Treatment of Hypoglycemia Following Gastric Bypass Surgery
Түлхүүр үгс
Хураангуй
Тодорхойлолт
Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed bariatric procedures used in the treatment of severe obesity. RYGB has in several studies been shown to result in significant and sustained weight loss. Moreover, RYGB has a beneficial effect on obese subjects with type 2 diabetes by improving blood glucose regulation, resulting in remission or partial remission of type 2 diabetes already days after surgery.
The changes of the anatomy of the stomach and small intestine cause a faster and more abrupt increase in blood glucose after a meal. As a consequence of the changed glucose absorption after RYGB and the increased insulin secretion, some subjects experience the condition named postprandial hyperinsulinemic hypoglycemia. Postprandial hyperinsulinemic hypoglycemia is typically seen years after RYGB and the symptoms vary from mild dizziness to confusion, loss of consciousness and seizures. The condition is characterized by large postprandial blood glucose variations accompanied by exaggerated insulin and glucagon-like peptide 1 (GLP-1) responses. Continuous glucose monitoring (CGM) have shown that subjects suffering from postprandial hyperinsulinemic hypoglycemia presents large variations in blood glucose from values below 3.5 mmol/L to diabetic values above 11.1 mmol/L within the first hour after a meal.
At present, there are no treatment guidelines beside dietary recommendations. Experimental treatment includes diet modifications, pharmaceutical treatments and surgical procedures. Several pharmaceutical agents have been attempted in the management of postprandial hyperinsulinemic hypoglycemia, but overall the existing studies consist of few case reports and case series evaluated primarily by relief of symptoms and not by CGM and hormonal analyses.
The study is designed as a randomized, non-blinded cross-over study including five treatment arms. The pharmaceutical agents are: a) Glucobay, b) Januvia, c) Verapamil, d) Victoza and e) Signifor. The treatment duration is 1 - 3 weeks, except for Signifor, which is administered for one day only. Each treatment period is separated by a wash out period of 7-10 days.
Sixteen none diabetic women are included in the study. They have undergone RYGB and have symptoms of postprandial hyperinsulinemic hypoglycemia. Moreover, former CGM has shown fluctuations in blood glucose of more than 5 mmol/L during daily living and with at least one blood glucose reading below 3.5 mmol/L.
Six days continuous glucose monitoring will be performed at run-in and during each treatment arm, except for e) Signifor due to the short treatment period. At the end of the CGM measurement a meal tolerance test (MTT) will be performed. During the MTT blood samples for glucose measurements and hormone assessments (insulin, C-peptide, GLP-1, gastric inhibitory peptide (GIP), glucagon, insulin like growth factor (IGF-1), epinephrine, norepinephrine) will be drawn continuously as well as continuous pulse recording and blood pressure measurements.
Огноо
| Сүүлд баталгаажуулсан: | 02/28/2018 |
| Эхлээд оруулсан: | 08/10/2015 |
| Тооцоолсон элсэлтийг оруулсан: | 08/16/2015 |
| Эхлээд нийтэлсэн: | 08/18/2015 |
| Сүүлийн шинэчлэлтийг оруулсан: | 03/05/2018 |
| Сүүлийн шинэчлэлтийг нийтэлсэн: | 03/06/2018 |
| Сургалтын бодит эхлэх огноо: | 09/30/2015 |
| Тооцоолсон анхан шатны ажил дуусах огноо: | 04/07/2017 |
| Судалгааны ажлыг дуусгах өдөр: | 04/07/2017 |
Нөхцөл байдал эсвэл өвчин
Хөндлөнгийн оролцоо / эмчилгээ
Drug: Glucobay
Drug: Januvia
Drug: Verapamil
Drug: Victoza
Drug: Signifor
Device: Continuous glucose monitoring (CGM)
Dietary Supplement: Meal tolerance test (MTT)
Үе шат
Arm Groups
| Гар | Хөндлөнгийн оролцоо / эмчилгээ |
|---|---|
| Experimental: Glucobay Tablet Glucobay (acarbose) 50 mg x 6 daily for 7 days. | Drug: Glucobay Se arm description |
| Experimental: Januvia Tablet Januvia (sitagliptin) 100 mg orally O.D for 7 days. | Drug: Januvia Se arm description |
| Experimental: Verapamil Tablet Verapamil 120 mg orally O.D for 7 days. | Drug: Verapamil Se arm description |
| Experimental: Victoza Subcutaneous injection of Victoza (liraglutide) 0,6-1,2 mg O.D for three weeks. | Drug: Victoza Se arm description |
| Experimental: Signifor Subcutaneous injection of Signifor (pasireotide) 300 µg as a single dose prior to a meal tolerance test. | Drug: Signifor Se arm description |
Эрхийн шалгуур
| Суралцах боломжтой нас | 25 Years Хэнд 25 Years |
| Суралцах боломжтой хүйс | Female |
| Эрүүл сайн дурын ажилтнуудыг хүлээн авдаг | Тийм ээ |
| Шалгуур үзүүлэлтүүд | Inclusion Criteria: - symptoms of postprandial hyperinsulinemic hypoglycemia. - fluctuations in blood glucose of more than 5 mmol/L during daily living - at least one blood glucose reading below 3.5 mmol/L. - More than 18 months since RYGB - HbA1c < 40 mmol/L - Hemoglobin > 7,3 mmol/L - Ferritin > 30 µg/L - Cobalamin > 150 picomol/L - Creatinine < 105 mmol/L - C peptide > 1,0 nmol/L - Insulin > 35 pmol/L - Normal EKG - Negative human chorionic gonadotropin (hCG) urine test - Females of reproductive age: use of safe contraception Exclusion Criteria: - Treatment for cardiovascular disease - Treatment with antipsychotics, antidepressants or anxiolytics - Smoking - Treatment for thyroid disease - Prior medical treatment of postprandial hyperinsulinemic hypoglycemia - Allergy for the study medicine |
Үр дүн
Анхан шатны үр дүнгийн арга хэмжээ
1. Changes in blood glucose (mmol/L) assessed by continuous glucose monitoring (CGM). [6 days CGM will be performed at week 1, 3, 5, 7 and 11.]
Хоёрдогч үр дүнгийн арга хэмжээ
1. Changes in glucose (mmol/L) in response to a meal tolerance test (MTT) [From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.]
2. Changes heart rate (beats/min) during the course of a meal tolerance test (MTT) [From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.]
3. Changes in insulin (pmol/L) in response to a meal tolerance test (MTT) [From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.]
4. Changes in C-peptide (nmol/L) in response to a meal tolerance test (MTT) [From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.]
5. Changes in Insulin-like growth factor 1 (nmol/L) in response to a meal tolerance test (MTT) [From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.]
6. Changes in glucagon (pmol/L) in response to a meal tolerance test (MTT) [From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.]
7. Changes in glucagon-like peptide 1 (pmol/L) in response to a meal tolerance test (MTT) [From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.]
8. Changes in gastric inhibitory peptide (pmol/L) in response to a meal tolerance test (MTT) [From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.]
9. Changes in epinephrine (pmol/L) in response to a meal tolerance test (MTT) [From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.]
10. Changes in norepinephrine (pmol/L) in response to a meal tolerance test (MTT) [From 20 minutes prior to a liquid test meal to 180 minutes following the meal ingestion.]
