J Endocrinol Metab

Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access

Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc

Journal website https://www.jofem.org

Original Article

Volume 14, Number 1, February 2024, pages 1-12

Associations Between Type 2 Diabetes Subtypes and Complications: Analysis of the Malaysia National Diabetes Registry

Figure 2. Malaysia NDR cluster boxplots, variables used in cluster analysis. MARD: mild age-related diabetes; MOD: mild obesity-related diabetes; NDR: National Diabetes Registry; SIDD: severe insulin deficient diabetes; SIRD: severe insulin-resistant diabetes.

Figure 3. Cumulative incidence curves and risk tables for diabetes complications, adjusted for age, sex, and ethnicity: (a) stage 3a and more severe chronic kidney disease; (b) retinopathy; (c) cerebrovascular disease; (d) ischemic heart disease; (e) diabetes foot ulcers; (f) limb amputations. Models adjusted for sex and age and stratified by diabetes subtype. MARD: mild age-related diabetes; MOD: mild obesity-related diabetes; SIDD: severe insulin deficient diabetes; SIRD: severe insulin-resistant diabetes.

**Table 1.** DM Subtype Characteristics
Subtype [3]	Label	Phenotypic features	Complication risk	Molecular profiles [5]
Adapted from Ahlqvist et al [3] and Slieker et al [5]. A1c: glycated hemoglobin; BMI: body mass index; DM: diabetes.
SIRD	Severe insulin-resistant diabetes	Obesity with severe insulin resistance and lipotoxicity, older and middle age at DM onset	Higher risk of fatty liver and kidney complications	Liver
MARD	Mild age-related diabetes	Leaner BMI, older age at DM onset	Lower risk of end-stage complications	Adipose tissue
SIDD	Severe insulin-deficient diabetes	Leaner BMI, high A1c, younger age at DM onset, longer DM duration	Higher risk of microangiopathic complications	Pancreatic islet biology
MOD	Mild obesity-related diabetes	Severe obesity, metabolically healthier, younger age at DM onset, shorter DM duration	Lower risk of diabetes complications	Adipose tissue

Table 1. DM Subtype Characteristics

Subtype [3]

Label

Phenotypic features

Complication risk

Molecular profiles [5]

Adapted from Ahlqvist et al [3] and Slieker et al [5]. A1c: glycated hemoglobin; BMI: body mass index; DM: diabetes.

SIRD

Severe insulin-resistant diabetes

Obesity with severe insulin resistance and lipotoxicity, older and middle age at DM onset

Higher risk of fatty liver and kidney complications

Liver

MARD

Mild age-related diabetes

Leaner BMI, older age at DM onset

Lower risk of end-stage complications

Adipose tissue

SIDD

Severe insulin-deficient diabetes

Leaner BMI, high A1c, younger age at DM onset, longer DM duration

Higher risk of microangiopathic complications

Pancreatic islet biology

MOD

Mild obesity-related diabetes

Severe obesity, metabolically healthier, younger age at DM onset, shorter DM duration

