Effects of acute NEFA manipulation on incretin-induced insulin secretion in participants with and without type 2 diabetes

Aims/hypothesis

Incretin effect—the potentiation of glucose-stimulated insulin release induced by the oral vs the i.v. route—is impaired in dysglycaemic states. Despite evidence from human islet studies that NEFA interfere with incretin function, little information is available about the effect in humans. We tested the impact of acute bidirectional NEFA manipulation on the incretin effect in humans.

Methods

Thirteen individuals with type 2 diabetes and ten non-diabetic volunteers had a 3 h OGTT, and, a week later, an i.v. isoglycaemic glucose infusion (ISO; OGTT matched). Both pairs of studies were repeated during an exogenous lipid infusion in the non-diabetic volunteers, and following acipimox administration (to inhibit lipolysis) in people with diabetes. Mathematical modelling of insulin secretion dynamics assessed total insulin secretion (TIS), beta cell glucose sensitivity (β-GS), glucose-induced potentiation (P_GLU) and incretin-induced potentiation (P_INCR); the oral glucose sensitivity index was used to estimate insulin sensitivity.

Results

Lipid infusion increased TIS (from 61 [interquartile range 26] to 78 [31] nmol/m² on OGTT and from 29 nmol/m² [26] to 57 nmol/m² [30] on ISO) and induced insulin resistance. P_INCR decreased from 1.6 [1.1] to 1.3 [0.1] (p?<?0.05). β-GS, P_GLU and glucagon, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) responses were unaffected. Acipimox (lowering NEFA by ~55%) reduced plasma glucose and TIS and enhanced insulin sensitivity, but did not change β-GS, P_INCR, P_GLU or glucagon, GLP-1 or GIP responses. As the per cent difference, incretin effect was decreased in non-diabetic participants and unchanged in those with diabetes.

Conclusions/interpretation

Raising NEFA selectively impairs incretin effect and insulin sensitivity in non-diabetic individuals, while acute NEFA reduction lowers plasma glucose and enhances insulin sensitivity in people with diabetes but does not correct the impaired incretin-induced potentiation.

     

GLP-1 and Adiponectin: Effect of Weight Loss After Dietary Restriction and Gastric Bypass in Morbidly Obese Patients with Normal and Abnormal Glucose Metabolism

Background  It has been proposed that there is improvement in glucose and insulin metabolism after weight loss in patients who underwent diet restriction and bariatric surgery. Methods  Eleven normal glucose tolerant (NGT) morbidly obese patients [body mass index (BMI), 46.1 ± 2.27 g/m²] and eight abnormal glucose metabolism (AGM) obese patients (BMI, 51.20 kg/m²) were submitted to diet-restriction and bariatric surgery. Prospective study on weight loss changes, over the glucose, insulin metabolism, glucagon-like peptide-1 (GLP-1), and adiponectin levels were evaluated by oral glucose tolerance test during three periods: T1 (first evaluation), T2 (pre-surgery), and T3 (9 months after surgery). Results  Insulin levels improved after surgery. T1 was 131.1 ± 17.60 pmol/l in the NGT group and 197.57 ± 57.94 pmol/l in the AGM group, and T3 was 72.48 ± 3.67 pmol/l in the NGT group and 61.2 ± 9.33 pmol/l in the AGM group. The major reduction was at the first hour of the glucose load as well as fasting levels. At 9 months after surgery (T3), GLP-1 levels at 30 and 60 min had significantly increased in both groups. It was observed that the AGM group had higher levels of GLP-1 at 30 min (34.06 ± 6.18 pmol/l) when compared to the NGT group (22.69 ± 4.04 pmol/l). Homeostasis model assessment of insulin resistance from the NGT and AGM groups had a significant reduction at periods T3 in relation to T1 and T2. Adiponectin levels had increased concentration in both groups before and after surgical weight loss. However, it did not have any statistical difference between periods T1 vs. T2. Conclusions  Weight loss by surgery leads to improvement in the metabolism of carbohydrates in relation to sensitivity to the insulin, contributing to the reduction of type 2 diabetes incidence. This improvement also was expressed by the improvement of the levels of adiponectin and GLP-1.     

