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OBJECTIVE--The antidiabetic properties of metformin are mediated through its ability to activate the AMP-activated protein kinase (AMPK). Activation of AMPK can suppress tumor formation and inhibit cell growth in addition [...]

OBJECTIVE--Metformin is actively transported into the liver by the organic cation transporter (OCT)1 (encoded by SLC22A1). In 12 normoglycemic individuals, reduced-function variants in SLC22A1 were shown to decrease the ability of metformin to reduce glucose excursion in response to oral glucose. We assessed the effect of two common loss-of-function polymorphisms in SLC22A1 on metformin response in a large cohort of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS--The Diabetes Audit and Research in Tayside Scotland (DARTS) database includes prescribing and biochemistry information and clinical phenotypes of all patients with diabetes within Tayside, Scotland, from 1992 onwards. R61C and 420del variants of SLC22A1 were genotyped in 3,450 patients with type 2 diabetes who were incident users of metformin. We assessed metformin response by modeling the maximum A1C reduction in 18 months after starting metformin and investigated whether a treatment target of A1C RESULTS--A total of 1,531 patients were identified with a definable metformin response. R61C and 420del variants did not affect the initial A1C reduction (P = 0.47 and P = 0.92, respectively), the chance of achieving a treatment target (P = 0.83 and P = 0.36), the average A1C on monotherapy up to 42 months (P = 0.44 and P = 0.75), or the hazard of monotherapy failure (P = 0.85 and P = 0.56). CONCLUSIONS--The SLC22A1 loss-of-function variants, R61C and 420del, do not attenuate the A1C reduction achieved by metformin in patients with type 2 diabetes., Metformin is recommended as first-line oral treatment in the joint American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) guidelines on the treatment of type 2 diabetes (1) [...]

OBJECTIVE--To derive and validate an absolute risk algorithm for major coronary heart disease (CHD) events in the U.K population with type 2 diabetes. RESEARCH DESIGN AND METHODS--A population cohort with [...]

A retrospective cohort study of resource use OBJECTIVE -- To compare the hospitalizations of people with type 1 and type 2 diabetes with those of the nondiabetic population of Tayside, [...]

There are few reliable data on the morbidity and mortality following first major lower extremity amputation (LEA) in diabetic and non diabetic subjects. We used the DARTS/MEMO databases to identify [...]

There are no data on the population-based adherence to oral hypoglycaemic drugs (OHD's) in the community. We studied all subjects in Tayside Scotland (population 392,000; type 2 diabetes [DM2] = [...]