Shinshu Med J, 71⑶：149～158, 2023

Trend of Diabetes Care for Elderly Patientsat a Single Center from 2009 to 2019
Yasuyuki Furukawa＊, Morito Nishizawa, Hirofumi Nakano and Hiroshi YuiInternal Medicine, Shiojiri Kyoritsu HospitalObjective : We performed a narrative analysis of the data of diabetes of elderly patients how the Japanese Clinical
Practice Guidelines have worked on glycemic control.
Methods : We analyzed two sets of data, one from patients who visited initially during April and June in 2009, 2014
and 2019, respectively, and the other from 168 patients followed for 10 years successively, with analysis on Hb(hemoglobin) A1c and the number of hypoglycemic agents (prescriptions)/patient.
Results : In the first set, the patient numbers were 351, 487 and 572 in each year with a mean age of 68.5, 70.5
and 71.7 years, respectively. The mean HbA1c, 7.3～7.4 ％, was not significantly different from each year, but
prescriptions/patient were greater in 2019 than in 2009, 1.7±1.3 (mean±SD) vs 1.2±1.1. Upon division into
Groups 1 to 3 by age, ＜65 years, 65 to 74 years, and ≥ 75 years old, respectively, HbA1c was greater in Group 1
than in Groups 2 and 3, and so were prescriptions/patient, especially DPP-4i and SGLT-2i. In the second set, themean HbA1c was greater with time and so were prescriptions/patient, 1.2±1.1 in 2009 vs 2.1±1.4 in 2019. Upon
division into three groups (T1, T2 and T3) by age tertile, with a mean age of 55.7, 66.0, and 75.4 years in 2009,
respectively, HbA1c was higher and the fraction of the patients having ＜7.0 ％ HbA1c less in T1 than in T3.
Prescriptions/patient were greater in T1 than in T3 all through the observation period.
Conclusion : Diabetes control has been at a reasonable level in the elderly patients ( ≥ 65 years) but not in the
middle-aged. Shinshu Med J 71 : 149―158, 2023
(Received for publication December 13, 2022 ; accepted in revised form January 23, 2023)
Key words : glycemic control, HbA1c, new class oral hypoglycemic agents, elderly patient
Abbreviations : RPG ; random sample plasma glucose, HbA1c ; hemoglobin A1c, SU ; sulphonylureas, α-GI ; alphaglucosidase inhibitor, DPP-4i ; dipeptidyl peptidase-IV inhibitor, SGLT-2i ; sodium glucose cotransporter 2 inhibitor,
CKD ; chronic kidney disease, CVD ; cardiovascular disease
rently1）, it is recommended the glycemic targets for

Ⅰ Introduction

older patients with diabetes be determined after

The aim of the Clinical Practice Guidelines for the

careful consideration of the patient’s age, duration ofTreatment of Diabetes has been to widely implement

diabetes, risk of hypoglycemia, qualitative and quan-evidence-based, rational, efficient and standardized

titative help from surrounding people, and most im-

clinical practice for diabetes all over Japan, and has

portantly the patient’s cognitive function. In addition,

1）

undergone revisions every 3 years since 2004 . The

one should pay close attention to the basic/instru-

notable changes in the recent Guidelines were mademental activities of daily living, and comorbidities/

for the treatment of diabetes in elderly people. Cur-

functional impairments1）.

＊

Corresponding author : Yasuyuki Furukawa
Internal Medicine, Shiojiri Kyoritsu Hospital, Sajiki 437,
Shiojiri City, Nagano 399-0716, Japan
E-mail : FurukawaY@chushin-miniren.gr.jp

No. 3, 2023

In this study, we performed a narrative analysis ofreal world data of diabetes of elderly people during
the last 10 years at a single center to see how the
Guidelines have worked on the glycemic control of149

Furukawa・Nishizawa・Nakano et al.
Table 1

Characteristics of the patients with diabetes registered in 2009, 2014 and 2019

Variable

2009

2014

2019

No. of patients
Female sex (％)
Ages (yr)351
4368.5±10.2487
4370.5±11.0572
4471.7±11.8＊＊＊

RPG (mg/dl)

167±76.2

166±62.9170±69.0ns

HbA1c (％)

