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Which Is the Best Treatment for Diabetes Complicated With Severe Obesity, Intensive Insulin Therapy or Basal Sumie Moriyamaa, c, Hidekatsu Yanaia, b, c, d mg/day, and insulin glargine 24 units/day) reduced body Letter to the Editor:
weight (from 92.1 to 86.0 kg) and HbA (from 10.3 to 9.2%) after 9 months (Fig. 1). However, we decided to change the Type 2 diabetes is commonly complicated with obesity. Al- treatment from BOT to the GLP-1 analog (liraglutide) use, though achieving a healthy weight and preventing weight because her HbA level was still high. At this time, her body gain are integral components of optimal diabetes manage- weight was 86 kg and height 149 cm (BMI 38.7 kg/m2). ment, an improvement of glycemic control with the treat- As a result of the measurement using abdominal computed ment usually induces weight gain . Until now, we do not tomography, abdominal circumference was 121.0 cm, while exactly understand which treatment is the best for diabetes subcutaneous fat area and visceral fat area were 374.5 and complicated with severe obesity. We will show the changes 362.6 cm2 (Fig. 2), respectively, showing severe obesity. To in body weight and glycemic control in a type 2 diabetic pa- understand her insulin-dependence, a glucagon loading test tient complicated with severe obesity, by the intensive insu- and the measurement of daily urinary C-peptide (CPR) level lin therapy (IIT), basal supported oral therapy (BOT), and were performed. Serum fasting CPR level and serum CPR level at 6 minutes after a glucagon loading were 1.28 and A 60-year-old woman was referred and admitted to our 3.31 ng/ml, respectively, and urinary CPR level was 40.6 μg/ hospital due to poor blood glucose control in spite of the day, which indicated that she has a suffi cient insulin secretion treatment by IIT. At the age of 47 she was diagnosed as type capacity. Therefore, we switched from BOT to the GLP-1 2 diabetes. For the last one year, she was treated with four analog use. Switching to the GLP-1 analog (liraglutide 0.9 daily insulin injections: three injections of insulin aspart mg/day) as monotherapy signifi cantly reduced body weight before breakfast (14 units), lunch (14 units), and dinner (14 (from 86.0 to 77.0 kg) after fi ve months, and the addition of units) and one of insulin detemir (18 units) at bedtime. Her daily 1 mg of glimepiride to the GLP-1 analog signifi cantly body weight was 92.1 kg and height 149 cm (BMI 41.5 kg/ reduced HbA (from 9.0 to 7.9%) (Fig. 1). m2). Fasting plasma glucose (284 mg/dl) and HbA (NGSP Therapeutic strategies to prevent or minimize weight value, 10.3%) levels were signifi cantly elevated. Switching gain, especially in obese diabetic patients, are very impor- from IIT to BOT (glimepiride 1 mg/day, metformin 1,000 tant to help diabetic patients manage their glycemic control and keep or improve their quality of life. However, an in-tensive therapy is likely to induce weight gain. Weight gain was identifi ed as a sequela of IIT in the Diabetes Control and Complications Trial (DCCT), which is a multicenter controlled clinical trial designated to determine the effects of two different diabetes treatment regimens on complications Manuscript accepted for publication October 12, 2011 of type 1 diabetic patients . Higher baseline HbA levels and greater decrements in HbA during intensive therapy Department of Internal Medicine, National Center for Global Health were both associated with greater weight gain in the DCCT. and Medicine, Kohnodai Hospital, Ichikawa, Japan In our patients, switching from IIT to BOT decreased daily Clinical Research Center, National Center for Global Health and Medicine, Kohnodai Hospital, Ichikawa, Japan insulin use from 60 units to 24 units, which may be associ- cSumie Moriyama and Hidekatsu Yanai contributed equally to this ated with weight loss. BOT has been reported to minimize weight gain compared with premixed insulin and prandial insulin regimens , supporting our result. The effects of liraglutide have been studied in the Lira- glutide Effect and Action in Diabetes (LEAD). In the LEAD-5 study, liraglutide added to metformin and sulfonylurea Articles The authors | Journal compilation J Endocrinol Metab and Elmer Press™ | www.jofem.org Figure 1. The changes in body weight and HbA1c levels by the intensive insulin therapy
(IIT), the basal supported oral therapy (BOT), and the glucagon-like peptide-1 (GLP-1)
produced signifi cant improvements in glycemic control and In conclusion, the GLP-1 analog use may be an excellent body weight compared with placebo and insulin glargine . therapeutic strategy for the diabetes management of type 2 In our patient, switching from BOT using insulin glargine to diabetic patients who have suffi cient insulin secretion capac- the GLP-1 analog use signifi cantly reduced body weight and ity, complicated with severe obesity.
HbA level, showing an agreement with the result of LEAD- 5 study. GLP-1 is released into the blood from intestinal L-cells in response to meal ingestion. GLP-1 stimulates insu- Acknowledgment
lin secretion from pancreatic ß-cells in a glucose-dependent manner, and slows gastric emptying, which may aid weight This work was supported by the Grant of National Center for loss and resulting amelioration in glycemic control .
Global Health and Medicine (22-120).
Figure 2. Abdominal computed tomography. Red and blue areas indicate visceral fat and subcutaneous
fat area, respectively.
Articles The authors | Journal compilation J Endocrinol Metab and Elmer Press™ | www.jofem.org Best Treatment for Diabetes With Obesity References
N, Antic S, Zdravkovic M, et al. Liraglutide vs insulin glargine and placebo in combination with metformin and 1. Davies M, Khunti K. Insulin management in overweight sulfonylurea therapy in type 2 diabetes mellitus (LEAD- or obese type 2 diabetes patients: the role of insulin 5 met+SU): a randomised controlled trial. Diabetologia. glargine. Diabetes Obes Metab. 2008;10 Suppl 2:42-49.
2. Weight gain associated with intensive therapy in the 4. Kjems LL, Holst JJ, Volund A, Madsbad S. The infl u- diabetes control and complications trial. The DCCT Re- ence of GLP-1 on glucose-stimulated insulin secretion: search Group. Diabetes Care. 1988;11(7):567-573.
effects on beta-cell sensitivity in type 2 and nondiabetic 3. Russell-Jones D, Vaag A, Schmitz O, Sethi BK, Lalic subjects. Diabetes. 2003;52(2):380-386.
Articles The authors | Journal compilation J Endocrinol Metab and Elmer Press™ | www.jofem.org
PERSPECTIVE Georgia’s Double Taxation Agreements Viewpoint of the OECD 1. Introduction B a k e r , i n t h e i n t r o d u c t i o n t o h i s b o o k , D o u b l e T a x a t i o n A g r e e m e n t s a n dInternational Tax Law, which was published in 1991,1 wrote: “This book is about atreaty which does not exist. No two states have ever concluded a treaty identicalto the OECD Mode