【論文】

The Suppression of Seasonal Exacerbation in HbA1c in
Mellitus Patients with Type 2 Diabetes in JapanAOSA Taishi【Abstract】
Type ２ diabetes mellitus patients show seasonal variation in their hemoglobin
A１c levels. Seasonal variation in hemoglobin A１c levels was able to observe intype ２ diabetes mellitus patients; it decreased between summer and autumn andincreased in winter to spring. HbA１c in diet-educated type ２ diabetic mellitus
patients decreased independently of seasonal variation. Furthermore, early intervention improved blood glucose levels effectively; this may prove to be importantin regulating carbohydrate metabolism in type ２ diabetes mellitus patients who
receive dietary education.
【Keywords】
Dietary education Type ２ diabetes mellitus HbA１c
Retrospective observational study

INTRODUCTION
The treatment of type ２ diabetes mellitus includes preventing lifestyle-related diseases bymanaging weight, blood glucose and serum lipid levels, and blood pressure; the aim is to inhibit the onset and development of additional serious illness. The treatment strategy for a patientʼs lifestyle is aimed at correcting eating behaviors, losing weight, and administering oral
medicine１―３）. Furthermore, appropriate choices of diet and exercise therapy and pharmacotherapy are important to the patientʼs lifestyle and activities of daily living４）. On the other
hand, blood glucose levels of the type ２ diabetes mellitus patient change seasonally, and lifestyle education and therapeutic reinforcement that consider this seasonal periodicity are required５，６）. However, dynamic changes in seasonal periodicity of the blood glucose levels by
dietary education（DE）intervention have rarely been studied. Here we analyzed time serieschanges in hemoglobin A１c（HbA１c）levels of type ２ diabetes mellitus patients and investigated the influence of DE on the seasonal periodicity of HbA１c.

１１７

MATERIALS AND METHODSPatients
This is a retrospective observational study of １３１ type ２ diabetes mellitus outpatients at
Inobe Hospital with whose HbA１c levels were ６．
５％, conducted from January １, ２０１２, toDecember ３１, ２０１４. Patients who had insulin therapy and any change of type ２ diabetes mellitus medication were not included. Because the Ethics Committee of Inobe Hospital waived thenecessity of approving the study, we registered it online in the University Hospitalʼs Medical
Information Network（No．
００００１４９７７）.
The DE intervention was used for ３７ patients（DE group）, and the nonintervention［usualcare（UC）］group contained ９４ patients. Table１shows clinical features of the study participants
at baseline. The baseline study period was defined as medical consultation during April ２０１２.
Follow-up assessments were conducted annually each April. Furthermore, this study divided
the four phases of spring, summer, autumn and winter in view of the characteristics of seasonalvariation in Japan７）. Since the study is a retrospective observational study, the patientʼs background, the disease period, the complications, the type and dose of oral hypoglycemic medications, and the history of dietary education were not considered. But patients using insulin
preparations were excluded from this study.

!

DE
A DE intervention was designed for those patients whose doctors judged that improvementin their eating habits were necessary. In addition, patients who consented to receive treatment toimprove their diet were defined as the DE group. Four periods for this DE intervention were
designated as follows: phase １［April to June（N＝１０）］, phase ２［July to September（N＝１３）］;
phase ３［October to December（N＝７）］, and phase ４［January to March（N＝７）］. At the patientsʼ monthly medical consultation, we performed an individual DE intervention of approximately １５ min. The DE contents were based on the living condition of a particular patient. Using a behavior modification theory８，９）and diabetes mellitus treatment guideline１０）,we set en１０）
ergy intake at ２５―３５ kcal/standard weight（kg）. First, we understood the patientʼs lifestylesituation and taste preferences. Then, we performed DE using the food exchange lists
method１１）, charting of the body weight１２）, and training in food selection１３）.
Charting of daily weight pattern
The charting enables objective visual depiction of body weight and eating behaviors of thepatients to support weight loss１４）. The patient recorded measurements four times every day:“just after waking up”, “just after breakfast”, “just after dinner”, and “just before going tobed”１２，１５）. This study required patients to chart their data during the entire DE intervention
period.

