Mechanisms of Post-Bariatric Hypoglycemia
Mechanisms of Post-Bariatric Hypoglycemia
批准号:
10313148
负责人:
Mary E Patti
金额:
$57.06万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-06-26 至 2023-05-31
中文摘要
摘要
英文摘要
Abstract
Bariatric surgery is increasingly recognized as a potent tool for the treatment of type 2 diabetes (T2D), yielding
not only weight loss but also rapid improvements in glycemia allowing discontinuation of diabetes-related
medication within days after surgery1. However, along with this metabolic success comes an increased
incidence of severe hypoglycemia (termed post-bariatric hypoglycemia; PBH) for a subset of patients. Severe
hypoglycemia causes not only distressing adrenergic and cholinergic symptoms but also neuroglycopenia and
hypoglycemia unawareness, impairing safety and increasing risk for disability, syncope, arrhythmias, seizures,
coma, and death. Although initially thought to occur in <1% of patients and isolated to roux-en-Y gastric bypass
(RYGB), latest estimates suggest that it occurs in ~30% of patients, after both RYGB and vertical sleeve
gastrectomy (SG), with similar presentation and spectrum of severity. Increased postprandial incretin and
insulin secretion, increased insulin sensitivity, and altered bile acid metabolism have all been implicated in the
pathogenesis of PBH. Recent work also suggests that RYGB reduces counterregulatory responses to
hypoglycemia. Together, these data suggest that, like the mechanisms that underlie the metabolic success of
surgery, the mechanism(s) that underlie PBH are multi-factorial. However, an important feature of PBH is the
timing of symptoms. While increases in incretins and improvements in glucose homeostasis occur almost
immediately, the onset of PBH typically occurs years postoperatively. Thus, there is more to PBH than
increased incretin and consequently insulin responses. The goal of this proposal is to utilize a combination
of preclinical and clinical studies to identify physiological and molecular mechanisms that underlie
PBH, to determine whether these changes also contribute to surgery-induced improvements in
glucose homeostasis, and to define potential therapeutic interventions for PBH. We will determine if
decreases in the counterregulatory hormonal responses to hypoglycemia precede bariatric surgery-induced
improvements in peripheral insulin sensitivity in rodents (Aim 1). We will test the hypothesis that
counterregulatory hormonal responses to hypoglycemia are impaired in post-bariatric patients with or without
PBH (Aim 2). Finally, we see that FGF19 is increased in patients with PBH and we will utilize both clinical and
preclinical strategies to answer the critical questions of what drives this increase in FGF19 (Aim 3) and whether
it is required for the development of PBH (Aim 4).
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会议论文
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Gene Expression in Prediabetes: Potential Role of PGC-1
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BIFUNCTIONAL MODULATION OF INSULIN ACTION BY AMINO ACIDS
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依托单位:
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依托单位:
BIFUNCTIONAL MODULATION OF INSULIN ACTION BY AMINO ACIDS
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财政年份:1997
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依托单位:
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项目类别:
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资助金额:$12.4万
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财政年份:1997
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依托单位:
BIFUNCTIONAL MODULATION OF INSULIN ACTION BY AMINO ACIDS
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