Seasonal Variations in Urinary Albumin-to-Creatinine Ratios in Patients With Type 2 Diabetes and Nephropathy

Daniel M. Keller, PhD

September 30, 2010

October 1, 2010 (Stockholm, Sweden) — Researchers found a seasonal variation in the urinary albumin-to-creatinine ratio (UACR) in Japanese patients with type 2 diabetes and early nephropathy. UACR peaked in winter, an effect at least partly attributable to seasonal changes in systolic blood pressure. The investigators suggested that clinicians consider this seasonal variation when evaluating the effect of drugs on diabetic nephropathy.

Reporting their findings during a poster session here at the European Association for the Study of Diabetes 46th Annual Meeting, the investigators noted that blood pressure has been seen to increase in winter, compared with summer, and some reports have shown a seasonal change in glycemic control and the onset of diabetes. However, until this study, it was not known whether kidney function in patients with diabetic nephropathy varied with the season in relation to blood pressure.

Therefore, a group led by Yoshiharu Wada, MD, from the Center for Diabetes and Endocrinology at the Tazuke Kofukai Foundation Medical Research Institute Kitano Hospital in Osaka, Japan, recruited 430 patients (275 male, 155 female) with type 2 diabetes, early nephropathy, and microalbuminuria. Their mean age was 64.8 years. Subjects visited the clinic regularly every 3 months, and data were collected at every visit from 2006 to 2009. Microalbuminuria was defined by a UACR of 30 to 300 mg/g of creatinine. Patients with an advanced stage of nephropathy with increased creatinine were excluded from the study.

The year was divided into 4 seasons: winter (December through February), spring (March through May), summer (June through August), and fall (September through November).

"There were significant seasonal variations in the [UACR], systolic blood pressure, and HbA1c [glycated hemoglobin]," Dr. Wada said. The UACR was highest in the winter, as was systolic blood pressure. In contrast, HbA1c peaked in spring. Estimated glomerular filtration rate (eGFR) and diastolic blood pressure showed no significant seasonal variations.

Seasonal Variation in Clinical Parameters Related to Diabetic Nephropathy With Microalbuminuria

Parameters Highest season Lowest season P value
UACR (mg/g of creatinine) Winter 72.8 ± 4.4 Summer 54.6 ± 3.4 .002
Systolic blood pressure (mm Hg) Winter 136 ± 0.68 Summer 133 ± 0.68 <.001
HbA1c (%) Spring 7.39 ± 0.03 Fall 7.15 ± 0.03 <.001

There was a significant correlation between systolic blood pressure and UACR (= .05, r = .79), with UACR rising with increased systolic pressure. The researchers observed no correlation between blood pressure and HbA1c or between HbA1c and UACR.

The fact that both UACR and systolic blood pressure were highest in winter and lowest in summer "suggests that the seasonal change in systolic blood pressure . . . may contribute to the variations in UACR," Dr. Wada said. He added that the seasonal change in blood pressure seen here is consistent with a previous report (Am J Geriatr Cardiol. 2004;13:267-272).

One meeting attendee wondered if the findings could be related to seasonal variations in serum vitamin D levels, and asked Dr. Wada if he had measured vitamin D in his subjects, to which Dr. Wada replied that he had not. Peter Rossing, MD, DMSc, chief physician at the Steno Diabetes Center in Gentofte, Denmark, said that at last year's American Society of Nephrology meeting, a study was presented showing that treatment with a vitamin D receptor activator could reduce albuminuria in type 2 diabetic patients (de Zeeuw D et al. Renal Week 2009: Abstract LB-002). Per-Henrik Groop, MD, DMSc, professor of nephrology at the University of Helsinki in Finland, suggested that Dr. Wada go back and analyze the vitamin D levels if he still has samples available.

Indeed, using data from the Third National Health and Nutrition Examination Survey, de Boer and colleagues (Am J Kidney Dis. 2007;50:69-77) found a stepwise increase in the prevalence of albuminuria with decreasing quartiles of serum 25-hydroxyvitamin D concentration (< .001). Even after adjustment for demographic variables, region, season of measurement, smoking status, body mass index, and eGFR, this relation persisted.

The lowest quartile for serum vitamin D had a relative risk for albuminuria of 1.37 (95% confidence interval, 1.10 - 1.71; =.006), compared with the highest quartile. With additional adjustment for blood pressure and diabetes, the risks were somewhat attenuated, but still statistically significant. Because this study was observational, the researchers could not determine any temporal or causal relation between vitamin D levels and albuminuria.

The Japanese investigators took blood samples at 4 time points 3 months apart. Being a bit provocative, Dr. Groop questioned what would happen if one took 4 samples on the same day, with a view that there might be diurnal variations that one should be aware of before concluding that all the variations seen were seasonal ones. An audience member from Finland, where the winters are cold and where "we have a rather nice summer," asked if the amount of exercise could have influenced Dr. Wada's results, but Dr. Wada said his group did not collect data on exercise.

The study had no commercial funding. Dr. Wada has disclosed no relevant financial relationships. Dr. Rossing is an employee of the Steno Diabetes Center, which is owned by Novo Nordisk. Dr. Groop reports being on an advisory board for Boehringer Ingelheim.

European Association for the Study of Diabetes (EASD) 46th Annual Meeting: Abstract 1214. September 23, 2010.