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Table 2

Associations among various early HbA1c exposure periods and subsequent outcomes

Microvascular events
Macrovascular events
Death
Early period and mean glycemic controln/total nAdjusted HR (95% CI)P valuen/total nAdjusted HR (95% CI)P valuen/total nAdjusted HR (95% CI)P value
0–1 year          
 HbA1c          
   <6.5% (<48 mmol/mol) 864/14,080 Reference  3,668/13,455 Reference  744/14,286 Reference  
   6.5% to <7.0% (48 to <53 mmol/mol) 372/5,774 1.204 (1.063–1.365) 0.004 1,497/5,552 1.188 (1.116–1.264) <0.0001 268/5,877 1.137 (0.985–1.313) 0.079 
   7.0% to <8.0% (53 to <64 mmol/mol) 385/4,656 1.391 (1.226–1.578) <0.0001 1,244/4,501 1.287 (1.203–1.377) <0.0001 224/4,730 1.290 (1.104–1.507) 0.001 
   8.0% to <9.0% (64 to <75 mmol/mol) 154/1,390 1.603 (1.340–1.917) <0.0001 383/1,351 1.369 (1.227–1.527) <0.0001 68/1,418 1.262 (0.978–1.628) 0.073 
   ≥9.0% (≥75 mmol/mol) 232/1,259 2.213 (1.892–2.590) <0.0001 382/1,220 1.485 (1.329–1.659) <0.0001 66/1,290 1.320 (1.017–1.713) 0.037 
   Missing 647/7,047 1.354 (1.218–1.505) <0.0001 1,899/6,867 1.112 (1.050–1.177) 0.0003 437/7,136 1.235 (1.094–1.394) 0.001 
0–2 years          
 HbA1c          
   <6.5% (<48 mmol/mol) 809/14,673 Reference  3,612/13,860 Reference  817/14,940 Reference  
   6.5% to <7.0% (48 to <53 mmol/mol) 451/7,517 1.259 (1.117–1.419) 0.0002 1,866/7,143 1.158 (1.093–1.228) <0.0001 368/7,675 1.093 (0.962–1.241) 0.172 
   7.0% to <8.0% (53 to <64 mmol/mol) 544/7,144 1.497 (1.331–1.684) <0.0001 1,788/6,842 1.264 (1.189–1.344) <0.0001 368/7,295 1.240 (1.088–1.414) 0.001 
   8.0% to <9.0% (64 to <75 mmol/mol) 258/2,529 1.700 (1.460–1.980) <0.0001 620/2,426 1.279 (1.168–1.401) <0.0001 128/2,592 1.274 (1.047–1.551) 0.016 
   ≥9.0% (≥75 mmol/mol) 408/2,159 2.756 (2.396–3.170) <0.0001 624/2,112 1.539 (1.400–1.692) <0.0001 126/2,235 1.528 (1.245–1.876) <0.0001 
0–3 years          
 HbA1c          
   <6.5% (<48 mmol/mol) 619/12,475 Reference  2,931/11,635 Reference  717/12,769 Reference  
   6.5% to <7.0% (48 to <53 mmol/mol) 412/7,883 1.194 (1.049–1.359) 0.007 1,818/7,347 1.126 (1.059–1.197) 0.0001 375/8,057 0.975 (0.856–1.109) 0.696 
   7.0% to <8.0% (53 to <64 mmol/mol) 551/8,310 1.453 (1.281–1.648) <0.0001 1,931/7,873 1.208 (1.134–1.286) <0.0001 433/8,541 1.189 (1.044–1.353) 0.009 
   8.0% to <9.0% (64 to <75 mmol/mol) 293/3,081 1.835 (1.571–2.145) <0.0001 732/2,952 1.329 (1.216–1.453) <0.0001 162/3,188 1.376 (1.145–1.654) 0.001 
   ≥9.0% (≥75 mmol/mol) 406/2,084 3.193 (2.738–3.723) <0.0001 563/2,041 1.471 (1.327–1.631) <0.0001 120/2,182 1.503 (1.211–1.865) 0.0002 
0–4 years          
 HbA1c          
   <6.5% (<48 mmol/mol) 493/10,627 Reference  2,322/9,692 Reference  621/10,898 Reference  
