Leah Lawrence

	This year brought continued positive data about the overall class effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes.

	“There is a whole set of information about the intersection of these drugs and their effect on heart disease and kidney disease,” Zachary T. Bloomgarden, MD, clinical professor of medicine, endocrinology, diabetes and bone disease at Mount Sinai in New York. “There are all of these tracks coming together that have the potential to totally change our treatment [of diabetes] over a short period of time.”

	For decades, metformin has been used as a first-line treatment for people diagnosed with type 2 diabetes. However, according to Bloomgarden, there is a possibility that the standard use of first-line metformin may be going away.

	“Metformin is anOK drug, but it has no particular intrinsic benefit for these patients,” Bloomgarden told 

. “Whereas, we have got multiple sources of evidence that suggest a real reduction in progression of kidney disease and a certain form of protection against heart disease outcomes with SGLT2 inhibitors.”

	To a lesser extent, the same is also true with glucagon-like peptide-1 receptor agonists, he added.

	“As we progress with this research we may be saying that-certainly for high-risk people characterized by either high risk heart disease or by kidney disease-that SGLT2s are associated with benefit in a variety of settings,” Bloomgarden said.

	The other big story of 2017 relates to continuous glucose monitoring (CGM). According to Bloomgarden, this type of technology was “sort of a dream” a decade ago, and is now a complete reality.

	The use of CGM should allow physicians and researchers to obtain profiles of glucose levels continuously for patients with type 1 or type 2 diabetes. These measurements will allow for more meaningful information beyond that gained with HbA1c testing or glucose self-monitoring.

	“We should really be able to better address hypoglycemia problems in a very meaningful way,” Bloomgarden said.

	Both of these advances do come with some questions of affordability, however.

	According to Bloomgarden, there are some issues when it comes to paying for SGLT2 inhibitors. He recalled a patient recently coming into the office worried because his insurance company would no longer cover his SGLT2 inhibitor after the end of the year. Bloomgarden said he spent about 20 minutes to 30 minutes with the patient on the phone with the insurance company trying to obtain prior authorization for the medications only to be disconnected.

	“This reflects another very important story in medical economics, which is the importance of developing ways of pushing back against pharmacy medicine managers now that we have the opportunity to give drugs that really reduce adverse outcomes,” Bloomgarden said.

	Expanding use of CGM has similar issues as well.

	“Affording this technology is still a question,” he said. “We hope to see this become a more available treatment technology.”

Articles

2017 has seen two key advancements for diabetes patients, but affordability remains an issue.

Physicians have new tools for treating, monitoring diabetes

	A type 2 diabetes diagnosis carries with it a two- to threefold increased risk for cardiovascular disease (CVD), including myocardial infarction, stroke, peripheral vascular disease and death from cardiovascular disease. Patients with type 2 diabetes also typically present with several conventional risk factors for CVD including hypertension, lipid disturbances and inflammation.

	“That increased risk above individuals who do not have diabetes-men or women who are age-matched-relates, it’s thought, to glucose elevations, but recent clinical trials do not indicate that glucose lowering is the major feature by which protection ensued,” Robert H. Eckel, MD, professor of medicine in the division of endocrinology, metabolism and diabetes, and cardiology at the University of Colorado School of Medicine.

	Eckel said historically, trials in type 2 diabetes have compared aggressive treatment with insulin-where the dosage is optimized to lower blood sugar to as close to normal as possible-compared with a group treated close to the standard of care.

	“The outcomes of these trials have had pluses and minus,” Eckel said. “There is the suggestion that there might be a benefit for lowering glucose alone but it is not convincing enough to say that it is the only important risk factor for heart disease in patients with diabetes. “

	In recent years, two new classes of drugs have shown benefit in reducing CVD events in patients with type 2 diabetes.

	The first, sodium-glucose cotransporter-2 (SGLT2) inhibitors, lower blood glucose by causing the kidneys to excrete sugar from the body through the urine.

	“Typically patients with diabetes can excrete glucose in their urine when glucose levels are above 200 mg/dL,” Eckel explained. “These drugs prevent the high glucose from occurring because they allow glucose to be excreted in urine when levels are still within the normal range.”

	According to Eckel, two drugs within this class have shown benefit on CVD outcomes.

	For example, results of the EASEL study, 

 showed that among patients with type 2 diabetes with established CVD, initiation on an SGLT2 inhibitor was associated with a lower rate of all-cause mortality, hospitalization for heart failure and major cardiovascular endpoints, compared with non-initiation.

	A second class of injectable drugs-glucagon-like peptide-1 (GLP-1) receptor antagonists-has also been shown to reduce the risk for CVD outcomes.

	“This is another class of drugs that is glucose lowering, but the amount of glucose lowering has not explained the entire benefit,” Eckel said.

	Now physicians are able to pick a drug that can reduce patients risk for CVD events beyond just lowering blood glucose, Eckel said. However, he pointed out that these new classes of drugs are expensive and access may be limited for people with no or inadequate insurance coverage.

	“I must admit as person who takes care of patients with diabetes that after a patient is treated with metformin, one of these agents should take second place to lower their glucose,” Eckel said. “That is particularly relevant because of the reduction in CVD events to follow.”

Glucose lowering drugs provide additional cardiovascular benefit to patients with diabetes. 

Physicians have more options to provide CVD protection in diabetic patients

	An association between high body mass index (BMI) and the risk for certain cancers, including colorectal, pancreas and kidney cancer, has been well established, with one study estimating that about 3% of all cancer cases in 2012 were attributable to high BMI.

