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AIM: The purpose of this study was to investigate which factors determine the initiation of glucose-lowering therapy in patients with Type 2 diabetes mellitus in general practice and their future glycaemic control. METHODS: All incident Type 2 diabetic patients in the general practices in a Dutch middle-sized town from 1994 to 2000 were identified. Factors associated with initiation of glucose-lowering therapy were obtained from clinical files and examined by Cox's regression analyses. Using anova, the associations between clinical characteristics at diagnosis and future glycaemic control were investigated. RESULTS: In total, 603 newly diagnosed patients with Type 2 diabetes mellitus were included in the study. In the first month following diagnosis, 319 (53%) started with oral therapy. One, two and three years after diagnosis of diabetes, the cumulative incidences were 71% (95% CI 66-73%), 75% (71-79%) and 81% (77-84%), respectively. Age, gender, body weight, blood pressure, history of cardiovascular disease or total serum cholesterol values were not associated with time to start of drug therapy. An increased plasma glucose level at diagnosis was strongly related to faster initiation of drug therapy and worse future glycaemic control. Immediate initiation of glucose-lowering medication was not related to future glycaemic control. CONCLUSION: This study shows that the initial severity of diabetes, assessed by the degree of hyperglycaemia at time of diagnosis, is a major factor in determining the time to start of glucose-lowering drugs and the likelihood of achieving target levels of glycaemic control in the future, independent of glucose-lowering strategy. Therefore, patients with high glucose levels at diagnosis need close monitoring from the beginning of their disease. Copyright 2004 Diabetes UK [ABSTRACT FROM AUTHOR]

Background: Several studies have indicated that type 2 diabetes mellitus is more common among schizophrenic patients than in the general population. In this study, we investigated whether the use of antipsychotic drugs in patients with diabetes leads to worsening of glycemic control., Method: In this cohort study, patients with newly diagnosed type 2 diabetes were selected from the PHARMO Record Linkage System, which comprises pharmacy records for all 320000 residents of 6 Dutch cities. In total, we identified 2585 patients with incident cases of type 2 diabetes who began treatment with oral hypoglycemic agents between 1991 and 1997 and had a medication history of at least 2 years after diagnosis of diabetes. A change in treatment from oral hypoglycemic agents alone to insulin therapy (with or without continuation of oral hypoglycemic agents) was considered a proxy for deterioration of beta-cell function. We compared the incidence of initiation of insulin therapy between users and nonusers of antipsychotic drugs by performing a Cox proportional hazards model analysis., Results: We found an increased risk for initiation of insulin therapy at 2 years after diagnosis of diabetes in users of antipsychotics compared with nonusers; the relative hazard (hazard ratio) was 2.0 (95% CI = 1.2 to 3.3), which did not change after adjustment for potential confounders. The risk decreased in the years after diagnosis of diabetes., Conclusion: It seems that use of antipsychotics by patients with type 2 diabetes mellitus is associated with initiation of insulin therapy (i.e., "secondary failure"), especially in the first 2 years of the disease.

Purpose: The objective of this study was to determine the association between different antihypertensive drug therapies and lower extremity amputations (LEAs) in type 2 diabetes patients., Methods: Data were obtained from the PHARMO Record Linkage System comprising pharmacy records and data on hospitalisations for all 450,000 residents of eight Dutch cities. In a nested case-control study among 12,140 type 2 diabetes patients who used antihypertensive drugs, 26 cases with a first LEA and 94 controls without a LEA matched on age, sex and calendar time were identified. Logistic regression was used to estimate the relative risk of LEA and to adjust for potential confounding factors., Results: Among type 2 diabetes patients who used antihypertensive drugs, subjects who used thiazide diuretics, alone or in combination, had a higher risk of LEA compared to subjects who used Angiotensin Converting Enzyme (ACE) inhibitor monotherapy (crude odds ratio (OR): 6.11 [95% confidence interval (CI): 1.32-28.27]). The use of thiazide diuretics was also associated with an increased risk of LEA when compared to the use of any non-thiazide antihypertensive drug (adjusted OR: 7.04 [1.10-45.30]). The increased risk of LEA associated with the use of thiazides compared to the use of non-thiazides depended on the duration of use (adjusted OR(< or = 365 days), 4.82 [0.61-38.34] and adjusted OR(>365 days), 26.16 [1.02-674.02], p-trend = 0.01)., Conclusions: Treatment with thiazide diuretics compared to treatment with other antihypertensive drugs was associated with excess amputations in type 2 diabetes patients. Due to several limitations of this study, our findings do not preclude the use of thiazides in type 2 diabetes mellitus patients as yet.

Objective: To assess whether switching to insulin therapy in patients with type 2 diabetes mellitus is associated with medication refill compliance of oral hypoglycemic agents., Research Design and Methods: The PHARMO Record Linkage System was used as data source for this study. Patients with newly treated type 2 diabetes mellitus were defined as subjects in whom oral hypoglycemic therapy was initiated between 1991 and 1998. We performed a matched case-control study in this cohort. Cases were patients who switched to insulin therapy. Date of switching in the case was defined as the index date. Controls were subjects still on oral therapy on the index date, matched on duration of diabetes and calendar time. We measured the medication refill compliance in the year starting 18 months before the index date and calculated various compliance indices., Results: In total, 411 cases and 411 matched controls were identified. Cases suffered more often from more severe comorbidity and used a higher number of oral hypoglycemic agents and concomitant non-diabetic drugs. The overall compliance rate did not differ significantly between cases and controls, the adjusted odds ratio (OR) was 1.3 (CI 95% 0.6-2.8). After performing multivariate logistic regression modeling, age at onset of diabetes, gender, comedication, combination therapy, and daily dosage frequency, were independently related to switching., Conclusions: We were unable to confirm the hypothesis that noncompliance with treatment is more prevalent in patients with secondary failure. Other variables, like comorbidity and disease-related factors seem to play a more important role in switching to insulin therapy.

