Summary. From a previously reported 5-year screening programme of 6,956 47-49-year-old Malm6 males, a series of 41 subjects with early-stage Type 2 (non-insulin-dependent) diabetes mellitus and 181 subjects with impaired glucose tolerance were selected for prospective study and to test the feasibility aspect of long-term intervention with an emphasis on life-style changes. A 5-year protocol, including an initial 6-months (randomised) pilot study, consisting of dietary treatment and/or increase of physical activity or training with annual check-ups, was completed by 90% of subjects. Body weight was reduced by 2.3-3.7 % among participants, whereas values increased by 0.5-1.7 % in non-intervened subjects with impaired glucose tolerance and in normal control subjects (p < 0.0001); maximal oxygen uptake (ml. min -1. kg -1) was increased by 10-14 % vs decreased by 5-9 %, respectively (p < 0.0001). Glucose tolerance was normalized in > 50% of subjects with impaired glucose tolerance, the accumulated incidence of diabetes was 10.6 %, and more than 50 % of the diabetic patients were in remission after a mean follow-up of 6 years. Blood pressure, lipids, and hyperinsulinaemia were reduced and early insulin responsiveness to glucose loading preserved. Improvement in glucose tolerance was correlated to weight reduction (r --0.19, p < 0.02) and increased fitness (r = 0.22, p < 0.02). Treatment was safe, and mortality was low (in fact 33 % lower than in the remainder of the cohort). We conclude that long-term intervention in the form of diet and physical exercise is feasible even on a large scale, and that substantial metabolic improvement can be achieved which may contribute to prevent or postpone manifest diabetes.Key words: Impaired glucose tolerance, Type 2 (non-insulindependent) diabetes mellitus, oral glucose tolerance test, insulin, long-term intervention, diet, physical exercise.Diabetes mellitus and its complications constitute a major health problem in modern societies [1,2]. Type 2 (non-insulin-dependent) diabetes is associated with an increased frequency of cardiovascular risk factors [3] and subsequent cardiovascular disease and mortality [4][5][6]; and in the agegroup under consideration here, the expected reduction in lifespanis 5-7 years [4]. Inpreviousstudies, annualprogression rates from impaired glucose tolerance (IGT) to Type 2 diabetes of 2-3 % have been found [7][8][9], though the causal link with known risk factors remains unclear [10]. Further preventive studies, with an emphasis on life-style changes, e. g., diet and physical exercise, are needed [11][12][13]. Apart from the fact that the efficacy of oral agents in preventing Type 2 diabetes and its sequelae has yet to be established [13], non-pharmacological treatment is an approach of great importance, not onlyvis-fi-vis glucosemetabolismbut also vis-a-vis the overallmetabolic profile [14,15].We have previously reported on studies where 6-12-month periods of dietary treatment or physical training (or both) were found to be beneficial in cases of IGT...

Objectives. To analyse the effects on mortality and cardiovascular morbidity in a population-based sample, invited to an intervention programme incorporating a baseline screening examination and treatment programmes for subjects with cardiovascular risk factors, high alcohol intake and, in women, suspicion of breast cancer on mammography. Setting. Section of Preventive Medicine, Department of Medicine, University Hospital, Malmo È, Sweden. Subjects. Birth cohorts (aged 32±51 years) invited to screening examination (men = 9.923; women = 4.422) were compared to birth cohorts not invited (men = 6.655; women = 4.290). Mean participation rate in the invited cohorts was 71% (range 64± 78%). Screening examination. Between 1974 and 1992 a baseline screening including a physical examination, blood pressure, a questionnaire regarding, e.g. family history, lifestyle, and socio-economic factors, laboratory tests of serum cholesterol, triglycerides, gamma-glutamyl-transferase, blood glucose before and after an oral glucose load, as well as a mammography examination in women, was performed. Interventions. Subjects with hypertension; hyperlipidaemia; diabetes or glucose intolerance; high alcohol intake; or, in women, suspicion of breast cancer were referred to special outpatient clinics.Main outcome measures. Total and cause-specific mortality, nonfatal myocardial infarction, and stroke, from the screening examination until the end of 1995, was followed in both the intervention and control groups, using national and/or local registries. Results. Total mortality did not differ significantly between the intervention group and control group. Cause-specific deaths were also similar except for other' deaths amongst men being significantly lower in the intervention group, mainly due to a lower mortality from`other' causes (suicide, alcohol related deaths) in men under 40 years of age at baseline. Women under 40 years of age had a significantly lower mortality from cancer in the intervention group than in the control group. Nonfatal myocardial infarction and stroke did not differ between intervention and control group in either sex. Within the invited birth cohorts, nonparticipants had a higher total and cause-specific mortality. Conclusions. Risk factor screening for major diseases such as cardiovascular disease, alcohol abuse, diabetes mellitus and breast cancer, and subsequent treatment of the detected risk factors/diseases ± The Malmo È Preventive Project ± did not reduce total mortality in the intervention group as a whole. In subjects under 40 years of age at entry, total mortality was lower in the intervention group than in the control group. In men, this seemed to be due to a reduction of alcohol-related deaths, whilst in women death from cancer was reduced.

