Type 2 Diabetes Excess Mortality at 'Historical Low' Overall

Marlene Busko

October 29, 2015

Adult patients in Sweden with type 2 diabetes had a 15% greater adjusted risk of dying within 5 years compared with same-aged individuals in the general public, which is a "historical low," Mauro Tancredi, MD, from the University of Gothenburg, Sweden, and colleagues report in a study published in the October 29 issue of the New England Journal of Medicine.

However, the study also showed that rates of all-cause or cardiovascular death were substantially higher in diabetic patients with worsening glycemic control or impaired renal function or those younger than 55.

As senior author Dr Marcus Lind (University of Gothenburg) explained to Medscape Medical News in an email, "detecting type 2 diabetes early and achieving good risk-factor control from diagnosis and onward was associated with low mortality, close to that of the general population for many patients with type 2 diabetes."

Thus, it is important to "maintain good glycemic control from the onset of the disease" and avoid hyperglycemia, which can lead to diabetic nephropathy and other complications.

Moreover, he said, "extra focus is needed on individuals younger than approximately 60 years, since there was a greater excess mortality [near that age], even if the glucose control was not very poor and no major renal complications existed."

In younger patients with type 2 diabetes, strict control of blood pressure, prescription of statins, aiming for good glycemic control, and avoiding microalbuminuria are probably not enough to lower the mortality rate to that of the general population, Tancredi and colleagues write. "Smoking cessation, increased physical activity, and the development of new cardiovascular-protective drugs, such as alternative lipid-lowering medications for persons who cannot take statins, may further improve outcomes," they suggest.

Glycemic Control, Kidney Function, and Mortality Risk

Lind and colleagues recently reported that in patients with type 1 diabetes, mortality increased markedly with poor glycemic control, and even patients with a recommended HbA1c <6.9%, had a risk of death that was twice that of the general population (N Engl J Med. 2014;371:1972-1982).

The current study aimed to evaluate the excess risk of death in patients with type 2 diabetes vs individuals in the general population and see how this risk varied with glycemic control and renal complications in patients aged 20 to 90-plus who were registered in the Swedish National Diabetes Register from 1998 to 2011.

They identified 435,369 patients with type 2 diabetes and randomly selected five controls for each patient from the general population in Sweden, matched for age, sex, and county.

The participants had a mean age of 66, and 45% were women. At baseline, patients in the diabetes group had a mean HbA1c of 7.1% and had had diabetes for a mean of 5.7 years.

During a mean follow-up of 4.6 years in the diabetes group and 4.8 years in the control group, 17.7% of patients with diabetes and 14.5% of controls died.

Most deaths were due to cardiovascular causes; patients with diabetes were more likely to die from CVD (7.9% vs 6.1%). Another 1.8% of patients with diabetes died from diabetes-related causes (including hypoglycemia and renal, vascular, and eye complications).

Older patients with normal kidney function and well-controlled type 2 diabetes had better survival than age-matched controls with normal kidney function, but the opposite was true for younger patients.

Adjusted Risk for All-Cause Death, Type 2 Diabetes vs No Diabetes*

Age, y HR (95% CI) P
< 55 1.60 (1.40–1.82) < .001
55–64 1.15 (1.08–1.22) < .001
65–74 0.87 (0.84–0.91) < .001
>75 0.76 (0.75–0.78) < .001
*All with normal kidney function; and patients with well-controlled type 2 diabetes

However, in each age category (<55, 55–64, 65–74, and >75) the risk of all-cause death increased with worse glycemic control and worse kidney function. The hazard ratios for all-cause death ranged from 2.61 to 1.04 among patients with microalbuminuria, from 3.78 to 1.40 among those with macroalbuminuria, and from 14.63 to 3.31 among those with stage 5 chronic kidney disease.

Clinical Implications for Young and Old Diabetic Patients

The increased mortality in patients with type 2 diabetes who were younger than 55, even those with on-target glycemic control and no renal complications, is "difficult to interpret," Lind acknowledged. "These patients had generally well-controlled blood pressure and typically received statins. The results imply that further improvements in the care for this patient group is needed."

On the other hand, 65- to 75-year-old patients with type 2 diabetes, well-controlled glycemic levels, and no renal complications had a lower risk of mortality during follow-up than individuals in the general population. It is "encouraging," Link said, that by reaching current guideline-recommended glycemic targets in this age group, "we can lower the mortality rate to that in the general population; [this means the] guidelines are working."

However, he noted, patients with clearly high HbA1c levels or signs of renal complications — often as result of earlier poor glycemic control — had excess mortality.

Finally, patients with type 2 diabetes in their late 70s and older had a significantly attenuated risk of death during follow-up, approaching that of the general population. However, patients with renal complications or very poor glycemic control (HbA1c >7.8%) had a worse survival. "It is therefore essential to [also] continue preventing diabetic complications…in older individuals," according to Lind.

In contrast to the historically low 15% excess mortality in the current cohort, excess mortality with type 2 diabetes was reported to be around 100% until about 2000 (N Engl J Med. 2011;364:829-841). And in a recent large population-based study of 14 million individuals in Canada and the United Kingdom, it was around 40% to 50% (Diabetologia. 2013;56:2601-2608), Lind explained. Of note, excess mortality declined during the current study, from 17% in the first half to 13% in the latter half.

"Similar evaluations need to be performed in other countries to confirm that excess mortality is low, since diabetes care, diet, and lifestyle, among other factors, may differ between countries," Lind said.

The study was supported by grants from the Swedish government; the Swedish Society of Medicine; the Health and Medical Care Committee of the Regional Executive Board, Region Västra Götaland; the Swedish Heart and Lung Foundation; Diabetes Wellness; and the Swedish Research Council. Dr Tancredi has no relevant financial relationships. Dr Lind reports receiving grants from the Swedish State, Swedish Society of Medicine, Region Västra Götaland, Swedish Heart and Lung Foundation, and Diabetes Wellness; research grants from AstraZeneca, Dexcom, and Novo Nordisk; and consulting for/receiving honoraria from AstraZeneca, Novo Nordisk, Medtronic, Eli Lilly, Pfizer, Abbott Scandinavia, Bayer, and Rubin Medical. Disclosures for the coauthors are listed on the journal website .

N Engl J Med. 2015;373:1720-1732. Abstract

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