１１８

The Suppression of Seasonal Exacerbation in HbA1c in Mellitus Patients with Type 2 Diabetes in Japan

Food selection training
This study performed food selection training in the DE intervention once a month. This is avirtual method to evaluate eating behavior using food cards１６）. We calculated nutrients andcalories in the ingredients of the foods that patients selected. They compared the nutrient values of their chosen foods and made voluntary choices. Food selection training was incorporated into the treatment program as a method to promote transformation of the eating behavior of the patient voluntarily１３）.
Clinical examination
Laboratory tests were performed at each medical consultation, and HbA１c（％）was assayedby the latex agglomeration turbidimetric method of Bio Majesty ９０３０（JEOL, Ltd., Tokyo, Ja１７）pan）in accordance with the National Glycohemoglobin Standardization Program（NGSP）.
We measured the height and weight of each patient each time to calculate body mass index（BMI, kg/m２）.
Endpoint
Monthly HbA１c levels were compared with the baseline levels. Furthermore, we compared
HbA１c levels every month for the DE and UC groups. We monitored HbA１c levels for １８months from the initial DE for examining the correction effect on HbA１c levels.
Statistical analysis
Statistical evaluations were performed with JMP（version１０．
０．
０，
windows from SAS）software using, and all parameters were non-normal distribution compliant by the Shapiro-Wilk
test. Continuous variables are presented as median and interquartile ranges（IQRs）. Categorical variables are presented as numbers. Pearsonʼs chi-square test was used for comparisons
between sex. Mann-Whitney U test were used for comparisons analysis between groups. Wilcoxon signed-rank test was used to compare the variational parameters each group. Statisticalsignificance was accepted at P ＜０．
０５．

Results
Clinical Characteristics of the Participants
All study population characteristics shown in Table１ failed to conform to the normal distribution according to the Shapiro-Wilk normality test（ P ＜０．
０５）. The only statistically significant differences in baseline characteristics between the groups were mean age（ P ＝０．
０１７１）,
mean body weight（ P ＝０．
０２１７）, and mean BMI（P ＝０．
００６８）. The mean age was significantly
lower in the DE group. In outcome, the mean BMI between the DE and UC groups were notsignificantly different（ P ＝０．
３３１７）, which implies that HbA１c was significantly lower in the
DE than in the UC group（ P ＝０．
０００７，
Table２）.

１１９

Table１．Baseline characteristics of the type ２ diabetes mellitus patients

For number of patients（N）and sex（Male / Female）, the table gives frequencies; other numbers represent medians [IQRs].
HbA１c（％）: hemoglobin A１c, a measure of long-term glucose control, UC: usual care group,
DE: dietary education group, IQRs: interquartile ranges.
Table２．Comparison of the effects of the dietary education group and the usual care groupMann-Whitney U test were used for comparison analysis. Data are shown as median［IQRs］.
HbA１c（％）: hemoglobin A１c, a measure of long-term glucose control, UC: usual care group,
DE: dietary education group, IQRs: interquartile ranges.

