As we do each month, let's begin with headlines that touch our medical lives. After the headlines we will bring you abstracts on high dose irbesartan seeming to give long-term renal protection in diabetes, solitary pancreas transplantation tied to increased mortality in diabetes, evidence of increased risk of stomach and uterine cancer in type 1 diabetes, and finally the unclear prophylactic effect of aspirin in diabetes.
The European Parliament voted in December to fund research using stem cells taken from human embryos. The assembly's opinion sends a message to the European Union, which is due to decide next month whether to lift a moratorium that prevents EU cash from going to such experiments, banned in several of the bloc's member states.
Intensive lifestyle interventions can help prevent diabetes, according to a 3-year study, the Finnish Diabetes Prevention Study (DPS) as published in the December, 2003 issue of Diabetes Care. In the DPS, 522 middle-aged, overweight subjects with impaired glucose tolerance were randomized to receive either usual care or intensive intervention aimed at reducing body weight and dietary and satiated fat and increasing physical activity and dietary fiber. "The intensive lifestyle intervention prolonged long-term changes in diet, physical activity and clinical and biochemical parameters, and reduced diabetes risk." The authors write, "This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system…In the long run, a lifestyle-intervention approach to weight control rather than a weight-reduction diet might be a more cost-efficient way to manage overweight in individuals at high risk for diabetes".
Diabetes Care, 2003 26:3215-3218 has an article which suggests that cinnamon may improve lipid and glucose control in patients with type 2 diabetes. Alam Khan, PhD from NWFP Agricultural University in Pakistan, and colleagues, examined aqueous extracts from cinnamon and found it increased in vitro glucose uptake and glycogen synthesis and increased phosporylation of the insulin receptor. In addition these cinnamon extracts are likely to aid in triggering the insulin cascade system". The authors concluded that "because cinnamon would not contribute to caloric intake, those with type 2 diabetes of those with elevated glucose, triglyceride, LDL cholesterol, or total cholesterol levels may benefit from regular inclusion of cinnamon in their daily diet."
American Heart Journal 2003; 146:848-853 has an article that concludes that beta-blocker therapy improves outcomes for diabetic patients with chronic heart failure, albeit not to the extent seen in patients without diabetes. The author Dr. Henry Krum et al from Melbourne, Australia note that the reluctance to treat diabetics with beta-blockers due to perceived detrimental effects on glucose metabolism and masking of hypoglycemic symptoms may be unfounded. They concluded that "…it is possible to conclude from the analysis that all patients with CHF who have symptoms both with and without diabetes mellitus, derive prognostic benefit from beta-blocking agents and should receive these drugs unless they are absolutely contraindicated or not tolerated."
Now we look at our abstracts. Diabetes Care 2003;26:3296-3302 has an article of interest titled High-dose irbesartan seems to confer long-term renal protection in diabetes, by Dr. Steen Andersen et al from the Steno Diabetes Center in Gentofte, Denmark. The researchers found that reductions in microalbuminuria in diabetic patients achieved with Angiotensin II receptor blocker (ARB) irbesartan appear to persist after antihypertensive treatment is stopped... Members of the IRMA-2 (Irbesartan in patients with type 2 diabetes and Microalbuminuria) Study Group previously showed that, among type 2 diabetic patients, irbesartan 300 mg daily reduced microalbuminuria by 37%. Whether these reductions persisted or what the mechanism of action was not known. The researchers followed 91 patients treated with irbesartan (300 or 150mg/d) or placebo for 24 months who then agreed to discontinue all anti-hypertension medication for 1 month. Fifteen patients required further treatment for hypertension before the 1-month follow-up period. It was reported that the urinary excretion rate remained 47% lower then baseline after the 30-day treatment period in the 300-mg group only. Rates returned to baseline values in the other two arms. The authors concluded that the 150-mg dose is insufficient for renoprotection, and "renoprotective therapy should aim to achieve the maximal antiproteinuric effect in addition to reduction of blood pressure. Doses even higher than 300 mg may provide additional protection", they add.
