Each month we present journal abstracts. As always, we begin with our Headlines that are short resumes of articles, and then present abstracts. These include articles on new agents that could counter diabetes, systolic BP predicts diabetic nephropathy progression, BNP testing useful in screening diabetes for left ventricular dysfunction, soy protein effects on lipids in postmenopausal woman, and new ADA position on dyslipidemia treatment in diabetic children.
HEADLINES:
U.S. regulators have issued a warning letter to Roche Diagnostics Corp. regarding what they said were "serious problems" in the manufacturing of insulin pumps at one of its plants in Switzerland. In a letter dated June 11, the Food and Drug Administration said it uncovered a variety of violations during inspections of the Disetronic Medical Systems plant in Burgdorf, Switzerland from Jan. 27 to Feb.5. Roche spokesman said the company was doing everything it could to bring all Disetronic facilities up to standards. It was pointed out that the violations were uncovered prior to Roche’s acquisition of Disetronic.
Many of you ask about taking supplements, so we are including this article from The Archives of Internal Medicine 2003;163:1587-1590 titled Glucosamine supplementation does not impair glucose control in type 2 diabetes by Dr. Daren A. Scroggie et al at Lackland Air Force Base. Glucosamine is increasingly used by people with type 2 diabetes and others to treat osteoarthritis, but animal studies suggest that high Glucosamine levels can raise plasma glucose levels. This is the first placebo-controlled, double-blind study of its kind, and the results showed that mean HbA1c levels changed very little. The authors concluded that "since patients with diabetes are at risk for toxic effects from some of the current treatments for osteoarthritis (NSAIDs in particular), Glucosamine may provide a safe alternative treatment for these patients,"
The American Journal of Epidemiology 2003;157:1092-1100 has an article titled Impaired glucose tolerance linked to increased risk of cancer mortality by Dr. Sharon H. Sayah et al from Social and Scientific Systems, Silver Spring, MD. The researchers knew that impaired glucose tolerance is linked to cardiovascular disease, but its relationship to cancer risk is unknown. They examined 3054 adults between ages 30 and 74 who had an oral glucose tolerance test at baseline. The researchers identified deaths by searching mortality files through 1992 and found 206 cancer deaths. On analysis, subjects with impaired glucose tolerance had the greatest adjusted relative hazard of cancer mortality compared to those with normal glucose tolerance. The most commonly reported cancer sites were the lung, colon, pancreas, breast, and prostate. Patients with impaired glucose tolerance had a relative risk of colon cancer that was 4.24 times higher than those with normal tolerance.
The authors suggest that this population be targeted for participation on colon cancer screening programs.
The American Journal of Cardiology 2003; 91:1421-1426 has an article titled CHD seen preventable in many patients with metabolic syndrome by Dr. Nathan D. Wong et al form Univ. of CA, Irvine. The group calculated the effects of controlling blood pressure and lipids to optimal levels in preventing CHD in patients between ages 34 and 74 with metabolic syndrome. They estimate that among 7.5 million men and 9.0 million women with metabolic syndrome, if left untreated, 1.5 million and .45 million women would experience CHD events over 10 years. Control of blood pressure, HDL cholesterol and LDL to normal levels resulted in preventing 51.3% of events in men and 42.6% for women; control to optimal levels resulted in preventing 80.5% and 82.1% of events, respectively. They concluded that "the large number of patients with metabolic syndrome who have inadequately controlled hypertension and hyperlipidemia may derive substantial benefit from aggressive management of such risk factors"
The Medical Letter:Vol.45,8/4/03,64 has a review of two medications that may cause hypoglycemia and hyperglycemia. The article indicates that two elderly patients died after taking gatifloxacin and developing hyperglycemia with no history of diabetes. In a post-marketing study of gatifloxacin (Tequin), some patients have required insulin treatment for hyperglycemia. The report indicates that Tequin may cause severe, persistent hypoglycemia in elderly diabetics taking hypoglycemic drugs. It may also cause hyperglycemia in people with no history of diabetes as stated above. These effects can occur with other fluoroquinolones as well.
ABSTRACTS:
New agents could counter diabetes in two ways, from Science 2003;301:370-373 is written by Dr. Joseph Grimsby et al from Hoffmann-La Roche Inc. Researchers have identified a class of small molecules that lower blood glucose levels in diabetes by enhancing both insulin secretion and glycogen storage. Impaired insulin secretion by the pancreas and increased hepatic glucose production are hallmarks of diabetes that lead to hyperglycemia. In this study, researchers screened more than 100,000 synthetic compounds for agents that would activate glucokinase which results in enhanced insulin secretion in the pancreas and which promotes the metabolism and storage of glucose as glycogen in the liver. After the researchers identified molecules that did both, they were tested in rodent models of type 2 diabetes. "The dual mechanism of action seen with these molecules clearly differentiates them" from other oral antidiabetic agents such as sulfonylureas.
Dr. Grimsby concluded with the good news that phase 1 studies of glucokinase activators will be conducted by the end of the year.
