Clare J. Lee

Hormonal Response to a Mixed-Meal Challenge After Reversal of Gastric Bypass for Hypoglycemia

CONTEXT Severe hypoglycemia is a rare and challenging complication of Roux-en-Y gastric bypass (RYGB), which is characterized by hypersecretion of insulin and incretin hormones in the postprandial state. OBJECTIVE The objective of the study was to determine the clinical and hormonal responses to a mixed-meal challenge after the reversal of RYGB in 2 patients with post-RYGB hypoglycemia. We hypothesized that the reversal of RYGB would lead to clinical improvement in hypoglycemia through the attenuation of incretin hormone secretion. DESIGN/SETTING/SUBJECTS/OUTCOME MEASURES: Two patients with post-RYGB hypoglycemia underwent a standardized meal tolerance test prior to and 8 and 18 months after RYGB reversal, respectively, with the measurement of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, and glucose levels. Gastric bypass was reversed by reattaching the small gastric pouch to the bypassed distal stomach and resecting the Roux limb to restore the normal flow of food bolus. RESULTS Both subjects showed persistent evidence of hypoglycemia with marked hyperinsulinemia after the RYGB reversal. GLP-1 levels after the RYGB reversal decreased by 76% and 70%, respectively, from their prereversal levels and to the level of nonhypoglycemic post-RYGB controls. In contrast, GIP levels after the RYGB reversal increased by 3-10 times the level before the reversal and 8-26 times that of the nonhypoglycemic post-RYGB controls. CONCLUSIONS Reversal of RYGB did not alleviate hyperinsulinemic hypoglycemia upon a mixed-meal challenge in our patients, thus suggesting its limited clinical benefit as treatment of post-RYGB hypoglycemia. The marked increase in GIP levels and concurrent decrease in GLP-1 levels in our patients suggest a possible role of GIP in persistent hyperinsulinemic hypoglycemia after the reversal of RYGB.

Prevalence of and risk factors for hypoglycemic symptoms after gastric bypass and sleeve gastrectomy.

Objective To determine the prevalence of and risk factors for postprandial hypoglycemic symptoms among bariatric surgery patients. Design and Methods A questionnaire including the Edinburgh hypoglycemia scale was mailed to patients who underwent either Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG) at a single center. Based on the questionnaire, we categorized the patients as having high or low suspicion for post-surgical, postprandial hypoglycemic symptoms. Results Of the 1119 patients with valid addresses, 40.2% (N=450) responded. Among the respondents, 34.2% had a high suspicion for symptoms of post-bariatric surgery hypoglycemia. In multivariate analyses, in addition to female sex (p=0.001), RYGB (p=0.004), longer time since surgery (p=0.013), lack of diabetes (p=0.040), the high suspicion group was more likely to report preoperative symptoms of hypoglycemia (p<0.001), compared to the low suspicion group. Similar results were observed when the high suspicion group was restricted to those requiring assistance from others, syncope, seizure with severe symptoms or medically confirmed hypoglycemia (N=52). Conclusion One third of RYGB or VSG reported postprandial symptoms concerning for post-surgical hypoglycemia, which was related to the presence of pre-operative hypoglycemic symptoms. Pre-operative screening for hypoglycemic symptoms may identify a group of patients at increased risk of post-bariatric surgery hypoglycemia.To determine the prevalence of and risk factors for postprandial hypoglycemic symptoms among bariatric surgery patients.

Risk of post-gastric bypass surgery hypoglycemia in nondiabetic individuals: A single center experience

The epidemiology of post‐gastric bypass surgery hypoglycemia (PGBH) is incompletely understood. This study aimed to evaluate the risk of PGBH among nondiabetic patients and associated factors.

Evaluation of the Association Between Preoperative Clinical Factors and Long-term Weight Loss After Roux-en-Y Gastric Bypass