Aims: The aim of the present study was to investigate whether use of specific antibiotic drugs decreases the risk of coronary heart disease in diabetes mellitus type 2 patients., Methods and Results: Data were obtained from the PHARMO Record Linkage System comprising pharmacy records and hospitalizations for all 450,000 residents of eight Dutch cities. In a nested case-control study among diabetes mellitus type 2 patients, 244 cases with a first hospitalization for coronary heart disease and 686 controls without coronary heart disease matched on age, sex, calendar time, and registration date in PHARMO RLS were selected. Use of antibiotic drugs among cases and controls was determined over 3 years prior to the event. Use of fluorquinolones for more than 14 days compared to no use of fluorquinolones was associated with a lower risk of coronary heart diseases (OR(adj)=0.30 (95%CI: 0.12-0.75)). No association between tetracycline, macrolide and lincosamide treatment, or other antibiotic drugs (penicillins, cephalosporines, sulphonamides and trimethoprim), and the risk of coronary heart disease was found., Conclusion: Our results suggest that treatment with fluorquinolones in doses commonly prescribed in routine clinical practice is associated with a reduction in the risk of coronary heart diseases among diabetes mellitus type 2 patients., (Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.)

Background: The aim of our study was to determine which factors are associated with switching from oral hypoglycaemic agents to insulin therapy in patients with type 2 diabetes mellitus in general practice., Methods: Longitudinal, observational study in a Dutch general healthcare centre. All pharmacologically treated patients with type 2 diabetes mellitus were included (n = 152). Comorbidity, laboratory results and medication use were obtained from the general practitioners' files., Results: A total of 31 (20.4%) patients switched from oral hypoglycaemic agents to insulin therapy; they were significantly younger at the onset of diabetes, 50.5 versus 57.7 years. Fasting blood glucose levels and HbA(1c) values were significantly higher after the switch compared with patients on oral treatment, 10.0 mmol/l versus 8.4 mmol/l and 8.8% versus 7.9%, respectively. Concerning comorbidity, they suffered more frequently from acute myocardial infarction, lipid disorders, depression, retinopathy and atrial fibrillation. Cardiovascular disease in general was more often present in patients who switched over to insulin, 77.4% versus 52.9% (OR 3.1; CI 1.2-7.6)., Conclusions: Patients who switch over to insulin therapy are younger at diagnosis, suffer from more health problems besides diabetes, especially cardiovascular disease, and have worse metabolic control, compared with users of oral hypoglycaemic agents.

Although patients with type 2 diabetes mellitus and cardiovascular disease share common risk factors, the link between these diseases remains largely unexplained. In this case-control study, the earlier use of cardiovascular drugs (before the diagnosis of diabetes) was investigated among cases with type 2 diabetes mellitus and controls without diabetes. Using the PHARMO database, we identified 4,864 patients who were prescribed oral hypoglycaemic agent (OHA) therapy between 1985-1998 in the Netherlands. For each case, two controls matched on age, sex and pharmacy were randomly selected. Controls had not received insulins or OHA therapy. There were 2,656 (55.0%) cases compared with 2,727 (28.1%) controls who used cardiovascular drugs at the start of OHA therapy. Cases had a 3.5-fold increased risk of cardiovascular drug use (OR(95% CI) = 3.5 [3.2-3.8]) compared to controls. Differences in cardiovascular drug use were noted as early as 7 years before the start of OHA therapy, distinguishing cases from controls. Our finding that patients with type 2 diabetes mellitus were more likely to receive treatment for cardiovascular disease several years before they start diabetes therapy supports the hypothesis of a common underlying mechanism of these two disorders and stresses the importance of the pre-diabetic state.

Objective: To investigate cardiovascular drug use and hospitalizations attributable to type 2 diabetes from 1 year before until 6 years after the start of oral antidiabetic therapy., Research Design and Methods: In this cohort study, 2,584 patients with type 2 diabetes were selected from the PHARMO Record Linkage System, comprising pharmacy records and hospitalizations for all 320,000 residents of six Dutch cities. Patients with type 2 diabetes were identified as incident oral antidiabetic drug users between 1992 and 1997. Nondiabetic subjects were 1:1-matched for age, sex, pharmacy, and index date and received no insulin, oral antidiabetic drugs, or glucose-testing supplies., Results: Patients with type 2 diabetes were more likely to use cardiovascular drugs (RR 1.28 [95% CI 1.23-1.34]) and to be hospitalized because of cardiovascular diseases (1.54 [1.33-1.78]) after the start of oral antidiabetic therapy than nondiabetic subjects. Differences between patients with type 2 diabetes and nondiabetic subjects lessened from 1 year before until 6 years after the start of oral antidiabetic therapy, reflected by decreasing attributable risks for diuretics, beta-blockers, calcium channel blockers, and cardiac and antithrombotic drugs. The difference in use of angiotensin-converting enzyme inhibitors and lipid-lowering drugs increased. Cardiovascular hospitalizations attributable to type 2 diabetes were approximately 50% in the years close to the start of oral antidiabetic treatment and decreased to approximately 33% in the following years., Conclusions: Although cardiovascular drug use and hospitalizations remained increased in patients with type 2 diabetes after the start of oral antidiabetic therapy, cardiovascular drug use attributable to type 2 diabetes decreased after the start of oral antidiabetic therapy, especially beta-blockers, whereas cardiovascular hospitalizations first decreased and then stabilized.