7.3±1.1

7.3±1.2

7.4±1.1ns

HbA1c＜7.0 ％46.7±50.0

48.7±50.0

40.6±49.1ns

Drugs

71.7±45.1

74.5±43.6

78.2±41.3ns

No. of drugs

1.2±1.1

1.4±1.2

1.7±1.3＊＊＊

InsulinSU

16.0±36.7
47.3±50.0

13.8±34.545.2±49.8

12.9±33.6ns
38.5±48.7＊

Metformin
α-GI

13.4±34.1

18.9±39.2

26.2±44.0＊＊＊

21.4±41.0
16.5±37.2014.8±35.5
8.8±28.440.5±49.1

10.3±30.4＊＊＊
6.6±24.9＊＊＊58.7±49.3＊＊＊00.4±6.417.3±37.9＊＊＊

CKD

11.7±32.2

17.5±38.0

17.8±38.3＊

CVD

71.8±45.1

76.6±57.3

74.8±43.4ns

Treatment (％)

Pioglitazone
DPP-4i
SGLT-2i
Complications

Data in 2009, 2014 and 2019 as a factor were analysed by one-way analysis of variance. Between
groups comparison was made by Bonferroni test.
ns not significant, ＊p＜0.05, ＊＊p＜0.01, ＊＊＊p＜0.001. The number of patients with type 1 diabetes
was 3, 3, and 8 in the year 2009, 2014, and 2019, respectively.
Abbreviations : RPG ; random sample plasma glucose, HbA1c ; hemoglobin A1c, SU ; sulphonylureas,
α-GI ; alpha-glucosidase inhibitor, DPP-4i ; dipeptidyl peptidase-Ⅳ inhibitor, SGLT-2i ; sodium
glucose cotransporter 2 inhibitor, CKD ; chronic kidney disease, CVD ; cardiovascular disease

the patients. We also focused our attention on thewith diabetes were 351, 487 and 572 in 2009, 2014

impact of the newer class oral hypoglycemic agentsand 2019, respectively (Table 1). The small number

1）-6）(OHAs)

such as dipeptidyl peptidase-IV inhibitorsof patients with type 1 diabetes were included(DPP-4i), sodium glucose cotransporter 2 inhibitors(Table 1). We analyzed them together to show the(SGLT-2i) and glucagon like peptide 1 receptor ago­

real world data of diabetes in our hospital. We ex­nist (GLP-1a) on the glycemia attained in the pa­

tracted data such as gender, age (years), random

tients with type 2 diabetes.

sample plasma glucose (RPG) (mg/dl), HbA1c (％), andⅡ Methods
Ａ

Patients

the information on prescribed drugs from the elec­
tronic charts. The information on the prescription
included the classes and dosing of OHAs (glinides

Diagnosis of diabetes was made according to thewere combined with sulphonylureas (SU) because

Japanese Clinical Practice Guideline for Diabetes

only a few patients were receiving glinides) and the1）2016 and a total of 1396 patients with type 2 diabetes

preparations and dosing of insulin. We also recorded

who visited our hospital for at least 3 months fromthe presence of chronic kidney disease (CKD), which

April 1 to June 30 in each year of 2009, 2014 and 2019,was diagnosed on the basis of the guideline, and hy­

were registered (Table 1). The numbers of patients

pertension and macrovascular events such as cere­

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Diabetes care for elderly patients

The proportion of the patients with a yearly mean

brovascular and cardiovascular (CVD) events on thebasis of the patient’s self-report.

HbA1c lower than 7.0 ％ was 46.7 (±50.0), 48.7 (±Ｂ

Study Design50.0) and 40.6 (±49.1) ％ in 2009, 2014 and 2019, re-Cross-sectional analysis

spectively, and the values were not significantly dif-First, we compared the characteristics of the patients registered in 2009, 2014 and 2019 depending on

ferent from each other.
２

Use of OHAs

The number of OHAs prescribed per patient was

the age.
The patients were classified into three groups ac-

1.2 (±1.1) in 2009 and 1.7 (±1.3) in 2019, with thecording to the age at registration : the middle-agedlatter significantly greater than the former (p＜0.001,(younger than 65 years), the elderly (65 to 74 years)

Table 1). On the other hand, the proportion of theand the advanced elderly (75 years and older) as

patients receiving exclusively non-pharmacologicalneeded.

treatment decreased from 28 ％ in 2009 to 22 ％ in

Longitudinal analysis

2019 (Table 1).

Second, to determine the long-term trend of pre-３ Pharmacological treatment including insulin

scription of hypoglycemic agents and insulin prepa-(Table 1)

rations and the level of glycemic control, the data

The fraction of patients with diabetes treated withfrom 168 patients who had been continually seen by

insulin and/or OHAs insignificantly increased fromus for the 10 years from 2009 to 2019 were analyzed.