Lower risk of diabetes complications

Adipose tissue

**Table 2.** Characteristics of Patients With Type 2 Diabetes
Characteristics	Overall	Female	Male
^aMetabolic syndrome was defined according to the Harmonized Metabolic Syndrome Definition guidelines [23] by meeting three or more criteria: 1) abdominal obesity was defined as waist circumference ≥ 80 cm in females and ≥ 90 cm in males; 2) hypertension was defined as blood pressure ≥ 130/85 mm Hg or previously diagnosed hypertension; 3) hypertriglyceridemia was defined as ≥ 1.7 mmol/L (150 mg/dL); 4) low high-density lipoprotein (HDL) cholesterol was defined as < 1.3 mmol/L (50 mg/dL) in females and < 1.0 mmol/L (40 mg/dL) in males; 5) all patients met criteria for impaired fasting glucose by virtue of type 2 diabetes diagnosis. ^bFasting glucose measurements may have been impacted by diabetes pharmacotherapy. A1c: glycated hemoglobin; BMI: body mass index; IQR: interquartile range; LDL: low-density lipoprotein; SD: standard deviation.
Total, n (%)	60,946	37,832 (62.1)	23,114 (37.9)
Age at the assessment, mean (SD), years	61.1 (10.7)	60.8 (10.8)	61.5 (10.7)
Age at assessment (years), n (%)
< 40.0 years	1,946 (3.2)	1,240 (3.3)	706 (3.1)
40.0 - 49.9 years	6,352 (10.4)	4,034 (10.7)	2,318 (10.0)
50.0 - 59.9 years	17,402 (28.6)	11,253 (29.7)	6,149 (26.6)
60.0 - 69.9 years	22,135 (36.3)	13,502 (35.7)	8,633 (37.3)
≥ 70.0 years	13,111 (21.5)	7,803 (20.6)	5,308 (23.0)
Age at diabetes diagnosis, mean (SD), years	53.3 (10.6)	52.8 (10.6)	54.0 (10.5)
Age at diabetes diagnosis, n (%)
< 40 .0 years	6,000 (9.8)	3,944 (10.4)	2,056 (8.9)
40.0 - 49.9 years	15,150 (24.9)	9,863 (26.1)	5,287 (22.9)
50.0 - 59.9 years	23,010 (37.8)	14,262 (37.7)	8,748 (37.8)
60.0 - 69.9 years	13,117 (21.5)	7,634 (20.2)	5,483 (23.7)
≥ 70.0 years	3,669 (6.0)	2,129 (5.6)	1,540 (6.7)
Diabetes duration, median (IQR), years	6.8 (3.6 - 11.0)	7.0 (3.8 - 11.4)	6.3 (3.3 - 10.7)
Diabetes duration > 10 years, n (%)	18,517 (30.4)	12,098 (32.0)	6,419 (27.8)
Ethnicity, n (%)
Malay	38,887 (63.8)	25,068 (66.3)	13,819 (59.8)
Chinese	10,156 (16.7)	5,314 (14.0)	4,842 (20.9)
Indian	5,044 (8.3)	3,084 (8.2)	1,960 (8.5)
Other	6,859 (11.3)	4,366 (11.5)	2,493 (10.8)
BMI, mean (SD), kg/m²	27.8 (5.2)	28.0 (5.4)	27.4 (4.8)
BMI, n (%)
Underweight (> 18.5)	977 (1.6)	663 (1.8)	314 (1.4)
Normal (18.5 - 24.9)	17,841 (29.3)	10,788 (28.5)	7,053 (30.5)
Overweight (25.0 - 29.9)	23,972 (39.3)	14,285 (37.8)	9,687 (41.9)
Obese (≥ 30.0)	18,156 (29.8)	12,096 (32.0)	6,060 (26.2)
Waist circumference, mean (SD), cm	93.3 (11.9)	92.2 (11.9)	95.1 (11.7)
Abdominal obesity, n (%)^a
No	11,524 (18.9)	4,556 (12.0)	6,968 (30.1)
Yes	49,422 (81.1)	33,276 (88.0)	16,146 (69.9)
Hypertension, n (%)^a
No	10,741 (17.7)	6,221 (16.5)	4,520 (19.6)
Yes	49,991 (82.3)	31,477 (83.5)	18,514 (80.4)
Triglyceridemia, median (IQR), mmol/L	1.40 (1.10 - 2.0)	1.4 (1.1 - 2.0)	1.4 (1.1 - 2.0)
Hypertriglyceridemia, n (%)^a
No	37,236 (61.1)	23,332 (61.7)	13,904 (60.2)
Yes	23,710 (38.9)	14,500 (38.3)	9,210 (39.8)
HDL, mean (SD), mmol/L	1.3 (0.4)	1.3 (0.4)	1.2 (0.3)
Low HDL, n (%)^a
No	33,710 (55.3)	19,195 (50.7)	14,515 (62.8)
Yes	27,236 (44.7)	18,637 (49.3)	8,599 (37.2)
LDL, mean (SD), mmol/L	2.91 (1.11)	2.98 (1.13)	2.80 (1.06)
Fasting serum glucose, mean (SD)^b, mmol/L	7.67 (2.87)	7.72 (2.92)	7.60 (2.80)
A1c, mean (SD), %	7.9 (2.1)	8.0 (2.1)	7.8 (2.0)
Diabetes medications, n (%)
None	1,770 (2.9)	1,148 (3.0)	622 (2.7)
Metformin	52,850 (86.7)	33,233 (87.8)	19,617 (84.9)
Sulfonylurea	29,083 (47.7)	17,344 (45.8)	11,739 (50.8)
Other oral	1,357 (2.2)	884 (2.3)	473 (2.0)
Insulin	18,826 (30.9)	11,955 (31.6)	6,871 (29.7)
Metabolic syndrome, n (%)^a
No	6,979 (11.5)	2,939 (7.8)	4,040 (17.5)
Yes	53,967 (88.5)	34,893 (92.2)	19,074 (82.5)

