Daniel M. Keller, PhD

October 18, 2012

BERLIN — Six months after initiating insulin therapy with insulin detemir (Det), patients with type 2 diabetes mellitus (T2DM) receiving a low-intensity dietary intervention were more likely to achieve better blood glucose control without hypoglycemic events compared with patients not receiving that form of dietary intervention.

However, the improvements in glycemic control, as indicated by glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG), were similar for the 2 groups, Priscilla Hollander, MD, PhD, reported in a poster session here at the European Association for the Study of Diabetes (EASD) 48th Annual Meeting.

Moreover, both groups in the randomized controlled trial lost weight during the study, with no significant difference between them, said Dr. Hollander, head of the diabetes programs at the Endocrine Center at Baylor University Medical Center in Dallas, Texas.

Weight gain is a common problem when initiating insulin therapy. Compared with neutral protamine Hagedorn (NPH) insulin, Det, a long-acting basal insulin analogue, may reduce the risk for weight gain as well as the incidence of hypoglycemia. Therefore, the researchers aimed to compare outcomes after a low-intensity dietary intervention vs standard basic lifestyle advice when insulin-naive T2DM patients initiated once-daily Det with metformin.

The investigators randomly assigned insulin-naive patients in this 26-week, multinational, controlled, open-label trial to Det (Det, n = 301) or to Det with the dietary intervention (Det+Diet, n = 306). At baseline, the Det group received basic lifestyle advice, whereas the Det+Diet group received the basic lifestyle advice plus 3 in-person meetings and 3 phone consultations with certified dieticians. The dieticians worked out meal plans and caloric goals, assessed habitual dietary intake, and provided dietary tips and adherence advice.

Insulin titration was conducted with a treat-to-target approach using a prebreakfast target plasma glucose level of 4.0 to 5.0 mmol/L.

The 2 groups were well matched for sex (approximately 50% men), age (56.5 - 58.2 years), duration of diabetes (8.5 years), HbA1c (7.9% - 8.0%), FPG (9.2 - 9.3 mmol/L), body weight (97 kg), and body mass index (BMI) (34.4 kg/m2).

Both Groups Lost Same Amount of Weight

After 26 weeks, both groups had a small amount weight loss. The Det+Diet group had lost a mean of 1.05 kg vs a mean of 0.56 kg in the Det group (P = .132). When stratified by baseline BMI in each group, the weight changes between the treatment groups did not differ significantly according to BMI (P = .414).

Dr. Hollander described the weight outcomes as "somewhat ambiguous." She noted that at the lowest baseline BMI, the Det+Diet group lost more weight, whereas at the highest BMI, the Det group had more weight loss. "It's interesting. It isn't clear what the effect of the stricter diet had, but actually both groups really had a tendency to actually lose weight rather than gain, even though they had lowered their [Hb]A1c by almost 1%," she told Medscape Medical News.

The Det+Diet group showed a nonsignificant trend toward better glycemic control compared with the Det group (mean HBA1c change: -0.93 ± 0.05% vs -0.80 ± 0.05%, respectively), yielding an estimated mean difference of 0.13% (95% confidence interval 0.00, 0.26, P = .053).

Each group achieved a reduction of about 3 mmol/L in mean FPG, with no significant difference between groups. Both groups had a mean reduction in energy intake from baseline, though the reduction was greatest in the Det group (787 kJ) compared with the Det+Diet group (553 kJ). That unexpected observation may be explained in part by the fact that more patients in the Det+Diet group increased their physical activity (25.5%) vs the Det group (19.9%).

The mean insulin dose for both groups increased from baseline (0.1 - 0.2 U/kg) to the end of the trial (Det+Diet to 0.95 U/kg; Det to 0.97 U/kg).

The Det+Diet group was significantly more likely to achieve an HbA1c less than 7.0% without minor or severe hypoglycemia (odds ratio [OR] = 0.61, P = .014) and with weight gain less than 0.5 kg (OR = 0.59, P = .005). However, the groups did not differ in the rates of all, severe, or nocturnal hypoglycemic episodes per exposure year. Dr. Hollander speculated that the Det+Diet group may have achieved lower HbA1c levels without a concomitant increase in hypoglycemia because they may have watched their diets more closely.

In conclusion, she said Det "lowered [Hb]A1c nicely, and actually most of the patients lost weight regardless of which [regimen] they were on. It's a little hard to explain, actually. The main thing to take [away] is they improved their glucose, and both groups lost weight, which shows that [insulin detemir] does seem to have a weight-sparing effect. How it does that is a little unclear."

Dr. Hollander emphasized that diet "plays a huge role in glucose control and weight," and no one should conclude from this study that it does not matter. Even the control (Det) patients received the standard American Diabetes Association diet approach.

Diabetologist Mariusz Tracz, MD, PhD, from the Medical University of Warsaw, in Poland, told Medscape Medical News that the study investigates an important question in diabetes, namely, how to reduce the disadvantages of insulin therapy, and specifically, the problems of hypoglycemia and weight gain.

To understand why there were no clear differences between the groups in terms of improvements in HbA1c and weight change, Dr. Tracz said, "We have to know more details about how the [diet] education programs were done. We know that one of the most important things in diabetes treatment is education, which is a fundamental part of the management," he said. "And the education in diet is especially important. But it is also a challenge, and you can do this in very different ways."

It would be informative, he said, if the authors would also analyze how different teaching programs used in the trial affect dietary habits. "In the future, it would be good to test 'high-intensity dietary intervention,' [because] maybe it could be more effective according to weight loss and improvement in HbA1c," he said. "It would be also interesting to look at the data in all the different participating countries with different eating habits."

Dr. Hollander made a similar point, noting that although all the dieticians came together to try to standardize their dietary advice, she suspected that different dietary habits in the different participating countries may have affected the results.

The study was supported by Novo Nordisk. Dr. Hollander has been on advisory boards for Novo Nordisk, Merck, and Pfizer. Dr. Tracz disclosed no relevant financial relationships.

European Association for the Study of Diabetes (EASD) 48th Annual Meeting: Abstract 939. Presented October 3, 2012.