As every month, we'll begin with our headlines and then go on to review some journal articles. These are about women and heart disease, change in cognitive function by glucose tolerance in older adults, hemoglobin A1c level and future cardiovascular events among women, and the relationship of retinal vessel caliber to the incidence and progression of diabetic retinopathy.
The headlines came hot and heavy this month, so let's start right in. The June 2004, Archives of Neurology reports on a skin patch containing the anesthetic lidocaine which can be used for treatment for hand and pain experienced by people with diabetes. Dr, Richard L. Barbano et al from the University of Rochester, NY, tested the patch on 56 patients for a three week treatment period. Patients reported reduction in pain and an improved quality of life with treatment. Significant improvements were noted in sleep quality as well as various psychological measures such as depression and anger. These benefits were maintained in a subgroup of patients treated for an additional five weeks.
The American Journal of Epidemiology, June 15, 2004 has an article by Dr. Steven S. Coughlin from the CDC in Atlanta which concludes that diabetes appears to increase the risk of death from a number of types of cancer, a fact that holds true even when accounting for obesity. The researchers examined a group of 467,922 men and 588,321 women who were cancer-free when the study began in 1982. After 16 years the authors uncovered a link between diabetes and death from colon and pancreatic cancer. In addition, in men diabetes seemed to increase the death risk from liver and bladder cancers, whereas in women an association with death and breast cancer was seen.
The July issue of Diabetes Care has an article by William Tamborlane et al of Yale which found that insulin pumps appear to work better than the newest long-acting insulin (Lantus) therapy in helping children with type 1 diabetes to maintain healthy blood glucose levels. The study involved 32 patients in a 16 week study.
Circulation, 2004 has an article written by Dr. Carmine Gazzarusa et al from Pavia, Italy. They found that if a man with type 2 diabetes also suffers from erectile dysfunction (ED), it strongly suggests that he could well have coronary artery disease that's not causing any symptoms. A strong association between ED and obvious, symptomatic heart disease has been seen in several studies, but until now the prevalence of ED has never been studies among diabetic patients with silent CAD. They looked at 133 men with uncomplicated diabetes and silent CAD (which was discovered by testing) and 127 with diabetes and no silent CAD. The team found that 33.8% of the men with silent heart disease had ED, compared with 4.7 % of those without CAD. The researchers found other factors were linked with silent CAD, but "ED appeared to be the most efficient predictor of silent CAD."
A studying the June 3, 2004 in the New England Journal of Medicine of very obese children suggests that half may have a worrisome cluster of health conditions that may increase their risk of developing diabetes and heart disease at an early age. Research at Yale University School of Medicine was reported by lead researcher Dr. Sonia Caprio who runs the pediatric obesity clinic there. The researchers tested 439 children and adolescents-244 who were moderately obese and 196 severely obese. They also tested 51 of their siblings who were overweight or lean. Metabolic syndrome was found in 50% of the severely obese and 39% of the moderately obese but not in any of their siblings. After obesity, high blood pressure was the most common condition. Seventy-seven of the participants were checked again about 2 years later. Twenty-four of the 34 had metabolic syndrome and 8 had developed type 2 diabetes. The syndrome developed in 16 of the 43 children who did not initially have it.
The June 15, 2004 issue of the Proceedings of the National Academy of Sciences has an article done by researchers at Cornell that suggests that higher than normal amounts of a selenium-containing enzyme could promote type 2 diabetes. The researchers found that mice with elevated levels of the antioxidant enzyme develop the precursors of diabetes at much higher rates than control mice. Selenium, a common dietary supplement, is an antioxidant. Many of the benefits of selenium are related to its role in the production of glutathione peroxide (GP), an antioxidant enzyme that helps detoxify the body. The lead author James McClung, PhD reported that his group found that mice that were bred to over express GP to up to three times above normal developed hyperglycemia, hyperinsulinemia and elevated plasma leptin. They became 36% heavier than and twice as fat as did the control mice. These conditions precede the development of type 2 diabetes. This finding suggests a new cause of insulin resistance and argues against the general belief that antioxidants are beneficial to insulin function. McClung noted that high levels of GP appear to promote diabetes by mopping up too many free radicals, which are needed to help switch insulin signaling on and off in glucose metabolism. Most people believe that both selenium and selenium-containing enzyme GP are good for health by protecting cells and tissues from oxidation. The study, however, suggests that they are a double-edged sword. Antioxidants can be harmful by neutralizing too many free radicals and interfering with insulin signaling, which results in promoting obesity, insulin resistance and possibly diabetes.
Hypertension 2004;43:1-7 has an article by Verdecchia, P et al which suggests that patients with new-onset diabetes being treated for hypertension and those with previous diagnosis of diabetes were 3 times more likely to have subsequent cardiovascular disease over a long-term follow-up period than treated hypertensive subjects who remained diabetes free. Initially 795 hypertensive subjects, 51 with type 2 diabetes, whose hypertension was untreated before the beginning of the study underwent a series of diagnostic procedures at baseline including 24-hour blood pressure (BP) monitoring and ECG. IN the absence of cardiovascular events, the same procedures were performed a medium of 3.1 years later.
After adjusting for confounding factors such as 24-hour ambulatory BP, the relative risk of cardiovascular events was 2.92 in the group with new diabetes and 3.57 in the group with established diabetes, when compared with subjects who remained free of diabetes. For each 1.58 mmol/L increase in serum glucose at the follow-up visit, the independent risk of cardiovascular events increased by 23%. The authors noted it was important to remark that the occurrence of new diabetes was an independent predictor of cardiovascular risk, whereas the use of diuretics, albeit predictive of new diabetics, did not show any independent relation with subsequent cardiovascular event. They suggest that patients with plasma glucose levels in the high normal levels and those being treated with diuretics should be monitored with care to prevent the occurrence of new diabetes.