Table 2. Characteristics of Patients With Type 2 Diabetes

Characteristics

Overall

Female

Male

^aMetabolic syndrome was defined according to the Harmonized Metabolic Syndrome Definition guidelines [23] by meeting three or more criteria: 1) abdominal obesity was defined as waist circumference ≥ 80 cm in females and ≥ 90 cm in males; 2) hypertension was defined as blood pressure ≥ 130/85 mm Hg or previously diagnosed hypertension; 3) hypertriglyceridemia was defined as ≥ 1.7 mmol/L (150 mg/dL); 4) low high-density lipoprotein (HDL) cholesterol was defined as < 1.3 mmol/L (50 mg/dL) in females and < 1.0 mmol/L (40 mg/dL) in males; 5) all patients met criteria for impaired fasting glucose by virtue of type 2 diabetes diagnosis. ^bFasting glucose measurements may have been impacted by diabetes pharmacotherapy. A1c: glycated hemoglobin; BMI: body mass index; IQR: interquartile range; LDL: low-density lipoprotein; SD: standard deviation.

Total, n (%)

60,946

37,832 (62.1)

23,114 (37.9)

Age at the assessment, mean (SD), years

61.1 (10.7)

60.8 (10.8)

61.5 (10.7)

Age at assessment (years), n (%)

< 40.0 years

1,946 (3.2)

1,240 (3.3)

706 (3.1)

40.0 - 49.9 years

6,352 (10.4)

4,034 (10.7)

2,318 (10.0)

50.0 - 59.9 years

17,402 (28.6)

11,253 (29.7)

6,149 (26.6)

60.0 - 69.9 years

22,135 (36.3)

13,502 (35.7)

8,633 (37.3)

≥ 70.0 years

13,111 (21.5)

7,803 (20.6)

5,308 (23.0)

Age at diabetes diagnosis, mean (SD), years

53.3 (10.6)

52.8 (10.6)

54.0 (10.5)

Age at diabetes diagnosis, n (%)

< 40 .0 years

6,000 (9.8)

3,944 (10.4)

2,056 (8.9)

40.0 - 49.9 years

15,150 (24.9)

9,863 (26.1)

5,287 (22.9)

50.0 - 59.9 years

23,010 (37.8)

14,262 (37.7)

8,748 (37.8)

60.0 - 69.9 years

13,117 (21.5)

7,634 (20.2)

5,483 (23.7)

≥ 70.0 years

3,669 (6.0)

2,129 (5.6)

1,540 (6.7)

Diabetes duration, median (IQR), years

6.8 (3.6 - 11.0)

7.0 (3.8 - 11.4)

6.3 (3.3 - 10.7)

Diabetes duration > 10 years, n (%)

18,517 (30.4)

12,098 (32.0)

6,419 (27.8)

Ethnicity, n (%)

Malay

38,887 (63.8)

25,068 (66.3)

13,819 (59.8)

Chinese

10,156 (16.7)

5,314 (14.0)

4,842 (20.9)

Indian

5,044 (8.3)

3,084 (8.2)

1,960 (8.5)

Other

6,859 (11.3)

4,366 (11.5)

2,493 (10.8)

BMI, mean (SD), kg/m²

27.8 (5.2)

28.0 (5.4)

27.4 (4.8)

BMI, n (%)

Underweight (> 18.5)

977 (1.6)

663 (1.8)

314 (1.4)

