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Importance The Roux-en-Y gastric bypass is effective in achieving established diabetes treatment targets, but durability is unknown. Objective To compare durability of Roux-en-Y gastric bypass added to intensive lifestyle and medical management in achieving diabetes control targets. Design, Setting, and Participants Observational follow-up of a randomized clinical trial at 4 sites in the United States and Taiwan, involving 120 participants who had a hemoglobin A1c(HbA1c) level of 8.0% or higher and a body mass index between 30.0 and 39.9 (enrolled between April 2008 and December 2011) were followed up for 5 years, ending in November 2016. Interventions Lifestyle-intensive medical management intervention based on the Diabetes Prevention Program and LookAHEAD trials for 2 years, with and without (60 participants each) Roux-en-Y gastric bypass surgery followed by observation to year 5. Main Outcomes and Measures The American Diabetes Association composite triple end point of hemoglobin A1cless than 7.0%, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood pressure less than 130 mm Hg at 5 years. Results Of 120 participants who were initially randomized (mean age, 49 years [SD, 8 years], 72 women [60%]), 98 (82%) completed 5 years of follow-up. Baseline characteristics were similar between groups: mean (SD) body mass index 34.4 (3.2) for the lifestyle–medical management group and 34.9 (3.0) for the gastric bypass group and had hemoglobin A1clevels of 9.6% (1.2) and 9.6% (1.0), respectively. At 5 years, 13 participants (23%) in the gastric bypass group and 2 (4%) in the lifestyle-intensive medical management group had achieved the composite triple end point (difference, 19%; 95% CI, 4%-34%;P = .01). In the fifth year, 31 patients (55%) in the gastric bypass group vs 8 (14%) in the lifestyle–medical management group achieved an HbA1clevel of less than 7.0% (difference, 41%; 95% CI, 19%-63%;P = .002). Gastric bypass had more serious adverse events than did the lifestyle–medical management intervention, 66 events vs 38 events, most frequently gastrointestinal events and surgical complications such as strictures, small bowel obstructions, and leaks. Gastric bypass had more parathyroid hormone elevation but no difference in B12deficiency. Conclusions and Relevance In extended follow-up of obese adults with type 2 diabetes randomized to adding gastric bypass compared with lifestyle and intensive medical management alone, there remained a significantly better composite triple end point in the surgical group at 5 years. However, because the effect size diminished over 5 years, further follow-up is needed to understand the durability of the improvement. Trial Registration clinicaltrials.gov Identifier:NCT00641251

Importance Controlling glycemia, blood pressure, and cholesterol is important for patients with diabetes. How best to achieve this goal is unknown. Objective To compare Roux-en-Y gastric bypass with lifestyle and intensive medical management to achieve control of comorbid risk factors. Design, Setting, and Participants A 12-month, 2-group unblinded randomized trial at 4 teaching hospitals in the United States and Taiwan involving 120 participants who had a hemoglobin A 1c (HbA 1c ) level of 8.0% or higher, body mass index (BMI) between 30.0 and 39.9, C peptide level of more than 1.0 ng/mL, and type 2 diabetes for at least 6 months. The study began in April 2008. Interventions Lifestyle-intensive medical management intervention and Roux-en-Y gastric bypass surgery. Medications for hyperglycemia, hypertension, and dyslipidemia were prescribed according to protocol and surgical techniques that were standardized. Main Outcomes and Measures Composite goal of HbA 1c less than 7.0%, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood pressure less than 130 mm Hg. Results All 120 patients received the intensive lifestyle-medical management protocol and 60 were randomly assigned to undergo Roux-en-Y gastric bypass. After 12-months, 28 participants (49%; 95% CI, 36%-63%) in the gastric bypass group and 11 (19%; 95% CI, 10%-32%) in the lifestyle-medical management group achieved the primary end points (odds ratio [OR], 4.8; 95% CI, 1.9-11.7). Participants in the gastric bypass group required 3.0 fewer medications (mean, 1.7 vs 4.8; 95% CI for the difference, 2.3-3.6) and lost 26.1% vs 7.9% of their initial body weigh compared with the lifestyle-medical management group (difference, 17.5%; 95% CI, 14.2%-20.7%). Regression analyses indicated that achieving the composite end point was primarily attributable to weight loss. There were 22 serious adverse events in the gastric bypass group, including 1 cardiovascular event, and 15 in the lifestyle-medical management group. There were 4 perioperative complications and 6 late postoperative complications. The gastric bypass group experienced more nutritional deficiency than the lifestyle-medical management group. Conclusions and Relevance In mild to moderately obese patients with type 2 diabetes, adding gastric bypass surgery to lifestyle and medical management was associated with a greater likelihood of achieving the composite goal. Potential benefits of adding gastric bypass surgery to the best lifestyle and medical management strategies of diabetes must be weighed against the risk of serious adverse events. Trial Registration clinicaltrials.gov Identifier: NCT00641251