71.7 (±45.1) ％ in 2009 to 78.2 (±41.3) ％ in 2019. De-Ｃtailed analysis revealed that the patients treated with

Statistical analysis
The data are shown as mean±SD. An analysis ofSU, alpha glucosidase inhibitor (α-GI) and pioglitazone

variance (one-way or two-way mixed model) was

significantly decreased (p＜0.05). On the other hand,used for the multiple comparisons and the Bonferroni

the fraction of patients receiving metformin, DPP-4i

test was used for comparisons between the two groups

and SGLT-2i increased significantly (p＜0.001).

if necessary. P values of less than .05 were considered
statistically significant.
Ⅲ Results

The patients with CKD, but not CVD, increased
gradually (p＜0.05) during the 10 years.
４ Age-related characteristics of the patients(Table 2)
The patients were classified into three groups on

Ａ Changes in HbA1c, RPG and drugs for thepatients in 2009, 2014 and 2019１ Characteristics of the patients registered in 2009,2014 and 2019the basis of age : ＜65 years (adults group : G1), 65-74
years (elderly group : G2) and ≥ 75 years (advanced
elderly group : G3).

The number of patients was 351, 487 and 572

The number of elderly (G2) and advanced elderly

in 2009, 2014 and 2019, respectively (Table 1). The

patients (G3) with diabetes increased with time butmean (±SD) age was progressively higher in thethe number of adults (G1) was not significantly differ-

later years : 68.5 (±10.2), 70.5 (±11.0) and 71.7 (±11.8)

ent during the 10 years.

years, respectively. The fraction of the middle-aged

RPG exhibited no significant change during the 10

patients was thus progressively less with time asyears. HbA1c in each group did not show significant

33 ％ (115 of 351) in 2009 and 22 ％ (125 of 572) in 2019change either except for the value in G1 being greater(Table 2). On the other hand, the fraction of advanced

in 2019 than those in G2 and G3 (p＜0.001).

elderly patients increased greater with time as 30 ％

５(104 of 351) in 2009 and 45 ％ (259 of 572) in 2019.

Fulfillment of the recommended HbA1c value
The HbA1c target was recommended to be ＜7.0 ％The RPG and the mean HbA1c were not signifi-

for the patients with diabetes at large and ＜8.0 ％cantly different among the patients in 2009, 2014 andfor the patients ≥ 75 years being treated by SU and/2019 (Table 1).

or insulin or having dementia (1). As shown in Table

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Table 2 Characteristics of the 3 groups, G1, G2 and G3, of the patients with diabetes in 2009, 2014 and 2019
Glycemia

2009

2014

2019

G1 ＜65 yrs.
G2 65～74 yrs.
G3 75 ≤ yrs.

57.1±6.7 (n＝115)69.5±2.9 (n＝132)
79.9＋3.9 (n＝104)56.2±7.4 (n＝125)69.4±2.8 (n＝175)
81.1＋4.6 (n＝187)54.4±8.0 (n＝125)
69.7±2.6 (n＝188)
81.6＋5.3 (n＝259)

G1 RPG (mg/dl)
G2 RPG (mg/dl)
G3 RPG (mg/dl)

159.4±89.2♯
163.4±60.8
186.6±75.8

154.6±65.0♯
166.9±62.3
173.8±61.2

164.6±79.5ns♯♯♯155.5±60.2ns
183.3±67.3ns

G1 HbA1c (％)
G2 HbA1c (％)
G3 HbA1c (％)

