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Obesity in type 2 diabetes increases major adverse CV event risk

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October 9, 2017

Uche Anyanwagu
Uchenna Anyanwagu
 

Adults with type 2 diabetes plus overweight or obesity who initiate insulin are at increased risk for a major adverse cardiovascular event and all-cause mortality compared with their normal-weight peers, study data show.

“Among patients with type 2 diabetes, obesity adversely affects the ability of insulin to reduce HbA1c level for up to 12 months, but not beyond 24 months,” Uchenna Anyanwagu, PhD, MSc, of the division of medical sciences and graduate entry medicine in the School of Medicine at the University of Nottingham in the United Kingdom, told Endocrine Today. “Surprisingly, people who are obese, however, had more significant reductions in their BMI compared to non-obese persons; while morbidly obese patients who are started on insulin therapy have a 30% increased risk of a composite event of mortality, stroke and myocardial infarction after 5 years.”

Anyanwagu and colleagues evaluated data from The Health Improvement Network on 12,725 adults (mean age, 58.6 years) with type 2 diabetes initiating insulin to determine the associations among insulin initiation and obesity, metabolic outcomes — including HbA1c and weight — CV events and mortality.

The primary outcomes included changes in HbA1c, weight and BMI from baseline to 6, 12, 24, 36, 48 and 60 months after index date and percent of participants achieving the HbA1c target of 7.5% or less.

Participants were divided into groups based on weight: normal BMI (n = 1,665), overweight (n = 3,022), obese class I (n = 3,712), obese class II (n = 2,637) and obese class III (n = 1,689).

More women were in the obese class III BMI group, and more men were in the normal BMI group. Baseline HbA1c and systolic blood pressure were highest in the obese class III group and lowest in the normal BMI group.

As BMI level rose, the odds for achieving HbA1c 7.5% or less significantly declined at 6 and 12 months compared with the normal-weight group; however, no significant differences in likelihood of achieving HbA1c target was observed among BMI groups at 24 months. At 6 months, HbA1c reductions were greater in all BMI groups compared with the normal-weight group — 0.1% in the overweight group (P = .075), 0.19% in the obese class I group (P < .001), 0.21% in the obese class II group (P < .001) and 0.29% in the obese class III group (P < .001) — after adjustment for age, sex, baseline HbA1c and duration of diabetes. At 12 months, reductions were slightly smaller, but still greater than that of the normal BMI group: 0.08% in the overweight group (P = .119), 0.17% in the obese class I group (P = .001), 0.19% in the obese class II group (P = .001) and 0.25% in the obese class III group (P < .001).

Through a mean follow-up of 4.38 years, there were 1,095 composite events of major adverse CV events for a crude event rate of 22.1 per 1,000 person-years. The risk for a major adverse CV event was 10% higher in the overweight group (adjusted HR = 1.1; 95% CI, 0.9-1.35), 5% higher in the obese class I group (aHR = 1.05; 95% CI, 0.86-1.29), 3% higher in the obese class II group (aHR = 1.03; 95% CI, 0.83-1.29) and 30% higher in the obese class III group (aHR = 1.3; 95% CI, 1.02-1.66) compared with the normal BMI group after adjustment for age, sex, use of lipid-lowering therapies and antihypertensive drugs, comorbidities of heart failure and coronary heart disease, albumin, glomerular filtration rate, lipid profile and the use of GLP-1 receptor agonists.

The risks for all-cause mortality were 9% higher in the overweight group (aHR = 1.09; 95% CI, 0.81-1.45), 12% higher in the obese class I group (aHR = 1.12; 95% CI, 0.84-1.49), 31% higher in the obese class II group (aHR = 1.31; 95% CI, 0.96-1.77) and 75% higher in the obese class III group (aHR = 1.75; 95% CI, 1.26-2.43) compared with the normal BMI group. The risks for CV events were also higher in the overweight (25%), obese class I (21%) and obese class III (34%) groups compared with the normal BMI group; however, risks for CV events were similar between the normal BMI and obese class III groups.

“While insulin treatment is associated with weight gain, baseline obesity confers only a marginal influence on its efficacy in achieving HbA1c target,” Anyanwagu said. “Nevertheless, morbidly obese patients, at the time of insulin initiation, appear to be at high risk of mortality. These findings provide important reassurances among patients with type 2 diabetes who gained weight following insulin treatment in routine clinical practice, but also suggested the need to consider alternative glucose-lowering therapy when faced with a morbidly obese patient who requires intensification of therapy.” – by Amber Cox

For more information:

Uchenna Anyanwagu, PhD, MSc, can be reached at uche.anyanwagu@nottingham.ac.uk.

Disclosures: The authors report no relevant financial disclosures.

itj+ Perspective

Alexander Turchin
Perspective

intimately interconnected, as obesity increases the risk for type 2 diabetes, while some of the commonly used treatments for diabetes (eg, insulin or sulfonylureas) lead to weight gain. Both obesity and diabetes are also known to lead to a broad range of adverse effects on health. In particular, both are independently associated with an increased risk for CV events and mortality. These risks are particularly high in patients who have both conditions. In the present study, the authors focused on a particularly vulnerable group — individuals whose diabetes has progressed to the extent that they need to start insulin therapy. The study adds to the body of evidence that these patients are at very high risk for adverse outcomes. At the relatively young mean age of 60 years, these patients’ annual rate of CV event or death exceeded 2%; patients who were morbidly obese had a 30% higher risk. At the same time, patients at a higher BMI took longer to achieve glycemic control, likely placing them at additional risk for macro- and microvascular complications of diabetes down the line. The implications of these findings for clinical practice are clear — these patients need especially close attention, focused on reducing their health risks by both improving their blood glucose control and reducing their weight. Both intensive lifestyle interventions as well as medications that can at the same time decrease glucose levels, body weight and CV risks (eg, GLP-1 receptor agonists or SGLT2 inhibitors) or metabolic surgery could be considered. This study is a call for help — and a call for action.

Alexander Turchin, MD, MS

Director of Quality in Diabetes
Division of Endocrinology, Diabetes and Hypertension
Brigham and Women’s Hospital

Disclosure: Turchin reports he is on the advisory board of Monarch Medical Technologies and receives research funding from Sanofi.