   6.5% to <7.0% (48 to <53 mmol/mol) 401/8,097 1.252 (1.091–1.436) 0.001 1,719/7,410 1.100 (1.031–1.174) 0.004 399/8,302 1.013 (0.889–1.155) 0.842 
   7.0% to <8.0% (53 to <64 mmol/mol) 542/9,306 1.461 (1.277–1.673) <0.0001 2,019/8,710 1.224 (1.145–1.308) <0.0001 482/9,608 1.224 (1.074–1.395) 0.002 
   8.0% to <9.0% (64 to <75 mmol/mol) 312/3,567 1.894 (1.608–2.231) <0.0001 770/3,352 1.299 (1.185–1.425) <0.0001 187/3,697 1.453 (1.211–1.742) <0.0001 
   ≥9.0% (≥75 mmol/mol) 412/2,115 3.687 (3.123–4.352) <0.0001 534/2,073 1.535 (1.374–1.714) <0.0001 118/2,232 1.676 (1.337–2.100) <0.0001 
0–5 years          
 HbA1c          
   <6.5% (<48 mmol/mol) 399/9,209 Reference  1,862/8,226 Reference  552/9,475 Reference  
   6.5% to <7.0% (48 to <53 mmol/mol) 377/8,244 1.263 (1.091–1.462) 0.002 1,596/7,389 1.102 (1.027–1.182) 0.007 423/8,465 1.070 (0.937–1.221) 0.318 
   7.0% to <8.0% (53 to <64 mmol/mol) 519/10,118 1.441 (1.246–1.666) <0.0001 2,038/9,315 1.259 (1.173–1.352) <0.0001 518/10,500 1.238 (1.083–1.415) 0.002 
   8.0% to <9.0% (64 to <75 mmol/mol) 331/3,841 2.111 (1.779–2.506) <0.0001 727/3,556 1.269 (1.150–1.400) <0.0001 200/3,984 1.554 (1.294–1.867) <0.0001 
   ≥9.0% (≥75 mmol/mol) 418/2,184 4.094 (3.427–4.893) <0.0001 524/2,134 1.596 (1.420–1.794) <0.0001 114/2,313 1.747 (1.382–2.208) <0.0001 
0–6 years          
 HbA1c          
   <6.5% (<48 mmol/mol) 343/8,192 Reference  1,524/7,122 Reference  505/8,463 Reference  
   6.5% to <7.0% (48 to <53 mmol/mol) 319/8,328 1.137 (0.970–1.333) 0.112 1,433/7,362 1.074 (0.996–1.159) 0.064 432/8,580 1.097 (0.959–1.255) 0.177 
   7.0% to <8.0% (53 to <64 mmol/mol) 523/10,696 1.543 (1.324–1.797) <0.0001 1,967/9,671 1.299 (1.204–1.402) <0.0001 547/11,120 1.278 (1.116–1.464) 0.0004 
   8.0% to <9.0% (64 to <75 mmol/mol) 322/4,034 2.252 (1.879–2.700) <0.0001 713/3,683 1.368 (1.233–1.517) <0.0001 207/4,199 1.561 (1.296–1.880) <0.0001 
   ≥9.0% (≥75 mmol/mol) 424/2,233 4.869 (4.030–5.882) <0.0001 486/2,158 1.734 (1.530–1.964) <0.0001 116/2,375 1.932 (1.523–2.451) <0.0001 
0–7 years          
 HbA1c          
  <6.5% (<48 mmol/mol) 272/7,372 Reference  1,222/6,245 Reference  476/7,660 Reference  
   6.5% to <7.0% (48 to <53 mmol/mol) 295/8,371 1.194 (1.006–1.418) 0.043 1,320/7,226 1.135 (1.046–1.232) 0.002 441/8,654 1.076 (0.938–1.233) 0.295 
   7.0% to <8.0% (53 to <64 mmol/mol) 481/11,178 1.606 (1.359–1.899) <0.0001 1,783/9,959 1.327 (1.221–1.442) <0.0001 562/11,672 1.269 (1.106–1.457) 0.001 
   8.0% to <9.0% (64 to <75 mmol/mol) 310/4,202 2.580 (2.123–3.135) <0.0001 689/3,797 1.577 (1.412–1.760) <0.0001 213/4,389 1.661 (1.378–2.003) <0.0001 
   ≥9.0% (≥75 mmol/mol) 414/2,201 6.437 (5.246–7.899) <0.0001 447/2,107 2.113 (1.847–2.417) <0.0001 115/2,362 2.181 (1.713–2.778) <0.0001 
Microvascular events
Macrovascular events
Death