7.4±1.2NS
7.2±1.0
7.2±1.1

7.4±1.2NS
7.3±1.2
7.2±1.2

7.6±1.4ns♯♯♯7.2±0.8ns
7.4±1.0ns

G1 HbA1c＜7.0 ％G2 HbA1c＜7.0 ％G3 HbA1c＜7.0 ％45.2±50.0NS
47.7±50.1
47.1±50.2

42.4±49.6NS
50.9±50.1
46.5±50.0

34.4±47.7ns NS
43.1±49.7ns
41.7±49.4ns

G1 HbA1c＜8.0 ％G2 HbA1c＜8.0 ％G3 HbA1c＜8.0 ％77.4±42.0NS
79.5±40.5
81.7±38.8

72.8±44.7NS
80.6±39.7
80.7±39.7

73.6±44.3ns♯
85.6±35.2ns
76.1±42.8ns

G1 No. of drugs
G2 No. of drugs
G3 No. of drugs

1.4±1.2♯
1.1±1.0
1.0±0.9

1.5±1.2NS
1.5±1.2
1.3±1.1

2.2±1.4＊＊＊♯♯♯
1.7±1.3＊＊＊
1.5±1.3＊＊

G1 Insulin
G2 Insulin
G3 Insulin

22.6±17.7♯
14.4±12.4
10.5±9.6

18.4±15.1NS
12.6±11.1
11.8±10.4

19.2±39.5ns♯♯
7.4±26.3ns
13.9±34.7ns

G1 SU
G2 SU
G3 SU

47.8±25.2NS
44.7±24.9
50.0±25.2

40.0±24.2NS
46.3±25.0
47.6±25.1

43.2±49.7ns NS
39.4±45.0ns
35.5±48.0＊＊

G1 Metformin
G2 Metformin
G3 Metformin

14.8±12.7NS
14.4±12.4
10.6±9.6

22.4±17.5NS
21.1±16.8
14.4±12.4

39.2±49.0＊＊＊♯♯♯
29.8±45.9＊＊17.4±38.0ns

G1 α-GIG2 α-GIG3 α-GI21.7±17.2NS
18.9±15.5
24.0±18.4

13.6±11.8NS
15.4±13.1
15.0±12.8

8.8±28.4＊NS
10.1±30.2ns
11.2±31.6＊＊

G1 Pioglitazone
G2 Pioglitazone
G3 Pioglitazone

31.3±21.7♯♯♯14.4±12.4
2.9±2.810.4±9.4NS
10.9±9.7
5.9±5.6

6.4±24.6＊＊＊NS
7.4±26.3ns
6.2±24.1ns

Treatment (％)

G1 DPP-4i
G2 DPP-4i
G3 DPP-4i00044.0±24.8NS
42.3±24.5
36.4±23.3

60.8±49.0＊＊＊NS
61.2±48.9＊＊＊56.0±49.7＊＊＊

G1 SGLT-2i
G2 SGLT-2i
G3 SGLT-2i0000.8±0.8NS
0.6±0.6040.0±49.2＊＊＊♯♯♯
14.9±35.2＊＊＊
8.1±27.3＊＊＊

G1 CKDG2 CKDG3 CKD

10.4±30.7NS
8.3±27.717.3±38.0

13.6±34.4NS
16.0±36.8
21.4±41.1

13.6±34.4ns♯♯♯10.1±30.2ns
25.5±43.7ns

G1 CVDG2 CVD
G3 CVD52.2±50.2♯♯♯76.5±42.687.5±33.2

60.8±49.0♯♯♯73.1±44.4
85.6±35.2

56.0±49.8ns♯♯♯70.7±25.1ns
86.9±33.8ns

Complications

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Diabetes care for elderly patients

2, the fraction of the patients with mean HbA1c ＜7.0

scribed after 2014 (p＜0.001).

％ and ＜8.0 ％ in G1 (＜65 years) was not significantly

CVD and CKD of patients with diabetes increased

different except in 2019, when the fraction having ＜during the 10 years (p＜0.001), especially (p＜0.001) in

8.0 ％ in G2 was greater than in G1 and G3.

the older groups (G2 and G3).

６ The trend of prescription of hypoglycemic agents

Ｂ Changes in HbA1c, RPG and drugs for patients

The number of the OHAs prescribed/patient withseen continuously from 2009 to 2019 : a longitudi-diabetes was significantly larger in G1, G2 and G3

nal analysis

groups with time over the 10 years (p＜0.01). The

The mean age (±SD) of the 168 patients with dia­

number of prescribed OHAs in G1 was significantly

betes treated successively for 10 years was from 65.7

greater (p＜0.05) than in G2 and G3 groups in 2009(±9.1) to 75.4 (±9.1) years (Table 3).

and 2019.

The mean HbA1c of the 168 patients increased

The fraction of insulin-treated patients was not
significantly different between each other over thesignificantly (p＜0.05) from 7.3 (±1.1) to 7.6 (±1.1)％ during the 10 years.