Importance Weight loss after bariatric surgery varies, yet preoperative clinical factors associated with long-term suboptimal outcomes are not well understood. Objective To evaluate the association between preoperative clinical factors and long-term weight loss after Roux-en-Y gastric bypass (RYGB). Design, Setting, and Participants From June 2001 to September 2007, this retrospective cohort study followed up RYGB patients before surgery to 7 to 12 years after surgery. The setting was a large rural integrated health system. Of 1033 eligible RYGB patients who consented to participate in longitudinal research and completed surgery before October 2007, a total of 726 (70.3%) had a weight entered in the electronic medical record 7 or more years after surgery and were included in the analyses after exclusions for pregnancy and mortality. Date of the long-term weight measurement was recorded between August 2010 and January 2016. Main Outcomes and Measures The primary outcome was percentage weight loss (%WL) at 7 to 12 years after surgery. Preoperative clinical factors (>200) extracted from the electronic medical record included medications, comorbidities, laboratory test results, and demographics, among others. Results Among the 726 study participants, 83.1% (n = 603) were female and 97.4% (n = 707) were of white race, with a mean (SD) preoperative body mass index (calculated as weight in kilograms divided by height in meters squared) of 47.5 (7.4). From the time of surgery to long-term follow-up (median, 9.3 postoperative years), the mean (SD) %WL was 22.5% (13.1%). Preoperative insulin use, history of smoking, and use of 12 or more medications before surgery were associated with greater long-term postoperative %WL (6.8%, 2.8%, and 3.1%, respectively). Preoperative hyperlipidemia, older age, and higher body mass index were associated with poorer long-term postoperative %WL (-2.8%, -8.8%, and -4.1%, respectively). Conclusions and Relevance Few preoperative clinical factors associated with long-term weight loss after RYGB were identified. Preoperative insulin use was strongly associated with better long-term %WL, while preoperative hyperlipidemia, higher body mass index, and older age were associated with poorer %WL. Our findings provide additional insight into preoperative identification of RYGB patients at higher risk for long-term suboptimal outcomes.

Risk factors for severe hypoglycemia in black and white adults with diabetes: The Atherosclerosis Risk in Communities (ARIC) Study

OBJECTIVE Severe hypoglycemia is a rare but important complication of type 2 diabetes. Few studies have examined the epidemiology of hypoglycemia in a community-based population. RESEARCH DESIGN AND METHODS We included 1,206 Atherosclerosis Risk in Communities (ARIC) Study participants with diagnosed diabetes (baseline: 1996–1998). Severe hypoglycemic events were identified through 2013 by ICD-9 codes from claims for hospitalizations, emergency department visits, and ambulance use. We used Cox regression to evaluate risk factors for severe hypoglycemia. RESULTS The mean age of participants was 64 years, 32% were black, and 54% were female. During a median follow-up period of 15.2 years, there were 185 severe hypoglycemic events. Important risk factors after multivariable adjustment were as follows: age (per 5 years: hazard ratio [HR] 1.24; 95% CI 1.07–1.43), black race (HR 1.39; 95% CI 1.02–1.88), diabetes medications (any insulin use vs. no medications: HR 3.00; 95% CI 1.71–5.28; oral medications only vs. no medications: HR 2.20; 95% CI 1.28–3.76), glycemic control (moderate vs. good: HR 1.78; 95% CI 1.11–2.83; poor vs. good: HR 2.62; 95% CI 1.67–4.10), macroalbuminuria (HR 1.95; 95% CI 1.23–3.07), and poor cognitive function (Digit Symbol Substitution Test z score: HR 1.57; 95% CI 1.33–1.84). In an analysis of nontraditional risk factors, low 1,5-anhydroglucitol, difficulty with activities of daily living, Medicaid insurance, and antidepressant use were positively associated with severe hypoglycemia after multivariate adjustment. CONCLUSIONS Poor glycemic control, glycemic variability as captured by 1,5-anhydroglucitol, kidney damage, and measures of cognitive and functional impairments were strongly associated with increased risk of severe hypoglycemia. These factors should be considered in hypoglycemia risk assessments when individualizing diabetes care for older adults.

The Association of Severe Hypoglycemia With Incident Cardiovascular Events and Mortality in Adults With Type 2 Diabetes

OBJECTIVE There is suggestive evidence linking hypoglycemia with cardiovascular disease, but few data have been collected in a community-based setting. Information is lacking on individual cardiovascular outcomes and cause-specific mortality. RESEARCH DESIGN AND METHODS We conducted a prospective cohort analysis of 1,209 participants with diagnosed diabetes from the Atherosclerosis Risk in Communities (ARIC) study (analytic baseline, 1996–1998). Severe hypoglycemic episodes were identified using first position ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls through 2013. Cardiovascular events and deaths were captured through 2013. We used adjusted Cox regression models with hypoglycemia as a time-varying exposure. RESULTS There were 195 participants with at least one severe hypoglycemic episode during a median fellow-up of 15.3 years. After severe hypoglycemia, the 3-year cumulative incidence of coronary heart disease was 10.8% and of mortality was 28.3%. After adjustment, severe hypoglycemia was associated with coronary heart disease (hazard ratio [HR] 2.02, 95% CI 1.27–3.20), all-cause mortality (HR 1.73, 95% CI 1.38–2.17), cardiovascular mortality (HR 1.64, 95% CI 1.15–2.34), and cancer mortality (HR 2.49, 95% CI 1.46–4.24). Hypoglycemia was not associated with stroke, heart failure, atrial fibrillation, or noncardiovascular and noncancer death. Results were robust within subgroups defined by age, sex, race, diabetes duration, and baseline cardiovascular risk. CONCLUSIONS Severe hypoglycemia is clearly indicative of declining health and is a potent marker of high absolute risk of cardiovascular events and mortality.

