Glycemic Control in Diabetic Patients after Bariatric Surgery

Transcription

1 Obesity Surgery, 14, Glycemic Control in Diabetic Patients after Bariatric Surgery Maria de Fátima Haueisen Sander Diniz, MD 1 ; Marco Túlio Costa Diniz, PhD 2 ; Soraya Rodrigues Almeida Sanches, PhD 2 ; Patrícia Paz Cabral de Almeida Salgado, MD 1 ; Maristane Mendes Andrade Valadão, MD 1 ; Cláudia Patrícia Freitas, MD 1 ; David José Vieira, MD 1 1 Serviço de Endocrinologia e Metabologia, 2 Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Background: Morbid obesity is associated with a high prevalence of diabetes mellitus, and weight loss is fundamental to improve glycemic control. The aim of the present study was to evaluate the impact of weight reduction during the late postoperative period ( 12 months) after gastric bypass on the glycemic control of diabetic patients. Methods: Fasting glycemia (glucose oxidase) and glycohemoglobin A1c (enzymatic fluorescence, reference value: 4-6%) were determined before and after surgery. Results were compared by the Student t-test for paired samples (P<0.05). Results: 23 women and 8 men with diabetes, with a mean follow-up of 27.2 months and a mean age of 42.5 years (30-68), were studied. Before surgery, mean ± SD weight, BMI, excess weight, glycemia and glycohemoglobin were 135.9±11.6 kg, 51.8±6.4 kg/m 2, 68.3±14.5kg, 173±71.2 mg/dl, and 7.4±1.9%, respectively. After surgery, mean weight, BMI, excess weight, percent weight loss, percent excess weight loss, glycemia and glycohemoglobin were 89.7±8.8 kg, 35±4.5 kg/m 2, 24.6±11.6 kg, 32.6%±1.8 ( %), 64.7±18.3%, 98±17.3 mg/dl (P<0.01), and 5.4±1.0% (P<0.05), respectively. Oral anti-diabetic drug and/or insulin treatment was discontinued in 89.2% of the patients. After surgery, 90.3% of the patients maintained glycohemoglobin A1c levels <7.0%. Conclusion: Weight loss led to a significant and sustained improvement of glycemic control in these patients submitted to bariatric surgery. Key words: Morbid obesity, diabetes, anti-obesity agents, bariatric surgery, gastric bypass Reprint requests to: Maria de Fátima Haueisen Sander Diniz, MD, Departamento de Clínica Médica da Faculdade de Medicina da UFMG, Av Alfredo Balena, andar, , Belo Horizonte, Minas Gerais, Brazil. mfhsdiniz@ufmg.br Introduction The prevalence of overweight and obesity is increasing in epidemic proportions in the western world. According to the National Health and Nutrition Examination Survey (NHANES III), 1,2 between one-third and half of American men and women older than 20 years are above the ideal weight, and about one-fourth are already obese (body mass index BMI 30 kg/m 2 ). With respect to morbid obesity (BMI 40 kg/m 2 ), data from the NHANES III found a prevalence of 3% in the American population. In Brazil, an increase in the prevalence of obesity has been observed, especially among youngsters, and involving severe forms. 3 The presence of morbid obesity is responsible for a significant increase in morbidity and mortality. 4,5 Patients with morbid obesity present a high incidence of co-morbidities, including insulin resistance, hyperinsulinemia and diabetes mellitus type 2 (DM2). 6-8 The risk of DM2 in patients with a BMI 25.0 kg/m 2 is three times higher than in the general population, 6 and the risk increases proportionally with increasing BMI. 9,10 Whereas the prevalence of DM2 is about 5.7% in the general population, Gleysteen et al, 14 Wittgrove et al 15 and Nova et al 16 reported prevalences of DM2 in morbidly obese individuals of 27, 32 and 34%, respectively. DM2 is the major cause of blindness, renal failure, neuropathy and amputations, and the main risk factor for cardiovascular disease. 12,13,17 DM2 reduces life FD-Communications Inc. Obesity Surgery, 14,