Early period and mean glycemic controln/total nAdjusted HR (95% CI)P valuen/total nAdjusted HR (95% CI)P valuen/total nAdjusted HR (95% CI)P value
0–1 year          
 HbA1c          
   <6.5% (<48 mmol/mol) 864/14,080 Reference  3,668/13,455 Reference  744/14,286 Reference  
   6.5% to <7.0% (48 to <53 mmol/mol) 372/5,774 1.204 (1.063–1.365) 0.004 1,497/5,552 1.188 (1.116–1.264) <0.0001 268/5,877 1.137 (0.985–1.313) 0.079 
   7.0% to <8.0% (53 to <64 mmol/mol) 385/4,656 1.391 (1.226–1.578) <0.0001 1,244/4,501 1.287 (1.203–1.377) <0.0001 224/4,730 1.290 (1.104–1.507) 0.001 
   8.0% to <9.0% (64 to <75 mmol/mol) 154/1,390 1.603 (1.340–1.917) <0.0001 383/1,351 1.369 (1.227–1.527) <0.0001 68/1,418 1.262 (0.978–1.628) 0.073 
   ≥9.0% (≥75 mmol/mol) 232/1,259 2.213 (1.892–2.590) <0.0001 382/1,220 1.485 (1.329–1.659) <0.0001 66/1,290 1.320 (1.017–1.713) 0.037 
   Missing 647/7,047 1.354 (1.218–1.505) <0.0001 1,899/6,867 1.112 (1.050–1.177) 0.0003 437/7,136 1.235 (1.094–1.394) 0.001 
0–2 years          
 HbA1c          
   <6.5% (<48 mmol/mol) 809/14,673 Reference  3,612/13,860 Reference  817/14,940 Reference  
   6.5% to <7.0% (48 to <53 mmol/mol) 451/7,517 1.259 (1.117–1.419) 0.0002 1,866/7,143 1.158 (1.093–1.228) <0.0001 368/7,675 1.093 (0.962–1.241) 0.172 
   7.0% to <8.0% (53 to <64 mmol/mol) 544/7,144 1.497 (1.331–1.684) <0.0001 1,788/6,842 1.264 (1.189–1.344) <0.0001 368/7,295 1.240 (1.088–1.414) 0.001 
   8.0% to <9.0% (64 to <75 mmol/mol) 258/2,529 1.700 (1.460–1.980) <0.0001 620/2,426 1.279 (1.168–1.401) <0.0001 128/2,592 1.274 (1.047–1.551) 0.016 
   ≥9.0% (≥75 mmol/mol) 408/2,159 2.756 (2.396–3.170) <0.0001 624/2,112 1.539 (1.400–1.692) <0.0001 126/2,235 1.528 (1.245–1.876) <0.0001 
0–3 years          
 HbA1c          
   <6.5% (<48 mmol/mol) 619/12,475 Reference  2,931/11,635 Reference  717/12,769 Reference  
   6.5% to <7.0% (48 to <53 mmol/mol) 412/7,883 1.194 (1.049–1.359) 0.007 1,818/7,347 1.126 (1.059–1.197) 0.0001 375/8,057 0.975 (0.856–1.109) 0.696 
   7.0% to <8.0% (53 to <64 mmol/mol) 551/8,310 1.453 (1.281–1.648) <0.0001 1,931/7,873 1.208 (1.134–1.286) <0.0001 433/8,541 1.189 (1.044–1.353) 0.009 
   8.0% to <9.0% (64 to <75 mmol/mol) 293/3,081 1.835 (1.571–2.145) <0.0001 732/2,952 1.329 (1.216–1.453) <0.0001 162/3,188 1.376 (1.145–1.654) 0.001 
   ≥9.0% (≥75 mmol/mol) 406/2,084 3.193 (2.738–3.723) <0.0001 563/2,041 1.471 (1.327–1.631) <0.0001 120/2,182 1.503 (1.211–1.865) 0.0002 
0–4 years          
 HbA1c          
   <6.5% (<48 mmol/mol) 493/10,627 Reference  2,322/9,692 Reference  621/10,898 Reference  
   6.5% to <7.0% (48 to <53 mmol/mol) 401/8,097 1.252 (1.091–1.436) 0.001 1,719/7,410 1.100 (1.031–1.174) 0.004 399/8,302 1.013 (0.889–1.155) 0.842 
   7.0% to <8.0% (53 to <64 mmol/mol) 542/9,306 1.461 (1.277–1.673) <0.0001 2,019/8,710 1.224 (1.145–1.308) <0.0001 482/9,608 1.224 (1.074–1.395) 0.002 