Effect of HbA１c on Seasonal Variation and Dietary Education
Amount of change in HbA１c from baseline levels in consecutive of １year are shown for
the UC group in Figure １. There were significant differences in HbA１c change amount from
June to January ２０１３：June（−０．
１
［−０．
３―０．
１］
％，P＝０．
０１０５）, July（−０．
１
［−０．
４―０．
１］
％，
P＝０．
００２１）
, August（−０．
２
［−０．
４―０．
０］
％，P＜０．
０００１）, September（−０．
２
［−０．
４―０．
０］
％，
P＜０．
０００１）
, October（−０．
２
［−０．
４―０．
０］
％，P＜０．
０００１）, November（−０．
２
［−０．
５―０．
０］
％，
P＜０．
０００１）
, December
（−０．
２
［−０．
５―０．
０］
％，P＜０．
０００１）, and January
（−０．
１
［−０．
４―０．
１］
％，
P＝０．
００１２）
. However, February
（−０．
１
［−０．
４―０．
２］
％，
P＝０．
０５２５）
, March（０［−０．
４―０．
２］
％，
P＝０．
２１２）
, and April（−０［−０．
３―０．
２］％，P＝０．
５９２２）did not show a significant difference.
To determine any effects on HbA１c levels by differences in the timing of the DE intervention,these patients were examined before and following intervention in one of four consecutive calendar quarters, phases １―４ from April ２０１３ to March ２０１４：phase １［April to June, N＝１０］,
phase ２［July to September，N＝１３］; phase ３［October to December，N＝７］, and phase ４［January to March，N＝７］. In the phase １ DE group, June（−０．
４５［−０．
８― −０．
１］
％，P＝
０．
０１０９）
, July（−０．
７５［−１．
２― −０．
３］％，P＝０．
０００２）, August（−０．
８５［−１．
３― −０．
４］
％，P＝
０．
００２４）
, September（−０．
７５［−１．
２０― −０．
２］％，P＝０．
０１７６）, November（−０．
５［−１．
４― −０．
３］

１２０

The Suppression of Seasonal Exacerbation in HbA1c in Mellitus Patients with Type 2 Diabetes in Japan％，P＝０．
０４４４）, February（−０．
６
［−１．
５―０．
０］
％，P＝０．
０３９９）, March（−０．
７［−１．
４― −０．
２］％，P＝０．
０００３）, and April（−１．
０［−１．
４― −０．
３］％，P＝０．
０００８）showed significantly decreased HbA１c levels compared with the UC group. Furthermore, HbA１c levels significantly
decreased（P＜０．
０５）from June to December and February to April compared with the Phase
１DE group baseline level（Fig．
１a）.
Second, in phase ２ DE group April（−０．
３
［−０．
８―０．
１］
％，P＝０．
０４８３）showed significantly
decreased（P＜０．
０５）HbA１c levels compared with the UC group. December HbA１c levelsignificantly decreased compared with the phase ２ DE group baseline（Fig．２b）.
In phase ３ DE group, March
（−０．
５
［−０．
７― −０．
１］％，P＝０．
０１５８）
and April（−０．
７
［−１．
３―
−０．
２］
％，P＝０．
０１２３）showed significantly decreased HbA１c levels compared with the UC
group. Furthermore, the phase ３ DE Group HbA１c levels significantly decreased （P＜０．
０５）
in October and March compared with the baseline（Fig．
１c）.
HbA１c levels of the phase ４ DE Group were lower than both the baseline level of thephase ４ DE Group（P＜０．
０５）and those of the UC Group（−０．
５［−０．
７― −０．
３］％，P＝０．
０９３）
in April（Fig．１d）.

Prolonged Effect of the HbA１c Correction by the DE Intervention
This study investigated changes in HbA１c levels an １８―month duration from the start of
the DE interventions（Fig．２）. HbA１c levels significantly decreased from the guidance at thestart（compared with their baseline）for the first １２ months（P＜０．
０５）, but it was not significant
thereafter.

１２１

Figure１．Change in HbA１c from baseline levels by differences in the timing of the DE intervention. The different intervention times（black lines）were（a）phase １（April to June）,（b）phase ２（July to September）,（c）phase ３（October to December）, and（d）phase ４（January＊＊
to March）. Data are shown as median, ２５th and ７５th percentiles. * P ＜０．
０５，
P ＜０．
０１ vs. the††UC group（Mann-Whitney U test）；†P ＜０．
０５，
P ＜０．
０１ vs. the DE group baseline（Wilcoxon

signed-rank test）；and P ＜０．
０５ vs. the UC group baseline（Wilcoxon signed-rank test）.

Figure２．
Prolonged effect of the dietary education. The x-axis was shown the progress of the＊＊months. Data are shown as median, ２５th and ７５th percentiles. * P ＜０．
０５，
P ＜０．
０１ vs. base-line（Wilcoxon signed-rank test）.