2 Diniz et al expectancy by about 35%. 17 It is known that weight loss leads to improvement or even remission of the metabolic disturbances shown by these obese and diabetic patients. 7,8 These data demonstrate the need for an effective therapy aimed at the loss and maintenance of weight in the long-term in order to prevent new cases of DM2 and to improve metabolic control. Conservative treatments such as low calorie diets, behavioral changes, physical exercise and the use of anti-obesity drugs are the first choice. Unfortunately, the outcomes of these measures are disappointing in the long-term, especially in patients with morbid obesity Bariatric surgery is currently considered to be the most effective therapeutic modality for the maintenance of a good glycemic control or for the cure of DM2 in morbidly obese patients. 22 Roux-en-Y gastric bypass (RYGBP) causes a significant and sustainable weight loss in the long-term, i.e. about 35% total weight loss and 40% to 85% excess body weight loss. 18,19,23,24 The aim of the present study was to evaluate the impact of weight reduction after RYGBP on the glycemic control of diabetic patients with morbid obesity at the University Hospital of the Federal University of Minas Gerais (UFMG), Brazil. Materials and Methods Morbidly obese (BMI 40 kg/m 2 ) and diabetic patients (according to the criteria of the American Diabetes Association 25 ) seen at the Endocrinology Service, University Hospital, UFMG, were followed-up between June 1995 and December The patients were treated with diet, oral anti-diabetic drugs and/or insulin and submitted to RYGBP at the Alpha Institute of Gastroenterology. After detailed information had been provided about the study, informed consent was obtained from all patients before surgery. All the patients were operated on by open Capella method. 26 The minimum postoperative follow-up period for inclusion in this study was 12 months. Patients with other diseases such as hemoglobinopathies and chronic renal failure, which are known to interfere with the measurement of glycohemoglobin, were excluded. The design of the study was retrospective, descriptive and cross-sectional. The following data obtained from the medical records were analyzed: age, gender, time of postoperative follow-up, weight, BMI, excess weight, percent of total weight loss and percent of excess weight loss (%EWL), current medication, fasting glycemia, and glycohemoglobin A1c (HbA1c) determined before surgery and during the late postoperative period (last medical visit performed). The following reference standards were used for assessment of the variables: BMI = kg/m 2 ; excess weight calculated by subtracting the ideal weight from the weight of the patient (considering upper limit of ideal to be a BMI of 25 kg/m 2 ); %EWL calculated according to [(operative weight follow-up weight)/ operative excess weight] x 100; 27 fasting glycemia determined by the glucose oxidase method (reference value: mg/dl); HbA1c determined by an enzymatic fluorescence method (reference value: 4.5 to 6.4%). With respect to current medication, the patients were divided according to current treatment for glycemic control before and after surgery: diet, oral anti-diabetic drugs, insulin, or insulin in combination with oral anti-diabetic drugs. Regarding metabolic control, the patients were classified based on the criteria established by the American Diabetes Association according to the levels of HbA1c before and after surgery: 7.0%, %, and >8.0%. The Student t-test for paired samples was used for statistical analysis, with P-values <0.05 being considered statistically significant. Results Twenty-three women (74.2%) and 8 men (25.5%) with DM2, with a mean age of 42.5 years (30 to 68 years) and a mean time of postoperative follow-up of 27.2±4.2 months (median 24 months, range 12 to 60 months) were studied. The patients presented a mean weight loss of 32.6%±1.8 ( ) and mean excess weight loss of 64.7±18.3% ( %) after surgery. The mean BMI decreased from 51.8±6.4 kg/m 2 ( ) before surgery to 35±4.5 kg/m 2 ( ) after surgery Obesity Surgery, 14, 2004

