After our monthly headlines we will present articles on the relation of retinal caliber to the incidence and progression of diabetic retinopathy, another warning about antipsychotic drugs and diabetic risk, a simple test points to diabetics' cardiac risks, acarbose reducing the risk of MI, and high cholesterol absorption and low synthesis in type 1 diabetes.
We begin our headlines with a list of new medications that are in the pipeline to control diabetes. Do note that other companies are also working on most of these families of medications.
1. Exanatide, made by Amylin Pharmaceuticals and Eli Lilly is an injection that is based on a protein found in the saliva of the venomous Gila monster. It lowers blood glucose levels only when it is too high. It is currently awaiting regulatory decision.
2. Exubera, made by Pfizer, Aventis, and Nektar Therapeutics is in late-stage trials. This is an inhaled insulin which in studies works as well as injected insulin for both type 1 and type 2 diabetics. There were some concerns that it might cause pulmonary problems, but a long-term study being conducted by Pfizer and Aventis could clear things up.
3. Galida is in late-stage trials and is made by AstraZeneca. Bristol-Myers is working on a similar medication called Muraglitazar. This is a medication that controls both cholesterol and blood sugar levels. So far in two recent attempts it faltered, causing cancer in the laboratory animals.
4. LAF237 by Novaris is racing a similar drug from Merck, MK-0431, to become the first pill to raise a protein called glucagon-like peptide. The result is a medication that only controls blood sugar when it is too high. Novaris is hoping to submit an application to regulators in 2006. Both of these drugs are in late-stage trials.
The Archives of Ophthalmology 2004;122:84-88 has an article titled The impact of diabetic retinopathy on participation in daily living by Ecosse L. Lamoureux, PhD et al from the Centre for Eye Research Australia. The authors wanted to examine the restriction of participation. They used the Impact of Vision Impairment questionnaire. People with diabetic retinopathy and visual acuity worse than 20/40 or 6/12 in the better eye were eligible. Results indicated that the highest restrictions were reported for the Leisure and Work, Mobility, and Consumer and Interaction domains. The researchers concluded that low-vision rehabilitation services aiming to improve outdoor mobility, print reading and participation in leisure activities and psychological health may be an effective strategy to help people with diabetic retinopathy increases their participation in daily activities.
JAMA 2004;291:335-342 has an article titled Poor control of vascular disease risk factors still seen among diabetics in US by Anthony Brown, M.D. Comparisons of data from two national health surveys revealed in this paper that in the last decade little progress has been made in improving the control of vascular disease risk factors. From early to late 1990's there was no improvement in control of blood glucose levels or blood pressure. In this study the author compared data form NHANES lll (1988-1994) with the NHANES (1999 and 2000). In the latest study about 37% of subjects achieved the target HbA1c goal of less than 7%, but a similar percentage had values above the recommended 8%. Neither was a significant change from the NHANES lll results. Further analysis of the newest data revealed that only 7.3 % blood pressure and cholesterol levels and HbA1c levels at or below the recommended levels.
The American Journal of Clinical Nutrition 2004;79:70-75 has an article titled Iron intake form red meat linked to increased diabetes risk by Dr. Rui Jiang et al from Harvard School of Public Health. Heme-iron intake from red meat appears to increase the risk for type 2 diabetes. The results of cross-sectional studies have suggested a link between excessive iron stores and the development of insulin resistance. The researchers conclude that they are unable to determine whether the association was due to heme iron per se or to other components of red meat.
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, MPH et al. This research examines the relationship between retinal arteriolar caliber to the incidence and progression of diabetic retinopathy in people with type 1 diabetes. Incidence findings in a population-based study of diabetic retinopathy in Wisconsin examined 996 people diagnosed with type 1 diabetes before 30 years of age. They went through a baseline examination and a 4-year, 10-year and 14-year follow-up. They concluded that larger arteriolar and venular caliber, independent of retinopathy severity level is associated with the progression of retinopathy, and larger caliber is associated with the 4-year incidence of proliferative retinopathy. Caliber of retinal vessels is not associated with incident retinopathy. They suggest that a quantitative measure of retinal vascular caliber provides additional information regarding the progression of retinopathy.
