老年糖尿病人的治療

Therapies for Treating Diabetes in the Elderly

林興中(Hing-Chung Lam)

《台灣老年醫學暨老年學雜誌》 12卷3期 (2017/08) Pp. 166-177

https://doi.org/10.29461/TGG.201708_12(3).0002

摘要

正常成人因老化過程導致胰島素分泌減少，加上肌肉日漸萎縮(肌少症)，內臟脂肪增加，運動量及身體活動量減少而可能引發胰島素阻抗，因此第2型糖尿病的發生會隨著年齡的增加而增加。2015年據國際糖尿病聯盟(International Diabetes Federation, IDF)報告，全世界老年人糖尿病的盛行率平均已達15%，而在已開發國家(美國、台灣等)更已超過20%。近年來一系列的糖尿病臨床研究(ACCORD、ADVANCE、VADT)主要是去探討嚴格血糖控制與心血管事件的影響。結果發現嚴格控制血糖雖然可以降低小血管併發症的發生，但大血管病變卻沒有獲得一致的結論，而低血糖的發生卻增加了。其中ACCORD試驗更因為在嚴格控制組的病人死亡風險增加，而提前終止試驗。這些研究結果顯示第二型糖尿病人的理想血糖控制目標，應該要作「個別化」考量。研究發現「失能」較「多重共病」在高齡者更能預測其死亡風險。一些研究也發現老年糖尿病人發生低血糖時其升糖素和交感神經等賀爾蒙的分泌均較年輕人為低，因此其自律神經反應的警覺認知也較不明顯，較容易發生嚴重低血糖。低血糖的發生可能會導致老年人的認知功能惡化、跌倒及骨折，因而造成病人的「失能」。因此在治療老年糖尿病人時，必須以防範低血糖的發生為首要考量。由於老年人肝、腎功能變差，也有較高的營養不良風險，加上「多重共病」，使用藥物也多，而藥物間交互作用的結果，造成藥物不良事件的發生機率也隨年齡增加而增加，因此適度調整血糖控制目標是必須的。例如：對於那些身心功能良好，沒有「多重共病」的健康老年糖尿病人，其糖化血色素A1c控制目標可以設定在7-7.5%之間(如能安全達標)。而具有「多重共病」，健康狀態很差，及「平均餘命」有限的老年糖尿病人，較適合將A1c控制目標設定在7.5%至9%，甚至更高。至於口服抗糖尿病藥物的使用，除非有禁忌，原則上仍以metformin為第一優先考量。在血糖控制目標無法達成，或對metformin不耐時，IDF、國際及歐洲老年醫學會建議可加上(或使用)DPP-4抑制劑，或在無低血糖風險或禁忌症時也可考慮加上風險較低或半衰期較短的sulfonylurea、或其他類抗糖尿病藥物。如果必須使用胰島素，也應儘量優先使用基礎胰島素治療，以降低發生低血糖的風險。

關鍵字

老年 ； 第2型糖尿病 ； 低血糖 ； 糖化血色素

並列摘要

The aging process in healthy adults can cause a decrease in insulin secretion, sarcopenia, increase in visceral fat, and decrease in exercise and physical activity. Together these may lead to cause insulin resistance and thus an increase in the prevalence of type 2 diabetes mellitus (T2DM) in the elderly. According to a report of International Diabetes Federation (IDF) in 2015, the prevalence of type 2 diabetes in the elderly was around 15% on average and exceeded 20% in developed countries like USA and Taiwan. Recently, a series of large prospective clinical trials were performed (ACCORD, ADVANCE, and VADT) to investigate the impact of intensive glycemic control on CV outcomes. Although the trials showed benefits in microvascular complications, they produced inconsistent results for the macrovascular complications, and increase in the risk of hypoglycemia; the ACCORD trial even experienced early termination due to an increased risk of death in the intensive therapy arm, thereby indicating the need to take into consideration of each individual’s specific characteristics on a case-by-case basis for achieving optimal glycemic control in people with T2DM. It is well known that disability, more than multi-morbidity, was predictive of mortality among older persons. Furthermore, elderly diabetic patients are prone to hypoglycemia due to hypoglycemia unawareness as a result of a decrease in the secretion of glucagon and adrenergic hormones during the period of hypoglycemia. Hypoglycemia may be associated with a higher risk of cognitive decline, falls and fractures, which in turn may result in functional impairment. Therefore, avoiding hypoglycemia is of paramount importance in treating diabetes in the elderly. As older patients are at increased risk for adverse drug events from most medications due to age-related changes in hepato-renal function, undernutrition, comorbidities, as well as polypharmacy, the target of diabetic control should be tailored accordingly. For example, it may be appropriate to set the target for glycosylated hemoglobin (A1c) between 7% and 7.5% if it can be safely achieved in healthy older adults with few comorbidities and good functional status. Higher A1c targets (7.5-9.0% or higher) are more appropriate for older adults with multiple comorbidities, poor health, and limited life expectancy. If an older adult is prescribed an oral antidiabetic agent, metformin, unless contraindicated, remains the preferred first-line agent in combination with lifestyle therapy. After the use of metformin, other glucose-lowering medication therapies should be individualized. For elderly patients not in target or with poor tolerance to metformin, the use of a dipeptidyl peptidase 4 (DPP4) inhibitor, or lower risk or short half-life sulfonylurea, or other agents, can also be considered as a second-line therapy if no hypoglycemic risk or contraindications exists. If insulin therapy is indicated, a basal insulin regimen may be safer in terms of hypoglycemia risk than a basal/bolus or premixed insulin regimen.

並列關鍵字

elderly ； type 2 diabetes mellitus ； hypoglycemia ； glycosylated hemoglobin