3 Glycemic Control after RYGBP A significant reduction in mean fasting glycemia and glycohemoglobin levels was observed after surgery, reaching values of nondiabetic patients (Table 1). Before surgery, 38.7% of the patients showed HbA1c levels 7.0% and 42.0% presented values >8.0%. After surgery, none of the patients showed HbA1c levels >8.0%, and most subjects (90.3%) had their levels reduced to <7.0% (Table 2). With respect to treatment for glycemic control, 9.7% of the patients only used a diet before surgery compared to 90.3% after the surgical procedure. The use of oral anti-diabetic drugs was discontinued after surgery in 19 of 21 of patients (90.5%) taking this type of medication. Among patients taking insulin, only one continued to use this drug after surgery, but with a 83.3% reduction in the dose. None of the patients required the use of insulin in combination with oral anti-diabetic drugs after surgery. Oral anti-diabetic drugs and/or insulin were withdrawn in 89.2% of the patients (Table 3). Table 1. Mean and standard deviation variables obtained before and after Roux-en-Y gastric bypass Variable Before After surgery surgery Weight (kg) ± ±8.8 BMI (kg/m 2 ) 51.8 ± ±4.5 Excess weight (kg) 68.3 ± ,6 ± 11.6 % Excess weight loss (%) - 64,7 ±18.3 Fasting glycemia (mg/dl) 173 ± ± 17.3* (9.6 ± 3.9 (5.4 ± 0.96 mmol/l) mmol/l) Glycohemoglobin A1c (%) 7.4 ± ± 1.0 *P<0.01 vs before surgery; P<0.05 vs before surgery. Table 2. Glycohemoglobin A1c levels before and after RYGBP Before After HbA1c surgery surgery 7.0% 12 patients (38.7%) 28 patients (90.3%) % 6 patients (19.3%) 3 patients (9.7%) > 8.0% 13 patients (42%) 0 patients (0%) Table 3. Current treatment for glycemic control before and after RYGBP Treatment Before surgery After surgery Diet 3 patients 28 patients (9.7%) (90.3%) Oral anti-diabetic 21 patients 2 patients drugs (67.7%) (6.5%) Insulin 4 patients 1 patient (12.9%) (3.2%) Insulin + Oral 3 patients 0 patients anti-diabetic drugs (9.7%) (0%) Discussion RYGBP is an effective operation for sustained weight loss and improvement of glycemic control in morbidly obese patients with DM2. Buffington and Cowan 28 demonstrated normalization of glycemia in 70% of diabetic patients with morbid obesity after RYGBP. Similar results with bariatric surgery have been reported by others. 14,15,29-32 Bariatric surgery is also effective in the long-term maintenance of good glycemic control. Pories et al 29 demonstrated glycemia and glycohemoglobin levels within reference values in 82.9% of patients with a diagnosis of DM2 14 years after the surgical procedure, while the remaining patients showed an important decline in the need for anti-diabetic medication, including a reduction in insulin doses. The patients studied here showed a mean total weight loss of 32.6% and a mean %EWL of 64.7% after RYGBP, similar to the 35% and 40-85% values reported in the literature, respectively. 18,19,23,24 In the present study, HbA1c levels continued to be normal in 90.3% of the patients during a postoperative follow-up period of 12 to 60 months, which also agrees with literature data The remaining patients presented an important reduction in the need for antidiabetic medication, with the only patient who continued taking insulin after surgery achieving an 83.3% reduction in the insulin dose. Metformin in lower doses is still prescribed in another two patients to maintain HbA1c levels <7.5%. These patients %EWL were 65.8%, 80% and 36.8%, not different from the others. It is also interesting to note that bariatric surgery does not only improve glycemic values but also Obesity Surgery, 14,