DISCUSSION
At baseline, the patients in the DE group were significantly younger and heavier than thosein the UC Group, without a marked difference in HbA１c levels（Table１）. The DE corrected
their HbA１c levels; and BMI was no longer significantly different from the UC Group（Table
２）.
Consideration of seasonal variation in HbA１c levels in type ２ diabetes mellitus patients demands more effective glycemic control. HbA１c levels decrease from summer to autumn, andin winter to spring, they show a tendency to increase. The DE markedly decreased HbA１clevels below the respective baseline levels in all four seasons（Fig．１）.
The presence of this seasonal variation in HbA１c levels of type ２ diabetes mellitus patients isalready known and has been associated with age, sex, region, and insulin administration５，６，１８）.
In Japanese type ２ diabetes mellitus patients, blood glucose and HbA１c levels are low insummer and high in winter and spring. It is believed that the seasonal variation in climate influences appetite; its decline with elevation of the ambient air temperature in summer and its
increase with the decrease in the temperature in winter may be the cause of the observed
seasonal variation in HbA１c levels６，１９）. The results of this study did not contradict these reports. However, DE intervention corrected HbA１c regardless of seasonality.
DE intervention in the phase １ DE group was able to inhibit baseline increase in HbA１c levels（Fig１a）. Along with the decrease in HbA１c in summer, glucose metabolism was effectively
improved by providing substantial dietary education. Therefore, an early DE intervention may
be important for improving the blood glucose levels of diabetic patients. Patients who gain

１２２

The Suppression of Seasonal Exacerbation in HbA1c in Mellitus Patients with Type 2 Diabetes in Japan

more knowledge regarding food can better recognize the characteristic appetite-regulating
mechanisms of taste, memory, learning, and experience that the effect of DE intervention cancontribute to correcting their eating behavior２０，２１）. Although the number of patients in thisstudy was limited, it is suggested that an effect on improving carbohydrate metabolism was
obtained by this DE intervention.
Furthermore, a prolonged effect of the DE intervention on glycemic control was obtainedfor １２ months, but a marked effect was not observed thereafter（Fig．
２）. The behavior modification deriving from the DE intervention possibly relapses over time２２）. From this observation,
the intervention of periodic education may help the behavior modification persist２３―２６）. Our
study findings suggest that the abovementioned dietary intervention may be necessary atleast once a year. Continuous charting of daily weight and continuous DE may also prove tobe important in promoting more effective treatment１４）. These possibilities await further investigation. In addition, it is worth investigating if continuous DE is similarly effective in patients
who are treated with insulin and/or oral hypoglycemic medications.
Limitations of this study were the limited number of patients and relatively short period of
observation and analysis. These factors must be considered in future studies. In addition, toachieve long-term glycemic control in these patients, annual reinforcement of dietary behavior
modification appears to be necessary. In conclusion, the presence of the seasonal variation in
HbA１c levels was clearly observed in type ２ diabetes mellitus patients. In addition, the DEintervention markedly improved seasonal variation in HbA１c and contributed to the carbohydrate metabolism correction of the HbA１c levels in the patients.

Acknowledgments
I thank directorʼs INOBE JUN-ICHI of the Inobe Hospital, who supported this study.

Conflicts of interest
I have no disclosure and financial support.

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１２４

The Suppression of Seasonal Exacerbation in HbA1c in Mellitus Patients with Type 2 Diabetes in Japan【要旨】
日本の糖尿病患者の糖代謝には季節変動が存在する。本研究は、栄養食事指導の介入による２型糖尿病患者の HbA１c の季節変動の有無を検討した。HbA１c の季節変動は、２型糖尿病患者において存在し、その推移は夏と秋の間に減少、冬と春に増加を示した。栄養食事指導は、介入する季節性に関係なく、HbA１c を低下させ、より効果的に糖代謝を是正した。

１２５