In the past we have brought you information about anti-psychotic medications and the risk for developing diabetes. Here we look at the warnings from four prominent medical organizations which were issued in Jan. of 2004. I highlight this here because we all know the difficult decisions we make when deciding how to treat patients with mental illness. The American Diabetes Association, American Psychiatric Association. American Association of Clinical Endocrinologists and the North American Association for the Study of Obesity published this in the Feb. issue of Diabetes Care. They found that the drugs known as atypical anti-psychotics, which are used to treat a variety of mental illnesses including schizophrenia, bipolar disorder, dementia, psychotic depression, autism, and developmental disorders may increase the risk of obesity, diabetes and high cholesterol all of which raise the risk of developing heart disease.
Diabetes Care 2004;27:208-215 has an article titled Simple test points to diabetics' cardiac risks by Dr. Alain Nitenberg et al. Epicardial coronary artery restriction in response to the cold pressor test indicates an increased likelihood of cardiovascular events in type 2 diabetics with no other cardiovascular risk factors. Dr. Nitenberg says the cold pressor test is a very simple method to show evidence of endothelial dysfunction in peripheral arteries. The researchers studied 72 patients without other major coronary risk factors and 56 controls. The average coronary diameter change in response to the test was an increase of 17.2% in controls. In diabetics, the corresponding response was 14.4%. No changes were seen in 8.9 % of controls and none showed constriction. No changes were seen in 26.4% of diabetics and none showed dilation.
After a mean follow-up of 45 months, there was one cardiovascular event in the control group and 26 in 18 diabetics. Furthermore, 23 of the events occurred in 16 of the 53 diabetic patients who showed coronary artery constriction. The remaining 3 were in 2 of the 19 diabetic patients who had no diameter change.
The researchers concluded that in the end, constriction of angiographically normal coronary arteries in response to the cold pressor test is predictive of cardiovascular risk. They added that this test does not require drug administration or an intravascular device. It might be used as "an easy means to evaluate the efficiency of therapy in high-risk patients."
The European Heart Journal 2004;25:10-16 has an article titled Acarbose reduces risk of MI in diabetics by Dr. M. Hanefeld at Technical University in Dresden. For patients with diabetes, treatment with acarbose reduces the risk of MI and other cardiovascular events, even among those already being treated for cardiovascular disease. In addition, to its effects on postprandial hyperglycemia, the alpha-glycosidase inhibitor acarbose is associated with improved lipid levels, blood pressure, and coagulation activation. The investigators conducted a meta-analysis of seven placebo-controlled studies evaluating the effects of acarbose. Trial duration ranged from 52 to 154 weeks. Included were 1248 patients treated with acarbose and 932 treated with placebo, among whom 56.55% and 60.2% respectively received concomitant cardiovascular medication. Diabetes duration in the two groups averaged 76.5 and 84.6 months.
Acarbose treatment prolonged the time to a newly diagnosed cardiovascular event. Events were experienced by 6.1% of those in the acarbose group and 9.4% in the placebo group-a significant relative risk reduction of 35%. Results remained significant after adjustment for weight, systolic blood pressure and triglycerides. The authors observed a 64% reduction in the risk for MI. Small but significant reductions in weight, systolic blood pressure and triglycerides, along with improved HbA1c levels and blood glucose levels, were also noted with acarbose treatment. The authors concluded that acarbose treatment results in a "reduction of postprandial hyperglycemia and improvement in other features of the metabolic syndrome"
High cholesterol absorption and low synthesis seen in type 1 diabetes is an article in Diabetes Care 2004;27:53-58 by Dr. Tau A. Miettinen at al from Helsinki. Low synthesis and high absorption of cholesterol are characteristic of type 1 diabetes according to these researchers. They examined cholesterol metabolism in 27 type 1 diabetics and matched type 2 diabetics. They used ratios of cholesterol precursor sterol to those of cholesterol as surrogate markers of synthesis. Ratios of cholesterol and plant sterols were employed as surrogate markers of cholesterol absorption. The team found that patients with type 2 diabetes had higher levels of HDL cholesterol and LDL triglycerides than those with type 1 diabetes. Furthermore, the ratios of all absorption sterols in serum and each lipoprotein were higher in patients with type 1 diabetes than those with type 2 diabetes. However, the ratios of the synthesis markers, especially cholesterol and lathosterol, were lower in type 1 than in type 2 diabetics. The results concluded that the results "can be interpreted to indicate high absorption." Low synthesis of cholesterol in patients with type 1 compared to type 2 diabetes they also point out that "these differences were present also in various lipoproteins."
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