Modern times

Diabetes reflects the society it afflicts, and the spreading global epidemic is a consequence of a more affluent lifestyle, longer life expectancy and better medical care as well as increasing obesity. Epidemiologists have charted this epidemic and others have aggravated it by lowering the threshold for its diagnosis. More controversially, the concept of prediabetes, a clinical designation that implies increased risk of both diabetes and cardiovascular disease, has been reintroduced. Critics dispute the utility of this diagnosis. Clinical practice has been dominated by aggressive marketing of new drugs for diabetes. Incretin-based therapies appear most promising among these, but outcome studies are still awaited, together with evidence of long term safety. In research, many of the same frustrations persist: for example, genome-wide searches have identified many more diabetes genes in type 1 and type 2 diabetes, but translational benefits have been few. Many trials of immunomodulation have been undertaken in type 1 diabetes, but with limited success. Closed loop glucose control systems are getting steadily better but a considerable cost. Islet cell transplantation has been increasingly successful, but has been limited by cost and islet availability: the quest for an endless supply of engineered cells continues. Happily, the prognosis of treated diabetes continues to improve.

The diabetes epidemic

The second half of C20 saw the continued growth of diabetes, now considered as a global epidemic. This reflects a more affluent lifestyle, longer life expectancy and better medical care as well as increasing obesity in more affluent populations. Diabetes epidemiology not only charted this epidemic, but enhanced it by lowering the glucose threshold for its diagnosis. The limiting factor has - and will probably always be - the lack of a clear risk threshold between "diabetes" and "non-diabetes". To set the threshold too high is to expose people to avoidable risk; set it too low and you overdiagnose and overtreat. The controversy seems set to continue.

Prediabetes

More controversially, the terms prediabetes, first introduced in 1933 and intermittently in fashion since then, was officially reintroduced by the American Diabetes Association. See Prediabetic states : IFG and IGT. The potential benefits include identification of dysglycaemia at a stage at which progression to overt diabetes could be prevented by lifestyle and other measures, and this would also allow other cardiovascular risk factors to be addressed. Potential disadvantages include overdiagnosis and "labelling" of individuals, some 50% of whom may never actually develop diabetes. Furthermore, the majority of people affected are elderly, and thus at relatively low risk of long term complications, and the evidence base for intervention on a population basis is lacking. Critics have considered this as evidence of "guild" behaviour by diabetes organizations anxious to boost public awareness of the condition, backed by pharmaceutical companies eager to extend their market[1].

Technology

The technology of diabetes management continues to improve with the introduction of better glucose sensors and control algorithms. The long term goal of "hands-off" glucose control by implanted or telemetric devices is still limited by lack of reliable and robust long term glucose monitoring systems. See Information technology in DM

Medication

Only three leading therapies were available for the glucose management of diabetes until the 1990s, human insulin, sulfonylureas and metformin; metformin was not available in the USA until 1995. There has been a rapid proliferation of new therapies since then, including Insulin analogues, Thiazolidinediones/ PPAR (TZDs), GLP-1 agonists and DPP-4 inhibitors (Incretin based treatment), and SGLT-2 inhibitors. Although the insulin analogues appear to benefit some patients, evidence-based reviews are unanimous that they should be considered as second-line choices for therapy. Two TZDs -troglitazone and rosiglitazone have been withdrawn from use for safety reasons. Pioglitazone remains an option, but is less widely used than previously. The incretin-based therapies are now widely-used, but await evidence of long-term benefit from outcome studies. The optimal use and sequence of therapies for type 2 diabetes following introduction of metformin remains uncertain, and the cost of new medications for diabetes continues to escalate at a rate far exceeding their demonstrated benefits[2].

Prognosis

Happily, the outlook for people with diabetes continues to improve[3]. Some have seen this as proof of the benefits of new glucose-lowering therapies, but is might also relate to lead-time bias (earlier diagnosis may appear to lengthen survival without necessarily changing the natural history of a disease), more effective implementation of strategies of cardiovascular protection, or to the declining mortality of cardiovascular disease in the population as a whole.

References

  1. ^ Yudkin JS et al. Intensified glucose control in type 2 diabetes - whose agenda? Lancet 2011;377:1220-2

  2. ^ Zhuo X et al. Change in medical spending attributable to diabetes: national data from 1987 to 2011. Diabetes Care 2015;38(4):581-7

  3. ^ Gregg EW et al. Changes in diabetes-related complications in the United States. New Engl J Med 2014;371:286-7

Comments

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    Pierre Lefèbvre added a compliment on 19 June 2015 at 10:13AM
    No one can beat Edwin in making so many wise and critical comments in so few words
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