Objective. —To study effects of variation in carbohydrate content of diet on glycemia and plasma lipoproteins in patients with non—insulin-dependent diabetes mellitus (NIDDM). Design. —A four-center randomized crossover trial. Setting. —Outpatient and inpatient evaluation in metabolic units. Patients. —Forty-two NIDDM patients receiving glipizide therapy. Interventions. —A high-carbohydrate diet containing 55% of the total energy as carbohydrates and 30% as fats was compared with a high—monounsaturated-fat diet containing 40% carbohydrates and 45% fats. The amounts of saturated fats, polyunsaturated fats, cholesterol, sucrose, and protein were similar. The study diets, prepared in metabolic kitchens, were provided as the sole nutrients to subjects for 6 weeks each. To assess longer-term effects, a subgroup of 21 patients continued the diet they received second for an additional 8 weeks. Main Outcome Measures. —Fasting plasma glucose, insulin, lipoproteins, and glycosylated hemoglobin concentrations. Twenty-four-hour profiles of glucose, insulin, and triglyceride levels. Results. —The site of study as well as the diet order did not affect the results. Compared with the high—monounsaturated-fat diet, the high-carbohydrate diet increased fasting plasma triglyceride levels and very low-density lipoprotein cholesterol levels by 24% ( P P =.0001), respectively, and increased daylong plasma triglyceride, glucose, and insulin values by 10% ( P =.03), 12% ( P P =.02), respectively. Plasma total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels remained unchanged. The effects of both diets on plasma glucose, insulin, and triglyceride levels persisted for 14 weeks. Conclusions. —In NIDDM patients, high-carbohydrate diets compared with high—monounsaturated-fat diets caused persistent deterioration of glycemic control and accentuation of hyperinsulinemia, as well as increased plasma triglyceride and very-low-density lipoprotein cholesterol levels, which may not be desirable. ( JAMA . 1994;271:1421-1428)

In Reply.— Dr Bernstein suggests that when diabetic individuals are treated with a few large doses of insulin each day, blood glucose levels are more variable than when they are treated with more frequent injections of small doses of insulin. We share this impression. However, many diabetic patients are unwilling to inject insulin four or five times daily as suggested by Dr Bernstein. Moreover, when this issue was studied systematically, Service and coworkers 1 found that individuals with unstable diabetes who were switched from one or two daily injections of intermediate-acting insulin to four daily injections of short-acting insulin did not demonstrate a reduction in the lability of blood glucose as measured by the mean amplitude of glycemic excursions. Regardless of whether patients with type I diabetes take one or two large doses or more frequent smaller doses of insulin each day, we believe that the day-to-day variability of blood glucose

Treatment of type I diabetes mellitus is hindered by the often large fluctuations in blood glucose concentration experienced by affected individuals. To determine to what extent day-to-day variation in blood glucose levels can be reduced if insulin is injected in the same anatomic region rather than in different regions using a rotational scheme, as is commonly recommended, 12 type I diabetic subjects were studied. Insulin injections were given in the abdomen for 3 days and rotated among arms, abdomen, and thighs for 3 days using a crossover design with random assignment of treatment order. Blood samples for measurement of plasma glucose levels were obtained at nine scheduled times on each day. Insulin dose, diet, and physical activity were held constant for each subject. During the abdominal injection period, the mean SD of plasma glucose levels and the mean variance of plasma glucose levels were both less at all nine time points than during the rotating injection period. Overall values for the SD of plasma glucose levels were 2.7 ± 0.2 mmol/L for the abdominal injection period and 3.7 ±0.3 mmol/L for the rotating injection period. Overall values for the variance of plasma glucose levels were 9.2 ± 1.4 mmol 2 /L 2 for the abdominal injection period and 17.4 ±2.2 mmol 2 /L 2 for the rotating injection period. We conclude that the common clinical practice of rotating the anatomic regions used for insulin injections increases day-to-day variation in blood glucose concentration. Use of a single anatomic region, eg, the abdomen, for all insulin injections may reduce this variation and allow greater precision in the adjustment of insulin doses. ( JAMA . 1990;263:1802-1806)

