The primary glucose-lowering effect of metformin resides in the gut, not the circulation

John B. Buse et al.  Diabetes Care.  Doi: 10.2337/dc15-0488

Until the publication of UKPDS results in 1998, there had been scepticism of how effective a treatment metformin (MF) was for glucose-lowering in type 2 diabetes (T2DM). Some even suggested its main effect was to enhance dietary compliance by inducing nausea. Today, we regard metformin as a ‘wonderdrug’, first in all diabetes guidelines and cheap to boot, but we still don’t really understand how it works. Intriguingly, there has previously been a small study showing that intravenous metformin had no impact on hepatic glucose production or peripheral glucose utilisation. These studies lend more weight to the hypothesis that the primary effect of MF is in the bowel. The authors first demonstrated that, dose-for-dose, the bioavailability of delayed-release MF (MFDR) was around 50% that of the standard and extended release MF preparations. They then showed a 40% higher potency in glucose-lowering of MFDR after 12 weeks administration in T2DM. MFDR has been formulated to deliver drug to the lower bowel with lower plasma exposure. At the same time, it is producing a better glycaemic response, consistent with a bowel-mediated mechanism of action for MF.

http://care.diabetesjournals.org/content/early/2015/08/07/dc15-0488.abstract

 

Insulin administered by needle-free jet injection corrects marked hyperglycaemia faster in overweight or obese patients with diabetes

Helena M. de Wit et al. Diabetes, Obesity and Metabolism. Doi: 10.1111/dom.12550

Insulin administration by jet injection is a needle-free alternative to conventional injections, which delivers insulin at high velocity (typically >100m/s) across the skin, dispensing it over a larger subcutaneous area than insulin injected with a needle. This method of insulin administration, first developed in the 1950s, is available in the UK and may be considered for needle phobic diabetic patients or any patient that would like the choice to take insulin without a needle. The device known as the InsujetTM, which was also assessed in this study, is bigger than the typical ‘insulin pen’ and it is more complex to use. Users, however, report less discomfort and the larger distribution of insulin in the subcutaneous tissue, leads to a more rapid onset of action. The authors hypothesised that jet injections would lead to a more rapid resolution of marked hyperglycaemia (18-23mmol/L) than subcutaneous administration of rapid-acting insulin analogue (aspart) and this was confirmed. Whether this is clinically relevant is doubtful and it will be interesting to see how it compares with the new ultra-fast acting insulin analogue currently in development.

http://onlinelibrary.wiley.com/doi/10.1111/dom.12550/abstract

 

Risk of atrial fibrillation in diabetes mellitus: A nationwide cohort study

Jannik L Pallisgaard et al. Preventative Cardiology. Doi: 10.1177/2047487315599892

The aim was to investigate the risk of atrial fibrillation (AF) in patients with diabetes in Denmark. Through nationwide registries the authors included people 18 years of age and without prior AF from 1996 to 2012. The cohort included 5,081,087 persons, 4,827,713 (95%) in the background population and 253,374 (5%) in the diabetes group. Incidence rates of AF per 1000 person years were stratified in four age groups: 18 to 39, 40 to 64, 65 to 74 and 75 to 100 years. Adjusted incidence rate ratios in the diabetes group were 2.34 (confidence intervals; 1.52–3.60), 1.52 (1.47–1.56), 1.20 (1.18–1.23) and 0.99 (0.97–1.01) in the four age groups, leading to the headline regarding screening. Whilst screening for AF is becoming feasible with mobile devices, there is an alternative interpretation of these data. First, in the very elderly diabetes cohort, the risk of AF was no different to that of the background population. Second, the youngest diabetes cohort had a lower incidence of AF than the background population aged over 40 years. Is screening justified? – I don’t think so.

http://cpr.sagepub.com/content/early/2015/08/07/2047487315599892.abstract

 

Hypoglycaemia in adults with insulin-treated diabetes in the UK: self-reported frequency and effects

M. Frier, M. M. Jensen and B. D. Chubb. Diabetic Medicine. Doi: 10.1111/dme.12878

Two major issues that affect insulin treated patients are weight gain and hypoglycaemia. With regard to the latter, many patients will do anything to avoid it, even if this means sacrificing tight glycaemic control. Whilst health care professionals usually focus on severe hypoglycaemia requiring third party assistance, non-severe hypoglycaemia which can be self treated by the patient can still be debilitating and have a significant impact on a patient’s quality of life. This UK based study quantified the self-reported frequency of non-severe hypoglycaemia and its effects in adults with insulin-treated diabetes. More than 1000 adults with insulin treated diabetes (Type 1 and Type 2) reported the frequency of hypoglycaemia. Type 1 patients had a mean of 2.4 episodes whilst Type 2 had a mean of 0.8 episodes per week. The consequences of these hypos including fatigue and poor concentration was significant especially with nocturnal hypos. Hypoglycaemia was followed by a period of looser control in most patients. The effect on employment was also significant with time lost. Of interest, most of these episodes were not reported to their health care professional reinforcing the under recognition that these episodes have on quality of life and overall control.

http://onlinelibrary.wiley.com/doi/10.1111/dme.12878/abstract

 

Fasting until noon triggers increased postprandial hyperglycemia and impaired insulin response after lunch and dinner in individuals with type 2 diabetes

Daniela Jakubowicz et al. Diabetes Care. Doi: 10.2337/dc15-0761

Breakfast – most important meal of the day or something to miss with minimal impact on glycaemia? Missing breakfast has been consistently linked with post prandial hyperglycaemia and elevated HbA1c in patients with Type 2 diabetes. This elegant cross over study (albeit of only 22 patients) looked at the metabolic changes resulting from a missed breakfast. Compared with patients who had breakfast, patients who missed it had significantly higher lunch and dinner post prandial glucose, free fatty acid and glucagon whilst their GLP1 and insulin levels were lower. Furthermore, the insulin peak was delayed 30 min after lunch and dinner when breakfast was missed. Overall, missing breakfast resulted in metabolic changes which persisted throughout the day. This study does reinforce the importance of breakfast on glycaemic control although the type of food eaten at the start of the day will also have an impact, for example calorie content, glycaemic index etc – not examined in this study.

http://care.diabetesjournals.org/content/early/2015/07/01/dc15-0761.short