As we do each month, we will begin with headlines. Please go over these and read more. Then we will bring you abstracts in more detail. This month we deal with the importance of tight control and neuropathy, diabetes and bone mineral density, microvascular complications at times of diagnosis of type 2 diabetes, incidence of end-stage renal disease, and finally we review an article on diabetes and drinking.
Very important: If you take Avandia or Actos to control your blood glucose levels, know that both can cause fluid buildup and heart failure in some patients. Six men developed poor kidney function or poor heart function after taking one of the medications. The findings were published in the September Mayo Clinic Proceedings. The first drug in this class, Rezulin, was pulled after about 100 people who took it died from liver failure. Talk to your physician if you take one of these.
There were two headlines about insulin and type 2 diabetes that caught our eye this month. Diabetes Care 2003;26:2231-2237 had an article by Dr. Michael Alvarsson et al from Stockholm concluded that for patients with recently diagnosed type 2 diabetes, insulin treatment achieves better results than does oral medication therapy. The researchers found that by the second year of therapy, those on glibenclamide had worsened results while those on insulin had stabilized. They conclude that more research is needed, but that if insulin therapy had been started earlier, we might have seen more lasting effects of insulin." The same issue of Diabetes Care had an article by Dr. Philip Raskin of The University of Texas Southwestern Medial Center who found that using the insulin pump in those with type 2 diabetes lowered hemoglobin A1c by about one half a percentage point.
Added to that was the fact that 93% of participants in the study preferred the pump to multiple injections because it was more convenient, offered greater flexibility and was easier to use.
There were many headlines which came out of the International Diabetes Federation Meetings in Paris. My favorite one was also noted on my Internet server and caught my eye. It appears that Eli Lilly has an experimental drug exenatide that not only controls type 2 diabetes but also reduces weight. The interesting fact is that this drug is made from the saliva of the Gila monster which lives in the Arizona desert. Its saliva secretions help prevent a sudden surge in blood glucose levels in response to the very infrequent meals that Gila monsters eat. The company has completed phase III trials.
The same meetings in Paris were presented with the bad news that more than 300 million people world wide are at risk for developing diabetes and the disease’s economic impact in some hard-hit countries could be higher than that of the AIDS pandemic. According to the Diabetes Atlas report, total direct healthcare spending on diabetes worldwide will be $213 billion, and $396 billion by 2025. The presenters called for action to be taken now to stop the rise of diabetes to reduce the risk of governments and social security systems failing to ensure appropriate care of the millions who will be affected by diabetes by 2025.
Finally, the International Diabetes Federation’s Task Force conducted its second Global Access to Insulin and Diabetes Supplies Survey and reported on its findings in Paris. 74 countries participated, and 30 admitted they cannot insure a continuous supply of insulin to people with type 1 diabetes. The reasons may be acute, such as political upheaval, natural disaster, or economic crisis. Even more challenging are the chronic reasons. which include the high cost of insulin, inadequate supply, poor quality, and transportation problems. The worst area was sub-Saharan Africa where no country reported 100% accessibility. For example in the Democratic Republic of Congo, less than 25% of type 1 diabetics have a regular supply of insulin. The group concluded that the international diabetes community has the responsibility to find solutions to this lack of access to insulin.
Our final headline comes from Circulation 2003;108 and is written by Dr. Ashish K Jha et al at Brigham and Women’s Hospital in Boston. Their study found that black women were twice as likely to sustain a coronary heart disease event compared to white women. While differences of risk factors explain a large part of the lack of correspondence, the black women still have a 50% greater risk after adjusting for risk factors and risk factor control. While Drs. Weintraub and Vaccarino of Emory University concur with the Boston team, they point out the event disparities "tend to be small." In the accompanying editorial, they suggest there are differences in patient characteristics, treatments or lifestyle that "must account for the increased event rates in black women."
We now look at journal articles of interest. The First was published in Diabetes Care 2003;26:2400-2404 and is titled Tight Glucose Control Over Long Term Protect Against Diabetic Neuropathy by Dr. Jakob R. Larson et al of Oslo. Optimal control of blood glucose is strongly associated with long-term preservation of peripheral nerve function in patients with type 1 diabetes. Dr. Larsen and his colleagues note that diabetic polyneuropathy is among the most common long-term complications of the condition. To examine associated factors, the researchers followed 39 diabetic patients over the course of 18 years. Their mean age was 25 years. At that point, they had diabetes for a mean of 12 years. HbA1c was charted prospectively, as was nerve conduction velocity (NCV) and nerve potential amplitude (NAPA) in the lower limbs, at baseline and at 8 and 18 years. HbA1c was found to be significantly associated with both NCV and NAPA at 18 years.