Normal (18.5 - 24.9)

17,841 (29.3)

10,788 (28.5)

7,053 (30.5)

Overweight (25.0 - 29.9)

23,972 (39.3)

14,285 (37.8)

9,687 (41.9)

Obese (≥ 30.0)

18,156 (29.8)

12,096 (32.0)

6,060 (26.2)

Waist circumference, mean (SD), cm

93.3 (11.9)

92.2 (11.9)

95.1 (11.7)

Abdominal obesity, n (%)^a

11,524 (18.9)

4,556 (12.0)

6,968 (30.1)

Yes

49,422 (81.1)

33,276 (88.0)

16,146 (69.9)

Hypertension, n (%)^a

10,741 (17.7)

6,221 (16.5)

4,520 (19.6)

Yes

49,991 (82.3)

31,477 (83.5)

18,514 (80.4)

Triglyceridemia, median (IQR), mmol/L

1.40 (1.10 - 2.0)

1.4 (1.1 - 2.0)

Hypertriglyceridemia, n (%)^a

37,236 (61.1)

23,332 (61.7)

13,904 (60.2)

Yes

23,710 (38.9)

14,500 (38.3)

9,210 (39.8)

HDL, mean (SD), mmol/L

1.3 (0.4)

1.2 (0.3)

Low HDL, n (%)^a

33,710 (55.3)

19,195 (50.7)

14,515 (62.8)

Yes

27,236 (44.7)

18,637 (49.3)

8,599 (37.2)

LDL, mean (SD), mmol/L

2.91 (1.11)

2.98 (1.13)

2.80 (1.06)

Fasting serum glucose, mean (SD)^b, mmol/L

7.67 (2.87)

7.72 (2.92)

7.60 (2.80)

A1c, mean (SD), %

7.9 (2.1)

8.0 (2.1)

7.8 (2.0)

Diabetes medications, n (%)

None

1,770 (2.9)

1,148 (3.0)

622 (2.7)

Metformin

52,850 (86.7)

33,233 (87.8)

19,617 (84.9)

Sulfonylurea

29,083 (47.7)

17,344 (45.8)

11,739 (50.8)

Other oral

1,357 (2.2)

884 (2.3)

473 (2.0)

Insulin

18,826 (30.9)

11,955 (31.6)

6,871 (29.7)

Metabolic syndrome, n (%)^a

6,979 (11.5)

2,939 (7.8)

4,040 (17.5)

Yes

53,967 (88.5)

34,893 (92.2)

19,074 (82.5)

**Table 3.** Four-Cluster Diabetes Subtyping With Characteristics of the Clusters (n = 60,946)
Clusters	BMI (kg/m²)	Age at diagnosis (years)	Diabetes duration (years)	Insulin resistance, cMetSyn	Glycemia, A1c (%)	Lipotoxicity, triglyceride-glucose index	Proportion of cases	Jaccard index
A1c: glycated hemoglobin; BMI: body mass index; cMetSyn: continuous metabolic syndrome z-score; MARD: mild age-related diabetes; MOD: mild obesity-related diabetes; SIDD: severe insulin deficient diabetes; SIRD: severe insulin-resistant diabetes.
SIRD	27.7	51	7.8	0.132	9.6	9.9	22%	0.92
MARD	25.0	61	5.8	-0.064	6.7	8.7	35%	0.93
SIDD	26.0	47	15.0	-0.040	8.7	8.9	19%	0.90
MOD	33.2	49	5.3	0.004	7.5	9.0	24%	0.93

Table 3. Four-Cluster Diabetes Subtyping With Characteristics of the Clusters (n = 60,946)

Clusters

BMI (kg/m²)

Age at diagnosis (years)

Diabetes duration (years)

Insulin resistance, cMetSyn

Glycemia, A1c (%)

Lipotoxicity, triglyceride-glucose index

Proportion of cases

Jaccard index

A1c: glycated hemoglobin; BMI: body mass index; cMetSyn: continuous metabolic syndrome z-score; MARD: mild age-related diabetes; MOD: mild obesity-related diabetes; SIDD: severe insulin deficient diabetes; SIRD: severe insulin-resistant diabetes.

