OBJECTIVEA trial was performed to establish whether our group care model for lifestyle intervention in type 2 diabetes can be exported to other clinics.RESEARCH DESIGN AND METHODSThis study was a 4-year, two-armed, multicenter controlled trial in 13 hospital-based diabetes clinics in Italy (current controlled trials no. ISRCTN19509463). A total of 815 non–insulin-treated patients aged <80 years with ≥1 year known diabetes duration were randomized to either group or individual care.RESULTSAfter 4 years, patients in group care had lower A1C, total cholesterol, LDL cholesterol, triglycerides, systolic and diastolic blood pressure, BMI, and serum creatinine and higher HDL cholesterol (P < 0.001, for all) than control subjects receiving individual care, despite similar pharmacological prescriptions. Health behaviors, quality of life, and knowledge of diabetes had become better in group care patients than in control subjects (P < 0.001, for all).CONCLUSIONSThe favorable clinical, cognitive, and psychological outcomes of group care can be reproduced in different clinical settings.

Antithyroid drugs may be proposed as the firstline therapy for hyperthyroidism due to Graves' disease since some patients undergo prolonged remission after drug withdrawal. On the other hand, some studies, though controversial, indicated that methimazole (MMI) has some immunomodulating activity. We retrospectively analyzed 384 consecutive patients newly diagnosed with Graves' disease in the years 1990-2002 to ascertain whether long-term therapy with low doses of MMI may prevent relapse of thyrotoxicosis. Two hundred and forty-nine patients were included in our study. The date of reduction of MMI dose to 5 mg/day was considered time 0 for survival analysis. In 121 MMI was discontinued in less than 15 months after time 0 (group D), while in the remaining 128 a daily MMI 2.5-5 mg dose was maintained (group M). One hundred and thirty-five patients were excluded for inadequate response to MMI, relapse of thyrotoxicosis that could be related to an improper withdrawal or reduction of MMI, inadequate or too short followup, iodide contamination, steroid or interferon therapy, pregnancy or post-partum. D and M groups did not differ for clinical and hormonal parameters except age, which was lower in D (p=0.019). Age > vs < 35 yr was relevant in survival analysis; therefore patients were divided in 2 groups according to this age cut-off. In younger patients relapse of thyrotoxicosis occurred in 15 patients of group D 2.4-39.6 months (median 19.0) after time 0, and 8 M after 5.9-40.0 (21.3) months, while 14 D and 5 M maintained euthyroidism until the end of the observation after 31.8-95.3 (56.6) months and 30.4-62.1 (46.5) months, respectively. Survival analysis indicated that the risk of relapse was similar in group D and M. In older patients relapse of thyrotoxicosis occurred in 40 patients of group D after 8.2-65.8 (25.4) months and 29 M after 5.8-62.5 (22.4) months, while 52 D and 86 M maintained euthyroidism until the end of the observation, 20.1-168.0 (46.7) months and 24.1-117.4 (53.4) months respectively. Survival analysis indicated that the risk of relapse was increased in group D. Therefore long-term treatment with low doses of MMI seems to prevent relapse in Graves' disease in patients above 35 yr of age. This should be confirmed in a prospective study.

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In newly diagnosed diabetics treated with Monotard (porcine monocomponent (MC) Lente insulin) for five years, no antibodies against porcine or bovine proinsulin were observed, but 2 of 13 subjects developed a-component antibodies. In newly diagnosed diabetics, treatment for the same period with conventional Lente insulin induced both proinsulin and a-component antibodies (in 5 and 8 of 10 cases, respectively). In 31 patients transferred from conventional Lente to Monotard, proinsulin and a-component antibody levels were significantly lower than in 22 patients maintained on conventional Lente after the 5-year follow-up period. No significant differences were noted between bovine and procine proinsulin antibodies. Insulin antibody production was similar to that of proinsulin antibody.

Aims In circulating lymphocytes of NIDDM patients pyruvate dehydrogenase (PDH), the major determinant in glucose consumption through oxidative pathways, is poorly active. The aim of this study is to examine whether sulphonylurea drug treatment revives PDH activity in circulating lymphocytes from NIDDM patients. Methods Twenty normal-weight individuals with NIDDM were enrolled in this study. They had maintained their glycaemic levels close to normal by means of a restricted diet that had no longer been successful in the proceeding 2 months. The treatment protocol consisted in 160 mg gliclazide daily for 5 weeks. Twenty healthy subjects, matched for age, body mass index and gender, were enrolled as a control group. Patients, before and after treatment, as well as controls were tested for PDH activity in their circulating lymphocytes. Nine other untreated patients and nine healthy subjects, with the above mentioned characteristics, were recruited for the assay of PDH activity in their circulating lymphocytes before and after exposure, in vitro, to gliclazide, to insulin, and to gliclazide and insulin in combination. Results In gliclazide-treated NIDDM patients, PDH activity in circulating lymphocytes recovered. In vitro, in circulating lymphocytes of untreated patients and controls insulin at 5 mU ml −1 was ineffective and highly effective, respectively, in raising enzyme activity; gliclazide at 10 ng ml −1 was ineffective on PDH in both groups, but in combination with insulin at 5 mU ml −1 in both groups PDH was as active as in cells of controls exposed to insulin only. In cells of controls, gliclazide alone at 25-50 ng ml −1 caused enzyme activation, whereas above 50 ng ml −1 it caused inhibition; in cells of patients below 50 ng ml −1 it had no effects, but at 50 ng mland above raised enzyme activity to the basal level of controls. Conclusions This study suggests that free gliclazide concentrations determine recovery of PDH activity in circulating lymphocytes of treated patients through drug-mediated enhanced insulin control over PDH or through the drug alone.Keywords: NIDDM, sulphonylureas, pyruvate dehydrogenase, circulating lymphocytescells. An understanding of the mechanisms underlying this Introduction benefit might throw new light on the mechanisms through which sulphonylureas behave as hypoglycaemic agents. Sulphonylurea drugs are largely employed to lower hyperglycaemia in patients with NIDDM. The mechanism In NIDDM patients systemic glucose consumption through oxidative pathways is abnormal and in tissues underlying this effect is still debated. Evidence indicates these drugs improve cell responsiveness to insulin or even actively involved in preserving glucose homeostasis, such as skeletal muscle [9][10][11], this alteration is accompanied by mimic some of the effects of insulin [1][2][3][4][5][6][7]. In a previous study it was observed that in circulating lymphocytes of poorly active PDH [12,13]. Further, in adipocytes from these patients [14] enzyme response to insulin is impaired. NIDDM patients the...