Effects of gastric bypass surgery in patients with type 2 diabetes and only mild obesity

Abstract

Objective: Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes in severely obese patients through mechanisms beyond just weight loss, and it may benefit less obese diabetic patients. We determined the long-term impact of RYGB on patients with diabetes and only class I obesity.

Research design and methods: Sixty-six consecutively selected diabetic patients with BMI 30-35 kg/m(2) underwent RYGB in a tertiary-care hospital and were prospectively studied for up to 6 years (median 5 years [range 1-6]), with 100% follow-up. Main outcome measures were safety and the percentage of patients experiencing diabetes remission (HbA(1c) <6.5% without diabetes medication).

Results: Participants had severe, longstanding diabetes, with disease duration 12.5 ± 7.4 years and HbA(1c) 9.7 ± 1.5%, despite insulin and/or oral diabetes medication usage in everyone. For up to 6 years following RYGB, durable diabetes remission occurred in 88% of cases, with glycemic improvement in 11%. Mean HbA(1c) fell from 9.7 ± 1.5 to 5.9 ± 0.1% (P < 0.001), despite diabetes medication cessation in the majority. Weight loss failed to correlate with several measures of improved glucose homeostasis, consistent with weight-independent antidiabetes mechanisms of RYGB. C-peptide responses to glucose increased substantially, suggesting improved β-cell function. There was no mortality, major surgical morbidity, or excessive weight loss. Hypertension and dyslipidemia also improved, yielding 50-84% reductions in predicted 10-year cardiovascular disease risks of fatal and nonfatal coronary heart disease and stroke.

Conclusions: This is the largest, longest-term study examining RYGB for diabetic patients without severe obesity. RYGB safely and effectively ameliorated diabetes and associated comorbidities, reducing cardiovascular risk, in patients with a BMI of only 30-35 kg/m(2).

Figures

Figure 1

Improvement in glycemic control during 6 years following RYGB. Mean (± SE) HbA1c (A) and FPG (B) for the entire cohort decreased from values representing poorly controlled diabetes, despite all patients being on diabetes medications at baseline, to the nondiabetic or normal range from 6 months through 6 years after RYGB, with 88% of patients discontinuing all diabetes medications. n = 66 at 0, 6, and 12 months; 59 at 24 months; 48 at 48 months; 37 at 60 months; and 30 at 72 months (i.e., 6 years). These n values decrease over time because not all patients have yet made it to the longer follow-up times; no one from the original cohort has been lost to follow-up. C: At the time of the latest follow-up, 88% of patients experienced remission of diabetes (i.e., HbA1c <6.5% off all diabetes medications), 11% had improved diabetes, and only 1 individual did not display a clear change in glycemic control. Remission occurred between 3 and 26 weeks after RYGB, and no one in the “diabetes remission” group has subsequently experienced a recrudescence of diabetes during follow-up. Classification as “diabetes improved” was based on participants’ status at the time of the latest follow-up. All patients who used insulin at baseline discontinued insulin usage between 3 and 14 weeks after surgery. D: Plasma glucose and C-peptide levels after an overnight fast and 120 min after a standardized mixed-macronutrient test meal, assessed before and after RYGB. Postoperative values are shown at the longest time point of individual follow-up. *Significant difference between equivalent preoperative and postoperative measurements (P < 0.004 in all cases). E–H: There was similar loss of adiposity over 6 years among patients who experienced full remission vs. only improvement of diabetes. Waist circumference (E and G) and total body weight (F and H) decreased markedly in both the “resolved” (n = 58) and “improved” (n = 7) diabetic groups. Reductions in both parameters were highly significant over the course of the study (P < 0.001 for all four panels shown in E–H), but there were no apparent differences in the magnitude of change in waist circumference or body weight between patients who experienced remission vs. only improvement of diabetes. Although mean waist circumference and body weight in the entire cohort increased modestly toward the end of the study, diabetes did not recur in any case where it had resolved. T2DM, type 2 diabetes. Data represent means ± SE.

Figure 1

Improvement in glycemic control during 6 years following RYGB. Mean (± SE) HbA1c (A) and FPG (B) for the entire cohort decreased from values representing poorly controlled diabetes, despite all patients being on diabetes medications at baseline, to the nondiabetic or normal range from 6 months through 6 years after RYGB, with 88% of patients discontinuing all diabetes medications. n = 66 at 0, 6, and 12 months; 59 at 24 months; 48 at 48 months; 37 at 60 months; and 30 at 72 months (i.e., 6 years). These n values decrease over time because not all patients have yet made it to the longer follow-up times; no one from the original cohort has been lost to follow-up. C: At the time of the latest follow-up, 88% of patients experienced remission of diabetes (i.e., HbA1c <6.5% off all diabetes medications), 11% had improved diabetes, and only 1 individual did not display a clear change in glycemic control. Remission occurred between 3 and 26 weeks after RYGB, and no one in the “diabetes remission” group has subsequently experienced a recrudescence of diabetes during follow-up. Classification as “diabetes improved” was based on participants’ status at the time of the latest follow-up. All patients who used insulin at baseline discontinued insulin usage between 3 and 14 weeks after surgery. D: Plasma glucose and C-peptide levels after an overnight fast and 120 min after a standardized mixed-macronutrient test meal, assessed before and after RYGB. Postoperative values are shown at the longest time point of individual follow-up. *Significant difference between equivalent preoperative and postoperative measurements (P < 0.004 in all cases). E–H: There was similar loss of adiposity over 6 years among patients who experienced full remission vs. only improvement of diabetes. Waist circumference (E and G) and total body weight (F and H) decreased markedly in both the “resolved” (n = 58) and “improved” (n = 7) diabetic groups. Reductions in both parameters were highly significant over the course of the study (P < 0.001 for all four panels shown in E–H), but there were no apparent differences in the magnitude of change in waist circumference or body weight between patients who experienced remission vs. only improvement of diabetes. Although mean waist circumference and body weight in the entire cohort increased modestly toward the end of the study, diabetes did not recur in any case where it had resolved. T2DM, type 2 diabetes. Data represent means ± SE.

Figure 2

Improvements in blood pressure and lipid levels during 6 years following RYGB. There were significant, progressive decreases in average systolic and diastolic blood pressure (P < 0.05 for both) in the entire cohort over the course of the study. There also were significant, progressive decreases over the course of the study in total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), and triglycerides (P = 0.003), as well as an increase in HDL cholesterol (P = 0.002). Data represent means ± SE for all patients; n values are the same as in Fig. 1.