JAMA 2003;290:2817-2823,2861-2863 has an article by Dr. David M.Harlan et al from the National Institutes of Health in Bethesda, MD titled Solitary pancreas transplantation tied to increased mortality in diabetes. Diabetics who received only a pancreas transplant are about 50% more likely to die in the next few years than their peers who are awaiting transplantation and receive conventional therapy. In contrast, simultaneous pancreas-kidney transplantation is associated with a reduction in mortality risk. In this study, the team assessed the outcomes of 11,572 diabetic patients who were on a waiting list for pancreas transplantation between 1995 and 2000. During this period, approximately half of the patients underwent transplantation, usually simultaneous pancreas-kidney transplantation. The 4-year survival rate for solitary pancreas recipients was 85.2%, while the rates for peers still on a waiting list were 92.1%. In regards to pancreas-after-kidney transplantation, the corresponding rates were 84.5% and 88.1%. Why the difference? "One possibility was that solitary pancreas transplantation is, for some unknown reason, a more complicated procedure with higher operative mortality," Dr Harlan commented. He continued, "However, we looked at that and post-surgical survival following both procedures was almost identical." He observed, "If you have diabetes and kidney failure, you're prognosis is dismal" and therefore there is less to lose and much more to gain from transplantation, Dr. Harlan explained. "In contrast, patients with poorly controlled diabetes, but without kidney failure, have a surprisingly good prognosis with conventional therapy, so solitary pancreas transplantation is a much riskier endeavor," he added. The results suggest that "the enthusiasm for simultaneous pancreas-kidney transplantation is probably justified," Dr David M. Nathan of the Harvard Medical School notes in a related editorial.
Journal of the National Cancer Institute 2003; 95:1797-1800 has an article by Dr. Weiman Ye at the Karolinska Institute in Stockholm and colleagues have an article titled Excess risk of stomach and uterine cancer seen in type 1 diabetes. Patients with type 1 diabetes have a higher risk for cancer than the general population, this Swedish study shows. The excess risks are most striking for malignancies of the stomach, cervix and endometrium. The researchers linked data from the Swedish Inpatient Register to the Swedish Cancer Register. They identified records for nearly 30,000 female patients resumed to have type 1 diabetes based on hospitalization for diabetes before age 31. After discounting the first year after hospital discharge, there were 355 incident cases of cancer among diabetic patients. Relative to the general population, this translated to a standardized incidence ratio (SIR) of 1.2 (i.e. a 20% increased risk), the investigators reported. The SIR for incident cervical cancer was 1.6 and was similar before and after 15 years' follow-up. During the first 14 years, diabetics were 4.8 times more likely than the general population to develop endometrial cancer. Therefore, the risk was still elevated, with an SIR of 2.2. In these women, the threat may be associated with their higher incidence of null parity, irregular menstruation and fertility disorders. Risk of cancer of the breast, colon and rectum, pancreas and kidney was unaffected by type 1 diabetes status. Cancer risk is already known to be increased with type 2 diabetes, but risks of specific cancers differ from those associated with type 1 diabetes. For example, pancreatic cancer incidence is higher among type 2 diabetes patients, which supports the theory that hyperinsulemia is the cause.
The December issue of Diabetes Care 2003; 26:3264-3272, 3349-3350 has a very timely article on the Prophylactic effect of aspirin unclear in diabetes by Michele Sacco, MD et al of the Primary Prevention Project (PPP) Collaborative Group. The prophylactic effect of low-dose aspirin is unclear in diabetes, according to this report. Because the Primary Prevention Project lacked sufficient power in the diabetic subgroup to see a clear effect, the editorialist suggests that the current guidelines still be followed. The PPP has recently shown that low-dose aspirin significantly reduces the risk of cardiovascular death by >40% in a population of 4,495 people with one or more cardiovascular risk factors after a medium follow-up of 3.7 years. "Diabetes is associated with a substantial increase in the risk of cardiovascular disease (CVD) and the use of low-dose aspirin is thus recommended by existing guidelines. Despite the general consensus, the evidence supporting the use of aspirin for the prevention of CVD in diabetic patients is surprisingly scant."
In this open trial with two-by-two factorial design, 1.031 people with diabetes were randomized to low-dose aspirin 100 mg/day and or vitamin E, 300 mg/day. Subjects were aged 50 years and had no history of previous cardiovascular event. The primary end point was a composite of cardiovascular death, stroke, or myocardial infarction.
Although the PPP trial was stopped prematurely because aspirin had a consistent benefit overall in nondiabetic subjects, aspirin treatment in diabetic patients was associated with a nonsignificant reduction in the main end point and in total cardiovascular events, and with a nonsignificant increase in cardiovascular deaths. Vitamin E was not associated with any significant reduction in any end points in either diabetic or nondiabetic subjects.
"Our data suggest a lower effect of primary prevention of CVD with low-dose aspirin in diabetic patients as opposed to subjects with other cardiovascular risk factors." The authors recommend further large-scale trials. "If confirmed, these findings might indicate that the anti-platelet activation effects of aspirin in diabetic patients are overwhelmed by aspirin-insensitive mechanisms of platelet activation in thrombus formation, thus making the balance between benefits and harms of aspirin treatment unfavorable."
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