Scientists have discovered s gene mutation that contributes to type 1 diabetes, a discovery that could help identify children at risk for developing diabetes. The gene mutation-called SUMO-4-is one of several that have been identified as contributors to type 1 diabetes. An article about the discovery by Medical College of Georgia researchers was published in the journal Nature Genetics on July 11, 2004. It is hoped that the finding will increase the accuracy of existing newborn screening.
The Archives of Internal Medicine, 2004;164:934-942 has an article titled Women and Heart Disease by Elizabeth Barrett-Connor, MD et al from the School of medicine of the University of California, San Diego. Cardiovascular disease (CVD) is the primary cause of death in women and women with type 2 diabetes are at greater risk of CVD compared to nondiabetic women. The increment in risk attributable to diabetes is greater in women than in men. The extent to which hyperglycemia contribute to heart disease risk has been examined in observational studies and clinical trials, although most included only men or did not analyze sex differences. The probable adverse influence of hyperglycemia is potentially medicated by impaired endothelial function, and/or by other mechanisms. Beyond high blood glucose level, a number of other common risk factors for CVD, including hypertension, dyslipidemia, and smoking are seen in women with diabetes and require special attention. Presentation and diagnosis of CVD may differ between women and men, regardless of the presence of diabetes. Recognizing the potential for atypical presentation of CVD in women and limitations of common diagnostic tools are important, treatment are important in preventing unnecessary delay in initiating proper treatment. Based on what we know today, treatment of CVD should be at least as aggressive in women-and especially in those with diabetes-as it is in men. Future trails should generate specific data on CVD in women, either by design of female-only studies or by subgroup analysis by sex.
The Archives of Internal Medicine, Vol.164 No.12, June 28, 2004 has an article titled Change in cognitive function by glucose tolerance status in older adults by Alka Kanaya, MD at al from The University of California, San Francisco. The researchers examined the 4-year change in cognitive performance among older adults according to glucose tolerance status. Three cognitive tests (Mini-Mental State Examination, verbal Fluency (VF) test, and Trail-Making Test) were measured 4 years apart in 999 white men and women aged 42 to 89 years who were enroll in the Rancho Bernardo Study. Participants were classified with normal (NGT), impaired (IGT) or diabetic glucose tolerance. Sex-specific linear regression models adjusted for age, education, depression score, apolopoptein E 4 allele, and current estrogen use. They checked for mediation by further adjusting for total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein, and triglyceride levels; blood pressure, Glycohemoglobin level; and microalbuminuria, retinopathy, stroke, or coronary heart disease. At baseline, mean cognitive scores did not differ between glucose tolerance groups. Women with diabetes had a four-fold increased risk of major cognitive decline on the VF test after 4 years compared with nondiabetic women. Performance on Mini-Mental State Examination and Trail Making Test B did not differ by baseline glucose status. The researchers concluded that elderly white women with diabetes had a more rapid decline in performance on the VT test compared to women with women with IGT or NGT. Better glucose control might ameliorate this decline.
We found another article about heart disease, diabetes and women. Hemoglobin A1c level and future cardiovascular events among women by Gavin Blake, MD, MPH, MSc et al is in Achieves of Internal Medicine, 2004;164:757-761. The researchers looked at hemoglobin A1c and how it is related to cardiovascular risk. They concluded a nest case-control study of the Women's Health Study cohort. They identified 464 case patients with incident myocardial infarction, stroke, or coronary revascularization and 928 unmatched subjects who remained free of cardiovascular events at case diagnosis. The mean follow-up was 7 years. Of the overall study population, 136 had a history of diabetes or an over elevated baseline A1c level (>6.4%) and were excluded from primary analysis. Among women without diabetes or an elevated baseline A1c were significantly higher among future cases than controls. Those with the highest A1c were among future cases than more often than controls. The researchers concluded that A1c level is associated with future cardiovascular risk among women without diabetes, but the relationship is largely attributable to a strong correlation with other cardiovascular risk factors. In contrast, diabetes is a strong independent determinant of cardiovascular risk even after adjustments for A1c levels.
The Archives of Ophthalmology, 2004;122:76-83 has an article titled The relation of retinal vessel caliber to the incidence and progression of diabetic retinopathy by Ronald Klein, MD, MPH et al from the University of Wisconsin Medical School in Madison. The researchers described the relation of retinal arteriolar and venular caliber to the incidence and progression of diabetic retinopathy in people with type 1 diabetes. The design looked at incidence findings in a population-based study of diabetic retinopathy in Wisconsin. Participants included 996 persons diagnosed as having diabetes before 30 years of age who took insulin and went baseline examination, 891 in the 4-year follow-up, 765 in the 10-year follow-up, and 634 in the 14-year follow-up. Retinal photographs of 7 standard fields were taken at all examinations. Computer-assisted grading was performed from a digitized image of field 1 to determine the average diameter of retinal arterioles and venules and their ratios. Main outcome measures included incidence and progression of retinopathy, incidence of proliferative retinopathy, and macular edema. The researchers concluded that larger arteriolar and venular caliber, independent of retinopathy severity level, is related to the progression of retinopathy, and larger venular caliber is associated with the 4-year incidence of proliferative retinopathy. Caliber of retinal vessels is not associated with incident retinopathy. These suggest a quantitative measure of retinal vascular caliber provides additional information regarding the risk for progression of retinopathy.
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