sex differences were evident in young adults, with an almost 1.5-fold increased risk in men (8.37/100,000, 95% CI 7.21-9.71 vs 5.00/100,000, CI 4.09-6.10). Seasonal trend was evident in childhood. Predictors of incidence rates were age, place of residence and interaction between sex and age; no temporal trend was detected. No significant differences were found in the two age-groups with respect to glycaemia, glycosuria, ketonuria, and fasting C-peptide levels. In conclusion, this study shows sex differences in IDDM risk in young adults; 55% of incident cases occurring in young adults; an independent contribution of urban/rural differences to IDDM risk; no temporal trend in 1984-91; a seasonal pattern of incidence in children; no significant differences in clinical presentation between age groups.

A human endogenous retroviral superantigen as candidate autoimmune gene in type I diabetes.

Microbial superantigens (SAGs) have been implicated in the pathogenesis of human autoimmune diseases. Preferential expansion of the Vveta7 T cell receptor positive T cell subset in patients suffering from acute-onset type I diabetes has indicated the presence of a surface membrane-bound SAG. Here, we have isolated a novel mouse mammary tumor virus-related human endogenous retrovirus. We further show that the N-terminal moiety of the envelope gene encodes an MHC class II-dependent SAG. We propose that expression of this SAG, induced in extrapancreatic and professional antigen-presenting cells, leads to beta-cell destruction via the systemic activation of autoreactive T cells. The SAG encoded by this novel retrovirus thus constitutes a candidate autoimmune gene in type I diabetes.

A cost-sharing formula for online circulation and a union catalog through a regional, multitype library cooperative.

The experience of the Capitol Region Library Council and the University of Connecticut Health Center in developing a cost allocation formula for a circulation and online catalog shared by twenty-nine libraries is reviewed. The resulting formula identifies a basic unit cost as a minimum for each system participant.