Metformin use is associated with cobalamin (vitamin B12) deficiency. However, the influence of both duration and dose of metformin is unclear. Studies using holotranscobalamin, a marker for cellular cobalamin deficiency, are scarce. We therefore investigated the prevalence of cobalamin deficiency in type 2 diabetes patients using both markers, and its relation with duration and dose of metformin use. This cross-sectional study among 550 type 2 diabetes patients using metformin (mean daily dose 1,306 mg; mean duration 64 months) was conducted in four primary care centers in Utrecht, the Netherlands. Cobalamin and holotranscobalamin concentrations were measured at the annual diabetes check. Detailed information on metformin use and confounding variables was collected from medical records. The prevalence of a cobalamin deficiency was 28.1 %, while a holotranscobalamin deficiency occurred in 3.9 % of the patients. Adjusting for multiple confounders, a 1 mg/day increase in daily metformin dose was associated (p < 0.001) with 0.042 (95 % CI -0.060, -0.023) decrease in cobalamin concentrations. Similarly, a 10 g increase of cumulative metformin dose was associated (p = 0.006) with -0.070 (-0.12, -0.021) lower cobalamin concentrations after adjustment for confounders. Duration of metformin use was not associated with cobalamin concentrations after multivariable adjustment. Similar results were observed for holotranscobalamin. Cobalamin deficiency occurs frequently among diabetes patients using metformin. A higher daily and cumulative doses of metformin were strongly associated with lower cobalamin and holotranscobalamin concentrations, while duration was not. It is thus important to account for metformin dose in recommendations for screening for cobalamin deficiency.

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Given that there are indications of overtreatment in older patients with type 2 diabetes in both the United States and Europe, we assessed the level of personalized diabetes treatment for older patients in primary care, focusing on overtreatment. Based on Dutch guidelines individuals aged ≥70 years were classified into 3 glycated haemoglobin (HbA1c) treatment target groups: 7% (53 mmol/mol), 7.5% (58 mmol/mol) and 8% (64 mmol/mol). In our cohort of 1002 patients (n = 319 aged ≥70 years), the 165 patients with HbA1c targets >7% had more micro- and macrovascular complications, more often used ≥5 medicines and were more often frail compared with those with an HbA1c target ≤7%. Of these 165 patients, 64 (38.8%) were overtreated; that is, 20% of all people aged ≥70 years. The majority of overtreated people were frail and used ≥5 medicines. Hypoglycaemia occurred in 20.3% of these patients and almost 30% reported accidents involving falls. Personalized treatment in older people with type 2 diabetes is not common practice. A substantial number of older people are overtreated, with probable harmful consequences. To prevent overtreatment, definition of lower HbA1c limits might be helpful.

The anti-inflammatory activity of hamamelis distillate has been evaluated with respect to drug concentration (0.64 mg/2.56 mg hamamelis ketone/100 g) and the effect of the vehicle (O/W emulsion with/without phosphatidylcholine (PC) in an experimental study. The effects were compared with those of chamomile cream, hydrocortisone 1% cream and 4 base preparations. Erythema was induced by UV irradiation and cellophane tape stripping of the horny layer in 24 healthy subjects per test. Skin blanching was quantified by visual scoring and chromametry. Drug effects were compared with one another and with an untreated control area, as well as with any action due to the vehicle. UV-induced erythema at 24 h was suppressed by low dose hamamelis PC-cream and hydrocortisone cream. Hydrocortisone appeared superior to both hamamelis vehicles, hamamelis cream (without PC) and chamomile cream. The latter preparation was also less potent than hamamelis PC-cream. Erythema 4 to 8 h after the stripping of the horny layer was suppressed by hydrocortisone (P < or = 0.05). Inflammation was also less pronounced following low dose hamamelis PC-cream and chamomile cream. Hamamelis PC-cream, however, appeared less potent than hydrocortisone. In general, visual scoring was more discriminatory than chromametry. The results have demonstrated an anti-inflammatory activity of hamamelis distillate in a PC-containing vehicle. A fourfold increase of drug concentration, however, did not produce an increase in activity.

See editorial comment on page 1107Background: Therapeutic inertia is considered to be an obstacle to effective blood pressure (BP) control.Aims: To identify patient characteristics associated with therapeutic inertia in patients with hypertension managed in primary care and to assess reasons not to intensify therapy.Methods: A Dutch cohort study was conducted using electronic health record data of patients registered in the Julius General Practitioners' Network (n ¼ 530 564). Patients with a diagnosis of hypertension, SBP at least 140 and/or DBP at least 90 mmHg, and one or two BP-lowering drug(s) were included. Therapeutic inertia was defined as not undertaking therapeutic action in follow-up despite uncontrolled BP. Multivariable logistic regression was used to identify characteristics associated with inertia. Furthermore, an exploratory survey was performed in which general practitioners of 114 patients were asked for reasons not to intensify treatment.Results: We identified 6400 (10% of all patients with hypertension) uncontrolled patients on one or two BPlowering drugs. Therapeutic inertia was 87%, similar in men and women. Older age, lower systolic, diastolic and near-target SBP, and diabetes were positively associated, while renal insufficiency and heart failure were inversely related to inertia. General practitioners did not intensify therapy because they first, considered office BP measurements as nonrepresentative (27%); second, waited for next BP readings (21%); third, wanted to optimize lifestyle first (19%). Eleven percent of patients explicitly did not want to change treatment. Conclusion:Therapeutic inertia is common in primary care patients with uncontrolled hypertension. Older age, and closer to target BP, but also concurrent diabetes were associated with inertia.

The objective of this study was to assess health related quality of life (QOL) in patients with type I diabetes mellitus (DMT1) and to compare their QOL with the QOL of persons of comparable age in the general population. Furthermore we wanted to investigate which factors mostly influence QOL. In a Dutch cohort of 281 patients with DMT1 QOL was assessed using two generic instruments: the EuroQol and the RAND-36. We performed regression analyses to investigate relationships between several demographic (e.g. sex, age, marital status) and diabetes-specific variables (e.g. HbA1c, frequency of insulin injection, presence of acute and chronic complications) and QOL. The Spearman rank correlations between RAND-36 domains and EuroQol were analysed. RAND-36 results showed, for almost all domains, a QOL comparable with persons of comparable age in the general population. In contrast the QOL measured with the EuroQol was lower for subjects with DMT1. Hyperglycaemic complaints and macrovascular complications had a profound negative influence on QOL. Most correlations between the RAND-36 results and the EuroQol results corresponded with our expectations. Longitudinal data and comparison with results of several diabetes-specific questionnaires should help to establish which instrument might be most appropriate to measure QOL in patients with DMT1.

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Cobalamin deficiency was associated with an increased risk of depression and worse cognitive performance, while holoTCII was not. Screening for cobalamin deficiency may be warranted in diabetes patients using metformin. Physicians should consider a cobalamin deficiency in diabetes patients using metformin with a depression or cognitive decline.