Diabetes, Obesity and Metabolism

Cover image for Vol. 18 Issue 8

Edited By: R. Donnelly and A. Garber

Impact Factor: 6.198

ISI Journal Citation Reports © Ranking: 2015: 13/131 (Endocrinology & Metabolism)

Online ISSN: 1463-1326

Review of Reviews 2016

Review of Reviews 2016: a virtual issue
Edited by: Richard IG Holt*

I. Introduction

The annual review of reviews has now become well established as part of the Diabetes, Obesity and Metabolism calendar. This freely available virtual issue of a selection of reviews accepted in the previous year continues to be a popular feature of the journal, at least judging by the number of downloads.

This year is my final year as Reviews Editor for Diabetes, Obesity and Metabolism. Having held the post since 2008, it is with sadness but some pride that I now hand over the reins to Dr Janet McGill of the Washington School of Medicine, St Louis, USA. My swansong is to compile this year’s review of reviews. During 2015, we have accepted a broad range of articles discussing different aspects of the management of diabetes, obesity and metabolism.

Insulin and its delivery remains an important area of development with new insulin analogues, biosimilar insulins and increasingly sophisticated insulin pumps (1-5). Other injectable therapies have also featured regularly with comparisons of different GLP-1 receptor agonists (6) and a greater appreciation of their effects beyond the pancreas (7). Glucagon may well be experiencing a resurgence in interest (8). Oral therapies for type 2 diabetes continue to spark debate and it is no surprise that in the year of the publication of the Empa Reg outcome study (9), there have been two reviews on SGLT-2 inhibitors (10;11).

A review of GPR40 agonists, a novel class of oral antidiabetes agents, has been published (12) while there has been on-going discussion about the cardiovascular safety of sulphonylureas more than 40 years after their introduction into clinical practice (13). Magnesium may also play an important role in carbohydrate metabolism and its replacement or supplementation may have a future place in the prevention of diabetes and its complications (14).

Although glycaemic management forms the bulk of the diabetes reviews, Diabetes, Obesity and Metabolism has a broader perspective, both looking to the future and also looking at treatment of diabetic complications and co-morbidities. A long term cure for type 1 diabetes through transplantation will depend on a better understanding of cellular biology of pancreatic cell and imaging of the pancreas, both of which have been subjects of reviews this year (15;16). Two articles have reviewed management of the diabetic foot from the perspective of vascular disease (17) and painful neuropathy (18). Gestational diabetes is the commonest medical condition in pregnancy and prevention is an important goal given its associated maternal and fetal morbidity (19;20). Within the field of obesity, Diabetes, Obesity and Metabolism has published reviews on a range of therapeutic options from lifestyle interventions (21) through pharmacological approaches (22) to bariatric surgery (23;24).

Selecting nine articles from this impressive list for the virtual issue is an invidious situation and inevitably I have had to leave out some excellent reviews that I would commend you to read.

However, in the end I have made a personal choice for inclusion. It is now nearly a century since the discovery of insulin by Banting and Best and it is amazing to see how far our understanding has come over that time. Nevertheless the ability to mimic the pattern of “normal” physiological insulin secretion remains elusive. The review by Home discusses how closely available and future insulin therapies and devices meet the ideal physiological insulin profile, and the challenges faced by healthcare professionals and people with diabetes in trying to achieve an optimum plasma insulin profile (1). GLP-1 receptor agonists are now firmly established as treatments for type 2 diabetes and obesity and are under investigation as a therapeutic option for type 1 diabetes. This class of drugs, however, is heterogeneous encompassing both human GLP-1 receptor analogues and exendin based molecules and both short and long acting treatments.

Given the widening array of available therapies, it is important that clinicians understand the differences between drugs in this class if they are to prescribe the most appropriate for their patients (6). Given the dual control of blood glucose, it has always surprised me that the manipulation glucagon has been ignored as a therapeutic option for diabetes but this may be changing with a resurgence in interest in glucagon. Lefebrvre and colleagues argue cogently that hyperglucagonaemia in diabetes can no longer be ignored or minimized (8).