Overall, the study indicated that both methods A and B had good ranking validity compared to the reference and that in most cases the combined method (B) performed slightly better than the extensive food frequency method (A).

Dose-effect titrated treatment with either metformin or glyburide promotes equal degrees of glycemic control. The former, but not the latter, is able to achieve this control without increasing body weight or hyperinsulinemia. Near-normal glycemia can be obtained by a combination of metformin and sulfonylurea, even in advanced NIDDM.

Cross-sectional studies have reported strong correlations between plasma levels of complement C3, insulin, and glucose. This prospective study explored whether elevated levels of C3, C4, and other inflammationsensitive plasma proteins (ISPs; fibrinogen, orosomucoid, ␣1-antitrypsin, haptoglobin, and ceruloplasmin) are associated with the development of diabetes. Plasma proteins were measured in 2,815 nondiabetic healthy men, age 38 -50 years, who were reexamined after a mean follow-up of 6.1 years. Diabetes development (n ‫؍‬ 123) was studied in relation to baseline levels of plasma proteins. After adjusting for age, screening year, and glucose at baseline, the odds ratio (95% CI) for developing diabetes was 1.00, 2.4 (1.1-5.3), 2.9 (1.4 -6.0), and 5.6 (2.8 -10.9), respectively, for men with C3 in the 1st, 2nd, 3rd, and 4th quartiles (trend: P < 0.00001). Fibrinogen, haptoglobin, C4, and the number of elevated ISPs were also related to future diabetes in this model. Only C3 was significantly associated with diabetes development after further adjustments for potential confounders, including BMI, insulin, and other inflammatory markers. We concluded that the risk of developing diabetes is related to levels of complement C3. Diabetes 54:570 -575, 2005 C omplement C3 and C4 are the major plasma proteins of the immune system complement pathways. The synthesis of these proteins is increased in response to inflammation and infection but at a slower rate than for traditional acute phase proteins (1,2). Both C3 and C4 have shown substantial correlations with obesity (3-6), and high gene expression of these complement components has been reported in omental adipose tissue in obese men (3). High C3 levels have been reported in subjects with diabetes and insulin resistance (6 -9).It has been shown that the cleavage product of C3, acylation-stimulating protein (ASP), is a paracrine metabolic factor that stimulates the uptake of glucose and fat storage in human adipose tissue (10 -12). ASP deficiency in mice has been associated with resistance to weight gain on a high-fat diet, despite increased food intake (13). However, whether C3 is associated with an increased risk of developing diabetes is unknown.Several inflammatory markers have been associated with the incidence of diabetes, including C-reactive protein (CRP) (14 -17), orosomucoid (18), sialic acid (18), white blood cells (18,19), and interleukin (IL)-6 (20). It has been proposed that diabetes is a disease of the innate immune system (21). However, several studies have reported a nonsignificant relation between inflammation and incidence of diabetes. Negative or inconclusive results have been reported for CRP (17,22), haptoglobin (18), fibrinogen (16,18), white blood cells (16), and ␣1-antitrypsin (18). It is unclear whether the discrepancies among studies are related to differences with respect to inflammatory markers, study populations, or other factors.Previous substudies from the Malmö Preventive Study have shown that the risk of developing cardiovascular diseases,...