Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial

Objectives To study the effect of insulin treatment in combination with metformin or an insulin secretagogue, repaglinide, on glycaemic regulation in non-obese patients with type 2 diabetes

Effect of Adjunct Metformin Treatment in Patients with Type-1 Diabetes and Persistent Inadequate Glycaemic Control. A Randomized Study

Despite intensive insulin treatment, many patients with type-1 diabetes (T1DM) have longstanding inadequate glycaemic control. Metformin is an oral hypoglycaemic agent that improves insulin action in patients with type-2 diabetes. We investigated the effect of a one-year treatment with metformin versus placebo in patients with T1DM and persistent poor glycaemic control.One hundred patients with T1DM, preserved hypoglycaemic awareness and HaemoglobinA(1c) (HbA(1c)) > or = 8.5% during the year before enrolment entered a one-month run-in on placebo treatment. Thereafter, patients were randomized (baseline) to treatment with either metformin (1 g twice daily) or placebo for 12 months (double-masked). Patients continued ongoing insulin therapy and their usual outpatient clinical care. The primary outcome measure was change in HbA(1c) after one year of treatment. At enrolment, mean (standard deviation) HbA(1c) was 9.48% (0.99) for the metformin group (n = 49) and 9.60% (0.86) for the placebo group (n = 51). Mean (95% confidence interval) baseline-adjusted differences after 12 months with metformin (n = 48) versus placebo (n = 50) were: HbA(1c), 0.13% (-0.19; 0.44), p = 0.422; Total daily insulin dose, -5.7 U/day (-8.6; -2.9), p<0.001; body weight, -1.74 kg (-3.32; -0.17), p = 0.030. Minor and overall major hypoglycaemia was not significantly different between treatments. Treatments were well tolerated.In patients with poorly controlled T1DM, adjunct metformin therapy did not provide any improvement of glycaemic control after one year. Nevertheless, adjunct metformin treatment was associated with sustained reductions of insulin dose and body weight. Further investigations into the potential cardiovascular-protective effects of metformin therapy in patients with T1DM are warranted.ClinicalTrials.gov NCT00118937

Agreement Between Fasting and Postprandial LDL Cholesterol Measured with 3 Methods in Patients with Type 2 Diabetes Mellitus

BACKGROUND: LDL cholesterol (LDL-C) is a modifiable cardiovascular disease risk factor. We used 3 LDL-C methods to study the agreement between fasting and postprandial LDL-C in type 2 diabetes (T2DM) patients. METHODS: We served 74 T2DM patients a standardized meal and sampled blood at fasting and 1.5, 3.0, 4.5, and 6.0 h postprandially. We measured LDL-C by use of modified beta quantification (MBQ), the Friedewald equation (FE), and a direct homogeneous assay (DA). We evaluated agreement using 95% limits of agreement (LOA) within +/- 0.20 mmol/L (+/- 7.7 mg/dL). RESULTS: LDL-C concentrations at all postprandial times disagreed with those at fasting for all methods. In 66 patients who had complete measurements with all LDL-C methods, maximum mean differences (95% LOA) in postprandial vs fasting LDL-C were -0.16 mmol/L (-0.51; 0.19) [-6.2 mg/dL (-19.7; 7.3)] with MBQ at 3 h; -0.36 mmol/L (-0.89; 0.17) [-13.9 mg/dL (-34; 6.6)] with FE at 4.5 h; and -0.24 mmol/L (-0.62; 0.05) [-9.3 mg/dL (-24; 1.9)] with DA at 6.0 h. In postprandial samples, FE misclassified 38% of patients (two-thirds of statin users) into lower Adult Treatment Panel III (ATP III) risk categories. Greater disagreement between fasting and postprandial LDL-C was observed in individuals with postprandial triglyceride concentrations >2.08 mmol/L (>184 mg/dL) and in women (interactions: P <= 0.038). CONCLUSIONS: Differences up to 0.89 mmol/L (34 mg/dL) between fasting and postprandial LDL-C concentrations, with postprandial LDL-C concentrations usually being lower, were found in T2DM by 3 different LDL-C methods. Such differences are potentially relevant clinically and suggest that, irrespective of measurement method, postprandial LDL-C concentrations should not be used to assess cardiovascular disease risk. (C) 2010 American Association for Clinical Chemistr

MYPLAN -mobile phone application to manage crisis of persons at risk of suicide: Study protocol for a randomized controlled trial