10 years. However, in each year, the fraction of insulin

The fraction of patients with HbA1c ＜7.0 ％ de­usage in G1 was greater than in G2 and G3 (p＜0.05,

creased from 47.0 (±50.1) to 26.8 (±44.4) ％ (p＜except for 2014). SU treatment tended to decrease in

0.001) but that with HbA1c ＜8.0 ％ did not decrease

the elderly groups during the 10 years. On the otherduring the 10 years.

hand, the fraction of metformin prescription has in­

The mean fraction of the patients receiving phar­creased significantly (p＜0.001) during the 10 years.

macological agents has significantly increased fromIn 2019, the younger the patients (G1), the more

69.0 ％ (±46.4) to 86.9 ％ (±33.8) (p＜0.001) (Table 3).

were treated by metformin (p＜0.001). The fraction ofThis was naturally associated with a decrease in thethe α-GI treatment also significantly decreased during

patients exclusively treated with diet and exercise.

the same period in G1 and G3 (p＜0.05). The fraction

The fraction of the patients treated with insulinof the patients treated by pioglitazone did not change

injection did not significantly change during thesignificantly in G2 and G3 but that in G1 was signifi­

10 years. This was also the case for those receiving

cantly decreased (p＜0.001). Consequently, the frac­SU, α-GI and pioglitazone. On the other hand, the frac­tion of the pioglitazone treatment in G1, at 2009, wastion of the patients treated with metformin, DPP-4i

greater than those in G2 and G3 (p＜0.001) but suchor SGLT-2i significantly increased (P＜0.001) (Table 3).

an age-related difference was not apparent in 2014

Upon dividing the 168 patients into three groups

and 2019. Treatment by the newly developed drugs,by age tertiles, the mean age of the three groups, T1,

DPP-4i and SGLT-2i, increased significantly (p＜T2 and T3, were 55.7 (±6.2), 66.0 (±2.4) and 75.4 (±0.001) yearly after marketing. DPP-4i treatment was3.2) years, respectively in 2009 (Table 4).

not significantly different among the 3 groups but

The mean HbA1c and RPG of the patients increased

the younger they were, the more SGLT-2i was pre­slightly during the 10 years (p＜0.05) (Fig. 1a, b).

Table 2The three groups, G1, G2 and G3, were less than 65 years (middle-aged group), 65 years andmore than 65 and less than 75 years (elderly group) and 75 years and more (advanced elderlygroup), respectively.
Data among the 3 groups, G1, G2 and G3 as a factor were analysed by one-way analysis ofvariance and data in 2009, 2014 and 2019 as a factor were analysed by one-way analysis ofvariance. Between groups comparison was made by the Bonferroni test.
ns not significant, ＊p＜0.05, ＊＊p＜0.01, ＊＊＊p＜0.001 in each group, G1, G2 and G3 among three
years.
NS not significant, ♯ p＜0.05, ♯♯ p＜0.01, ♯♯♯ p＜0.001 among the 3 groups, G1, G2 and G3, in2009, 2014 and 2019.
Abbreviations are the same as Table 1.

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Table 3Characteristics of the patients with diabetes treated successively for 10 years from 2009 to 2019
2009

2014

2019

168
47.6
65.7±9.1

70.5±9.1

75.4±9.1＊＊＊

RPG (mg/dl)

161±67.2

171±60.8

180±69.4＊

HbA1c (％)

7.3±1.1

7.4±1.2

7.6±1.1＊

HbA1c＜7.0 ％47.0±50.1

38.7±48.8

26.8±44.4＊＊＊

HbA1c＜8.0 ％80.4±39.8

77.4±42.073.2±44.4ns

Drugs

69.0±46.4

80.4±39.8

86.9±33.8＊＊＊

No. of drugs

1.2＋1.1

1.7＋1.3

2.1＋1.4＊＊＊

Insulin14.3±35.1

14.9±35.7

19.0±39.4ns

SU
Metformin
α-GI

48.2±50.1
13.7±34.5

50.6±50.1
26.8±44.4

49.4±50.1ns
35.1±47.9＊＊＊

20.8±40.7
19.0±39.4

22.0±41.6
11.9±32.5

16.7±37.4ns
12.5±33.2ns

DPP-4i042.3±49.5

64.9±47.9＊＊＊

SGLT-2i0

1.2±10.9

16.1±36.8＊＊＊

CKD

4.8±21.4

14.9±35.6

24.4±43.1＊＊＊

CVD

64.9±47.977.4±42.0

82.7±37.9＊＊＊No. of patients
Female sex (％)
Ages (yr)Glycemia

Treatment (％)

Pioglitazone

Complications

Data in 2009, 2014 and 2019 as a factor were analysed by one-way analysis of variance. Between
groups comparison was made by the Bonferroni test.
ns not significant, ＊p＜0.05, ＊＊p＜0.01, ＊＊＊p＜0.001.
Abbreviations are the same as Table 1.

