Intensifying a dual oral agent regimen of metformin plus insulin secretagogue by adding pioglitazone significantly improves glycemic control in comparison with adding placebo in patients with baseline glycated hemoglobin (HbA1c) levels of less than 8.5%, albeit with increased weight gain, French researchers report.

“Early combination therapy, including the use of metformin plus a thiazolidinedione and a sulfonylurea, is gaining increasing acceptance and may offer some advantages over the earlier introduction of insulin,” explain Guillaume Charpentier (Centre Hospitalier Sud Francilien, Corbeil Essonnes) and co-workers.

But they add that “the question remains as to when the optimal time is to introduce a third oral agent versus insulin in failing dual therapy.“

To investigate the glycemic effects of triple oral therapy that includes pioglitazone versus dual oral therapy plus placebo, the researchers randomly assigned 299 patients with Type 2 diabetes inadequately controlled with metformin and an insulin secretagogue to add-on pioglitazone 30 mg/day or placebo for 7 months.

For the last 4 months of the study the dose of pioglitazone was dependent on HbA1c levels: 30 mg pioglitazone if HbA1c levels were less than or equal to 6.5%, and up to 45 mg if HbA1c levels were greater than 6.5%.

Presenting the findings in the journal Diabetes, Obesity and Metabolism, the authors report that after 7 months the addition of pioglitazone to existing metformin and a sulfonylurea or glinide resulted in a between-group difference in HbA1c levels of 1.18% in favor of pioglitazone. The thiazolidinedione reduced mean HbA1c level from a baseline of 8.2% to a level of 7.3%, whereas in the placebo group there was a slight increase to 8.4%. Decreases in fasting plasma glucose were also significantly greater in the pioglitazone group.

“Almost half (44.4%) of the patients in the pioglitazone group who had a baseline HbA1c level of less than 8.5% achieved the HbA1c target of less than 7.0% by final visit compared with 4.9% in the placebo group,” note the authors.

When baseline HbA1c levels were greater than 8.5%, 13% of patients achieved the HbA1c target of less than 7.0% in the pioglitazone group compared with none in the placebo group. This suggests that the addition of a thiazolidinedione to failing dual oral therapy is most effective when baseline HbA1c is less than 8.5% and that insulin should be considered in patients with higher levels, say the authors.

In agreement with other studies, pioglitazone was associated with improvements in indices of beta-cell function including homeostasis model assessment of beta-cell function (HOMA-B).

Mean body weight increased by 3.9 kg in the pioglitazone group compared with no change in the placebo group, but overall tolerability was good apart from an increased incidence of edema with pioglitazone.

“Future studies should address the potential benefits of early triple therapy with a thiazolidinedione in terms of weight gain, compliance, and overall tolerability compared with early insulin therapy,” the authors conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

Free abstract

Arterial stiffness is linked to both glycated hemoglobin (HbA1c) and duration of diabetes in patients with concomitant hypertension, highlighting the importance of early glycemic control for prevention of atherosclerotic disease in patients with Type 2 diabetes.

In people with diabetes, increased arterial stiffness is a strong risk factor for early mortality and is exacerbated by hypertension. To evaluate the associations between these risk factors, Yuhong Chen (Ruijin Hospital, Shanghai, China) and co-workers recruited 1000 patients with Type 2 diabetes with or without hypertension between 2005 and 2007.

Brachial-ankle pulse wave velocity (Ba-PWV) was used as a non-invasive measure of arterial stiffness. Duration of Type 2 diabetes was confirmed by clinical records and a detailed medical examination was performed.

To investigate the correlation between arterial stiffness and glycemic control, patients with diabetes and hypertension were divided into three subgroups based on HbA1c levels: less than 6.5%, 6.5% to less than 7.0%, and greater than 7.0%. All patients with diabetes were also divided into subgroups in terms of duration of diabetes: less than 5 years, 5 to 10 years, and greater than 10 years.

Ba-PWV was significantly higher in the 562 patients with diabetes and hypertension (1779 cm/s) than in the 438 patients without hypertension (1691 cm/s), despite similar levels of glycemic control.

Arterial stiffness correlated positively with HbA1c in patients with diabetes and hypertension, but not in patients without hypertension. In patients with hypertension, Ba-PWV was significantly higher in those with HbA1c levels of at least 7.0% compared with those who had HbA1c levels of less than 6.5%, leading the authors to suggest that arterial stiffness was associated with glycemic control.

Arterial stiffness was associated with HbA1c in all three divisions of diabetes duration in hypertensive patients, and increased progressively with increasing duration of diabetes. In patients without hypertension, arterial stiffness was only associated with a diabetes duration of greater than 10 years.

The authors suggest that hypertension is an additive risk factor for arterial stiffness in patients with diabetes causing earlier and faster development of atherosclerosis.

“Ba-PWV positively correlates with HbA1c and duration of diabetes in subjects with diabetes and hypertension, suggesting the importance of early glycemic control in the prevention of arterial stiffness and vascular complications,” they conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

Free abstract

Because diabetics can be found functioning normally everywhere, finding them on a baseball diamond, football field or in a gym is to be expected. Despite the fact that it is a serious disease, with guidance, control and modern day medicine, the diabetic can excel in an assortment of sports. Numerous successful athletes and sports personalities have lived with diabetes. They learned how to control their illness and it did not interfere with their profession.

Some examples of celebrated sports heroes who had diabetes are the boxing champ Joe Frazier, baseball’s legendary Ty Cobb, and tennis great Arthur Ashe. These sports legends were able to get to the top of their profession in spite of having diabetes because they learned how to live with it. And those around them, like coaches and trainers, were schooled in what to do if an emergency should occur.

Diabetic athletes participate in numerous sports, like track, basketball, and soccer. In order to compete safely in these sports the athlete must understand what the illness is and what needs to be done to control it. Things like testing your blood sugar prior to the activity and immediately after, re-checking it every thirty minutes during the activity, never begin play too soon after eating and always wearing shoes that fit well to avoid foot injuries that are common due to circulation problems that come with the illness.

In order for the diabetic athlete to compete and excel in organized sports activities safely, he or she must make sure that those around them, like coaches, trainers, sports medicine professionals and gymnasium staff, are aware of their condition so that they can respond properly if a crisis should occur. Since intense physical exertion brings down the quantity of sugar in the blood stream, diabetic athletes must see to it that these people recognize and understand the symptoms of hypoglycemia and hyperglycemia. Not sharing this information if an emergency should materialize might leave them and the diabetic in a perilous situation.

The athlete with diabetes must wear a medical bracelet at all times. They should join and participate in support organizations where they can engage and share their concerns and difficulties with others in their same situation. And, the diabetic athlete must likewise be knowledgeable of his or her body’s reactions to changes in sugar and insulin levels. Recognizing these changes will help them to take the necessary action needed to return them to normal levels and to keep competing and winning in their chosen sport.