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​英訳サンプル:       7​

There was no evidence of effect modification according to sex for participants without diabetes (P = 0.86 for interaction) or for participants with diabetes (P = 0.72 for interaction). Similarly, there was no evidence of effect modification according to age at study entry among participants without diabetes (P = 0.84). However, there was a suggestion of possible effect modification according to age at study entry among participants with diabetes, but the effect was not significant (P = 0.13). We estimated the hazard ratios for study entry at 70 to 78 years of age for participants with diabetes+ (Fig. S2 in the Supplementary Appendix). An increased risk associated with both higher and lower glucose levels appeared to be especially prominent among participants who were older at study entry.
非糖尿病の参加者(相関はP = 0.86)または糖尿病の参加者(相関はP = 0.72)の性別による影響は確認されず、また、試験登録時における非糖尿病の参加者の年齢による影響も認められなかった(P = 0.84)。しかし、試験登録時における糖尿病の参加者の年齢による影響は、有意ではないものの生じていた可能性がある(P = 0.13)。我々は糖尿病の参加者を対象に、70~78歳での試験登録時のハザード比を評価した(付録の図.S2)。高血糖値と低血糖値の両方に関連したリスクの増加は、試験登録時に高齢であるほど顕著になる可能性があった。
Among people without diabetes, no individual participant had data that had a particularly marked influence on model parameter estimates (see the Results S1 section and Fig. S3 in the Supplementary Appendix). Some people with diabetes did have data that had a marked influence on model parameter estimates, and we reviewed their medical records. We repeated our primary analyses after excluding data from one participant with acromegaly (Fig. S4 in the Supplementary Appendix) and after excluding data from that participant and two other participants, each of whom had an atypical natural history of type 2 diabetes (Fig. S5 in the Supplementary Appendix). The exclusion of these data resulted in the near elimination of the suggestion of elevated risk at the lowest glucose levels.

Additional adjustment for the APOE genotype did not change our findings (Table S6 in the Supplementary Appendix). Point estimates were similar when 2-year windows of glucose exposure were used rather than 5-year windows, although the risk of dementia was significant only for participants with diabetes when the 2-year window of glucose exposure was used (Table S7 in the Supplementary Appendix). Results were similar when exposure was estimated assuming more dispersed or less dispersed prior distributions for glucose and hemoglobin A1c (Table S8 in the Supplementary Appendix). Results were similar when we accounted for the differences between fasting and random glucose levels (Table S9 in the Supplementary Appendix).

Any rise in glycemia is the net result of glucose influx exceeding glucose outflow from the plasma compartment. In the fasting state, hyperglycemia is directly related to increased hepatic glucose production. In the postprandial state, further glucose excursions result from the combination of insufficient suppression of this glucose output and defective insulin stimulation of glucose disposal in target tissues, mainly skeletal muscle. Once the renal tubular transport maximum for glucose is exceeded, glycosuria curbs, though does not prevent, further hyperglycemia.


Abnormal islet cell function is a key and requisite feature of type 2 diabetes. In early disease stages, insulin production is normal or increased in absolute terms, but disproportionately low for the degree of insulin sensitivity, which is typically reduced. However, insulin kinetics, such as the ability of the pancreatic b-cell to release adequate hormone in phase with rising glycemia, are profoundly compromised. This functional islet incompetence is the main quantitative determinant of hyperglycemia and progresses over time. In addition, in type 2 diabetes, pancreatic a-cells hypersecrete glucagon, further promoting hepatic glucose production.

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