HbA1c was not significantly different between T1, T2

The profile of pharmacological treatment was sig-

and T3. However, an increase in RPG was significant

nificantly different among the 3 groups (Table 4).

among the 3 groups (p＜0.01, Fig. 1a). The percent of

The fraction of the patients treated with metformin

the patients with HbA1c ＜7.0 ％ decreased duringsignificantly increased (p＜0.001) and the younger thethe 10 years (p＜0.001) and the decrease was lesspatients, the more metformin (interaction between

in T1 than in T2 and T3 (p＜0.05, Fig. 1c). Percent

years and tertiles was significant (p＜0.01). In addition,changes in the fraction of HbA1c ＜8.0 ％ were not

the fraction of the treatment with pioglitazone wassignificantly different among the three groups during

greater (p＜0.001) in T1 and T2 than in T3 ; however,the 10 years (Fig. 1d).

it tended to decrease in T1 and T2 during the 10

In general, insulin and/or oral hypoglycemic agentsyears. Use of the newer oral hypoglycemic drugs,

were prescribed more frequently in the patients suc-

DPP-4i and SGLT-2i, was significantly (p＜0.001) in-

cessively seen for 10 years than in others. The

creased year by year after their appearance on thefraction increased up to 92.9±26.0 ％ in T1 (p＜0.001)

market. The frequency of use of the DPP-4i treat-(Table 4). Younger patients (T1) were treated with ament was not significantly different among the threegreater number of pharmacological agents than in T2

tertiles. The younger the patients, the greater was

and T3 (interaction between years and tertiles was

the frequency of use of SGLT-2i (interaction be-

p＜0.05, Fig. 1e).

tween years and tertiles was p＜0.001). On the other154

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Diabetes care for elderly patients

hand, in each fraction of the drug treatment with in­detail our real world-data obtained during a 10-year

sulin, SU, alpha-GI, there were no significant changes

period to evaluate the practical outcomes.
The primary data was that the patients older thanamong years and the three tertiles.
The prevalence of CKD and CVD of the 168 patients

65 years were treated relatively well for the 10 years

with diabetes increased year by year. The older thefrom 2009 to 2019, in consideration of the guide­

patients, the greater the prevalence was (the interac­lines in Japan and the ADA1）2）. However, the glycemiction for CKD but not CVD was p＜0.05) (Table 4).

outcomes in the adult patients younger than 65 years
were far from optimal. In other words, we need ad­

Ⅳ Discussion

ditional efforts for the patients with diabetes toGood control of blood glucose and HbA1c of pa­

achieve better glycemic control in this segment ofpatients.

tients with diabetes lowers the risk of diabetes7）-11）. However, too rapid

The UK Prospective Diabetes Study (UKPDS) Group

and/or too much lowering of glycemia especially instrongly reinforced metformin to treat patients withthe elderly are most likely associated with paradoxi­

type 2 diabetes in 19988）. DPP-4i, SGLT-2i and GLP-

cally increased morbidity and mortality12）13）. Guide­

1a were introduced into the market thereafter, inlines provided by the authorities thus indicate it is2010s3）5）6）. The guidelines recommend judicious use

advisable to keep finely adjusted glycemic targets inof the newer agents in patients with diabetes1）. We

the elderly, which is not always practically feasible inhave employed such newly developed agents posi­

the real world. Thus, we looked back and analyzed intively and tended to replace SU with them (Table 1).

related events and mortality

a:RPG (mg/dl)

b:HbA1c (%)
8

250
200

7.5

150
Ys p<0.05
Ts p<0 01
Int ns

100
50
0

6.5
2009

2014

2019

c:HbA1c<7.0% (%)
100

60
40

2014

2014

2019

e:No. of drugs
3
T1

80
2

60

Ys ns
Ts ns
Int ns

20
2009

2019

100

40

20
0

2009

d:HbA1c<8.0% (%)