SIRD

27.7

7.8

0.132

9.6

9.9

22%

0.92

MARD

25.0

5.8

-0.064

6.7

8.7

35%

0.93

SIDD

26.0

15.0

-0.040

8.7

8.9

19%

0.90

MOD

33.2

5.3

0.004

7.5

9.0

24%

0.93

**Table 4.** Characteristics of Patients With Type 2 Diabetes by Cluster Allocation
Characteristics	MARD	SIDD	MOD	SIRD
^aMetabolic syndrome was defined according to the Harmonized Metabolic Syndrome Definition guidelines [13] by meeting three or more criteria: 1) abdominal obesity was defined as waist circumference ≥ 80 cm in females and ≥ 90 cm in males; 2) hypertension was defined as blood pressure ≥ 130/85 mm Hg or previously diagnosed hypertension; 3) hypertriglyceridemia was defined as ≥ 1.7 mmol/L (150 mg/dL); 4) low high-density lipoprotein (HDL) cholesterol was defined as < 1.3 mmol/L (50 mg/dL) in females and < 1.0 mmol/L (40 mg/dL) in males; 5) all patients met criteria for impaired fasting glucose by virtue of type 2 diabetes diagnosis. A1c: glycated hemoglobin; BMI: body mass index; cMetSyn: continuous metabolic syndrome z-score; LDL: low-density lipoprotein; MARD: mild age-related diabetes; MOD: mild obesity-related diabetes; SD: standard deviation; SIDD: severe insulin deficient diabetes; SIRD: severe insulin-resistant diabetes.
n (%)	21,059 (35.6)	11,751 (19.3)	14,700 (24.1)	13,436 (22.0)
Female, n (%)	12,365 (58.8)	7,558 (64.2)	9,646 (65.6)	8,263 (61.5)
Male, n (%)	8,673 (41.2)	4,215 (35.8)	5,042 (34.4)	5,176 (38.5)
Malay ethnicity, n (%)	12,379 (58.8)	7,362 (62.5)	9,912 (67.5)	9,234 (68.7)
Chinese ethnicity, n (%)	4,694 (22.3)	2,055 (17.5)	1,394 (9.5)	2,013 (15.0)
Indian ethnicity, n (%)	1,376 (6.5)	1,556 (13.2)	1,276 (8.7)	835 (6.2)
Other ethnicity, n (%)	2,589 (12.3)	800 (6.8)	2,113 (14.4)	1,357 (10.1)
Age at diabetes diagnosis (years), mean (SD)	61.1 (8.2)	47.2 (8.5)	48.8 (9.0)	51.2 (9.7)
Diabetes duration (years), mean (SD)	5.76 (3.53)	15.02 (5.37)	5.27 (3.39)	7.80 (4.54)
Diabetes duration > 10 years, n (%)	2,911 (13.8)	10,089 (85.9)	1,494 (10.2)	4,023 (29.9)
A1c (%), mean (SD)	6.7 (1.1)	8.8 (2.1)	7.5 (1.5)	9.6 (2.3)
No diabetes medications, n (%)	1,075 (5.1)	135 (1.1)	383 (2.6)	177 (1.3)
Oral diabetes medications, n (%)	19,343 (91.9)	10,328 (87.7)	13,666 (93.0)	12,053 (89.7)
Insulin pharmacotherapy, n (%)	2,364 (11.2)	6,559 (55.7)	3,482 (23.7)	6,421 (47.8)
LDL, mmol/L, mean (SD)	2.76 (1.02)	2.85 (1.07)	2.95 (1.04)	3.15 (1.29)
Triglyceride-glucose index, mean (SD)	8.67 (0.43)	8.86 (0.47)	9.02 (0.40)	9.90 (0.46)
BMI (kg/m²), mean (SD)	24.96 (3.49)	26.04 (3.94)	33.17 (4.83)	27.67 (4.32)
cMetSyn score, mean (SD)	-0.06 (0.08)	-0.04 (0.08)	0.00 (0.07)	0.13 (0.10)
Metabolic syndrome, n (%)^a	16,735 (79.5)	9,954 (84.7)	14,141 (96.2)	13,137 (97.8)
Chronic kidney disease, stage 3a or worse, n (%)	6,807 (32.7)	4,696 (40.5)	3,356 (23.1)	5,056 (38.2)
Retinopathy, n (%)	4,337 (21.0)	3,556 (30.8)	1,962 (13.6)	2,844 (21.6)
Cerebrovascular disease, n (%)	343 (1.7)	237 (2.0)	134 (0.9)	211 (1.6)
Ischemic heart disease, n (%)	1,228 (5.9)	1,013 (8.7)	555 (3.8)	808 (6.1)
Diabetes foot ulcers, n (%)	129 (0.6)	232 (2.0)	117 (0.8)	206 (1.6)
Limb amputations, n (%)	65 (0.3)	112 (1.0)	32 (0.2)	79 (0.6)