Systolic BP predicts diabetic nephropathy progression in the Archives of Internal Medicine 2003; 163:1555-1565 is written by Dr. George L. Bakris et al of Rush Medical College in Chicago. In this study the researchers used a Cox proportional hazards regression model to examine the effects of baseline systolic pressure, diastolic blood pressure, and pulse pressure on renal outcomes in patients with established nephropathy and hypertension associated with type 2 diabetes. Included were 1513 patients enrolled in the Reduction of Endpoints in NIDDM (non-insulin dependent diabetes mellitus) with the Angiotensin ll Antagonist Losartan (RENAAL) study. The main outcome measures were doubling of serum creatinine, end-stage renal disease (ESRD), or death. The team also examined the effects of the Angiotensin receptor blocker losartan potassium on composite and renal outcomes.
Multivariate analysis demonstrated that the risk for ESRD of death increased by 6.7% for every 10mmHg rise in baseline systolic blood pressure. After adjusting for urinary albumin-creatinine ratio, serum creatinine, serum albumin, HbA1c, and hemoglobin, every 10 mmHg rise in diastolic blood pressure decreased the risk by 10.9%. Those randomized to the losartan group with a baseline pulse above 90mmHg had a 53.5% risk reduction for ESRD alone and a 35.5% risk reduction for ESRD or death compared to the placebo group. Dr. Bakris’s group concluded "Our findings provide strong support for aggressive reduction for people with nephropathy from type 2 diabetes."
BNP testing useful in screening diabetics for left ventricular dysfunction by Dr. Robert R. Henry from VA San Diego Healthcare System is published in Diabetes Care 2003;2003:2081-2087. Measuring B-type natriuretic peptide (BNP) levels was found to be reliable in detecting left ventricular dysfunction in diabetics according to Dr.Henry, who evaluated BNP testing as a method to screen diabetics. BNP levels were correlated with echocardiography findings in 172 diabetics who had a clinical indication for echocardiography and in 91 diabetics that did not. Patients with a clinical indication for echocardiography had significantly higher BNP levels that those who did not. At optimal cutoff values, BNP testing had a sensitivity of 86%, specificity of 92%, positive predictive value of 92%, and negative predictive value of 77% in detecting LV dysfunction in patients with a clinical indication for echocardiography.
In patients without a clinical indication for echocardiography, the negative predictive value increased to 90%, while other values fell slightly. The findings indicate the BNP testing can reliably detect ventricular dysfunction regardless of whether a clinical indication for echocardiography exists or not. Although BNP testing should not be used to establish the diagnosis of heart failure, the results indicate that a normal BNP level virtually rules out ventricular dysfunction.
Clinical Endocrinology 2003; 58:704-709 has an article titled Soy protein with isoflavones has a favorable effect on lipids in post menopausal women, by Dr. Helena J. Teede et al from Monash University, Australia. In a placebo-controlled, double-blind study; the researchers examined the effect of a soy protein supplement containing isoflavones on lipids and bone resorption in postmenopausal women. One hundred six women were randomized over dietary soy supplementation or placebo. The researchers measured lipid profile, including total, LDL and HDL cholesterol and triacylglycerol. They used pryidinoline and deoxypyredinoline as markers of bone resorption. To assess compliance, the team measured urinary isoflavones excretion. Seventy-eight women were included in the final analysis. The investigators observed a significantly greater increase in urinary isoflavones excretion in the soy group compared with the placebo group.
Overall, 92.9% and 93.6% of women in the soy and placebo groups were compliant. Compared with the placebo group, women in the soy group had significant improvements in lipid profiles, with decreases observed in LDL cholesterol, triacylglycerol and LDL: HDL ratio. There were no significant changes from baseline in the two markers of bone resorption for soy vs. placebo. The researchers conclude that isoflavone-containing soy protein has potential health benefits but is not a replacement for HRT.
Diabetes Care 2003;26:2194-2197 has an article titled New ADA position statement on dyslipidemia treatment in diabetic children written by Nathaniel Clark, MD, MS, RD et al from the ADA. While the ADA has stated lipid goals for adults, no similar guidelines exist for children. To address this, a panel of physicians from the fields of pediatric cardiology, endocrinology and nephrology met in July 2002 to formulate recommendations regarding lipid management of children with diabetes. Although the panel concluded that evidence is insufficient for specific lipid abnormalities documented in children with diabetes, most reviews speculate that the abnormalities seen in diabetic adults are also seen in children and adolescents. Children with elevated cholesterol levels are more likely than the general population to have high levels in adulthood.
Risk factors contributing to the early onset of coronary heart disease (CHD) in children and adolescents include elevated LDL cholesterol levels, families with a history of CHD or peripheral vascular disease before age 55, smoking, hypertension, HDL levels less than 35mg/dl, obesity, physical inactivity, and diabetes. The panel recommended that children over 2 years should be monitored only in the presence of a positive family history. In children with diabetes, this protocol should be modified based on age and type of diabetes. Treatment recommendation for elevated lipid levels are also similar to established pediatric guidelines modified to reflect the higher CVD risk status of diabetic patients. Comprehensive cardiovascular risk management in children with diabetes should include monitoring blood pressure, anti-tobacco counseling, promotion of physical activity, and management of obesity. The authors discuss the use of resins or bile sequestrants as well as statins for elevated lipid levels.
They suggest treating elevated triglycerides with glucose control and weight control unless they rise to levels of 1000mg.dl. At that level they suggest treatment with a fibric acid medication to avoid pancreatitis. You can find the entire report on the ADA site, with all of its recommendations.
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