Background: Persons with a past episode of self-harm or severe suicidal ideation are at elevated risk of self-harm as well as dying by suicide. It is well established that suicidal ideation fluctuates over time. Previous studies have shown that a personal safety plan can assist in providing support, when a person experiences suicide ideation, and help seeking professional assistance if needed. The aim of the trial is to determine whether a newly developed safety mobile app is more effective in reducing suicide ideation and other symptoms, compared to a safety plan on paper. Methods/design: The trial is designed as a two-arm, observer-blinded, parallel-group randomized clinical superiority trial, where participants will either receive: (1) Experimental intervention: the safety plan provided as the app MyPlan, or (2) Treatment as Usual: the safety plan in the original paper format. Based on a power calculation, a total of 546 participants, 273 in each arm will be included. They will be recruited from Danish Suicide Prevention Clinics. Both groups will receive standard psychosocial therapeutic care, up to 8-10 sessions of supportive psychotherapy. Primary outcome will be reduction in suicide ideation after 12 months. Follow-up interviews will be conducted at 3, 6, 9, and 12 months after date of inclusion. Discussion: A safety plan is a mandatory part of the treatment in the Suicide Prevention Clinics in Demark. There are no studies investigating the effectiveness of a safety plan app compared to a safety plan on paper on reducing suicide ideation in patients with suicide ideation and suicidal behavior. The trial will gain new knowledge of whether modern technology can augment the effects of traditional personalized safety planning. Trial registration: ClinicalTrials.gov, NCT02877316. Registered on 19 August 2016

Elevated transferrin saturation and risk of diabetes:Three population-based studies

OBJECTIVE: We tested the hypothesis that elevated transferrin saturation is associated with an increased risk of any form of diabetes, as well as type 1 or type 2 diabetes separately. RESEARCH DESIGN AND METHODS: We used two general population studies, The Copenhagen City Heart Study (CCHS, N = 9,121) and The Copenhagen General Population Study (CGPS, N = 24,195), as well as a 1:1 age- and sex-matched population-based case-control study with 6,129 patients with diabetes from the Steno Diabetes Centre and 6,129 control subjects, totaling 8,535 patients with diabetes and 37,039 control subjects. RESULTS: In the combined studies, odds ratios in those with transferrin saturation ≥50% vs. <50% were 2.1 (95% CI 1.3–3.4; P = 0.003) for any form of diabetes; 2.6 (1.2–5.6; P = 0.01) for type 1 diabetes; and 1.7 (1.4–2.1; P = 0.001) for type 2 diabetes. CONCLUSIONS: Elevated transferrin saturation confers a two- to threefold increased risk of developing any form of diabetes, as well as type 1 and type 2 diabetes separately

Total mortality by elevated transferrin saturation in patients with diabetes

OBJECTIVE: It is not known to what extent iron overload predicts prognosis in patients with diabetes after diagnosis or whether iron overload is a risk factor independent of the HFE genotype. We investigated total and cause-specific mortality according to increased transferrin saturation (≥50 vs. <50%), whether mortality is driven by the HFE genotype, and whether early measurement of transferrin saturation helps to predict mortality outcome. RESEARCH DESIGN AND METHODS: Cohort 1 included patients with late-onset type 1 diabetes (n = 716) with a cross-sectional measurement of transferrin saturation and HFE genotype. Cohort 2 included consecutively recruited patients with any diabetes (n = 6,120), transferrin saturation measurement at referral, and HFE genotype if transferrin saturation was above 50%. RESULTS: In cohort 1, the hazard ratio for total mortality was 2.3 (95% CI 1.3–3.9; P = 0.002) and for cause-specific mortality by neoplasms was 5.8 (2.4–14; P = 0.00007) in patients with transferrin saturation ≥50 vs. <50%. Excluding genotypes C282Y/C282Y and C282Y/H63D gave similar results. The hazard ratio for total mortality was 4.0 (1.2–13; P = 0.01) and for cause-specific mortality by neoplasms was 13 (3.6–49; P = 0.0001) in patients with C282Y/C282Y versus wild type. In cohort 2, total mortality was not different in patients with transferrin saturation ≥50 vs. <50%. In patients with late-onset type 1 diabetes and transferrin saturation ≥50%, the hazard ratio for total mortality was 0.4 (0.2–0.9; P = 0.03) in cohort 2 versus cohort 1. CONCLUSIONS: Increased transferrin saturation and HFE genotype C282Y/C282Y predict total mortality in patients with late-onset type 1 diabetes, and increased transferrin saturation after diagnosis is an independent risk factor. Early measurement of transferrin saturation in these patients leading to early intervention improves life expectancy