4 Diniz et al reduces or delays the onset of diabetes in patients with morbid obesity. The SOS-study (Swedish Obese Subjects) compared two groups of patients with class III obesity and demonstrated a 32-fold reduction in the incidence of DM2 after 2 years of postoperative follow-up and a 5-fold reduction after 8 years for patients submitted to bariatric surgery. 36 RYGBP is also responsible for a reduction in the mortality associated with DM2. In a study analyzing the mortality of diabetic patients with morbid obesity submitted to RYGBP over a period of 25 years, mean mortality was 9% compared to the 28% observed for the non-operated control group. 37,38 This reduction in mortality is probably a consequence not only of the improvement of glycemic control, but also of other co-morbidities common in patients with diabetes and obesity such as systemic arterial hypertension and coronary disease. 32,33,35,39 The United Kingdon Prospective Diabetes Study (UKDPDS) has demonstrated the importance of a reduction of HbA1c levels in the prevention of chronic microvascular complications of DM2. 40 We may assume that the reduction in HbA1c levels observed after sustained weight loss might also help in the prevention of complications observed in morbidly obese individuals. The present study demonstrated a significant improvement of glycemic control in obese patients after RYGBP, with prolonged follow-up being fundamental for the assessment of the impact of improved control of DM2 on the prevention of chronic complications after bariatric surgery. References 1. National Institutes of Health, National Heart, Lung and Blood Institute - Clinical guidelines on the identification, evaluation and treatment of overweight and obesity in adults-the evidence report. Obes Res 1998; 6 (Suppl 2): 51S-209S. 2. Flegal KM, Carrol MD, Kuczmarski RJ et al. Overweight and obesity in the United States: prevalence and trends, Int J Obes 1998; 22: Monteiro CA, Mondini L, Souza AL et al. The nutrition transition in Brazil. Eur J Clin Nutr 1995; 49: Drenick EJ, Bale GS, Seltzer F et al. Excessive mortality and causes of death in morbidly obese men. JAMA 1980; 243: McGinnis JM, Foege WH. Actual causes of death in the United States. JAMA 1993; 270: Pi-Sunyer FX. The medical risk of obesity. Obes Surg 2002; 12 (Suppl 1): 6S-11S. 7. Stunkard AJ. Current view on obesity. Am J Med 1996; 100: Pi-Sunyer FX. Short-term medical benefits and adverse effects of weight loss. Ann Intern Med 1993; 119: Colditz GA, Willett WC, Ronitzky A et al. Weight gain as a risk factor for clinical diabetes mellitus in woman. Ann Intern Med 1995; 122: Perry IJ, Wannamethee SG, Walker MK et al. Prospective study of risk factors for development of non-insulin dependent diabetes in middle aged British men. BMJ 1995; 310: Meigs JB, Nathan DM, Wilson PWF et al. Metabolic risk factors worsen continuously across the spectrum of nondiabetic glucose tolerance. Ann Intern Med 1998; 128: CDC s Diabetes and Public Health Resource. National Diabetes Fact Sheet Website at National Diabetes Data Group: Diabetes in America, 2nd edition. National Institute of Health, National Insitute of Diabetes and Digestive and Kidney Diseases. NIH Publication No , 1993: Gleysteen JJ, Barboriak JJ, Sasse EA. Sustained coronary risk factor reduction after gastric bypass for morbid obesity. Am J Clin Nutr 1990; 51: Wittgrove AC, Clark W, Schubert KR et al. Laparoscopic gastric bypass, Roux-en-Y: technique and results in 75 patients with 3-30 months follow-up. Obes Surg 1996; 6: Noya G, Cossu ML, Coppola M et al. Biliopancreatic diversion for treatment of morbid obesity: experience in 50 cases. Obes Surg 1998; 8: Lean MEJ, Powrie JK, Anderson AS et al. Obesity, weight loss and prognosis in type 2 diabetes. Diabetes Med 1990; 7: Benotti PN, Forse RA. The role of gastric surgery in the multidisciplinary management of severe obesity. Am J Surg 1995; 169: Kolanowski J. Surgical treatment of morbid obesity. Brit Med Bull 1997; 53: Gastrointestinal surgery for severe obesity. National 1054 Obesity Surgery, 14, 2004

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