I was at the EASD when the Empa Reg Outcome study was presented; after so many negative cardiovascular outcome trials had been published, the excitement was tangible as the impressive reductions in cardiovascular mortality were reported (9). The study has raised many questions; why is cardiovascular mortality reduced but there was little effect on myocardial infarction; what is the mechanism? Although the reviews in Diabetes, Obesity and Metabolism do not answer these questions, they provide insights into the effects of SGLT-2 inhbitors on metabolism and energy homeostasis (11) and how SGLT-2 inhibitors might be combined with DPP-4 inhibitors (10).

A cure for type 1 diabetes requires an understanding of how β-cells regenerate if transplantation is to become a realistic choice for people with diabetes. Co-transplantation of accessory non-islet cells with islet cells appears to improve the outcome of experimental islet transplantation and the latest insights are presented by Staels and colleagues (15).

As the rates of type 2 diabetes and its risk factors increases in the general population, so does the number of women with gestational diabetes as it shares many risk factors with type 2 diabetes. As insulin resistance increases during pregnancy, it unmasks those at later risk of type 2 diabetes as β-cell reserve is exceeded. Over 25 trials have been undertaken to assess whether it is possible to prevent diabetes and these are reviewed by Simmons (20).

Only four different interventions (healthy eating alone, healthy eating with physical activity, myoinositol supplementation and probiotic treatment) during pregnancy have shown a benefit but even these results have not been replicated. This suggests that a greater societal benefit may be achieved by intervening in women before they become pregnant. Lifestyle interventions are also needed to treat and prevent obesity although they only achieve modest reductions in weight in people with type 2 diabetes (21); however, bariatric surgery cannot be considered a viable option for most people with obesity, not least because of the problem of post-operative hypoglycaemia. The mechanisms and treatment of this challenging clinical problem are discussed in the final review in the virtual issue (24).

I hope you find this year’s virtual issue as enjoyable as previous years and that it will inspire you to contribute to Diabetes Obesity and Metabolism. Conflict of Interest RH was the Reviews Editor of Diabetes, Obesity and Metabolism from 2008-2015.

II. Selected Reviews

Plasma insulin profiles after subcutaneous injection: how close can we get to physiology in people with diabetes?
Home, Philip

A review of head-to-head comparisons of GLP-1 receptor agonists
Madsbad, Sten

Inhibiting or Antagonizing Glucagon: A Progress in Diabetes Care?
Lefebvre, Pierre

Energy balance and metabolic changes with SGLT2 inhibition
Wilding, John

Potential for Combination of Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Co-Transporter-2 Inhibitors for the Treatment of Type 2 Diabetes
Sharma, Morali

Accessory cells for beta cell transplantation
De Leu, Nico

Prevention of Gestational Diabetes Mellitus: Where are we now?
Simmons, David

Effectiveness of lifestyle-based weight loss interventions for adults with type 2 diabetes: A systematic review and meta-analysis
Reeves, Marina

Hypoglycemia following gastric bypass: mechanisms and treatment
Ritz, Patrick

III. Reference List

(1) Home PD. Plasma insulin profiles after subcutaneous injection: how close can we get to physiology in people with diabetes? Diabetes Obes Metab 2015 Nov;17(11):1011-20.

(2) Dailey G, Lavernia F. A review of the safety and efficacy data for insulin glargine 300 units/ml, a new formulation of insulin glargine. Diabetes Obes Metab 2015 Dec;17(12):1107-14.

(3) Heinemann L, Home PD, Hompesch M. Biosimilar insulins: guidance for data interpretation by clinicians and users. Diabetes Obes Metab 2015 Oct;17(10):911-8.

(4) Russell-Jones D, Danne T, Hermansen K, Niswender K, Robertson K, Thalange N, et al. Weight-sparing effect of insulin detemir: a consequence of central nervous system-mediated reduced energy intake? Diabetes Obes Metab 2015 Oct;17(10):919-27.