Table 4. Characteristics of Patients With Type 2 Diabetes by Cluster Allocation

Characteristics

MARD

SIDD

MOD

SIRD

^aMetabolic syndrome was defined according to the Harmonized Metabolic Syndrome Definition guidelines [13] by meeting three or more criteria: 1) abdominal obesity was defined as waist circumference ≥ 80 cm in females and ≥ 90 cm in males; 2) hypertension was defined as blood pressure ≥ 130/85 mm Hg or previously diagnosed hypertension; 3) hypertriglyceridemia was defined as ≥ 1.7 mmol/L (150 mg/dL); 4) low high-density lipoprotein (HDL) cholesterol was defined as < 1.3 mmol/L (50 mg/dL) in females and < 1.0 mmol/L (40 mg/dL) in males; 5) all patients met criteria for impaired fasting glucose by virtue of type 2 diabetes diagnosis. A1c: glycated hemoglobin; BMI: body mass index; cMetSyn: continuous metabolic syndrome z-score; LDL: low-density lipoprotein; MARD: mild age-related diabetes; MOD: mild obesity-related diabetes; SD: standard deviation; SIDD: severe insulin deficient diabetes; SIRD: severe insulin-resistant diabetes.

n (%)

21,059 (35.6)

11,751 (19.3)

14,700 (24.1)

13,436 (22.0)

Female, n (%)

12,365 (58.8)

7,558 (64.2)

9,646 (65.6)

8,263 (61.5)

Male, n (%)

8,673 (41.2)

4,215 (35.8)

5,042 (34.4)

5,176 (38.5)

Malay ethnicity, n (%)

12,379 (58.8)

7,362 (62.5)

9,912 (67.5)

9,234 (68.7)

Chinese ethnicity, n (%)

4,694 (22.3)

2,055 (17.5)

1,394 (9.5)

2,013 (15.0)

Indian ethnicity, n (%)

1,376 (6.5)

1,556 (13.2)

1,276 (8.7)

835 (6.2)

Other ethnicity, n (%)

2,589 (12.3)

800 (6.8)

2,113 (14.4)

1,357 (10.1)

Age at diabetes diagnosis (years), mean (SD)

61.1 (8.2)

47.2 (8.5)

48.8 (9.0)

51.2 (9.7)

Diabetes duration (years), mean (SD)

5.76 (3.53)

15.02 (5.37)

5.27 (3.39)

7.80 (4.54)

Diabetes duration > 10 years, n (%)

2,911 (13.8)

10,089 (85.9)

1,494 (10.2)

4,023 (29.9)

A1c (%), mean (SD)

6.7 (1.1)

8.8 (2.1)

7.5 (1.5)

9.6 (2.3)

No diabetes medications, n (%)

1,075 (5.1)

135 (1.1)

383 (2.6)

177 (1.3)

Oral diabetes medications, n (%)

19,343 (91.9)

10,328 (87.7)

13,666 (93.0)

12,053 (89.7)

Insulin pharmacotherapy, n (%)

2,364 (11.2)

6,559 (55.7)

3,482 (23.7)

6,421 (47.8)

LDL, mmol/L, mean (SD)

2.76 (1.02)

2.85 (1.07)

2.95 (1.04)

3.15 (1.29)

Triglyceride-glucose index, mean (SD)

8.67 (0.43)

8.86 (0.47)

