Close Concerns Weblog

Diabetes means cancer too? Maybe...

Inoue M, Iwasaki M, Otani T, Sasazuki S, Noda M, Tsugane S. "Diabetes Mellitus and the Risk of Cancer: Results From a Large-Scale Population-Based Cohort Study in Japan." Archives of Internal Medicine, September 25, 2006; 166:1871-1877. http://archinte.ama-assn.org/cgi/content/abstract/166/17/1871?etoc

Researchers from the Japan Public Health Center-Based Prospective Study Group published a report in the Archives of Internal Medicine today which showed a link between diabetes and the risk of total cancer, and in particular several forms of cancer specific to abdominal sites.

The study group included a total of 97,771 Japanese adults (46,548 men and 51,223 women) aged 40 to 69 years who responded to a baseline questionnaire between January 1990 and December 1994. All participants were followed up for cancer incidence through December 31, 2003. At baseline, 6.7% of the men and 3.1% of the women had a history of diabetes.

A total of 6462 cases of newly diagnosed cancer were recorded over the course of the study. Overall, a history of diabetes was associated with a 27% increase in cancer incidence for men and a 21% increase in cancer incidence for women. Cancers of the liver, pancreas, kidney, and ovaries were most strongly associated with diabetes; colon cancer and stomach cancer were also associated but less strongly.

Total cancer incidence in men was 3,907 cases, with 366 cases in men with diabetes. The hazard ratio (HR) for cancer incidence for men with diabetes was 1.27. The HR was especially high for liver cancer (312 cases total, 52 in men with diabetes, HR = 2.24), pancreatic cancer (118 cases total, 16 in men with diabetes, HR = 1.85), and kidney cancer (99 cases total, 13 in men with diabetes, HR = 1.92). Also raised for men with diabetes was the risk of colon cancer (491 cases total, 46 in men with diabetes, HR =1.36) and stomach cancer (977 cases total, 87 in men with diabetes, HR = 1.23).

Total cancer incidence in women was 2,555 cases, with 104 cases in women with diabetes. The hazard ratio (HR) for cancer incidence for women with diabetes was 1.21, lower than for men, and only borderline statistically significant. The HR was higher for ovarian cancer (74 cases total, 5 in women with diabetes, HR = 2.24) and liver cancer (120 cases total, 10 in women with diabetes, HR = 1.94), and was also increased for stomach cancer (362 cases total, 20 in women with diabetes, HR = 1.61).

Unfortunately, there's not enough data to show which direction the causal link between diabetes and cancer runs, if there is one. It may be that the two diseases are linked only indirectly, for example through a mutual source in hereditary or environmental factors. Nonetheless, these study results are interesting and we would like to see further studies done to elucidate the link between diabetes and cancers in the abdominal area.

Another complications drug – SPP301 for diabetic nephropathy reports positive Phase 2b data and enters phase 3

"SPP301 Phase IIb Results in Diabetic Nephropathy Presented at ASN"

IN BRIEF

Speedel announced positive Phase IIb results for SPP301, an endothelin-A receptor antagonist (ERA), in diabetic nephropathy (DN) on November 11 at the American Society of Nephrology (ASN) Meeting in Philadelphia.  These results indicate that SPP301 significantly decreases urinary albumin excretion rate (UAER) and total cholesterol in patients with diabetic kidney disease when administered on top of standard treatment with ACE-inhibitors or ARBs.  Based on these positive results, Speedel began a Phase III trial of SPP301 in July 2005.   

SPP301 IS CURRENTLY IN PHASE 3

§    SPP301 is a once daily oral ERA that Speedel licensed from Roche in October 2000.  It was specifically optimized for improved liver safety. 

§    SPP301 is the only ERA currently in development for diabetic nephropathy. 

§    Phase 3 testing began in July 2005 and is expected to be completed in approximately 3.5 years. 

§    The FDA has granted Fast Track status for SPP301 in DN and has agreed to a Special Protocol Assessment defining Phase III design and endpoints. 

Diabetic nephropathy

Diabetic nephropathy is one of those complications we always vaguely hear about but don’t write much about.  DN affects 20-40% of patients with Type 1 or Type 2 diabetes, which translates in to 8 million people in the U.S., Europe, and Japan according to Speedel's estimates.  DN is the leading cause of end-stage renal disease in the U.S.  Current treatment options are limited to anti-hypertensives and renin angiotensin inhibitors, which slow the progression of the disease.  However, the mortality rate remains high.   

Phase IIb results indicate strong efficacy and good safety

SPP301 results in substantial additional benefit when administered on top of standard treatment (ACEI or ARB).

§    All four doses of SPP301 (5, 10, 25, and 50 mg) significantly decreased UAER compared to placebo, with the highest 2 doses demonstrating the greatest reduction in UAER. 

§    All doses also significantly reduced total cholesterol compared to placebo.

§    SPP301 also had an additive effect on reduction in proteinuria.  In 55% of patients across all dose groups, SPP301 reduced proteinuria by at least 30% on top of standard treatment.  Data from the US National Kidney Foundation suggests that such a sizable reduction in proteinuria could reduce morbidity and mortality in patients with DN.

§    Although other ERAs have previously been associated with liver toxicity, SPP301 did not result in significant increases in liver enzymes compared to placebo. 

§    This looks like a nice drug – lipid lowering, complication reducing, oral, once-daily pill…Now we just need to make sure that it is safe and then reimbursed!  Can’t imagine there would be any problems with the latter…On the safety front, liver problems remind us of Rezulin and make us catch our breath a bit…

                                                                

IMPLICATIONS

§    These results are important because diabetic nephropathy is a large and growing unmet medical need with a high mortality rate and limited treatment options. SPP301 and ERA may offer clinicians a novel approach to treating DN. 

§    We believe that we are going to start seeing an increase in the number of drugs for complications of diabetes, such as SPP301.  Although we need to both treat and prevent complications, the key question is whether it is better to treat or prevent complications. 

New study finds high rates of kidney disease in relatives of those on dialysis

"At Risk: Doctors Issue Alert to Dialysis Patients' Families"
Eric Nagourney, NYT, Nov. 8, 2005

A team led by Dr. Barry Freedman of Wake Forest University Baptist Medical Center reported in the American Journal of Nephrology that people on dialysis are much more likely than those who are not to have close family members with kidney disease. A review of 25,000 patients in the Southeast showed that 23% of patients on dialysis had relatives with end-stage kidney disease. 2005 data from the U.S. Renal Data System suggested that the prevalence of ESRD is 15 per million, or 0.0015%. The recognition that family members are at high risk may lead to earlier screening, and early detection of kidney disease can dramatically improve outcomes.

See below for the full article.