In particular, over the study period, in patients with the highest mean HbA1c (8.4% or more), there was a significant reduction in nerve function. In such patients, the mean NCV in the tibial nerve fell from 47 to 31 meters per second. Furthermore, the number of nerves with NCV and NAPA below the reference level was significantly associated with mean HbA1c. Overall, mean HbA1c below 8.4% was associated with "near normal" nerve function. Summing up, Dr. Larsen told Reuters Health that even after 30 years of diabetes, "most patients who managed to have good glycemic control hardly had any reduction in nerve conduction parameters. This is a good argument the clinician has for in encouraging good glycemic control—targeting a low HbA1c type 1 diabetes."
Low Bone Mineral Density Seen Early in Diabetic Women by Dr. Teresa Quattrin et al in Diabetes Care 2003;2003;26:2365-2369 is mandatory reading for postmenopausal women with diabetes. Women with type 1 diabetes exhibit bone mineral density (BMD) differences early in life, with significant differences seen in the post-teenage years according to this journal article. Dr. Quattrin of the Women and Children’s Hospital of Buffalo and her colleagues compared BMD in young women with type 1 diabetes versus non-diabetic controls. In addition, they looked for any association with BMD, diabetes duration, HbA1c, and biomarkers of bone metabolism. Dual-energy x-ray absorptiometry scan was used to measure BMD in 39 teenage and 33 post-teenage diabetic females and 91 female age-adjusted controls. Compared with controls, diabetic women older than age 20 had significantly lower age-and-body-mass-index-(BMI)-adjusted BMD values at the femoral neck and lateral spine.
The values were not significantly different for those younger than 20 years of age. No differences were observed at the anterior/posterior spine, wrist, or whole body. "No association was found between BMD and diabetes duration or glycemic control". The team believes that the findings may partially explain the high incidence of hip fractures in postmenopausal diabetic women. They hope this and other research will lead to better understanding of the mechanisms at work in this setting and "ultimately to implement strategies for prevention of bone loss and fracture."
Lancet 2003 June 14;361:2005-16 has an article about results of the randomized placebo-controlled U.K. Heart Protection Study, which are of interest to all of us. It concerns statins and those with diabetes, as reported by Sir Brian Jarman, PHD. FRCP, FRCGP, FFPHM, FMedSCi. In this large study, simvastatin therapy (40mg daily) reduced morbidity and mortality among 20,000 patients with total cholesterol levels of at least 135mg/dL, and with coronary disease, other arterial disease, hypertension, or diabetes (Journal Watch Jul30 2002). Now, the researchers report results from the trial’s subgroup of nearly 6000 diabetic patients, most of whom had type 2 diabetes. At baseline, mean total cholesterol level was 220 mg/dL, and mean LDL cholesterol level was 124 mg/dL. The rate of major vascular events was 25% in the placebo group and 20% in the simvastatin group—a significant 22% difference.
Even among participants who had pretreatment LDL cholesterol levels lower than 116 mg/dL and without diagnosed arterial disease at study entry, the vascular event rate was significantly lower in the simvastatin group (8% vs.11%). Among participants who experienced first major vascular events after randomization, subsequent events were significantly less common in the simvastatin group. The authors estimate that 5 years of treatment would prevent about 45 major vascular events per 1000 patients and suggest that statins should be offered to high-risk diabetic patients regardless of their cholesterol levels.
Diabetes Care 26:2604-2608,2003 has an article titled Microvascular Complications at Time of Diagnosis of Type 2 Diabetes Are Similar Among Diabetic Patients Detected by Targeted Screening and Patients Newly Diagnosed in General Practice by Annemieke M.W Spijkerman, PhD et al of the Netherlands. The researchers investigated whether screening-detected diabetic patients differ from diabetic patients newly diagnosed in general practice with regard to the presence of microvascular complications. Diabetic patients, identified by a population-based targeted screening procedure consisting of a screening questionnaire and a fasting capillary whole-blood glucose measurement followed by diagnostic testing, were compared with patients newly diagnosed with diabetes in general practice.