(5) Davis T, Salahi A, Welsh JB, Bailey TS. Automated insulin pump suspension for hypoglycaemia mitigation: development, implementation and implications. Diabetes Obes Metab 2015 Dec;17(12):1126-32.

(6) Madsbad S. A review of head-to-head comparisons of GLP-1 receptor agonists. Diabetes Obes Metab 2015 Oct 29.

(7) Smits MM, Tonneijck L, Muskiet MH, Kramer MH, Cahen DL, van Raalte DH. Gastrointestinal actions of GLP-1 based therapies: glycaemic control beyond the pancreas. Diabetes Obes Metab 2015 Oct 24.

(8) Lefebvre PJ, Paquot N, Scheen AJ. Inhibiting or antagonizing glucagon: making progress in diabetes care. Diabetes Obes Metab 2015 Aug;17(8):720-5.

(9) Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015 Nov 26;373(22):2117-28.

(10) Sharma MD. Potential for combination of dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors for the treatment of type 2 diabetes. Diabetes Obes Metab 2015 Jul;17(7):616-21.

(11) Rajeev SP, Cuthbertson DJ, Wilding JP. Energy balance and metabolic changes with SGLT2 inhibition. Diabetes Obes Metab 2015 Sep 25.

(12) Mancini AD, Poitout V. GPR40 agonists for the treatment of type 2 diabetes: life after 'TAKing' a hit. Diabetes Obes Metab 2015 Jul;17(7):622-9.

(13) Abdelmoneim AS, Eurich DT, Light PE, Senior PA, Seubert JM, Makowsky MJ, et al. Cardiovascular safety of sulphonylureas: over 40 years of continuous controversy without an answer. Diabetes Obes Metab 2015 Jun;17(6):523-32.

(14) Mooren FC. Magnesium and disturbances in carbohydrate metabolism. Diabetes Obes Metab 2015 Sep;17(9):813-23.

(15) Staels W, De Groef S., Heremans Y, Coppens V, Van Gassen N., Leuckx G, et al. Accessory cells for beta-cell transplantation. Diabetes Obes Metab 2015 Aug 20.

(16) Laurent D, Vinet L, Lamprianou S, Daval M, Filhoulaud G, Ktorza A, et al. Pancreatic beta-cell imaging in humans: fiction or option? Diabetes Obes Metab 2015 Jul 31.

(17) Forsythe RO, Brownrigg J, Hinchliffe RJ. Peripheral arterial disease and revascularization of the diabetic foot. Diabetes Obes Metab 2015 May;17(5):435-44.

(18) Javed S, Alam U, Malik RA. Burning through the pain: treatments for diabetic neuropathy. Diabetes Obes Metab 2015 Dec;17(12):1115-25.

(19) Isolauri E, Rautava S, Collado MC, Salminen S. Role of probiotics in reducing the risk of gestational diabetes. Diabetes Obes Metab 2015 Aug;17(8):713-9.

(20) Simmons D. Prevention of gestational diabetes mellitus: Where are we now? Diabetes Obes Metab 2015 Sep;17(9):824-34.

(21) Terranova CO, Brakenridge CL, Lawler SP, Eakin EG, Reeves MM. Effectiveness of lifestyle-based weight loss interventions for adults with type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab 2015 Apr;17(4):371-8.

(22) Fujioka K. Current and emerging medications for overweight or obesity in people with comorbidities. Diabetes Obes Metab 2015 Nov;17(11):1021-32.

(23) Coen PM, Goodpaster BH. A role for exercise after bariatric surgery? Diabetes Obes Metab 2015 Jul 31.

(24) Ritz P, Vaurs C, Barigou M, Hanaire H. Hypoglycaemia following gastric bypass: mechanisms and treatment. Diabetes Obes Metab 2015 Oct 28.

*Richard IG Holt
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, UK
Address for Correspondence: Professor Richard IG Holt, IDS Building (MP887), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
Tel: +44 23 8120 4665
Fax: +44 23 8120 4221
E-mail: R.I.G.Holt@southampton.ac.uk