Clinical BriefsBy Louis Kuritzky

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville

Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.

Diabetes and Cognitive Function

Source: Spauwen PJ, et al. Effects of type 2 diabetes on 12-year cognitive change: Results from the Maastricht
Aging Study. Diabetes Care 2013;36: 1554-1561.

The relationship between vascular disease and type 2 diabetes is consistent: Risk for microvascular events (retinopathy, neuropathy, and nephropathy) and macrovascular events (stroke and MI) is increased compared to non-diabetics. Additionally, when diabetics suffer macrovascular events, the consequences are typically more severe than similar events in non-diabetics.

The etiology of cognitive impairment is often multifactorial, including vascular insufficiency. Diabetics have a higher prevalence of cognitive impairment than non-diabetics, but the rate of cognitive decline in diabetics has not been studied.

The Maastricht Aging Study is comprised of 10,396 adults residing in the province of Limburg, the Netherlands. A sample from this population (n = 1290) underwent extensive neuropsychological testing at baseline, 6 years, and 12 years. At baseline, approximately 5% of the population had type 2 diabetes, with an incidence of an additional 5% over subsequent 6-year intervals.

When compared with controls, diabetics had a significant rate of cognitive decline over 6 and 12 years. Even when adjusted for variables that are more commonly comorbid in diabetics (hypertension, dyslipidemia, obesity), the acceleration in cognitive decline was greater in diabetics. As might be intuitive, diabetics with baseline cognitive impairment progressed at a more rapid rate than those without. Whether any specific intervention among diabetics (e.g., better control of glucose, lipids, blood pressure) might ameliorate the exaggerated rate of cognitive decline remains to be determined.

Low Creatinine Excretion Associated with Mortality in Type 2 Diabetes

Source: Sinkeler SJ, et al. Creatinine excretion rate and mortality in type 2 diabetes and nephropathy. Diabetes Care 2013;36:1489-1494.

Creatinine excretion (cer), as measured by the 24-hour urinary excretion of creatinine, has recently been noted to be associated with increased mortality, both in persons with underlying renal disease and the general population. CER reflects overall lean muscle mass, so that declines in CER may simply reflect deconditioning, loss of muscle mass, cachexia, malnutrition, etc., each of which may have a negative impact on mortality.

Sinkeler et al report on data accrued from two previously completed trials of angiotensin receptor blockers in diabetic nephropathy: Reduction of Endpoints in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan trial and the Irbesartan Diabetic Nephropathy trial. Twenty-four hour urinary CER was measured at baseline for the majority (n = 2360) of participants. Since mortality data from both trials are available, the relationship between CER and mortality can be evaluated.

Across the population studied, each halving decrement of CER was associated with a doubling of mortality risk. Since the primary association of CER is with muscle mass, the authors pose the interesting question of whether efforts expended to improve muscle mass, such as enhanced exercise and nutrition, might favorably effect mortality in this population.

Benefits of Screening for Lung Cancer with Low-Dose CT

Source: The National Lung Screening Trial Research Team. Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med 2013;368:1980-1991.

Lung cancer (lca) is responsible for more deaths than any other cancer worldwide. The burgeoning growth of smoking in developing countries suggests that this dismaying fact is unlikely to diminish in the foreseeable future. Clinical trials of screening for LCA through chest x-ray (CXR) did not show improved outcomes, likely because of its relatively poor discriminative ability in early disease.

The National Lung Screening Trial enrolled smokers and ex-smokers with at least a 30 pack-year history. Participants were randomized to an annual low-dose CT × 3 (n = 26,714) or standard chest x-ray (n = 26,035).

A positive radiographic finding on at least screening was seen in three times as many CT screenees as chest x-ray (27.3% vs 9.2%). LCA was diagnosed in 1.1% of the CT group vs 0.7% in the CXR group.

Screening for LCA was found to reduce LCA-related mortality by 20% and all-cause mortality by 7%.

Most of the abnormalities detected by low-dose CT screening were benign, so that the positive-predictive value for a positive CT was only 3.8% (i.e., about 4% of study subjects with any positive suspicious finding on CT turned out to have LCA). Reassuringly, repeatedly negative low-dose CT had a negative predictive value of 99.9% (i.e., essentially no one who had negative sequential CT screening was diagnosed with LCA during the screening and follow-up period).