Ys p<0 001
Ts p<0.05
Int ns80

Ys p<0 01
Ts ns
Int ns

7

0

2009

2014

2019

T2
T3

1
0

Ys p<0 001
Ts p<0.001
Int p<0.05

2009

2014

2019

Fig. 1 Changes in characteristics of the 3 tertiles, T1, T2 and T3 from the 168 patients with diabetes
treated successively for 10 years.
We divided the 168 patients into thirds, 56 patients each (T1 : solid line, T2 : dotted line and T3 : broken line).
Panels a : RPG (mg/dl), b : HbA1c (％), c : HbA1c＜7.0 ％, d : HbA1c＜8.0 ％ and e : No. of drugs present meanchanges in RPG, mean changes in HbA1c (％), mean fraction of the changes in completed less than 7 ％, mean
fraction of the changes in completed less than 8 ％ and mean number of drugs prescribed in 3 tertiles patientswith diabetes in 2009, 2014 and 2019, respectively. Standard deviations (Table 4) are not shown. Ys, 3 years,
Ts, 3 tertiles, Int, interaction between Ys and Ts.
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Furukawa・Nishizawa・Nakano et al.
Table 4 Characteristics of the 3 subgroups, tertiles T1, T2 and T3, of the patients with diabetes treatedsuccessively for 10 years from 2009 to 2019
Variable

156

2009

2014

2019

T1 Ages (n＝56)
T2 Ages (n＝56)
T3 Ages (n＝56)55.7±6.2
66.0±2.475.4±3.2

60.5±6.2
70.9±2.480.2±3.2

65.4±6.3
75.7±2.3
85.0±3.2

T1 RPG (mg/dl)
T2 RPG (mg/dl)
T3 RPG (mg/dl)

157±72.6
164±58.4
162＋70.8160±53.0
183±70.5
170±56.5

158±64.9＊♯♯
192±80.0
190±57.4

T1 HbA1c (％)
T2 HbA1c (％)
T3 HbA1c (％)

7.4±1.1
7.3±1.1
7.1±1.0

7.5±1.0
7.6±1.5
7.2±1.1

7.6±1.3＊NS
7.6±0.97.5±1.0

T1 HbA1c＜7.0 ％T2 HbA1c＜7.0 ％T3 HbA1c＜7.0 ％39.3±49.3
50.0±50.5
51.8±50.4

28.6±45.6
35.7±48.3
51.8±50.4

25.0±43.7＊＊＊♯23.2±42.6
32.1±47.1

T1 HbA1c＜8.0 ％T2 HbA1c＜8.0 ％T3 HbA1c＜8.0 ％Treatment (％)

78.6±41.4
78.6±41.4
83.9±37.1

73.2±44.7
78.6±41.4
80.4±40.1

75.0±43.7ns NS
73.2±44.771.4±45.6

T1 Drugs
T2 Drugs
T3 Drugs

69.6±46.4
71.4±45.6
66.1±47.8

85.7±35.3
80.4±40.1
75.0±43.7

92.9＋26.0＊＊＊♯91.1＋28.8
76.8＋42.6

T1 No. of drugs
T2 No. of drugs
T3 No. of drugs

1.2±1.1
1.3±1.2
1.0±0.91.8±1.3
1.8±1.4
1.4±1.2

2.7±1.4＊＊＊♯♯♯＋
2.2±1.4
1.5±1.2

T1 Insulin
T2 Insulin
T3 Insulin

21.4±41.4
12.5±33.4
8.9±28.8

19.6±40.1
14.3±35.3
10.7±31.2

17.9±38.6ns NS
25.0±43.7
14.3±35.3

T1 SU
T2 SU
T3 SU

41.1±49.6
53.6±50.3
50.0±50.5

50.0±50.5
53.6±50.3
48.2±50.4

62.5±48.9ns NS
46.4±50.3
39.3±49.3

T1 Metformin
T2 Metformin
T3 Metformin

12.5±33.4
17.9±38.6
10.7±31.7

28.6±45.6
33.9±47.8
17.9±38.6

57.1±49.9＊＊＊♯♯♯＋＋
32.1±47.1
16.1±37.1

T1 α-GIT2 α-GIT3 α-GI

16.1±37.1
23.2±42.6
23.2±42.6

19.6±40.1
23.2±42.6
23.2±42.6

10.7±31.2ns NS
23.2±42.6
16.1±37.1

T1 Pioglitazone
T2 Pioglitazone
T1 Pioglitazone

26.8±44.7
26.8±44.7
3.6±18.717.9±38.6
12.5±33.4
5.4±22.717.9±38.6ns♯♯♯10.7±31.2
8.9±28.8