Patient knowledge and interest on dialysis efficiency: a survey

BACKGROUND: Therapeutic compliance is fundamental on dialysis; however following a therapy requires a prior understanding of it. Aim of the study was to assess the need and interest for information on dialysis efficiency and to prepare a dedicated teaching tool. METHODS: 72 patients, on hemodialysis in two limited-care satellite units, were given a questionnaire testing knowledge and interest on dialysis efficiency. In a subsequent second phase, following patients' suggestions, a cartoon book was prepared and opinions recorded. RESULTS: 63 patients' returned the questionnaire. 79.4% had basic knowledge on routine blood tests, 30.1% were aware of their specific meaning. All patients asked for further information, preferring books to other media. The book "Kt/V as cartoon" was distributed; 71.2% read it, 93% scored it as good-very good. In the Unit employing flexible dialysis schedules, 22/42 patients increased dialysis time. CONCLUSIONS: Despite insufficient knowledge on dialysis efficiency, patient interest is high. An educational program is feasible and may also give practical results, such as self-increase in dialysis time.     

HOSPITALIZATION TIME AFTER OPEN APPENDECTOMY BY THREE DIFFERENT SURGICAL TECHNIQUES

Background

The choice of surgical technique to approach the appendicular stump depends mostly on skill and personal preference of the surgeon or on the protocol used in the service, and the influence of this choice in hospitalization time is not evaluated.

Aim

To evaluate the relation between surgical technique and postoperative hospitalization time in patients presenting with acute appendicitis.

Methods

Retrospective analysis of 180 patients who underwent open appendectomy. These where divided into three groups according to surgical technique: conventional appendectomy (simple ligation of the stump), tobacco pouch suture and Parker-Kerr suture. Data where crossed with hospitalization time (until three days, from four to six days and over seven days).

Results

A hundred and eighty patients with age from 15 to 85 years where included. From these, 95 underwent conventional technique, had an average hospitalization time of 3,9 days and seven had complications (surgical site infection, seroma, suture dehiscence and evisceration). In 67 patients, tobacco pouch suture was chosen and had average hospitalization time of 3,7 days and two complications (infection and seroma). In 18 Parker-Kerr suture was made, with average hospitalization time of 2,6 days, with no complication. Contingency coefficient between the variables hospitalization time and technique was 0,255 and Cramér''s V was 0,186.

Conclusion

There was tendency to larger hospitalization time and larger number of complications in conventional appendectomy, whereas in patients where Parker-Kerr suture was performed, hospitalization time was significantly smaller.     

Insulin resistance in nondiabetic morbidly obese patients: effect of bariatric surgery

OBJECTIVE: To evaluate insulin action on substrate use and insulinemia in nondiabetic class III obese patients before and after weight loss induced by bariatric surgery. RESEARCH METHODS AND PROCEDURES: Thirteen obese patients (four men/nine women; BMI = 56.3 +/- 2.7 kg/m2) and 13 lean subjects (five men/eight women; BMI = 22.4 +/- 0.5 kg/m2) underwent euglycemic clamp, oral glucose tolerance test, and indirect calorimetry. The study was carried out before (Study I) and after ( approximately 40% relative to initial body weight; Study II) weight loss induced by Roux-en-Y Gastric bypass with silastic ring surgery. RESULTS: The obese patients were insulin resistant (whole-body glucose use = 19.7 +/- 1.5 vs. 51.5 +/- 2.4 micromol/min per kilogram fat-free mass, p < 0.0001) and hyperinsulinemic in the fasting state (332 +/- 86 vs. 85 +/- 5 pM, p < 0.0001) and during the oral glucose tolerance test compared with the lean subjects. Fasting plasma insulin normalized after weight loss, whereas whole-body glucose use increased (35.5 +/- 3.7 micromol/min per kilogram fat-free mass, p < 0.05 vs. Study I). The higher insulin clearance of obese did not change during the follow-up period. Insulin-induced glucose oxidation and nonoxidative glucose disposal were lower in the obese compared with the lean group (all p < 0.05). In Study II, the former increased slightly, whereas nonoxidative glucose disposal reached values similar to those of the control group. Fasting lipid oxidation was higher in the obese than in the control group and did not change significantly in Study II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs. Study I). DISCUSSION: The rapid weight loss after surgery in obese class III patients normalized insulinemia and improved insulin sensitivity almost entirely due to glucose storage, whereas fasting lipid oxidation remained high.