9.02 (0.40)

9.90 (0.46)

BMI (kg/m²), mean (SD)

24.96 (3.49)

26.04 (3.94)

33.17 (4.83)

27.67 (4.32)

cMetSyn score, mean (SD)

-0.06 (0.08)

-0.04 (0.08)

0.00 (0.07)

0.13 (0.10)

Metabolic syndrome, n (%)^a

16,735 (79.5)

9,954 (84.7)

14,141 (96.2)

13,137 (97.8)

Chronic kidney disease, stage 3a or worse, n (%)

6,807 (32.7)

4,696 (40.5)

3,356 (23.1)

5,056 (38.2)

Retinopathy, n (%)

4,337 (21.0)

3,556 (30.8)

1,962 (13.6)

2,844 (21.6)

Cerebrovascular disease, n (%)

343 (1.7)

237 (2.0)

134 (0.9)

211 (1.6)

Ischemic heart disease, n (%)

1,228 (5.9)

1,013 (8.7)

555 (3.8)

808 (6.1)

Diabetes foot ulcers, n (%)

129 (0.6)

232 (2.0)

117 (0.8)

206 (1.6)

Limb amputations, n (%)

65 (0.3)

112 (1.0)

32 (0.2)

79 (0.6)

**Table 5.** Hazard Ratios and 95% Confidence Intervals for Diabetes Complications by Cluster Compared to MARD
Outcome	n	MOD vs. MARD	SIDD vs. MARD	SIRD vs. MARD
Cox regression models adjusted for age, sex, and ethnicity. *Statistically significant. MARD: mild age-related diabetes; MOD: mild obesity-related diabetes; SIDD: severe insulin deficient diabetes; SIRD: severe insulin-resistant diabetes.
Chronic kidney disease, stage 3a or worse	60,155	0.90 (0.86 - 0.95)*	0.25 (0.24 - 0.26)*	0.77 (0.74 - 0.80)*
Retinopathy	59,832	0.68 (0.64 - 0.72)*	0.28 (0.27 - 0.30)*	0.59 (0.56 - 0.63)*
Cerebrovascular disease	60,070	0.69 (0.55 - 0.86)*	0.57 (0.47 - 0.69)*	0.84 (0.70 - 1.01)
Ischemic heart disease	60,087	1.02 (0.91 - 1.13)	0.83 (0.76 - 0.91)*	1.08 (0.98 - 1.18)
Diabetes foot ulcers	60,129	1.07 (0.82 - 1.41)	0.82 (0.64 - 1.04)	1.43 (1.13 - 1.81)*
Limb amputations	60,116	0.53 (0.34 - 0.84)*	0.73 (0.51 - 1.04)	1.03 (0.72 - 1.46)

Table 5. Hazard Ratios and 95% Confidence Intervals for Diabetes Complications by Cluster Compared to MARD

Outcome

MOD vs. MARD

SIDD vs. MARD

SIRD vs. MARD

Cox regression models adjusted for age, sex, and ethnicity. *Statistically significant. MARD: mild age-related diabetes; MOD: mild obesity-related diabetes; SIDD: severe insulin deficient diabetes; SIRD: severe insulin-resistant diabetes.

Chronic kidney disease, stage 3a or worse

60,155

0.90 (0.86 - 0.95)*

0.25 (0.24 - 0.26)*

0.77 (0.74 - 0.80)*

Retinopathy

59,832

0.68 (0.64 - 0.72)*

0.28 (0.27 - 0.30)*

0.59 (0.56 - 0.63)*

Cerebrovascular disease

60,070

0.69 (0.55 - 0.86)*

0.57 (0.47 - 0.69)*

0.84 (0.70 - 1.01)

Ischemic heart disease

60,087

1.02 (0.91 - 1.13)

0.83 (0.76 - 0.91)*

1.08 (0.98 - 1.18)

Diabetes foot ulcers

60,129

1.07 (0.82 - 1.41)

0.82 (0.64 - 1.04)

1.43 (1.13 - 1.81)*

Limb amputations

60,116

0.53 (0.34 - 0.84)*

0.73 (0.51 - 1.04)

1.03 (0.72 - 1.46)