T1 DPP-4i
T2 DPP-4i
T3 DPP-4i

00046.4±50.3
42.9±49.9
37.5±48.9

67.9±47.1＊＊＊NS
69.6±46.4
57.1±49.9

T1 SGLT-2i
T2 SGLT-2i
T3 SGLT-2i
Complications000

1.8±13.4
1.8±13.4035.7±48.3＊＊＊♯♯♯＋＋＋
12.5±33.4
0

T1 CKDT2 CKDT3 CKD

7.1±26.0
1.8±13.4
5.4±22.7

10.7±31.2
8.9±28.825.0±43.7

10.7±31.2＊＊＊♯♯♯＋
25.0±43.7
37.5±48.9

T1 CVDT2 CVDT3 CVD46.4±50.3
62.5±48.9
85.7±35.3

64.3±48.3
75.0±43.7
92.9±26.0

67.9±47.1＊＊＊♯♯♯
85.7±35.3
94.6±22.7
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Diabetes care for elderly patientsAt the same time, we were enthusiastic regarding ato some extent.

team effort to sustain the patient’s positive stanceComplications, especially CVD, of the patients withtoward diabetes management. Namely, we recom­

diabetes are major factors determining long-term

mend the patients with diabetes to learn how to copeprognoses. Although the direct treatment outcome inwith diabetes through nursing, nutritional and phar­this aspect was not obtainable in our study, relatively

macological counseling by qualified medical staff.

poor glycemic control especially in the younger pa­

However, the patients less than 65 years were intients was an alarming sign. We need to pay close

general rather reluctant to join these activities mostly

attention to a possible relationship between undesir­due to their busy working and life styles. This, on theable HbA1c values of the patients less than 65 years

other hand, may have pushed us to prescribe a larger

and vascular events.

number of drugs to improve their glycemic control.

The present study is retrospective. It contains many

Duration of diabetes is an important risk factor for

limitations, not determining the order of OHAs, not14）

mortality and morbidity in patients with diabetes .

averaging the number of patients seen by each doctor,

Our longitudinal data in the patients successively

not normalizing the backgrounds of patients, and sotreated for 10 years clearly indicated the treatment

on. Most importantly, the treatment targets were notoutcome was far from ideal. The HbA1c target was

pre-determined between four doctors mainly respon­recommended to be ＜7.0 ％ for patients with diabetes

sible for the management of the patients with diabe­at large and ＜8.0 ％ for patients ＞75 years who aretes. The data collection, especially regarding vascular1）

treated by SU and/or insulin or having dementia .

complications, was far from complete. However, within

The Guidelines might relate in part to the tenden­these limitations, we believe this paper describes thecy of the worse fraction of the patients with mean

important faces of treatment outcome regarding

HbA1c ＜7.0 ％ in 2019 (Table 2) because the frac­

HbA1c and glycemia of patients with diabetes at large.

tion of the patients with mean HbA1c ＜7.0 ％ in G3

Ⅴ

in 2019 tended to be less than that in 2009. Now, weneed to strengthen our strategies to obtain better
glycemic control. The so-called empowerment ap­
proach15） and syndemic approach16） would be appro­

Conflict of Interests

None.
Acknowledgement

priate here, although the adherence of the adult

The authors would like to gratefully thank Dr. Toru

patients would be worse than that of the elderly pa­

Aizawa, MD, PhD, Diabetes Centre, Aizawa Hospitaltients, which is not shown exactly from the present

for his advice and suggestions including language instudy.

our study, and all medical staff and patients who par­DPP-4i and SGLT-2i were introduced to the market
in 2009 and 2014, respectively, in Japan. Thus, we oftenprescribed them in addition to metformin according

ticipated in this study.
Compliance with Ethical Standards

to the guidelines by the JDS and the ADA1）17）. Our

The project was studied with humans but it isdata suggest that these drugs improved the glycemic

retrospective, and was approved by the ethics com­control of the adult and older patients with diabetes

mittee of Shiojiri Kyoritsu Hospital.

Table 4

Data were analysed by two-way analysis of variance. Two factors were years, 2009, 2014 and2019, and tertiles, T1, T2 and T3. Between groups comparison was made by the Bonferroni test.
ns not significant, ＊p＜0.05, ＊＊p＜0.01, ＊＊＊p＜0.001 among years, 2009, 2014 and 2019.
NS not significant, ♯ p＜0.05, ♯♯ p＜0.01, ♯♯♯ p＜0.001 among tertiles, T1, T2 and T3.
＋p＜0.05, ＋＋p＜0.01, ＋＋＋p＜0.001 interaction between years and tertiles.
Abbreviations are the same as Table 1.

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Furukawa・Nishizawa・Nakano et al.

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