• Abnormal serum creatinine (1.6 mg/dL) and creatinine clearance (33 mL/min) levels found in a 50-year-old woman during fasting were corrected with refeeding. Five healthy subjects who fasted for 96 hours demonstrated an increase in their mean serum creatinine level from 1.0±0.08 to 1.7±0.11 mg/dL as determined by Jaffe's method. This increase was probably an artifact caused by the rise in the serum acetoacetate level during fasting. The serum creatinine level determined by an enzymatic method and serum urea nitrogen level did not change substantially during the fast. We conclude that fasting may cause an artifactual increase in the serum creatinine level determined by Jaffe's method, the method used by most clinical laboratories. ( Arch Intern Med 1984;144:1575-1576)

To learn more about the metabolic effects of dietary fructose and sucrose, 12 type I and 12 type II diabetic subjects were fed three isocaloric (or isoenergic) diets for eight days each according to a randomized, crossover design. The three diets provided, respectively, 21% of the energy as fructose, 23% of the energy as sucrose, and almost all carbohydrate energy as starch. The fructose diet resulted in significantly lower one- and two-hour postprandial plasma glucose levels, overall mean plasma glucose levels, and urinary glucose excretion in both type I and type II subjects than did the starch diet. There were no significant differences between the sucrose and starch diets in any of the measures of glycemic control in either subject group. The fructose and sucrose diets did not significantly increase serum triglyceride values when compared with the starch diet, but both increased postprandial serum lactate levels. We conclude that short-term replacement of other carbohydrate sources in the diabetic diet with fructose will improve glycemic control, whereas replacement with sucrose will not aggravate glycemic control.

• Five patients from two unrelated families were found to have goiter and elevated serum concentrations of thyroxine (T 4 ) and triiodothyronine (T 3 ) without symptoms or signs of hyperthyroidism. All had measurable concentrations of thyroid stimulating hormone (TSH), and in four who were tested, there was an increase in TSH concentration following thyrotropin releasing hormone (TRH) administration. We believe these five patients have general resistance to the effects of thyroid hormones and need elevated concentrations of T 4 and T 3 to maintain a eumetabolic state. Study of nuclear T 3 receptors from cultured fibroblasts of one patient disclosed a normal equilibrium association constant and a maximal binding capacity that was greater than normal control values. These findings suggest that thyroid hormone resistance in this patient is not due to a decrease in either the affinity or the number of specific nuclear T 3 receptors. This disorder can easily be confused with Graves' disease and result in inappropriate treatment for hyperthyroidism, as was the case in three of our patients. ( Arch Intern Med 1982;142:1867-1871)

To evaluate the mechanism of cyclosporine-induced hyperkalemia, the renin-angiotensin-aldosterone system and renal potassium clearance were compared in ten renal transplant recipients treated with cyclosporine and treated with azathioprine. After stimulation by a low-sodium diet and furosemide, cyclosporine-treated patients demonstrated lower plasma renin activity when supine (1.9 +/- 0.3 v 7.8 +/- 1.4 ng/mL/hr) and after standing (3.0 +/- 0.7 v 12.2 +/- 1.5 ng/mL/hr). Supine plasma aldosterone levels tended to be lower in cyclosporine-treated patients, (4.8 +/- v 10.5 +/- 2.6 ng/dL), although standing plasma aldosterone levels were not different (10.8 +/- 3.0 v 12.3 +/- 2.0 ng/dL). After administration of 0.75 mEq of potassium chloride per kilogram of body weight, cyclosporine-treated patients excreted 52% +/- 7.1% of the potassium load in six hours compared with excretion of 67% +/- 7.0% by the azathioprine-treated patients, although there was no difference in plasma aldosterone levels in response to the potassium load in the two groups. These data suggest that cyclosporine causes suppression of plasma renin activity and a tubular insensitivity to aldosterone, both of which may impair potassium excretion.