Doctor's Review: Medicine on the Move

October 27, 2021

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Conference proceedings: The Endrocrine Society’s Meeting and Expo

Hormones in Houston

Cities don't get much more American than Houston, Texas, but medical conferences don't get much more cosmopolitan than ENDO 2012, which was held there from June 23 to 26 this year.

The Endocrine Society has historically bounced between East and West Coast venues in successive years, but this year it opted for the far South. That didn't stop some 7000 endocrinologists from the four corners of the earth coming to talk testosterone, vitamin D, appetite, metabolism and obesity, endocrine disruptors and, of course, a whole lot of diabetes.

First, the good news

MOTM previously reported tantalizing hints from the Canadian Urology Association's 2011 meeting that taking metformin might reduce prostate cancer incidence among people with diabetes. ENDO 2012 brought further hope on this front, with a large Mexican review suggesting that the protective effect extends to other cancer sites.

Dr Diego Espinoza-Peralta, an endocrinologist with Mexico’s National Institute of Medical Sciences and Nutrition, and colleagues reviewed seven studies including 32,400 subjects with type 2 diabetes. They found a relative cancer risk of 0.62 in those who had taken daily metformin compared to those who had taken none. The benefit was mostly concentrated in cancer types known to occur more often in type 2 diabetes, particularly breast and colorectal. Pancreatic cancer rates were unaffected — though a week before ENDO 2012, the American Association for Cancer Research heard that metformin could destroy pancreatic cancer stem cells in rats. Much remains to be learned, but the least we can say is that this ubiquitous, low-cost drug is ageing remarkably gracefully.

The same can't be said of sulfonylureas, three of which — glipizide, glyburide and glimepiride — were analyzed against metformin in over 24,000 patients and found distinctly wanting, each bringing a more than 50 percent increase in overall mortality.

“We have clearly demonstrated that metformin is associated with a substantial reduction in mortality risk and, thus, should be the preferred first-line agent, if one has a choice between metformin and a sulfonylurea,” said study lead author Kevin M. Pantalone, from Summa Western Reserve Hospital in Ohio. The entire sulfonylurea class is falling out of favour in the world of diabetes.

Testosterone-fuelled in Texas

The male hormone has often been implicated in a vicious circle of aging and obesity. Levels often decline in older male patients, especially the overweight, and low testosterone contributes to further weight gain.

“Obesity is associated with reduced testosterone and low testosterone induces weight gain,” noted researcher Fred Saad of Bayer Pharma in Berlin. But the circle can be virtuous too. Using long-acting testosterone injections and longer follow-up, his team achieved an average 13-percent weight loss in overweight men after five years.

Another study presented by Dr Aksam Yassin of the Institute of Urology and Andrology in Norderstedt-Hamburg found that testosterone improved symptoms of metabolic syndrome or prediabetes in men with late-onset hypogonadism. “This intervention improved all three components of obesity, including waist circumference, weight and body-mass index; diabetes control; poor lipids profile and blood pressure,” said Yassin, calling the therapy “both essential and safe in elderly patients with symptomatic late onset hypogonadism or testosterone deficiency.”

Apply, don’t multiply

A transdermal gel could be the answer to hassle-free, reversible male contraception, said Dr Christine Wang, professor at Harbor-UCLA Medical Center, whose team added a synthetic progestin called Nestorone to a testosterone gel and achieved very low sperm counts in 89 percent of subjects and aspermia in 78 percent.

“Men can use transdermal gels at home— unlike the usual injections and implants, which must be given in a health care provider’s office,” said Dr Wang, adding that the gel showed few adverse effects, and unlike other progestins tried in male contraception, Nestorone has no androgenic effects such as acne or hypercholesteremia.

Under the knife

Bariatric surgery has shown good results in reversing type 2 diabetes, at least over the medium term. An Indian study suggested that it need not be a full gastric bypass, and that patients do not have to be obese to benefit. The key to success, it seems, is intervening early, with subjects who have had diabetes for less than 10 years experiencing significantly greater success.

“Modified bariatric surgery such as sleeve gastrectomy should be considered at an earlier stage of type 2 diabetes, rather than as a last resort,” said Kirtikumar Modi, an endocrinologist at Medwin Hospital in Hyderabad, India. His team achieved remission (defined as A1c below 6.5 without drugs or insulin) at 20 months post-surgery in 20 of 43 patients. And of 30 who had high blood pressure before surgery, 27 became normotensive. In sleeve gastrectomy with ileal interposition, the distance from stomach to ileum is reduced. In patients with a BMI over 30, said Dr Modi, it showed results comparable to gastric bypass, achieving 85 percent remission.

But Yessica Ramos, MD, of Mayo Clinic Arizona in Scottsdale, found that with longer follow-up, some of the successes in bariatric surgery begin to slip away. About 21 percent of those who achieved remission in her study became diabetic again three to five years post-surgery.

“The recurrence rate was mainly influenced by a longstanding history of type 2 diabetes before the surgery,” she noted, lending further support to the new notion that bariatric surgery is an intervention for early, not late diabetes.

D is for debate

Evidence is adding up that low levels of vitamin D increase risk of diabetes. Joanna Mitri of Tufts Medical Center in Boston said her group found that patients in the highest quintile for vitamin D levels had a 48 percent lower risk of having the metabolic syndrome than those in the lowest quintile. Those with the highest vitamin D levels had smaller waist circumference, higher HDL cholesterol and lower blood sugar.

“If a causal relationship can be established in ongoing and planned studies of vitamin D,” she said, “this link will be of public health importance because vitamin D supplementation is easy and inexpensive.”

One group worth screening for vitamin D status is obese adolescents, who had extraordinarily high levels of deficiency in a study performed at Columbia University Medical Center. Concerns about the effects of vitamin D supplementation on kidney stone formation were raised in a study sponsored by the National Institute on Aging, but the unfortunate practice of studying vitamin D supplementation in tandem with calcium supplementation continues, making it impossible to tease apart the effects. In this study, variations in calcium dosage did seem to affect hypercalciuria, while changes in vitamin D did not — a logical enough result. That would also explain why vitamin D supplementation proved safe in a Veterans' Affairs study of hyperparathyroidism patients with hypercalcemia.

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