   8.0% to <9.0% (64 to <75 mmol/mol) 312/3,567 1.894 (1.608–2.231) <0.0001 770/3,352 1.299 (1.185–1.425) <0.0001 187/3,697 1.453 (1.211–1.742) <0.0001 
   ≥9.0% (≥75 mmol/mol) 412/2,115 3.687 (3.123–4.352) <0.0001 534/2,073 1.535 (1.374–1.714) <0.0001 118/2,232 1.676 (1.337–2.100) <0.0001 
0–5 years          
 HbA1c          
   <6.5% (<48 mmol/mol) 399/9,209 Reference  1,862/8,226 Reference  552/9,475 Reference  
   6.5% to <7.0% (48 to <53 mmol/mol) 377/8,244 1.263 (1.091–1.462) 0.002 1,596/7,389 1.102 (1.027–1.182) 0.007 423/8,465 1.070 (0.937–1.221) 0.318 
   7.0% to <8.0% (53 to <64 mmol/mol) 519/10,118 1.441 (1.246–1.666) <0.0001 2,038/9,315 1.259 (1.173–1.352) <0.0001 518/10,500 1.238 (1.083–1.415) 0.002 
   8.0% to <9.0% (64 to <75 mmol/mol) 331/3,841 2.111 (1.779–2.506) <0.0001 727/3,556 1.269 (1.150–1.400) <0.0001 200/3,984 1.554 (1.294–1.867) <0.0001 
   ≥9.0% (≥75 mmol/mol) 418/2,184 4.094 (3.427–4.893) <0.0001 524/2,134 1.596 (1.420–1.794) <0.0001 114/2,313 1.747 (1.382–2.208) <0.0001 
0–6 years          
 HbA1c          
   <6.5% (<48 mmol/mol) 343/8,192 Reference  1,524/7,122 Reference  505/8,463 Reference  
   6.5% to <7.0% (48 to <53 mmol/mol) 319/8,328 1.137 (0.970–1.333) 0.112 1,433/7,362 1.074 (0.996–1.159) 0.064 432/8,580 1.097 (0.959–1.255) 0.177 
   7.0% to <8.0% (53 to <64 mmol/mol) 523/10,696 1.543 (1.324–1.797) <0.0001 1,967/9,671 1.299 (1.204–1.402) <0.0001 547/11,120 1.278 (1.116–1.464) 0.0004 
   8.0% to <9.0% (64 to <75 mmol/mol) 322/4,034 2.252 (1.879–2.700) <0.0001 713/3,683 1.368 (1.233–1.517) <0.0001 207/4,199 1.561 (1.296–1.880) <0.0001 
   ≥9.0% (≥75 mmol/mol) 424/2,233 4.869 (4.030–5.882) <0.0001 486/2,158 1.734 (1.530–1.964) <0.0001 116/2,375 1.932 (1.523–2.451) <0.0001 
0–7 years          
 HbA1c          
  <6.5% (<48 mmol/mol) 272/7,372 Reference  1,222/6,245 Reference  476/7,660 Reference  
   6.5% to <7.0% (48 to <53 mmol/mol) 295/8,371 1.194 (1.006–1.418) 0.043 1,320/7,226 1.135 (1.046–1.232) 0.002 441/8,654 1.076 (0.938–1.233) 0.295 
   7.0% to <8.0% (53 to <64 mmol/mol) 481/11,178 1.606 (1.359–1.899) <0.0001 1,783/9,959 1.327 (1.221–1.442) <0.0001 562/11,672 1.269 (1.106–1.457) 0.001 
   8.0% to <9.0% (64 to <75 mmol/mol) 310/4,202 2.580 (2.123–3.135) <0.0001 689/3,797 1.577 (1.412–1.760) <0.0001 213/4,389 1.661 (1.378–2.003) <0.0001 
   ≥9.0% (≥75 mmol/mol) 414/2,201 6.437 (5.246–7.899) <0.0001 447/2,107 2.113 (1.847–2.417) <0.0001 115/2,362 2.181 (1.713–2.778) <0.0001 

All models adjusted for year of diagnosis, age at diagnosis, sex, race/ethnicity, BMI, systolic and diastolic blood pressure, total cholesterol, HDL cholesterol, smoking status, HbA1c after each early period, and comorbidity.

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