Retinopathy was assessed with fundus photography, impaired foot sensitivity was assessed with Semmes-Weinstein monofilaments, and the presence of microalbuminuria was measured by means of the albumin-to-creatinine ratio (ACR). A total of 195 screening-detected type 2 diabetic patients and 60 patients newly diagnosed in general practice participated in the medical examination. The prevalence of retinopathy was higher in screening-detected type 2 diabetic patients than in patients newly diagnosed in general practice, but not significantly higher. The prevalence of retinopathy was 7.6% in screening-detected type 2 diabetic patients and 1.9% in patients newly diagnosed in general practice. The prevalence of impaired foot sensitively was similar in both groups. The ACR was 0.61 in the screening-detected type 2 diabetic patients and 0.99 in patients newly diagnosed in general practice.
The difference in prevalence of microalbuminuria was 17.2% in screening-detected type 2 diabetic patients, and higher in patients newly diagnosed in general practice, respectively. The researchers concluded that targeted screening for type 2 diabetes (with screening questionnaire as a first step) resulted in the identification of previously undiagnosed diabetic patients with a considerable prevalence of microvascular complications.
The American Journal Of Kidney Disease 2003;42:117-124 has an article has an article to make all of us with type 1 diabetes smile. Incidence of End-Stage Renal Disease in Type 1 Diabetes Declining by Dr. Rimei Nishimura of Tokyo. An international team led by Dr. Nishimura analyzed the incidence of end-stage renal disease and related mortality in 975 patients in Pennsylvania, who had developed type 1 diabetes at least 19 years earlier. When the study was performed, 104 of the patients had developed end-stage renal disease. 29 patients received dialysis, 44 received dialysis followed by renal transplantation, 26 had successful transplants without having been on dialysis, and 5 patients has to resume dialysis after unsuccessful kidney transplants. The authors found that 20-year cumulative incidence rates of end stage renal disease had declined over time.
Specifically, they said, this rate was 9.2% for patients diagnosed with diabetes between 1965 and 1969, 4.7% for patients diagnosed between 1970 and 1974, and 3.6% for those diagnosed between 1975 and 1979. Five-year cumulative survival rates after the introduction of renal replacement therapy—either dialysis or transplantation—also rose over time. For patients diagnosed between 1965 and 1969, 1970 and 1974, and 1975 and 1979, these rates were 58.8%, 73.5%, and 87.5% respectively. However, this increase was not significant, "probably because of the small number of events. The incidence of end stage renal disease...in this cohort...declined, reflecting in all probability the better glycemic control and blood pressure treatment available since the early 1980s" the investigators conclude.
Our last article was found in Clinical Psychiatry News, Aug. 2002 Page 38 by Damian McNamara titled For Diabetics, Drinking Tied to Mortality Drop. This is an interesting article based on the San Antonio Heart Study because it seems to say that people with diabetes who consume up to seven alcoholic drinks per week have a 35% reduction in all-cause mortality compared to diabetics who abstain. Consuming the same amount of alcohol protected non-diabetics to a lesser extent, reducing mortality by 20%. The analysis also suggested that the type of alcoholic drink makes a difference. Researchers gathered baseline data on 3,788 Mexican American and European American men and women between the ages of 35 and 65 years of age. The data included results of a 2-hour oral glucose tolerance test and the self-reported frequency of alcohol intake.
Cox proportional hazard ratios were used to analyze the risk of mortality in 503 participants who met the WHO’s 1999 criteria for diabetes, compared with the mortality risk of nondiabetic participants. The data were adjusted for age, body mass index, smoking status, geographic location, gender, ethnicity, and socioeconomic status. "The surprising finding was when we divided groups into those with and without diabetes, those with diabetes who consumed alcohol more than zero but under seven drinks per week were protected." After a mean follow-up of 14 years, light drinking was associated with a 35% reduction in the risk of all-cause mortality among diabetics, compared with abstainers. For light drinkers without diabetes, there was a 20% reduction in mortality, compared to abstainers. The protective effect of alcohol decreased in those who reported more than 14 drinks per week. Beer drinking did not cut mortality significantly in any study group.
Mixed drinks and/or liquor were mildly protective in diabetics, but actually increased mortality in non-diabetics. Diabetics who reported drinking any amount of wine had the greatest benefit—a 65% reduction in mortality. "The striking thing to me is if you have diabetes, you have a staggeringly high mortality rate, about 40% AT 14 YEARS. If you drink wine, the mortality rate approaches that of non-diabetics." Many questions remain, including the causes of death. A possible confounder in the study is what was called "healthy drinker/sick abstainer."
BSP
