Data from a British registry of patients with type 2 diabetes (T2DM) show decreased survival at low as well as high glycated hemoglobin (A1C) levels.
Background: Recent clinical trials have failed to demonstrate benefit with intensive glycemic control and raised concerns about the optimum target for A1C.
Methods: Investigators analyzed data from the following two cohorts of patients, aged at least 50 years with T2DM, who were identified from a British primary care database:
- Cohort 1: Individuals (n = 27,965) whose treatment regimens had been intensified from oral monotherapy to combination therapy with oral glucose-lowering agents.
- Cohort 2: Individuals (n = 20,005) whose treatment regimens had been intensified from oral therapy to combination regimens that included insulin.
Results:
- Mean and median follow-up in the two cohorts were, respectively, 4.5 years and 3.9 years (Cohort 1) and 5.2 years and 4.4 years (Cohort 2).
- Unadjusted all-cause mortality rates in both cohorts were greatest in the lowest and highest deciles (Tables 1 and 2).
- Adjusted hazard ratios for all-cause mortality by decile in Cohort 1 (with decile 4 [median A1C 7.5%] as reference) were:
- Decile 1: 1.30 (95% confidence interval [CI] 1.07-1.58, P = 0.0072)
- Decile 10: 1.93 (95% CI 1.55-2.42, P < 0.0001)
- Corresponding hazard ratios for Cohort 2 were:
- Decile 1: 1.79 (95% CI 1.45-2.22, P < 0.0001)
- Decile 10: 1.80 (95% CI 1.49-2.17, P < 0.0001)
Table 1. A1C values and survival in Cohort 1 |
|
A1C decile |
|
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
n |
3513 |
3501 |
3374 |
3136 |
2884 |
2684 |
2437 |
2334 |
2133 |
1969 |
A1C*, % |
6.42 |
6.94 |
7.27 |
7.54 |
7.82 |
8.11 |
8.44 |
8.85 |
9.41 |
10.47 |
All-cause mortality, n (%) |
301
(9) |
238
(7) |
231
(7) |
207
(7) |
190
(7) |
179
(7) |
175
(7) |
168
(7) |
161
(8) |
185
(9) |
*Mean of values recorded between first prescription of intensified therapy and outcome event |
Table 2. A1C values and survival in Cohort 2 |
|
A1C decile |
|
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
n |
1289 |
1291 |
1424 |
1661 |
1878 |
2148 |
2354 |
2463 |
2660 |
2837 |
A1C*, % |
6.38 |
6.95 |
7.28 |
7.55 |
7.83 |
8.11 |
8.45 |
8.87 |
9.42 |
10.56 |
All-cause mortality, n (%) |
232
(18) |
204 (16) |
209 (15) |
192 (12) |
211 (11) |
271 (13) |
305 (13) |
334 (14) |
404 (15) |
472 (17) |
*Mean of values recorded between first prescription of intensified therapy and outcome event |
Conclusions: Regardless of glucose-lowering treatment regimen, an A1C of approximately 7.5% was associated with lowest mortality.
Comment: "Our findings suggest that diabetes guidelines might need revision to include a definition of an HbA1C [A1C] minimum value," write the authors. |
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