A systematic review of commercial weight loss programmes’ effect on glycemic outcomes among overweight and obese adults with and without type 2 diabetes mellitus

We examined the glycemic benefits of commercial weight loss programmes as compared with control/education or counselling among overweight and obese adults with and without type 2 diabetes mellitus (T2DM).

The effect of vitamin D supplementation on glucose metabolism in type 2 diabetes mellitus: A systematic review and meta-analysis of intervention studies

AIMS We aimed to assess whether vitamin D supplementation improves glucose metabolism in adults with type 2 diabetes. METHODS PubMed and Cochrane database were searched up to July 1st 2016 for randomized controlled trials that assessed the relationship between vitamin D supplementation and glucose metabolism (change in hemoglobin A1C (HbA1C) and fasting blood glucose (FBG)) among adults with type 2 diabetes. RESULTS Twenty nine trials (3324 participants) were included in the systematic review. Among 22 studies included in the meta-analysis, 19 reported HbA1C, 16 reported FBG outcomes and 15 were deemed poor quality. There was a modest reduction in HbA1C (-0.32% [-0.53 to -0.10], I2=91.9%) compared to placebo after vitamin D supplementation but no effect on FBG (-2.33mg/dl [-6.62 to 1.95], I2=59.2%). In studies achieving repletion of vitamin D deficiency (n=7), there were greater mean reductions in HbA1C (-0.45%, [-1.09 to 0.20]) and FBG (-7.64mg/dl [-16.25 to 0.97]) although not significant. CONCLUSIONS We found a modest reduction of HbA1C after vitamin D treatment in adults with type 2 diabetes albeit with substantial heterogeneity between studies and no difference in FBG. Larger studies are needed to further evaluate the glycemic effects of vitamin D treatment especially in patients with vitamin D deficiency.

Levothyroxine Dosing Following Bariatric Surgery

BackgroundBased on the mechanisms of drug absorption, increased levothyroxine requirements are expected after bariatric surgery. However, there are conflicting data on this topic. This review evaluates the effects of bariatric surgery on levothyroxine dosing.MethodsData were obtained from PubMed, Scopus, and review of published bibliographies.ResultsSix of 10 studies demonstrated decreased postoperative requirements. Most demonstrated correlations between weight loss and dose. Only 3 case reports and 1 case series demonstrated increased levothyroxine requirements, attributed to malabsorption.ConclusionsThe loss of both fat and lean body mass may counteract malabsorptive effects from surgery, resulting in decreased postoperative levothyroxine requirements. In addition, the reversal of impaired levothyroxine pharmacokinetics and an altered set point of thyroid hormone homeostasis may also contribute to postoperative levothyroxine reductions.

Weight regain in patients with symptoms of post–bariatric surgery hypoglycemia

BACKGROUND Weight regain (WR) and symptoms of post-bariatric surgery hypoglycemia (PBSH) are metabolic complications observed in a subset of postbariatric patients. Whether hypoglycemic symptoms are an important driver of increased caloric intake and WR after bariatric surgery is unknown. OBJECTIVE This study aims to determine whether patients with PBSH symptoms have greater odds for WR. SETTING Tertiary academic hospital. METHODS Patients who underwent Roux-en-Y gastric bypass or sleeve gastrectomy at our tertiary academic hospital from August 2008 to August 2012 were mailed a survey, from which weight trajectory and PBSH symptoms were assessed. Percent WR was calculated as 100×(current weight-nadir weight)/(preoperative weight-nadir weight) and was compared between dates of survey completion and bariatric surgery. The primary outcome was WR≥10%, as a reflection of the median WR among respondents. Multivariable logistic regression was used to determine clinical factors that indicate greater odds for WR≥10% at the P<.05 level. RESULTS Of 1119 potential patients, 428 respondents (40.6%) were eligible for analysis. WR was observed in 79.2% (n = 339), while 20.8% (n = 89) experienced either weight loss or no WR at a mean of 40.6±14.5 months. Median WR was 10.8% (interquartile range, 5.6-19.4). Odds of WR≥10% was significantly increased in those who experienced PBSH symptoms (odds ratio [OR] = 1.66; 95% confidence interval [CI]: 1.04-2.65), reported less adherence to nutritional guideline (OR = 2.36; 95% CI: 1.52-3.67), and had a longer time since surgery (OR = 1.05; 95% CI: 1.03-1.07). CONCLUSIONS We found evidence that the presence of PBSH symptoms was associated with WR. Future studies should elucidate the role of hypoglycemia among other factors in post-bariatric surgery WR.