	However, the link between diabetes and cancer was established only just recently, according to Henry Chi Hang Fung, MD, vice chair of hematology at Fox Chase Cancer Center in Philadelphia.

 found that diabetes and high BMI were the cause of 5.6% of new cancer cases worldwide in 2012. The study quantified the proportion of cancer attributable to diabetes and high BMI. They used data on the incidence of 12 types of cancer from 175 countries in 2012 and combined it with data on high BMI and diabetes. The researchers matched the data sets by age group and sex to take account of age differences using diabetes and BMI data from 2002 to calculate cancer incidence in 2012 attributable to these risks.

	The increase in the number of people with diabetes between 1980 and 2002 led to a 26.1% increase in new cases of attributable cancers. There were no data establishing the cause for the relationship between diabetes and cancer but some proposed mechanisms included hyperinsulinemia, chronic inflammation or dysregulation of sex hormone activity. Prospective studies “with more accurate assessments of adiposity, diabetes, and metabolic health,” are needed to draw conclusions about the relationship, according to the study.

	Fung related the results of this study to the relationship between smoking and cancer.

	“Not everyone who smokes will get cancer, and every cancer is associated with smoking, not only just lung cancer,” Fung told 

. “Similarly, there is no model showing that because you have diabetes you will then get cancer.”

	However, the results of this study, and any future studies linking diabetes to cancer, should bring attention to what Fung called an important public health issue.

	“If more and more patients are getting diabetes and it is associated with cancer, then the incidence of cancer will also be increasing,” Fung said.

	With smoking, research has shown that if rates of smoking decrease so does the incidence of lung cancer.

	“Moving forward, the question will be: If we can control diabetes, can we decrease the rate of cancer?,” Fung said. “That has not yet been addressed.”

	For the time being, the growing association between cancer, obesity and diabetes does not necessarily change health practice, according to Fung.

	“There is no need to do more screening in these patients because the diabetes itself is not causing the cancer,” Fung said. In fact, Fung implied that efforts should be made to control diabetes and obesity for their sake alone and not because of a possible association with cancer.

	Indeed, commenting on the study, lead author Jonathan Pearson-Stuttard of the Imperial College in London, said in a statement, “As the prevalence of these cancer risk factors increases, clinical and public health efforts should focus on identifying preventive and screening measures for populations and for individual patients. It is important that effective food policies are implemented to tackle the rising prevalence of diabetes, high BMI and the diseases related to these risk factors.” 

Diabetes and high BMI were responsible for an estimated 800,000 new cases of cancer worldwide in 2012.

Physicians shouldn’t underestimate link between diabetes, cancer

	Increasing a child’s average nightly sleep duration may help to reduce the risk of type 2 diabetes by lowering several markers of the disease, according to the results of a recent study published in 

The study found a strong inverse association between sleep duration and adiposity, insulin resistance and fasting glucose.

	“Sleep duration has been shown to be associated with type 2 diabetes and adiposity in adults though the relationship is complex,” Claire M. Nightingale, PhD, of the Population Health Research Institute at St George’s, University of London told 

. “Sleep duration has also been associated with adiposity in children with increased sleep duration being associated with lower levels of adiposity, though the association with type 2 diabetes risks has been little studied in children.”

	Nightingale and colleagues conducted a cross-sectional study of 4,525 children aged 9 years to 10 years from the United Kingdom. Participants reported usual time of going to bed and getting up on a school day. Based on these data, the researchers calculated sleep time, which was then evaluated with fasting blood samples and physical measures including height, weight, bioimpedance and blood pressure.

	The average duration of nightly sleep was 10.5 hours. Those participants with longer sleep duration were slightly younger and more likely to be girls.

	“We found that longer sleep duration in children aged 9 to10 was associated with lower levels of adiposity (body mass index, fat mass index) and type 2 diabetes risk markers (insulin resistance, fasting insulin and fasting glucose) but not with cardiovascular disease markers,” Nightingale said.

	In adjusted models, an additional hour sleep duration was associated with 0.19 lower BMI, 0.03 kg/m

 lower fat mass index, 2.9% lower homeostasis model assessment insulin resistance and 0.24% lower fasting glucose. No associations were found between sleep duration and HbA1c, lipids or blood pressure. These findings persisted after accounting for differences in adiposity and were unchanged after adjusting for differences in physical activity.

	“Increasing the mean weekday sleep duration by half an hour could potentially be associated with a 0.1 kg/m² lower body mass index and a 0.5% reduction in insulin resistance,” Nightingale said.

	According to Nightingale, intervention studies are needed to establish whether these associations are causal, and this could provide a strategy for the early prevention of type 2 diabetes.

	In an editorial that accompanied the study, Nicole Glaser, MD, and Dennis Styne, MD, of the division of pediatrics at University of California Davis in Sacramento, California, pointed out the difficulty in establishing a causal relationship between sleep duration and type 2 diabetes risk.

	“It is possible that short sleep duration and risk factors for type 2 diabetes might reflect separate but related alterations in hypothalamic functions controlling sleep and those modulating neuroendocrine regulators of appetite and insulin sensitivity,” they wrote. “To disprove this hypothesis and support a causal relationship, it is necessary to demonstrate that reductions in sleep duration increase risk factors for type 2 diabetes and that increasing sleep duration has the reverse effect.”

	However, they noted that a trial like this would present ethical challenges. 

Study shows that longer sleep duration was associated with reductions in several markers for type 2 diabetes. 

Author | Leah Lawrence

Articles

Physicians have new tools for treating, monitoring diabetes

Physicians have more options to provide CVD protection in diabetic patients

Physicians shouldn’t underestimate link between diabetes, cancer

Longer sleep duration could lessen children’s risk for T2D